FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Heske, CM
Yeung, C
Mendoza, A
Baumgart, JT
Edessa, LD
Wan, XL
Helman, LJ
AF Heske, Christine M.
Yeung, Choh
Mendoza, Arnulfo
Baumgart, Joshua T.
Edessa, Leah D.
Wan, Xiaolin
Helman, Lee J.
TI The Role of PDGFR-beta Activation in Acquired Resistance to IGF-1R
Blockade in Preclinical Models of Rhabdomyosarcoma
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID FACTOR-I RECEPTOR; SMALL-MOLECULE INHIBITOR; GROWTH-FACTOR-II;
MONOCLONAL-ANTIBODY; SARCOMA ALLIANCE; MECHANISMS; PATHWAY; KINASE;
TUMORS; COLLABORATION
AB To determine what alternative pathways may act as mechanisms of bypass resistance to type 1 insulin-like growth factor receptor (IGF-1R) blockade in rhabdomyosarcoma (RMS), we compared expression of receptor tyrosine kinase activity in a number of IGF-1R antibody-resistant and -sensitive RMS cell lines. We found that platelet-derived growth factor receptor beta (PDGFR-beta) activity was upregulated in three xenograft-derived IGF-1R antibody-resistant cell lines that arose from a highly sensitive fusion-positive RMS cell line (Rh41). Furthermore, we identified four additional fusion-negative RMS cell lines that similarly upregulated PDGFR-beta activity when selected for IGF-1R antibody resistance in vitro. In the seven cell lines described, we observed enhanced growth inhibition when cells were treated with dual IGF-1R and PDGFR-beta inhibition in vitro. In vivo studies have confirmed the enhanced effect of targeting IGF-1R and PDGFR-beta in several mouse xenograft models of fusion-negative RMS. These findings suggest that PDGFR-beta acts as a bypass resistance pathway to IGF-1R inhibition in a subset of RMS. Therapy co-targeting these receptors may be a promising new strategy in RMS care.
C1 [Heske, Christine M.; Yeung, Choh; Mendoza, Arnulfo; Baumgart, Joshua T.; Edessa, Leah D.; Wan, Xiaolin; Helman, Lee J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Heske, CM (reprint author), NIH, Pediat Oncol Branch, Bldg 10,Room 1W-3816,10 Ctr Dr, Bethesda, MD 20892 USA.
EM christine.heske@nih.gov
FU Intramural Research Program of National Institutes of Health, the
National Cancer Institute; Intramural Research Program of National
Institutes of Health, Center for Cancer Research; Conquer Cancer
Foundation of ASCO Young Investigator Award - Quad W Foundation
FX This work was supported by grants from the Intramural Research Program
of National Institutes of Health, the National Cancer Institute, and the
Center for Cancer Research and by a Conquer Cancer Foundation of ASCO
Young Investigator Award supported by the Quad W Foundation. Any
opinions, findings, and conclusions expressed in this material are those
of the authors and do not necessarily reflect those of the American
Society of Clinical Oncology or the Conquer Cancer Foundation.
NR 22
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD DEC
PY 2016
VL 9
IS 6
BP 540
EP 547
DI 10.1016/j.tranon.2016.09.002
PG 8
WC Oncology
SC Oncology
GA EK4OE
UT WOS:000393905600009
PM 27835791
ER
PT J
AU Campbell, SM
Ulrich, CM
Grady, C
AF Campbell, Stephen M.
Ulrich, Connie M.
Grady, Christine
TI A Broader Understanding of Moral Distress
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Article
DE decision making; medicine; moral theory; professional ethics;
professional-patient relationship
ID CARE
AB On the traditional view, moral distress arises only in cases where an individual believes she knows the morally right thing to do but fails to perform that action due to various constraints. We seek to motivate a broader understanding of moral distress. We begin by presenting six types of distress that fall outside the bounds of the traditional definition and explaining why they should be recognized as forms of moral distress. We then propose and defend a new and more expansive definition of moral distress and examine how it can enable the development of a taxonomy of moral distress.
C1 [Campbell, Stephen M.] Bentley Univ, Waltham, MA USA.
[Ulrich, Connie M.] Univ Penn, Philadelphia, PA 19104 USA.
[Grady, Christine] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Campbell, SM (reprint author), Bentley Univ, Dept Philosophy, 175 Forest St, Waltham, MA 02452 USA.
EM scampbell@bentley.edu
NR 25
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Z9 14
U1 3
U2 3
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD DEC
PY 2016
VL 16
IS 12
BP 2
EP 9
DI 10.1080/15265161.2016.1239782
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EF1WN
UT WOS:000390115900009
ER
PT J
AU Rosner, MH
Edeani, A
Yanagita, M
Glezerman, IG
Leung, N
AF Rosner, Mitchell H.
Edeani, Amaka
Yanagita, Motoko
Glezerman, Ilya G.
Leung, Nelson
TI Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal
Gammopathy of Renal Significance
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHAIN DEPOSITION DISEASE; FREE LIGHT-CHAINS; STEM-CELL TRANSPLANTATION;
HIGH-DOSE MELPHALAN; MULTIPLE-MYELOMA; AL AMYLOIDOSIS; FIBRILLARY
GLOMERULONEPHRITIS; UNDETERMINED SIGNIFICANCE; PROLIFERATIVE
GLOMERULONEPHRITIS; WALDENSTROM MACROGLOBULINEMIA
AB Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.
C1 [Rosner, Mitchell H.] Univ Virginia Hlth Syst, Div Nephrol, Charlottesville, VA USA.
[Edeani, Amaka] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
[Yanagita, Motoko] Kyoto Univ, Grad Sch Med, Dept Nephrol, Kyoto, Japan.
[Glezerman, Ilya G.] Mem Sloan Kettering Canc Ctr, Dept Med, Renal Serv, 1275 York Ave, New York, NY 10021 USA.
[Glezerman, Ilya G.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Leung, Nelson] Mayo Clin, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55905 USA.
[Leung, Nelson] Mayo Clin, Div Hematol, Rochester, MN USA.
RP Leung, N (reprint author), Mayo Clin, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55905 USA.
EM leung.nelson@mayo.edu
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health; Berrien
Community Foundation Lucille Kirshenbaum Fund; Omeros Corp.; MSK Cancer
Center Support Grant/Core Grant [P30 CA008748]
FX The work of A.E. is supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. The work of N.L. is supported by
donations from Mr. and Mrs. Ted Kirshenbaum, Dr. Gary Kohler, and Anne
Drennan; the Berrien Community Foundation Lucille Kirshenbaum Fund; the
Southshore Development Company; and grants from Omeros Corp. I.G.G. is
supported by MSK Cancer Center Support Grant/Core Grant (P30 CA008748).
NR 68
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U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD DEC
PY 2016
VL 11
IS 12
BP 2280
EP 2287
DI 10.2215/CJN.02920316
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA EE3OF
UT WOS:000389498200026
PM 27526705
ER
PT J
AU Simonsen, L
Gog, JR
Olson, D
Viboud, C
AF Simonsen, Lone
Gog, Julia R.
Olson, Don
Viboud, Cecile
TI Infectious Disease Surveillance in the Big Data Era: Towards Faster and
Locally Relevant Systems
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE big data; medical claims; Internet search queries; syndromic data; death
certificates; electronic patient records; influenza; infectious diseases
surveillance; real-time monitoring
ID PUBLIC-HEALTH SURVEILLANCE; UNITED-STATES; INFLUENZA; FLU; TIME
AB While big data have proven immensely useful in fields such as marketing and earth sciences, public health is still relying on more traditional surveillance systems and awaiting the fruits of a big data revolution. A new generation of big data surveillance systems is needed to achieve rapid, flexible, and local tracking of infectious diseases, especially for emerging pathogens. In this opinion piece, we reflect on the long and distinguished history of disease surveillance and discuss recent developments related to use of big data. We start with a brief review of traditional systems relying on clinical and laboratory reports. We then examine how large-volume medical claims data can, with great spatiotemporal resolution, help elucidate local disease patterns. Finally, we review efforts to develop surveillance systems based on digital and social data streams, including the recent rise and fall of Google Flu Trends. We conclude by advocating for increased use of hybrid systems combining information from traditional surveillance and big data sources, which seems the most promising option moving forward. Throughout the article, we use influenza as an exemplar of an emerging and reemerging infection which has traditionally been considered a model system for surveillance and modeling.
C1 [Simonsen, Lone; Olson, Don; Viboud, Cecile] US NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD USA.
[Simonsen, Lone] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Gog, Julia R.] Univ Cambridge, Dept Appl Math & Theoret Phys, Cambridge, England.
RP Simonsen, L (reprint author), Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
EM lsimonsen2@gmail.com
FU DHS RAPIDD program; European Commission; Lundbeck Foundation; Fogarty
International Center, NIH
FX This work was supported by the DHS RAPIDD program, maintained by the
Fogarty International Center, National Institutes of Health (NIH;
support to L. S. and J. R. G.); the European Commission (Marie Curie
senior fellowship to L. S.); the Lundbeck Foundation (visiting
professorship grant to L. S.); and the in-house research program of the
Fogarty International Center, NIH (support to C. V. and D. O.).
NR 48
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U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2016
VL 214
SU 4
BP S380
EP S385
DI 10.1093/infdis/jiw376
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EJ3RW
UT WOS:000393130300002
ER
PT J
AU Solem, RC
Ruellas, A
Ricks-Oddie, JL
Kelly, K
Oberoi, S
Lee, J
Miller, A
Cevidanesh, L
AF Solem, R. Christian
Ruellas, Antonio
Ricks-Oddie, Joni L.
Kelly, Katherine
Oberoi, Snehlata
Lee, Janice
Miller, Arthur
Cevidanesh, Lucia
TI Congenital and acquired mandibular asymmetry: Mapping growth and
remodeling in 3 dimensions (vol 150, pg 238, 2016)
SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS
LA English
DT Correction
C1 [Solem, R. Christian] Univ Calif Los Angeles, Sect Orthodont, Los Angeles, CA 90024 USA.
[Ruellas, Antonio] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Ruellas, Antonio] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA.
[Ricks-Oddie, Joni L.] Univ Calif Los Angeles, Inst Digital Res & Educ, Los Angeles, CA USA.
[Kelly, Katherine; Cevidanesh, Lucia] Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA.
[Oberoi, Snehlata] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA.
[Lee, Janice] Natl Inst Dent & Craniofacial Research, NIH, Bethesda, MD USA.
[Miller, Arthur] Univ Calif San Francisco, Sch Dent, San Francisco, CA USA.
RP Solem, RC (reprint author), Univ Calif Los Angeles, Sect Orthodont, Los Angeles, CA 90024 USA.
NR 1
TC 0
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U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0889-5406
EI 1097-6752
J9 AM J ORTHOD DENTOFAC
JI Am. J. Orthod. Dentofac. Orthop.
PD DEC
PY 2016
VL 150
IS 6
BP 911
EP 912
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA EI8DH
UT WOS:000392734900008
ER
PT J
AU Varga, TV
Winters, AH
Jablonski, KA
Horton, ES
Khare-Ranade, P
Knowler, WC
Marcovina, SM
Renstrom, F
Watson, KE
Goldberg, R
Florez, JC
Pollin, TI
Franks, PW
AF Varga, Tibor V.
Winters, Alexandra H.
Jablonski, Kathleen A.
Horton, Edward S.
Khare-Ranade, Prajakta
Knowler, William C.
Marcovina, Santica M.
Renstrom, Frida
Watson, Karol E.
Goldberg, Ronald
Florez, Jose C.
Pollin, Toni I.
Franks, Paul W.
CA Diabetes Prevention Program Res Gr
TI Comprehensive Analysis of Established Dyslipidemia-Associated Loci in
the Diabetes Prevention Program
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE clinical trial; genetics; lifestyle; lipids; lipoproteins; molecular
epidemiology; polymorphism, genetic
ID LOW-DENSITY-LIPOPROTEIN; REACTOME PATHWAY KNOWLEDGEBASE;
CARDIOVASCULAR-DISEASE RISK; CORONARY-ARTERY-DISEASE; BODY-MASS INDEX;
GENETIC-VARIANTS; SATURATED-FAT; LIFE-STYLE; CHOLESTEROL; POPULATION
AB Background-We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial.
Methods and Results-We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at P<0.05 with baseline lipid traits. Trait-specific genetic risk scores were robustly associated (3x10(-4)>P>1.1x10(-16)) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (beta=-0.11 mu mol/L per genetic risk scores risk allele; 95% confidence interval, -0.188 to -0.033; P=5x10(-3); P-interaction=1x10(-3) for lifestyle versus placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-year compared with participants at lower genetic risk at baseline for 17 of the 20 traits.
Conclusions-Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits.
C1 [Varga, Tibor V.; Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Winters, Alexandra H.; Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Winters, Alexandra H.; Pollin, Toni I.] Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA.
[Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Horton, Edward S.; Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Khare-Ranade, Prajakta] Washington Univ, St Louis, MO USA.
[Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Marcovina, Santica M.] Univ Washington, Northwest Lipid Metab & Diabet Res Labs, Seattle, WA 98195 USA.
[Renstrom, Frida] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Watson, Karol E.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Goldberg, Ronald] Univ Miami, Leonard M Miller Sch Med, Div Endocrinol Diabet & Metab, Lipid Disorders Clin,Diabet Res Inst, Coral Gables, FL 33124 USA.
[Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Franks, Paul W.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
RP Franks, PW (reprint author), Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, CRC, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden.
EM Paul.Franks@med.lu.se
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
Office of Research on Minority Health; National Institute of Child
Health and Human Development; National Institute on Aging; Centers for
Disease Control and Prevention; Office of Research on Women's Health;
American Diabetes Association; National Institutes of Health/NIDDK
[R01DK072041]; Swedish Heart-Lung Foundation; Faculty of Medicine at
Umea University; EPiHealth (Lund University)
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health provided funding to the
clinical centers and the Coordinating Center for the design and conduct
of the study, and collection, management, analysis, and interpretation
of the data. The Southwestern American Indian Centers were supported
directly by the NIDDK and the Indian Health Service. The General
Clinical Research Center Program, National Center for Research
Resources, supported data collection at many of the clinical centers.
Funding for data collection and participant support was also provided by
the Office of Research on Minority Health, the National Institute of
Child Health and Human Development, the National Institute on Aging, the
Centers for Disease Control and Prevention, the Office of Research on
Women's Health, and the American Diabetes Association. Bristol-Myers
Squibb and Parke-Davis provided medication. This research was also
supported, in part, by the intramural research program of the NIDDK.
LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed
Care, Merck, Nike Sports Marketing, Slim Fast Foods, and Quaker Oats
donated materials, equipment, or medicines for concomitant conditions.
McKesson BioServices, Matthews Media Group, and the Henry M. Jackson
Foundation provided support services under subcontract with the
Coordinating Center. A complete list of centers, investigators, and
staff is shown in the Acknowledgments. The Diabetes Prevention Program
Genetics Project was supported by National Institutes of Health/NIDDK
grant R01DK072041; additional funding from the Swedish Heart-Lung
Foundation supported the costs of data analysis (for Dr Varga). Part of
the work described in this article was undertaken as part of the 2013 to
2014 BLUE ScY educational exchange program, which was supported by the
Faculty of Medicine at Umea University and EPiHealth (Lund University;
for Dr Varga).
NR 40
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2016
VL 9
IS 6
BP 495
EP +
DI 10.1161/CIRCGENETICS.116.001457
PG 169
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA EH5OZ
UT WOS:000391823900005
PM 27784733
ER
PT J
AU Natarajan, P
Bis, JC
Bielak, LF
Cox, AJ
Dorr, M
Feitosa, MF
Franceschini, N
Guo, X
Hwang, SJ
Isaacs, A
Jhun, MA
Kavousi, M
Li-Gao, R
Lyytikainen, LP
Marioni, RE
Schminke, U
Stitziel, NO
Tada, H
van Setten, J
Smith, AV
Vojinovic, D
Yanek, LR
Yao, J
Yerges-Armstrong, LM
Amin, N
Baber, U
Borecki, IB
Carr, JJ
Chen, YDI
Cupples, LA
de Jong, PA
de Koning, H
de Vos, BD
Demirkan, A
Fuster, V
Franco, OH
Goodarzi, MO
Harris, TB
Heckbert, SR
Heiss, G
Hoffmann, U
Hofman, A
Isgum, I
Jukema, JW
Kahonen, M
Kardia, SLR
Kral, BG
Launer, LJ
Massaro, J
Mehran, R
Mitchell, BD
Jr, THM
de Mutsert, R
Newman, AB
Nguyen, KD
North, KE
O'Connell, JR
Oudkerk, M
Pankow, JS
Peloso, GM
Post, W
Province, MA
Raffield, LM
Raitakari, OT
Reilly, DF
Rivadeneira, F
Rosendaal, F
Sartori, S
Taylor, KD
Teumer, A
Trompet, S
Turner, ST
Uitterlinden, AG
Vaidya, D
van der Lugt, A
Volker, U
Wardlaw, JM
Wassel, CL
Weiss, S
Wojczynski, MK
Becker, DM
Becker, LC
Boerwinkle, E
Bowden, DW
Deary, IJ
Dehghan, A
Felix, SB
Gudnason, V
Lehtimaki, T
Mathias, R
Mook-Kanamori, DO
Psaty, BM
Rader, DJ
Rotter, JI
Wilson, JG
van Duijn, CM
Volzke, H
Kathiresan, S
Peyser, PA
O'Donnell, CJ
AF Natarajan, Pradeep
Bis, Joshua C.
Bielak, Lawrence F.
Cox, Amanda J.
Dorr, Marcus
Feitosa, Mary F.
Franceschini, Nora
Guo, Xiuqing
Hwang, Shih-Jen
Isaacs, Aaron
Jhun, Min A.
Kavousi, Maryam
Li-Gao, Ruifang
Lyytikainen, Leo-Pekka
Marioni, Riccardo E.
Schminke, Ulf
Stitziel, Nathan O.
Tada, Hayato
van Setten, Jessica
Smith, Albert V.
Vojinovic, Dina
Yanek, Lisa R.
Yao, Jie
Yerges-Armstrong, Laura M.
Amin, Najaf
Baber, Usman
Borecki, Ingrid B.
Carr, J. Jeffrey
Chen, Yii-Der Ida
Cupples, L. Adrienne
de Jong, Pim A.
de Koning, Harry
de Vos, Bob D.
Demirkan, Ayse
Fuster, Valentin
Franco, Oscar H.
Goodarzi, Mark O.
Harris, Tamara B.
Heckbert, Susan R.
Heiss, Gerardo
Hoffmann, Udo
Hofman, Albert
Isgum, Ivana
Jukema, J. Wouter
Kahonen, Mika
Kardia, Sharon L. R.
Kral, Brian G.
Launer, Lenore J.
Massaro, Joe
Mehran, Roxana
Mitchell, Braxton D.
Jr, Thomas H. Mosley
de Mutsert, Renee
Newman, Anne B.
Nguyen, Khanh-dung
North, Kari E.
O'Connell, Jeffrey R.
Oudkerk, Matthijs
Pankow, James S.
Peloso, Gina M.
Post, Wendy
Province, Michael A.
Raffield, Laura M.
Raitakari, Olli T.
Reilly, Dermot F.
Rivadeneira, Fernando
Rosendaal, Frits
Sartori, Samantha
Taylor, Kent D.
Teumer, Alexander
Trompet, Stella
Turner, Stephen T.
Uitterlinden, Andre G.
Vaidya, Dhananjay
van der Lugt, Aad
Volker, Uwe
Wardlaw, Joanna M.
Wassel, Christina L.
Weiss, Stefan
Wojczynski, Mary K.
Becker, Diane M.
Becker, Lewis C.
Boerwinkle, Eric
Bowden, Donald W.
Deary, Ian J.
Dehghan, Abbas
Felix, Stephan B.
Gudnason, Vilmundur
Lehtimaki, Terho
Mathias, Rasika
Mook-Kanamori, Dennis O.
Psaty, Bruce M.
Rader, Daniel J.
Rotter, Jerome I.
Wilson, James G.
van Duijn, Cornelia M.
Volzke, Henry
Kathiresan, Sekar
Peyser, Patricia A.
O'Donnell, Christopher J.
CA CHARGE Consortium
TI Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE carotid intima-media thickness; coronary artery calcification; exome;
genome-wide association study; genomics
ID CORONARY-ARTERY CALCIFICATION; INTIMA-MEDIA THICKNESS; HEART-DISEASE
RISK; DEFECTIVE APOLIPOPROTEIN B-100; BEAM COMPUTED-TOMOGRAPHY; OLD
ORDER AMISH; CARDIOVASCULAR RISK; III HYPERLIPOPROTEINEMIA;
MYOCARDIAL-INFARCTION; AORTIC CALCIFICATION
AB Background-The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.
Methods and Results-We studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3x10(-10)). The APOE epsilon 2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1x10(-12)) and 1.4% reduced carotid intima-media thickness (P=4x10(-14)) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the epsilon 2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of epsilon 2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1x10(-11)).
Conclusions-Exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE epsilon 2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.
C1 [Natarajan, Pradeep; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Natarajan, Pradeep; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Natarajan, Pradeep; Peloso, Gina M.; Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA.
[Bielak, Lawrence F.; Jhun, Min A.; Kardia, Sharon L. R.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Cox, Amanda J.; Raffield, Laura M.; Bowden, Donald W.] Wake Forest Hlth Sci, Diabet Heart Study, Winston Salem, NC USA.
[Dorr, Marcus; Felix, Stephan B.] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
[Schminke, Ulf] Univ Med Greifswald, Dept Neurol, Greifswald, Germany.
[Teumer, Alexander; Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Volker, Uwe; Weiss, Stefan] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Dorr, Marcus; Teumer, Alexander; Volker, Uwe; Weiss, Stefan; Felix, Stephan B.; Volzke, Henry] DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
[Feitosa, Mary F.; Stitziel, Nathan O.; Province, Michael A.; Wojczynski, Mary K.] Washington Univ, Sch Med, Dept Genet, Div Stat Genet, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Genet, Div Cardiovasc, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA.
[Franceschini, Nora; Heiss, Gerardo; North, Kari E.] Univ N Carolina, Gilling Sch Global Publ Hlth, Epidemiol, Chapel Hill, NC USA.
[Guo, Xiuqing; Yao, Jie; Chen, Yii-Der Ida; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Guo, Xiuqing; Yao, Jie; Chen, Yii-Der Ida; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Hwang, Shih-Jen] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA.
[Kavousi, Maryam; Vojinovic, Dina; Amin, Najaf; Demirkan, Ayse; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Dehghan, Abbas; van Duijn, Cornelia M.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[van der Lugt, Aad] Univ Med Ctr Rotterdam, Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Dehghan, Abbas] Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
[Isaacs, Aaron] Maastricht Univ, Maastricht Ctr Syst Biol MaCSBio, Maastricht, Netherlands.
[Li-Gao, Ruifang; de Mutsert, Renee; Rosendaal, Frits; Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
[Jukema, J. Wouter; Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, Tampere, Finland.
[Marioni, Riccardo E.; Wardlaw, Joanna M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Marioni, Riccardo E.] Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Wardlaw, Joanna M.] Univ Edinburgh, Div Neuroimaging Sci, Edinburgh, Midlothian, Scotland.
[Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
[Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Tada, Hayato] Kanazawa Univ, Grad Sch Med, Div Cardiovasc Med, Kanazawa, Ishikawa, Japan.
[van Setten, Jessica] Univ Med Ctr Utrecht, Cardiol, Utrecht, Netherlands.
[de Jong, Pim A.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[de Vos, Bob D.; Isgum, Ivana] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands.
[Smith, Albert V.; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Yanek, Lisa R.; Kral, Brian G.; Post, Wendy; Vaidya, Dhananjay; Becker, Diane M.; Becker, Lewis C.; Mathias, Rasika] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Baber, Usman; Fuster, Valentin; Mehran, Roxana; Sartori, Samantha] Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY 10029 USA.
[Borecki, Ingrid B.] Regeneron Pharmaceut Inc, Analyt Genet, Tirrytown, NY USA.
[Carr, J. Jeffrey] Vanderbilt, Radiol, Cardiovasc Med & Biomed Informat, Nashville, TN USA.
[Cupples, L. Adrienne; Massaro, Joe; Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA.
[de Koning, Harry] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res, NIH, Baltimore, MD 21224 USA.
[Jukema, J. Wouter] Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Netherlands Heart Inst, InterUniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Mitchell, Braxton D.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
[Jr, Thomas H. Mosley] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr Med, Jackson, MS 39216 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Nguyen, Khanh-dung] Merck & Co Inc, MRL, Genet & Pharmacogen Dept, Boston, MA USA.
[Reilly, Dermot F.] Merck Sharpe & Dohme Corp, Genet & Pharmacogen Dept, Boston, MA USA.
[Oudkerk, Matthijs] Univ Groningen, Univ Med Ctr Groningen, Ctr Med Imaging North East Netherlands, Groningen, Netherlands.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Netherlands Consortium Hlth Aging, Rotterdam, Netherlands.
[Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Wassel, Christina L.] Univ Vermont, Dept Pathol & Lab Med, Colchester, Essex, England.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Volzke, Henry] German Ctr Diabet Res DZD, Greifswald, Germany.
[O'Donnell, Christopher J.] Boston Vet Affairs Healthcare Syst, Div Cardiol, Boston, MA USA.
RP O'Donnell, CJ (reprint author), Harvard Med Sch, Boston Vet Affairs Healthcare Syst, 1400 Vet Foreign Wars Pkwy,Bldg 1 5B-113, Boston, MA 02132 USA.; Natarajan, P (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Natarajan, P (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
EM pnatarajan@partners.org; odonnellc@nhlbi.nih.gov
RI Fuster, Valentin/H-4319-2015; Feitosa, Mary/K-8044-2012;
OI Fuster, Valentin/0000-0002-9043-9986; Feitosa, Mary/0000-0002-0933-2410;
Carr, John/0000-0002-4398-8237; Mitchell, Braxton/0000-0003-4920-4744;
Vaidya, Dhananjay/0000-0002-7164-1601; Pankow, James/0000-0001-7076-483X
FU John S. LaDue Memorial Fellowship in Cardiology, Harvard Medical School;
NWO VENI grant (VENI) [91616079]; National Heart, Lung, and Blood
Institute [R01HL105756, R01HL120393]; Data Supplement
FX Dr Natarajan is supported by the John S. LaDue Memorial Fellowship in
Cardiology, Harvard Medical School. Dr Kavousi is supported by the NWO
VENI grant (VENI, 91616079). Infrastructure for the CHARGE Consortium
(Cohorts for Heart and Aging Research in Genomic Epidemiology) is
supported in part by the National Heart, Lung, and Blood Institute grant
R01HL105756. Funding support for the CHARGE Consortium Exome Chip
analyses is provided in part by the National Heart, Lung, and Blood
Institute grant R01HL120393. Please refer to the Data Supplement
regarding additional sources of funding.
NR 88
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2016
VL 9
IS 6
BP 511
EP +
DI 10.1161/CIRCGENETICS.116.001572
PG 57
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA EH5OZ
UT WOS:000391823900007
PM 27872105
ER
PT J
AU Clayton, JA
AF Clayton, Janine Austin
TI Sex influences in neurological disorders: case studies and perspectives
SO DIALOGUES IN CLINICAL NEUROSCIENCE
LA English
DT Editorial Material
DE sex difference; gender; brain research; hormone; clinical trial
ID TEMPORAL-LOBE EPILEPSY; PARKINSONS-DISEASE; GENDER-DIFFERENCES;
MULTIPLE-SCLEROSIS; MURINE MODEL; CHROMOSOME COMPLEMENT; PROBABLE
MIGRAINE; NONMOTOR SYMPTOMS; ISCHEMIC-STROKE; NITRIC-OXIDE
AB Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies. Research conducted in these areas so far has shed light on the underlying mechanisms of the disease and offers the promise to help develop more personalized treatments for both men and women. (C) 2016, AICH - Servier Research Group
C1 [Clayton, Janine Austin] NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
RP Clayton, JA (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
EM janine.clayton@nih.gov
FU Office of Research on Women's Health of the National Institutes of
Health
FX This manuscript has not been published elsewhere. There are no conflicts
of interest. The authors alone are responsible for the content and
writing of the paper. This work was funded by the Office of Research on
Women's Health of the National Institutes of Health.
NR 51
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PU INST CONFERENCE HIPPOCRATE
PI SURESNESS-CEDEX
PA 50 RUE CARNOT, SURESNESS-CEDEX, 92284, FRANCE
SN 1294-8322
EI 1958-5969
J9 DIALOGUES CLIN NEURO
JI Dialogues Clin. Neurosci.
PD DEC
PY 2016
VL 18
IS 4
BP 357
EP 360
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA EJ7AQ
UT WOS:000393373600002
PM 28179807
ER
PT J
AU Blanco, C
Wall, MM
Lindquist, MA
Rodriguez-Fernandez, JM
Franco, S
Wang, S
Olfson, M
AF Blanco, Carlos
Wall, Melanie M.
Lindquist, Martin A.
Rodriguez-Fernandez, Jorge Mario
Franco, Silvia
Wang, Shuai
Olfson, Mark
TI Generalizability of Neuroimaging Studies in 5 Common Psychiatric
Disorders Based on the National Epidemiologic Survey on Alcohol and
Related Conditions (NESARC)
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; INTERVIEW SCHEDULE AUDADIS;
GENERAL-POPULATION SAMPLE; MAJOR DEPRESSIVE DISORDER; RESEARCH DOMAIN
CRITERIA; COMMUNITY SAMPLES; MENTAL-DISORDERS; PRECISION MEDICINE;
DIAGNOSTIC MODULES; ANXIETY DISORDERS
AB Objective: Although neuroimaging studies have an important role in psychiatric nosology and treatment development, little is known about the representativeness of participants in neuroimaging research. We estimated the effects of commonly used study eligibility criteria on the representativeness of neuroimaging research participants in relation to the general population with the psychiatric disorders of interest.
Methods: Common eligibility criteria were applied from 112 published neuroimaging studies of DSM-IV nicotine dependence (13 studies), alcohol dependence (12 studies), drug use disorders (13 studies), major depressive disorder (MDD) (37 studies), and posttraumatic stress disorder (PTSD) (36 studies) to representative US samples with these conditions from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093). The analyses were repeated with NESARC respondents with the disorders and substantial psychosocial impairment.
Results: Most NESARC respondents with nicotine dependence (64.1%), alcohol dependence (57.7%), drug use disorders (86.6%), and PTSD (66.9%), though not with MDD (18.2%), would have been excluded by eligibility criteria used in at least half of the relevant neuroimaging studies. Across the diagnostic groups, comorbid psychiatric and general medical conditions resulted in the largest percentages of exclusions. Corresponding analyses limited to respondents with substantial impairment excluded larger percentages with nicotine dependence (77.6%), alcohol dependence (75.8%), drug use disorders (93.5%), and PTSD (76.8%), though not MDD (18.3%).
Conclusions: Neuroimaging studies tend to recruit highly selected samples with the psychiatric disorders of interest that markedly underrepresent individuals with common comorbid conditions. Larger studies with less restrictive eligibility criteria may promote translation of advances in neuroimaging research to populations commonly encountered in clinical practice. (C) Copyright 2016 Physicians Postgraduate Press, Inc.
C1 [Blanco, Carlos] NIDA, Rockville, MD USA.
[Wall, Melanie M.; Rodriguez-Fernandez, Jorge Mario; Franco, Silvia; Wang, Shuai; Olfson, Mark] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA.
[Wall, Melanie M.] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA.
[Lindquist, Martin A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
RP Olfson, M (reprint author), Columbia Univ, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA.
EM mo49@cumc.columbia.edu
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural
Program, NIAAA, National Institutes of Health (NIH); NIH grants
[DA019606, MH076051, MH082773]; Agency for Healthcare Research and
Quality grant [HS02112]; New York State Psychiatric Institute
FX The National Epidemiologic Survey on Alcohol and Related Conditions was
sponsored by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and funded, in part, by the Intramural Program, NIAAA, National
Institutes of Health (NIH). Work on this article was supported by NIH
grants DA019606, MH076051, and MH082773; Agency for Healthcare Research
and Quality grant HS02112; and the New York State Psychiatric Institute
(Drs Blanco, Olfson, and Wall).
NR 56
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PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD DEC
PY 2016
VL 77
IS 12
BP E1618
EP E1625
DI 10.4088/JCP.15m10264
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA EJ2EL
UT WOS:000393022700010
PM 28086006
ER
PT J
AU Korkut, S
Bastug, O
Raygada, M
Hatipoglu, N
Kurtoglu, S
Kendirci, M
Lyssikatos, C
Stratakis, CA
AF Korkut, Sabriye
Bastug, Osman
Raygada, Margarita
Hatipoglu, Nihal
Kurtoglu, Selim
Kendirci, Mustafa
Lyssikatos, Charalampos
Stratakis, Constantine A.
TI Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency in
Two Neonates
SO JOURNAL OF CLINICAL RESEARCH IN PEDIATRIC ENDOCRINOLOGY
LA English
DT Article
DE Deletions; X-chromosome; glycerol kinase; adrenal insufficiency
AB Contiguous gene deletions of chromosome Xp21 can lead to glycerol kinase deficiency and severe adrenocortical insufficiency (AI) in a male newborn among other problems. We describe our experience with two such patients who presented with dysmorphic facies, AI, and pseudo-hypertriglyceridemia. Both infants had normal serum 17-hidroxyprogesterone levels, and adrenal glands could not be observed with ultrasonography. Creatine kinase and triglyceride levels were measured to elucidate the etiology of adrenal hypoplasia and were above normal limits in both cases. Both patients required steroid and salt supplementation. They were both found to have Xp21.2 deletions (DMD, NR0B1, GK, IL1RAPL1). We conclude that AI in the context of other genetic abnormalities should prompt chromosomal investigations in the absence of another unifying explanation.
C1 [Korkut, Sabriye; Bastug, Osman; Kurtoglu, Selim] Erciyes Univ, Fac Med, Dept Pediat, Div Neonatol, Kayseri, Turkey.
[Raygada, Margarita; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Raygada, Margarita; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Endocrinol & Genet, Pediat Endocrinol Interinst Training Program, Bethesda, MD USA.
[Hatipoglu, Nihal; Kurtoglu, Selim; Kendirci, Mustafa] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Endocrinol, Kayseri, Turkey.
[Kendirci, Mustafa] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Metab, Kayseri, Turkey.
RP Korkut, S (reprint author), Erciyes Univ, Fac Med, Dept Pediat, Div Neonatol, Kayseri, Turkey.
EM sabriyeyaman@hotmail.com
NR 11
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PU GALENOS YAYINCILIK
PI FINDIKZADE
PA ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY
SN 1308-5727
EI 1308-5735
J9 J CLIN RES PEDIATR E
JI J. Clin Res. Pediatr. Endocrinol.
PD DEC
PY 2016
VL 8
IS 4
BP 468
EP 471
DI 10.4274/jcrpe.2539
PG 4
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA EJ2LA
UT WOS:000393040300014
PM 27087023
ER
PT J
AU Bansal, S
Chowell, G
Simonsen, L
Vespignani, A
Viboud, C
AF Bansal, Shweta
Chowell, Gerardo
Simonsen, Lone
Vespignani, Alessandro
Viboud, Cecile
TI Big Data for Infectious Disease Surveillance and Modeling
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE big data; infectious diseases; surveillance; disease models;
transmission; social media; Internet search queries; electronic health
records; mobility; adverse events; outbreaks
AB We devote a special issue of the Journal of Infectious Diseases to review the recent advances of big data in strengthening disease surveillance, monitoring medical adverse events, informing transmission models, and tracking patient sentiments and mobility. We consider a broad definition of big data for public health, one encompassing patient information gathered from high-volume electronic health records and participatory surveillance systems, as well as mining of digital traces such as social media, Internet searches, and cell-phone logs. We introduce nine independent contributions to this special issue and highlight several cross-cutting areas that require further research, including representativeness, biases, volatility, and validation, and the need for robust statistical and hypotheses-driven analyses. Overall, we are optimistic that the big-data revolution will vastly improve the granularity and timeliness of available epidemiological information, with hybrid systems augmenting rather than supplanting traditional surveillance systems, and better prospects for accurate infectious diseases models and forecasts.
C1 [Bansal, Shweta; Chowell, Gerardo; Simonsen, Lone; Viboud, Cecile] NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
[Bansal, Shweta] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Simonsen, Lone] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Vespignani, Alessandro] Northeastern Univ, Network Sci Inst, Boston, MA 02115 USA.
RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Bansal, Shweta/0000-0002-1740-5421
FU RAPIDD (Research And Policy for Infectious Diseases Dynamics) Program of
the Science & Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; European
Commission; Lundbeck Foundation; Fogarty International Center; Defense
Threat Reduction Agency [1-0910039]; National Institutes of Health
[MIDAS-U54-GM111274]
FX This work was supported by the RAPIDD (Research And Policy for
Infectious Diseases Dynamics) Program of the Science & Technology
Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health (L. S. and S. B.);
the European Commission (Marie Curie Senior fellowship to L. S.); the
Lundbeck Foundation (visiting professorship grant to L. S.); the
in-house research program of Fogarty International Center (G. C. and C.
V.); the Defense Threat Reduction Agency (grant 1-0910039 to A. V.); and
the National Institutes of Health (grant MIDAS-U54-GM111274 to A. V.).
NR 23
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U1 6
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2016
VL 214
SU 4
BP S375
EP S379
DI 10.1093/infdis/jiw400
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EJ3RW
UT WOS:000393130300001
ER
PT J
AU Chowell, G
Cleaton, JM
Viboud, C
AF Chowell, Gerardo
Cleaton, Julie M.
Viboud, Cecile
TI Elucidating Transmission Patterns From Internet Reports: Ebola and
Middle East Respiratory Syndrome as Case Studies
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE transmission chain; cluster; Internet data stream; big data;
transmission patterns; exposure setting; contact network; reproduction
number; Ebola; MERS
ID VIRUS DISEASE EVD; SYNDROME CORONAVIRUS; PUBLIC-HEALTH;
HEMORRHAGIC-FEVER; RISK-FACTORS; DYNAMICS; OUTBREAK; SURVEILLANCE;
MODELS; UGANDA
AB The paucity of traditional epidemiological data during epidemic emergencies calls for alternative data streams to characterize the key features of an outbreak, including the nature of risky exposures, the reproduction number, and transmission heterogeneities. We illustrate the potential of Internet data streams to improve preparedness and response in outbreak situations by drawing from recent work on the 2014-2015 Ebola epidemic in West Africa and the 2015 Middle East respiratory syndrome (MERS) outbreak in South Korea. We show that Internet reports providing detailed accounts of epidemiological clusters are particularly useful to characterize time trends in the reproduction number. Moreover, exposure patterns based on Internet reports align with those derived from epidemiological surveillance data on MERS and Ebola, underscoring the importance of disease amplification in hospitals and during funeral rituals (associated with Ebola), prior to the implementation of control interventions. Finally, we discuss future developments needed to generalize Internet-based approaches to study transmission dynamics.
C1 [Chowell, Gerardo; Cleaton, Julie M.] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Chowell, G (reprint author), Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
EM gchowell@gsu.edu
FU Division of International Epidemiology and Population Studies, Fogarty
International Center, National Institutes of Health (NIH); RAPIDD
Program, Science and Technology Directorate, Department of Homeland
Security; National Science Foundation (NDF) [1414374]; United Kingdom
Biotechnology and Biological Sciences Research Council [BB/M008894/1]
FX This work was supported by the Division of International Epidemiology
and Population Studies, Fogarty International Center, National
Institutes of Health (NIH; support to G. C. and C. V.); the RAPIDD
Program, Science and Technology Directorate, Department of Homeland
Security (support to G. C. and C. V.); the National Science Foundation
(NDF; grant 1414374 to G. C.), as part of the joint NSF-NIH-US
Department of Agriculture Ecology and Evolution of Infectious Diseases
program; and the United Kingdom Biotechnology and Biological Sciences
Research Council (grant BB/M008894/1).
NR 42
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U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2016
VL 214
SU 4
BP S421
EP S426
DI 10.1093/infdis/jiw356
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EJ3RW
UT WOS:000393130300009
ER
PT J
AU Lee, EC
Asher, JM
Goldlust, S
Kraemer, JD
Lawson, AB
Bansal, S
AF Lee, Elizabeth C.
Asher, Jason M.
Goldlust, Sandra
Kraemer, John D.
Lawson, Andrew B.
Bansal, Shweta
TI Mind the Scales: Harnessing Spatial Big Data for Infectious Disease
Surveillance and Inference
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE spatial big data; spatial epidemiology; disease mapping; infectious
diseases; digital epidemiology; statistical bias
AB Spatial big data have the velocity, volume, and variety of big data sources and contain additional geographic information. Digital data sources, such as medical claims, mobile phone call data records, and geographically tagged tweets, have entered infectious diseases epidemiology as novel sources of data to complement traditional infectious disease surveillance. In this work, we provide examples of how spatial big data have been used thus far in epidemiological analyses and describe opportunities for these sources to improve disease-mitigation strategies and public health coordination. In addition, we consider the technical, practical, and ethical challenges with the use of spatial big data in infectious disease surveillance and inference. Finally, we discuss the implications of the rising use of spatial big data in epidemiology to health risk communication, and public health policy recommendations and coordination across scales.
C1 [Lee, Elizabeth C.; Goldlust, Sandra; Bansal, Shweta] Georgetown Univ, Dept Biol, 408 Reiss Sci Bldg, Washington, DC 20057 USA.
[Kraemer, John D.] Georgetown Univ, Dept Hlth Syst Adm, Washington, DC USA.
[Asher, Jason M.] Leidos, Washington, DC USA.
[Lawson, Andrew B.] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC USA.
[Bansal, Shweta] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Bansal, S (reprint author), Georgetown Univ, Dept Biol, 408 Reiss Sci Bldg, Washington, DC 20057 USA.
EM shweta.bansal@georgetown.edu
OI Lee, Elizabeth/0000-0002-4156-9637; Bansal, Shweta/0000-0002-1740-5421
FU Jayne Koskinas Ted Giovanis Foundation for Health and Policy; National
Cancer Institute [R01CA172805]; RAPIDD Program of the Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX This work was supported by the Jayne Koskinas Ted Giovanis Foundation
for Health and Policy (dissertation support grant to E. C. L.); the
National Cancer Institute (grant R01CA172805 to A. B. L.); and the
RAPIDD Program of the Science & Technology Directorate, Department of
Homeland Security and the Fogarty International Center, National
Institutes of Health.
NR 31
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U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2016
VL 214
SU 4
BP S409
EP S413
DI 10.1093/infdis/jiw344
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EJ3RW
UT WOS:000393130300007
ER
PT J
AU Jenkins, DE
Sreenivasan, D
Carman, F
Samal, B
Eiden, LE
Bunn, SJ
AF Jenkins, Danielle E.
Sreenivasan, Dharshini
Carman, Fiona
Samal, Babru
Eiden, Lee E.
Bunn, Stephen J.
TI Interleukin-6-mediated signaling in adrenal medullary chromaffin cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE chromaffin cell; cytokine; inflammation; interleukin-6; STAT3; tyrosine
hydroxylase
ID TUMOR-NECROSIS-FACTOR; NEUROPEPTIDE GENE-EXPRESSION; HORMONE-RELATED
PROTEIN; TYROSINE-HYDROXYLASE; CATECHOLAMINE RELEASE; GLUCOCORTICOID
SECRETION; ADRENOCHROMAFFIN CELLS; TRANSCRIPTION FACTORS;
ADRENOCORTICAL-CELLS; CA2+ CHANNELS
AB The pro-inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-1 beta/alpha modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Since interleukin-6 (IL6) also plays a key integrative role during inflammation, we have examined its ability to affect both tyrosine hydroxylase activity and adrenomedullary gene transcription in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). Consistent with ERK1/2 activation, IL6 rapidly increased tyrosine hydroxylase phosphorylation (serine-31) and activity, as well as up-regulated genes, encoding secreted proteins including galanin, vasoactive intestinal peptide, gastrin-releasing peptide, and parathyroid hormone-like hormone. The effects of IL6 on the entire bovine chromaffin cell transcriptome were compared to those generated by G-protein-coupled receptor (GPCR) agonists (histamine and pituitary adenylate cyclase-activating polypeptide) and the cytokine receptor agonists (interferon-a and tumor necrosis factor-a). Of 90 genes up-regulated by IL6, only 16 are known targets of IL6 in the immune system. Those remaining likely represent a combination of novel IL6/STAT3 targets, ERK1/2 targets and, potentially, IL6-dependent genes activated by IL6-induced transcription factors, such as hypoxia-inducible factor 1 alpha. Notably, genes induced by IL6 include both neuroen-docrine-specific genes activated by GPCR agonists, and transcripts also activated by the cytokines. These results suggest an integrative role for IL6 in the fine-tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge.
C1 [Jenkins, Danielle E.; Carman, Fiona; Bunn, Stephen J.] Univ Otago, Otago Sch Med Sci, Ctr Neuroendocrinol, Dept Anat, POB 913, Dunedin, New Zealand.
[Sreenivasan, Dharshini] Univ Auckland, Auckland Bioengn Inst, Auckland, New Zealand.
[Samal, Babru; Eiden, Lee E.] NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Bunn, SJ (reprint author), Univ Otago, Otago Sch Med Sci, Ctr Neuroendocrinol, Dept Anat, POB 913, Dunedin, New Zealand.
EM stephen.bunn@anatomy.otago.ac.nz
FU NIMH Intramural Research Program [Z01 MH002386-21]; University of Otago
Research Grant
FX We thank Chang-Mei Hsu and Shirley Douglas for their expert technical
assistance in preparation of adrenal medullary cell cultures, RNA for
microarray, and qRT-PCR analysis. Djida Ait-Ali is thanked for
substantive intellectual and technical contributions to this project,
which cannot be acknowledged by authorship solely because she could not
be contacted and therefore her assent to authorship could not be
obtained. This work was supported by NIMH Intramural Research Program
Project Z01 MH002386-21 and a University of Otago Research Grant. The
authors declare no conflicts of interest.
NR 78
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2016
VL 139
IS 6
BP 1138
EP 1150
DI 10.1111/jnc.13870
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA EJ2KK
UT WOS:000393038700015
PM 27770433
ER
PT J
AU Feng, LR
Dickinson, K
Kline, N
Saligan, LN
AF Feng, Li Rebekah
Dickinson, Kristin
Kline, Neila
Saligan, Leorey N.
TI Different Phenotyping Approaches Lead to Dissimilar Biologic Profiles in
Men With Chronic Fatigue After Radiation Therapy
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Cancer-related fatigue; radiation therapy; prostate cancer;
transcriptome profiles; fatigue phenotypes
ID CANCER-RELATED FATIGUE; NEUROPATHIC PAIN; FUNCTIONAL ASSESSMENT; SYSTEM;
POPULATION; BIOGENESIS; DIAGNOSIS; DEPRESSION; EXOSOMES; ANEMIA
AB Context. Cancer-related fatigue (CRF) persists months after treatment completion. Although a CRF biomarker has not yet been identified, validated self-report questionnaires are used to define and phenotype CRF in the discovery of potential biomarkers.
Objectives. The purposes of this study are to identify CRF subjects using three well-known CRF phenotyping approaches using validated self-report questionnaires and to compare the biologic profiles that are associated with each CRF phenotype.
Methods. Fatigue in men with nonmetastatic prostate cancer receiving external beam radiation therapy was measured at baseline (T1), midpoint (T2), end point (T3), and one-year post-external beam radiation therapy (T4) using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and Patient Reported Outcomes Measurement Information System-Fatigue. Chronic fatigue (CF) and nonfatigue subjects were grouped based on three commonly used phenotyping approaches: 1) T4 FACTF < 43; 2) T1-T4 decline in FACT-F score >= 3 points; 3) T4 Patient Reported Outcomes Measurement Information System-Fatigue T-score > 50. Differential gene expressions using whole-genome microarray analysis were compared in each of the phenotyping criterion.
Results. The study enrolled 43 men, where 34% -38% had CF based on the three phenotyping approaches. Distinct gene expression patterns were observed between CF and nonfatigue subjects in each of the three CRF phenotyping approaches: 1) Approach 1 had the largest number of differentially expressed genes and 2) Approaches 2 and 3 had 40 and 21 differentially expressed genes between the fatigue groups, respectively.
Conclusion. The variation in genetic profiles for CRF suggests that phenotypic profiling for CRF should be carefully considered because it directly influences biomarker discovery investigations. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine.
C1 [Feng, Li Rebekah; Dickinson, Kristin; Saligan, Leorey N.] NINR, NIH, 9000 Rockville Pike,Bldg 3, Bethesda, MD 20892 USA.
[Kline, Neila] Vassar Coll, Poughkeepsie, NY 12601 USA.
RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 3, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
OI Saligan, Leorey/0000-0001-9481-7836
FU Division of Intramural Research, National Institute of Nursing Research,
National Institutes of Health
FX This study is fully supported by the Division of Intramural Research,
National Institute of Nursing Research, National Institutes of Health.
NR 36
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD DEC
PY 2016
VL 52
IS 6
BP 832
EP 840
DI 10.1016/j.jpainsymman.2016.07.007
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA EJ4KE
UT WOS:000393184800320
PM 27521284
ER
PT J
AU Berger, A
Sloan, DH
AF Berger, Ann
Sloan, Danetta Hendricks
TI Development of an instrument to Assess Psycho-social Spiritual Healing:
The NIH HEALS
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
C1 [Berger, Ann; Sloan, Danetta Hendricks] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD DEC
PY 2016
VL 52
IS 6
MA B11-A
BP E21
EP E22
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA EJ4KE
UT WOS:000393184800037
ER
PT J
AU Sloan, D
Berger, A
AF Sloan, Danetta
Berger, Ann
TI Development of the HEALS: Healing Experience in All Life Stressors
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
C1 [Sloan, Danetta; Berger, Ann] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD DEC
PY 2016
VL 52
IS 6
MA P295
BP E144
EP E144
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA EJ4KE
UT WOS:000393184800285
ER
PT J
AU Weaver, M
October, T
Hinds, P
AF Weaver, Meaghann
October, Tessie
Hinds, Pamela
TI Incorporating Good Patient, Parent, and Provider Definitions to Improve
Care Interactions and Psychosocial Outcomes for Children with Cancer,
Their Families, and Their Care Teams
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
C1 [Weaver, Meaghann] NIH, Bldg 10, Bethesda, MD 20892 USA.
[October, Tessie; Hinds, Pamela] Childrens Natl Hlth Syst, Washington, DC USA.
NR 0
TC 0
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD DEC
PY 2016
VL 52
IS 6
MA D03-A
BP E30
EP E31
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA EJ4KE
UT WOS:000393184800054
ER
PT J
AU Kubota, Y
London, SJ
Cushman, M
Chamberlain, AM
Rosamond, WD
Heckbert, SR
Zakai, N
Folsom, AR
AF Kubota, Y.
London, S. J.
Cushman, M.
Chamberlain, A. M.
Rosamond, W. D.
Heckbert, S. R.
Zakai, N.
Folsom, A. R.
TI Lung function, respiratory symptoms and venous thromboembolism risk: the
Atherosclerosis Risk in Communities Study
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE chronic obstructive pulmonary disease; lung function; respiratory
symptoms; restrictive lung disease; venous thromboembolism
ID OBSTRUCTIVE PULMONARY-DISEASE; CORONARY-HEART-DISEASE;
CARDIOVASCULAR-DISEASE; AIRWAY-OBSTRUCTION; COPD; POPULATION; MORTALITY;
EXACERBATIONS; EPIDEMIOLOGY; ASSOCIATIONS
AB Background: The evidence for the association between chronic obstructive pulmonary disease (COPD) and venous thromboembolism (VTE) is limited. There is no study investigating the association between restrictive lung disease (RLD) and respiratory symptoms with VTE. Objectives: To investigate prospectively the association of lung function and respiratory symptoms with VTE. Patients/Methods: In 1987-1989, we assessed lung function by using spirometry, and obtained information on respiratory symptoms (cough, phlegm, and dyspnea) in 14 654 participants aged 45-64 years, without a history of VTE or anticoagulant use, and followed them through 2011. Participants were classified into four mutually exclusive groups: 'COPD' (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] below the lower limit of normal [LLN]), 'RLD' (FEV1/FVC >= LLN and FVC < LLN), `respiratory symptoms with normal spirometic results' (without RLD or COPD), and 'normal' (without respiratory symptoms, RLD, or COPD). Results: We documented 639 VTEs (238 unprovoked and 401 provoked VTEs). After adjustment for VTE risk factors, VTE risk was increased for individuals with either respiratory symptoms with normal spirometric results (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12-1.73) or COPD (HR 1.33, 95% CI 1.07-1.67) but not for those with RLD (HR 1.15, 95% CI 0.82-1.60). These elevated risks of VTE were derived from both unprovoked and provoked VTE. Moreover, FEV1 and FEV1/FVC showed dose-response relationships with VTE. COPD was more strongly associated with pulmonary embolism than with deep vein thrombosis. Conclusions: Obstructive spirometric patterns were associated with an increased risk of VTE, suggesting that COPD may increase the risk of VTE. Respiratory symptoms may represent a novel risk marker for VTE.
C1 [Kubota, Y.; Folsom, A. R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 South 2nd St,Suite 300, Minneapolis, MN 55454 USA.
[Kubota, Y.] Osaka Univ, Grad Sch Med, Publ Hlth, Dept Social Med, Osaka, Japan.
[London, S. J.] NIEHS, US Dept HHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Cushman, M.; Zakai, N.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Cushman, M.; Zakai, N.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Chamberlain, A. M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Rosamond, W. D.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Heckbert, S. R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Folsom, AR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 South 2nd St,Suite 300, Minneapolis, MN 55454 USA.
EM folso001@umn.edu
OI London, Stephanie/0000-0003-4911-5290
FU Nippon Foundation; National Institute of Environmental Health Sciences
(NIH). National Heart, Lung, and Blood Institute (NHLBI) [R01-HL0597367,
HHSN268201100005C, HHSN26820 1100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268
201100011C, HHSN268201100012C]
FX The authors thank the staff and participants of the ARIC Study for their
important contributions. Y. Kubota's fellowship at the School of Public
Health, University of Minnesota is supported by grants from the Nippon
Foundation. S. J. London is supported by the Intramural Research Program
of the National Institute of Environmental Health Sciences (NIH).
National Heart, Lung, and Blood Institute (NHLBI) support: R01-HL0597367
and contracts HHSN268201100005C, HHSN26820 1100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268
201100011C, and HHSN268201100012C.
NR 35
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD DEC
PY 2016
VL 14
IS 12
BP 2394
EP 2401
DI 10.1111/jth.13525
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA EJ2OX
UT WOS:000393051000011
PM 27696765
ER
PT J
AU Poston, L
Caleyachetty, R
Cnattingius, S
Corvalan, C
Uauy, R
Herring, S
Gillman, MW
AF Poston, Lucilla
Caleyachetty, Rishi
Cnattingius, Sven
Corvalan, Camila
Uauy, Ricardo
Herring, Sharron
Gillman, Matthew W.
TI Preconceptional and maternal obesity: epidemiology and health
consequences
SO LANCET DIABETES & ENDOCRINOLOGY
LA English
DT Article
ID BODY-MASS INDEX; MIDDLE-INCOME COUNTRIES; GESTATIONAL DIABETES-MELLITUS;
INTERPREGNANCY WEIGHT CHANGE; ADVERSE PREGNANCY OUTCOMES; INDEPENDENT
RISK-FACTOR; LOW-BIRTH-WEIGHT; CESAREAN DELIVERY; UNITED-STATES;
PREPREGNANCY WEIGHT
AB Obesity in women of reproductive age is increasing in prevelance worldwide. Obesity reduces fertility and increases time taken to conceive, and obesity-related comorbidities (such as type 2 diabetes and chronic hypertension) heighten the risk of adverse outcomes for mother and child if the woman becomes pregnant. Pregnant women who are obese are more likely to have early pregnancy loss, and have increased risk of congenital fetal malformations, delivery of large for gestational age infants, shoulder dystocia, spontaneous and medically indicated premature birth, and stillbirth. Late pregnancy complications include gestational diabetes and pre-eclampsia, both of which are associated with long-term morbidities post partum. Women with obesity can also experience difficulties during labour and delivery, and are more at risk of post-partum haemorrhage. Long-term health risks are associated with weight retention after delivery, and inherent complications for the next pregnancy. The wellbeing of the next generation is also compromised. All these health issues could be avoided by prevention of obesity among women of reproductive age, which should be viewed as a global public health priority. For women who are already obese, renewed efforts should be made towards improved management during pregnancy, especially of blood glucose, and increased attention to postpartum weight management. Effective interventions, tailored to ethnicity and culture, are needed at each of these stages to improve the health of women and their children in the context of the global obesity epidemic.
C1 [Poston, Lucilla] Kings Coll London, Fac Life Sci & Med, Div Womens Hlth, London, England.
[Caleyachetty, Rishi] Univ Birmingham, Inst Appl Hlth Res, Birmingham, W Midlands, England.
[Cnattingius, Sven] Karolinska Univ Sjukhuset, Dept Med Solna, Stockholm, Sweden.
[Corvalan, Camila] Univ Chile, Inst Nutr & Food Technol, Santiago, Chile.
[Uauy, Ricardo] Pontificia Univ Catolica Chile, Div Pediat, Fac Med, Santiago, Chile.
[Uauy, Ricardo; Herring, Sharron] Temple Univ, Ctr Obes Res & Educ, Dept Med, Philadelphia, PA 19122 USA.
[Uauy, Ricardo; Herring, Sharron] Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA.
[Gillman, Matthew W.] NIH, Off Director, Environm Influences Child Hlth Outcomes ECHO, Rockville, MD USA.
RP Poston, L (reprint author), St Thomas Hosp, KCL Div Womens Hlth, London SE1 7EH, England.
EM lucilla.poston@kcl.ac.uk
FU US National Institutes of Health; Doris Duke Charitable Foundation;
Health Resources and Services Administration
FX LP reports grants from Abbott Nutrition and NESTEC, outside the
submitted work. SH reports grants from the US National Institutes of
Health, Doris Duke Charitable Foundation, and Health Resources and
Services Administration during the conduct of the study.
NR 119
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U1 8
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2213-8587
J9 LANCET DIABETES ENDO
JI Lancet Diabetes Endocrinol.
PD DEC
PY 2016
VL 4
IS 12
BP 1025
EP 1036
DI 10.1016/S2213-8587(16)30217-0
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EJ2FO
UT WOS:000393025700029
PM 27743975
ER
PT J
AU Pettifor, A
MacPhail, C
Hughes, JP
Selin, A
Wang, J
Gomez-Olive, FX
Eshleman, SH
Wagner, RG
Mabuza, W
Khoza, N
Suchindran, C
Mokoena, I
Twine, R
Andrew, P
Townley, E
Laeyendecker, O
Agyei, Y
Tollman, S
Kahn, K
AF Pettifor, Audrey
MacPhail, Catherine
Hughes, James P.
Selin, Amanda
Wang, Jing
Gomez-Olive, F. Xavier
Eshleman, Susan H.
Wagner, Ryan G.
Mabuza, Wonderful
Khoza, Nomhle
Suchindran, Chirayath
Mokoena, Immitrude
Twine, Rhian
Andrew, Philip
Townley, Ellen
Laeyendecker, Oliver
Agyei, Yaw
Tollman, Stephen
Kahn, Kathleen
TI The effect of a conditional cash transfer on HIV incidence in young
women in rural South Africa (HPTN 068): a phase 3, randomised controlled
trial
SO LANCET GLOBAL HEALTH
LA English
DT Article
ID TRANSACTIONAL SEX; PREVALENCE; INFECTION; RISK; ASSOCIATION; HEALTH
AB Background Cash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa. However, scarce evidence is available about their effect on reducing HIV acquisition. We aimed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa.
Methods We did a phase 3, randomised controlled trial (HPTN 068) in the rural Bushbuckridge subdistrict in Mpumalanga province, South Africa. We included girls aged 13-20 years if they were enrolled in school grades 8-11, not married or pregnant, able to read, they and their parent or guardian both had the necessary documentation necessary to open a bank account, and were residing in the study area and intending to remain until trial completion. Young women (and their parents or guardians) were randomly assigned (1:1), by use of numbered sealed envelopes containing a randomisation assignment card which were numerically ordered with block randomisation, to receive a monthly cash transfer conditional on school attendance (>= 80% of school days per month) versus no cash transfer. Participants completed an Audio Computer-Assisted Self-Interview (ACASI), before test HIV counselling, HIV and herpes simplex virus (HSV)-2 testing, and post-test counselling at baseline, then at annual follow-up visits at 12, 24, and 36 months. Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit. A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome, HIV incidence, to compare the intervention and control groups. This study is registered at ClinicalTrials. gov (NCT01233531).
Findings Between March 5, 2011, and Dec 17, 2012, we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme (n=1225) or not (control group; n=1223). At baseline, the median age of girls was 15 years (IQR 14-17) and 672 (27%) had reported to have ever had sex. 107 incident HIV infections were recorded during the study: 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group. HIV incidence was not significantly different between those who received a cash transfer (1.94% per person-years) and those who did not (1.70% per person-years; hazard ratio 1.17, 95% CI 0.80-1.72, p=0.42).
Interpretation Cash transfers conditional on school attendance did not reduce HIV incidence in young women. School attendance significantly reduced risk of HIV acquisition, irrespective of study group. Keeping girls in school is important to reduce their HIV-infection risk.
C1 [Pettifor, Audrey] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Pettifor, Audrey; Selin, Amanda; Suchindran, Chirayath] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Suchindran, Chirayath] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Pettifor, Audrey; MacPhail, Catherine; Gomez-Olive, F. Xavier; Wagner, Ryan G.; Mabuza, Wonderful; Mokoena, Immitrude; Twine, Rhian; Tollman, Stephen; Kahn, Kathleen] Univ Witwatersrand, Med Res Council Wits Rural Publ Hlth & Hlth Trans, Sch Publ Hlth, Fac Hlth Sci, Johannesburg, South Africa.
[Pettifor, Audrey; MacPhail, Catherine; Khoza, Nomhle] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
[MacPhail, Catherine] Univ New England, Sch Hlth, Armidale, NSW, Australia.
[Hughes, James P.; Wang, Jing] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Hughes, James P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Eshleman, Susan H.; Agyei, Yaw] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Laeyendecker, Oliver] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Laeyendecker, Oliver] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Andrew, Philip] FHI 360, Durham, NC USA.
[Townley, Ellen] NIAID, Div AIDS Henry M Jackson Fdn, NIH, Baltimore, MD USA.
[Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Baltimore, MD USA.
[Wagner, Ryan G.; Tollman, Stephen; Kahn, Kathleen] Umea Ctr Global Hlth Res, Umea, Sweden.
[Wagner, Ryan G.; Tollman, Stephen; Kahn, Kathleen] INDEPTH Network, Accra, Ghana.
RP Pettifor, A (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
EM apettif@email.unc.edu
FU National Institute of Allergy and Infectious Diseases, National
Institute of Mental Health of the National Institutes of Health
FX National Institute of Allergy and Infectious Diseases, National
Institute of Mental Health of the National Institutes of Health.
NR 31
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Z9 2
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD DEC
PY 2016
VL 4
IS 12
BP E978
EP E988
DI 10.1016/S2214-109X(16)30253-4
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EJ2FV
UT WOS:000393026400031
PM 27815148
ER
PT J
AU Meissner, EG
McLaughlin, M
Matthews, L
Gharib, AM
Wood, BJ
Levy, E
Sinkus, R
Virtaneva, K
Sturdevant, D
Martens, C
Porcella, SF
Goodman, ZD
Kanwar, B
Myers, RP
Subramanian, M
Hadigan, C
Masur, H
Kleiner, DE
Heller, T
Kottilil, S
Kovacs, JA
Morse, CG
AF Meissner, Eric G.
McLaughlin, Mary
Matthews, Lindsay
Gharib, Ahmed M.
Wood, Bradford J.
Levy, Elliot
Sinkus, Ralph
Virtaneva, Kimmo
Sturdevant, Dan
Martens, Craig
Porcella, Stephen F.
Goodman, Zachary D.
Kanwar, Bittoo
Myers, Robert P.
Subramanian, Mani
Hadigan, Colleen
Masur, Henry
Kleiner, David E.
Heller, Theo
Kottilil, Shyam
Kovacs, Joseph A.
Morse, Caryn G.
TI Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected
adults: results of a 6-month open-label safety trial
SO LIVER INTERNATIONAL
LA English
DT Article
DE hepatic venous pressure gradient; lysyl oxidases; magnetic resonance
elastography; transforming growth factor beta-3
ID HEPATITIS-C VIRUS; MAGNETIC-RESONANCE ELASTOGRAPHY; SIMPLE NONINVASIVE
INDEX; OXIDASE-LIKE 2; LYSYL OXIDASE; NONALCOHOLIC STEATOHEPATITIS;
CIRRHOSIS; DISEASE; THERAPY; MICROENVIRONMENT
AB Background: Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. Aim: The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease. Methods: Eighteen subjects with advanced liver fibrosis received simtuzumab 700 mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis. Results: Treatment was well-tolerated with no discontinuations due to adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-beta 3 and IL-10 pathways with treatment. Conclusion: In this open-label, pilot clinical trial, simtuzumab treatment was well-tolerated in HCV- and HIV-infected subjects with advanced liver disease. Putative modulation of TGF-beta 3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.
C1 [Meissner, Eric G.; McLaughlin, Mary; Hadigan, Colleen; Kottilil, Shyam] NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA.
[Meissner, Eric G.] Med Univ South Carolina, Dept Microbiol & Immunol, Div Infect Dis, Charleston, SC 29425 USA.
[Meissner, Eric G.; Matthews, Lindsay; Masur, Henry; Kovacs, Joseph A.; Morse, Caryn G.] NIH, Ctr Clin, Dept Crit Care Med, AIDS Sect, Bethesda, MD 20892 USA.
[Gharib, Ahmed M.] NIDDK, Biomed & Metab Imaging Branch, Bethesda, MD 20892 USA.
[Wood, Bradford J.; Levy, Elliot] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Sinkus, Ralph] Kings Coll London, Biomed Engn Imaging Sci & Biomed Engn Div, London, England.
[Virtaneva, Kimmo; Sturdevant, Dan; Martens, Craig; Porcella, Stephen F.] NIAID, Rocky Mt Lab, Genom Unit, Res Technol Sect, Hamilton, MT 59840 USA.
[Goodman, Zachary D.] Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA.
[Kanwar, Bittoo; Myers, Robert P.; Subramanian, Mani] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
[Kleiner, David E.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Heller, Theo] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA.
RP Morse, CG (reprint author), NIH, Ctr Clin, Bldg 10,2C145, Bethesda, MD 20892 USA.
EM cmorse@cc.nih.gov
OI Morse, Caryn/0000-0002-1177-4365
FU United States National Institutes of Health (NIH) Intramural Research
Program; NIH Bench to Bedside Award - Office of AIDS Research; National
Cancer Institute [HHSN261200800001E]; NIH; Gilead Sciences; NIH Clinical
Center, NIAID; NIDDK
FX Supported by the United States National Institutes of Health (NIH)
Intramural Research Program, NIH Clinical Center, NIAID, NIDDK and, in
part, by an NIH Bench to Bedside Award funded by the Office of AIDS
Research. Funded in part with federal funds from the National Cancer
Institute, under contract HHSN261200800001E. This study was partially
funded by a Collaborative Research and Development Agreement between NIH
and Gilead Sciences.
NR 33
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1478-3223
EI 1478-3231
J9 LIVER INT
JI Liver Int.
PD DEC
PY 2016
VL 36
IS 12
BP 1783
EP 1792
DI 10.1111/liv.13177
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EJ3HS
UT WOS:000393103800010
PM 27232579
ER
PT J
AU Bao, R
Liu, Y
Savarino, SJ
Xia, D
AF Bao, Rui
Liu, Yang
Savarino, Stephen J.
Xia, Di
TI Off-pathway assembly of fimbria subunits is prevented by chaperone CfaA
of CFA/I fimbriae from enterotoxigenic E. coli
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID UROPATHOGENIC ESCHERICHIA-COLI; FACTOR ANTIGEN-I; PILUS BIOGENESIS;
STRUCTURAL BASIS; FOLDING ENERGY; USHER PATHWAY; PROTEIN; RECOGNITION;
MECHANISM; BACTERIA
AB The assembly of the class 5 colonization factor antigen I (CFA/I) fimbriae of enterotoxigenic E. coli was proposed to proceed via the alternate chaperoneusher pathway. Here, we show that in the absence of the chaperone CfaA, CfaB, the major pilin subunit of CFA/I fimbriae, is able to spontaneously refold and polymerize into cyclic trimers. CfaA kinetically traps CfaB to form a metastable complex that can be stabilized by mutations. Crystal structure of the stabilized complex reveals distinctive interactions provided by CfaA to trap CfaB in an assembly competent state through donor-strand complementation (DSC) and cleft-mediated anchorage. Mutagenesis indicated that DSC controls the stability of the chaperonesubunit complex and the cleft-mediated anchorage of the subunit C-terminus additionally assist in subunit refolding. Surprisingly, over-stabilization of the chaperone-subunit complex led to delayed fimbria assembly, whereas destabilizing the complex resulted in no fimbriation. Thus, CfaA acts predominantly as a kinetic trap by stabilizing subunit to avoid its off-pathway self-polymerization that results in energetically favorable trimers and could serve as a driving force for CFA/I pilus assembly, representing an energetic landscape unique to class 5 fimbria assembly.
C1 [Bao, Rui] Sichuan Univ, Div Infect Dis, Collaborat Innovat Ctr Biotherapy, Natl Key Lab Biotherapy,West China Hosp, Chengdu 610041, Peoples R China.
[Bao, Rui; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Yang; Savarino, Stephen J.] Naval Med Res Ctr, Enter Dis Dept, Infect Dis Directorate, Silver Spring, MD 20910 USA.
[Savarino, Stephen J.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM xiad@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Trans NIH/FDA Intramural Biodefense Program;
National Natural Science Foundation of China [81501787]; U.S. Army
Military Infectious Diseases Research Program Work Unit [A0307]; Henry
M. Jackson Foundation for the Advancement of Military Medicine
FX The authors wish to thank the beam line staff of the SER-CAT at APS, ANL
for assistance in data collection and George Leiman for editorial
assistance. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research and by a grant from the Trans NIH/FDA Intramural
Biodefense Program (to D.X.) and by the National Natural Science
Foundation of China (Programs 81501787 to R.B.). The research was also
supported by the U.S. Army Military Infectious Diseases Research Program
Work Unit Number A0307 (to S.J.S.), and by the Henry M. Jackson
Foundation for the Advancement of Military Medicine (S.J.S.).
NR 40
TC 0
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD DEC
PY 2016
VL 102
IS 6
BP 975
EP 991
DI 10.1111/mmi.13530
PG 17
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA EJ3XK
UT WOS:000393145300002
PM 27627030
ER
PT J
AU Norris, SA
Jinnah, HA
Espay, AJ
Klein, C
Bruggemann, N
Barbano, RL
Malaty, IAC
Rodriguez, RL
Vidailhet, M
Roze, E
Reich, SG
Berman, BD
LeDoux, MS
Richardson, SP
Agarwal, P
Mari, Z
Ondo, WG
Shih, LC
Fox, SH
Berardelli, A
Testa, CM
Cheng, FCF
Truong, D
Nahab, FB
Xie, T
Hallett, M
Rosen, AR
Wright, LJ
Perlmutter, JS
AF Norris, Scott A.
Jinnah, H. A.
Espay, Alberto J.
Klein, Christine
Brueggemann, Norbert
Barbano, Richard L.
Malaty, Irene Andonia C.
Rodriguez, Ramon L.
Vidailhet, Marie
Roze, Emmanuel
Reich, Stephen G.
Berman, Brian D.
LeDoux, Mark S.
Richardson, Sarah Pirio
Agarwal, Pinky
Mari, Zoltan
Ondo, William G.
Shih, Ludy C.
Fox, Susan H.
Berardelli, Alfredo
Testa, Claudia M.
Cheng, Florence Ching-Fen
Truong, Daniel
Nahab, Fatta B.
Xie, Tao
Hallett, Mark
Rosen, Ami R.
Wright, Laura J.
Perlmutter, Joel S.
TI Clinical and Demographic Characteristics Related to Onset Site and
Spread of Cervical Dystonia
SO MOVEMENT DISORDERS
LA English
DT Article
DE spasmodic torticollis; focal; segmental; geste antagoniste; neck
ID IDIOPATHIC TORSION DYSTONIA; MOVEMENT-DISORDERS; FOCAL DYSTONIA; TREMOR;
BLEPHAROSPASM; RISK; TORTICOLLIS; MULTICENTER; SYMPTOMS; FEATURES
AB Background: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort.
Methods: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread.
Results: Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age.
Conclusions: Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. (C) 2016 International Parkinson and Movement Disorder Society.
C1 [Norris, Scott A.; Wright, Laura J.; Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Neurol, Campus Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA.
[Jinnah, H. A.; Rosen, Ami R.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Espay, Alberto J.] Univ Cincinnati, Dept Neurol, James J & Joan A Gardner Family Ctr Parkinsons Di, Cincinnati, OH USA.
[Klein, Christine; Brueggemann, Norbert] Univ Lubeck, Inst Neurogenet, Lubeck, Germany.
[Klein, Christine; Brueggemann, Norbert] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Barbano, Richard L.] Univ Rochester, Dept Neurol, Rochester, NY USA.
[Malaty, Irene Andonia C.; Rodriguez, Ramon L.] Univ Florida, Dept Neurol, Gainesville, FL USA.
[Vidailhet, Marie; Roze, Emmanuel] Sorbonne Univ, Hop Univ Pitie Salpetriere, Paris, France.
[Reich, Stephen G.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[Berman, Brian D.] Univ Colorado Denver, Sch Med, Dept Neurol, Aurora, CO USA.
[LeDoux, Mark S.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
[LeDoux, Mark S.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
[Richardson, Sarah Pirio] Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA.
[Agarwal, Pinky] Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Mari, Zoltan] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Ondo, William G.] Houston Methodist, Dept Neurol, Houston, TX USA.
[Shih, Ludy C.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Fox, Susan H.] Univ Toronto, Univ Hlth Network, Dept Med, Div Neurol, Toronto, ON, Canada.
[Berardelli, Alfredo] Sapienza Univ Rome, Dept Neurol & Psychiat, Rome, Italy.
[Berardelli, Alfredo] IRCCS Neuromed, Rome, Italy.
[Testa, Claudia M.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA.
[Cheng, Florence Ching-Fen] West Mead Hosp, Dept Neurol, Westmead, NSW, Australia.
[Truong, Daniel] Parkinson & Movement Disorder Inst, Fountain Valley, CA USA.
[Nahab, Fatta B.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Xie, Tao] Univ Chicago, Med Ctr, Dept Neurol, Chicago, IL 60637 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Neurobiol, St Louis, MO USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Phys Therapy, St Louis, MO USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Occupat Therapy, St Louis, MO USA.
RP Norris, SA (reprint author), Washington Univ, Sch Med, Dept Neurol, Campus Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA.
EM norriss@npg.wustl.edu
FU Dystonia Coalition, a part of the Rare Diseases Clinical Research
Network (RDCRN), an initiative of the Office of Rare Diseases Research
(ORDR), NCATS [U54NS065701, U54TR001456]; NCATS; National Institute of
Neurological Diseases and Stroke (NINDS); NIH NINDS [NS065701, NS058714,
NS41509, NS075321]; Murphy Fund; American Parkinson Disease Association
(APDA) Center for Advanced PD Research at Washington University; Greater
St. Louis Chapter of the APDA, McDonnell Center for Higher Brain
Function; Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund);
Barnes-Jewish Hospital Foundation (Parkinson Disease Research Fund)
FX Dystonia Coalition (U54NS065701 and U54TR001456), a part of the Rare
Diseases Clinical Research Network (RDCRN), an initiative of the Office
of Rare Diseases Research (ORDR), NCATS. The Dystonia Coalition is
funded through collaboration between NCATS and the National Institute of
Neurological Diseases and Stroke (NINDS). The study was also supported
by grants from the NIH NINDS (NS065701, NS058714, NS41509, NS075321),
Murphy Fund, American Parkinson Disease Association (APDA) Center for
Advanced PD Research at Washington University; Greater St. Louis Chapter
of the APDA, McDonnell Center for Higher Brain Function; and the
Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and the
Parkinson Disease Research Fund).
NR 40
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD DEC
PY 2016
VL 31
IS 12
BP 1874
EP 1882
DI 10.1002/mds.26817
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA EJ3PD
UT WOS:000393123200018
PM 27753188
ER
PT J
AU Neveu, MA
De Preter, G
Marchand, V
Bol, A
Brender, JR
Saito, K
Kishimoto, S
Porporato, PE
Sonveaux, P
Gregoire, V
Feron, O
Jordan, BF
Krishna, MC
Gallez, B
AF Neveu, Marie-Aline
De Preter, Geraldine
Marchand, Valerie
Bol, Anne
Brender, Jeffery R.
Saito, Keita
Kishimoto, Shun
Porporato, Paolo E.
Sonveaux, Pierre
Gregoire, Vincent
Feron, Olivier
Jordan, Benedicte F.
Krishna, Murali C.
Gallez, Bernard
TI Multimodality Imaging Identifies Distinct Metabolic Profiles In Vitro
and In Vivo
SO NEOPLASIA
LA English
DT Article
ID ELECTRON-PARAMAGNETIC-RESONANCE; CANCER-CELLS; AEROBIC GLYCOLYSIS;
ENERGY-METABOLISM; TUMOR-CELLS; OXYGEN; PROLIFERATION; THERAPY; MICE;
LINK
AB The study of alterations of tumor metabolism should allow the identification of new targets for innovative anticancer strategies. Metabolic alterations are generally established in vitro, and conclusions are often extrapolated to the in vivo situation without further tumor metabolic phenotyping. To highlight the key role of microenvironment on tumor metabolism, we studied the response of glycolytic and oxidative tumor models to metabolic modulations in vitro and in vivo. MDA-MB-231 and SiHa tumor models, characterized in vitro as glycolytic and oxidative, respectively, were studied. Theoretically, when passing from a hypoxic state to an oxygenated state, a Warburg phenotype should conserve a glycolytic metabolism, whereas an oxidative phenotype should switch from glycolytic to oxidative metabolism (Pasteur effect). This challenge was applied in vitro and in vivo to evaluate the impact of different oxic conditions on glucose metabolism. F-18-fluorodeoxyglucose uptake, lactate production, tumor oxygenation, and metabolic fluxes were monitored in vivo using positron emission tomography, microdialysis, electron paramagnetic resonance imaging, and C-13-hyperpolarizated magnetic resonance spectroscopy, respectively. In vitro, MDA-MB-231 cells were glycolytic under both hypoxic and oxygenated conditions, whereas SiHa cells underwent a metabolic shift after reoxygenation. On the contrary, in vivo, the increase in tumor oxygenation (induced by carbogen challenge) led to a similar metabolic shift in glucose metabolism in both tumor models. The major discordance in metabolic patterns observed in vitro and in vivo highlights that any extrapolation of in vitro metabolic profiling to the in vivo situation should be taken cautiously and that metabolic phenotyping using molecular imaging is mandatory in vivo.
C1 [Neveu, Marie-Aline; De Preter, Geraldine; Marchand, Valerie; Jordan, Benedicte F.; Gallez, Bernard] Catholic Univ Louvain, LDRI, Biomed Magnet Resonance Res Grp, Brussels, Belgium.
[Bol, Anne; Gregoire, Vincent] Catholic Univ Louvain, Dept Radiat Oncol, Brussels, Belgium.
[Bol, Anne; Gregoire, Vincent] Catholic Univ Louvain, Inst Expt & Clin Res IREC, Ctr Mol Imaging Radiotherapy & Oncol, Brussels, Belgium.
[Brender, Jeffery R.; Saito, Keita; Kishimoto, Shun; Krishna, Murali C.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Porporato, Paolo E.; Sonveaux, Pierre; Feron, Olivier] Catholic Univ Louvain, Inst Expt & Clin Res IREC, Pole Pharmacol & Therapeut, Brussels, Belgium.
RP Gallez, B (reprint author), Catholic Univ Louvain, LDRI, Biomed Magnet Resonance Unit, REMA, Ave Mounier 73-08, B-1200 Brussels, Belgium.
EM bernard.gallez@uclouvain.be
FU Belgian National Fund for Scientific Research (F.S.R.-FNRS) [PDR
T.0107.13]; Fonds Joseph Maisin; Action de Recherches Concertees [ARC
14/19-058]; Belgian Science Policy Office Interuniversity Attraction
Pole IUAP [P7/03]; National Institute of Health
FX This study was funded by grants from the Belgian National Fund for
Scientific Research (F.S.R.-FNRS; PDR T.0107.13), the Fonds Joseph
Maisin, the Action de Recherches Concertees ARC 14/19-058, Belgian
Science Policy Office Interuniversity Attraction Pole IUAP #P7/03, and
intramural National Institute of Health funds. M.A.N. is a Research
Fellow and P.E.P. a Senior Postdoctoral Fellow of F.R.S.-FNRS. P.S. and
B.F.J. are Research Associates of F.R.S.-FNRS.
NR 31
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U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1476-5586
J9 NEOPLASIA
JI Neoplasia
PD DEC
PY 2016
VL 18
IS 12
BP 742
EP 752
DI 10.1016/j.neo.2016.10.010
PG 11
WC Oncology
SC Oncology
GA EJ2RF
UT WOS:000393057700004
PM 27889643
ER
PT J
AU Rodriquez, EJ
Oh, SS
Perez-Stable, EJ
Schroeder, SA
AF Rodriquez, Erik J.
Oh, Sam S.
Perez-Stable, Eliseo J.
Schroeder, Steven A.
TI Changes in Smoking Intensity Over Time by Birth Cohort and by Latino
National Background, 1997-2014
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID CIGARETTE-SMOKING; MEXICAN-AMERICANS; ASIAN-AMERICANS; UNITED-STATES;
ACCULTURATION; HISPANICS; BEHAVIOR; CALIFORNIA; TOBACCO; ADULTS
AB Introduction: The purpose of the study was to describe changes in smoking intensity among US Latinos and non-Latinos from 1997 to 2014.
Methods: National Health Interview Survey data between 1997 and 2014 were used to determine the number of cigarettes smoked per day (CPD) among Latino and non-Latino adults who had smoked at least 100 cigarettes in their lifetime and were currently smoking every day or some days (ie, current smokers).
Results: CPD declined steadily throughout the observation period and were consistently lower for Latino than for non-Latino smokers. However, decreases were not equal across birth cohorts, genders, or among Latino national background groups. CPD declined most among Mexican men and least among younger generations, Cuban women, and acculturated Latina women. Additionally, declines in smoking intensity seemed to slow over time among low CPD consumers.
Conclusions: Although smoking intensity has decreased substantially since the late 1990s, CPD data suggest that declines are slowing among younger generations and certain Latina women. Effective tobacco control strategies should be developed to discourage even very light and non-daily smoking.
Implications: Few studies have been conducted on how smoking intensity has changed since the late 1990s. Between 2004 and 2011, when the decline in smoking prevalence slowed, it is unknown how smoking intensity (ie, CPD) changed by age. Additionally, no research has assessed differences and changes in smoking intensity over time among Latinos. From this study we learned that smoking intensity declined significantly since the late 1990s, but this decline slowed among younger generations of smokers and certain Latina women. Findings suggest that future patterns of smoking intensity may only marginally decline in the near future.
C1 [Rodriquez, Erik J.; Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Multiethn Hlth Equ Res Ctr, San Francisco, CA USA.
[Rodriquez, Erik J.; Perez-Stable, Eliseo J.; Schroeder, Steven A.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA.
[Rodriquez, Erik J.; Perez-Stable, Eliseo J.; Schroeder, Steven A.] Univ Calif San Francisco, Dept Med, Ctr Tobacco Control Res & Educ, San Francisco, CA USA.
[Rodriquez, Erik J.; Oh, Sam S.; Perez-Stable, Eliseo J.; Schroeder, Steven A.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Schroeder, Steven A.] Univ Calif San Francisco, Dept Med, Smoking Cessat Leadership Ctr, San Francisco, CA USA.
[Perez-Stable, Eliseo J.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA.
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
RP Rodriquez, EJ (reprint author), Univ Calif San Francisco, Dept Med, 3333 Calif St,Suite 335,Box 0856, San Francisco, CA 94143 USA.
EM erikr@ucsf.edu
FU Clinical and Translational Science Institute at the University of
California, San Francisco [K19683L]; Resource Centers for Minority Aging
Research of the National Institute on Aging, National Institutes of
Health (Center for Aging in Diverse Communities) [P30 AG15272]; Cancer
Education and Control Development Program in Tobacco Control of the
National Cancer Institute, National Institutes of Health (Center for
Tobacco Control Research and Education) [R25 CA113710]; National Latino
Cancer Research Network of the National Cancer Institute, National
Institutes of Health (Redes En Accion) [U01 CA86117, U54 CA153511]
FX This study was funded in part by grants from the Clinical and
Translational Science Institute at the University of California, San
Francisco (Strategic Opportunities Support, K19683L); Resource Centers
for Minority Aging Research of the National Institute on Aging, National
Institutes of Health (Center for Aging in Diverse Communities, P30
AG15272); Cancer Education and Control Development Program in Tobacco
Control of the National Cancer Institute, National Institutes of Health
(Center for Tobacco Control Research and Education, R25 CA113710); and
the National Latino Cancer Research Network of the National Cancer
Institute, National Institutes of Health (Redes En Accion, U01 CA86117
and U54 CA153511). The study sponsors played no role in the design of
the study, writing of the manuscript, or decision to submit the
manuscript for publication.
NR 47
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD DEC
PY 2016
VL 18
IS 12
BP 2225
EP 2233
DI 10.1093/ntr/ntw203
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA EJ4NF
UT WOS:000393193300008
PM 27613930
ER
PT J
AU Young, WC
Nadarajah, SR
Berger, AM
AF Young, William C.
Nadarajah, Sheeba R.
Berger, Ann M.
TI Supportive medical care in life-threatening illness: A pilot study
SO PALLIATIVE & SUPPORTIVE CARE
LA English
DT Article
DE Medical care; Cancer; Cardiac illness; Life-transforming change;
Qualitative research
ID POSTTRAUMATIC GROWTH; CANCER; PAIN
AB Objective: The goal of this pilot study was to identify the processes by which healing occurs in patients who experience a life-threatening illness.
Method: Healing was examined by using two qualitative studies that employed a semistructured interview process (interviews lasted between 30 and 115 minutes). There were 10 cardiac event survivors and 9 cancer survivors. These participants came from a community hospital setting (cardiac), nonmedical holistic services organization (cancer), and a research hospital (cancer). Before participants could take part in the study, they were administered preliminary screening measurements, the first of which was an instrument similar to the Distress Thermometer. Participants then self-reported their positive life-transforming changes. If one to three changes were reported six months after onset of the illness, participants were deemed to have passed the screening. Finally, participants were tested for speaking volume and clarity.
Results: An overall theme that was prevalent throughout the interviews wasmedical support. Participants found that their positive, life-transforming changes were typically connected with supportive caregivers who helped to create a culture of care. They also indicated that an absence of this medical supportive care hindered development of such life-transforming changes.
Significance of Results: Our results indicate that a medical care team will be more effective if a positive culture of care is created. This can be implemented if the team provides comfort, which involves being more engaged in the treatment of patients aswell as being more attentive to their psychosocial needs.
C1 [Young, William C.; Berger, Ann M.] NIH, Pain & Palliat Care Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2-1733, Bethesda, MD 20892 USA.
[Nadarajah, Sheeba R.] Bowie State Univ, Dept Nursing, Bowie, MD USA.
RP Berger, AM (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2-1733, Bethesda, MD 20892 USA.
EM aberger@cc.nih.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1478-9515
EI 1478-9523
J9 PALLIAT SUPPORT CARE
JI Palliat. Support Care
PD DEC
PY 2016
VL 14
IS 6
BP 680
EP 685
DI 10.1017/S147895151600033X
PG 6
WC Health Policy & Services
SC Health Care Sciences & Services
GA EJ4IX
UT WOS:000393181400011
PM 27215292
ER
PT J
AU Coleman, CN
Koerner, JF
AF Coleman, C. Norman
Koerner, John F.
TI BIODOSIMETRY: MEDICINE, SCIENCE, AND SYSTEMS TO SUPPORT THE MEDICAL
DECISION-MAKER FOLLOWING A LARGE SCALE NUCLEAR OR RADIATION INCIDENT
SO RADIATION PROTECTION DOSIMETRY
LA English
DT Article; Proceedings Paper
CT 4th EPR BioDose Meeting
CY OCT 04-08, 2015
CL Hanover, NH
SP Int Assoc Biol & EPR Radiat Dosimetry
ID SCARCE RESOURCES; MASS-CASUALTY; DETONATION; MANAGEMENT; ALLOCATION;
STANDARDS; TOOLS
AB The public health and medical response to a radiological or nuclear incident requires the capability to sort, assess, treat, triage and to ultimately discharge, refer or transport people to their next step in medical care. The size of the incident and scarcity of resources at the location of each medical decision point will determine how patients are triaged and treated. This will be a rapidly evolving situation impacting medical responders at regional, national and international levels. As capabilities, diagnostics and medical countermeasures improve, a dynamic system-based approach is needed to plan for and manage the incident, and to adapt effectively in real time. In that the concepts and terms can be unfamiliar and possibly confusing, resources and a concept of operations must be considered well in advance. An essential underlying tenet is that medical evaluation and care will be managed by healthcare professionals with biodosimetry assays providing critical supporting data.
C1 [Coleman, C. Norman; Koerner, John F.] Dept Hlth & Human Serv, Chem Biol Radiol Nucl & Explos Branch, Off Emergency Management, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA.
[Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Koerner, JF (reprint author), Dept Hlth & Human Serv, Chem Biol Radiol Nucl & Explos Branch, Off Emergency Management, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA.
EM john.koerner@hhs.gov
NR 19
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0144-8420
EI 1742-3406
J9 RADIAT PROT DOSIM
JI Radiat. Prot. Dosim.
PD DEC 1
PY 2016
VL 172
IS 1-3
BP 38
EP 46
DI 10.1093/rpd/ncw155
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA EJ4HX
UT WOS:000393178600004
PM 27473694
ER
PT J
AU Simon, SL
Bouville, A
AF Simon, Steven L.
Bouville, Andre
TI LONG-TERM BIODOSIMETRY REDUX
SO RADIATION PROTECTION DOSIMETRY
LA English
DT Article; Proceedings Paper
CT 4th EPR BioDose Meeting
CY OCT 04-08, 2015
CL Hanover, NH
SP Int Assoc Biol & EPR Radiat Dosimetry
ID RADIATION; EXPOSURE
AB This paper revisits and reiterates the needs, purposes and requirements of biodosimetric assays for long-term dose and health risk assessments. While the most crucial need for biodosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure assessment. Hence, the needs for retrospective dose estimation are likely to be greater in the future. The value of biodosimetry can be considerably enhanced with the development of new or improved methods, particularly with suitability for application at long periods of time after exposure.
C1 [Simon, Steven L.; Bouville, Andre] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Simon, SL (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
National Institute of Allergy and Infectious Diseases; National Cancer
Institute, NIAID [Y2-Al-5077]; NCI [Y3-CO-5117]
FX This research was supported in part by the Intramural Research Program
of the NIH and the National Cancer Institute and the Intra-Agency
agreement between the National Institute of Allergy and Infectious
Diseases and the National Cancer Institute, NIAID agreement # Y2-Al-5077
and NCI agreement # Y3-CO-5117.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0144-8420
EI 1742-3406
J9 RADIAT PROT DOSIM
JI Radiat. Prot. Dosim.
PD DEC 1
PY 2016
VL 172
IS 1-3
BP 244
EP 247
DI 10.1093/rpd/ncw156
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA EJ4HX
UT WOS:000393178600028
PM 27412511
ER
PT J
AU Symons, R
Morris, JZ
Wu, CO
Pourmorteza, A
Ahlman, MA
Lima, JAC
Chen, MY
Mallek, M
Sandfort, V
Bluemke, DA
AF Symons, Rolf
Morris, Justin Z.
Wu, Colin O.
Pourmorteza, Amir
Ahlman, Mark A.
Lima, Joao A. C.
Chen, Marcus Y.
Mallek, Marissa
Sandfort, Veit
Bluemke, David A.
TI Coronary CT Angiography: Variability of CT Scanners and Readers in
Measurement of Plaque Volume
SO RADIOLOGY
LA English
DT Article
ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; INTRAVASCULAR ULTRASOUND;
ATHEROSCLEROTIC PLAQUE; ARTERY CALCIFICATION; DIAGNOSTIC-ACCURACY;
STATIN THERAPY; DUAL-SOURCE; QUANTIFICATION; BURDEN; TRIAL
AB Purpose: To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume.
Materials and Methods: This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years +/- 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and BlandAltman analysis were used to assess interreader, intrareader, and interstudy reproducibility.
Results: Baseline and repeat coronary CT angiography scans were acquired within 19 days +/- 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs >= 0.96) without bias. Scanner variability was 618.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to 629.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an a error of.05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up.
Conclusion: State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scanre-scan reproducibility. (C) RSNA, 2016
C1 [Symons, Rolf; Morris, Justin Z.; Pourmorteza, Amir; Ahlman, Mark A.; Mallek, Marissa; Sandfort, Veit; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Chen, Marcus Y.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
EM david.bluemke@nih.gov
OI Symons, Rolf/0000-0001-7889-6773
FU National Institutes of Health Intramural Research program [ZIACL090019,
ZIAEB000072]
FX Supported by National Institutes of Health Intramural Research program
(ZIACL090019, ZIAEB000072).
NR 39
TC 0
Z9 0
U1 2
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2016
VL 281
IS 3
BP 737
EP 748
DI 10.1148/radiol.2016161670
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EJ4QI
UT WOS:000393201500008
PM 27636027
ER
PT J
AU de Gonzalez, AB
Ntowe, E
Kitahara, CM
Gilbert, E
Miller, DL
Kleinerman, RA
Linet, MS
AF de Gonzalez, Amy Berrington
Ntowe, Estelle
Kitahara, Cari M.
Gilbert, Ethel
Miller, Donald L.
Kleinerman, Ruth A.
Linet, Martha S.
TI Long-term Mortality in 43 763 US Radiologists Compared with 64 990 US
Psychiatrists
SO RADIOLOGY
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; RADIATION-EXPOSURE; PHYSICIAN SPECIALISTS;
BRITISH RADIOLOGISTS; CIRCULATORY DISEASE; IONIZING-RADIATION; CANCER
INCIDENCE; UNITED-STATES; RISK; WORKERS
AB Purpose: To compare mortality rates from all causes, specific causes, total cancers, and specific cancers to assess whether differences between radiologists and psychiatrists are consistent with known risks of radiation exposure and the changes in radiation exposure to radiologists over time.
Materials and Methods: The authors used the American Medical Association Physician Masterfile to construct a cohort of 43 763 radiologists (20% women) and 64 990 psychiatrists (27% women) (comparison group) who graduated from medical school in 1916-2006. Vital status was obtained from record linkages with the Social Security Administration and commercial databases, and cause of death was obtained from the National Death Index. Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for all causes and specific causes of death.
Results: During the follow-up period (1979-2008), 4260 male radiologists and 7815 male psychiatrists died. The male radiologists had lower death rates (all causes) compared with the psychiatrists (RR = 0.94; 95% CI: 0.90, 0.97), similar cancer death rates overall (RR = 1.00; 95% CI: 0.93, 1.07), but increased acute myeloid leukemia and/or myelodysplastic syndrome death rates (RR = 1.62; 95% CI: 1.05, 2.50); these rates were driven by those who graduated before 1940 (RR = 4.68; 95% CI: 0.91, 24.18). In these earliest workers (before 1940) there were also increased death rates from melanoma (RR = 8.75; 95% CI: 1.89, 40.53), non-Hodgkin lymphoma (NHL) (RR = 2.69; 95% CI: 1.33, 5.45), and cerebrovascular disease (RR = 1.49; 95% CI: 1.11, 2.01). The 208 deaths in female radiologists precluded detailed investigation, and the number of female radiologists who graduated before 1940 was very small (n = 47).
Conclusion: The excess risk of acute myeloid leukemia and/or myelodysplastic syndrome mortality in radiologists who graduated before 1940 is likely due to occupational radiation exposure. The melanoma, NHL, and cerebrovascular disease mortality risks are possibly due to radiation. The authors found no evidence of excess mortality in radiologists who graduated more recently, possibly because of increased radiation protection and/or lifestyle changes. (C) RSNA, 2016
C1 [de Gonzalez, Amy Berrington; Ntowe, Estelle; Kitahara, Cari M.; Gilbert, Ethel; Kleinerman, Ruth A.; Linet, Martha S.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Miller, Donald L.] FDA Off In Vitro Diagnost & Radiol Hlth, White Oak Campus, Silver Spring, MD USA.
RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
FU National Institutes of Health Intramural Research Program [Z01
CP010133-21]
FX Supported by National Institutes of Health Intramural Research Program
(grant Z01 CP010133-21).
NR 34
TC 1
Z9 1
U1 2
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2016
VL 281
IS 3
BP 847
EP 857
DI 10.1148/radiol.2016152472
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EJ4QI
UT WOS:000393201500018
ER
PT J
AU Behl, M
Rice, JR
Smith, MV
Co, CA
Bridge, MF
Hsieh, JH
Freedman, JH
Boyd, WA
AF Behl, Mamta
Rice, Julie R.
Smith, Marjo V.
Co, Caroll A.
Bridge, Matthew F.
Hsieh, Jui-Hua
Freedman, Jonathan H.
Boyd, Windy A.
TI Comparative Toxicity of Organophosphate Flame Retardants and
Polybrominated Diphenyl Ethers to Caenorhabditis elegans
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE Caenorhabditis elegans; flame retardants; mitochondrial toxicity
ID MESSENGER-RNA EXPRESSION; THYROID-HORMONE LEVELS; C. ELEGANS;
HOUSE-DUST; TRIS(1,3-DICHLORO-2-PROPYL) PHOSPHATE; DEVELOPMENTAL
EXPOSURE; CHICKEN EMBRYOS; NEURONAL CELLS; PBDE MIXTURE; LIFE-SPAN
AB With the phasing-out of the polybrominated diphenyl ether (PBDE) flame retardants due to concerns regarding their potential developmental toxicity, the use of replacement compounds such as organophosphate flame retardants (OPFRs) has increased. Limited toxicity data are currently available to estimate the potential adverse health effects of the OPFRs. The toxicological effects of 4 brominated flame retardants, including 3 PBDEs and 3,3', 5,5'-tetrabromobisphenol A, were compared with 6 aromatic OPFRs and 2 aliphatic OPFRs. The effects of these chemicals were determined using 3 biological endpoints in the nematode Caenorhabditis elegans (feeding, larval development, and reproduction). Because C. elegans development was previously reported to be sensitive to mitochondrial function, results were compared with those from an in vitro mitochondrial membrane permeabilization (MMP) assay. Overall 11 of the 12 flame retardants were active in 1 or more C. elegans biological endpoints, with only tris(2-chloroethyl) phosphate inactive across all endpoints including the in vitro MMP assay. For 2 of the C. elegans endpoints, at least 1 OPFR had similar toxicity to the PBDEs: triphenyl phosphate (TPHP) inhibited larval development at levels comparable to the 3 PBDEs; whereas TPHP and isopropylated phenol phosphate (IPP) affected C. elegans reproduction at levels similar to the PBDE commercial mixture, DE-71. The PBDEs reduced C. elegans feeding at lower concentrations than any OPFR. In addition, 9 of the 11 chemicals that inhibited C. elegans larval development also caused significant mitochondrial toxicity. These results suggest that some of the replacement aromatic OPFRs may have levels of toxicity comparable to PBDEs.
C1 [Behl, Mamta; Rice, Julie R.; Hsieh, Jui-Hua; Boyd, Windy A.] NIEHS, Div Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Smith, Marjo V.; Co, Caroll A.; Bridge, Matthew F.] Social Sci Syst Inc, Durham, NC USA.
[Freedman, Jonathan H.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
RP Boyd, WA (reprint author), NIEHS, Div Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Boyd, WA (reprint author), NIEHS, Div Natl Toxicol Program, Mail Drop K2-04,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM boydw@niehs.nih.gov
FU National Toxicology Program Division; Intramural Research Program of the
National Institute of Environmental Health Sciences (NIEHS)/National
Institutes of Health (NIH) [Z01ES102045, Z01ES102046]
FX This work was supported in part by the National Toxicology Program
Division and by the Intramural Research Program of the National
Institute of Environmental Health Sciences (NIEHS)/National Institutes
of Health (NIH) (Z01ES102045 and Z01ES102046).
NR 70
TC 0
Z9 0
U1 14
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD DEC
PY 2016
VL 154
IS 2
BP 241
EP 252
DI 10.1093/toxsci/kfw162
PG 12
WC Toxicology
SC Toxicology
GA EJ5VJ
UT WOS:000393286500007
PM 27566445
ER
PT J
AU Knudsen, GA
Sanders, JM
Birnbaum, LS
AF Knudsen, Gabriel A.
Sanders, J. Michael
Birnbaum, Linda S.
TI Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl
2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice:
Effects of Dose, Route, and Repeated Administration
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate; disposition; metabolism
ID MIXTURE FIREMASTER(R) 550; IN-VITRO METABOLISM; HUMAN EXPOSURE;
HOUSE-DUST; INDOOR DUST; PHASE-OUT; ACCUMULATION; ESTERASES; CHINA;
LIVER
AB 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW549.92 g/mol; CAS 183658-27-7) is a brominated component of flame retardant mixtures used as substitutes for some PBDEs. EH-TBB is added to various consumer products, including polyurethane foams, and has been detected in humans. The present study characterized the fate of EH-TBB in rodents. [C-14]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1-100 mu mol/kg (similar to 0.05-55 mg/kg) or repeated administration (0.1 mu mol/kg/day x 5-10 days) by gavage to female Hsd: Sprague DawleySD (SD) rats. Cumulative excretion via feces increased (39-60%) with dose (0.1-10 mu mol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [C-14]-radioactivity in urine and feces of a 100 mu mol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 mu mol/kg dose in urine and less in feces than did gavaged rats, indicating partial biliary elimination of systemically available compound. No tissue bioaccumulation was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA-sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice indicated minimal sex-or species differences are likely for the disposition of EH-TBB. Approximately 85% of a 0.1 mu mol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels.
C1 [Knudsen, Gabriel A.; Sanders, J. Michael; Birnbaum, Linda S.] NCI, Lab Toxicol & Toxicokinet, Res Triangle Pk, NC USA.
RP Knudsen, GA (reprint author), 111 TW Alexander Dr,BG 101,Rm C202A, Res Triangle Pk, NC 27709 USA.
EM gabriel.knudsen@nih.gov
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health [ZIA BC 011476]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health [Project
ZIA BC 011476].
NR 49
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD DEC
PY 2016
VL 154
IS 2
BP 392
EP 402
DI 10.1093/toxsci/kfw176
PG 11
WC Toxicology
SC Toxicology
GA EJ5VJ
UT WOS:000393286500020
PM 27613714
ER
PT J
AU Riley, WT
Martin, CA
Rivera, DE
Hekler, EB
Adams, MA
Buman, MP
Pavel, M
King, AC
AF Riley, William T.
Martin, Cesar A.
Rivera, Daniel E.
Hekler, Eric B.
Adams, Marc A.
Buman, Matthew P.
Pavel, Misha
King, Abby C.
TI Development of a dynamic computational model of social cognitive theory
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Dynamical system modeling; Computational modeling; Control systems
engineering; Health behavior theory; Social cognitive theory
ID PHYSICAL-ACTIVITY RESEARCH; SELF-EFFICACY; ADAPTIVE INTERVENTIONS;
HEALTH-PROMOTION; BEHAVIOR-CHANGE; SUPPORT; SYSTEMS; ADULTS; GIRLS
AB Social cognitive theory (SCT) is among the most influential theories of behavior change and has been used as the conceptual basis of health behavior interventions for smoking cessation, weight management, and other health behaviors. SCT and other behavior theories were developed primarily to explain differences between individuals, but explanatory theories of within-person behavioral variability are increasingly needed as new technologies allow for intensive longitudinal measures and interventions adapted from these inputs. These within-person explanatory theoretical applications can be modeled as dynamical systems. SCT constructs, such as reciprocal determinism, are inherently dynamical in nature, but SCT has not been modeled as a dynamical system. This paper describes the development of a dynamical system model of SCT using fluid analogies and control systems principles drawn from engineering. Simulations of this model were performed to assess if the model performed as predicted based on theory and empirical studies of SCT. This initial model generates precise and testable quantitative predictions for future intensive longitudinal research. Dynamic modeling approaches provide a rigorous method for advancing health behavior theory development and refinement and for guiding the development of more potent and efficient interventions.
C1 [Riley, William T.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Martin, Cesar A.; Rivera, Daniel E.] Arizona State Univ, CSEL, Sch Engn Matter Transport & Energy, Tempe, AZ USA.
[Hekler, Eric B.; Adams, Marc A.; Buman, Matthew P.] Arizona State Univ, Sch Nutr & Hlth Promot, Tempe, AZ USA.
[Pavel, Misha] Northeastern Univ, Boston, MA 02115 USA.
[King, Abby C.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[King, Abby C.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Med, Stanford, CA 94305 USA.
RP Riley, WT (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
EM wiriley@mail.nih.gov
RI Adams, Marc/C-3513-2013
OI Adams, Marc/0000-0001-6310-1472
FU National Science Foundation [IIS-1449751]; National Institute on Drug
Abuse [K25DA021173]; National Institute of Nursing Research
[P20NR015320]; National Heart, Lung, and Blood Institute [R01HL116448];
National Institute of Diabetes and Digestive and Kidney Diseases
[R01DK102016]; National Institute of Biomedical Imaging and
Bioengineering [U54EB020405]
FX DR and EH were supported by a grant from National Science Foundation
(IIS-1449751). DR also was supported by a grant from the National
Institute on Drug Abuse (K25DA021173). MP was supported by a grant from
the National Institute of Nursing Research (P20NR015320). AK was
supported by grants from National Heart, Lung, and Blood Institute
(R01HL116448), National Institute of Diabetes and Digestive and Kidney
Diseases (R01DK102016), and National Institute of Biomedical Imaging and
Bioengineering (U54EB020405). This paper represents the views and
perspectives of the authors, not the funders or the National Institutes
of Health. All authors participated in this article and take
responsibility for the integrity of the conceptualizations and models
described.
NR 47
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U1 2
U2 2
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD DEC
PY 2016
VL 6
IS 4
BP 483
EP 495
DI 10.1007/s13142-015-0356-6
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EJ5YU
UT WOS:000393296000001
PM 27848208
ER
PT J
AU Jackson, DN
Chou, WYS
Coa, KI
Oh, A
Hesse, B
AF Jackson, Devlon N.
Chou, Wen-Ying Sylvia
Coa, Kisha I.
Oh, April
Hesse, Bradford
TI Implications of social media use on health information technology
engagement: Data from HINTS 4 cycle 3
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Internet access; Social media use; Health information technology
engagement; Communication inequalities
ID NATIONAL TRENDS SURVEY; CONSUMERS PERCEPTIONS; INTERNET; COMMUNICATION;
COMPLEMENTARITY; OUTCOMES; RECORDS; ADULTS
AB Little is known about the association between Internet/social media use and health information technology (HIT) engagement. This study examines patterns of social media use and HIT engagement in the U.S.A. using data from the 2013 Health Information National Trends Survey (N = 3,164). Specifically, predictors of two HIT activities (i.e., communicating with a healthcare provider using the Internet or email and tracking personal health information electronically) are examined. Persons who were females, higher education, non-Hispanic others, having a regular healthcare provider, and ages 35-44 were more likely to participate in HIT activities. After controlling for sociode-mographics and health correlates, social media use was significantly associated with HIT engagement. To our knowledge, this is one of the first studies to systematically examine the use and relationships across multiple types of health-related online media.
C1 [Jackson, Devlon N.; Chou, Wen-Ying Sylvia; Coa, Kisha I.; Oh, April; Hesse, Bradford] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Jackson, Devlon N.] Univ Maryland, Maryland Ctr Hlth Equ, College Pk, MD 20742 USA.
RP Jackson, DN (reprint author), NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.; Jackson, DN (reprint author), Univ Maryland, Maryland Ctr Hlth Equ, College Pk, MD 20742 USA.
EM djacks04@umd.edu
FU National Institutes of Health, National Cancer Institute; Westat
FX The first author of this manuscript did not receive any funding support
to conduct this research. The National Institutes of Health, National
Cancer Institute and funding partner, Westat, provided funding support
for the development of this publicly accessible secondary data set.
NR 42
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U1 1
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PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD DEC
PY 2016
VL 6
IS 4
BP 566
EP 576
DI 10.1007/s13142-016-0437-1
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EJ5YU
UT WOS:000393296000008
PM 27628436
ER
PT J
AU Madan, RA
Gulley, JL
AF Madan, Ravi A.
Gulley, James L.
TI Personalized peptide vaccine in prostate cancer: capitalizing on
existing immunity
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
ID SIPULEUCEL-T; IMMUNOTHERAPY; CHEMOTHERAPY; SURVIVAL; TRIAL; MEN
C1 [Madan, Ravi A.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
RP Madan, RA (reprint author), NCI, Genitourinary Malignancies Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM madanr@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH
FX The authors would like to acknowledge the support of the Center for
Cancer Research, National Cancer Institute, NIH.
NR 9
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U1 3
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PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD DEC
PY 2016
VL 5
SU 7
BP S1333
EP S1335
DI 10.21037/tcr.2016.12.27
PG 3
WC Oncology
SC Oncology
GA EJ6KY
UT WOS:000393329400007
ER
PT J
AU Hua, ZY
Gu, X
Dong, YD
Tan, F
Liu, ZH
Thiele, CJ
Li, ZJ
AF Hua, Zhongyan
Gu, Xiao
Dong, Yudi
Tan, Fei
Liu, Zhihui
Thiele, Carol J.
Li, Zhijie
TI PI3K and MAPK pathways mediate the BDNF/TrkB-increased metastasis in
neuroblastoma
SO TUMOR BIOLOGY
LA English
DT Article
DE Neuroblastoma; BDNF; TrkB; Metastasis
ID TO-MESENCHYMAL TRANSITION; NEUROTROPHIC FACTOR; RECEPTOR TRKB;
HEPATOCELLULAR-CARCINOMA; MOLECULAR-BIOLOGY; INDUCED APOPTOSIS;
POOR-PROGNOSIS; LUNG-CANCER; IN-VITRO; EXPRESSION
AB Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells. A tumor xenograft model using SCID-Beige mice was utilized to detect the metastasis of NB tumors in vivo. Inhibitors of PI3K, MAPK, Akt, and mTOR were used. Western blotting was performed to study the expressions of P-Akt, P-Erk, and P-mTOR. Our results showed that in TrkB-expressing NB cells, BDNF treatment significantly increased gap closing (P < 0.01) in scratch wound healing assay, also significantly enhanced the numbers of migrating cells (P < 0.01) and invading cells (P < 0.01) in the Boyden chamber migration and invasion assays. In vivo, NB distant metastases were significantly increased in mice with TrkB-expressing xenograft tumors compared to those with non-TrkB-expressing tumors (P < 0.05). Pre-treatment with any of the inhibitors for PI3K (LY294002), MAPK (PD98059), Akt (perifosine), or mTOR (rapamycin) blocked the BDNF/TrkB-induced increases of cell migration and invasion in TB3 cells, and also blocked the BDNF/TrkB-induced expressions of P-Akt, P-Erk, and P-mTOR. These data indicated that BDNF/TrkB increased metastasis in NB via PI3K/Akt/mTOR and MAPK pathways, and BDNF/TrkB and the downstream targets may be potential targets for the treatment of NB metastasis.
C1 [Hua, Zhongyan; Gu, Xiao; Dong, Yudi; Li, Zhijie] China Med Univ, Shengjing Hosp, Med Res Ctr, 36 Sanhao St, Shenyang 110004, Peoples R China.
[Gu, Xiao] China Med Univ, Shengjing Hosp, Dept Oncol, Shenyang, Peoples R China.
[Tan, Fei] China Med Univ, Shengjing Hosp, Dept Neurol, Shenyang, Peoples R China.
[Liu, Zhihui; Thiele, Carol J.] NCI, Cellular & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Li, ZJ (reprint author), China Med Univ, Shengjing Hosp, Med Res Ctr, 36 Sanhao St, Shenyang 110004, Peoples R China.
EM lizhijie68@hotmail.com
FU National Natural Science Foundation of China [81272538, 81472359];
Liaoning Climbing Scholar Foundation; Society Development Foundation of
Liaoning Province [2012225016]; NCI Intramural Research Program at
National Cancer Institute at the National Institutes of Health
FX This work was supported by the National Natural Science Foundation of
China (Nos. 81272538 and 81472359), 2013 Liaoning Climbing Scholar
Foundation, Society Development Foundation of Liaoning Province (No.
2012225016), and NCI Intramural Research Program at National Cancer
Institute at the National Institutes of Health.
NR 43
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Z9 0
U1 3
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1010-4283
EI 1423-0380
J9 TUMOR BIOL
JI Tumor Biol.
PD DEC
PY 2016
VL 37
IS 12
BP 16227
EP 16236
DI 10.1007/s13277-016-5433-z
PG 10
WC Oncology
SC Oncology
GA EJ0ZX
UT WOS:000392941000087
ER
PT J
AU Jenkins, RA
AF Jenkins, Richard A.
TI Clinical Community Psychology: Reflections on the Decades Following
Swampscott
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Editorial Material
DE Swampscott conference; Clinical-community
ID MENTAL-HEALTH POLICY; CHRONIC-PATIENT; DEINSTITUTIONALIZATION; STATES;
CARE
AB The Swampscott report was foundational, but in some ways reflected divisions within community psychology that have continued into the present. Community psychologists trained in the 1970s and, especially, the 1980s confronted a period where the original focus of community mental health began to have less influence in the mental health field due to a variety of public policies, and the growth of third party payments as a significant source of health care funding. Programs that engaged communities and provided a base for prevention interventions were greatly curtailed because of changes in federal legislation and limited opportunities for state and local funding, although prevention interventions found growing interest from research funders. Clinical and community psychologists who trained in this period increasingly looked to a variety of areas outside of mental health. Consequently, the field of community psychology has become more applied and less academic, with increased attention to advocacy, theory, and global perspectives. The sweep of these changes and their implications for the future of the field are discussed here.
C1 [Jenkins, Richard A.] NIDA, Bethesda, MD 20892 USA.
EM jenkinsri@mail.nih.gov
NR 34
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0091-0562
EI 1573-2770
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD DEC
PY 2016
VL 58
IS 3-4
BP 269
EP 275
DI 10.1002/ajcp.12040
PG 7
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA EI6QW
UT WOS:000392621900006
ER
PT J
AU Lowe, SR
Kwok, RK
Payne, J
Engel, LS
Galea, S
Sandler, DP
AF Lowe, Sarah R.
Kwok, Richard K.
Payne, Julianne
Engel, Lawrence S.
Galea, Sandro
Sandler, Dale P.
TI Why Does Disaster Recovery Work Influence Mental Health?: Pathways
through Physical Health and Household Income
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Article
DE Disaster recovery work; Deepwater Horizon oil spill; Post-traumatic
stress; Major depression; Generalized anxiety; Physical health; Income;
Path analysis
ID SOCIAL SUPPORT; EXXON-VALDEZ; OIL-SPILL; DISORDERS; ASSOCIATION;
DEPRESSION; DISTRESS; EXPOSURE; PTSD; LIFE
AB Disaster recovery work increases risk for mental health problems, yet the mechanisms underlying this association are unclear. We explored links from recovery work to post-traumatic stress (PTS), major depression (MD), and generalized anxiety disorder (GAD) symptoms through physical health symptoms and household income in the aftermath of the Deepwater Horizon oil spill. As part of the NIEHS GuLF STUDY, participants (N=10,141) reported on cleanup work activities, spill-related physical health symptoms, and household income at baseline, and mental health symptoms an average of 14.69weeks (SD=16.79) thereafter. Cleanup work participation was associated with higher physical health symptoms, which in turn were associated with higher PTS, MD, and GAD symptoms. Similar pattern of results were found in models including workers only and investigating the influence of longer work duration and higher work-related oil exposure on mental health symptoms. In addition, longer worker duration and higher work-related oil exposure were associated with higher household income, which in turn was associated with lower MD and GAD symptoms. These findings suggest that physical health symptoms contribute to workers' risk for mental health symptoms, while higher household income, potentially from more extensive work, might mitigate risk.
C1 [Lowe, Sarah R.] Montclair State Univ, Dept Psychol, Montclair, NJ 07043 USA.
[Kwok, Richard K.; Engel, Lawrence S.; Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Payne, Julianne] RTI Int, Res Triangle Pk, NC USA.
[Engel, Lawrence S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Galea, Sandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM lowes@mail.montclair.edu
OI Kwok, Richard/0000-0002-6794-8360; Sandler, Dale/0000-0002-6776-0018
FU NIH Common Fund; NIH, National Institute of Environmental Sciences [ZO1
ES 102945]
FX This study was funded by the NIH Common Fund and the Intramural Program
of the NIH, National Institute of Environmental Sciences (ZO1 ES
102945).
NR 35
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U1 11
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0091-0562
EI 1573-2770
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD DEC
PY 2016
VL 58
IS 3-4
BP 354
EP 364
DI 10.1002/ajcp.12091
PG 11
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA EI6QW
UT WOS:000392621900017
PM 27704561
ER
PT J
AU Newman, JD
Navas-Acien, A
Kuo, CC
Guallar, E
Howard, BV
Fabsitz, RR
Devereux, RB
Umans, JG
Francesconi, KA
Goessler, W
Best, LT
Tellez-Plaza, M
AF Newman, Jonathan D.
Navas-Acien, Ana
Kuo, Chin-Chi
Guallar, Eliseo
Howard, Barbara V.
Fabsitz, Richard R.
Devereux, Richard B.
Umans, Jason G.
Francesconi, Kevin A.
Goessler, Walter
Best, Lyle T.
Tellez-Plaza, Maria
TI Peripheral Arterial Disease and Its Association With Arsenic Exposure
and Metabolism in the Strong Heart Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE arsenic; metabolism; peripheral vascular disease
ID ANKLE-BRACHIAL INDEX; INCIDENT CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS;
DRINKING-WATER; RISK-FACTORS; CAROTID ATHEROSCLEROSIS; BLACKFOOT
DISEASE; VASCULAR-DISEASE; UNITED-STATES; DIABETES-MELLITUS
AB At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45-74 years in 1989-1991 were reexamined in 1993-1995 and 1997-1999, respectively, for incident PAD defined as either ABI < 0.9 or ABI > 1.4. A total of 286 and 206 incident PAD cases were identified for ABI < 0.9 and ABI > 1.4, respectively. The sum of inorganic and methylated urinary arsenic species (SAs) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of SAs with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI < 0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI > 1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI > 1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate SAs and increased arsenic methylation were associated with ABI > 1.4 but not with ABI < 0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure.
C1 [Newman, Jonathan D.] NYU Med Ctr, Div Cardiol, New York, NY 10016 USA.
[Newman, Jonathan D.] NYU Med Ctr, Dept Med, Ctr Prevent Cardiovasc Dis, New York, NY 10016 USA.
[Navas-Acien, Ana; Kuo, Chin-Chi; Tellez-Plaza, Maria] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Navas-Acien, Ana; Kuo, Chin-Chi; Guallar, Eliseo] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Navas-Acien, Ana; Kuo, Chin-Chi; Guallar, Eliseo] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kuo, Chin-Chi] China Med Univ, Kidney Inst, Taichung, Taiwan.
[Kuo, Chin-Chi] China Med Univ, Div Nephrol, Dept Internal Med, China Med Univ Hosp, Taichung, Taiwan.
[Kuo, Chin-Chi] China Med Univ, Coll Med, Taichung, Taiwan.
[Guallar, Eliseo] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
[Howard, Barbara V.; Umans, Jason G.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Howard, Barbara V.; Umans, Jason G.] Georgetown Univ, Hyattsville, MD USA.
[Fabsitz, Richard R.] NHLBI, Epidemiol Branch, Bldg 10, Bethesda, MD 20892 USA.
[Devereux, Richard B.] Cornell Univ, Div Cardiol, Dept Med, Weill Cornell Med Coll, New York, NY 10021 USA.
[Francesconi, Kevin A.; Goessler, Walter] Karl Franzens Univ Graz, Inst Chem Analyt Chem, Graz, Austria.
[Best, Lyle T.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
[Tellez-Plaza, Maria] Hosp Clin Valencia, INCLIVA Biomed Res Inst, Valencia, Spain.
RP Newman, JD (reprint author), NYU, Sch Med, Div Cardiol, Translat Res Bldg,Room 853, New York, NY 10016 USA.; Newman, JD (reprint author), NYU, Sch Med, Dept Med, Ctr Prevent Cardiovasc Dis, Translat Res Bldg,Room 853, New York, NY 10016 USA.
EM Jonathan.Newman@nyumc.org
OI Newman, Jonathan/0000-0001-6855-7305
FU National Heart, Lung, and Blood Institute [HL090863, K23HL125991,
5T32HL007024, HL41642, HL41652, HL41654, HL65521]; National Institute of
Environmental Health Sciences [P42ES10349, R01ES021367, R01ES025216];
American Heart Association [15MCPRP24480132]; National Institute of
Diabetes and Digestive and Kidney Diseases [U24DK076169-09, 25732-60];
Strategic Action for Research in Health Sciences Program from Spanish
Ministry of Economy and Competitiveness [CP12/ 03080]; European Funds
for Regional Development
FX This work was supported by grants from the National Heart, Lung, and
Blood Institute (grants HL090863, K23HL125991, and 5T32HL007024; Strong
Heart Study grants HL41642, HL41652, HL41654, and HL65521), the National
Institute of Environmental Health Sciences (grants P42ES10349,
R01ES021367, and R01ES025216), the American Heart Association (grant
15MCPRP24480132), and the National Institute of Diabetes and Digestive
and Kidney Diseases (grant U24DK076169-09, subcontract 25732-60).
M.T.-P. was supported by the Strategic Action for Research in Health
Sciences Program (grant CP12/ 03080) from the Spanish Ministry of
Economy and Competitiveness and the European Funds for Regional
Development.
NR 70
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U1 4
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 1
PY 2016
VL 184
IS 11
BP 806
EP 817
DI 10.1093/aje/kww002
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI8AC
UT WOS:000392725400004
PM 27810857
ER
PT J
AU Xu, J
Khincha, PP
Giri, N
Alter, BP
Savage, SA
Wong, JMY
AF Xu, Jialin
Khincha, Payal P.
Giri, Neelam
Alter, Blanche P.
Savage, Sharon A.
Wong, Judy M. Y.
TI Investigation of chromosome X inactivation and clinical phenotypes in
female carriers of DKC1 mutations
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID LINKED DYSKERATOSIS-CONGENITA; TELOMERE BIOLOGY DISORDERS;
RIBOSOMAL-RNA; IN-SITU; MESSENGER-RNA; DISEASE; PSEUDOURIDINE;
MAINTENANCE; DEFICIENCY; LENGTH
AB Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer susceptibility syndrome caused by germline mutations in telomere biology genes. Germline mutations in DKC1, which encodes the protein dyskerin, cause X-linked recessive DC. Because of skewed X-chromosome inactivation, female DKC1 mutation carriers do not typically develop clinical features of DC. This study evaluated female DKC1 mutation carriers with DC-associated phenotypes to elucidate the molecular features of their mutations, in comparison with unaffected carriers and mutation-negative female controls. All female DKC1 mutation carriers had normal leukocyte subset telomere lengths and similarly skewed X-inactivation in multiple tissue types, regardless of phenotype. We observed dyskerin expression, telomerase RNA accumulation, and pseudouridylation present in all mutation carriers at levels comparable to healthy wild-type controls. Our study suggests that mechanisms in addition to X chromosome inactivation, such as germline mosaicism or epigenetics, may contribute to DC-like phenotypes present in female DKC1 mutation carriers. Future studies are warranted to understand the molecular mechanisms associated with the phenotypic variability in female DKC1 mutation carriers, and to identify those at risk of disease. (C) 2016 Wiley Periodicals, Inc.
C1 [Xu, Jialin; Wong, Judy M. Y.] Univ British Columbia, Fac Pharmaceut Sci, Mol & Cellular Pharmacol Grp, Vancouver, BC, Canada.
[Khincha, Payal P.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Wong, JMY (reprint author), Univ British Columbia, Fac Pharmaceut Sci, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.; Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E454, Bethesda, MD 20892 USA.
EM savagesh@mail.nih.gov; judy.wong@ubc.ca
FU Westat, Inc [HHSN261201100018C]; Natural Sciences and Engineering
Research Council of Canada; Intramural Research Program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health
FX Contract grant sponsor: Westat, Inc; Contract grant number:
HHSN261201100018C.; Contract grant sponsor: Natural Sciences and
Engineering Research Council of Canada; Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health.
NR 32
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD DEC
PY 2016
VL 91
IS 12
BP 1215
EP 1220
DI 10.1002/ajh.24545
PG 6
WC Hematology
SC Hematology
GA EI8BY
UT WOS:000392730900021
PM 27570172
ER
PT J
AU Salem, D
Stetler-Stevenson, M
Yuan, C
Landgren, O
AF Salem, Dalia
Stetler-Stevenson, Maryalice
Yuan, Constance
Landgren, Ola
TI Myeloma minimal residual disease testing in the United States: Evidence
of improved standardization
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Letter
ID MULTIPLE-MYELOMA; FLOW-CYTOMETRY; CONSENSUS GUIDELINES
C1 [Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA.
RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA.
EM landgrec@mskcc.org
RI Salem, Dalia/R-9314-2016
OI Salem, Dalia/0000-0002-4209-2260
FU Intramural Research Program of the National Cancer Institute of the
National Institutes of Health
FX Contract grant sponsor: Intramural Research Program of the National
Cancer Institute of the National Institutes of Health.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD DEC
PY 2016
VL 91
IS 12
BP E502
EP E503
DI 10.1002/ajh.24540
PG 3
WC Hematology
SC Hematology
GA EI8BY
UT WOS:000392730900008
PM 27556705
ER
PT J
AU Rodgers, GP
AF Rodgers, Griffin P.
TI First Lecture to New Doctors: 5 Lessons Learned
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
C1 [Rodgers, Griffin P.] NIDDK, NIH, Bldg 31,Room 9A52,31 Ctr Dr, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NIDDK, NIH, Bldg 31,Room 9A52,31 Ctr Dr, Bethesda, MD 20892 USA.
EM Rebecca.Cerio@nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD DEC
PY 2016
VL 352
IS 6
BP 615
EP 617
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA EI8DX
UT WOS:000392736700011
PM 27916217
ER
PT J
AU Pomann, GM
Staicu, AM
Lobaton, EJ
Mejia, AF
Dewey, BE
Reich, DS
Sweeney, EM
Shinohara, RT
AF Pomann, Gina-Maria
Staicu, Ana-Maria
Lobaton, Edgar J.
Mejia, Amanda F.
Dewey, Blake E.
Reich, Daniel S.
Sweeney, Elizabeth M.
Shinohara, Russell T.
TI A LAG FUNCTIONAL LINEAR MODEL FOR PREDICTION OF MAGNETIZATION TRANSFER
RATIO IN MULTIPLE SCLEROSIS LESIONS
SO Annals of Applied Statistics
LA English
DT Article
DE Functional data analysis; functional linear model; magnetization
transfer ratio; image analysis
ID SPARSE LONGITUDINAL DATA; DIAGNOSTIC-CRITERIA; REGRESSION-ANALYSIS;
CONTRAST SYNTHESIS; MRI; BRAIN; REMYELINATION; DEMYELINATION; EVOLUTION;
CURVES
AB We propose a lag functional linear model to predict a response using multiple functional predictors observed at discrete grids with noise. Two procedures are proposed to estimate the regression parameter functions: (1) an approach that ensures smoothness for each value of time using generalized cross-validation; and (2) a global smoothing approach using a restricted maximum likelihood framework. Numerical studies are presented to analyze predictive accuracy in many realistic scenarios. The methods are employed to estimate a magnetic resonance imaging (MRI)-based measure of tissue damage (the magnetization transfer ratio, or MTR) in multiple sclerosis (MS) lesions, a disease that causes damage to the myelin sheaths around axons in the central nervous system. Our method of estimation of MTR within lesions is useful retrospectively in research applications where MTR was not acquired, as well as in clinical practice settings where acquiring MTR is not currently part of the standard of care. The model facilitates the use of commonly acquired imaging modalities to estimate MTR within lesions, and outperforms cross-sectional models that do not account for temporal patterns of lesion development and repair.
C1 [Pomann, Gina-Maria] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Staicu, Ana-Maria] North Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA.
[Lobaton, Edgar J.] North Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA.
[Mejia, Amanda F.] Indiana Univ, Dept Stat, Bloomington, IN 47405 USA.
[Dewey, Blake E.; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Sweeney, Elizabeth M.] Rice Univ, Dept Stat, Houston, TX 77005 USA.
[Shinohara, Russell T.] Univ Penn, Ctr Clin Epidemiol, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Shinohara, Russell T.] Univ Penn, Biostat Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Pomann, GM (reprint author), Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
EM gp43@duke.edu; astaicu@ncsu.edu; edgar.lobaton@ncsu.edu;
mandy.mejia@gmail.com; blake.dewey@nih.gov; reichds@ninds.nih.gov;
esweene6@jhu.edu; rshi@mail.med.upenn.edu
FU Intramural Research Program of NINDS
FX We would like to acknowledge the conscientious efforts of the
hard-working Associate Editor, whose clear guidance led to this
publication. The study was supported in part by the Intramural Research
Program of NINDS. Its contents are solely the responsibility of the
authors and do not necessarily represent the official view of the
granting organizations.
NR 53
TC 0
Z9 0
U1 0
U2 0
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 1932-6157
J9 ANN APPL STAT
JI Ann. Appl. Stat.
PD DEC
PY 2016
VL 10
IS 4
BP 2325
EP 2348
DI 10.1214/16-AOAS981
PG 24
WC Statistics & Probability
SC Mathematics
GA EI9HR
UT WOS:000392819100028
ER
PT J
AU Ferris, RL
Geiger, JL
Trivedi, S
Schmitt, NC
Heron, DE
Johnson, JT
Kim, S
Duvvuri, U
Clump, DA
Bauman, JE
Ohr, JP
Gooding, WE
Argiris, A
AF Ferris, R. L.
Geiger, J. L.
Trivedi, S.
Schmitt, N. C.
Heron, D. E.
Johnson, J. T.
Kim, S.
Duvvuri, U.
Clump, D. A.
Bauman, J. E.
Ohr, J. P.
Gooding, W. E.
Argiris, A.
TI Phase II trial of post-operative radiotherapy with concurrent cisplatin
plus panitumumab in patients with high-risk, resected head and neck
cancer
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE panitumumab; head and neck squamous cell carcinoma; clinical trial;
cisplatin chemoradiotherapy
ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; STAT1 ACTIVATION;
CHEMOTHERAPY; CETUXIMAB; CHEMORADIOTHERAPY; THERAPY
AB Background: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC.
Patients and methods: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or >= 2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30mg/m(2) and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS).
Results: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%).
Conclusions: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted.
C1 [Ferris, R. L.; Heron, D. E.; Clump, D. A.; Bauman, J. E.; Ohr, J. P.; Gooding, W. E.] Univ Pittsburgh, Canc Immunol Program, Inst Canc, Pittsburgh, PA USA.
[Ferris, R. L.; Trivedi, S.; Heron, D. E.; Johnson, J. T.; Kim, S.; Duvvuri, U.] Univ Pittsburgh, Dept Otolaryngol, Div Head & Neck Surg, Pittsburgh, PA USA.
[Ferris, R. L.] Univ Pittsburgh, Div Hematol Oncol, Immunol, Pittsburgh, PA USA.
[Geiger, J. L.; Bauman, J. E.; Ohr, J. P.] Univ Pittsburgh, Div Hematol Oncol, Internal Med, Pittsburgh, PA USA.
[Schmitt, N. C.; Clump, D. A.] Johns Hopkins Univ, Dept Otolaryngol, Baltimore, MD USA.
[Schmitt, N. C.] NIDCD, Tumor Biol Sect, NIH, Bethesda, MD USA.
[Heron, D. E.] Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA USA.
[Argiris, A.] Hygeia Hosp, Dept Med Oncol, Athens, Greece.
[Argiris, A.] Thomas Jefferson Univ, Dept Med Oncol, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
RP Ferris, RL (reprint author), Hillman Canc Ctr Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA.
EM ferrrl@upmc.edu
FU National Institute of Health [R01 DE 019727, P50 CA097190, T32
CA060397]; University of Pittsburgh Cancer Institute [P30 CA047904]
FX This work was supported by National Institute of Health (grants R01 DE
019727, P50 CA097190, T32 CA060397) and used the University of
Pittsburgh Cancer Institute award P30 CA047904.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2016
VL 27
IS 12
BP 2257
EP 2262
DI 10.1093/annonc/mdw428
PG 7
WC Oncology
SC Oncology
GA EI9JW
UT WOS:000392825100018
PM 27733374
ER
PT J
AU Hagelstein, V
Ortland, I
Wilmer, A
Mitchell, SA
Jaehde, U
AF Hagelstein, V.
Ortland, I.
Wilmer, A.
Mitchell, S. A.
Jaehde, U.
TI Validation of the German patient-reported outcomes version of the common
terminology criteria for adverse events (PRO-CTCAE (TM))
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE cancer; German; patient-reported outcomes; PRO-CTCAE; questionnaire;
validation
ID STEM-CELL TRANSPLANTATION; CANCER; RELIABILITY; INSTRUMENT; VALIDITY;
ONCOLOGY
AB Background: Integrating the patient's perspective has become an increasingly important component of adverse event reporting. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE (TM)). This instrument has been translated into German and linguistically validated; however, its quantitative measurement properties have not been evaluated.
Patients and methods: A German language survey that included 31 PRO-CTCAE items, as well as the EORTC QLQ-C30 and the Oral Mucositis Daily Questionnaire (OMDQ), was distributed at 10 cancer treatment settings in Germany and Austria. Item quality was assessed by analysis of acceptability and comprehensibility. Reliability was evaluated by using Cronbach's' alpha and validity by principal components analysis (PCA), multitrait-multimethod matrix (MTMM) and known groups validity techniques.
Results: Of 660 surveys distributed to the study centres, 271 were returned (return rate 41%), and data from 262 were available for analysis. Participants' median age was 59.7 years, and 69.5% of the patients were female. Analysis of item quality supported the comprehensibility of the 31 PRO-CTCAE items. Reliability was very good; Cronbach's' alpha correlation coefficients were >0.9 for almost all item clusters. Construct validity of the PRO-CTCAE core item set was shown by identifying 10 conceptually meaningful item clusters via PCA. Moreover, construct validity was confirmed by the MTMM: monotrait-heteromethod comparison showed 100% high correlation, whereas heterotrait-monomethod comparison indicated 0% high correlation. Known groups validity was supported; PRO-CTCAE scores were significantly lower for those with impaired versus preserved health-related quality of life.
Conclusion: A set of 31 items drawn from the German PRO-CTCAE item library demonstrated favourable measurement properties. These findings add to the body of evidence that PRO-CTCAE provides a rigorous method to capture patient self-reports of symptomatic toxicity for use in cancer clinical trials.
C1 [Hagelstein, V.; Ortland, I.; Wilmer, A.; Jaehde, U.] Univ Bonn, Inst Pharm, Clin Pharm, Immenburg 4, D-53121 Bonn, Germany.
[Mitchell, S. A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Rockville, MD USA.
RP Jaehde, U (reprint author), Univ Bonn, Inst Pharm, Clin Pharm, Immenburg 4, D-53121 Bonn, Germany.
EM u.jaehde@uni-bonn.de
NR 21
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2016
VL 27
IS 12
BP 2294
EP 2299
DI 10.1093/annonc/mdw422
PG 7
WC Oncology
SC Oncology
GA EI9JW
UT WOS:000392825100024
PM 27681863
ER
PT J
AU Hirsch, D
Ried, T
AF Hirsch, Daniela
Ried, Thomas
TI Targeting colorectal cancer (stem-like) cells using LGR5 directed
antibody drug conjugates
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID STEM/PROGENITOR CELLS; SMALL-INTESTINE; OVEREXPRESSION; IDENTIFICATION;
REGENERATION; RECEPTORS; MARKER; TUMORS; COLON
C1 [Hirsch, Daniela] Heidelberg Univ, Univ Med Ctr Mannheim, Inst Pathol, Mannheim, Germany.
[Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov
NR 26
TC 0
Z9 0
U1 2
U2 2
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD DEC
PY 2016
VL 4
IS 24
AR 508
DI 10.21037/atm.2016.11.78
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI7DE
UT WOS:000392656900030
PM 28149870
ER
PT J
AU Kim, C
Giaccone, G
AF Kim, Chul
Giaccone, Giuseppe
TI Lessons learned from BATTLE-2 in the war on cancer: the use of Bayesian
method in clinical trial design
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ADAPTIVE RANDOMIZATION;
KRAS MUTATION; PHASE-II; BREAST-CANCER; THERAPY; CHEMOTHERAPY;
PREDICTOR; MUTANT
C1 [Kim, Chul] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 24
TC 0
Z9 0
U1 1
U2 1
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD DEC
PY 2016
VL 4
IS 23
AR 466
DI 10.21037/atm.2016.11.48
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EI7CA
UT WOS:000392653700015
PM 28090522
ER
PT J
AU Xu, ZL
Taylor, JA
Leung, YK
Ho, SM
Niu, L
AF Xu, Zongli
Taylor, Jack A.
Leung, Yuet-Kin
Ho, Shuk-Mei
Niu, Liang
TI oxBS-MLE: an efficient method to estimate 5-methylcytosine and
5-hydroxymethylcytosine in paired bisulfite and oxidative bisulfite
treated DNA
SO BIOINFORMATICS
LA English
DT Article
ID CONVERSION
AB Motivation: 5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are important epigenetic regulators of gene expression. 5mC and 5hmC levels can be computationally inferred at single base resolution using sequencing or array data from paired DNA samples that have undergone bisulfite and oxidative bisulfite conversion. Current estimation methods have been shown to produce irregular estimates of 5hmC level or are extremely computation intensive.
Results: We developed an efficient method oxBS-MLE based on binomial modeling of paired bisulfite and oxidative bisulfite data from sequencing or array analysis. Evaluation in several datasets showed that it outperformed alternative methods in estimate accuracy and computation speed.
C1 [Xu, Zongli; Taylor, Jack A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Taylor, Jack A.] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Leung, Yuet-Kin; Ho, Shuk-Mei; Niu, Liang] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA.
RP Niu, L (reprint author), Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA.
EM niulg@ucmail.uc.edu
OI xu, zongli/0000-0002-9034-8902
FU Center for Environmental Genetics grant (NIEHS award) [P30ES00606];
NIEHS [ES022071]; NIH (NIEHS) [Z01 ES049033, Z01 ES049032]
FX This research was supported by the Center for Environmental Genetics
grant (NIEHS award P30ES00606), NIEHS grant (ES022071), and Intramural
Research Program of the NIH (NIEHS Z01 ES049033 and Z01 ES049032).
NR 10
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD DEC 1
PY 2016
VL 32
IS 23
BP 3667
EP 3669
DI 10.1093/bioinformatics/btw527
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA EI8IM
UT WOS:000392749500018
PM 27522082
ER
PT J
AU Zarate, CA
Machado-Vieira, R
AF Zarate, Carlos A., Jr.
Machado-Vieira, Rodrigo
TI GSK-3: A key regulatory target for ketamine's rapid antidepressant
effects mediated by enhanced AMPA to NMDA throughput
SO BIPOLAR DISORDERS
LA English
DT Editorial Material
DE alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA);
glycogen synthase kinase 3 (GSK-3); ketamine
ID GLYCOGEN-SYNTHASE KINASE-3; RECEPTOR ANTAGONISTS; BIPOLAR DISORDER; MOOD
DISORDERS; DOUBLE-BLIND; DEPRESSION; INHIBITION; PHOSPHORYLATION;
MECHANISMS; INCREASES
C1 [Zarate, Carlos A., Jr.; Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) [ZIA MH002857]; NARSAD Independent Investigator Award;
Brain and Behavior Mood Disorders Research Award
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH; ZIA MH002857), by a NARSAD Independent
Investigator Award to CAZ, and by a Brain and Behavior Mood Disorders
Research Award to CAZ. CAZ is listed as a co-inventor on a patent for
the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other
stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine
metabolites in the treatment of depression and neuropathic pain. CAZ is
listed as co-inventor on a patent application for the use of
(2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the
treatment of depression, anxiety, anhedonia, suicidal ideation, and
post-traumatic stress disorders; he has assigned his patent rights to
the U.S. government but will share a percentage of any royalties that
may be received by the government. RM-V has no conflicts of interest to
disclose, financial or otherwise.
NR 32
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD DEC
PY 2016
VL 18
IS 8
BP 702
EP 705
DI 10.1111/bdi.12452
PG 4
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA EI9GX
UT WOS:000392817000010
PM 27900801
ER
PT J
AU Psachoulia, K
Chamberlain, KA
Heo, D
Davis, SE
Paskus, JD
Nanescu, SE
Dupree, JL
Wynn, TA
Huang, JK
AF Psachoulia, Konstantina
Chamberlain, Kelly A.
Heo, Dongeun
Davis, Stephanie E.
Paskus, Jeremiah D.
Nanescu, Sonia E.
Dupree, Jeffrey L.
Wynn, Thomas A.
Huang, Jeffrey K.
TI IL4I1 augments CNS remyelination and axonal protection by modulating T
cell driven inflammation
SO BRAIN
LA English
DT Article
DE inflammation; remyelination; macrophages; interleukin-4 induced 1
(IL4I1); experimental autoimmune encephalomyelitis (EAE)
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGRESSIVE
MULTIPLE-SCLEROSIS; MATRIX METALLOPROTEINASE-12; THERAPEUTIC STRATEGIES;
MACROPHAGE ACTIVATION; INDUCED DEMYELINATION; SPINAL-CORD; MICROGLIA;
DISEASE; DIFFERENTIATION
AB Myelin regeneration (remyelination) is a spontaneous process that occurs following central nervous system demyelination. However, for reasons that remain poorly understood, remyelination fails in the progressive phase of multiple sclerosis. Emerging evidence indicates that alternatively activated macrophages in central nervous system lesions are required for oligodendrocyte progenitor differentiation into remyelinating oligodendrocytes. Here, we show that an alternatively activated macrophage secreted enzyme, interleukin-four induced one (IL4I1), is upregulated at the onset of inflammation resolution and remyelination in mouse central nervous system lesions after lysolecithin-induced focal demyelination. Focal demyelination in mice lacking IL4I1 or interleukin 4 receptor alpha (IL4R alpha) results in increased proinflammatory macrophage density, remyelination impairment, and axonal injury in central nervous system lesions. Conversely, recombinant IL4I1 administration into central nervous system lesions reduces proinflammatory macrophage density, enhances remyelination, and rescues remyelination impairment in IL4R alpha deficient mice. We find that IL4I1 does not directly affect oligodendrocyte differentiation, but modulates inflammation by reducing interferon gamma and IL17 expression in lesioned central nervous system tissues, and in activated T cells from splenocyte cultures. Remarkably, intravenous injection of IL4I1 into mice with experimental autoimmune encephalomyelitis at disease onset significantly reversed disease severity, resulting in recovery from hindlimb paralysis. Analysis of post-mortem tissues reveals reduced axonal dystrophy in spinal cord, and decreased CD4(+) T cell populations in spinal cord and spleen tissues. These results indicate that IL4I1 modulates inflammation by regulating T cell expansion, thereby permitting the formation of a favourable environment in the central nervous system tissue for remyelination. Therefore, IL4I1 is a potentially novel therapeutic for promoting central nervous system repair in multiple sclerosis.
C1 [Psachoulia, Konstantina; Chamberlain, Kelly A.; Heo, Dongeun; Davis, Stephanie E.; Paskus, Jeremiah D.; Nanescu, Sonia E.; Huang, Jeffrey K.] Georgetown Univ, Dept Biol, 37th & O St,NW, Washington, DC 20057 USA.
[Dupree, Jeffrey L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Huang, JK (reprint author), Georgetown Univ, Dept Biol, 37th & O St,NW, Washington, DC 20057 USA.
EM jeffrey.huang@georgetown.edu
OI Huang, Jeffrey/0000-0003-0996-9451
FU NIH-NINDS [1R21NS091890-01, 5T32NS041218]; National Multiple Sclerosis
Society [PP2159]; Georgetown University; Georgetown College; TurnFirst
RDS Scholarship; NIH-NCATS [TL1TR001431]; NIH-NINDS Center [5P30
NS047463]; NIH-NCI Cancer Center [P30 CAO16059]
FX This project was supported, in part, by funding from the NIH-NINDS grant
1R21NS091890-01 (J.K.H.), National Multiple Sclerosis Society grant
PP2159 (J.K.H.), Georgetown University Music for the Mind Award
(J.K.H.), Georgetown University Partners in Research Award (J.K.H.),
Georgetown College (J.K.H.), NIH-NINDS Training Award 5T32NS041218
(K.A.C), TurnFirst RDS Scholarship (S.E.D), and NIH-NCATS Training Award
TL1TR001431 (S.E.D). Transmission electron microscopy was performed at
the VCU - Dept. of Anatomy and Neurobiology Microscopy Facility,
supported, in part, by funding from NIH-NINDS Center Core grant 5P30
NS047463 and NIH-NCI Cancer Center grant P30 CAO16059 (J.L.D).
NR 63
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD DEC
PY 2016
VL 139
BP 3121
EP 3136
DI 10.1093/brain/aww254
PN 12
PG 16
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA EI7US
UT WOS:000392709800015
PM 27797811
ER
PT J
AU Muller, SH
Girard, SL
Hopfner, F
Merner, ND
Bourassa, CV
Lorenz, D
Clark, LN
Tittmann, L
Soto-Ortolaza, AI
Klebe, S
Hallett, M
Schneider, SA
Hodgkinson, CA
Lieb, W
Wszolek, ZK
Pendziwiat, M
Lorenzo-Betancor, O
Poewe, W
Ortega-Cubero, S
Seppi, K
Rajput, A
Hussl, A
Rajput, AH
Berg, D
Dion, PA
Wurster, I
Shulman, JM
Srulijes, K
Haubenberger, D
Pastor, P
Vilarino-Guell, C
Postuma, RB
Bernard, G
Ladwig, KH
Dupre, N
Jankovic, J
Strauch, K
Panisset, M
Winkelmann, J
Testa, CM
Zeuner, KE
Reischl, E
Ross, OA
Arzberger, T
Chouinard, S
Deuschl, G
Louis, ED
Kuhlenbaumer, G
Rouleau, GA
AF Mueller, Stefanie H.
Girard, Simon L.
Hopfner, Franziska
Merner, Nancy D.
Bourassa, Cynthia V.
Lorenz, Delia
Clark, Lorraine N.
Tittmann, Lukas
Soto-Ortolaza, Alexandra I.
Klebe, Stephan
Hallett, Mark
Schneider, Susanne A.
Hodgkinson, Colin A.
Lieb, Wolfgang
Wszolek, Zbigniew K.
Pendziwiat, Manuela
Lorenzo-Betancor, Oswaldo
Poewe, Werner
Ortega-Cubero, Sara
Seppi, Klaus
Rajput, Alex
Hussl, Anna
Rajput, Ali H.
Berg, Daniela
Dion, Patrick A.
Wurster, Isabel
Shulman, Joshua M.
Srulijes, Karin
Haubenberger, Dietrich
Pastor, Pau
Vilarino-Guell, Carles
Postuma, Ronald B.
Bernard, Genevieve
Ladwig, Karl-Heinz
Dupre, Nicolas
Jankovic, Joseph
Strauch, Konstantin
Panisset, Michel
Winkelmann, Juliane
Testa, Claudia M.
Zeuner, Kirsten E.
Reischl, Eva
Ross, Owen A.
Arzberger, Thomas
Chouinard, Sylvain
Deuschl, Guenther
Louis, Elan D.
Kuhlenbaeumer, Gregor
Rouleau, Guy A.
TI Genome-wide association study in essential tremor identifies three new
loci
SO BRAIN
LA English
DT Article
DE genome-wide association study; movement disorders; tremor; genetics;
essential tremor
ID QUALITY-CONTROL; DISEASE; GENETICS; TOOL
AB We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.
C1 [Mueller, Stefanie H.; Hopfner, Franziska; Schneider, Susanne A.; Berg, Daniela; Zeuner, Kirsten E.; Deuschl, Guenther; Kuhlenbaeumer, Gregor] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Neurol, Kiel, Germany.
[Girard, Simon L.] Univ Quebec Chicoutimi, Dept Sci Fondamentales, Saguenay, PQ, Canada.
[Girard, Simon L.; Merner, Nancy D.; Bourassa, Cynthia V.; Dion, Patrick A.; Postuma, Ronald B.; Bernard, Genevieve; Rouleau, Guy A.] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ, Canada.
[Merner, Nancy D.] Auburn Univ, Dept Drug Discovery & Dev, Harrison Sch Pharm, Auburn, AL 36849 USA.
[Lorenz, Delia] Univ Wurzburg, Univ Childrens Hosp, Wurzburg, Germany.
[Clark, Lorraine N.] Columbia Univ, Taub Inst, Dept Pathol & Cell Biol, New York, NY USA.
[Tittmann, Lukas] Christian Albrechts Univ Kiel, Inst Epidemiol, Kiel, Germany.
[Tittmann, Lukas; Lieb, Wolfgang] Biobank POPGEN, Kiel, Germany.
[Soto-Ortolaza, Alexandra I.; Wszolek, Zbigniew K.; Ross, Owen A.] Mayo Clin, Dept Neurosci & Neurol, Jacksonville, FL USA.
[Klebe, Stephan] Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany.
[Klebe, Stephan] Univ Hosp Freiburg, Dept Neurol, Freiburg, Germany.
[Hallett, Mark; Haubenberger, Dietrich] NINDS, Intramural Res Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Schneider, Susanne A.] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany.
[Hodgkinson, Colin A.] NIAAA, NIH, Bethesda, MD USA.
[Pendziwiat, Manuela] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Paediat Neurol, Kiel, Germany.
[Lorenzo-Betancor, Oswaldo; Ortega-Cubero, Sara; Pastor, Pau] Univ Navarra, CIBERNED, Ctr Investi Biomed Red Enfermedades Neurodegenera, Neurogenet,Div Neurosci,Ctr Appl Med Res CIMA, E-31080 Pamplona, Spain.
[Lorenzo-Betancor, Oswaldo; Ortega-Cubero, Sara; Pastor, Pau] Univ Barcelona, Hosp Univ Mutua Terrassa, Dept Neurol, Barcelona, Spain.
[Poewe, Werner; Seppi, Klaus; Hussl, Anna] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.
[Rajput, Alex; Rajput, Ali H.] Univ Saskatchewan, Saskatoon, SK, Canada.
[Rajput, Alex; Rajput, Ali H.] Saskatoon Hlth Reg, Saskatoon, SK, Canada.
[Wurster, Isabel; Srulijes, Karin] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Wurster, Isabel; Srulijes, Karin] German Ctr Neurodegenerat Dis, Tubingen, Germany.
[Shulman, Joshua M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
[Vilarino-Guell, Carles] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Postuma, Ronald B.] Montreal Gen Hosp, Dept Neurol, Montreal, PQ, Canada.
[Bernard, Genevieve] Montreal Childrens Hosp, Div Pediat Neurol, Dept Pediat, Montreal, PQ, Canada.
[Bernard, Genevieve] Montreal Childrens Hosp, Div Pediat Neurol, Dept Neurol, Montreal, PQ, Canada.
[Bernard, Genevieve] Montreal Childrens Hosp, Div Pediat Neurol, Dept Neurosurg, Montreal, PQ, Canada.
[Ladwig, Karl-Heinz; Reischl, Eva] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
[Ladwig, Karl-Heinz] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychosomat Med & Psychotherapy, Munich, Germany.
[Dupre, Nicolas] Univ Laval, CHU Quebec Enfant Jesus, Fac Med, Quebec City, PQ, Canada.
[Strauch, Konstantin] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
[Strauch, Konstantin] Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Jankovic, Joseph; Panisset, Michel; Chouinard, Sylvain] Ctr Hosp Univ Montreal, Unite Troubles mouvement Andre Barbeau, Montreal, PQ, Canada.
[Winkelmann, Juliane] Helmholtz Zentrum Munchen, Inst Neurogen, Munich, Germany.
[Winkelmann, Juliane] Tech Univ Munich, Klinikum Rechts Isar, Neurol Klin & Poliklin, Munich, Germany.
[Winkelmann, Juliane] Munich Cluster Syst Neurol Synergy, Munich, Germany.
[Testa, Claudia M.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA.
[Testa, Claudia M.] Virginia Commonwealth Univ, Parkinsons & Movement Disorders Ctr, Richmond, VA USA.
[Reischl, Eva] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Arzberger, Thomas] Univ Munich, Ctr Neuropathol & Prion Res, D-80539MU Munich, Germany.
[Arzberger, Thomas] Ludwig Maximilians Univ Munchen, Ctr Neuropathol & Prion Res, Munich, Germany.
[Louis, Elan D.] Yale Univ, Yale Sch Med, Dept Neurol, New Haven, CT USA.
RP Rouleau, GA (reprint author), McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ, Canada.
EM guy.rouleau@mcgill.ca
RI Pastor, Pau/C-9834-2009; Lieb, Wolfgang/C-1990-2012; Vilarino-Guell,
Carles/D-8628-2011
OI Pastor, Pau/0000-0002-7493-8777; Vilarino-Guell,
Carles/0000-0002-5612-5940
FU CIHR; Canada Research Chair in genetics of the nervous system; DFG
[KU1194/9-1]; National Institutes of Health [NIH R01 NS073872]; FRQS;
NIH [R01 NS073872]; Munich Center of Health Sciences (MC-Health);
Ludwig-Maximilians-Universitat as part of LMUinnovativ; Mayo Clinic
Florida Research Committee [NS072187]
FX This study was made possible by funding from the CIHR, Canada Research
Chair in genetics of the nervous system and from the DFG (KU1194/9-1)
and from the National Institutes of Health (NIH R01 NS073872). S.L.G. is
grateful to FRQS for financial support. G.A.R. is grateful to CIHR and
to the Canada Research Chair in genetics of the nervous system. G.K.,
G.D. and F.H. are grateful to the DFG for financial support
(KU1194/9-1). E.D.L. and L.N.C. were supported by NIH R01 NS073872. KORA
research was supported within the Munich Center of Health Sciences
(MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ.
The Mayo Clinic Florida is a Morris K. Udall Parkinson's Disease
Research Center of Excellence (NINDS P50 #NS072187), and this work was
supported by the Mayo Clinic Florida Research Committee. This research
was supported by a donation of the Rhein-Taunus-Krematorium. C.M.T. is
grateful to the Emory ADRC and National Institute of Aging (P50
AG025688).
NR 19
TC 1
Z9 1
U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD DEC
PY 2016
VL 139
BP 3163
EP 3169
DI 10.1093/brain/aww242
PN 12
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA EI7US
UT WOS:000392709800018
PM 27797806
ER
PT J
AU Uhde, M
Ajamian, M
Li, XT
Wormser, GP
Marques, A
Alaedini, A
AF Uhde, Melanie
Ajamian, Mary
Li, Xueting
Wormser, Gary P.
Marques, Adriana
Alaedini, Armin
TI Expression of C-Reactive Protein and Serum Amyloid A in Early to Late
Manifestations of Lyme Disease
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Lyme disease; Borrelia burgdorferi; acute-phase response; inflammation;
post-treatment Lyme disease syndrome
ID BODY-FAT; ARTHRITIS; CHILDREN; SAA; CRP
AB Background. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.
Methods. Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.
Results. CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.
Conclusions. These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection.
C1 [Uhde, Melanie; Ajamian, Mary; Li, Xueting; Alaedini, Armin] Columbia Univ, Dept Med, Med Ctr, 1130 St Nicholas Ave,9th Flr, New York, NY 10032 USA.
[Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA.
[Marques, Adriana] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Alaedini, A (reprint author), Columbia Univ, Dept Med, Med Ctr, 1130 St Nicholas Ave,9th Flr, New York, NY 10032 USA.
EM aa819@columbia.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) of NIH
[R56AI093763, U54AI057158]; National Institute of Allergy and Infectious
Diseases (NIAID) of NIH (Center of Excellence); Global Lyme Alliance;
Intramural Research Program of NIAID
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (NIAID) of NIH (grants R56AI093763 to A. A., and
U54AI057158 to A. A.; principal investigator of the Center of Excellence
Grant, W. I. Lipkin), the Global Lyme Alliance (A. A.), and the
Intramural Research Program of NIAID (A. R. M.).
NR 25
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 1
PY 2016
VL 63
IS 11
BP 1399
EP 1404
DI 10.1093/cid/ciw599
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EI7WA
UT WOS:000392713900001
PM 27585799
ER
PT J
AU Playford, EG
Lipman, J
Jones, M
Lau, AF
Kabir, M
Chen, SCA
Marriott, DJ
Seppelt, I
Gottlieb, T
Cheung, W
Iredell, JR
McBryde, ES
Sorrell, TC
AF Playford, E. Geoffrey
Lipman, Jeffrey
Jones, Michael
Lau, Anna F.
Kabir, Masrura
Chen, Sharon C. -A.
Marriott, Deborah J.
Seppelt, Ian
Gottlieb, Thomas
Cheung, Winston
Iredell, Jonathan R.
McBryde, Emma S.
Sorrell, Tania C.
TI Problematic Dichotomization of Risk for Intensive Care Unit
(ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive
Model to Categorize 3 Levels of Risk From a Multicenter Prospective
Cohort of Australian ICU Patients
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE invasive candidiasis; risk prediction; critical care; prophylaxis;
candidemia
ID CRITICALLY-ILL; FUNGAL-INFECTIONS; SURGICAL-PATIENTS; COLONIZATION;
VALIDATION; BLOOD; METAANALYSIS; PROPHYLAXIS; INITIATION; MORTALITY
AB Background. Delayed antifungal therapy for invasive candidiasis (IC) contributes to poor outcomes. Predictive risk models may allow targeted antifungal prophylaxis to those at greatest risk.
Methods. A prospective cohort study of 6685 consecutive nonneutropenic patients admitted to 7 Australian intensive care units (ICUs) for >= 72 hours was performed. Clinical risk factors for IC occurring prior to and following ICU admission, colonization with Candida species on surveillance cultures from 3 sites assessed twice weekly, and the occurrence of IC >= 72 hours following ICU admission or <= 72 hours following ICU discharge were measured. From these parameters, a risk-predictive model for the development of ICU-acquired IC was then derived.
Results. Ninety-six patients (1.43%) developed ICU-acquired IC. A simple summation risk-predictive model using the 10 independently significant variables associated with IC demonstrated overall moderate accuracy (area under the receiver operating characteristic curve = 0.82). No single threshold score could categorize patients into clinically useful high-and low-risk groups. However, using 2 threshold scores, 3 patient cohorts could be identified: those at high risk (score >= 6, 4.8% of total cohort, positive predictive value [PPV] 11.7%), those at low risk (score <= 2, 43.1% of total cohort, PPV 0.24%), and those at intermediate risk (score 3-5, 52.1% of total cohort, PPV 1.46%).
Conclusions. Dichotomization of ICU patients into high-and low-risk groups for IC risk is problematic. Categorizing patients into high-, intermediate-, and low-risk groups may more efficiently target early antifungal strategies and utilization of newer diagnostic tests.
C1 [Playford, E. Geoffrey] Princess Alexandra Hosp, Infect Management Serv, Brisbane, Qld, Australia.
[Playford, E. Geoffrey] Univ Queensland, Sch Med, Brisbane, Qld, Australia.
[Lipman, Jeffrey] Royal Brisbane & Womens Hosp, Dept Intens Care, Brisbane, Qld, Australia.
[Lipman, Jeffrey] Univ Queensland, Brisbane, Qld, Australia.
[Jones, Michael] Macquarie Univ, Dept Psychol, Sydney, NSW, Australia.
[Lau, Anna F.; Kabir, Masrura; Iredell, Jonathan R.; Sorrell, Tania C.] Westmead Inst Med Res, Ctr Infect Dis & Microbiol, Westmead, NSW, Australia.
[Chen, Sharon C. -A.] Westmead Hosp, Inst Clin Pathol & Med Res, Ctr Infect Dis & Microbiol Lab Serv, Westmead, NSW, Australia.
[Chen, Sharon C. -A.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Marriott, Deborah J.] St Vincent Hosp, Dept Microbiol & Infect Dis, Worcester, MA 01604 USA.
[Seppelt, Ian] Univ Sydney, Dept Intens Care Med, Nepean Hosp, Sydney, NSW 2006, Australia.
[Gottlieb, Thomas] Concord Hosp, Dept Microbiol & Infect Dis, Concord, NSW, Australia.
[Cheung, Winston] Concord Hosp, Dept Intens Care Med, Concord, NSW, Australia.
[Iredell, Jonathan R.; Sorrell, Tania C.] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.
[McBryde, Emma S.] Univ Melbourne, Royal Melbourne Hosp, Victorian Infect Dis Serv, Melbourne, Vic 3010, Australia.
[Lau, Anna F.] NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
[McBryde, Emma S.] James Cook Univ, Australian Inst Trop Med & Hyg, Townsville, Qld, Australia.
RP Sorrell, TC (reprint author), Westmead Inst Med Res, Marie Bashir Inst, Level 4,196 Hawkesbury Rd, Westmead, NSW 2145, Australia.
EM tania.sorrell@sydney.edu.au
FU National Health and Medical Research Council of Australia [512307];
National Health and Medical Research Council of Australia (Centre for
Research Excellence) [264625]; Australian Universities Postgraduate
award; Pfizer Pharmaceuticals
FX This work was supported by the National Health and Medical Research
Council of Australia (project grant number 512307, Centre for Research
Excellence grant number 264625); an Australian Universities Postgraduate
award to A. F. L.; and an investigator-initiated grant from Pfizer
Pharmaceuticals. T. C. S. is a Sydney Medical Foundation Fellow.
NR 29
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 1
PY 2016
VL 63
IS 11
BP 1463
EP 1469
DI 10.1093/cid/ciw610
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EI7WA
UT WOS:000392713900010
PM 27601224
ER
PT J
AU Alvarado, MC
Malkova, L
Bachevalier, J
AF Alvarado, Maria C.
Malkova, Ludise
Bachevalier, Jocelyne
TI Development of relational memory processes in monkeys
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Article
DE Relational memory; Development; Medial temporal lobe; Prefrontal;
Macaque
ID TRANSVERSE-PATTERNING PROBLEM; OBJECT RECOGNITION MEMORY; RHESUS
MACAQUES; HIPPOCAMPAL-FORMATION; PERIRHINAL CORTEX; LOCATION MEMORY;
DAMAGE; LESIONS; TASK; ASSOCIATIONS
AB The present study tested whether relational memory processes, as measured by the transverse patterning problem, are late-developing in nonhuman primates as they are in humans. Eighteen macaques ranging from 3 to 36 months of age, were trained to solve a set of visual discriminations that formed the transverse patterning problem. Subjects were trained at 3, 4-6, 12, 15-24 or 36 months of age to solve three discriminations as follows: 1) A+ vs. B-; 2) B+ vs. C-; 3) C+ vs. A. When trained concurrently, subjects must adopt a relational strategy to perform accurately on all three problems. All 36 month old monkeys reached the criterion of 90% correct, but only one 24-month-old and one 15-month-old did, initially. Three-month old infants performed at chance on all problems. Six and 12-month-olds performed at 75-80% correct but used a linear' or elemental solution (e.g. A > B > C), which only yields correct performance on two problems. Retraining the younger subjects at 12, 24 or 36 months yielded a quantitative improvement on speed of learning, and a qualitative improvement in 24-36 month old monkeys for learning strategy. The results suggest that nonspatial relational memory develops late in macaques (as in humans), maturing between 15 and 24 months of age. (C) 2016 The Authors. Published by Elsevier Ltd.
C1 [Alvarado, Maria C.; Bachevalier, Jocelyne] Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA.
[Malkova, Ludise] Georgetown Univ, Washington, DC 20057 USA.
[Malkova, Ludise] NIMH, Bethesda, MD 20892 USA.
RP Alvarado, MC (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA.
EM malvara@emory.edu
FU Intramural Research Program of the National Institute of Mental
Health/National Institutes of Health/Department of Health and Human
Services; NIMH [MH58846]; NICHD [HD35471]; ORIP/OD [P51OD011132]
FX This project was funded in part by the Intramural Research Program of
the National Institute of Mental Health/National Institutes of
Health/Department of Health and Human Services; and by NIMH grantMH58846
and NICHD grant HD35471 to JB. Writing of this manuscript was supported
in part by ORIP/OD P51OD011132 (formerly NCRR P51RR000165).
NR 36
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
EI 1878-9307
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD DEC
PY 2016
VL 22
BP 27
EP 35
DI 10.1016/j.dcn.2016.10.007
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA EI7XD
UT WOS:000392716900004
PM 27833046
ER
PT J
AU Stern, ST
Martinez, MN
Stevens, DM
AF Stern, Stephan T.
Martinez, Marilyn N.
Stevens, David M.
TI When Is It Important to Measure Unbound Drug in Evaluating Nanomedicine
Pharmacokinetics?
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Editorial Material
ID PLASMA-PROTEIN BINDING; ALBUMIN-BOUND PACLITAXEL; IN-VIVO; NONLINEAR
PHARMACOKINETICS; ANTICANCER AGENTS; CANCER-PATIENTS; CREMOPHOR-FREE;
PHASE-I; DELIVERY; NANOPARTICLE
AB Nanoformulations have become important tools for modifying drug disposition, be it from the perspective of enabling prolonged drug release, protecting the drug molecule from metabolism, or achieving targeted delivery. When examining the in vivo pharmacokinetic properties of these formulations, most investigations either focus on systemic concentrations of total (encapsulated plus unencapsulated) drug, or concentrations of encapsulated and unencapsulated drug. However, it is rare to find studies that differentiate between protein-bound and unbound (free) forms of the unencapsulated drug. In light of the unique attributes of these formulations, we cannot simply assume it appropriate to rely upon the protein-binding properties of the traditionally formulated or legacy drug when trying to define the pharmacokinetic or pharmacokinetic/pharmacodynamic characteristics of these nanoformulations. Therefore, this commentary explores reasons why it is important to consider not only unencapsulated drug, but also the portion of unencapsulated drug that is not bound to plasma proteins. Specifically, we highlight those situations when it may be necessary to include measurement of unencapsulated, unbound drug concentrations as part of the nanoformulation pharmacokinetic evaluation.
C1 [Stern, Stephan T.; Stevens, David M.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Canc Res Technol Program, Nanotechnol Characterizat Lab, Frederick, MD USA.
[Martinez, Marilyn N.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,HFV-100, Rockville, MD 20855 USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,HFV-100, Rockville, MD 20855 USA.
EM marilyn.martinez@fda.hhs.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Institutes of Health National Cancer Institute
[HHSN261200800e001E]
FX This work was supported in whole or in part with federal funds from the
National Institutes of Health National Cancer Institute [Grant
HHSN261200800e001E].
NR 54
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PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD DEC
PY 2016
VL 44
IS 12
BP 1934
EP 1939
DI 10.1124/dmd.116.073148
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EI8AN
UT WOS:000392726600010
PM 27670412
ER
PT J
AU Nickbakhsh, S
Hall, MD
Dorigatti, I
Lycett, SJ
Mulatti, P
Monne, I
Fusaro, A
Woolhouse, MEJ
Rambaut, A
Kao, RR
AF Nickbakhsh, Sema
Hall, Matthew D.
Dorigatti, Ilaria
Lycett, Samantha J.
Mulatti, Paolo
Monne, Isabella
Fusaro, Alice
Woolhouse, Mark E. J.
Rambaut, Andrew
Kao, Rowland R.
TI Modelling the impact of co-circulating low pathogenic avian influenza
viruses on epidemics of highly pathogenic avian influenza in poultry
SO Epidemics
LA English
DT Article
DE Epidemiology; Interference; Cross-protection; Poultry; Mathematical
modelsa
ID HONG-KONG; A VIRUS; H5N1; HEMAGGLUTININ; INTERFERENCE; TRANSMISSION;
EMERGENCE; INFECTION; VIRULENCE; CHICKENS
AB It is well known that highly pathogenic avian influenza (HPAI) viruses emerge through mutation of precursor low pathogenic avian influenza (LPAI) viruses in domestic poultry populations. The potential for immunological cross-protection between these pathogenic variants is recognised but the epidemiological impact during co-circulation is not well understood. Here we use mathematical models to investigate whether altered flock infection parameters consequent to primary LPAI infections can impact on the spread of HPAI at the population level. First we used mechanistic models reflecting the co-circulatory dynamics of LPAI and HPAI within a single commercial poultry flock. We found that primary infections with LPAI led to HPAI prevalence being maximised under a scenario of high but partial cross-protection. We then tested the population impact in spatially-explicit simulations motivated by a major avian influenza A(H7N1) epidemic that afflicted the Italian poultry industry in 1999-2001. We found that partial cross-protection can lead to a prolongation of HPAI epidemic duration. Our findings have implications for the control of HPAI in poultry particularly for settings in which LPAI and HPAI frequently co-circulate. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Nickbakhsh, Sema; Kao, Rowland R.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Glasgow, Lanark, Scotland.
[Hall, Matthew D.; Lycett, Samantha J.; Woolhouse, Mark E. J.; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Hall, Matthew D.; Lycett, Samantha J.; Woolhouse, Mark E. J.; Rambaut, Andrew] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland.
[Dorigatti, Ilaria] Imperial Coll London, Sch Publ Hlth, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England.
[Mulatti, Paolo; Monne, Isabella; Fusaro, Alice] Ist Zooprofilatt Sperimentale Venezie, Legnaro, PD, Italy.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Nickbakhsh, Sema] Univ Glasgow, MRC, Ctr Virus Res Inst Infect Immun & Inflammat, Glasgow G61 1QH, Lanark, Scotland.
[Hall, Matthew D.] Imperial Coll London, Dept Infect Dis Epidemiol, London W2 1PG, England.
[Lycett, Samantha J.] Univ Edinburgh, Infect & Immun Div, Roslin Inst & R D SVS, Edinburgh EH25 9RG, Midlothian, Scotland.
RP Kao, RR (reprint author), Univ Glasgow, 464 Bearsden Rd, Glasgow G61 1QH, Lanark, Scotland.
EM rowland.kao@glasgow.ac.uk
OI Mulatti, Paolo/0000-0001-8188-997X; Lycett,
Samantha/0000-0003-3159-596X; Kao, Rowland/0000-0003-0919-6401; Fusaro,
Alice/0000-0002-8213-5472
FU Scottish Government's EPIC Centre of Expertise on Animal Disease
Outbreaks [65206]; Wellcome Trust [WT/093724]; European Union Seventh
Framework Programme [FP7] [278433-PREDEMIC]; Bill and Melinda Gates
Foundation [P20064, P46908]; University of Edinburgh
FX We thank Giovanni Cattoli, Stefano Marangon, and Marco de Nardi for
assistance with providing genetic sequences, epidemiological data and
input. We also thank Melissa Ward, Joseph Hughes, and Pablo Murcia for
helpful discussions. We also thank an anonymous referee for helpful
comments. This study was supported by The Scottish Government's EPIC
Centre of Expertise on Animal Disease Outbreaks (65206), VIZIONS a
strategic award from the Wellcome Trust (WT/093724), the European Union
Seventh Framework Programme [FP7/2007-2013] under Grant Agreement no
278433-PREDEMIC, and the Bill and Melinda Gates Foundation (grants
P20064 and P46908). SJL is supported by a Chancellors Fellowship from
the University of Edinburgh.
NR 34
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U1 7
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD DEC
PY 2016
VL 17
BP 27
EP 34
DI 10.1016/j.epidem.2016.10.005
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA EJ1CQ
UT WOS:000392948300004
PM 27788412
ER
PT J
AU Werkman, M
Tildesley, MJ
Brooks-Pollock, E
Keeling, MJ
AF Werkman, Marleen
Tildesley, Michael J.
Brooks-Pollock, Ellen
Keeling, Matt J.
TI Preserving privacy whilst maintaining robust epidemiological predictions
SO EPIDEMICS
LA English
DT Article
DE Metapopulation; Simulations; Stochastic model; Spatial aggregation
ID MOUTH-DISEASE; GREAT-BRITAIN; METAPOPULATION MODEL; FOOT; SPREAD;
DYNAMICS; STRATEGIES; MOVEMENTS; IMPACT; UK
AB Mathematical models are invaluable tools for quantifying potential epidemics and devising optimal control strategies in case of an outbreak. State-of-the-art models increasingly require detailed individual farm-based and sensitive data, which may not be available due to either lack of capacity for data collection or privacy concerns. However, in many situations, aggregated data are available for use. In this study, we systematically investigate the accuracy of predictions made by mathematical models initialised with varying data aggregations, using the UK 2001 Foot-and-Mouth Disease Epidemic as a case study. We consider the scenario when the only data available are aggregated into spatial grid cells, and develop a metapopulation model where individual farms in a single subpopulation are assumed to behave uniformly and transmit randomly. We also adapt this standard metapopulation model to capture heterogeneity in farm size and composition, using farm census data. Our results show that homogeneous models based on aggregated data overestimate final epidemic size but can perform well for predicting spatial spread. Recognising heterogeneity in farm sizes improves predictions of the final epidemic size, identifying risk areas, determining the likelihood of epidemic take-off and identifying the optimal control strategy. In conclusion, in cases where individual farm-based data are not available, models can still generate meaningful predictions, although care must be taken in their interpretation and use. (C) 2016 Published by Elsevier B.V.
C1 [Werkman, Marleen; Tildesley, Michael J.; Keeling, Matt J.] Univ Warwick, Math Inst, WIDER Ctr, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.
[Werkman, Marleen; Tildesley, Michael J.; Keeling, Matt J.] Univ Warwick, Sch Life Sci, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.
[Werkman, Marleen] Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Infect Dis Epidemiol, St Marys Campus, London, England.
[Tildesley, Michael J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Brooks-Pollock, Ellen] Univ Bristol, Sch Social & Community Med, Oakfield Grove BS8 2BN, Clifton, England.
RP Werkman, M (reprint author), Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Infect Dis Epidemiol, St Marys Campus, London, England.
EM m.werkman@imperial.ac.uk
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) Program,
Science and Technology Directorate, US Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Foreign
Animal Disease Modeling Program, Science and Technology Directorate, US
Department of Homeland Security [ST108-000017]; BBSRC [BB/K010972/3];
ERA-NET anihwa scheme; Department for Environment, Food & Rural Affairs
(Defra)
FX This work was made possible by funding from the Research and Policy for
Infectious Disease Dynamics (RAPIDD) Program, Science and Technology
Directorate, US Department of Homeland Security and Fogarty
International Center, National Institutes of Health and the Foreign
Animal Disease Modeling Program, Science and Technology Directorate, US
Department of Homeland Security (Grant ST108-000017) and BBSRC (grant
no. BB/K010972/3). MJK was funded through the ERA-NET anihwa scheme with
funding provided by the Department for Environment, Food & Rural Affairs
(Defra). Data was kindly provided by Defra. We are thankful to Colleen
Webb and Uno Wennergren for useful discussion on this manuscript.
NR 26
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD DEC
PY 2016
VL 17
BP 35
EP 41
DI 10.1016/j.epidem.2016.10.004
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA EJ1CQ
UT WOS:000392948300005
PM 27792892
ER
PT J
AU Xin, W
Edwards, N
Bonci, A
AF Xin, Wendy
Edwards, Nicholas
Bonci, Antonello
TI VTA dopamine neuron plasticity - the unusual suspects
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Review
DE astrocyte; dopamine; GABA; inhibition; plasticity; VTA
ID VENTRAL TEGMENTAL AREA; LONG-TERM POTENTIATION; ASTROCYTIC GLUTAMATE
UPTAKE; IN-VIVO; SYNAPTIC PLASTICITY; D-SERINE; NMDA-RECEPTORS;
SUBSTANTIA-NIGRA; GABA(B) RECEPTORS; PREFRONTAL CORTEX
AB Dopamine neurons in the ventral tegmental area (VTA) are involved in a variety of physiological and pathological conditions, ranging from motivated behaviours to substance use disorders. While many studies have shown that these neurons can express plasticity at excitatory and inhibitory synapses, little is known about how inhibitory inputs and glial activity shape the output of DA neurons and therefore, merit greater discussion. In this review, we will attempt to fill in a bit more of the puzzle, with a focus on inhibitory transmission and astrocyte function. We summarize the findings within the VTA as well as observations made in other brain regions that have important implications for plasticity in general and should be considered in the context of DA neuron plasticity.
C1 [Xin, Wendy; Edwards, Nicholas; Bonci, Antonello] NIDA, Synapt Plast Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Xin, Wendy; Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
RP Bonci, A (reprint author), NIDA, Synapt Plast Sect, Intramural Res Program, Baltimore, MD 21224 USA.; Bonci, A (reprint author), Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
EM Antonello.bonci@nih.gov
OI Xin, Wendy/0000-0002-1425-834X
NR 140
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U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD DEC
PY 2016
VL 44
IS 12
BP 2975
EP 2983
DI 10.1111/ejn.13425
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA EJ1CS
UT WOS:000392948500001
PM 27711998
ER
PT J
AU Rupp, B
Wlodawer, A
Minor, W
Helliwell, JR
Jaskolski, M
AF Rupp, Bernhard
Wlodawer, Alexander
Minor, Wladek
Helliwell, John R.
Jaskolski, Mariusz
TI Correcting the record of structural publications requires joint effort
of the community and journal editors
SO FEBS Journal
LA English
DT Article
DE biomolecular crystallography; database integrity; error correction;
structural databases; X-ray crystal structure models
ID CRYSTAL-STRUCTURE PAPERS; UNUSUAL-FEATURES; PLASTICITY; BACTERIAL; MODEL
AB Seriously flawed and even fictional models of biomolecular crystal structures, although rare, still persist in the record of structural repositories and databases. The ensuing problems of database contamination and persistence of publications based on incorrect structure models must be effectively addressed. The burden cannot be simply left to the critical voices who take the effort to contribute dissenting comments that are mostly ignored. The entire structural biology community, and particularly the journal editors who exercise significant power in this respect, must engage in a constructive dialog lest structural biology lose its credibility as an evidence-based empirical science.
C1 [Rupp, Bernhard] Kk Hofkristallamt, 991 Audrey Pl, Vista, CA 92084 USA.
[Rupp, Bernhard] Med Univ Innsbruck, Dept Genet Epidemiol, A-6020 Innsbruck, Austria.
[Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21701 USA.
[Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA.
[Helliwell, John R.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England.
[Jaskolski, Mariusz] Adam Mickiewicz Univ, Polish Acad Sci, Ctr Biocrystallog Res, Inst Bioorgan Chem,Dept Crystallog,Fac Chem, Poznan, Poland.
RP Rupp, B (reprint author), Kk Hofkristallamt, 991 Audrey Pl, Vista, CA 92084 USA.
EM br@hofkristallamt.org
OI Minor, Wladek/0000-0001-7075-7090
FU Austrian Science Foundation (FWF) [P28395-B26]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; [U01-HG008424]
FX BR enjoys partial support from the Austrian Science Foundation (FWF)
under project P28395-B26. This work was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research and by U01-HG008424 grant to WM.
NR 33
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD DEC
PY 2016
VL 283
IS 24
BP 4452
EP 4457
DI 10.1111/febs.13765
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EI8GT
UT WOS:000392744800004
PM 27229767
ER
PT J
AU Gildersleeve, J
AF Gildersleeve, Jeffrey
TI Understanding and Exploiting Anti-Glycan Immunity to Improve Cancer Care
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 19-22, 2016
CL New Orleans, LA
SP Soc Glycobiol
C1 [Gildersleeve, Jeffrey] NCI, Biol Chem Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2016
VL 26
IS 12
MA 26
BP 1385
EP 1385
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EJ0XX
UT WOS:000392935600030
ER
PT J
AU Nita-Lazar, A
Nuccio, AG
Daniels, CM
AF Nita-Lazar, Aleksandra
Nuccio, Arthur G.
Daniels, Casey M.
TI ADP-ribosylation in the innate immune response
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 19-22, 2016
CL New Orleans, LA
SP Soc Glycobiol
C1 [Nita-Lazar, Aleksandra; Nuccio, Arthur G.; Daniels, Casey M.] NIAID, Cellular Networks Prote Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU Intramural research Program of NIAID, NIH
FX This research was supported by the Intramural research Program of NIAID,
NIH.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2016
VL 26
IS 12
MA 71
BP 1402
EP 1402
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EJ0XX
UT WOS:000392935600074
ER
PT J
AU Olivier-Van Stichelen, S
Wang, P
Ohde, J
Comly, M
Love, DC
Hanover, JA
AF Olivier-Van Stichelen, Stephanie
Wang, Peng
Ohde, Joshua
Comly, Marcy
Love, Dona C.
Hanover, John A.
TI Nutrient-driven O-GlcNAc cycling impacts Neurodevelopmental Timing and
Metabolism
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 19-22, 2016
CL New Orleans, LA
SP Soc Glycobiol
C1 [Olivier-Van Stichelen, Stephanie; Wang, Peng; Ohde, Joshua; Comly, Marcy; Hanover, John A.] NIDDK, NIH, Bethesda, MD USA.
[Love, Dona C.] NCI, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2016
VL 26
IS 12
MA 110
BP 1418
EP 1419
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EJ0XX
UT WOS:000392935600113
ER
PT J
AU Bond, MR
St Amand, MM
Kolodrubetz, MC
Shiloach, J
Hanover, J
AF Bond, Michelle R.
St Amand, Melissa M.
Kolodrubetz, Marcella C.
Shiloach, Joseph
Hanover, Johna.
TI O-GlcNAcase knockout disrupts mammalian cell autophagy
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 19-22, 2016
CL New Orleans, LA
SP Soc Glycobiol
C1 [Bond, Michelle R.; Kolodrubetz, Marcella C.; Hanover, Johna.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[St Amand, Melissa M.] Schafer Corp, Arlington, VA 22203 USA.
[Shiloach, Joseph] NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2016
VL 26
IS 12
MA 159
BP 1439
EP 1439
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EJ0XX
UT WOS:000392935600162
ER
PT J
AU Zhao, P
Zhou, TQ
Ou, L
Yu, WH
Kwong, P
Alter, G
Tiemeyer, M
Wells, L
AF Zhao, Peng
Zhou, Tongqi
Ou, Li
Yu, Wenhan
Kwong, Peter
Alter, Galit
Tiemeyer, Michael
Wells, Lance
TI Characterizing glycoproteins using EndoH/PNGaseF in combination with
high-resolution accurate-mass (HRAM) mass spectrometry
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 19-22, 2016
CL New Orleans, LA
SP Soc Glycobiol
C1 [Zhao, Peng; Tiemeyer, Michael; Wells, Lance] Univ Georgia, Complex Carbohydrate Res Ctr, 220 Riverbend Rd, Athens, GA 30602 USA.
[Yu, Wenhan; Alter, Galit] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Zhou, Tongqi; Ou, Li; Kwong, Peter] NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2016
VL 26
IS 12
MA 214
BP 1462
EP 1462
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EJ0XX
UT WOS:000392935600217
ER
PT J
AU Voorhoeve, A
Edejer, TTT
Kapiriri, L
Norheim, OF
Snowden, J
Basenya, O
Bayarsaikhan, D
Chentaf, I
Eyal, N
Folsom, A
Halina, R
Hussein, T
Morales, C
Ostmann, F
Ottersen, T
Prakongsai, P
Saenz, C
Saleh, K
Sommanustweechai, A
Wikler, D
Zakariah, A
AF Voorhoeve, Alex
Edejer, Tessa T. T.
Kapiriri, Lydia
Norheim, Ole F.
Snowden, James
Basenya, Olivier
Bayarsaikhan, Dorjsuren
Chentaf, Ikram
Eyal, Nir
Folsom, Amanda
Halina, Rozita
Hussein, Tun
Morales, Cristian
Ostmann, Florian
Ottersen, Trygve
Prakongsai, Phusit
Saenz, Carla
Saleh, Karima
Sommanustweechai, Angkana
Wikler, Daniel
Zakariah, Afisah
TI Three Case Studies in Making Fair Choices on the Path to Universal
Health Coverage
SO Health and Human Rights
LA English
DT Article
ID CARE; EXPERIENCE; COUNTRIES
AB The goal of achieving Universal Health Coverage (UHC) can generally be realized only in stages. Moreover, resource, capacity, and political constraints mean governments often face difficult trade-offs on the path to UHC. In a 2014 report, Making fair choices on the path to UHC, the WHO Consultative Group on Equity and Universal Health Coverage articulated principles for making such trade-offs in an equitable manner. We present three case studies which illustrate how these principles can guide practical decision-making. These case studies show how progressive realization of the right to health can be effectively guided by priority-setting principles, including generating the greatest total health gain, priority for those who are worse off in a number of dimensions (including health, access to health services, and social and economic status), and financial risk protection. They also demonstrate the value of a fair and accountable process of priority setting.
C1 [Voorhoeve, Alex] London Sch Econ, Dept Philosophy Log & Sci Method, Houghton St, London WC2A 2AE, England.
[Edejer, Tessa T. T.] World Hlth Org, Costs Effectiveness Expenditure & Prior Setting H, Geneva, Switzerland.
[Kapiriri, Lydia] McMaster Univ, Dept Hlth Aging & Soc, Hamilton, ON, Canada.
[Norheim, Ole F.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Global Hlth Prior, Bergen, Norway.
[Snowden, James] Ctr Effect Altruism, Giving What We Can, Oxford, England.
[Basenya, Olivier] Minist Hlth, Bujumbura, Burundi.
[Bayarsaikhan, Dorjsuren] World Hlth Org, Dept Hlth Syst Governance & Financing, Geneva, Switzerland.
[Chentaf, Ikram] Minist Hlth, Cooperat Div, Rabat, Morocco.
[Eyal, Nir] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Folsom, Amanda] Results Dev Inst, Washington, DC USA.
[Halina, Rozita] Minist Hlth, Planning & Dev Div, Unit Natl Hlth Financing, Putrajaya, Malaysia.
[Morales, Cristian] PAHO WHO Cuba, Havana, Cuba.
[Ostmann, Florian] UCL, Sch Publ Policy, London, England.
[Ottersen, Trygve] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Ottersen, Trygve] Univ Oslo, Ctr Global Hlth, Oslo Grp Global Hlth Policy, Bergen, Norway.
[Prakongsai, Phusit] Minist Publ Hlth, Bur Int Hlth, Nonthaburi, Thailand.
[Saenz, Carla] Pan Amer Hlth Org, Washington, DC USA.
[Saleh, Karima] World Bank, Hlth, 1818 H St NW, Washington, DC 20433 USA.
[Sommanustweechai, Angkana] Minist Publ Hlth, Nonthaburi, Thailand.
[Wikler, Daniel] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Eth & Populat Hlth, Boston, MA 02115 USA.
[Zakariah, Afisah] Minist Hlth, Policy Planning Monitoring & Evaluat, Accra, Ghana.
RP Voorhoeve, A (reprint author), London Sch Econ, Dept Philosophy Log & Sci Method, Houghton St, London WC2A 2AE, England.; Voorhoeve, A (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM a.e.voorhoeve@lse.ac.uk
FU Ministry of Foreign Affairs of Norway; Norwegian Agency for Development
Cooperation (NORAD); Norwegian Research Council; Pan-American Health
Organization; British Arts and Humanities Research Council
[AH/J006033/1]; Uehiro Centre for Practical Ethics
FX Work on these case studies was supported by the Ministry of Foreign
Affairs of Norway, the Norwegian Agency for Development Cooperation
(NORAD), the Norwegian Research Council, the Pan-American Health
Organization, grant AH/J006033/1 of the British Arts and Humanities
Research Council, and the Uehiro Centre for Practical Ethics. We thank
Daniel Cotlear, Agnes Couffinhal, Amanda Glassman, Gina Lagomarsino,
Ewan Rodgers, Hasbullah Thabrany, two anonymous referees and the editors
of this journal for their comments. The opinions expressed are the views
of the authors, who alone are responsible for the views expressed in
this publication. They do not represent any position, decision, or
policy of Giving What We Can, the Ministries of Health of Burundi,
Ghana, Malaysia, or Morocco, the US National Institutes of Health, the
US Public Health Service, the US Department of Health and Human
Services, the Pan-American Health Organization, the World Bank, or the
World Health Organization.
NR 38
TC 0
Z9 0
U1 3
U2 3
PU HARVARD UNIV PRESS
PI CAMBRIDGE
PA 79 GARDEN ST, CAMBRIDGE, MA 02138 USA
SN 1079-0969
EI 2150-4113
J9 HEALTH HUM RIGHTS
JI Health Hum. Rights
PD DEC
PY 2016
VL 18
IS 2
SI SI
BP 11
EP 22
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI8IJ
UT WOS:000392749200003
ER
PT J
AU Engel, KW
Khan, I
Arany, PR
AF Engel, Karl W.
Khan, Imran
Arany, Praveen R.
TI Cell lineage responses to photobiomodulation therapy
SO Journal of Biophotonics
LA English
DT Article
DE photobiomodulation; low level laser; light therapy; wound healing; oral
cell lines; catalase; melatonin; NIR laser phototoxicity
ID LEVEL LASER THERAPY; ANTIOXIDANT ENZYMES; ANIMAL-MODEL; STEM-CELLS;
KERATINOCYTES; CATALASE; PROLIFERATION; MECHANISMS; MUCOSITIS; RADICALS
AB Photobiomodulation (PBM) therapy has been noted to promote cell proliferation and growth in many different cell types shown both in vitro and in vivo. Currently, treatment regimens are used in the clinic for a variety of ailments, including wound healing. However, most protocols treat an anatomical site without considering individual cell types constituting the target tissues. This study investigates the maximal dose threshold for oral keratinocyte and fibroblast cell types treated with near-infrared laser therapy. We observed keratinocytes have increased sensitivity to laser irradiances (>0.047 W/cm(2), 300 sec, 14.2 J/cm(2)) compared to the fibroblast cells (>0.057 W/cm(2), 300 sec, 15.1 J/cm(2)) (p < 0.0001). Laser treatments were noted to generate increased reactive oxygen species (ROS) levels in keratinocytes compared to fibroblasts that appeared to inversely correlate with higher basal catalase expression. To validate these observations, melatonin was used to treat keratinocytes to induce catalase activity (p < 0.0001). Increased melatonin-induced catalase levels were noted to significantly improve keratinocyte survival to phototoxic laser doses. These observations suggest that clinical laser dosing should account for differential effects of lasers on individual cell types to improve safety and clinical efficacy of PBM therapy.
[GRAPHICS]
.
C1 [Engel, Karl W.; Khan, Imran; Arany, Praveen R.] Natl Inst Dent & Craniofacial Res, Cell Regulat & Control Unit, NIH, 30 Convent Dr, Bethesda, MD 20814 USA.
[Arany, Praveen R.] SUNY Buffalo, Dept Oral Biol, Sch Dent Med, 3435 Main St, Buffalo, NY 14214 USA.
RP Arany, PR (reprint author), Natl Inst Dent & Craniofacial Res, Cell Regulat & Control Unit, NIH, 30 Convent Dr, Bethesda, MD 20814 USA.; Arany, PR (reprint author), SUNY Buffalo, Dept Oral Biol, Sch Dent Med, 3435 Main St, Buffalo, NY 14214 USA.
EM prarany@buffalo.edu
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health
FX We would like to thank Elieza Tang for help with experiments in the
project. This work was supported by the Intramural Research program of
the National Institute of Dental and Craniofacial Research, National
Institutes of Health.
NR 39
TC 1
Z9 1
U1 1
U2 1
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1864-063X
EI 1864-0648
J9 J BIOPHOTONICS
JI J. Biophotonics
PD DEC
PY 2016
VL 9
IS 11-12
SI SI
BP 1148
EP 1156
DI 10.1002/jbio.201600025
PG 9
WC Biochemical Research Methods; Biophysics; Optics
SC Biochemistry & Molecular Biology; Biophysics; Optics
GA EJ0QS
UT WOS:000392915800004
PM 27392170
ER
PT J
AU Kim, C
Rajan, A
DeBrito, PA
Giaccone, G
AF Kim, Chul
Rajan, Arun
DeBrito, Pedro A.
Giaccone, Giuseppe
TI Metastatic lymphoepithelioma-like carcinoma of the lung treated with
nivolumab: a case report and focused review of literature
SO TRANSLATIONAL LUNG CANCER RESEARCH
LA English
DT Review
DE Lymphoepithelioma-like carcinoma of the lung (LELC of the lung);
immunotherapy; nivolumab
ID EPSTEIN-BARR-VIRUS; CELL CARCINOMA; PD-1 BLOCKADE; MULTIMODALITY
TREATMENT; CANCER-IMMUNOTHERAPY; PEMBROLIZUMAB; RECEPTOR; OUTCOMES;
THERAPY; EXPRESSION
AB In recent years, significant advances have been made in cancer immunotherapy. Here, we present the first report of a patient with lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus (EBV)-associated lung cancer, who was treated with nivolumab, a fully human IgG4 anti-PD-1 monoclonal antibody. We also carry out a focused review to identify and examine studies of LELC of the lung in the literature. This case report highlights the need to further assess the role of immune checkpoint inhibitors in LELC of the lung.
C1 [Kim, Chul; Rajan, Arun] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[DeBrito, Pedro A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pathol, 3970 Reservoir Rd, Washington, DC 20007 USA.
[Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3970 Reservoir Rd, Washington, DC 20007 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 40
TC 0
Z9 0
U1 2
U2 2
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-6751
EI 2226-4477
J9 TRANSL LUNG CANCER R
JI Transl. Lung Cancer Res.
PD DEC
PY 2016
VL 5
IS 6
BP 720
EP 726
DI 10.21037/tlcr.2016.11.06
PG 7
WC Oncology
SC Oncology
GA EI5QW
UT WOS:000392550400021
PM 28149767
ER
PT J
AU Del Rivero, J
Enewold, L
Thomas, A
AF Del Rivero, Jaydira
Enewold, Lindsey
Thomas, Anish
TI Metastatic lung cancer in the age of targeted therapy: improving
long-term survival
SO TRANSLATIONAL LUNG CANCER RESEARCH
LA English
DT Article
DE Lung cancer; epidermal growth factor receptor (EGFR); genetics;
erlotinib; survival
ID GROWTH-FACTOR RECEPTOR; 1ST-LINE TREATMENT; EGFR MUTATIONS; OPEN-LABEL;
PHASE-III; CHEMOTHERAPY; ERLOTINIB; ADENOCARCINOMA; GEFITINIB; AFATINIB
AB Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level.
C1 [Del Rivero, Jaydira] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Enewold, Lindsey] NCI, Healthcare Assessment Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Thomas, Anish] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM lindsey.enewold@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute.
NR 22
TC 0
Z9 0
U1 1
U2 1
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-6751
EI 2226-4477
J9 TRANSL LUNG CANCER R
JI Transl. Lung Cancer Res.
PD DEC
PY 2016
VL 5
IS 6
BP 727
EP 730
DI 10.21037/tlcr.2016.11.08
PG 4
WC Oncology
SC Oncology
GA EI5QW
UT WOS:000392550400022
PM 28149768
ER
PT J
AU Bae, WK
Ik-Joo, C
Kang, K
Hennighausen, L
AF Bae, W. K.
Ik-Joo, C.
Kang, K.
Hennighausen, L.
TI Oncogenic deregulation of the methyltransferase EZH2 in hepatocellular
carcinoma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Bae, W. K.; Ik-Joo, C.] Chonnam Natl Univ, Hwasun Hosp, Hematol Oncol, Hwasun, Jeonnam, South Korea.
[Kang, K.] Dankook Univ, Dept Microbiol, Cheonan, South Korea.
[Hennighausen, L.] NIDDKD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 262
BP S88
EP S88
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500252
ER
PT J
AU Berdeja, JG
Lin, Y
Raje, N
Siegel, D
Munshi, N
Turka, A
Lam, LP
Quigley, MT
Kochenderfer, JN
AF Berdeja, J. G.
Lin, Y.
Raje, N.
Siegel, D.
Munshi, N.
Turka, A.
Lam, L. P.
Quigley, M. T.
Kochenderfer, J. N.
TI Clinical remissions and limited toxicity in a first-in-human multicenter
study of bb2121, a novel anti-BCMA CAR T cell therapy for
relapsed/refractory multiple myeloma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Berdeja, J. G.] Sarah Cannon Res Inst, Nashville, TN USA.
[Berdeja, J. G.] Tennessee Oncol, Nashville, TN USA.
[Lin, Y.] Mayo Clin, Rochester, MN USA.
[Raje, N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Munshi, N.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Turka, A.; Lam, L. P.; Quigley, M. T.] Bluebird Bio Inc, Cambridge, MA USA.
[Kochenderfer, J. N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 14LBA
BP S5
EP S5
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500009
ER
PT J
AU Bernal, F
Whiting, AL
Aguilar, F
Marshall, E
AF Bernal, F.
Whiting, A. L.
Aguilar, F.
Marshall, E.
TI Disruption of the linear ubiquitin chain assembly complex (LUBAC) with
hydrocarbon stapled alpha helices
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Bernal, F.; Whiting, A. L.; Aguilar, F.; Marshall, E.] NCI, NIH, CCR, LPDS, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 425
BP S139
EP S139
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500408
ER
PT J
AU Chen, A
Conley, B
Hamilton, S
Williams, M
O'Dwyer, P
Arteaga, C
Gray, R
McShane, L
Li, S
Rubinstein, L
Patton, D
Sazali, K
Zwiebel, J
Mitchell, E
Smith, ML
Dragaud, D
Little, R
Comis, R
Abrams, J
Flaherty, K
AF Chen, A.
Conley, B.
Hamilton, S.
Williams, M.
O'Dwyer, P.
Arteaga, C.
Gray, R.
McShane, L.
Li, S.
Rubinstein, L.
Patton, D.
Sazali, K.
Zwiebel, J.
Mitchell, E.
Smith, M. L.
Dragaud, D.
Little, R.
Comis, R.
Abrams, J.
Flaherty, K.
TI NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial: A novel
public-private partnership
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Chen, A.] NCI, Early Clin Trials Dev Program, Bethesda, MD 20892 USA.
[Conley, B.] NCI, CDP, Bethesda, MD 20892 USA.
[Hamilton, S.] MD Anderson, Pathol, Houston, TX USA.
[Williams, M.] NCI, Mol Characterizat Lab, Frederick, MD 21701 USA.
[O'Dwyer, P.] Univ Penn, Med, Philadelphia, PA 19104 USA.
[Arteaga, C.] NCI, Med Hem Onc, Nashville, TN USA.
[Gray, R.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA.
[McShane, L.; Rubinstein, L.; Zwiebel, J.; Little, R.; Abrams, J.] NCI, CTEP, Rockville, MD USA.
[Li, S.] Dana Farber, Hematol Oncol, Boston, MA USA.
[Patton, D.] NCI, CBIIT, Rockville, MD USA.
[Sazali, K.; Dragaud, D.; Comis, R.] ECOG ACRIN, Canc Res Grp, Philadelphia, PA USA.
[Mitchell, E.] Thomas Jefferson Univ, Med Oncol, Philadelphia, PA USA.
[Smith, M. L.] ECOG ACRIN, Cacner Advocacy Comm, Philadelphia, PA USA.
[Flaherty, K.] Mass Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 418
BP S137
EP S137
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500401
ER
PT J
AU Coyne, GO
Chen, AP
Kummar, S
Meehan, RS
Collins, J
Zlott, J
Kelly, K
Lenz, HJ
Newman, EM
Morgan, R
Juwara, L
Eiseman, J
Beumer, JH
Tomaszewski, J
Doroshow, J
AF Coyne, G. O'Sullivan
Chen, A. P.
Kummar, S.
Meehan, R. S.
Collins, J.
Zlott, J.
Kelly, K.
Lenz, H. J.
Newman, E. M.
Morgan, R.
Juwara, L.
Eiseman, J.
Beumer, J. H.
Tomaszewski, J.
Doroshow, J.
TI Phase I trial of oral 5-fluoro-2 '-deoxycytidine with oral
tetrahydrouridine in patients with advanced solid tumors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Coyne, G. O'Sullivan; Chen, A. P.; Kummar, S.; Meehan, R. S.; Collins, J.; Zlott, J.; Tomaszewski, J.; Doroshow, J.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Kelly, K.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA USA.
[Lenz, H. J.] USC, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Newman, E. M.; Morgan, R.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Juwara, L.] Frederick Natl Lab, DCTD, Frederick, MD USA.
[Eiseman, J.; Beumer, J. H.] Univ Pittsburgh, UPMC, Inst Canc, Pittsburgh, PA 15260 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 269
BP S90
EP S90
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500259
ER
PT J
AU Ferry-Galow, K
Makhlouf, H
Kinders, R
Chen, A
Doroshow, JH
Parchment, R
AF Ferry-Galow, K.
Makhlouf, H.
Kinders, R.
Chen, A.
Doroshow, J. H.
Parchment, R.
TI Suitability of post-diagnostic core needle tumor biopsies for
correlative studies of molecular drug action (pharmacodynamics)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Ferry-Galow, K.; Kinders, R.; Parchment, R.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Appl Dev Directorate, Frederick, MD USA.
[Makhlouf, H.] NCI, Div Canc Treatment & Diag, Canc Diag Program, Rockville, MD USA.
[Chen, A.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Early Clin Trials Dev Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 185
BP S65
EP S66
PG 2
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500179
ER
PT J
AU Houghton, P
Kang, M
Reynolds, CP
Kurmasheva, R
Smith, M
AF Houghton, P.
Kang, M.
Reynolds, C. P.
Kurmasheva, R.
Smith, M.
TI Initial testing by the Pediatric Preclinical Testing Program (PPTP) of
the ATR Inhibitor VX-970 alone or in combination with cisplatin in
pediatric solid tumor xenografts
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Houghton, P.; Kurmasheva, R.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Kang, M.; Reynolds, C. P.] Texas Tech Univ, Hlth Sci Ctr, Ctr Canc, Lubbock, TX 79430 USA.
[Smith, M.] NCI, Canc Treatment & Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 132
BP S49
EP S49
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500126
ER
PT J
AU Meehan, RS
Kummar, S
Coyne, GO
Zlott, J
Horneffer, Y
Juwara, L
Streicher, H
Sharon, E
Harris, P
Doroshow, JH
Chen, A
AF Meehan, R. S.
Kummar, S.
Coyne, G. O'Sullivan
Zlott, J.
Horneffer, Y.
Juwara, L.
Streicher, H.
Sharon, E.
Harris, P.
Doroshow, J. H.
Chen, A.
TI Phase I study of ganetespib and ziv-aflibercept in patients with
advanced gastrointestinal carcinomas, non-squamous non-small cell lung
carcinomas, urothelial carcinomas, and sarcomas
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Meehan, R. S.; Kummar, S.; Coyne, G. O'Sullivan; Zlott, J.; Horneffer, Y.; Streicher, H.; Sharon, E.; Harris, P.; Doroshow, J. H.; Chen, A.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Juwara, L.] Frederick Natl Lab Canc Res, DCTD, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 466
BP S152
EP S153
PG 2
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500448
ER
PT J
AU Strauss, J
Heery, C
Schlom, J
Madan, RA
Lamping, E
Marte, J
Cordes, L
Lan, Y
Mahnke, L
Helwig, C
Lo, KM
Gulley, J
AF Strauss, J.
Heery, C.
Schlom, J.
Madan, R. A.
Lamping, E.
Marte, J.
Cordes, L.
Lan, Y.
Mahnke, L.
Helwig, C.
Lo, K. M.
Gulley, J.
TI A phase I, open-label, multiple-ascending-dose trial to investigate the
safety, tolerability, pharmacokinetics, biological, and clinical
activity of M7824, a novel bifunctional fusion protein targeting the
PD-L1 and TGF-beta pathways, in patients with metastatic or locally
advanced solid tumors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Strauss, J.] NCI, Ctr Canc Res, NIH, Med Oncol Serv, Bethesda, MD 20892 USA.
[Heery, C.; Schlom, J.; Madan, R. A.] NCI, Ctr Canc Res, NIH, Genitourinary Malignancies Branch,Lab Tumor Immun, Bethesda, MD 20892 USA.
[Lamping, E.] NCI, NIH, Off Clin Director, Bethesda, MD 20892 USA.
[Marte, J.] NCI, NIH, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
[Cordes, L.] NCI, NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lan, Y.; Lo, K. M.] EMD Serono Inc, TIP Immunooncol, Billerca, MA USA.
[Mahnke, L.] EMD Serono Inc, Clin Dev, Billerca, MA USA.
[Helwig, C.] Merck KGaA, Biostat Oncol, Darmstadt, Germany.
[Gulley, J.] NCI, NIH, Genitourinary Malignancies Branch, Lab Tumor Immunol & Biol,Med Oncol Serv,Ctr Canc, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 314
BP S103
EP S104
PG 2
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500301
ER
PT J
AU Teicher, B
Kunkel, M
Evans, D
Delosh, R
Laudeman, J
Chad, O
Reinhart, R
Michael, S
Thomas, S
Kaur, G
Monks, A
Morris, J
AF Teicher, B.
Kunkel, M.
Evans, D.
Delosh, R.
Laudeman, J.
Chad, O.
Reinhart, R.
Michael, S.
Thomas, S.
Kaur, G.
Monks, A.
Morris, J.
TI Adult and pediatric sarcoma cell line screen findings in Notch, DNA
repair and cell cycle gene and miR expression and compound response
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Teicher, B.; Kunkel, M.; Kaur, G.; Morris, J.] NCI, DCTD, Bethesda, MD 20892 USA.
[Evans, D.; Delosh, R.; Laudeman, J.; Chad, O.; Reinhart, R.; Michael, S.; Thomas, S.; Monks, A.; Morris, J.] Leidos, Frederick Natl Lab Canc Res, Target Validat & Screening Lab, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 232
BP S78
EP S78
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500222
ER
PT J
AU Wan, X
Issak, S
Yeung, C
McCalla, A
Helman, L
AF Wan, X.
Issak, S.
Yeung, C.
McCalla, A.
Helman, L.
TI Histone deacetylase inhibition triggers suppression of the IGF-1R/Akt
pathway in rhabdomyosarcoma and Pax3-Foxo1 in alveolar rhabdomyosarcoma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Wan, X.; Issak, S.; Yeung, C.; McCalla, A.; Helman, L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 102
BP S40
EP S40
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500095
ER
PT J
AU Yang, SX
Nguyen, D
Hollingshead, M
Rubinstein, L
Doroshow, JH
AF Yang, S. X.
Nguyen, D.
Hollingshead, M.
Rubinstein, L.
Doroshow, J. H.
TI DNMT3B expression patterns in human lymphomas and xenograft tumors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 29-DEC 02, 2016
CL Munich, GERMANY
SP EORTC, Natl Canc Inst, Amer Assoc Canc Res
C1 [Yang, S. X.; Nguyen, D.] NCI, DCTD NCTVL, Bethesda, MD 20892 USA.
[Hollingshead, M.] NCI, DCTD BTB, Bethesda, MD 20892 USA.
[Rubinstein, L.] NCI, DCTD BRB, Bethesda, MD 20892 USA.
[Doroshow, J. H.] NCI, DCTD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD DEC
PY 2016
VL 69
SU 1
MA 178
BP S63
EP S63
PG 1
WC Oncology
SC Oncology
GA EF7IO
UT WOS:000390503500172
ER
PT J
AU Nadon, NL
AF Nadon, Nancy L.
TI The NIA interventions testing program announces the 2016 solicitation of
proposals
SO AGING CELL
LA English
DT Editorial Material
DE aging; health span; lifespan
ID LIFE-SPAN; MICE
AB The NIA Interventions Testing Program encourages participation by the research community though its annual call-for-proposals. This Short Take serves as a brief introduction to the program and announcement for the next proposal receipt date.
C1 [Nadon, Nancy L.] NIA, Bethesda, MD 20892 USA.
RP Nadon, NL (reprint author), NIA, Div Aging Biol, 7201 Wisconsin Ave,GW 3N300, Bethesda, MD 20892 USA.
EM nadonn@nia.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD DEC
PY 2016
VL 15
IS 6
BP 1153
EP 1153
DI 10.1111/acel.12542
PG 1
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA EI1ZR
UT WOS:000392286200016
ER
PT J
AU Tanamas, SK
Wong, E
Backholer, K
Abdullah, A
Wolfe, R
Barendregt, J
Peeters, A
AF Tanamas, Stephanie K.
Wong, Evelyn
Backholer, Kathryn
Abdullah, Asnawi
Wolfe, Rory
Barendregt, Jan
Peeters, Anna
TI Age of onset of obesity and risk of type 2 diabetes
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH
LA English
DT Article
DE obesity; body mass index; obese-years; age of onset; type 2 diabetes
ID DURATION
AB Objective: To compare a simple measure - age of onset of obesity - to an obese-years construct (a product of duration and magnitude of obesity) as risk factors for type 2 diabetes.
Method: Participants from the Framingham Heart Study who were not obese and did not have diabetes at baseline were included (n=4,320). The Akaike Information Criterion (AIC) was computed to compare four Cox proportional hazards models with incident diabetes as the outcome and: (i) obese-years; (ii) age of onset of obesity; (iii) body mass index (BMI); and (iv) age of onset of obesity plus magnitude of BMI combined, as exposures.
Results: AIC indicated that the model with obese-years provided a more effective explanation of incidence of type 2 diabetes compared to the remaining three models. Models including age of onset of obesity plus BMI were not appreciably different from the model with BMI alone, except in those aged >= 60.
Conclusions: While obese-years was the optimal obesity construct to explain risk of type 2 diabetes, age of onset may be a useful, practical addition to current BMI in the elderly. Implications: Where computation of obese-years is not possible or impractical, age of onset of obesity combined with BMI may provide a useful alternative.
C1 [Tanamas, Stephanie K.; Wong, Evelyn; Backholer, Kathryn; Peeters, Anna] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Abdullah, Asnawi] Univ Muhammadiyah Aceh, Dept Biostat & Populat Hlth, Fac Publ Hlth, Banda Aceh, Indonesia.
[Abdullah, Asnawi] Monash Univ, Dept Epidemiol & Prevent Med, Fac Publ Hlth, Clayton, Vic, Australia.
[Barendregt, Jan] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
RP Tanamas, SK (reprint author), NIDDK, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM stephanie.tanamas@nih.gov
FU National Health and Medical Research Council (NHMRC) [1044366]; NHLBI
FX This study was supported by the National Health and Medical Research
Council (NHMRC 1044366). The FHS is conducted and supported by the NHLBI
in collaboration with study investigators. The manuscript was prepared
using a limited access data set obtained from the NHLBI and does not
necessarily reflect the opinions or views of the FHS or the NHLBI. The
authors thank the FHS investigators for permission to use their data set
for the present study.
NR 7
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1326-0200
EI 1753-6405
J9 AUST NZ J PUBL HEAL
JI Aust. N. Z. Publ. Health
PD DEC
PY 2016
VL 40
IS 6
BP 579
EP 581
DI 10.1111/1753-6405.12593
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI7DB
UT WOS:000392656600016
PM 27774719
ER
PT J
AU Smith, CL
Reese, TS
AF Smith, Carolyn L.
Reese, Thomas S.
TI Adherens Junctions Modulate Diffusion between Epithelial Cells in
Trichoplax adhaerens
SO BIOLOGICAL BULLETIN
LA English
DT Article
ID EVOLUTION; ORIGIN; PLACOZOA; LOCOMOTION; CNIDARIANS; SYSTEMS; GENOME;
BRAIN; VIEW
AB Trichoplax adhaerens is the sole named member of Placozoa, an ancient metazoan phylum. This coin-shaped animal glides on ventral cilia to find and digest algae on the substrate. It has only six cell types, all but two of which are incorporated into the epithelium that encloses it. The upper epithelium is thin, composed of a pavement of relatively large polygonal disks, each bearing a cilium. The lower epithelium is thick and composed primarily of narrow ciliated cells that power locomotion. Interspersed among these cells are two different secretory cells: one containing large lipophilic granules that, when released, lyse algae under the animal; the other, less abundant, is replete with smaller secretory granules containing neuropeptides. All cells within both epithelia are joined by adherens junctions that are stabilized by apical actin networks. Cells are held in place during shape changes or under osmotic stress, but dissociate in low calcium. Neither tight, septate, nor gap junctions are evident, leaving only the adherens junction to control the permeability of the epithelium. Small (<4 kDa) fluorescent dextrans introduced into artificial seawater readily penetrate into the animal between the cells. Larger dextrans enter slowly, except in animals treated with reduced calcium, indicating that the adherens junctions form a circumferential belt around each cell that impedes diffusion into the animal. During feeding, the limited permeability of the adherens junctions helps to confine material released from lysed algae within the narrow space under the animal, where it is absorbed by endocytosis.
C1 [Smith, Carolyn L.; Reese, Thomas S.] NINDS, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
RP Reese, TS (reprint author), NINDS, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM treese@mbl.edu
NR 36
TC 0
Z9 0
U1 1
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0006-3185
EI 1939-8697
J9 BIOL BULL-US
JI Biol. Bull.
PD DEC
PY 2016
VL 231
IS 3
BP 216
EP 224
PG 9
WC Biology; Marine & Freshwater Biology
SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology
GA EI2WA
UT WOS:000392347900006
PM 28048952
ER
PT J
AU Yonemori, K
Hirakawa, A
Kawachi, A
Kinoshita, F
Okuma, H
Nishikawa, T
Tamura, K
Fujiwara, Y
Takebe, N
AF Yonemori, Kan
Hirakawa, Akihiro
Kawachi, Asuka
Kinoshita, Fumie
Okuma, Hitomi
Nishikawa, Tadaaki
Tamura, Kenji
Fujiwara, Yasuhiro
Takebe, Naoko
TI Drug induced interstitial lung disease in oncology phaseI trials
SO CANCER SCIENCE
LA English
DT Article
DE Drug induced interstitial lung disease; investigational new drug;
oncology; phaseI trial pulmonary toxicity
ID CANCER-STUDY-GROUP; JAPANESE PATIENTS; GEFITINIB
AB Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phaseI trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phaseI trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phaseI trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients.
C1 [Yonemori, Kan; Kawachi, Asuka; Okuma, Hitomi; Nishikawa, Tadaaki; Tamura, Kenji; Fujiwara, Yasuhiro] Natl Canc Ctr, Dept Breast & Med Oncol, Natl Canc Ctr, Tokyo, Japan.
[Yonemori, Kan; Fujiwara, Yasuhiro] Natl Canc Ctr, Off Adv Med Care Evaluat, Tokyo, Japan.
[Yonemori, Kan; Takebe, Naoko] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Hirakawa, Akihiro; Kinoshita, Fumie] Nagoya Univ, Biostat & Bioinformat Sect, Ctr Adv Med & Clin Res, Grad Sch Med, Nagoya, Aichi, Japan.
RP Takebe, N (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.; Yonemori, K (reprint author), Natl Canc Ctr, Dept Breast & Med Oncol, Natl Canc Ctr Hosp, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan.
EM kyonemor@ncc.go.jp; takeben@mail.nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
EI 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD DEC
PY 2016
VL 107
IS 12
BP 1830
EP 1836
DI 10.1111/cas.13087
PG 7
WC Oncology
SC Oncology
GA EH7VT
UT WOS:000391981400014
PM 27685762
ER
PT J
AU Abu-Tayeh, H
Weidenfeld, K
Zhilin-Roth, A
Schif-Zuck, S
Thaler, S
Cotarelo, C
Tan, TZ
Thiery, JP
Green, JE
Klorin, G
Sabo, E
Sleeman, JP
Tzukerman, M
Barkan, D
AF Abu-Tayeh, Hanan
Weidenfeld, Keren
Zhilin-Roth, Alisa
Schif-Zuck, Sagi
Thaler, Sonja
Cotarelo, Cristina
Tan, Tuan Z.
Thiery, Jean P.
Green, Jeffrey E.
Klorin, Geula
Sabo, Edmond
Sleeman, Jonathan P.
Tzukerman, Maty
Barkan, Dalit
TI 'Normalizing' the malignant phenotype of luminal breast cancer cells via
alpha(v) beta(3)-integrin
SO CELL DEATH & DISEASE
LA English
DT Article
ID BASEMENT-MEMBRANE CULTURES; EMBRYONIC STEM-CELLS; ADULT HUMAN BREAST;
MAMMARY-GLAND; EXPERIMENTAL PLATFORM; BIOLOGICAL-ACTIVITY; TUMOR-GROWTH;
IN-VITRO; INTEGRIN; MORPHOGENESIS
AB Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v) beta(3) integrin (Int-alpha v beta 3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-alpha v beta 3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids' reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAM(high)CD49f(low)CD24(+) and Int-alpha v beta 3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-alpha v beta 3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-alpha v beta 3 were injected into a humanized mouse model, differentiated tumors developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-alpha v beta 3 can potentially promote 'normalization' of their malignant phenotype and may prevent the malignant cells from progressing.
C1 [Abu-Tayeh, Hanan; Weidenfeld, Keren; Zhilin-Roth, Alisa; Schif-Zuck, Sagi; Barkan, Dalit] Univ Haifa, Dept Human Biol, Haifa, Israel.
[Thaler, Sonja; Sleeman, Jonathan P.] Heidelberg Univ, Med Fac Mannheim, Ctr Biomed & Med Technol Mannheim CBTM, Mannheim, Germany.
[Cotarelo, Cristina] Univ Med Ctr Mainz, Dept Pathol, Langenbeckstr, Mainz, Germany.
[Tan, Tuan Z.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore.
[Thiery, Jean P.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore.
[Thiery, Jean P.] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore.
[Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Klorin, Geula; Sabo, Edmond] Rambam Med Ctr, Dept Pathol, Haifa, Israel.
[Sleeman, Jonathan P.] Karlsruhe Inst Technol, Inst Genet & Toxikol, Campus Nord, Karlsruhe, Germany.
[Tzukerman, Maty] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
[Tzukerman, Maty] Technion Israel Inst Technol, Res Inst, Haifa, Israel.
RP Barkan, D (reprint author), Univ Haifa, Dept Human Biol, Fac Nat Sci, IL-31905 Haifa, Israel.
EM dalitbrk@gmail.com
FU University of Haifa; Daniel M. Soref Charitable Trust; Skirball
Foundation; Richard D. Satell Foundation; Sohnis family; Forman family;
Israel Science Foundation [62/10 MT]
FX We thank Dr. Amiram Ariel for the use of FACSCanto II (BD) equipment. We
Thank Professor Israel Voldavsky and Dr. Neta Ilan for providing the
immunohistochemistry platform. This research was supported by the
British and Swiss friends of University of Haifa (DB) and by grants from
the Daniel M. Soref Charitable Trust, Skirball Foundation, Richard D.
Satell Foundation, Sohnis and Forman families and the Israel Science
Foundation (Grant No. 62/10 MT).
NR 55
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD DEC
PY 2016
VL 7
AR e2491
DI 10.1038/cddis.2016.387
PG 15
WC Cell Biology
SC Cell Biology
GA EH5LY
UT WOS:000391815800012
PM 27906177
ER
PT J
AU Chen, X
Cao, XW
Sun, XH
Lei, R
Chen, PF
Zhao, YX
Jiang, YH
Yin, J
Chen, R
Ye, DJ
Wang, Q
Liu, ZJ
Liu, SH
Cheng, CY
Mao, J
Hou, YY
Wang, ML
Siebenlist, U
Chin, YE
Wang, Y
Cao, L
Hu, GH
Zhang, XR
AF Chen, Xi
Cao, Xinwei
Sun, Xiaohua
Lei, Rong
Chen, Pengfei
Zhao, Yongxu
Jiang, Yuhang
Yin, Jie
Chen, Ran
Ye, Deji
Wang, Qi
Liu, Zhanjie
Liu, Sanhong
Cheng, Chunyan
Mao, Jie
Hou, Yingyong
Wang, Mingliang
Siebenlist, Ulrich
Chin, Y. Eugene
Wang, Ying
Cao, Liu
Hu, Guohong
Zhang, Xiaoren
TI Bcl-3 regulates TGF beta signaling by stabilizing Smad3 during breast
cancer pulmonary metastasis
SO CELL DEATH & DISEASE
LA English
DT Article
ID GROWTH-FACTOR-BETA; CANDIDATE PROTOONCOGENE BCL-3; FAMILY-MEMBER BCL-3;
ONCOPROTEIN BCL-3; P50 HOMODIMERS; ROLES; CELLS; DEGRADATION;
ACTIVATION; TRANSITION
AB Transforming growth factor beta (TGF beta) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the I kappa B family, serves as a critical regulator in TGF beta signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGF beta signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGF beta treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.
C1 [Chen, Xi; Cao, Xinwei; Sun, Xiaohua; Lei, Rong; Chen, Pengfei; Zhao, Yongxu; Jiang, Yuhang; Yin, Jie; Chen, Ran; Ye, Deji; Wang, Qi; Liu, Zhanjie; Liu, Sanhong; Cheng, Chunyan; Mao, Jie; Chin, Y. Eugene; Wang, Ying; Hu, Guohong; Zhang, Xiaoren] Shanghai Jiao Tong Univ, Sch Med SJTUSM, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China.
[Chen, Xi; Cao, Xinwei; Sun, Xiaohua; Lei, Rong; Chen, Pengfei; Zhao, Yongxu; Jiang, Yuhang; Yin, Jie; Chen, Ran; Ye, Deji; Wang, Qi; Liu, Zhanjie; Liu, Sanhong; Cheng, Chunyan; Mao, Jie; Chin, Y. Eugene; Wang, Ying; Hu, Guohong; Zhang, Xiaoren] Chinese Acad Sci, SIBS, Shanghai 200025, Peoples R China.
[Hou, Yingyong] Fudan Univ, Zhongshan Hosp, Dept Pathol, Sch Med, Shanghai 200032, Peoples R China.
[Wang, Mingliang] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China.
[Siebenlist, Ulrich] NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Chin, Y. Eugene] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Sch Med, Shanghai 200240, Peoples R China.
[Cao, Liu] Liaoning Prov Collaborat Innovat Ctr Aging Relate, Shenyang 110001, Peoples R China.
[Cao, Liu] China Med Univ, Key Iaboratory Med Cell Biol, Shenyang 110001, Peoples R China.
RP Hu, GH; Zhang, XR (reprint author), Shanghai Jiao Tong Univ, Inst Hlth Sci, Sch Med, Key Lab Stem Cell Biol,Shanghai Inst Biol Sci, Room 1126,Biol Res Bldg A,320 Yueyang Rd, Shanghai 200025, Peoples R China.
EM ghhu@sibs.ac.cn; xrzhang@sibs.ac.cn
FU National Basic Research Program [2014CB541904, 2014CB943600]; National
Natural Science Foundation of China [31570902, 31370881]
FX This study was supported by grants from the National Basic Research
Program (2014CB541904, 2014CB943600), the National Natural Science
Foundation of China (31570902, 31370881). We thank Drs. F Liu for her
gifts of antibodies, A Chariot and Y Zhang for their constructs, H Wei
and Y Liu for their suggestions, and Q Jing for his support.
NR 47
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Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD DEC
PY 2016
VL 7
AR e2508
DI 10.1038/cddis.2016.405
PG 12
WC Cell Biology
SC Cell Biology
GA EH5LY
UT WOS:000391815800026
PM 27906182
ER
PT J
AU Griner, LAM
Zhang, XH
Guha, R
McKnight, C
Goldlust, IS
Lal-Nag, M
Wilson, K
Michael, S
Titus, S
Shinn, P
Thomas, CJ
Ferrer, M
AF Griner, Lesley A. Mathews
Zhang, Xiaohu
Guha, Rajarshi
McKnight, Crystal
Goldlust, Ian S.
Lal-Nag, Madhu
Wilson, Kelli
Michael, Sam
Titus, Steve
Shinn, Paul
Thomas, Craig J.
Ferrer, Marc
TI Large-scale pharmacological profiling of 3D tumor models of cancer cells
SO CELL DEATH & DISEASE
LA English
DT Article
ID BREAST-CANCER; DNA-REPAIR; STEM-CELLS; PHARMACOKINETICS; METABOLISM;
PHARMACODYNAMICS; CARFILZOMIB; VALIDATION; SPHEROIDS; SCREEN
AB The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells.
C1 [Griner, Lesley A. Mathews; Zhang, Xiaohu; Guha, Rajarshi; McKnight, Crystal; Goldlust, Ian S.; Lal-Nag, Madhu; Wilson, Kelli; Michael, Sam; Titus, Steve; Shinn, Paul; Thomas, Craig J.; Ferrer, Marc] NIH, Natl Ctr Advancing Translat Sci, Div Preclin Innovat, Bldg 10, Bethesda, MD 20892 USA.
RP Griner, LAM; Ferrer, M (reprint author), NCATS, 9800 Med Ctr Dr Bldg B,Room 3005 Stop Code 3370, Rockville, MD 20850 USA.
EM mathews.lesley1@gmail.com; ferrerm@mail.nih.gov
FU NIH Intramural Research Program at NCATS
FX We would like to thank Kyle Brimacombe for the formatting of the figures
for the manuscript, Christopher Dextras for help with quantitation of
the apoptosis dot blots, and Dr Serena Silver for critical reading of
the manuscript. This work was funded by the NIH Intramural Research
Program at NCATS.
NR 42
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD DEC
PY 2016
VL 7
AR e2492
DI 10.1038/cddis.2016.360
PG 11
WC Cell Biology
SC Cell Biology
GA EH5LY
UT WOS:000391815800004
ER
PT J
AU Lipton, SA
Rezaie, T
Nutter, A
Lopez, KM
Parker, J
Kosaka, K
Satoh, T
McKercher, SR
Masliah, E
Nakanishi, N
AF Lipton, Stuart A.
Rezaie, Tayebeh
Nutter, Anthony
Lopez, Kevin M.
Parker, James
Kosaka, Kunio
Satoh, Takumi
McKercher, Scott R.
Masliah, Eliezer
Nakanishi, Nobuki
TI Therapeutic advantage of pro-electrophilic drugs to activate the
Nrf2/ARE pathway in Alzheimer's disease models
SO CELL DEATH & DISEASE
LA English
DT Article
ID CARNOSIC ACID; MOUSE MODEL; TRANSGENIC MOUSE; PROTEIN; ANTIOXIDANT;
MECHANISMS; EXPRESSION; DEPLETION; DEFICITS; INJURY
AB Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-beta (A beta)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric A beta. For in vivo studies, we used two transgenic mouse models of AD, human amyloid precursor protein (hAPP)-J20 mice and triple transgenic (3xTg AD) mice. We treated these mice trans-nasally with CA twice weekly for 3 months. Subsequently, we performed neurobehavioral tests and quantitative immunohistochemistry to assess effects on AD-related phenotypes, including learning and memory, and synaptic damage. In vitro, CA reduced dendritic spine loss in rat neurons exposed to oligomeric A beta. In vivo, CA treatment of hAPP-J20 mice improved learning and memory in the Morris water maze test. Histologically, CA increased dendritic and synaptic markers, and decreased astrogliosis, A beta plaque number, and phospho-tau staining in the hippocampus. We conclude that CA exhibits therapeutic benefits in rodent AD models and since the FDA has placed CA on the 'generally regarded as safe' (GRAS) list, thus obviating the need for safety studies, human clinical trials will be greatly expedited.
C1 [Lipton, Stuart A.; Lopez, Kevin M.; Parker, James; McKercher, Scott R.; Nakanishi, Nobuki] Scintillon Inst, Neurodegenerat Dis Ctr, 6868 Nancy Ridge Dr, San Diego, CA 92121 USA.
[Lipton, Stuart A.; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Lipton, Stuart A.; Rezaie, Tayebeh; Nutter, Anthony; Lopez, Kevin M.; Parker, James; Satoh, Takumi; McKercher, Scott R.; Nakanishi, Nobuki] Sanford Burnham Prebys Med Discovery Inst, Neurosci & Aging Res Ctr, La Jolla, CA 92037 USA.
[Kosaka, Kunio] Nagase CO LTD, Ctr Res & Dev, Kobe, Hyogo 6512241, Japan.
[Rezaie, Tayebeh] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Satoh, Takumi] Tokyo Univ Technol, Sch Biosci & Biotechnol, Dept Antiaging Food Res, Tokyo 1920982, Japan.
RP Lipton, SA; Nakanishi, N (reprint author), Scintillon Inst, Neurodegenerat Dis Ctr, 6868 Nancy Ridge Dr, San Diego, CA 92121 USA.; Lipton, SA; Nakanishi, N (reprint author), Univ Calif San Diego, 6868 Nancy Ridge Dr, San Diego, CA 92121 USA.
EM slipton@ucsd.edu; nnakanishi@scintillon.org
FU NIH [R21 NS080799, P01 HD029587, P30 NS076411]; Brain & Behavior
Research Foundation
FX This work was supported in part by NIH grants R21 NS080799, P01
HD029587, and the La Jolla Interdisciplinary Neuroscience Center Core
Grant P30 NS076411 and by a Distinguished Investigator Award from the
Brain & Behavior Research Foundation (to SAL). WE appreciate the
contributions of Sara Sanz-Blasco, Zaneta Cha, Brian Lee and Marcos
Valencia.
NR 28
TC 1
Z9 1
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD DEC
PY 2016
VL 7
AR e2499
DI 10.1038/cddis.2016.389
PG 8
WC Cell Biology
SC Cell Biology
GA EH5LY
UT WOS:000391815800013
PM 27906174
ER
PT J
AU Kadri, SS
Miller, AC
Hohmann, S
Bonne, S
Nielsen, C
Wells, C
Gruver, C
Quraishi, SA
Sun, JF
Cai, RM
Morris, PE
Freeman, BD
Holmes, JH
Cairns, BA
Suffredini, AF
AF Kadri, Sameer S.
Miller, Andrew C.
Hohmann, Samuel
Bonne, Stephanie
Nielsen, Carrie
Wells, Carmen
Gruver, Courtney
Quraishi, Sadeq A.
Sun, Junfeng
Cai, Rongman
Morris, Peter E.
Freeman, Bradley D.
Holmes, James H.
Cairns, Bruce A.
Suffredini, Anthony F.
CA US Critical Illness Injury Trials
Smoke Inhalation Associated Acute
TI Risk Factors for In-Hospital Mortality in Smoke Inhalation- Associated
Acute Lung Injury Data From 68 United States Hospitals
SO CHEST
LA English
DT Article
DE adult respiratory distress syndrome; burns; epidemiology; risk factors;
smoke inhalation
ID BURN PATIENTS; MECHANICAL VENTILATION; RESUSCITATION; PROGNOSIS;
OUTCOMES; SCORE
AB BACKGROUND: Mortality after smoke inhalation-associated acute lung injury (SI-ALI) remains substantial. Age and burn surface area are risk factors of mortality, whereas the impact of patient-and center-level variables and treatments on survival are unknown.
METHODS: We performed a retrospective cohort study of burn and non-burn centers at 68 US academic medical centers between 2011 and 2014. Adult inpatients with SI-ALI were identified using an algorithm based on a billing code for respiratory conditions from smoke inhalation who were mechanically ventilated by hospital day 4, with either a length-of-stay >= 5 days or death within 4 days of hospitalization. Predictors of in-hospital mortality were identified using logistic regression. The primary outcome was the odds ratio for in-hospital mortality.
RESULTS: A total of 769 patients (52.9 +/- 18.1 years) with SI-ALI were analyzed. In-hospital mortality was 26% in the SI-ALI cohort and 50% in patients with >= 20% surface burns. In addition to age > 60 years (OR 5.1, 95% CI 2.53-10.26) and >= 20% burns (OR 8.7, 95% CI 4.55-16.75), additional risk factors of in-hospital mortality included initial vasopressor use (OR 5.0, 95% CI 3.16-7.91), higher diagnostic-related group-based risk-of-mortality assignment and lower hospital bed capacity (OR 2.3, 95% CI 1.23-4.15). Initial empiric antibiotics (OR 0.93, 95% CI 0.58-1.49) did not impact survival. These new risk factors improved mortality prediction by 9.9% (P < .001).
CONCLUSIONS: In addition to older age and major surface burns, mortality in SI-ALI is predicted by initial vasopressor use, higher diagnostic-related group-based risk-of-mortality assignment, and care at centers with < 500 beds, but not by initial antibiotic therapy.
C1 [Kadri, Sameer S.; Miller, Andrew C.; Sun, Junfeng; Cai, Rongman; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
[Kadri, Sameer S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Miller, Andrew C.] West Virginia Univ, Dept Emergency Med, Morgantown, WV 26506 USA.
[Hohmann, Samuel] Univ Hlth Syst Consortium, Chicago, IL USA.
[Hohmann, Samuel] Rush Univ, Dept Hlth Syst Management, Chicago, IL 60612 USA.
[Bonne, Stephanie; Freeman, Bradley D.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Nielsen, Carrie; Cairns, Bruce A.] Univ North Carolina Hosp, North Carolina Jaycee Burn Ctr, Chapel Hill, NC USA.
[Wells, Carmen; Gruver, Courtney; Holmes, James H.] Wake Forest Sch Med, Wake Forest Med Ctr, Dept Gen Surg, Winston Salem, NC USA.
[Quraishi, Sadeq A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anethesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Quraishi, Sadeq A.] Harvard Med Sch, Dept Anesthesia, Boston, MA USA.
[Morris, Peter E.] Wake Forest Sch Med, Wake Forest Med Ctr, Div Pulm & Crit Care Med, Winston Salem, NC USA.
RP Kadri, SS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM sameer.kadri@nih.gov
FU Intramural Research Program, National Institutes of Health
FX This study was funded by the Intramural Research Program, National
Institutes of Health.
NR 30
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD DEC
PY 2016
VL 150
IS 6
BP 1260
EP 1268
DI 10.1016/j.chest.2016.06.008
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA EI1VQ
UT WOS:000392274600026
PM 27316558
ER
PT J
AU Drabek, J
Smolikova, M
Kalendar, R
Pinto, FAL
Pavlousek, P
Kleparnik, K
Frebort, I
AF Drabek, Jiri
Smolikova, Michaela
Kalendar, Ruslan
Pinto, Fernando A. Lopes
Pavlousek, Pavel
KleparnIk, Karel
Frebort, Ivo
TI Design and validation of an STR hexaplex assay for DNA profiling of
grapevine cultivars
SO ELECTROPHORESIS
LA English
DT Article
DE Grapevine DNA analysis; Multiplex PCR; STRs; Vitis vinifera L
ID VITIS-VINIFERA L.; POLYMERASE-CHAIN-REACTION; MICROSATELLITE MARKERS;
MOLECULAR TOOLS; GENETIC-MARKERS; MULTIPLEX PCR; IDENTIFICATION; WINES;
SET; DIFFERENTIATION
AB Although the analysis of length polymorphism at STR loci has become a method of choice for grape cultivar identification, the standardization of methods for this purpose lags behind that of methods for DNA profiling in human and animal forensic genetics. The aim of this study was thus to design and validate a grapevine STR protocol with a practically useful level of multiplexing. Using free bioinformatics tools, published primer sequences, and nucleotide databases, we constructed and optimized a primer set for the simultaneous analysis of six STR loci (VVIi51, scu08vv, scu05vv, VVMD17, VrZAG47, and VrZAG83) by multiplex PCR and CE with laser-induced fluorescence, and tested it on 90 grape cultivars. The new protocol requires subnanogram quantities of the DNA template and enables automated, high-throughput genetic analysis with reasonable discriminatory power. As such, it represents a step toward further standardization of grape DNA profiling.
C1 [Drabek, Jiri] Palacky Univ, Fac Med & Dent, Inst Mol & Translat Med, Hnevotinska 5, Olomouc 77900, Czech Republic.
[Smolikova, Michaela] Palacky Univ, Dept Biochem, Olomouc, Czech Republic.
[Kalendar, Ruslan] Univ Helsinki, LUKE BI Plant Genome Dynam, Inst Biotechnol, Helsinki, Finland.
[Kalendar, Ruslan] Minist Educ & Sci Republ Kazakhstan, Sci Comm, RSE Natl Ctr Biotechnol, Astana, Kazakhstan.
[Pinto, Fernando A. Lopes] Uppsala Univ, Dept Photochem & Mol Sci, Uppsala, Sweden.
[Pavlousek, Pavel] Mendel Univ Brno, Dept Viticulture & Enol, Brno, Czech Republic.
[KleparnIk, Karel] ASCR, Inst Analyt Chem, Brno, Czech Republic.
[Frebort, Ivo] Palacky Univ, Fac Sci, Ctr Reg Hana Biotechnol & Agr Res, Olomouc, Czech Republic.
RP Drabek, J (reprint author), Palacky Univ, Fac Med & Dent, Inst Mol & Translat Med, Hnevotinska 5, Olomouc 77900, Czech Republic.
EM jiri.drabek@upol.cz
RI Kalendar, Ruslan/D-9751-2012
OI Kalendar, Ruslan/0000-0003-3986-2460
FU [LO1304]; [LM2010004]; [TE02000058]
FX This work was supported by grants LO1304, LM2010004, and TE02000058. We
thank Drs. S. Lalet, N. Goto-Yamamoto, M. Galimberti, Nikos, J. Benes,
O. Jandurova, P. Kocar, P. Madera, M. Michlovsky, P. Pavlousek, J.
Stavek, and M. Prazak for grapevine samples. Wealso thank Profs. L.
Bocak, M. Navratil, and Dr. M. Valarik (Olomouc, the Czech Republic) for
generously providing access to instruments, and Veronika Toupalikova,
MSc. for technical help in addressing reviewers' comments.
NR 69
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0173-0835
EI 1522-2683
J9 ELECTROPHORESIS
JI Electrophoresis
PD DEC
PY 2016
VL 37
IS 23-24
BP 3059
EP 3067
DI 10.1002/elps.201600068
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA EI3VW
UT WOS:000392421400003
PM 27696463
ER
PT J
AU Chawla, N
Blanch-Hartigan, D
Virgo, KS
Ekwueme, DU
Han, XS
Forsythe, L
Rodriguez, J
McNeel, TS
Yabroff, KR
AF Chawla, Neetu
Blanch-Hartigan, Danielle
Virgo, Katherine S.
Ekwueme, Donatus U.
Han, Xuesong
Forsythe, Laura
Rodriguez, Juan
McNeel, Timothy S.
Yabroff, K. Robin
TI Quality of Patient-Provider Communication Among Cancer Survivors:
Findings From a Nationally Representative Sample
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID PROSTATE-CANCER; UNITED-STATES; CARE PLANS; PHYSICAL-ACTIVITY; OF-CARE;
EXPERIENCES; OUTCOMES; BREAST; SURVEILLANCE; TIME
AB Purpose
Although patient-provider communication is an essential component of health care delivery, little is known about the quality of these discussions among patients with cancer.
Methods
Data are from the 2011 Medical Expenditure Panel Survey Experiences with Cancer survey among 1,202 adult cancer survivors. We evaluated discussions with any provider after a cancer diagnosis about: (1) follow-up care; (2) late or long-term treatment effects; (3) lifestyle recommendations, such as diet, exercise, and quitting smoking; and (4) emotional or social needs. Using a response scale ranging from "did not discuss" to "discussed in detail," a summary score was constructed to define communication quality as high, medium, or low. Patient factors associated with the quality of provider discussions were examined using multivariable polytomous logistic regression analyses.
Results
At the time of the survey, approximately one half of the patients (46%) were either within 1 year (24.1%) or between 1 and 5 years (22.0%) of treatment. More than one third of cancer survivors reported that they did not receive detailed communication about follow-up care, and more than one half reported that they did not receive detailed communication regarding late or long-term effects, lifestyle recommendations, or emotional and social needs. Only 24% reported high-quality communication for all four elements, indicating that the vast majority experienced suboptimal communication. In multivariable analysis, survivors reporting a high communication quality with providers included those who were within 1 year of treatment, between the ages of 18 and 64 years, non-Hispanic black or other ethnicity, and married.
Conclusion
Study findings demonstrate gaps in the communication quality experienced by cancer survivors in the United States and help identify survivors for targeted interventions.
C1 Kaiser Permanente Northern Calif, Oakland, CA USA.
NCI, Bethesda, MD 20892 USA.
Informat Management Serv Inc, Rockville, MD USA.
Bentley Univ, Waltham, MA USA.
Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
Ctr Dis Control & Prevent, Atlanta, GA USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
Patient Ctr Outcomes Res Inst, Washington, DC USA.
RP Chawla, N (reprint author), Kaiser Permanente Northern CA, Div Res, 2000 Broadway Ave, Oakland, CA 94612 USA.
EM neetu.chawla@kp.org
NR 53
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD DEC
PY 2016
VL 12
IS 12
BP E964
EP E971
DI 10.1200/JOP.2015.006999
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EI3II
UT WOS:000392383200013
PM 27221992
ER
PT J
AU Knani, I
Earley, BJ
Udi, S
Nemirovski, A
Hadar, R
Gammal, A
Cinar, R
Hirsch, HJ
Pollak, Y
Gross, I
Eldar-Geva, T
Reyes-Capo, DP
Han, JC
Haqq, AM
Gross-Tsur, V
Wevrick, R
Tam, J
AF Knani, Ibrahim
Earley, Brian J.
Udi, Shiran
Nemirovski, Alina
Hadar, Rivka
Gammal, Asaad
Cinar, Resat
Hirsch, Harry J.
Pollak, Yehuda
Gross, Itai
Eldar-Geva, Talia
Reyes-Capo, Daniela P.
Han, Joan C.
Haqq, Andrea M.
Gross-Tsur, Varda
Wevrick, Rachel
Tam, Joseph
TI Targeting the endocannabinoid/CB1 receptor system for treating obesity
in Pradere-Willi syndrome
SO MOLECULAR METABOLISM
LA English
DT Article
DE Endocannabinoids; PWS; Magel2; Peripheral CB1 blockade; Metabolic
syndrome
ID CANNABINOID CB1 RECEPTORS; CARDIOMETABOLIC RISK-FACTORS; ENERGY-BALANCE;
ANTAGONIST SR141716; OVERWEIGHT PATIENTS; LEPTIN RESISTANCE;
ADIPOSE-TISSUE; FOOD-INTAKE; EXPRESSION; NEURONS
AB Objective: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects.
Methods: We studied eCB 'tone' in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice.
Results: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB 'tone', manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days) reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype.
Conclusions: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS. (C) 2016 The Author(s). Published by Elsevier GmbH.
C1 [Knani, Ibrahim; Udi, Shiran; Nemirovski, Alina; Hadar, Rivka; Gammal, Asaad; Tam, Joseph] Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Obes & Metab Lab,Inst Drug Res, Jerusalem, Israel.
[Earley, Brian J.; Cinar, Resat] NIAAA, Lab Physiol Studies, Bethesda, MD USA.
[Hirsch, Harry J.; Pollak, Yehuda; Gross, Itai; Gross-Tsur, Varda] Shaare Zedek Med Ctr, Dept Pediat, Neuropediat Unit, Jerusalem, Israel.
[Eldar-Geva, Talia] Shaare Zedek Med Ctr, Dept Obstet & Gynecol, Reprod Endocrinol & Genet Unit, Jerusalem, Israel.
[Reyes-Capo, Daniela P.; Han, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Metab & Neuroendocrinol, Bethesda, MD USA.
[Han, Joan C.] Univ Tennessee, Ctr Hlth Sci, Le Bonheur Childrens Hosp, Dept Pediat,Childrens Fdn Res Inst, Memphis, TN 38163 USA.
[Han, Joan C.] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
[Haqq, Andrea M.] Univ Alberta, Dept Pediat, Edmonton, AB, Canada.
[Wevrick, Rachel] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada.
RP Tam, J (reprint author), Inst Drug Res, Obes & Metab Lab, Sch Pharm, Fac Med, POB 12065, IL-91120 Jerusalem, Israel.
EM yossit@ekmd.huji.ac.il
FU Foundation for Prader Willi Research (FPWR) grants; Israel Science
Foundation (ISF) (ISF Grant) [617/14]; Canadian Institutes of Health
Research [MOP 130367]; Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
Pradere-Willi Syndrome Association (USA) grant
FX This work was supported by Foundation for Prader Willi Research (FPWR)
grants to JT and AMH, the Israel Science Foundation (ISF) (ISF Grant
#617/14 to JT), the Canadian Institutes of Health Research (MOP 130367
to RW), the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (JCH), and a
Pradere-Willi Syndrome Association (USA) grant to JCH. We are grateful
to Dr. Dinorah Barasch for her technical assistance with the LC-MS/MS
analysis, and to Ms. Nava Badichi for administrative assistance in
coordinating human blood sampling and data analysis.
NR 63
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2212-8778
J9 MOL METAB
JI Mol. Metab.
PD DEC
PY 2016
VL 5
IS 12
BP 1187
EP 1199
DI 10.1016/j.molmet.2016.10.004
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EI3DN
UT WOS:000392370000005
PM 27900261
ER
PT J
AU Klaus, A
Plenz, D
AF Klaus, Andreas
Plenz, Dietmar
TI A Low-Correlation Resting State of the Striatum during Cortical
Avalanches and Its Role in Movement Suppression
SO PLOS BIOLOGY
LA English
DT Article
ID FAST-SPIKING INTERNEURONS; RANGE TEMPORAL CORRELATIONS; SPINY PROJECTION
NEURONS; BASAL GANGLIA; CHOLINERGIC INTERNEURONS; SYNAPTIC-TRANSMISSION;
CELL ASSEMBLIES; FUNCTIONAL-ORGANIZATION; GABAERGIC INTERNEURONS;
DOPAMINERGIC-NEURONS
AB During quiet resting behavior, involuntary movements are suppressed. Such movement control is attributed to cortico-basal ganglia loops, yet population dynamics within these loops during resting and their relation to involuntary movements are not well characterized. Here, we show by recording cortical and striatal ongoing population activity in awake rats during quiet resting that intrastriatal inhibition maintains a low-correlation striatal resting state in the presence of cortical neuronal avalanches. Involuntary movements arise from disturbed striatal resting activity through two different population dynamics. Nonselectively reducing intrastriatal.-aminobutyric acid (GABA) receptor-A inhibition synchronizes striatal dynamics, leading to involuntary movements at low rate. In contrast, reducing striatal interneuron (IN)-mediated inhibition maintains decorrelation and induces intermittent involuntary movements at high rate. This latter scenario was highly effective in modulating cortical dynamics at a subsecond timescale. To distinguish intrastriatal processing from loop dynamics, cortex-striatum-midbrain cultures, which lack feedback to cortex, were used. Cortical avalanches in vitro were accompanied by low-correlated resting activity in the striatum and nonselective reduction in striatal inhibition synchronized striatal neurons similar to in vivo. Importantly, reduction of inhibition from striatal INs maintained low correlations in the striatum while reorganizing functional connectivities among striatal neurons. Our results demonstrate the importance of two major striatal microcircuits in distinctly regulating striatal and cortical resting state dynamics. These findings suggest that specific functional connectivities of the striatum that are maintained by local inhibition are important in movement control.
C1 [Klaus, Andreas; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
[Klaus, Andreas] Champalimaud Ctr Unknown, Champalimaud Neurosci Program, Ave Brasilia, Lisbon, Portugal.
RP Klaus, A (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.; Klaus, A (reprint author), Champalimaud Ctr Unknown, Champalimaud Neurosci Program, Ave Brasilia, Lisbon, Portugal.
EM andreas.klaus@neuro.fchampalimaud.org
OI Klaus, Andreas/0000-0002-4133-351X
FU NIMH Division of Intramural Research Programs; NIH-Karolinska Institute
FX This work was supported by the NIMH Division of Intramural Research
Programs. AK was in addition supported by the NIH-Karolinska Institute
joint PhD program. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 90
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD DEC
PY 2016
VL 14
IS 12
AR e1002582
DI 10.1371/journal.pbio.1002582
PG 30
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EH9VQ
UT WOS:000392120100011
PM 27923040
ER
PT J
AU Barik, D
Ball, DA
Peccoud, J
Tyson, JJ
AF Barik, Debashis
Ball, David A.
Peccoud, Jean
Tyson, John J.
TI A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback
Regulation in Limiting Cellular Variability
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MULTISITE PROTEIN-PHOSPHORYLATION; APC-DEPENDENT PROTEOLYSIS;
BUDDING-YEAST; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; MITOTIC EXIT;
POSITIVE FEEDBACK; G1 CYCLINS; PHOSPHATASE CDC14; DNA-REPLICATION
AB The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of similar to 30 mutant yeast strains that have not yet been characterized experimentally.
C1 [Barik, Debashis] Univ Hyderabad, Sch Chem, Hyderabad, Telangana, India.
[Ball, David A.; Peccoud, Jean; Tyson, John J.] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
[Tyson, John J.] Virginia Polytech Inst & State Univ, Dept Biol Sci, Blacksburg, VA 24061 USA.
[Ball, David A.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Peccoud, Jean] Colorado State Univ, Dept Chem & Biol Engn, Ft Collins, CO 80523 USA.
RP Barik, D (reprint author), Univ Hyderabad, Sch Chem, Hyderabad, Telangana, India.; Tyson, JJ (reprint author), Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.; Tyson, JJ (reprint author), Virginia Polytech Inst & State Univ, Dept Biol Sci, Blacksburg, VA 24061 USA.
EM dbariksc@uohyd.ac.in; tyson@vt.edu
OI Barik, Debashis/0000-0003-1681-1273; Tyson, John/0000-0001-7560-6013
FU University Grants Commission (India) [F30-24/2014(BSR)]; National
Institutes of Health (USA) [1R01-GM078989-09]
FX This work was supported by funding from the University Grants Commission
(India) Start-Up Research Grant F30-24/2014(BSR) to DB and from the
National Institutes of Health (USA) 1R01-GM078989-09 to JJT and JP. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 90
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U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD DEC
PY 2016
VL 12
IS 12
AR e1005230
DI 10.1371/journal.pcbi.1005230
PG 36
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA EH9XT
UT WOS:000392126000020
PM 27935947
ER
PT J
AU Neuwald, AF
Altschul, SF
AF Neuwald, Andrew F.
Altschul, Stephen F.
TI Inference of Functionally-Relevant N-acetyltransferase Residues Based on
Statistical Correlations
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENTS; PROTEIN DOMAIN HIERARCHIES; GIBBS SAMPLING
STRATEGIES; JOINT BAYESIAN-ESTIMATION; DIRECT-COUPLING ANALYSIS;
METHIONINE SULFOXIMINE; STRUCTURE PREDICTION; EVOLUTIONARY TRACE;
ACCURATE ALIGNMENT; CLUSTAL OMEGA
AB Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs), which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC) sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and pi-pi stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu).
C1 [Neuwald, Andrew F.] Univ Maryland, Sch Med, Inst Genome Sci, BioPark II,Room 617, Baltimore, MD 21201 USA.
[Neuwald, Andrew F.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, BioPark II,Room 617, Baltimore, MD 21201 USA.
[Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Neuwald, AF (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, BioPark II,Room 617, Baltimore, MD 21201 USA.; Neuwald, AF (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, BioPark II,Room 617, Baltimore, MD 21201 USA.
EM aneuwald@som.umaryland.edu
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX SFA was supported by the Intramural Research Program of the National
Institutes of Health, National Library of Medicine. AFN received no
specific funding for this work. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 93
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD DEC
PY 2016
VL 12
IS 12
AR e1005294
DI 10.1371/journal.pcbi.1005294
PG 30
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA EH9XT
UT WOS:000392126000052
PM 28002465
ER
PT J
AU Shi, JX
Park, JH
Duan, JB
Berndt, ST
Moy, W
Yu, K
Song, L
Wheeler, W
Hua, X
Silverman, D
Garcia-Closas, M
Hsiung, CA
Figueroa, JD
Cortessis, VK
Malats, N
Karagas, MR
Vineis, P
Chang, IS
Lin, DX
Zhou, BS
Seow, A
Matsuo, K
Hong, YC
Caporaso, NE
Wolpin, B
Jacobs, E
Petersen, GM
Klein, AP
Li, DH
Risch, H
Sanders, AR
Hsu, L
Schoen, RE
Brenner, H
Stolzenberg-Solomon, R
Gejman, P
Lan, Q
Rothman, N
Amundadottir, LT
Landi, MT
Levinson, DF
Chanock, SJ
Chatterjee, N
AF Shi, Jianxin
Park, Ju-Hyun
Duan, Jubao
Berndt, Sonja T.
Moy, Winton
Yu, Kai
Song, Lei
Wheeler, William
Hua, Xing
Silverman, Debra
Garcia-Closas, Montserrat
Hsiung, Chao Agnes
Figueroa, Jonine D.
Cortessis, Victoria K.
Malats, Nuria
Karagas, Margaret R.
Vineis, Paolo
Chang, I-Shou
Lin, Dongxin
Zhou, Baosen
Seow, Adeline
Matsuo, Keitaro
Hong, Yun-Chul
Caporaso, Neil E.
Wolpin, Brian
Jacobs, Eric
Petersen, Gloria M.
Klein, Alison P.
Li, Donghui
Risch, Harvey
Sanders, Alan R.
Hsu, Li
Schoen, Robert E.
Brenner, Hermann
Stolzenberg-Solomon, Rachael
Gejman, Pablo
Lan, Qing
Rothman, Nathaniel
Amundadottir, Laufey T.
Landi, Maria Teresa
Levinson, Douglas F.
Chanock, Stephen J.
Chatterjee, Nilanjan
CA MGS Mol Genetics Schizophrenia GWA
GAME-ON TRICL Transdisciplinary Re
PRACTICAL PRostate Canc Assoc Grp
PanScan Consortium
GAME-ON ELLIPSE Consortium
TI Winner's Curse Correction and Variable Thresholding Improve Performance
of Polygenic Risk Modeling Based on Genome-Wide Association Study
Summary-Level Data
SO PLOS GENETICS
LA English
DT Article
ID BODY-MASS INDEX; SUSCEPTIBILITY LOCI; HUMAN HEIGHT; PARTITIONING
HERITABILITY; PSYCHIATRIC-DISORDERS; INCREASES ACCURACY;
GENETIC-VARIATION; COMMON VARIANTS; CANCER RISK; PREDICTION
AB Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R-2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R-2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R-2 to 3.53% (P = 2x10(-5)). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure.
C1 [Shi, Jianxin; Berndt, Sonja T.; Yu, Kai; Song, Lei; Hua, Xing; Silverman, Debra; Garcia-Closas, Montserrat; Figueroa, Jonine D.; Caporaso, Neil E.; Stolzenberg-Solomon, Rachael; Lan, Qing; Rothman, Nathaniel; Amundadottir, Laufey T.; Chanock, Stephen J.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Park, Ju-Hyun] Dongguk Univ, Dept Stat, Seoul, South Korea.
[Duan, Jubao; Gejman, Pablo] Univ Chicago, North Shore Univ Hlth Syst, Pritzker Sch Med, Ctr Psychiat Genet,Dept Psychiat & Behav Sci,Res, Evanston, IL USA.
[Moy, Winton] Northern Illinois Univ, Dept Stat, De Kalb, IL USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Hsiung, Chao Agnes] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
[Figueroa, Jonine D.] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Cortessis, Victoria K.] Univ Southern Calif, USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Cortessis, Victoria K.] Univ Southern Calif, USC Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA.
[Cortessis, Victoria K.] Univ Southern Calif, USC Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Karagas, Margaret R.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
[Vineis, Paolo] Human Genet Fdn, Turin, Italy.
[Vineis, Paolo] Imperial Coll London, MRC, PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England.
[Chang, I-Shou] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing, Peoples R China.
[Lin, Dongxin] Peking Union Med Coll, Beijing, Peoples R China.
[Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China.
[Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang, Peoples R China.
[Seow, Adeline] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Chikusa Ku, Nagoya, Aichi, Japan.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Wolpin, Brian] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wolpin, Brian] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Wolpin, Brian] Harvard Med Sch, Boston, MA USA.
[Jacobs, Eric] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Klein, Alison P.; Chatterjee, Nilanjan] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Klein, Alison P.] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Hsu, Li] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA.
[Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Brenner, Hermann] Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Chatterjee, Nilanjan] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
RP Shi, JX; Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.; Chatterjee, N (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.; Chatterjee, N (reprint author), Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM Jianxin.Shi@nih.gov; nilanjan@jhu.edu
RI Brenner, Hermann/B-4627-2017
OI Brenner, Hermann/0000-0002-6129-1572
FU NIH Intramural Research program; NIH [U19 CA148127]; National Cancer
Institute, National Institutes of Health, U.S. Department of Health and
Human Services [U01 CA137088, R01 CA059045]; Regional Council of Pays de
la Loire; Groupement des Entreprises Francaises dans la Lutte contre le
Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale
Contre le Cancer (LRCC); National Institutes of Health [R01 CA60987, R01
CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA151993, P50
CA127003, UM1 CM 86107, R01 CM 37178, P01 CA87969, R01 CA042182, R37
CA54281, P01 CA033619, R01 CA63464, U01 CA074783, R01 CA076366, K05
CA154337]; German Research Council (Deutsche Forschungsgemeinschaft) [BR
1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry
of Education and Research [01KH0404, 01ER0814]; Ontario Research Fund;
Canadian Institutes of Health Research; Ontario Institute for Cancer
Research; Ontario Ministry of Research and Innovation; National Heart,
Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN271201100004C]
FX The research was supported by the NIH Intramural Research program. The
TRICL Consortium was supported by NIH grant U19 CA148127. Funding for
GECCO consortium: National Cancer Institute, National Institutes of
Health, U.S. Department of Health and Human Services (U01 CA137088; R01
CA059045). ASTERISK: a Hospital Clinical Research Program (PHRC) and
supported by the Regional Council of Pays de la Loire, the Groupement
des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the
Association Anne de Bretagne Genetique and the Ligue Regionale Contre le
Cancer (LRCC). COLO2&3: National Institutes of Health (R01 CA60987).
DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR
1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German
Federal Ministry of Education and Research (01KH0404 and 01ER0814).
DALS: National Institutes of Health (R01 CA48998 to M. L. Slattery).
HPFS is supported by the National Institutes of Health (P01 CA 055075,
UM1 CA167552, R01 137178, R01 CA151993 and P50 CA127003), NHS by the
National Institutes of Health (UM1 CM 86107, R01 CM 37178, P01 CA87969,
R01 CA151993 and P50 CA127003) and PHS by the National Institutes of
Health (R01 CA042182). MEC: National Institutes of Health (R37 CA54281,
P01 CA033619, and R01 CA63464). OFCCR: National Institutes of Health,
through funding allocated to the Ontario Registry for Studies of
Familial Colorectal Cancer (U01 CA074783); see CCFR section above.
Additional funding toward genetic analyses of OFCCR includes the Ontario
Research Fund, the Canadian Institutes of Health Research, and the
Ontario Institute for Cancer Research, through generous support from the
Ontario Ministry of Research and Innovation. PMH: National Institutes of
Health (R01 CA076366 to P.A. Newcomb). VITAL: National Institutes of
Health (K05 CA154337). WHI: The WHI program is funded by the National
Heart, Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 60
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U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD DEC
PY 2016
VL 12
IS 12
AR e1006493
DI 10.1371/journal.pgen.1006493
PG 24
WC Genetics & Heredity
SC Genetics & Heredity
GA EI0CD
UT WOS:000392138700036
PM 28036406
ER
PT J
AU Zhang, HH
Kamiya, N
Tsuji, T
Takeda, H
Scott, G
Rajderkar, S
Ray, MK
Mochida, Y
Allen, B
Lefebvre, V
Hung, IH
Ornitz, DM
Kunieda, T
Mishina, Y
AF Zhang, Honghao
Kamiya, Nobuhiro
Tsuji, Takehito
Takeda, Haruko
Scott, Greg
Rajderkar, Sudha
Ray, Manas K.
Mochida, Yoshiyuki
Allen, Benjamin
Lefebvre, Veronique
Hung, Irene H.
Ornitz, David M.
Kunieda, Tetsuo
Mishina, Yuji
TI Elevated Fibroblast Growth Factor Signaling Is Critical for the
Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice
SO PLOS GENETICS
LA English
DT Article
ID VAN-CREVELD-SYNDROME; INDIAN HEDGEHOG; PRIMARY CILIUM; CHONDROCYTE
PROLIFERATION; THANATOPHORIC DYSPLASIA; SKELETAL DEVELOPMENT;
BONE-DEVELOPMENT; RECEPTOR-3 GENE; DIFFERENTIATION; ACTIVATION
AB Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling. In this report, we comprehensively analyze limb skeletogenesis in Evc2 mutant mice and in cell and tissue cultures derived from these mice. Both in vivo and in vitro data demonstrate elevated Fibroblast Growth Factor (FGF) signaling in Evc2 mutant growth plates, in addition to compromised but not abrogated Hedgehog-PTHrP feedback loop. Elevation of FGF signaling, mainly due to increased Fgf18 expression upon inactivation of Evc2 in the perichondrium, critically contributes to the pathogenesis of limb dwarfism. The limb dwarfism phenotype is partially rescued by inactivation of one allele of Fgf18 in the Evc2 mutant mice. Taken together, our data uncover a novel pathogenic mechanism to understand limb dwarfism in patients with Ellis-van Creveld syndrome.
C1 [Zhang, Honghao; Kamiya, Nobuhiro; Rajderkar, Sudha; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Kamiya, Nobuhiro; Takeda, Haruko; Mishina, Yuji] NIEHS, RDBL, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Tsuji, Takehito; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama, Japan.
[Scott, Greg; Ray, Manas K.; Mishina, Yuji] NIEHS, Knock Out Core, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Mochida, Yoshiyuki] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA.
[Allen, Benjamin] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Lefebvre, Veronique] Cleveland Clin, Dept Cellular & Mol Med, Lerner Res Inst, Cleveland, OH 44106 USA.
[Hung, Irene H.] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT USA.
[Hung, Irene H.; Ornitz, David M.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
[Kamiya, Nobuhiro] Tenri Univ, Fac Budo & Sport Studies, Nara, Japan.
[Takeda, Haruko] Univ Liege, Unit Anim Genom, GIGA R, Liege, Belgium.
[Takeda, Haruko] Univ Liege, Fac Vet Med, Liege, Belgium.
RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.; Mishina, Y (reprint author), NIEHS, RDBL, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Mishina, Y (reprint author), NIEHS, Knock Out Core, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM mishina@umich.edu
OI Rajderkar, Sudha/0000-0003-2001-3450
FU NIH [R01DE020843, YMi R01HD049808, R01DE019527]; Washington University
Musculoskeletal Research Center [P30 AR057235]; DDRCC [P30 DK052574];
University of Michigan
FX This work was supported by NIH grants (R01DE020843 to YMi R01HD049808 to
DMO, and R01DE019527 to YMo), Washington University Musculoskeletal
Research Center (P30 AR057235) and DDRCC (P30 DK052574), and University
of Michigan funds (M-Cubed fund, Hedgehog pathway cancer therapy and
taste and smell defects, Team A). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD DEC
PY 2016
VL 12
IS 12
AR e1006510
DI 10.1371/journal.pgen.1006510
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA EI0CD
UT WOS:000392138700044
PM 28027321
ER
PT J
AU Shi, JX
Hua, X
Zhu, B
Ravichandran, S
Wang, MY
Nguyen, C
Brodie, SA
Palleschi, A
Alloisio, M
Pariscenti, G
Jones, K
Zhou, WY
Bouk, AJ
Boland, J
Hicks, B
Risch, A
Bennett, H
Luke, BT
Song, L
Duan, JB
Liu, PY
Kohno, T
Chen, QR
Meerzaman, D
Marconett, C
Laird-Offringa, I
Mills, I
Caporaso, NE
Gail, MH
Pesatori, AC
Consonni, D
Bertazzi, PA
Chanock, SJ
Landi, MT
AF Shi, Jianxin
Hua, Xing
Zhu, Bin
Ravichandran, Sarangan
Wang, Mingyi
Nguyen, Cu
Brodie, Seth A.
Palleschi, Alessandro
Alloisio, Marco
Pariscenti, Gianluca
Jones, Kristine
Zhou, Weiyin
Bouk, Aaron J.
Boland, Joseph
Hicks, Belynda
Risch, Adam
Bennett, Hunter
Luke, Brian T.
Song, Lei
Duan, Jubao
Liu, Pengyuan
Kohno, Takashi
Chen, Qingrong
Meerzaman, Daoud
Marconett, Crystal
Laird-Offringa, Ite
Mills, Ian
Caporaso, Neil E.
Gail, Mitchell H.
Pesatori, Angela C.
Consonni, Dario
Bertazzi, Pier Alberto
Chanock, Stephen J.
Landi, Maria Teresa
TI Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A
Retrospective Study
SO PLOS MEDICINE
LA English
DT Article
ID BREAST-CANCER CELLS; FAMILY TRANSCRIPTION FACTOR; GASTRIC-CANCER; MUTUAL
EXCLUSIVITY; DNA METHYLATION; TUMOR MUTATIONS; CPG SITES; EXPRESSION;
GENE; IDENTIFICATION
AB Background
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression.
Methods and Findings
We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5x10(-50)). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5x10(-4)) were associated with increased risk of distant metastasis. Our study's limitations include a small number of LUAD patients for subgroup analyses and a single-sample design for investigation of subclonality.
Conclusions
These data provide a genomic characterization of LUAD pathogenesis and progression. The distinct clonal and subclonal mutation signatures suggest possible diverse carcinogenesis pathways for endogenous and exogenous exposures, and may serve as a foundation for more effective treatments for this lethal disease. LUAD's high heterogeneity emphasizes the need to further study this tumor type and to associate genomic findings with clinical outcomes.
C1 [Shi, Jianxin; Hua, Xing; Zhu, Bin; Wang, Mingyi; Brodie, Seth A.; Jones, Kristine; Zhou, Weiyin; Bouk, Aaron J.; Boland, Joseph; Hicks, Belynda; Bennett, Hunter; Song, Lei; Caporaso, Neil E.; Gail, Mitchell H.; Chanock, Stephen J.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ravichandran, Sarangan; Luke, Brian T.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA.
[Wang, Mingyi; Brodie, Seth A.; Jones, Kristine; Zhou, Weiyin; Bouk, Aaron J.; Boland, Joseph; Hicks, Belynda; Song, Lei] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD USA.
[Nguyen, Cu; Chen, Qingrong; Meerzaman, Daoud] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Palleschi, Alessandro] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Thorac Surg, Milan, Italy.
[Alloisio, Marco] Ist Clin Humanitas, Div Thorac Surg, Milan, Italy.
[Pariscenti, Gianluca] Community Hosp, Thorac Surg Unit, Brescia, Italy.
[Risch, Adam] Informat Management Serv Inc, Rockville, MD USA.
[Duan, Jubao] Univ Chicago, Pritzker Sch Med, North Shore Univ Hlth Syst Res Inst, Ctr Psychiat Genet,Dept Psychiat & Behav Sci, Evanston, IL USA.
[Liu, Pengyuan] Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Liu, Pengyuan] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA.
[Kohno, Takashi] Natl Canc Ctr, Div Genome Biol, Tokyo, Japan.
[Marconett, Crystal; Laird-Offringa, Ite] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Surg, Los Angeles, CA USA.
[Marconett, Crystal; Laird-Offringa, Ite] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA USA.
[Mills, Ian] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Prostate Canc UK Movember Ctr Excellence Prostate, Belfast, Antrim, North Ireland.
[Pesatori, Angela C.; Consonni, Dario; Bertazzi, Pier Alberto] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy.
[Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov
RI Risch, Angela/H-2669-2013; bertazzi, pietro alberto/D-5039-2017;
OI Risch, Angela/0000-0002-8026-5505; bertazzi, pietro
alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252;
Palleschi, Alessandro/0000-0003-4510-5167; RAVICHANDRAN,
SARANGAN/0000-0001-6349-0172
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, United States Department of Health and
Human Services, Bethesda, MD; NIH [1 R01 HL114094]; Thomas G. Labrecque
Foundation; Norris Comprehensive Cancer Center from the National Cancer
Institute [P30CA014089]
FX This work was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, United States Department of Health and
Human Services, Bethesda, MD. CM and ILO were supported by NIH grant (1
R01 HL114094, NHLBI: http://www.nhlbi.nih.gov/). ILO was supported by
the Thomas G. Labrecque Foundation (https:// tglfoundation.com/), and in
part by the Norris Comprehensive Cancer Center core grant, award number
P30CA014089 from the National Cancer Institute
(https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-in
stitute-nci). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 54
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD DEC
PY 2016
VL 13
IS 12
AR e1002162
DI 10.1371/journal.pmed.1002162
PG 24
WC Medicine, General & Internal
SC General & Internal Medicine
GA EI0DJ
UT WOS:000392142400002
PM 27923066
ER
PT J
AU Osamor, PE
Grady, C
AF Osamor, Pauline E.
Grady, Christine
TI Zika Virus: Promoting Male Involvement in the Health of Women and
Families
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
C1 [Osamor, Pauline E.; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Osamor, PE (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM pauline.osamor@nih.gov
NR 14
TC 0
Z9 0
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD DEC
PY 2016
VL 10
IS 12
AR e0005127
DI 10.1371/journal.pntd.0005127
PG 5
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA EI0IX
UT WOS:000392158100020
PM 28033340
ER
PT J
AU Adnan, S
Reeves, RK
Gillis, J
Wong, FE
Yu, Y
Camp, JV
Li, QS
Connole, M
Li, Y
Piatak, M
Lifson, JD
Li, WJ
Keele, BF
Kozlowski, PA
Desrosiers, RC
Haase, AT
Johnson, RP
AF Adnan, Sama
Reeves, R. Keith
Gillis, Jacqueline
Wong, Fay E.
Yu, Yi
Camp, Jeremy V.
Li, Qingsheng
Connole, Michelle
Li, Yuan
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Li, Wenjun
Keele, Brandon F.
Kozlowski, Pamela A.
Desrosiers, Ronald C.
Haase, Ashley T.
Johnson, R. Paul
TI Persistent Low-Level Replication of SIV Delta nef Drives Maturation of
Antibody and CD8 T Cell Responses to Induce Protective Immunity against
Vaginal SIV Infection
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; HIGHLY PATHOGENIC SIV; RHESUS MACAQUES;
ATTENUATED SIV; VACCINE PROTECTION; HIV-1 INFECTION; LIVE; CHALLENGE;
TRANSMISSION; EFFICACY
AB Defining the correlates of immune protection conferred by SIV Delta nef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIV Delta nef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIV Delta nef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIV Delta nef antigenic load. In conclusion, maturation of SIV Delta nef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.
C1 [Adnan, Sama; Johnson, R. Paul] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Adnan, Sama; Reeves, R. Keith; Gillis, Jacqueline; Wong, Fay E.; Yu, Yi; Connole, Michelle; Johnson, R. Paul] Harvard Med Sch, New England Primate Res Ctr, Southborough Campus,Pine Hill Dr, Southborough, MA 01772 USA.
[Reeves, R. Keith] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA.
[Li, Qingsheng] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
[Li, Qingsheng] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
[Li, Yuan; Piatak, Michael, Jr.; Lifson, Jeffrey D.; Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Li, Wenjun] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Desrosiers, Ronald C.] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA.
[Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, MMC 196,420 Delaware St SE, Minneapolis, MN 55455 USA.
[Johnson, R. Paul] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
RP Johnson, RP (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.; Johnson, RP (reprint author), Harvard Med Sch, New England Primate Res Ctr, Southborough Campus,Pine Hill Dr, Southborough, MA 01772 USA.; Johnson, RP (reprint author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
EM rpaul.johnson@emory.edu
FU International AIDS Vaccine Initiative; National Institutes of Health
[AI071306, AI095985]; Office of Research Infrastructure Programs [P51
OD011103, RR00168, P51 OD011132]; Emory Center for AIDS Research
[P30AI050409]; Harvard Multidisciplinary Training grant [T32
AI07387-24]; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the International AIDS Vaccine Initiative
(www.iavi.org). It was also funded by National Institutes of Health
(http://www.nih.gov) grants AI071306 (RPJ), AI095985 (RPJ), and grants
P51 OD011103 (formerly RR00168) and P51 OD011132 from the Office of
Research Infrastructure Programs, and the Emory Center for AIDS Research
(P30AI050409). The research was also funded by the Harvard
Multidisciplinary Training grant (T32 AI07387-24). In addition, this
research was supported by the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E (BFK, JDL).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
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U1 0
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006104
DI 10.1371/journal.ppat.1006104
PG 29
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100065
PM 27959961
ER
PT J
AU Ericsen, AJ
Lauck, M
Mohns, MS
DiNapoli, SR
Mutschler, JP
Greene, JM
Weinfurter, JT
Lehrer-Brey, G
Prall, TM
Gieger, SM
Buechler, CR
Crosno, KA
Peterson, EJ
Reynolds, MR
Wiseman, RW
Burwitz, BJ
Estes, JD
Sacha, JB
Friedrich, TC
Brenchley, JM
O'Connor, DH
AF Ericsen, Adam J.
Lauck, Michael
Mohns, Mariel S.
DiNapoli, Sarah R.
Mutschler, James P.
Greene, Justin M.
Weinfurter, Jason T.
Lehrer-Brey, Gabrielle
Prall, Trent M.
Gieger, Samantha M.
Buechler, Connor R.
Crosno, Kristin A.
Peterson, Eric J.
Reynolds, Matthew R.
Wiseman, Roger W.
Burwitz, Benjamin J.
Estes, Jacob D.
Sacha, Jonah B.
Friedrich, Thomas C.
Brenchley, Jason M.
O'Connor, David H.
TI Microbial Translocation and Inflammation Occur in Hyperacute
Immunodeficiency Virus Infection and Compromise Host Control of Virus
Replication
SO PLOS PATHOGENS
LA English
DT Article
ID CD4(+) T-CELLS; POLYMERASE-CHAIN-REACTION; IMMUNE ACTIVATION;
HIV-INFECTION; VIRAL REPLICATION; SIV INFECTION; PLASMA-LEVELS; SOLUBLE
CD14; ENDOTOXEMIA; EXPRESSION
AB Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS)-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque 'elite controllers' with a short-course of dextran sulfate sodium (DSS)-stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host's capacity to contain infection.
C1 [Ericsen, Adam J.; Lauck, Michael; Mohns, Mariel S.; Greene, Justin M.; Weinfurter, Jason T.; Gieger, Samantha M.; Buechler, Connor R.; Reynolds, Matthew R.; Wiseman, Roger W.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Ericsen, Adam J.] Univ Wisconsin, Virol Training Program, Madison, WI USA.
[DiNapoli, Sarah R.; Brenchley, Jason M.] NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD USA.
[Mutschler, James P.; Lehrer-Brey, Gabrielle; Prall, Trent M.; Crosno, Kristin A.; Peterson, Eric J.; Friedrich, Thomas C.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Burwitz, Benjamin J.; Sacha, Jonah B.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Oregon Natl Primate Res Ctr, Portland, OR 97201 USA.
[Burwitz, Benjamin J.; Sacha, Jonah B.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Estes, Jacob D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Friedrich, Thomas C.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.; O'Connor, DH (reprint author), Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
EM doconnor@primate.wisc.edu
OI Mohns, Mariel/0000-0002-3609-8447; Lauck, Michael/0000-0003-2813-3705;
Ericsen, Adam/0000-0003-4176-8270; Friedrich, Thomas/0000-0001-9831-6895
FU National Institutes of Health [R01 AI077376, R01 AI084787, T32
AI078985]; National Center for Research Resources [P51 RR000167, P51
OD011092]; Research Facilities Improvement Program [RR15459-01,
RR020141-01]; Division of Intramural Research at the National Institutes
of Allergies and Infectious Diseases; National Cancer Institute (NIH)
[HHSN261200800001E]
FX This research was supported by National Institutes of Health
(http://www.nih.gov) grants R01 AI077376, awarded to DHO, R01 AI084787,
awarded to DHO and TCF, and T32 AI078985 supporting AJE. This work was
conducted at facilities supported (P51 RR000167 and P51 OD011092) by
National Center for Research Resources (htttp://www.ncrr.nih.gov), and
in a facility constructed with support (RR15459-01 and RR020141-01) from
the Research Facilities Improvement Program. Funding for this study was
provided in part by the Division of Intramural Research at the National
Institutes of Allergies and Infectious Diseases
(htttp://www.niaid.nih.gov). This work was supported in part with
federal funds from the National Cancer Institute
(htttp://www.cancer.nih.gov) (NIH Contract HHSN261200800001E). The
content of this publication does not necessarily reflect the views or
policies of DHHS, or does the mention of trade names, commercial
products, or organizations imply endorsement by the US Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006048
DI 10.1371/journal.ppat.1006048
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100029
PM 27926931
ER
PT J
AU Furuyama, W
Marzi, A
Carmody, AB
Maruyama, J
Kuroda, M
Miyamoto, H
Nanbo, A
Manzoor, R
Yoshida, R
Igarashi, M
Feldmann, H
Takada, A
AF Furuyama, Wakako
Marzi, Andrea
Carmody, Aaron B.
Maruyama, Junki
Kuroda, Makoto
Miyamoto, Hiroko
Nanbo, Asuka
Manzoor, Rashid
Yoshida, Reiko
Igarashi, Manabu
Feldmann, Heinz
Takada, Ayato
TI Fc gamma-receptor IIa-mediated Src Signaling Pathway Is Essential for
the Antibody-Dependent Enhancement of Ebola Virus Infection
SO PLOS PATHOGENS
LA English
DT Article
ID PROTEIN-TYROSINE KINASE; NIEMANN-PICK C1; CYTOPLASMIC DOMAIN; IN-VITRO;
DC-SIGN; CELLS; ENTRY; DENGUE; GLYCOPROTEIN; MACROPHAGES
AB Antibody-dependent enhancement (ADE) of Ebola virus (EBOV) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fc gamma-receptor IIa (Fc gamma RIIa)-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs) is required for ADE of EBOV infection. We found that deletion of the Fc gamma RIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface Fc gamma RIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection.
C1 [Furuyama, Wakako; Maruyama, Junki; Kuroda, Makoto; Miyamoto, Hiroko; Manzoor, Rashid; Yoshida, Reiko; Igarashi, Manabu; Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Carmody, Aaron B.] NIAID, Res Technol Branch, Div Intramural Res, NIH, Hamilton, MT USA.
[Nanbo, Asuka] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido, Japan.
[Igarashi, Manabu; Takada, Ayato] Hokkaido Univ, Global Stn Zoonosis Control, Global Inst Collaborat Res & Educ, Sapporo, Hokkaido, Japan.
[Takada, Ayato] Univ Zambia, Sch Vet Med, Lusaka, Zambia.
[Kuroda, Makoto] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
RP Takada, A (reprint author), Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.; Takada, A (reprint author), Hokkaido Univ, Global Stn Zoonosis Control, Global Inst Collaborat Res & Educ, Sapporo, Hokkaido, Japan.; Takada, A (reprint author), Univ Zambia, Sch Vet Med, Lusaka, Zambia.
EM atakada@czc.hokudai.ac.jp
RI Nanbo, Asuka/C-6630-2012
OI Nanbo, Asuka/0000-0001-8764-1350
FU KAKENHI [14J06186, 15H01249]; Ministry of Education, Culture, Sports,
Science and Technology (MEXT); Japan Society for the Promotion of
Science (JSPS), Japan; Japan Initiative for Global Research Network on
Infectious Diseases (J-GRID) from Ministry of Education, Culture, Sport,
Science & Technology in Japan; Japan Agency for Medical Research and
Development (AMED); Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health, USA
FX This work was supported by KAKENHI (14J06186 and 15H01249),
Grants-in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology (MEXT) and the Japan Society for
the Promotion of Science (JSPS), Japan, and partly by the Japan
Initiative for Global Research Network on Infectious Diseases (J-GRID)
from Ministry of Education, Culture, Sport, Science & Technology in
Japan, and Japan Agency for Medical Research and Development (AMED), and
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 62
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006139
DI 10.1371/journal.ppat.1006139
PG 22
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100074
PM 28036370
ER
PT J
AU Lubaki, NM
Younan, P
Santos, RI
Meyer, M
Iampietro, M
Koup, RA
Bukreyev, A
AF Lubaki, Ndongala Michel
Younan, Patrick
Santos, Rodrigo I.
Meyer, Michelle
Iampietro, Mathieu
Koup, Richard A.
Bukreyev, Alexander
TI The Ebola Interferon Inhibiting Domains Attenuate and Dysregulate
Cell-Mediated Immune Responses
SO PLOS PATHOGENS
LA English
DT Article
ID INFLUENZA-VIRUS INFECTION; NATURAL-KILLER-CELLS; CLASS-I MOLECULES;
CD8(+) T-CELLS; PBL-SCID MICE; DENDRITIC CELLS; NK CELLS;
ZAIRE-EBOLAVIRUS; VIRAL-INFECTION; IFN-ALPHA
AB Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m). Peripheral blood mononuclear cells (PBMCs) from cytomegalovirus (CMV)-seropositive donors were inoculated with the panel of viruses and stimulated with CMV pp65 peptides. Disabling of the VP35 IID resulted in increased proliferation and higher percentages of CD4(+) T cells secreting IFN. and/or TNFa. To address the role of aberrant DC maturation in the IID-mediated suppression of T cell responses, CMV-stimulated DCs were infected with the panel of viruses and co-cultured with autologous T-lymphocytes. Infection with EBOV/VP35m infection resulted in a significant increase, as compared to wt EBOV, in proliferating CD4(+) cells secreting IFN gamma, TNF alpha and IL-2. Experiments with expanded CMV-specific T cells demonstrated their increased activation following co-cultivation with CMV-pulsed DCs pre-infected with EBOV/VP24m, EBOV/VP35m and EBOV/VP35m/VP24m, as compared to wt EBOV. Both IIDs were found to block phosphorylation of TCR complex-associated adaptors and downstream signaling molecules. Next, we examined the effects of IIDs on the function of B cells in infected PBMC. Infection with EBOV/VP35m and EBOV/VP35m/VP24m resulted in significant increases in the percentages of phenotypically distinct B-cell subsets and plasma cells, as compared to wt EBOV, suggesting inhibition of B cell function and differentiation by VP35 IID. Finally, infection with EBOV/VP35m increased activation of NK cells, as compared to wt EBOV. These results demonstrate a global suppression of cell-mediated responses by EBOV IIDs and identify the role of DCs in suppression of T-cell responses.
C1 [Lubaki, Ndongala Michel; Younan, Patrick; Santos, Rodrigo I.; Meyer, Michelle; Iampietro, Mathieu; Bukreyev, Alexander] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Lubaki, Ndongala Michel; Younan, Patrick; Santos, Rodrigo I.; Meyer, Michelle; Iampietro, Mathieu; Bukreyev, Alexander] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Bukreyev, Alexander] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
RP Bukreyev, A (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.; Bukreyev, A (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.; Bukreyev, A (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
EM alexander.bukreyev@utmb.edu
FU National Institutes of Health / National Institute of Allergy and
Infectious Diseases [U19AI109945]; John Sealy Memorial Endowment;
McLaughlin Fellowship
FX This study was funded by the National Institutes of Health / National
Institute of Allergy and Infectious Diseases, grant U19AI109945 (AB),
John Sealy Memorial Endowment
http://research.utmb-edu/sealy/Awardees.aspx Pilot Grant "Mechanisms of
'Immune Paralysis' in Ebola Infections (AB), and McLaughlin Fellowship
http://www.utmb.edu/mclaughlin/posdoctoral.shtml .shtml (NML). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 94
TC 0
Z9 0
U1 8
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006031
DI 10.1371/journal.ppat.1006031
PG 34
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100018
PM 27930745
ER
PT J
AU Mehedi, M
McCarty, T
Martin, SE
Le Nouen, C
Buehler, E
Chen, YC
Smelkinson, M
Ganesan, S
Fischer, ER
Brock, LG
Liang, B
Munir, S
Collins, PL
Buchholz, UJ
AF Mehedi, Masfique
McCarty, Thomas
Martin, Scott E.
Le Nouen, Cyril
Buehler, Eugen
Chen, Yu-Chi
Smelkinson, Margery
Ganesan, Sundar
Fischer, Elizabeth R.
Brock, Linda G.
Liang, Bo
Munir, Shirin
Collins, Peter L.
Buchholz, Ursula J.
TI Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate
Human Respiratory Syncytial Virus Spread
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN DENDRITIC CELLS; GROWTH CONE MOTILITY; IN-VITRO MODEL;
PARAINFLUENZA VIRUS; HUMAN METAPNEUMOVIRUS; CELLULAR ACTIN; F-ACTIN;
INFECTION; COMPLEX; MORPHOGENESIS
AB Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells. Consistent with reduced spread, there was a 10-fold reduction in the release of infectious progeny virions in ARP2-depleted cells at 72 hr post-infection. In addition, we found that RSV infection induced filopodia formation and increased cell motility in A549 cells and that this phenotype was ARP2 dependent. Filopodia appeared to shuttle RSV to nearby uninfected cells, facilitating virus spread. Expression of the RSV F protein alone from a plasmid or heterologous viral vector in A549 cells induced filopodia, indicating a new role for the RSV F protein, driving filopodia induction and virus spread. Thus, this study identified roles for ARP2 and filopodia in RSV-induced cell motility, RSV production, and RSV cell-to-cell spread.
C1 [Mehedi, Masfique; McCarty, Thomas; Le Nouen, Cyril; Brock, Linda G.; Liang, Bo; Munir, Shirin; Collins, Peter L.; Buchholz, Ursula J.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Martin, Scott E.; Buehler, Eugen; Chen, Yu-Chi] Natl Ctr Adv Translat Sci, Div Preclin Innovat, Rockville, MD USA.
[Smelkinson, Margery; Ganesan, Sundar] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Fischer, Elizabeth R.] NIAID, Microscopy Unit, Rocky Mt Labs, Res Technol Branch,NIH, Hamilton, MT USA.
[Martin, Scott E.] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA.
RP Mehedi, M (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM masfique.mehedi@nih.gov
OI Mehedi, Masfique/0000-0003-1728-3126
FU Intramural Research Program of NIAID, NIH
FX This study was supported by the Intramural Research Program of NIAID,
NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 62
TC 0
Z9 0
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006062
DI 10.1371/journal.ppat.1006062
PG 35
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100039
PM 27926942
ER
PT J
AU Ratner, D
Orning, MPA
Proulx, MK
Wang, DH
Gavrilin, MA
Wewers, MD
Alnemri, ES
Johnson, PF
Lee, B
Mecsas, J
Kayagaki, N
Goguen, JD
Lien, E
AF Ratner, Dmitry
Orning, M. Pontus A.
Proulx, Megan K.
Wang, Donghai
Gavrilin, Mikhail A.
Wewers, Mark D.
Alnemri, Emad S.
Johnson, Peter F.
Lee, Bettina
Mecsas, Joan
Kayagaki, Nobuhiko
Goguen, Jon D.
Lien, Egil
TI The Yersinia pestis Effector YopM Inhibits Pyrin Inflammasome Activation
SO PLOS PATHOGENS
LA English
DT Article
ID III SECRETION SYSTEM; NF-KAPPA-B; BURKHOLDERIA-CENOCEPACIA; C/EBP-BETA;
VIRULENCE; CASPASE-1; GTPASES; FEVER; LIPOPOLYSACCHARIDE; RECOGNITION
AB Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1 beta and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. Some effectors, like Y. pestis YopM, may block inflammasome activation. Here we show that YopM prevents Y. pestis induced activation of the Pyrin inflammasome induced by the RhoA-inhibiting effector YopE, which is a GTPase activating protein. YopM blocks YopE-induced Pyrin-mediated caspase-1 dependent IL-1 beta/IL-18 production and cell death. We also detected YopM in a complex with Pyrin and kinases RSK1 and PKN1, putative negative regulators of Pyrin. In contrast to wild-type mice, Pyrin deficient mice were also highly susceptible to an attenuated Y. pestis strain lacking YopM, emphasizing the importance of inhibition of Pyrin in vivo. A complex interplay between the Y. pestis T3SS and IL-1 beta/IL-18 production is evident, involving at least four inflammasome pathways. The secreted effector YopJ triggers caspase-8-dependent IL-1 beta activation, even when YopM is present. Additionally, the presence of the T3SS needle/translocon activates NLRP3 and NLRC4-dependent IL-1 beta generation, which is blocked by YopK, but not by YopM. Taken together, the data suggest YopM specificity for obstructing the Pyrin pathway, as the effector does not appear to block Y. pestis-induced NLRP3, NLRC4 or caspase-8 dependent caspase-1 processing. Thus, we identify Y. pestis YopM as a microbial inhibitor of the Pyrin inflammasome. The fact that so many of the Y. pestis T3SS components are participating in regulation of IL-1 beta/IL-18 release suggests that these effects are essential for maximal control of innate immunity during plague.
C1 [Ratner, Dmitry; Orning, M. Pontus A.; Wang, Donghai; Lien, Egil] UMass Med Sch, Div Infect Dis & Immunol, Program Innate Immun, Dept Med, Worcester, MA 01655 USA.
[Orning, M. Pontus A.; Lien, Egil] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Ctr Mol Inflammat Res, Trondheim, Norway.
[Proulx, Megan K.; Goguen, Jon D.] UMass Med Sch, Dept Microbiol & Physiol Syst, Worcester, MA USA.
[Wang, Donghai] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Gavrilin, Mikhail A.; Wewers, Mark D.] Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Davis Heart & Lung Res Inst,Wexner Med Ctr, Columbus, OH 43210 USA.
[Alnemri, Emad S.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Johnson, Peter F.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Lee, Bettina; Kayagaki, Nobuhiko] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
[Mecsas, Joan] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Lien, E (reprint author), UMass Med Sch, Div Infect Dis & Immunol, Program Innate Immun, Dept Med, Worcester, MA 01655 USA.; Lien, E (reprint author), Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Ctr Mol Inflammat Res, Trondheim, Norway.
EM Egil.Lien@umassmed.edu
OI Proulx, Megan/0000-0002-9524-8302; Wewers, Mark/0000-0002-7079-5633;
Johnson, Peter/0000-0002-4145-4725
FU National Institutes of Health [AI07538, U19 AI057319, AI095213,
HL076278, AR055398, AI113166, AI110695]; Norwegian Cancer Society;
Research Council of Norway Center of Excellence Funding Scheme Project
[223255/F50]; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research
FX The work was supported by National Institutes of Health Grants AI07538
and U19 AI057319 (to EL), AI095213 (to DR), HL076278 (to MAG and MDW),
AR055398 (to ESA), AI113166 (to JM), AI110695 (to DW), the Norwegian
Cancer Society, and Research Council of Norway Center of Excellence
Funding Scheme Project 223255/F50 (to EL). The research of PFJ was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. URLs: https://www.nih.gov/, https://kreftforeningen.no/,
http://www.forskningsradet.no/en/Home_page/1177315753906,
http://www.cancer.gov/
NR 46
TC 0
Z9 0
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006035
DI 10.1371/journal.ppat.1006035
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100020
PM 27911947
ER
PT J
AU Swanson, PA
Hart, GT
Russo, MV
Nayak, D
Yazew, T
Pena, M
Khan, SM
Janse, CJ
Pierce, SK
McGavern, DB
AF Swanson, Phillip A., II
Hart, Geoffrey T.
Russo, Matthew V.
Nayak, Debasis
Yazew, Takele
Pena, Mirna
Khan, Shahid M.
Janse, Chris J.
Pierce, Susan K.
McGavern, Dorian B.
TI CD8(+) T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria
via Luminal Antigen-Specific Engagement of Brain Vasculature
SO PLOS PATHOGENS
LA English
DT Article
ID CHEMOKINE RECEPTOR 2; FALCIPARUM-MALARIA; ENDOTHELIAL-CELLS;
MULTIPLE-SCLEROSIS; MALIAN CHILDREN; IN-VIVO; PATHOGENESIS; PARASITE;
MICE; INFECTION
AB Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death. At the peak of ECM, we revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8(+) T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells (pRBCs) from cerebral blood vessels, but were not required for the disease. Interestingly, the majority of disease-inducing parasite-specific CD8(+) T cells interacted with the lumen of brain vascular endothelial cells (ECs), where they were observed surveying, dividing, and arresting in a cognate peptide-MHC I dependent manner. These activities were critically dependent on IFN-gamma, which was responsible for activating cerebrovascular ECs to upregulate adhesion and antigen-presenting molecules. Importantly, parasite-specific CD8(+) T cell interactions with cerebral vessels were impaired in chimeric mice rendered unable to present EC antigens on MHC I, and these mice were in turn resistant to fatal brainstem pathology. Moreover, anti-adhesion molecule (LFA-1 / VLA-4) therapy prevented fatal disease by rapidly displacing luminal CD8(+) T cells from cerebrovascular ECs without affecting extravascular T cells. These in vivo data demonstrate that parasite-specific CD8(+) T cell-induced fatal vascular breakdown and subsequent neuronal death during ECM is associated with luminal, antigen-dependent interactions with cerebrovasculature.
C1 [Swanson, Phillip A., II; Russo, Matthew V.; McGavern, Dorian B.] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Hart, Geoffrey T.; Yazew, Takele; Pena, Mirna; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Nayak, Debasis] Indian Inst Technol Indore, Ctr Biosci & Biomed Engn, Indore, Madhya Pradesh, India.
[Khan, Shahid M.; Janse, Chris J.] Leiden Univ, Leiden Malaria Res Grp, Ctr Infect Dis, Dept Parasitol,Med Ctr, Leiden, Netherlands.
RP McGavern, DB (reprint author), NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
FU National Institutes of Health
FX This research was supported by the intramural program at the National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 91
TC 0
Z9 0
U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2016
VL 12
IS 12
AR e1006022
DI 10.1371/journal.ppat.1006022
PG 34
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EI0YQ
UT WOS:000392202100017
PM 27907215
ER
PT J
AU Ognibene, FP
Gallin, JI
Baum, BJ
Wyatt, RG
Gottesman, MM
AF Ognibene, Frederick P.
Gallin, John I.
Baum, Bruce J.
Wyatt, Richard G.
Gottesman, Michael M.
TI Outcomes From the NIH Clinical Research Training Program: A Mentored
Research Experience to Enhance Career Development of
Clinician-Scientists
SO ACADEMIC MEDICINE
LA English
DT Article
ID PHYSICIAN-SCIENTIST; MEDICAL-STUDENTS; INVESTIGATOR; CHALLENGES;
CURRICULUM; WORKFORCE; FUTURE; HEALTH; SCHOOL; DUKE
AB Purpose
Clinician-scientists are considered an endangered species for many reasons, including challenges with establishing and maintaining a career pipeline. Career outcomes from yearlong medical and dental students' research enrichment programs have not been well determined. Therefore, the authors assessed career and research outcome data from a cohort of participants in the National Institutes of Health (NIH) Clinical Research Training Program (CRTP).
Method
The CRTP provided a yearlong mentored clinical or translational research opportunity for 340 medical and dental students. Of these, 135 completed their training, including fellowships, from 1997 to January 2014. Data for 130 of 135 were analyzed: time conducting research, types of public funding (NIH grants), and publications from selfreported surveys that were verified via the NIH Research Portfolio Online Reporting Tools Web site and PubMed.
Results
Nearly two-thirds (84 of 130) indicated that they were conducting research, and over half of the 84 (approximately one-third of the total cohort) spent more than 25% of time conducting research. Of those 84, over 25% received grant support from the NIH, and those further in their careers published more scholarly manuscripts.
Conclusions
Data suggest that the CRTP helped foster the careers of research-oriented medical and dental students as measured by time conducting research, successful competition for federal funding, and the publication of their research. Longer follow-up is warranted to assess the impact of these mentored research experiences. Investments in mentored research programs for health professional students are invaluable to support the dwindling pipeline of biomedical researchers and clinician-scientists.
C1 [Ognibene, Frederick P.] NIH, Educ Affairs & Strateg Partnerships, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Ognibene, Frederick P.] NIH, Clin Res Training Program, Bldg 10, Bethesda, MD 20892 USA.
[Gallin, John I.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Gallin, John I.] NIH, Clin Res, Bldg 10, Bethesda, MD 20892 USA.
[Gallin, John I.] NIH, Clin Res Training, Bldg 10, Bethesda, MD 20892 USA.
[Baum, Bruce J.] NIH, Med Res Scholars Program, Bldg 10, Bethesda, MD 20892 USA.
[Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
[Wyatt, Richard G.] NIH, Off Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Gottesman, Michael M.] NIH, Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
RP Ognibene, FP (reprint author), NIH, Bldg 10 CRC,6-5530, Bethesda, MD 20892 USA.
EM fognibene@cc.nih.gov
FU NIH Common Fund
FX The authors wish to thank the 130 Clinical Research Training Program
alumni for participating in this long-term follow-up, and for providing
their responses to annual career outcome surveys. The authors also thank
Ms. Jennifer Simmons and Mr. Kenny J. Williams from the National
Institutes of Health (NIH) Clinical Center's Office of Clinical Research
Training and Medical Education for their assistance in collecting and
providing baseline analysis of the data and Dr. Elaine K. Gallin for her
thoughtful review of this manuscript. The authors thank the NIH Common
Fund and the staff of the NIH Office of Strategic Coordination, Division
of Program Coordination, Planning, and Strategic Initiatives for their
guidance and program support.
NR 22
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD DEC
PY 2016
VL 91
IS 12
BP 1684
EP 1690
DI 10.1097/ACM.0000000000001245
PG 7
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA EH7NL
UT WOS:000391959600049
ER
PT J
AU Keutgen, XM
Nilubol, N
Agarwal, S
Welch, J
Cochran, C
Marx, SJ
Weinstein, LS
Simonds, WF
Kebebew, E
AF Keutgen, Xavier M.
Nilubol, Naris
Agarwal, Sunita
Welch, James
Cochran, Craig
Marx, Steve J.
Weinstein, Lee S.
Simonds, William F.
Kebebew, Electron
TI Reoperative Surgery in Patients with Multiple Endocrine Neoplasia Type 1
Associated Primary Hyperparathyroidism
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID TERM-FOLLOW-UP; PARATHYROIDECTOMY; OPERATION; MANAGEMENT; MEN1
AB Background. Persistent/recurrent primary hyperparathyroidism (pHPT) occurs frequently in multiple endocrine neoplasia type 1 (MEN1). We assessed the usefulness of intraoperative PTH (IOPTH) and preoperative localizing studies based on the outcome of patients with MEN1-associated pHPT undergoing reoperative surgery.
Methods. A retrospective analysis identified MEN1 patients with persistent/recurrent pHPT. Patient outcome was defined as postoperative serum calcium and PTH levels (cured, persistent or recurrent) at last follow-up. Positive predictive value (PPV) was calculated for imaging studies and IOPTH.
Results. Thirty patients with MEN1-associated recurrent/persistent pHPT underwent 69 reoperative parathyroidectomies. Median follow-up time was 33 months. Persistent pHPT occurred in four (13 %) patients. IOPTH had a 92 % PPV for postoperative eucalcemia. Ultrasound and Tc99msestamibi had sensitivities of 100 and 85 % for localizing an enlarged parathyroid gland. However, five (17 %) patients had additional enlarged glands, not visualized preoperatively that were removed after IOPTH did not drop appropriately. Bone mineral density scores did not improve after reoperation (p = 0.60), but the rate of postoperative nephrocalcinosis did (p = 0.046). Patients with pancreatic neuroendocrine tumors had significantly higher rates of persistent/recurrent pHPT compared with those without (40 vs. 0 %, p = 0.021). Intraoperative and delayed parathyroid autotransplantation was performed in nine (30 %) and four (14 %) patients, respectively.
Conclusions. Although preoperative localizing studies are helpful for guiding reoperative strategy in MEN1 with persistent/recurrent pHPT, additional enlarged glands may be missed by conventional imaging. IOPTH should therefore be employed routinely in this setting. Routine cryopreservation should be considered in all patients. Pancreatic manifestation may be associated with earlier recurrence or persistent disease.
C1 [Keutgen, Xavier M.; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Agarwal, Sunita; Welch, James; Cochran, Craig; Marx, Steve J.; Weinstein, Lee S.; Simonds, William F.] Natl Inst Diabet & Digest & Kidney Dis, Metab Dis Branch, NIH, Bethesda, MD USA.
RP Keutgen, XM (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM xavier.keutgen@nih.gov
OI Weinstein, Lee/0000-0002-1899-5152
NR 24
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD DEC
PY 2016
VL 23
SU 5
BP S701
EP S707
DI 10.1245/s10434-016-5467-x
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA EH1FK
UT WOS:000391508800026
PM 27464610
ER
PT J
AU Satoh, K
Sadowski, SM
Dieckmann, W
Quezado, M
Nilubol, N
Kebebew, E
Patel, D
AF Satoh, Kei
Sadowski, Samira M.
Dieckmann, William
Quezado, Martha
Nilubol, Naris
Kebebew, Electron
Patel, Dhaval
TI F-18-FDG PET/CT Volumetric Parameters are Associated with Tumor Grade
and Metastasis in Pancreatic Neuroendocrine Tumors in von Hippel-Lindau
Disease
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID TOTAL LESION GLYCOLYSIS; POSITRON-EMISSION-TOMOGRAPHY; BODY
RADIATION-THERAPY; FINE-NEEDLE-ASPIRATION; PROGNOSTIC VALUE; ENDOCRINE
TUMORS; CLINICAL UTILITY; LABELING INDEX; CANCER; NEOPLASMS
AB Background. Approximately 8-17 % of patients with von Hippel-Lindau (VHL) syndrome develop pancreatic neuroendocrine tumors (PNETs), with 11-20 % developing metastases. Tumor grade is predictive of prognosis.
Objective. The aim of this study was to determine if preoperative metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with metastatic disease and tumor grade.
Methods. Sixty-two patients with VHL-associated PNETs prospectively underwent F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT). MTV, TLG, and maximum standardized uptake value (SUVmax) were measured using a semi-automatic method. Surgically resected PNETs were classified according to 2010 World Health Organization tumor grade classification. MTV, TLG, and SUVmax were analyzed by metastatic disease and tumor grade using the MannWhitney test.
Results. A total of 88 PNETs were identified by CT and F-18-FDG PET/CT, 10 of which were non-FDG-avid. Histologic grading was available for 20 surgical patients. Patients with metastatic PNETs had a higher TLG (median 25.9 vs. 7.7 mean SUV [SUVmean]* mL; p = 0.0092) compared with patients without metastasis, while patients with grade 2 PNETs had a higher MTV (median 6.9 vs. 2.6 mL; p = 0.034) and TLG (median 41.2 vs. 13.1 SUVmean* mL; p = 0.0035) compared with patients with grade 1 PNETs. No difference in tumor size or SUVmax was observed between the groups.
Conclusions. Patients with metastatic PNETs have a higher TLG compared with patients without metastasis. Grade 2 PNETs have a higher MTV and TLG compared with grade 1 PNETs. Tumor size and SUVmax were not associated with grade. Volumetric parameters on F-18-FDG PET/CT may be useful in detecting higher grade PNETs with a higher malignant potential that may need surgical intervention.
C1 [Satoh, Kei; Sadowski, Samira M.; Nilubol, Naris; Kebebew, Electron; Patel, Dhaval] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Satoh, Kei] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Dieckmann, William] NIH, PET Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Patel, D (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM pateldt@nih.gov
FU NIH Medical Research Scholars Program by NIH
FX This research was made possible through the NIH Medical Research
Scholars Program, a public-private partnership supported jointly by the
NIH and generous contributions to the Foundation for the NIH from Pfizer
Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The
American Association for Dental Research, The Howard Hughes Medical
Institute, and the Colgate-Palmolive Company, as well as other private
donors. For a complete list, please visit the Foundation website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram.
NR 45
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD DEC
PY 2016
VL 23
SU 5
BP S714
EP S721
DI 10.1245/s10434-016-5541-4
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA EH1FK
UT WOS:000391508800028
PM 27638678
ER
PT J
AU Jha, S
Bhattacharyya, T
AF Jha, Smita
Bhattacharyya, Timothy
TI Utilization and cost of anti-osteoporosis therapy among US Medicare
beneficiaries
SO ARCHIVES OF OSTEOPOROSIS
LA English
DT Article
DE Osteoporosis; Cost; Brand name drugs; Generic drugs; Primary care
providers; Utilization
ID PRIMARY-CARE PHYSICIANS; LOW BONE-DENSITY; POSTMENOPAUSAL OSTEOPOROSIS;
GENERIC DRUGS; FRACTURE RISK; UNITED-STATES; ALENDRONATE; WOMEN; TRIAL;
BRAND
AB A Summary There is a strong impetus to prevent and treat osteoporosis to prevent fractures. $990 million dollars was spent on anti-osteoporosis drugs in 2013. As we shift our focus on primary prevention of fractures, providers are encouraged to find themost cost-effective anti-osteoporosis therapy for patients.
Purpose Osteoporosis is a major global problem with osteoporotic fractures posing a potentially avoidable burden on healthcare resources. We studied the utilization and cost of anti-osteoporotic therapy using the 2013 Medicare Part D data.
Methods Descriptive data were produced from Microsoft Excel and SPSS regarding the anti-osteoporotic drugs of interest.
Results In total, Medicare and its beneficiaries spent approximately $990 million on anti-osteoporotic therapy in 2013. Despite this cost, only one in two adults with osteoporosis aged 65 and older received a prescription for an anti-osteoporosis drug. $756 million (77 %) was attributable to brand name drugs which accounted for 2,459,931 claims (22 %). Generic dispensing rate varied from 57-86 % (mean 77 + 6) across the different states in the USA. States that mandate substitution with generic equivalents had a higher generic dispensing rate compared to the states that permit generic substitution (92 vs. 90 %; p < 0.05). After adjusting for claim counts, we found that if the states that permit substitution with generic equivalents showed the same generic dispensing rate of 92 % as the states that mandate such substitution, there is a potential for savings of $7.5 million, approximately 9 % of the total expenditure in these states on oral bisphosphonates alone. Thirty-eight percent of the total prescriptions from orthopedic surgeons were for Forteo (R) or Prolia (R) compared to 12.5 % from specialists.
Conclusions These findings highlight the need for ongoing training for physicians who engage in the care of patients with osteoporosis to manage the disease in a cost-effective manner.
C1 [Jha, Smita; Bhattacharyya, Timothy] NIAMSD, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 4-1341, Bethesda, MD 20892 USA.
RP Jha, S (reprint author), NIAMSD, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 4-1341, Bethesda, MD 20892 USA.
EM smita.jha@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of
Health (NIH)
FX We thank Dr. Abhijit Dasgupta, PhD, for his kind review of statistical
methods. This research was supported by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) of the National Institutes of Health (NIH).
NR 34
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U1 5
U2 5
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 1862-3522
EI 1862-3514
J9 ARCH OSTEOPOROS
JI Arch. Osteoporos.
PD DEC
PY 2016
VL 11
IS 1
AR 28
DI 10.1007/s11657-016-0283-2
PG 8
WC Endocrinology & Metabolism; Orthopedics
SC Endocrinology & Metabolism; Orthopedics
GA EH0BC
UT WOS:000391426300005
PM 27576482
ER
PT J
AU Gabriel, EE
Daniels, MJ
Halloran, ME
AF Gabriel, Erin E.
Daniels, Michael J.
Halloran, M. Elizabeth
TI Comparing Biomarkers as Trial Level General Surrogates
SO BIOMETRICS
LA English
DT Article
DE Bayesian non-parametrics; Cross-Validation; Meta-analysis; Surrogate
markers; Vaccines
ID PENTAVALENT ROTAVIRUS VACCINE; RANDOMIZED CLINICAL-TRIALS; END-POINTS;
IMMUNOGENICITY; METAANALYSIS; VALIDATION; INFANTS; MODELS
AB An intermediate response measure that accurately predicts efficacy in a new setting can reduce trial cost and time to product licensure. In this article, we define a trial level general surrogate, which is an intermediate response that can be used to accurately predict efficacy in a new setting. Methods for evaluating general surrogates have been developed previously. Many methods in the literature use trial level intermediate responses for prediction. However, all existing methods focus on surrogate evaluation and prediction in new settings, rather than comparison of candidate general surrogates, and few formalize the use of cross validation to quantify the expected prediction error. Our proposed method uses Bayesian non-parametric modeling and cross-validation to estimate the absolute prediction error for use in evaluating and comparing candidate trial level general surrogates. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate trial level general surrogates in several multi-national trials of a pentavalent rotavirus vaccine. We identify at least one immune measure that has potential value as a trial level general surrogate and use it to predict efficacy in a new trial where the clinical outcome was not measured.
C1 [Gabriel, Erin E.] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Daniels, Michael J.] Univ Texas Austin, Dept Stat & Data Sci, Austin, TX 78712 USA.
[Daniels, Michael J.] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
[Halloran, M. Elizabeth] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Halloran, M. Elizabeth] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Halloran, M. Elizabeth] Ctr Inference & Dynam Infect Dis, Seattle, WA USA.
RP Gabriel, EE (reprint author), NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM erin.gabriel@nih.gov; mjdaniels@austin.utexas.edu; betz@fhcrc.org
OI Gabriel, Erin/0000-0002-0504-8404
FU National Institutes of Health [R01 CA183854, R37 AI032042]; NIAID NIH
[R37AI054165]
FX We are grateful to Merck & Co. Inc. (Kenilworth, New Jersey) for sharing
their RotaTeqTM clinical trial data with us. The authors received no
funding from Merck & Co. Inc. for this analysis nor did Merck & Co. Inc.
influence the analysis in any way. M.J. Daniels was partially supported
by National Institutes of Health R01 CA183854. M.E. Halloran was
partially supported by National Institutes of Health R37 AI032042. We
would also like to acknowledge Peter Gilbert, Michael Sachs, and James
Dai for their helpful ideas, programming expertise and discussions.
Peter Gilbert is partially supported by NIAID NIH Award Number
R37AI054165. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health. This work utilized the computational resources of
the NIH HPC Biowulf cluster (http://hpc.nih.gov).
NR 24
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2016
VL 72
IS 4
BP 1046
EP 1054
DI 10.1111/biom.12513
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA EH7DC
UT WOS:000391932100004
PM 27038302
ER
PT J
AU Rueda, C
Fernandez, MA
Barragan, S
Mardia, KV
Peddada, SD
AF Rueda, Cristina
Fernandez, Miguel A.
Barragan, Sandra
Mardia, Kanti V.
Peddada, Shyamal D.
TI Circular Piecewise Regression with Applications to Cell-Cycle Data
SO BIOMETRICS
LA English
DT Article
DE Circular data; Circular-circular regression; Change points; Gene
expression; Generalized AIC; Von Mises distribution
ID MODEL SELECTION; REGULATED GENES; ORDER; IDENTIFICATION; FREEDOM; CIRCLE
AB Applications of circular regression models appear in many different fields such as evolutionary psychology, motor behavior, biology, and, in particular, in the analysis of gene expressions in oscillatory systems. Specifically, for the gene expression problem, a researcher may be interested in modeling the relationship among the phases of cell-cycle genes in two species with differing periods. This challenging problem reduces to the problem of constructing a piecewise circular regression model and, with this objective in mind, we propose a flexible circular regression model which allows different parameter values depending on sectors along the circle. We give a detailed interpretation of the parameters in the model and provide maximum likelihood estimators. We also provide a model selection procedure based on the concept of generalized degrees of freedom. The model is then applied to the analysis of two different cell-cycle data sets and through these examples we highlight the power of our new methodology.
C1 [Rueda, Cristina; Fernandez, Miguel A.; Barragan, Sandra] Univ Valladolid, Dept Estadist eIO, E-47011 Valladolid, Spain.
[Mardia, Kanti V.] Univ Oxford, Dept Stat, Oxford, England.
[Mardia, Kanti V.] Univ Leeds, Dept Stat, Leeds, W Yorkshire, England.
[Peddada, Shyamal D.] NIEHS, Biostat & Computat Biol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Rueda, C (reprint author), Univ Valladolid, Dept Estadist eIO, E-47011 Valladolid, Spain.
EM crueda@eio.uva.es; miguelaf@eio.uva.es; sandraba@eio.uva.es;
K.V.Mardia@leeds.ac.uk; peddada@niehs.nih.gov
OI Fernandez, Miguel/0000-0002-1272-8950
FU Spanish MCI grant [MTM2012-37129]; Junta de Castilla y Leon; European
Social Fund within Programa Operativo Castilla y Leon; Intramural
Research Program of the NIEHS [Z01 ES101744-04]
FX This work was supported by Spanish MCI grant (MTM2012-37129 to S.B.,
C.R., and M.A.F.), Junta de Castilla y Leon and the European Social Fund
within the Programa Operativo Castilla y Leon (2007-2013 to S.B.) and
the Intramural Research Program of the NIEHS (Z01 ES101744-04 to
S.D.P.). The authors thank the anonymous reviewers and the associate
editor for several useful comments which improved this manuscript.
NR 29
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2016
VL 72
IS 4
BP 1266
EP 1274
DI 10.1111/biom.12512
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA EH7DC
UT WOS:000391932100026
PM 26991351
ER
PT J
AU Potgieter, CJ
Wei, RB
Kipnis, V
Freedman, LS
Carroll, RJ
AF Potgieter, Cornelis J.
Wei, Rubin
Kipnis, Victor
Freedman, Laurence S.
Carroll, Raymond J.
TI Moment Reconstruction and Moment-Adjusted Imputation When Exposure Is
Generated by a Complex, Nonlinear Random Effects Modeling Process
SO BIOMETRICS
LA English
DT Article
DE Berkson-type error; Classical measurement error; Computer models;
Healthy Eating Index-2005; Latent variable models; Moment-adjusted
imputation; Moment reconstruction; Nutritional epidemiology
ID MEASUREMENT ERROR MODEL; LOGISTIC-REGRESSION; INTAKE DISTRIBUTIONS;
BERKSON ERRORS; CALIBRATION; VARIABLES; DESIGNS; HEALTH; RISK
AB For the classical, homoscedastic measurement error model, moment reconstruction (Freedman et al., 2004, 2008) and moment-adjusted imputation (Thomas et al., 2011) are appealing, computationally simple imputation-like methods for general model fitting. Like classical regression calibration, the idea is to replace the unobserved variable subject to measurement error with a proxy that can be used in a variety of analyses. Moment reconstruction and moment-adjusted imputation differ from regression calibration in that they attempt to match multiple features of the latent variable, and also to match some of the latent variable's relationships with the response and additional covariates. In this note, we consider a problem where true exposure is generated by a complex, nonlinear random effects modeling process, and develop analogues of moment reconstruction and moment-adjusted imputation for this case. This general model includes classical measurement errors, Berkson measurement errors, mixtures of Berkson and classical errors and problems that are not measurement error problems, but also cases where the data-generating process for true exposure is a complex, nonlinear random effects modeling process. The methods are illustrated using the National Institutes of Health-AARP Diet and Health Study where the latent variable is a dietary pattern score called the Healthy Eating Index-2005. We also show how our general model includes methods used in radiation epidemiology as a special case. Simulations are used to illustrate the methods.
C1 [Potgieter, Cornelis J.] Southern Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA.
[Wei, Rubin] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20814 USA.
[Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Carroll, Raymond J.] Univ Technol Sydney, Sch Math & Phys Sci, Sydney, NSW 2007, Australia.
RP Potgieter, CJ (reprint author), Southern Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA.
EM cpotgieter@smu.edu; weirubin@gmail.com; kipnisv@mail.nih.gov;
lsf@actcom.co.il; carroll@stat.tamu.edu
FU National Cancer Institute [U01-CA057030]
FX The research of Potgieter, Wei, and Carroll was supported by a grant
from the National Cancer Institute (U01-CA057030).
NR 29
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2016
VL 72
IS 4
BP 1369
EP 1377
DI 10.1111/biom.12524
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA EH7DC
UT WOS:000391932100036
PM 27061196
ER
PT J
AU Sharov, AA
AF Sharov, Alexei A.
TI Evolutionary Biosemiotics and Multilevel Construction Networks
SO BIOSEMIOTICS
LA English
DT Article
DE Evolutionary semiotics; Constructivism; Semiotic network; Evolvability;
Metasystem transition; Constraints on learning
ID LIFE; ORIGIN; PROTEINS; PATTERNS; SURFACE; CANCER; WORLD; MODEL
AB In contrast to the traditional relational semiotics, biosemiotics decisively deviates towards dynamical aspects of signs at the evolutionary and developmental time scales. The analysis of sign dynamics requires constructivism (in a broad sense) to explain how new components such as subagents, sensors, effectors, and interpretation networks are produced by developing and evolving organisms. Semiotic networks that include signs, tools, and subagents are multilevel, and this feature supports the plasticity, robustness, and evolvability of organisms. The origin of life is described here as the emergence of simple self-constructing semiotic networks that progressively increased the diversity of their components and relations. Primitive organisms have no capacity to classify and track objects; thus, we need to admit the existence of proto-signs that directly regulate activities of agents without being associated with objects. However, object recognition and handling became possible in eukaryotic species with the development of extensive rewritable epigenetic memory as well as sensorial and effector capacities. Semiotic networks are based on sequential and recursive construction, where each step produces components (i.e., agents, scaffolds, signs, and resources) that are needed for the following steps of construction. Construction is not limited to repair and reproduction of what already exists or is unambiguously encoded, it also includes production of new components and behaviors via learning and evolution. A special case is the emergence of new levels of organization known as metasystem transition. Multilevel semiotic networks reshape the phenotype of organisms by combining a mosaic of features developed via learning and evolution of cooperating and/or conflicting subagents.
C1 [Sharov, Alexei A.] NIA, Genet Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Sharov, AA (reprint author), NIA, Genet Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sharoval@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging (NIA/NIH)
[Z01 AG000656-13]
FX This paper was supported entirely by the Intramural Research Program of
the National Institute on Aging (NIA/NIH), project Z01 AG000656-13. The
content of the paper is not endorsed by the funding organization.
NR 73
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U1 2
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1875-1342
EI 1875-1350
J9 BIOSEMIOTICS-NETH
JI Biosemiotics
PD DEC
PY 2016
VL 9
IS 3
BP 399
EP 416
DI 10.1007/s12304-016-9269-0
PG 18
WC Humanities, Multidisciplinary; History & Philosophy Of Science
SC Arts & Humanities - Other Topics; History & Philosophy of Science
GA EH0KC
UT WOS:000391451800007
PM 28163801
ER
PT J
AU Yanik, EL
AF Yanik, E. L.
TI Skin cancer in the end-stage renal disease population: unique risk
factors for patients on dialysis
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Editorial Material
ID PHOTOTHERAPY; ULTRAVIOLET
C1 [Yanik, E. L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Yanik, EL (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM eliza-beth.yanik@nih.gov
OI Yanik, Elizabeth/0000-0002-5835-0201
NR 10
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD DEC
PY 2016
VL 175
IS 6
BP 1136
EP 1137
DI 10.1111/bjd.15032
PG 2
WC Dermatology
SC Dermatology
GA EH5NZ
UT WOS:000391821300041
PM 27996124
ER
PT J
AU Nemeth, K
Gorog, A
Mezey, E
Pinter, D
Kuroli, E
Harsing, J
Kovacs, L
Fischer, M
Rady, P
Sillo, P
Tyring, S
Karpati, S
AF Nemeth, K.
Gorog, A.
Mezey, E.
Pinter, D.
Kuroli, E.
Harsing, J.
Kovacs, L.
Fischer, M.
Rady, P.
Sillo, P.
Tyring, S.
Karpati, S.
TI Cover Image: Detection of hair follicle-associated Merkel cell
polyomavirus in an immunocompromised host with follicular spicules and
alopecia
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Letter
C1 [Nemeth, K.; Gorog, A.; Pinter, D.; Kuroli, E.; Harsing, J.; Sillo, P.; Karpati, S.] Semmelweis Univ, Dept Dermatol, Budapest, Hungary.
[Kovacs, L.] Semmelweis Univ, Dept Pediat 1, Budapest, Hungary.
[Nemeth, K.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA.
[Mezey, E.] NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA.
[Fischer, M.] Univ Maryland, Sch Med, Dept Dermatol, Baltimore, MD 21201 USA.
[Rady, P.; Tyring, S.] Univ Texas Houston, Sch Med, Dept Dermatol, Houston, TX USA.
RP Nemeth, K; Karpati, S (reprint author), Semmelweis Univ, Dept Dermatol, Budapest, Hungary.; Nemeth, K (reprint author), Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA.
EM knemeth@mcw.edu; skarpati@t-online.hu
NR 1
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD DEC
PY 2016
VL 175
IS 6
BP 1409
EP 1409
DI 10.1111/bjd.15039
PG 1
WC Dermatology
SC Dermatology
GA EH5NZ
UT WOS:000391821300101
PM 27996135
ER
PT J
AU Sadlier, M
Storan, E
Fitzgerald, S
Neville, S
Watson, R
Irvine, A
Leahy, R
Milner, J
O'Regan, G
AF Sadlier, M.
Storan, E.
Fitzgerald, S.
Neville, S.
Watson, R.
Irvine, A.
Leahy, R.
Milner, J.
O'Regan, G.
TI Novel gain of function mutation in STAT5b presenting with urticaria,
atopic dermatitis, alopecia areata, granulomatous dermatitis and complex
autoimmunity
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the British-Society-for-Paediatric-Dermatology
CY NOV 18-19, 2016
CL Sheffield, ENGLAND
SP British Soc Paediat Dermatol
C1 [Sadlier, M.; Storan, E.; Fitzgerald, S.; Neville, S.; Watson, R.; Irvine, A.; O'Regan, G.] Our Ladys Childrens Hosp Crumlin, Dept Dermatol, Dublin, Ireland.
[Leahy, R.] Our Ladys Childrens Hosp Crumlin, Dept Immunol, Dublin, Ireland.
[Milner, J.] NIAID, Genet & Pathogenesis Allergy Sect, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD DEC
PY 2016
VL 175
IS 6
MA P4
BP E156
EP E156
PG 1
WC Dermatology
SC Dermatology
GA EH5NZ
UT WOS:000391821300019
ER
PT J
AU Cooper, LL
Palmisano, JN
Benjamin, EJ
Larson, MG
Vasan, RS
Mitchell, GF
Hamburg, NM
AF Cooper, Leroy L.
Palmisano, Joseph N.
Benjamin, Emelia J.
Larson, Martin G.
Vasan, Ramachandran S.
Mitchell, Gary F.
Hamburg, Naomi M.
TI Microvascular Function Contributes to the Relation Between Aortic
Stiffness and Cardiovascular Events The Framingham Heart Study
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE arteries; cardiovascular diseases; endothelium; pulse wave analysis;
vascular stiffness
ID FLOW-MEDIATED DILATION; PULSE-WAVE VELOCITY; END-ORGAN DAMAGE; ARTERIAL
STIFFNESS; PREDICTIVE-VALUE; BRACHIAL-ARTERY; VASA VASORUM; PRESSURE;
RISK; DISEASE
AB Background Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Interrelations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied.
Methods and Results We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51 +/- 11 years; 54% women) in 2 generations of Framingham I Ieart Study participants. During follow-up (0,02-13,83 years), 232 participants (5%) experienced new-onset CVD events, In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1,32; 95% confidence interval ICU 1.07-1.63; P=0,01) and lower hyperemic mean flow velocity (HR, 0,84; 95% CI, 0.71-0,99; P=0,04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1,12; 95% CI, 0.99-1,27; P=0,06), baseline brachial diameter (HR, 1.09; 95% CI, 0,90-1,31; P=0,39), and flow-mediated vasodilation (11R, 0,85; 95% CI, 0,69-1,04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity.
Conclusions Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling,
C1 [Cooper, Leroy L.; Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
[Cooper, Leroy L.] Brown Univ, Cardiovasc Res Ctr, Lifespan Cardiovasc Inst, W Alpert Med Sch, Providence, RI 02912 USA.
[Palmisano, Joseph N.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02218 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.] Boston Univ, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.] NHLBI, Framingham Study, Bldg 10, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02218 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.; Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 88 E Newton St,Suite C-818, Boston, MA 02218 USA.
RP Hamburg, NM (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 88 E Newton St,Suite C-818, Boston, MA 02218 USA.
EM nhamburg@bu.edu
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, HHSN268201500001I, HL076784, AG028321, HL070100,
HL060040, HL080124, HL071039, HL077447, HL107385, HL126136, HL128914,
2-K24-HL04334]; UNCF/Merck Science Initiative
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract Nos. N01-HC-25195 and
HHSN268201500001I) and by HL076784, AG028321, HL070100, HL060040,
HL080124, HL071039, HL077447, HL107385, HL126136, HL128914, and
2-K24-HL04334. Dr Cooper was supported by the UNCF/Merck Science
Initiative.
NR 41
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD DEC
PY 2016
VL 9
IS 12
AR e004979
DI 10.1161/CIRCIMAGING.116.004979
PG 13
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EH5OO
UT WOS:000391822800004
ER
PT J
AU Mehta, NN
AF Mehta, Nehal N.
TI Positron Emission Tomography Assessment of Left Main Coronary Arterial
Inflammation With Coronary Computed Tomographic Angiography Validation
Before and After Statin Therapy More Promise for Fluorodeoxyglucose
Vascular Uptake?
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE Editorials; atherosclerosis; carotid artery; coronary artery disease;
inflammation; positron emission tomography
ID FDG PET/CT; ATHEROSCLEROSIS; REDUCTION; CALCIUM; EVENTS; RISK
C1 [Mehta, Nehal N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometabol Dis, Clin Res Ctr, 10 Ctr Dr,Room 5-5140, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
NR 14
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD DEC
PY 2016
VL 9
IS 12
AR e005745
DI 10.1161/CIRCIMAGING.116.005745
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EH5OO
UT WOS:000391822800012
ER
PT J
AU Rogers, T
Lederman, RJ
AF Rogers, Toby
Lederman, Robert J.
TI Exercise Magnetic Resonance Imaging Is a Gas
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE Editorials; cardiac output; cardiopulmonary exercise test; congenital
heart defects; magnetic resonance imaging; pediatrics; pulmonary
hypertension
ID MRI; CATHETERIZATION
C1 [Rogers, Toby; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA.
RP Rogers, T (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA.
EM toby.rogers@nih.gov
NR 10
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD DEC
PY 2016
VL 9
IS 12
AR e005795
DI 10.1161/CIRCIMAGING.116.005795
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EH5OO
UT WOS:000391822800013
ER
PT J
AU Yeboah, J
Bertoni, A
Qureshi, W
Aggarwal, S
Lima, JAC
Kawel-Boehm, N
Bluemke, DA
Shah, SJ
AF Yeboah, Joseph
Bertoni, Alain
Qureshi, Waqas
Aggarwal, Shivani
Lima, Joao A. C.
Kawel-Boehm, Nadine
Bluemke, David A.
Shah, Sanjiv J.
TI Pedal Edema as an Indicator of Early Heart Failure in the Community
Prevalence and Associations With Cardiac Structure/Function and
Natriuretic Peptides (MESA [Multiethnic Study of Atherosclerosis])
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE cardiac structure and function; heart failure; natriuretic peptides;
orthopnea; paroxysmal nocturnal dyspnea; pedal edema
ID PRESERVED EJECTION FRACTION; RIGHT VENTRICLE; PRACTICE GUIDELINES;
CLINICAL-TRIALS; TASK-FORCE; MANAGEMENT; DYSFUNCTION; PROGNOSIS;
DIAGNOSIS; VALUES
AB Background-The prevalence of pedal edema (PE) and its associations with abnormal cardiac structure/function, natriuretic peptides, and incident heart failure (HF) is unknown, especially in community-dwelling adults without a history of cardiovascular disease.
Methods and Results-Out of 5004 MESA (Multiethnic Study of Atherosclerosis) participants who had cardiac magnetic resonance imaging, 4196 had complete data and were included in this analysis (3501 for the right ventricle analysis). Logistic regression and Cox proportional hazard analyses were used to assess the associations among self-reported PE, 2-pillow orthopnea, paroxysmal nocturnal dyspnea, left and right ventricular structure and function, natriuretic peptide levels, and incident HF. PE was present in 28% of the participants. PE was not associated with overt left or right ventricular systolic dysfunction (ejection fraction <50%). PE was associated with 2-pillow orthopnea (odds ratio 1.66; 95% confidence interval [CI], 1.30-2.12), paroxysmal nocturnal dyspnea (odds ratio 1.95; 95% CI, 1.55-2.44), and abnormal N-terminal pro-B-type natriuretic peptide levels (defined as >400 pg/mL; odds ratio 1.80; 95% CI, 1.21-2.68) in adjusted models. After a mean of 10.2 years of follow-up, 184/4196 (4.4%) participants had an adjudicated incident HF hospitalization. PE was associated with incident HF hospitalization in models adjusted for age, sex, and race (hazard ratio 1.44; 95% CI, 1.05-1.97). This association persisted after adding additional covariates, including comorbidities, baseline left ventricular ejection fraction, and antecedent myocardial infarction (hazard ratio 1.43; 95% CI, 1.02-1.99). The association of PE with incident HF was attenuated by further adjustment for N-terminal pro-B-type natriuretic peptide.
Conclusions-PE is prevalent in community-dwelling adults without clinically recognized cardiovascular disease and associated with future hospitalized HF.
C1 [Yeboah, Joseph; Qureshi, Waqas; Aggarwal, Shivani] Wake Forest Univ, Sch Med, Heart & Vasc Ctr Excellence, Winston Salem, NC 27109 USA.
[Bertoni, Alain] Wake Forest Univ, Sch Med, Dept Epidemiol, Winston Salem, NC 27109 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Cardiol & Radiol, Baltimore, MD USA.
[Kawel-Boehm, Nadine] Kantonsspital Graubuenden Clin Radiol, Loestr 170, CH-7000 Chur, Switzerland.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Shah, Sanjiv J.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA.
RP Yeboah, J (reprint author), Wake Forest Sch Med, Heart & Vasc Ctr Excellence, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jyeboah@wakehealth.edu
FU National Heart, Lung, and Blood Institute [HHSN268201500003I,
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168,
N01-HC-95169]; NCRR [UL1-TR-000040, UL1-TR-001079]
FX This research was supported by contracts HHSN268201500003I,
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168,
and N01-HC-95169 from the National Heart, Lung, and Blood Institute and
by grants UL1-TR-000040 and UL1-TR-001079 from NCRR.
NR 28
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD DEC
PY 2016
VL 9
IS 12
AR e003415
DI 10.1161/CIRCHEARTFAILURE.116.003415
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EH5PD
UT WOS:000391824300005
ER
PT J
AU Vo, LC
Snyder, C
McCracken, C
McDougle, CJ
McCracken, JT
Aman, MG
Tierney, E
Arnold, LE
Levi, D
Kelleman, M
Carroll, D
Morrissey, J
Vitiello, B
Scahill, L
AF Vo, Lan Chi
Snyder, Christopher
McCracken, Courtney
McDougle, Christopher J.
McCracken, James T.
Aman, Michael G.
Tierney, Elaine
Arnold, L. Eugene
Levi, Daniel
Kelleman, Michael
Carroll, Deirdre
Morrissey, John
Vitiello, Benedetto
Scahill, Lawrence
TI No Apparent Cardiac Conduction Effects of Acute Treatment with
Risperidone in Children with Autism Spectrum Disorder
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
DE risperidone; electrocardiogram; QTc; autism spectrum disorder; cardiac
conduction
ID PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT BEHAVIOR CHECKLIST; QT
INTERVAL; ANTIPSYCHOTIC TREATMENT; ADOLESCENTS; RISK; DRUG;
SCHIZOPHRENIA; ARIPIPRAZOLE; MEDICATIONS
AB Objectives: Risperidone is approved for the treatment of serious behavioral problems in children with autism spectrum disorder (ASD). This study examined the effects of risperidone on cardiac conduction in children with ASD.
Methods: Data were collected from an 8-week, five-site trial conducted by the Research Units on Pediatric Psychopharmacology Autism Network. Children (age 5-17 years) were randomly assigned to risperidone (n = 49) or placebo (n = 52) under double-blind conditions. Risperidone was superior to placebo in reducing serious behavioral problems. A standard 12-lead, electrocardiogram (ECG) was obtained in most subjects at screening and week 8. A pediatric electrophysiologist blind to treatment assignment reviewed all available ECGs for readability, abnormalities, and cardiac conduction parameters, including QTc. The electrophysiologist measurements were compared to machine readings. A second blinded electrophysiologist examined all available ECGs for abnormalities and a 20% random sample for QTc.
Results: Of the 101 randomized subjects in the trial, complete pretreatment and week 8 data were available on 65 subjects (placebo n = 30; risperidone n = 35). The electrophysiologist did not identify any cardiac conduction adverse effects of risperidone and there was no difference in mean change on the QTc compared to placebo. The Bland-Altman plot showed a systematic bias in QTc measurements by the electrophysiologist and machine. Machine readings produced higher values than the electrophysiologist for shorter QTc intervals and machine scoring was lower than electrophysiologist readings for longer QTc values (p = 0.001). Two electrophysiologists had overall percent agreements of 82.9% (95% CI: 76.3 to 89.6) on qualitative assessment and 88.6% (95% CI: 79.3 to 98.0) on QTc interval.
Conclusion: Using conventional doses during acute treatment in children with ASD and serious behavioral problems, there was no difference in the mean change in QTc between risperidone and placebo. Compared to the electrophysiologist, the machine readings may miss elevated QTc measurements.
C1 [Vo, Lan Chi] Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA.
[Snyder, Christopher] Rainbow Babies & Childrens Hosp, Div Pediat Cardiol, Univ Hosp, 2101 Adelbert Rd, Cleveland, OH 44106 USA.
[McCracken, Courtney; Kelleman, Michael] Childrens Hosp Atlanta, Atlanta, GA USA.
[McCracken, Courtney; Kelleman, Michael] Emory Univ, Sch Med, Atlanta, GA USA.
[McDougle, Christopher J.] Harvard Med Sch, Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA USA.
[McCracken, James T.] Univ Calif Los Angeles, Div Child Psychiat, Los Angeles, CA USA.
[Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA.
[Tierney, Elaine] Kennedy Krieger Inst, Baltimore, MD USA.
[Levi, Daniel; Morrissey, John] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA.
[Carroll, Deirdre] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Scahill, Lawrence] Emory Univ, Sch Med, Marcus Autism Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
RP Scahill, L (reprint author), Emory Univ, Sch Med, Marcus Autism Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
EM lawrence.scahill@emory.edu
FU National Institute of Mental Health [N01MH70009, N01MH70010, N01MH70001,
N01MH80011, R25MH101079]; National Institutes of Health [M01 RR00750,
M01 RR00052, M01 RR00034, M01 RR06022]; National Center for Advancing
Translational Sciences of the National Institutes of Health [UL1
TR000454]; Marcus Foundation; Children's Hospital Trust Fund
FX Supported by contracts from the National Institute of Mental Health
(N01MH70009, to Dr. Scahill; N01MH70010, to Dr. J. McCracken;
N01MH70001, to Dr. McDougle; and N01MH80011, to Dr. Aman). General
Clinical Research Center grants from the National Institutes of Health
(M01 RR00750, to Indiana University; M01 RR00052, to Johns Hopkins
University; M01 RR00034, to Ohio State University; and M01 RR06022, to
Yale University). The project was the National Center for Advancing
Translational Sciences of the National Institutes of Health UL1 TR000454
(Emory University) as well as the Marcus Foundation and the Children's
Hospital Trust Fund. Dr. Vo has received training support from the
National Institute of Mental Health (R25MH101079) to Emory University.
NR 41
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PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD DEC
PY 2016
VL 26
IS 10
BP 900
EP 908
DI 10.1089/cap.2016.0090
PG 9
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA EH5TT
UT WOS:000391836500006
PM 27726426
ER
PT J
AU Southey, MC
Goldgar, DE
Winqvist, R
Pylkas, K
Couch, F
Tischkowitz, M
Foulkes, WD
Dennis, J
Michailidou, K
van Rensburg, EJ
Heikkinen, T
Nevanlinna, H
Hopper, JL
Dork, T
Claes, KBM
Reis, J
Teo, ZL
Radice, P
Catucci, I
Peterlongo, P
Tsimiklis, H
Odefrey, FA
Dowty, JG
Schmidt, MK
Broeks, A
Hogervorst, FB
Verhoef, S
Carpenter, J
Clarke, C
Scott, RJ
Fasching, PA
Haeberle, L
Ekici, AB
Beckmann, MW
Peto, J
dos-Santos-Silva, I
Fletcher, O
Johnson, N
Bolla, MK
Sawyer, EJ
Tomlinson, I
Kerin, MJ
Miller, N
Marme, F
Burwinkel, B
Yang, RX
Guenel, P
Truong, T
Menegaux, F
Sanchez, M
Bojesen, S
Nielsen, SF
Flyger, H
Benitez, J
Zamora, MP
Perez, JIA
Menendez, P
Anton-Culver, H
Neuhausen, S
Ziogas, A
Clarke, CA
Brenner, H
Arndt, V
Stegmaier, C
Brauch, H
Bruning, T
Ko, YD
Muranen, TA
Aittomaki, K
Blomqvist, C
Bogdanova, NV
Antonenkova, NN
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Spurdle, AB
Wauters, E
Smeets, D
Beuselinck, B
Floris, G
Chang-Claude, J
Rudolph, A
Seibold, P
Flesch-Janys, D
Olson, JE
Vachon, C
Pankratz, VS
McLean, C
Haiman, CA
Henderson, BE
Schumacher, F
Le Marchand, L
Kristensen, V
Alnaes, GG
Zheng, W
Hunter, DJ
Lindstrom, S
Hankinson, SE
Kraft, P
Andrulis, I
Knight, JA
Glendon, G
Mulligan, AM
Jukkola-Vuorinen, A
Grip, M
Kauppila, S
Devilee, P
Tollenaar, RAEM
Seynaeve, C
Hollestelle, A
Garcia-Closas, M
Figueroa, J
Chanock, SJ
Lissowska, J
Czene, K
Darabi, H
Eriksson, M
Eccles, DM
Rafiq, S
Tapper, WJ
Gerty, SM
Hooning, MJ
Martens, JWM
Collee, JM
Tilanus-Linthorst, M
Hall, P
Li, JM
Brand, JS
Humphreys, K
Cox, A
Reed, MWR
Luccarini, C
Baynes, C
Dunning, AM
Hamann, U
Torres, D
Ulmer, HU
Rudiger, T
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Slager, S
Toland, AE
Ambrosone, CB
Yannoukakos, D
Swerdlow, A
Ashworth, A
Orr, N
Jones, M
Gonzalez-Neira, A
Pita, G
Alonso, MR
Alvarez, N
Herrero, D
Tessier, DC
Vincent, D
Bacot, F
Simard, J
Dumont, M
Soucy, P
Eeles, R
Muir, K
Wiklund, F
Gronberg, H
Schleutker, J
Nordestgaard, BG
Weischer, M
Travis, RC
Neal, D
Donovan, JL
Hamdy, FC
Khaw, KT
Stanford, JL
Blot, WJ
Thibodeau, S
Schaid, DJ
Kelley, JL
Maier, C
Kibel, AS
Cybulski, C
Cannon-Albright, L
Butterbach, K
Park, J
Kaneva, R
Batra, J
Teixeira, MR
Kote-Jarai, Z
Al Olama, AA
Benlloch, S
Renner, SP
Hartmann, A
Hein, A
Ruebner, M
Lambrechts, D
Van Nieuwenhuysen, E
Vergote, I
Lambretchs, S
Doherty, JA
Rossing, MA
Nickels, S
Eilber, U
Wang-Gohrke, S
Odunsi, K
Sucheston-Campbell, LE
Friel, G
Lurie, G
Killeen, JL
Wilkens, LR
Goodman, MT
Runnebaum, I
Hillemanns, PA
Pelttari, LM
Butzow, R
Modugno, F
Edwards, RP
Ness, RB
Moysich, KB
du Bois, A
Heitz, F
Harter, P
Kommoss, S
Karlan, BY
Walsh, C
Lester, J
Jensen, A
Kjaer, SK
Hogdall, E
Peissel, B
Bonanni, B
Bernard, L
Goode, EL
Fridley, BL
Vierkant, RA
Cunningham, JM
Larson, MC
Fogarty, ZC
Kalli, KR
Liang, D
Lu, KH
Hildebrandt, MAT
Wu, XF
Levine, DA
Dao, F
Bisogna, M
Berchuck, A
Iversen, ES
Marks, JR
Akushevich, L
Cramer, DW
Schildkraut, J
Terry, KL
Poole, EM
Stampfer, M
Tworoger, SS
Bandera, EV
Orlow, I
Olson, SH
Bjorge, L
Salvesen, HB
van Altena, AM
Aben, KKH
Kiemeney, LA
Massuger, LFAG
Pejovic, T
Bean, Y
Brooks-Wilson, A
Kelemen, LE
Cook, LS
Le, ND
Grski, B
Gronwald, J
Menkiszak, J
Hogdall, CK
Lundvall, L
Nedergaard, L
Engelholm, SA
Dicks, E
Tyrer, J
Campbell, I
McNeish, I
Paul, J
Siddiqui, N
Glasspool, R
Whittemore, AS
Rothstein, JH
McGuire, V
Sieh, W
Cai, H
Shu, XO
Teten, RT
Sutphen, R
McLaughlin, JR
Narod, SA
Phelan, CM
Monteiro, AN
Fenstermacher, D
Lin, HY
Permuth, JB
Sellers, TA
Chen, YA
Tsai, YY
Chen, ZH
Gentry-Maharaj, A
Gayther, SA
Ramus, SJ
Menon, U
Wu, AH
Pearce, CL
Van den Berg, D
Pike, MC
Dansonka-Mieszkowska, A
Plisiecka-Halasa, J
Moes-Sosnowska, J
Kupryjanczyk, J
Pharoah, PDP
Song, HL
Winship, I
Chenevix-Trench, G
Giles, GG
Tavtigian, SV
Easton, DF
Milne, RL
AF Southey, Melissa C.
Goldgar, David E.
Winqvist, Robert
Pylkas, Katri
Couch, Fergus
Tischkowitz, Marc
Foulkes, William D.
Dennis, Joe
Michailidou, Kyriaki
van Rensburg, Elizabeth J.
Heikkinen, Tuomas
Nevanlinna, Heli
Hopper, John L.
Doerk, Thilo
Claes, Kathleen B. M.
Reis-Filho, Jorge
Teo, Zhi Ling
Radice, Paolo
Catucci, Irene
Peterlongo, Paolo
Tsimiklis, Helen
Odefrey, Fabrice A.
Dowty, James G.
Schmidt, Marjanka K.
Broeks, Annegien
Hogervorst, Frans B.
Verhoef, Senno
Carpenter, Jane
Clarke, Christine
Scott, Rodney J.
Fasching, Peter A.
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Peto, Julian
dos-Santos-Silva, Isabel
Fletcher, Olivia
Johnson, Nichola
Bolla, Manjeet K.
Sawyer, Elinor J.
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Marme, Federik
Burwinkel, Barbara
Yang, Rongxi
Guenel, Pascal
Therese Truong
Menegaux, Florence
Sanchez, Marie
Bojesen, Stig
Nielsen, Sune F.
Flyger, Henrik
Benitez, Javier
Pilar Zamora, M.
Arias Perez, Jose Ignacio
Menendez, Primitiva
Anton-Culver, Hoda
Neuhausen, Susan
Ziogas, Argyrios
Clarke, Christina A.
Brenner, Hermann
Arndt, Volker
Stegmaier, Christa
Brauch, Hiltrud
Bruening, Thomas
Ko, Yon-Dschun
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Spurdle, Amanda B.
Wauters, Els
Smeets, Dominiek
Beuselinck, Benoit
Floris, Giuseppe
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Olson, Janet E.
Vachon, Celine
Pankratz, Vernon S.
McLean, Catriona
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Kristensen, Vessela
Alnaes, Grethe Grenaker
Zheng, Wei
Hunter, David J.
Lindstrom, Sara
Hankinson, Susan E.
Kraft, Peter
Andrulis, Irene
Knight, Julia A.
Glendon, Gord
Mulligan, Anna Marie
Jukkola-Vuorinen, Arja
Grip, Mervi
Kauppila, Saila
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Hollestelle, Antoinette
Garcia-Closas, Montserrat
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Czene, Kamila
Darabi, Hatef
Eriksson, Mikael
Eccles, Diana M.
Rafiq, Sajjad
Tapper, William J.
Gerty, Sue M.
Hooning, Maartje J.
Martens, John W. M.
Collee, J. Margriet
Tilanus-Linthorst, Madeleine
Hall, Per
Li, Jingmei
Brand, Judith S.
Humphreys, Keith
Cox, Angela
Reed, Malcolm W. R.
Luccarini, Craig
Baynes, Caroline
Dunning, Alison M.
Hamann, Ute
Torres, Diana
Ulmer, Hans Ulrich
Ruediger, Thomas
Jakubowska, Anna
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Slager, Susan
Toland, Amanda E.
Ambrosone, Christine B.
Yannoukakos, Drakoulis
Swerdlow, Anthony
Ashworth, Alan
Orr, Nick
Jones, Michael
Gonzalez-Neira, Anna
Pita, Guillermo
Rosario Alonso, M.
Alvarez, Nuria
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Simard, Jacques
Dumont, Martine
Soucy, Penny
Eeles, Rosalind
Muir, Kenneth
Wiklund, Fredrik
Gronberg, Henrik
Schleutker, Johanna
Nordestgaard, Borge G.
Weischer, Maren
Travis, Ruth C.
Neal, David
Donovan, Jenny L.
Hamdy, Freddie C.
Khaw, Kay-Tee
Stanford, Janet L.
Blot, William J.
Thibodeau, Stephen
Schaid, Daniel J.
Kelley, Joseph L.
Maier, Christiane
Kibel, Adam S.
Cybulski, Cezary
Cannon-Albright, Lisa
Butterbach, Katja
Park, Jong
Kaneva, Radka
Batra, Jyotsna
Teixeira, Manuel R.
Kote-Jarai, Zsofia
Al Olama, Ali Amin
Benlloch, Sara
Renner, Stefan P.
Hartmann, Arndt
Hein, Alexander
Ruebner, Matthias
Lambrechts, Diether
Van Nieuwenhuysen, Els
Vergote, Ignace
Lambretchs, Sandrina
Doherty, Jennifer A.
Rossing, Mary Anne
Nickels, Stefan
Eilber, Ursula
Wang-Gohrke, Shan
Odunsi, Kunle
Sucheston-Campbell, Lara E.
Friel, Grace
Lurie, Galina
Killeen, Jeffrey L.
Wilkens, Lynne R.
Goodman, Marc T.
Runnebaum, Ingo
Hillemanns, Peter A.
Pelttari, Liisa M.
Butzow, Ralf
Modugno, Francesmary
Edwards, Robert P.
Ness, Roberta B.
Moysich, Kirsten B.
du Bois, Andreas
Heitz, Florian
Harter, Philipp
Kommoss, Stefan
Karlan, Beth Y.
Walsh, Christine
Lester, Jenny
Jensen, Allan
Kjaer, Susanne Kruger
Hogdall, Estrid
Peissel, Bernard
Bonanni, Bernardo
Bernard, Loris
Goode, Ellen L.
Fridley, Brooke L.
Vierkant, Robert A.
Cunningham, Julie M.
Larson, Melissa C.
Fogarty, Zachary C.
Kalli, Kimberly R.
Liang, Dong
Lu, Karen H.
Hildebrandt, Michelle A. T.
Wu, Xifeng
Levine, Douglas A.
Dao, Fanny
Bisogna, Maria
Berchuck, Andrew
Iversen, Edwin S.
Marks, Jeffrey R.
Akushevich, Lucy
Cramer, Daniel W.
Schildkraut, Joellen
Terry, Kathryn L.
Poole, Elizabeth M.
Stampfer, Meir
Tworoger, Shelley S.
Bandera, Elisa V.
Orlow, Irene
Olson, Sara H.
Bjorge, Line
Salvesen, Helga B.
van Altena, Anne M.
Aben, Katja K. H.
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Pejovic, Tanja
Bean, Yukie
Brooks-Wilson, Angela
Kelemen, Linda E.
Cook, Linda S.
Le, Nhu D.
Grski, Bohdan
Gronwald, Jacek
Menkiszak, Janusz
Hogdall, Claus K.
Lundvall, Lene
Nedergaard, Lotte
Engelholm, Svend Aage
Dicks, Ed
Tyrer, Jonathan
Campbell, Ian
McNeish, Iain
Paul, James
Siddiqui, Nadeem
Glasspool, Rosalind
Whittemore, Alice S.
Rothstein, Joseph H.
McGuire, Valerie
Sieh, Weiva
Cai, Hui
Shu, Xiao-Ou
Teten, Rachel T.
Sutphen, Rebecca
McLaughlin, John R.
Narod, Steven A.
Phelan, Catherine M.
Monteiro, Alvaro N.
Fenstermacher, David
Lin, Hui-Yi
Permuth, Jennifer B.
Sellers, Thomas A.
Chen, Y. Ann
Tsai, Ya-Yu
Chen, Zhihua
Gentry-Maharaj, Aleksandra
Gayther, Simon A.
Ramus, Susan J.
Menon, Usha
Wu, Anna H.
Pearce, Celeste L.
Van den Berg, David
Pike, Malcolm C.
Dansonka-Mieszkowska, Agnieszka
Plisiecka-Halasa, Joanna
Moes-Sosnowska, Joanna
Kupryjanczyk, Jolanta
Pharoah, Paul D. P.
Song, Honglin
Winship, Ingrid
Chenevix-Trench, Georgia
Giles, Graham G.
Tavtigian, Sean V.
Easton, Doug F.
Milne, Roger L.
CA kConFab Investigators
Australian Ovarian Canc Study Grp
TI PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID BREAST-CANCER; PROSTATE-CANCER; OVARIAN-CANCER; BRCA2-INTERACTING
PROTEIN; SUSCEPTIBILITY LOCI; FAMILY REGISTRY; GENE; MUTATIONS; BRCA1;
METAANALYSIS
AB Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.
Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.
Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1x10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9x10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.
Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
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[Weischer, Maren] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Weischer, Maren] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Neal, David] Univ Cambridge, Addenbrookes Hosp, Surg Oncol Urooncol S4, Box 279,Hills Rd, Cambridge, England.
[Neal, David] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England.
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[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Old Rd,Campus Res Bldg,Off Roosevelt Dr, Oxford OX3 7DQ, England.
[Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
[Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
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[Kelley, Joseph L.; Edwards, Robert P.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Maier, Christiane] Univ Hosp Ulm, Dept Urol, Ulm, Germany.
[Maier, Christiane] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany.
[Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, 45 Francis St,ASB 2-3, Boston, MA 02115 USA.
[Kibel, Adam S.] Washington Univ, St Louis, MO USA.
[Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Cannon-Albright, Lisa] Univ Utah, Dept Med, Sch Med, Div Genet Epidemiol, Salt Lake City, UT 84112 USA.
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[Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, 2 Zdrave St, Sofia 1431, Bulgaria.
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[Batra, Jyotsna] Queensland Univ Technol, Australian Prostate Canc Res Ctr Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia.
[Batra, Jyotsna] Queensland Univ Technol, Sch Life Sci, Brisbane, Qld, Australia.
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[Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal.
[Renner, Stefan P.; Hein, Alexander; Ruebner, Matthias] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Univ Str 21-23, D-91054 Erlangen, Germany.
[Hartmann, Arndt] Friedrich Alexander Univ Erlangen Nuremberg, Inst Pathol, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Univ Str 21-23, D-91054 Erlangen, Germany.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Van Nieuwenhuysen, Els; Vergote, Ignace; Lambretchs, Sandrina] Geisel Sch Med Dartmouth, Dept Epidemiol, Lebanon, NH USA.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Hannover, Germany.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Nickels, Stefan; Eilber, Ursula] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Odunsi, Kunle; Sucheston-Campbell, Lara E.; Friel, Grace] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Lurie, Galina; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Killeen, Jeffrey L.] Univ Hawaii, Dept Pathol, Kapiolani Med Ctr Women & Children, John A Burns Sch Med, Honolulu, HI 96826 USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Community & Populat Hlth Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA.
[Runnebaum, Ingo] Friedrich Schiller Univ, Jena Univ Hosp, Dept Gynecol & Obstet, Jena, Germany.
[Hillemanns, Peter A.] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00029, Hus, Finland.
[Modugno, Francesmary] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Modugno, Francesmary] Ovarian Canc Ctr Excellence, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[du Bois, Andreas; Heitz, Florian; Harter, Philipp] Evang Huyssens Stiftung Knappschaft GmbH, Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany.
[du Bois, Andreas; Heitz, Florian; Harter, Philipp; Kommoss, Stefan] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany.
[Kommoss, Stefan] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany.
[Karlan, Beth Y.; Walsh, Christine; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Kjaer, Susanne Kruger; Hogdall, Claus K.] Rigshosp, Dept Obstet & Gynecol, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
[Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Bernard, Loris] IEO, Dept Expt Oncol, Milan, Italy.
[Bernard, Loris] Cogentech Canc Genet Test Lab, Milan, Italy.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Kalli, Kimberly R.] Mayo Clin, Dept Med Oncol, Rochester, MN USA.
[Liang, Dong] Texas Southern Univ, Coll Pharm & Hlth Sci, Houston, TX USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Levine, Douglas A.; Dao, Fanny; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, 1275 York Ave, New York, NY 10021 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Marks, Jeffrey R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Akushevich, Lucy; Schildkraut, Joellen] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA.
[Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Stampfer, Meir; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Stampfer, Meir; Tworoger, Shelley S.] Harvard Med Sch, Boston, MA USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bandera, Elisa V.] State Univ New Jersey, Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA.
[Orlow, Irene; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
[Bjorge, Line; Salvesen, Helga B.] Haukeland Univ Horpital, Dept Gynecol & Obstet, Bergen, Norway.
[Bjorge, Line; Salvesen, Helga B.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway.
[van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, Nijmegen, Netherlands.
[Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
[Aben, Katja K. H.] Netherlands Comprehens Canc Org, Utrecht, Netherlands.
[Aben, Katja K. H.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Pejovic, Tanja; Bean, Yukie] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada.
[Kelemen, Linda E.] Med Univ South Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC USA.
[Kelemen, Linda E.] Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC USA.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Grski, Bohdan; Gronwald, Jacek] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Menkiszak, Janusz] Pomeranian Med Univ, Dept Gynecol Surg & Gynecol Oncol Adults & Adoles, Szczecin, Poland.
[Lundvall, Lene] Univ Copenhagen, Rigshosp, Gyn Clin, Copenhagen, Denmark.
[Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, Copenhagen, Denmark.
[Engelholm, Svend Aage] Univ Copenhagen, Rigshosp, Dept Oncol, Copenhagen, Denmark.
[Dicks, Ed; Tyrer, Jonathan; Pharoah, Paul D. P.; Song, Honglin] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England.
[Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, St Andrews Pl, East Melbourne, Australia.
[McNeish, Iain] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Inst Canc Sci, Glasgow, Lanark, Scotland.
[Paul, James] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
[Siddiqui, Nadeem; Glasspool, Rosalind] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow, Lanark, Scotland.
[Whittemore, Alice S.; Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[Teten, Rachel T.; Sutphen, Rebecca] Univ S Florida, Coll Med, Epidemiol Ctr, Tampa, FL USA.
[McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada.
[Narod, Steven A.] Univ Toronto, Womens Coll, Res Inst, Toronto, ON, Canada.
[Phelan, Catherine M.; Monteiro, Alvaro N.; Permuth, Jennifer B.; Sellers, Thomas A.; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Fenstermacher, David; Lin, Hui-Yi; Chen, Y. Ann; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL USA.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Womens Canc, London, England.
[Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Van den Berg, David; Pike, Malcolm C.] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
[Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland.
[Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta] Inst Oncol, Warsaw, Poland.
[Winship, Ingrid] Univ Melbourne Hlth, Dept Med, Melbourne, Vic, Australia.
[Winship, Ingrid] Royal Melbourne Hosp, Melbourne, Vic 3050, Australia.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Cancer Epidemiol Ctr, Melbourne, Vic, Australia.
RP Southey, MC (reprint author), Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic 3010, Australia.
EM msouthey@unimelb.edu.au
RI Hein, Alexander/F-6999-2010; Gronwald, Jacek/A-4576-2017; Menkiszak,
Janusz/I-4036-2014; Jansen van Rensburg, Elizabeth
(Lizette)/B-9104-2011; Hartikainen, Jaana/E-6256-2015; salvesen,
Helga/C-1187-2017; Knight, Julia/A-6843-2012; Brooks-Wilson,
Angela/E-9399-2012; Bruning, Thomas/G-8120-2015; Brenner,
Hermann/B-4627-2017; Peissel, Bernard/E-8187-2017; Dork,
Thilo/J-8620-2012;
OI Dunning, Alison Margaret/0000-0001-6651-7166; Winship,
Ingrid/0000-0001-8535-6003; Arndt, Volker/0000-0001-9320-8684; Li,
Jingmei/0000-0001-8587-7511; Hein, Alexander/0000-0003-2601-3398;
Gronwald, Jacek/0000-0002-3643-2871; salvesen,
Helga/0000-0002-4438-8831; Brooks-Wilson, Angela/0000-0003-1009-6408;
Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; Peissel, Bernard/0000-0001-9233-3571;
Yannoukakos, Drakoulis/0000-0001-7509-3510
FU European Community [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK
[C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007,
C5047/A10692, CRUK C8197/A10123]; National Institutes of Health
[CA128978]; Post-Cancer GWAS initiative [1 U19 CA 148537]; Department of
Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research
(CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen
Foundation for the Cure; Breast Cancer Research Foundation; Ovarian
Cancer Research Fund; Susan G Komen
FX Funding for the iCOGS infrastructure came from: the European Community's
Seventh Framework Programme under grant agreement no 223175
(HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118,
C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692,
CRUK C8197/A10123), the National Institutes of Health (CA128978) and
Post-Cancer GWAS initiative (No. 1 U19 CA 148537-the GAME-ON
initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian
Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks
of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer
Research Foundation, the Ovarian Cancer Research Fund and Susan G Komen
(WF).
NR 35
TC 4
Z9 4
U1 12
U2 12
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD DEC
PY 2016
VL 53
IS 12
BP 800
EP 811
DI 10.1136/jmedgenet-2016-103839
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA EH0MC
UT WOS:000391457200003
PM 27595995
ER
PT J
AU Postmus, I
Warren, HR
Trompet, S
Arsenault, BJ
Avery, CL
Bis, JC
Chasman, DI
de Keyser, CE
Deshmukh, HA
Evans, DS
Feng, QP
Li, XH
Smit, RAJ
Smith, AV
Sun, FG
Taylor, KD
Arnold, AM
Barnes, MR
Barratt, BJ
Betteridge, J
Boekholdt, SM
Boerwinkle, E
Buckley, BM
Chen, YDI
de Craen, AJM
Cummings, SR
Denny, JC
Dube, MP
Durrington, PN
Eiriksdottir, G
Ford, I
Guo, XQ
Harris, TB
Heckbert, SR
Hofman, A
Hovingh, GK
Kastelein, JJP
Launer, LJ
Liu, CT
Liu, YM
Lumley, T
McKeigue, PM
Munroe, PB
Neil, A
Nickerson, DA
Nyberg, F
O'Brien, E
O'Donnell, CJ
Post, W
Poulter, N
Vasan, RS
Rice, K
Rich, SS
Rivadeneira, F
Sattar, N
Sever, P
Shaw-Hawkins, S
Shields, DC
Slagboom, PE
Smith, NL
Smith, JD
Sotoodehnia, N
Stanton, A
Stott, DJ
Stricker, BH
Sturmer, T
Uitterlinden, AG
Wei, WQ
Westendorp, RGJ
Whitsel, EA
Wiggins, KL
Wilke, RA
Ballantyne, CM
Colhoun, HM
Cupples, LA
Franco, OH
Gudnason, V
Hitman, G
Palmer, CNA
Psaty, BM
Ridker, PM
Stafford, JM
Stein, CM
Tardif, JC
Caulfield, MJ
Jukema, JW
Rotter, JI
Krauss, RM
AF Postmus, Iris
Warren, Helen R.
Trompet, Stella
Arsenault, Benoit J.
Avery, Christy L.
Bis, Joshua C.
Chasman, Daniel I.
de Keyser, Catherine E.
Deshmukh, Harshal A.
Evans, Daniel S.
Feng, QiPing
Li, Xiaohui
Smit, Roelof A. J.
Smith, Albert V.
Sun, Fangui
Taylor, Kent D.
Arnold, Alice M.
Barnes, Michael R.
Barratt, Bryan J.
Betteridge, John
Boekholdt, S. Matthijs
Boerwinkle, Eric
Buckley, Brendan M.
Chen, Y-D Ida
de Craen, Anton J. M.
Cummings, Steven R.
Denny, Joshua C.
Dube, Marie Pierre
Durrington, Paul N.
Eiriksdottir, Gudny
Ford, Ian
Guo, Xiuqing
Harris, Tamara B.
Heckbert, Susan R.
Hofman, Albert
Hovingh, G. Kees
Kastelein, John J. P.
Launer, Leonore J.
Liu, Ching-Ti
Liu, Yongmei
Lumley, Thomas
McKeigue, Paul M.
Munroe, Patricia B.
Neil, Andrew
Nickerson, Deborah A.
Nyberg, Fredrik
O'Brien, Eoin
O'Donnell, Christopher J.
Post, Wendy
Poulter, Neil
Vasan, Ramachandran S.
Rice, Kenneth
Rich, Stephen S.
Rivadeneira, Fernando
Sattar, Naveed
Sever, Peter
Shaw-Hawkins, Sue
Shields, Denis C.
Slagboom, P. Eline
Smith, Nicholas L.
Smith, Joshua D.
Sotoodehnia, Nona
Stanton, Alice
Stott, David J.
Stricker, Bruno H.
Sturmer, Til
Uitterlinden, Andre G.
Wei, Wei-Qi
Westendorp, Rudi G. J.
Whitsel, Eric A.
Wiggins, Kerri L.
Wilke, Russell A.
Ballantyne, Christie M.
Colhoun, Helen M.
Cupples, L. Adrienne
Franco, Oscar H.
Gudnason, Vilmundur
Hitman, Graham
Palmer, Colin N. A.
Psaty, Bruce M.
Ridker, Paul M.
Stafford, Jeanette M.
Stein, Charles M.
Tardif, Jean-Claude
Caulfield, Mark J.
Jukema, J. Wouter
Rotter, Jerome I.
Krauss, Ronald M.
TI Meta-analysis of genome-wide association studies of HDL cholesterol
response to statins
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; TRANSFER PROTEIN GENE; CORONARY
ATHEROSCLEROSIS; CARDIOVASCULAR EVENTS; LOWERING RESPONSE; LDL
CHOLESTEROL; ATORVASTATIN; DISEASE; RISK; LIPIDS
AB Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation.
Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.
Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
C1 [Postmus, Iris; Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Warren, Helen R.; Barnes, Michael R.; Munroe, Patricia B.; Shaw-Hawkins, Sue; Caulfield, Mark J.] Queen Mary Univ London, Dept Clin Pharmacol, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.
[Warren, Helen R.; Barnes, Michael R.; Munroe, Patricia B.; Shaw-Hawkins, Sue; Caulfield, Mark J.] Queen Mary Univ London, Barts NIHR Cardiovasc Biomed Res Unit, London EC1M 6BQ, England.
[Trompet, Stella; Smit, Roelof A. J.; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Arsenault, Benoit J.; Dube, Marie Pierre; Tardif, Jean-Claude] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Avery, Christy L.; Sturmer, Til; Whitsel, Eric A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Bis, Joshua C.; Lumley, Thomas; Sotoodehnia, Nona; Wiggins, Kerri L.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Chasman, Daniel I.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[de Keyser, Catherine E.; Hofman, Albert; Stricker, Bruno H.; Uitterlinden, Andre G.; Franco, Oscar H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Deshmukh, Harshal A.; Colhoun, Helen M.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland.
[Evans, Daniel S.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Feng, QiPing] Vanderbilt Univ, Dept Clin Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Li, Xiaohui; Taylor, Kent D.; Chen, Y-D Ida; Guo, Xiuqing; Rotter, Jerome I.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA.
[Li, Xiaohui; Taylor, Kent D.; Chen, Y-D Ida; Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Li, Xiaohui; Taylor, Kent D.; Chen, Y-D Ida; Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA.
[Smith, Albert V.; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland.
[Sun, Fangui; Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Arnold, Alice M.; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Barratt, Bryan J.] AstraZeneca Res & Dev, Personalised Healthcare & Biomarkers, Alderley Pk, England.
[Betteridge, John] Univ Coll London Hosp, London, England.
[Boekholdt, S. Matthijs] Acad Med Ctr, Dept Cardiol, Amsterdam, North Holland, Netherlands.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
[Buckley, Brendan M.] Univ Coll Cork, Dept Pharmacol & Therapeut, Western Rd, Cork, Ireland.
[Denny, Joshua C.; Wei, Wei-Qi] Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Denny, Joshua C.; Stein, Charles M.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Durrington, Paul N.] Univ Manchester, Sch Biosci, Cardiovasc Res Grp, Manchester, Lancs, England.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Harris, Tamara B.; Launer, Leonore J.] NIA, Lab Epidemiol, Demog, Biometry,NIH, Bethesda, MD 20892 USA.
[Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Hofman, Albert; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands.
[Hovingh, G. Kees; Kastelein, John J. P.] Acad Med Ctr, Dept Vasc Med, Amsterdam, North Holland, Netherlands.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland, New Zealand.
[McKeigue, Paul M.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Neil, Andrew] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England.
[Nickerson, Deborah A.; Smith, Joshua D.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Nyberg, Fredrik] AstraZeneca Gothenburg, Med Evidence & Observat Res, Molndal, Sweden.
[Nyberg, Fredrik] Univ Gothenburg, Unit Occupat & Environm Med, Gothenburg, Sweden.
[O'Brien, Eoin; Shields, Denis C.] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland.
[O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Cardiol Div, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Post, Wendy] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA.
[Poulter, Neil; Sever, Peter] Imperial Coll London, Int Ctr Circulatory Hlth, London, England.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Framingham, MA USA.
[Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Rivadeneira, Fernando; Stricker, Bruno H.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Sattar, Naveed] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Shields, Denis C.] Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA.
[Sotoodehnia, Nona] Univ Washington, Harborview Med Ctr, Div Cardiol, 325 9Th Ave, Seattle, WA 98104 USA.
[Stanton, Alice] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland.
[Stanton, Alice] Beaumont Hosp, Dublin, Ireland.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands.
[Westendorp, Rudi G. J.] Univ Copenhagen, Ctr Hlth Ageing, Dept Publ Hlth, Copenhagen, Denmark.
[Whitsel, Eric A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Wilke, Russell A.] Sanford Healthcare, Dept Internal Med, Sioux Falls, SD USA.
[Wilke, Russell A.] Univ South Dakota, Dept Med, Sioux Falls, SD USA.
[Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Colhoun, Helen M.] Univ Dundee, Dept Publ Hlth, Dundee, Scotland.
[Hitman, Graham] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Stafford, Jeanette M.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Stein, Charles M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Dept Atherosclerosis Res, Oakland, CA 94609 USA.
RP Krauss, RM (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA.
EM rkrauss@chori.org
RI Palmer, Colin/C-7053-2008;
OI Palmer, Colin/0000-0002-6415-6560; Colhoun, Helen/0000-0002-8345-3288;
Dube, Marie-Pierre/0000-0001-8442-4393
FU Bristol-Myers Squibb, USA; European Union [HEALTH-F2-2009-223004];
Netherlands Consortium for Healthy Ageing [NGI: 05060810]; Pfizer USA;
National Institutes for Health Research (NIHR); NIHR Biomedical Research
Centre at Imperial College; International Centre for Circulatory Health
Charity; Medical Research Council [G952010]; Pfizer; Diabetes UK
[07/0003525]; Department of Health; National Institutes of Health from
the National Heart, Lung, and Blood Institute [U19 HL069757]; National
Center for Advancing Translational Sciences [UL1TR000124, 2 UL1
TR000445]; NIH [N01-AG-1-2100]; NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic
Parliament); National Heart, Lung and Blood Institute
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367,
R01HL086694]; National Human Genome Research Institute [U01HG004402,
U01-HG04603]; National Institutes of Health [HHSN268200625226C,
UL1RR025005, HHSN268200782096C]; NIH Roadmap for Medical Research;
National Center for Research Resources [UL1 RR024975]; National
Institute of General Medical Sciences [RC2-GM092318]; NHLBI
[HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295,
R01HL087652, R01HL105756, R01HL103612, R01HL120393, HL085251, HL073410,
HL068986]; National Institute on Aging (NIA) [R01AG023629]; National
Center for Advancing Translational Sciences, CTSI [UL1TR000124];
National Institute of Diabetes and Digestive and Kidney Disease Diabetes
Research Center (DRC) [DK063491]; National Heart Lung and Blood
Institute of the National Institutes of Health; Boston University School
of Medicine [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine; Boston Medical Center; NIA [N01AG62101,
N01AG62103, N01AG62106, 1R01AG032098-01A1]; Intramural Research Program
of the NIH, National Institute on Aging; National Heart, Lung and Blood
Institute (NHLBI); Clinical Translational Science Institute
[UL1RR033176]; Erasmus Medical Center; Erasmus University Rotterdam;
Netherlands Organization for Health Research and Development (ZonMw);
Research Institute for Diseases in the Elderly; Ministry of Education,
Culture and Science; Ministry of Health Welfare and Sports; European
Commission; Municipality of Rotterdam; Netherlands Genomics Initiative
(NGI) Netherlands Organization for Scientific Research (NOW)
[050-060-810]; AstraZeneca; Wellcome Trust [084727/Z/08/Z,
085475/Z/08/Z, 085475/B/08/Z]; EU IMI-SUMMIT programme; [N01 HC-95159];
[N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163];
[N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167];
[N01-HC-95168]; [N01-HC-95169]; [RR-024156]
FX PROSPER/PHASE: The Prospective Study of Pravastatin in the Elderly at
Risk (PROSPER) trial was supported by an investigator initiated grant
from Bristol-Myers Squibb, USA. The study was conducted, analysed and
reported independently of the company. The GWAS project PHASE has
received funding from the European Union's Seventh Framework Programme
(FP7/2007-2013) under grant agreement HEALTH-F2-2009-223004. A part of
the genotyping was funded by The Netherlands Consortium for Healthy
Ageing (NGI: 05060810). Professor Dr J W Jukema is an established
clinical investigator of The Netherlands Heart Foundation (2001 D 032).
ASCOT: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) trial was
funded by an investigator initiated grant from Pfizer USA. The study was
investigator-led and was conducted, analysed and reported independently
of the company. The Genome-wide Association Scan was funded by the
National Institutes for Health Research (NIHR) as part of the portfolio
of translational research of the NIHR Biomedical Research Unit at Barts
and the NIHR Biomedical Research Centre at Imperial College, the
International Centre for Circulatory Health Charity and the Medical
Research Council through G952010. CARDS: The authors thank the other
investigators, the staff and the participants of the CARDS study. A full
list of CARDS investigators can be found in original CARDS paper. 38
CARDS was funded by grants to the Universities of London and Manchester
by Pfizer, Diabetes UK and the Department of Health. PARC: This research
was supported by the National Institutes of Health: grant U19 HL069757
from the National Heart, Lung, and Blood Institute; and grant
UL1TR000124 from the National Center for Advancing Translational
Sciences. TNT: The TNT study was funded by Pfizer, who also provided
support for genotyping. AGES: This study has been funded by NIH contract
N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association) and the Althingi (the Icelandic
Parliament). The study is approved by the Icelandic National Bioethics
Committee, VSN: 00-063. The researchers are indebted to the participants
for their willingness to participate in the study. ARIC: The
Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung and Blood
Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C and HHSN268201100012C),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. The authors thank the staff and participants
of the ARIC study for their important contributions. Infrastructure was
partly supported by Grant Number UL1RR025005, a component of the
National Institutes of Health and NIH Roadmap for Medical Research.
BioVU: BioVU receives support through the National Center for Research
Resources UL1 RR024975, which is now the National Center for Advancing
Translational Sciences, 2 UL1 TR000445. Genotyping was supported via
grant U01-HG04603 from the National Human Genome Research Institute and
RC2-GM092318 from the National Institute of General Medical Sciences.;
CHS: This CHS research was supported by NHLBI contracts
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants U01HL080295, R01HL087652, R01HL105756, R01HL103612 and
R01HL120393 with additional contribution from the National Institute of
Neurological Disorders and Stroke (NINDS). Additional support was
provided through R01AG023629 from the National Institute on Aging (NIA).
A full list of principal CHS investigators and institutions can be found
at CHS-NHLBI.org. The provision of genotyping data were supported in
part by the National Center for Advancing Translational Sciences, CTSI
grant UL1TR000124, and the National Institute of Diabetes and Digestive
and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
Framingham HS: The Framingham Heart Study work was supported by the
National Heart Lung and Blood Institute of the National Institutes of
Health and Boston University School of Medicine (contract no.
N01-HC-25195), its contract with Affymetrix, Inc for genotyping services
(contract no. N02-HL-6-4278) and based upon analyses by Framingham Heart
Study investigators participating in the SNP Health Association Resource
(SHARe) project. A portion of this research was conducted using the
Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center. Also supported
by R01HL103612 (PI Psaty, subcontract PI, Vasan). Health ABC: The Health
ABC study was supported by NIA contracts N01AG62101, N01AG62103 and
N01AG62106. The genome-wide association study was funded by NIA grant
1R01AG032098-01A1 to Wake Forest University Health Sciences and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. HVH: This Heart and Vascular Health Study research was supported
by NHLBI grants HL085251, HL073410, HL085251 and HL068986. MESA: The
Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health
Association Resource (SHARe) are conducted and supported by the National
Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA
investigators. Support is provided by grants and contracts N01 HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and
RR-024156. Additional funding was supported in part by the Clinical
Translational Science Institute grant UL1RR033176 and is now at the
National Center for Advancing Translational Sciences, CTSI grant
UL1TR000124. The authors thank the other investigators in the
Pharmarcogenetics Working Group, the staff and the participants of the
MESA study for their valuable contributions. A full list of
participating MESA investigators and institutions can be found at
http://www.mesa-nhlbi.org.; Rotterdam Study: The Rotterdam Study is
supported by the Erasmus Medical Center and Erasmus University
Rotterdam; the Netherlands Organization for Health Research and
Development (ZonMw); the Research Institute for Diseases in the Elderly;
the Ministry of Education, Culture and Science; the Ministry of Health
Welfare and Sports; the European Commission and Municipality of
Rotterdam. This work was supported by the Netherlands Genomics
Initiative (NGI) Netherlands Organization for Scientific Research (NOW;
050-060-810). JUPITER: Genetic analysis in JUPITER was supported by a
research grant from AstraZeneca to DC and PM. GoDARTS: We are grateful
to all the participants who took part in this study, to the general
practitioners, to the Scottish School of Primary Care for their help in
recruiting the participants, and to the whole team, which includes
interviewers, computer and laboratory technicians, clerical workers,
research scientists, volunteers, managers, receptionists and nurses. The
Wellcome Trust provides support for Wellcome Trust UK Type 2 Diabetes
Case Control Collection (GoDARTS) and informatics support is provided by
the Chief Scientist Office. The Wellcome Trust funds the Scottish Health
Informatics Programme, provides core support for the Wellcome Trust
Centre for Human Genetics in Oxford and funds the Wellcome Trust Case
Control Consortium 2. This research was specifically funded by Diabetes
UK (07/0003525) and the Wellcome Trust (084727/Z/08/Z, 085475/Z/08/Z,
085475/B/08/Z). Genotyping of the GoDARTS samples (sample 2) was also
funded as part of the EU IMI-SUMMIT programme.
NR 38
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U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD DEC
PY 2016
VL 53
IS 12
BP 835
EP +
DI 10.1136/jmedgenet-2016-103966
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA EH0MC
UT WOS:000391457200007
PM 27587472
ER
PT J
AU Kurtz, SL
Bosio, CM
De Pascalis, R
Elkins, KL
AF Kurtz, Sherry L.
Bosio, Catharine M.
De Pascalis, Roberto
Elkins, Karen L.
TI GM-CSF has disparate roles during intranasal and intradermal Francisella
tularensis infection
SO MICROBES AND INFECTION
LA English
DT Article
DE GM-CSF; Alveolar macrophage; Francisella; Immunity
ID COLONY-STIMULATING FACTOR; LIVE VACCINE STRAIN; FACTOR-DEFICIENT MICE;
ALVEOLAR MACROPHAGES; IMMUNITY; HOST; TUBERCULOSIS; INTERFERON;
TULAREMIA; LUNGS
AB Our laboratory has employed in vitro and in vivo mouse models based on Francisella tularensis Live Vaccine Strain (LVS)-induced protection to elucidate immune correlates for intracellular bacteria. Among the effectors found was GM-CSF, a pleiotropic cytokine that is integral to the development and proliferation of myeloid cells, including alveolar macrophages. GM-CSF has roles in resistance to primary murine infection with several intracellular pathogens, but its role during Francisella infection is unknown. Francisella is an intracellular pathogen that infects lungs after inhalation, primarily invading alveolar macrophages. Here we show that GM-CSF has route-dependent roles during primary infection of mice with LVS. GM-CSF deficient (GM-CSF KO) mice were slightly more susceptible than wild type to intradermal infection, but had increased resistance to intranasal infection. Similarly, these mice had increased resistance to pulmonary infection with virulent F. tularensis (SchuS4). LVS-vaccinated GM-CSF KO mice had normal adaptive immune responses, as measured by T cell activities after LVS intradermal or intranasal vaccination, and survived lethal secondary LVS challenge. GM-CSF KO mice also had robust humoral responses, producing elevated levels of serum antibodies following LVS vaccination compared to wild type mice. Taken together, our data demonstrates that the absence of GM-CSF improves resistance to pulmonary, but not intradermal, infection with Francisella. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Kurtz, Sherry L.; De Pascalis, Roberto; Elkins, Karen L.] US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20903 USA.
[Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT 59480 USA.
RP Elkins, KL (reprint author), US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial & Allergen Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,Bldg 52-72,Room 5330 5348, Silver Spring, MD 20993 USA.
EM karen.elkins@fda.hhs.gov
NR 28
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U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
EI 1769-714X
J9 MICROBES INFECT
JI Microbes Infect.
PD DEC
PY 2016
VL 18
IS 12
BP 758
EP 767
DI 10.1016/j.micinf.2016.07.003
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA EH4ZB
UT WOS:000391781300005
PM 27475899
ER
PT J
AU Sissung, TM
Deeken, J
Leibrand, CR
Price, DK
Ehrlich, S
Steinberg, SM
Liewehr, DJ
Dahut, W
Figg, WD
AF Sissung, Tristan M.
Deeken, John
Leibrand, Crystal R.
Price, Douglas K.
Ehrlich, Sheryl
Steinberg, Seth M.
Liewehr, David J.
Dahut, William
Figg, William D.
TI Identification of novel SNPs associated with risk and prognosis in
patients with castration-resistant prostate cancer
SO PHARMACOGENOMICS
LA English
DT Article
DE castration-resistant prostate cancer; genotype; metabolism; outcome;
survival; transport
ID CYTOCHROME-P450 CYP 1A1; GENETIC POLYMORPHISMS; JAPANESE POPULATION;
ANDROGEN BIOSYNTHESIS; SUSCEPTIBILITY; GENOTYPES; VARIANTS; SRD5A2; M1
AB Aim: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). Materials & methods: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. Results: No relation to risk was found. Three SNPs were associated with CRPC prognosis in Caucasians: ABCB11 rs7602171G>A (p = 0.003; n = 30; hazard ratio [HR]: 0.307), GSTP1 rs1799811C>T (p = 0.001; n = 38; HR: 0.254) and SLC5A6 rs1395 (p = 0.004; n = 35; HR: 3.15). Two other polymorphisms among Caucasians were associated with interesting trends: ABCB4 rs2302387C>T (p = 0.039) and ABCC5 rs939339A>G (p = 0.018). Conclusion: This exploratory study is the first to show that polymorphisms in several absorption, distribution, metabolism and elimination genes may be associated with CRPC prognosis.
C1 [Sissung, Tristan M.; Leibrand, Crystal R.; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
[Deeken, John] Inova Comprehens Canc & Res Inst, Falls Church, VA 22042 USA.
[Price, Douglas K.; Ehrlich, Sheryl; Figg, William D.] NCI, Mol Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
[Steinberg, Seth M.; Liewehr, David J.] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Shady Grove, MD 20850 USA.
[Dahut, William] NCI, Prostate Canc Clin Res Sect, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
RP Sissung, TM (reprint author), NCI, Clin Pharmacol Program, Off Clin Director, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM sissungt@mail.nih.gov
NR 36
TC 0
Z9 0
U1 1
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1462-2416
EI 1744-8042
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD DEC
PY 2016
VL 17
IS 18
BP 1979
EP 1986
DI 10.2217/pgs-2016-0134
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EH6EP
UT WOS:000391865900003
PM 27883295
ER
PT J
AU Goold, S
Rowe, Z
Calhoun, K
Campbell, T
Danis, M
Hammad, A
Salman, C
Szymecko, L
Coombe, C
AF Goold, Susan
Rowe, Zachary
Calhoun, Karen
Campbell, Terrance
Danis, Marion
Hammad, Adnan
Salman, Cengiz
Szymecko, Lisa
Coombe, Chris
TI The State as Community in Community-Based Participatory Research
SO PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION
LA English
DT Article
DE Community health partnerships; Community health research; health
disparities; process issues; Great Lakes Region; health priorities
ID PARTNERSHIPS LESSONS; DEFINITION; STRATEGIES
AB Background: Community-based participatory research (CBPR) typically defines communities by geography, ethnicity, shared health needs, or some combination.
Objectives: We describe a CBPR project aiming to engage diverse minority and underserved communities throughout Michigan in deliberations about health research priorities.
Methods: A steering committee (SC) with 15 members from minority and underserved communities and 4 members from research organizations led the project, with the help of regional advisory groups (RAGs) formed at the SC's request. Evaluation of the SC used questionnaires, focused group discussion, and review of SC meetings to describe engagement, partnership, and communication.
Lessons Learned: An academic-community partnership with a diverse, dispersed, and broadly defined community found value in RAGs, dedicated academic staff, face-to-face meetings, varied communication modalities, capacity building tailored to varying levels of CBPR experience, and ongoing evaluation.
Conclusions: A geographically and culturally diverse partnership presents challenges and opportunities in representativeness, relationship building, capacity building, and communication.
C1 [Goold, Susan] Univ Michigan, Gen Med, Ann Arbor, MI 48109 USA.
[Rowe, Zachary] Friends Parkside, Detroit, MI USA.
[Calhoun, Karen] City Connect Detroit, Detroit, MI USA.
[Calhoun, Karen] Michigan Inst Clin & Hlth Res, Ann Arbor, MI USA.
[Campbell, Terrance] YOUR Ctr, Flint, MI USA.
[Danis, Marion] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD USA.
[Hammad, Adnan] Arab Community Ctr Econ & Social Serv, Dearborn, MI USA.
[Salman, Cengiz; Szymecko, Lisa] Univ Michigan, Gen Med, Ann Arbor, MI 48109 USA.
[Salman, Cengiz; Szymecko, Lisa] Ctr Bioeth & Social Sci Humanities, Ann Arbor, MI USA.
[Coombe, Chris] Univ Michigan, Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
RP Goold, S (reprint author), Univ Michigan, Gen Med, Ann Arbor, MI 48109 USA.
NR 20
TC 0
Z9 0
U1 1
U2 1
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1557-0541
EI 1557-055X
J9 PROG COMM HLTH PARTN
JI Prog. Community Health Partnersh.
PD WIN
PY 2016
VL 10
IS 4
BP 515
EP 522
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EH6RS
UT WOS:000391902200005
ER
PT J
AU Pongas, G
Cheson, BD
AF Pongas, Georgios
Cheson, Bruce D.
TI PI3K signaling pathway in normal B cells and indolent B-cell
malignancies
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Chronic lymphocytic leukemia; Indolent non-Hodgkin lymphoma; PI3K;
Lymphoma; Leukemia; Idelalisib
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PHOSPHOINOSITIDE 3-KINASE; TYROSINE
PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; EMBRYONIC LETHALITY;
IDELALISIB; RECEPTOR; LYMPHOMA; CD19; ACTIVATION
AB In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3K delta inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and relapsed follicular lymphoma (FL). Following its approval, several trials investigating various PI3K delta inhibitors as single agents or in combination with chemoimmunotherapy or other molecular targeted agents in CLL and indolent NHL (iNHL) have uncovered some severe autoimmune related toxicities. This review discusses and summarizes the biologic basis and the clinical experience of the PI3K delta inhibitors in indolent B-cell malignancies. Published by Elsevier Inc.
C1 [Pongas, Georgios] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA.
[Pongas, Georgios] NCI, Womens Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Cheson, Bruce D.] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Pongas, G (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 4B-55, Bethesda, MD 20892 USA.
EM georgios.pongas@nih.gov
FU Acerta; Roche-Genentech; Celgene; Pharmacyclics; Pfizer; Gilead
FX G.P declares no competing financial interests. B.D.C received consulting
fees from Acerta, Roche-Genentech, Celgene, Pharmacyclics, and Pfizer,
and research funding to his institution from Acerta, Roche-Genentech,
Celgene, Pharmacyclics, and Gilead.
NR 77
TC 1
Z9 1
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD DEC
PY 2016
VL 43
IS 6
BP 647
EP 654
DI 10.1053/j.seminoncol.2016.11.011
PG 8
WC Oncology
SC Oncology
GA EH6QY
UT WOS:000391900200004
PM 28061982
ER
PT J
AU Ahn, IE
Mailankody, S
AF Ahn, Inhye E.
Mailankody, Sham
TI Controversies in multiple myeloma: Evidence-based update
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Multiple myeloma Smoldering multiple myeloma; Treatment; Risk-benefit;
Evidence; Cost
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; LENALIDOMIDE PLUS
DEXAMETHASONE; INTERNATIONAL STAGING SYSTEM; MARROW PLASMA-CELLS;
TERM-FOLLOW-UP; RANDOMIZED-TRIAL; WORKING GROUP; HIGH-RISK; AUTOLOGOUS
TRANSPLANTATION
AB The US Food and Drug Administration (FDA) approved 10 new drugs for the treatment of multiple myeloma (MM) over the last two decades. The influx of new anti-myeloma agents with high efficacy and acceptable tolerability add complexity to the clinical decision-making process. First, treatment of smoldering multiple myeloma (SMM) remains investigational to date, although a randomized trial showed a survival gain in high-risk patients receiving lenalidomide. Second, in newly diagnosed MM, the majority of contemporary induction regimens have been studied in single-arm trials or compared to an older regimen, which complicates evidence-based treatment selection. Third, the role of consolidation chemotherapy followed by autologous stem cell transplant (ASCT) needs to be revisited in the context of highly effective agents, as newer regimens - such as carfilzomib, lenalidomide, and dexamethasone are able to achieve extremely deep responses equivalent to or exceeding those seen after conventional induction and ASCT. Fourth, risks and benefits of maintenance therapy should also be redefined and individualized, as long-term survival and safety data accumulate. Here we selected four clinical settings where controversies exist, reviewed evidences behind conflicting treatment strategies, and asked myeloma experts to discuss evidence-based recommendations. (C) 2016 Elsevier. All rights reserved.
C1 [Ahn, Inhye E.] NCI, NIH, Bethesda, MD 20892 USA.
[Mailankody, Sham] Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA.
RP Mailankody, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dept Hematol Oncol, Myeloma Serv, 1233 York Ave, New York, NY 10065 USA.
EM mailanks@mskcc.org
FU Memorial Sloan Kettering Core Grant [P30 CA008748]
FX Grant support from Memorial Sloan Kettering Core Grant (P30 CA008748) .
NR 68
TC 0
Z9 0
U1 2
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD DEC
PY 2016
VL 43
IS 6
BP 666
EP 675
DI 10.1053/j.seminoncol.2016.10.006
PG 10
WC Oncology
SC Oncology
GA EH6QY
UT WOS:000391900200006
PM 28061984
ER
PT J
AU Kazandjian, D
AF Kazandjian, Dickran
TI Multiple myeloma epidemiology and survival: A unique malignancy
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Multiple myeloma; Smoldering myeloma; MGUS; Epidemiology; Health
disparity
ID UNDETERMINED SIGNIFICANCE MGUS; LONG-TERM SURVIVAL; MONOCLONAL
GAMMOPATHY; RACIAL DISPARITIES; NATIONAL-HEALTH; POPULATION; PROGNOSIS;
CRITERIA; YOUNGER
AB Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times. Advancements in the diagnosis, monitoring, and treatment of MM are of the utmost importance as the general population lives longer due to other improvements in health care. The recent introduction of novel therapies has been paralleled by advancements in the monitoring of MM, namely, by the availability exquisitely sensitive techniques in detecting minimal residual disease. As drug development and technology continues to improve, it will be important to design rationale clinical trials enrolling patient populations that represent the overall population, including racial minorities and the elderly, so that trial results can be appropriately extrapolated. Herein, the changing epidemiology, improvements in survival, and the health disparity observed in important subgroups of MM are reviewed. Published by Elsevier Inc.
C1 [Kazandjian, Dickran] NCI, Myeloma Program, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Kazandjian, D (reprint author), NCI, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA.
EM kazandjiandg@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 38
TC 0
Z9 0
U1 5
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD DEC
PY 2016
VL 43
IS 6
BP 676
EP 681
DI 10.1053/j.seminoncol.2016.11.004
PG 6
WC Oncology
SC Oncology
GA EH6QY
UT WOS:000391900200007
PM 28061985
ER
PT J
AU Kazandjian, D
Landgren, O
AF Kazandjian, Dickran
Landgren, Ola
TI A look backward and forward in the regulatory and treatment history of
multiple myeloma: Approval of novel-novel agents, new drug development,
and longer patient survival
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Myeloma; Smoldering; FDA; EMA; Approvals
ID PHASE-3 TRIAL; BONE-MARROW; DEXAMETHASONE; LENALIDOMIDE; BORTEZOMIB;
INHIBITOR; THERAPY; MULTICENTER; COMBINATION; DARATUMUMAB
AB The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time. We aim to review and give further insight into drug development and novel drug approvals that have revolutionized the treatment of MM. Published by Elsevier Inc.
C1 [Kazandjian, Dickran] NCI, Myeloma Program, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kazandjian, Dickran] US FDA, Off Hematol & Oncol Prod, Bethesda, MD USA.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA.
RP Kazandjian, D (reprint author), NCI, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kazandjiandg@mail.nih.gov
FU Memorial Sloan Kettering Core Grant [P30 CA008748]
FX Memorial Sloan Kettering Core Grant, (P30 CA008748) for grant support.
NR 30
TC 0
Z9 0
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD DEC
PY 2016
VL 43
IS 6
BP 682
EP 689
DI 10.1053/j.seminoncol.2016.10.008
PG 8
WC Oncology
SC Oncology
GA EH6QY
UT WOS:000391900200008
PM 28061986
ER
PT J
AU Lu, TYL
Pugach, O
Somerville, R
Rosenberg, SA
Kochendefer, JN
Better, M
Feldman, SA
AF Lu, Tangying Lily
Pugach, Omar
Somerville, Robert
Rosenberg, Steven A.
Kochendefer, James N.
Better, Marc
Feldman, Steven A.
TI A Rapid Cell Expansion Process for Production of Engineered Autologous
CAR-T Cell Therapies
SO HUMAN GENE THERAPY METHODS
LA English
DT Article
DE anti-CD19 CAR; transduction; expansion; cryopreservation; GMP; closed
system
ID CHIMERIC-ANTIGEN-RECEPTOR; B-CELL; ADOPTIVE IMMUNOTHERAPY; LYMPHOMA;
TRANSPLANTATION; MALIGNANCIES; REGRESSION; DEPLETION
AB The treatment of B-cell malignancies by adoptive cell transfer (ACT) of anti-CD19 chimeric antigen receptor T cells (CD19 CAR-T) has proven to be a highly successful therapeutic modality in several clinical trials.(1-6) The anti-CD19 CAR-T cell production method used to support initial trials relied on numerous manual, open process steps, human serum, and 10 days of cell culture to achieve a clinical dose.(7) This approach limited the ability to support large multicenter clinical trials, as well as scale up for commercial cell production. Therefore, studies were completed to streamline and optimize the original National Cancer Institute production process by removing human serum from the process in order to minimize the risk of viral contamination, moving process steps from an open system to functionally closed system operations in order to minimize the risk of microbial contamination, and standardizing additional process steps in order to maximize process consistency. This study reports a procedure for generating CD19 CAR-T cells in 6 days, using a functionally closed manufacturing process and defined, serum-free medium. This method is able to produce CD19 CAR-T cells that are phenotypically and functionally indistinguishable from cells produced for clinical trials by the previously described production process.
C1 [Lu, Tangying Lily; Somerville, Robert; Rosenberg, Steven A.; Feldman, Steven A.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kochendefer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Pugach, Omar] ImaginAb Inc, Inglewood, CA USA.
[Pugach, Omar; Better, Marc] KITE Pharma, Santa Monica, CA USA.
RP Feldman, SA (reprint author), NCI, Surg Branch, ACRF, 10 Ctr Dr,MSC 1201,Bldg 10,1B37A, Bethesda, MD 20892 USA.
EM feldmanst@mail.nih.gov
FU Kite Pharma, Inc. through collaborative research and development
agreement (CRADA); Surgery Branch, NCI, National Institutes of Health
FX This work was supported, in part, by Kite Pharma, Inc., through a
collaborative research and development agreement (CRADA) with Surgery
Branch, NCI, National Institutes of Health. Thanks also go to David
Stroncek and the Department of Transfusion Medicine, National Institutes
of Health, for technical input and discussion.
NR 29
TC 0
Z9 0
U1 6
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1946-6536
EI 1946-6544
J9 HUM GENE THER METHOD
JI Hum. Gene Ther. Methods
PD DEC
PY 2016
VL 27
IS 6
BP 209
EP 218
DI 10.1089/hgtb.2016.120
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA EG5VF
UT WOS:000391112100001
PM 27897048
ER
PT J
AU Guzelsoy, M
Kirkali, Z
AF Guzelsoy, Muhammet
Kirkali, Ziya
TI Role of Transition Zone Index in the Prediction of Clinical Benign
Prostatic Hyperplasia
SO JOURNAL OF UROLOGICAL SURGERY
LA English
DT Article
DE Clinical benign prostatic hyperplasia; transurethral prostatectomy;
tissue amount; transition zone volume; transition zone index
ID SYMPTOMS; VOLUME; SIZE; THERAPY; WEIGHT; GLAND; FLOW
AB Objective
The objective of this study was to determine the role of the transition zone (TZ) index (TZI) in the prediction of clinical benign prostatic hyperplasia (BPH) in patients who underwent transurethral prostatectomy (TUR-P) and to analyze the correlation between the amount of resected tissue and TZ volume (TZV).
Materials and Methods
Twenty-six male clinical BPH patients with obstructive complaints and 17 male benign prostate enlargement (BPE) patients without any complaints were included in the study. Both the groups were over the age of 50. Clinical BPH patients underwent complete TUR-P. Statistical analysis was done with SPSS. Sensitivity, specificity, positive and negative predictive values of TZI-as a method of assessing clinical BPH-were measured.
Results
There was a statistically significant difference in prostate volume, uroflowmetry patterns, prostate-specific antigen (PSA), International prostate symptom score (IPSS), TZV and TZI between the two groups. There was a correlation between TZV and the amount of resected tissue (r= 0.97; p<0.0001). TZI also correlated with IPSS, quality of life (QL) and maximum flow rate (MFR) (r= 0.58, p< 0001; r= 0.56, p< 0.000; r=-0.70, p< 0.0001, respectively).
Conclusion
TZI > 0.40 has a high level of sensitivity and specificity in the prediction of clinical BPH among patients who undergo TUR-P due to obstructive symptoms and reported as BPH. There is a strong correlation between the amount of resected tissue and TZV. TZI is a valuable tool in diagnosis, and TZV gives valuable information about the patient to the surgeon.
C1 [Guzelsoy, Muhammet] Yuksek Ihtisas Training & Res Hosp, Urol Clin, Bursa, Turkey.
[Kirkali, Ziya] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA.
RP Guzelsoy, M (reprint author), Yuksek Ihtisas Training & Res Hosp, Urol Clin, Bursa, Turkey.
EM muhammetguzelsoy@yahoo.com.tr
NR 25
TC 0
Z9 0
U1 0
U2 0
PU GALENOS YAYINCILIK
PI FINDIKZADE
PA ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY
SN 2148-9580
J9 J UROL SURG
JI J. Urol. Surg.
PD DEC
PY 2016
VL 3
IS 4
BP 114
EP 118
DI 10.4274/jus.960
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA EG6SM
UT WOS:000391176400002
ER
PT J
AU Burgess, S
Cheng, LZ
Gu, F
Huang, JJ
Huang, ZW
Lin, S
Li, JS
Li, W
Qin, W
Sun, YJ
Zhou, SY
Wei, WS
Wu, Q
Wang, HY
Wang, XQ
Xiong, JW
Xi, JZ
Yang, H
Zhou, B
Zhang, B
AF Burgess, Shawn
Cheng, Linzhao
Gu, Feng
Huang, Junjiu
Huang, Zhiwei
Lin, Shuo
Li, Jinsong
Li, Wei
Qin, Wei
Sun, Yujie
Zhou Songyang
Wei, Wensheng
Wu, Qiang
Wang, Haoyi
Wang, Xiaoqun
Xiong, Jing-Wei
Xi, Jianzhong
Yang, Hui
Zhou, Bin
Zhang, Bo
TI Questions about NgAgo
SO PROTEIN & CELL
LA English
DT Letter
C1 [Burgess, Shawn] NHGRI, NIH, Bethesda, MD 20892 USA.
[Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
[Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Baltimore, MD 21205 USA.
[Gu, Feng] Wenzhou Med Univ, Hosp Eye, Ctr Vis Res, Wenzhou 325035, Peoples R China.
[Huang, Junjiu; Zhou Songyang] Sun Yat Sen Univ, Sch Life Sci, Stem Cell & Funct Genom Lab, Guangzhou 510275, Guangdong, Peoples R China.
[Huang, Zhiwei] Harbin Inst Technol, HIT Ctr Life Sci, Harbin 150080, Peoples R China.
[Lin, Shuo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
[Li, Jinsong; Zhou, Bin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
[Li, Wei; Wang, Haoyi] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.
[Qin, Wei] Peking Univ, Shenzhen Grad Sch, Coll Chem Biol & Biotechnol, Shenzhen 518055, Peoples R China.
[Sun, Yujie] PKU BIOPIC, Beijing 100871, Peoples R China.
[Wei, Wensheng] Peking Univ, CLS, ICG, BIOPIC, Beijing 100871, Peoples R China.
[Wei, Wensheng] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
[Wu, Qiang] Shanghai Jiao Tong Univ, Inst Syst Biomed, Ctr Comparat Biomed, Shanghai 200240, Peoples R China.
[Wang, Xiaoqun] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
[Xiong, Jing-Wei] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China.
[Xi, Jianzhong] Peking Univ, Coll Engn, Beijing 100871, Peoples R China.
[Yang, Hui] Shanghai Chinese Acad Sci, Inst Neurosci, Lab Dis Models Nonhuman Primates, Shanghai 200031, Peoples R China.
[Zhang, Bo] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
RP Cheng, LZ (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.; Cheng, LZ (reprint author), Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Baltimore, MD 21205 USA.; Lin, S (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.; Wang, HY (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.; Wei, WS (reprint author), Peking Univ, CLS, ICG, BIOPIC, Beijing 100871, Peoples R China.; Wei, WS (reprint author), Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
EM LCheng2@jhmi.edu; shuolin@g.ucla.edu; wswei@pku.edu.cn;
wanghaoyi@ioz.ac.cn
NR 0
TC 2
Z9 2
U1 3
U2 3
PU HIGHER EDUCATION PRESS
PI BEIJING
PA NO 4 DEWAI DAJIE, BEIJING 100120, PEOPLES R CHINA
SN 1674-800X
EI 1674-8018
J9 PROTEIN CELL
JI Protein Cell
PD DEC
PY 2016
VL 7
IS 12
BP 913
EP 915
DI 10.1007/s13238-016-0343-9
PG 3
WC Cell Biology
SC Cell Biology
GA EH0DB
UT WOS:000391431600008
PM 27848216
ER
PT J
AU Lai, YT
Hura, GL
Dyer, KN
Tang, HYH
Tainer, JA
Yeates, TO
AF Lai, Yen-Ting
Hura, Greg L.
Dyer, Kevin N.
Tang, Henry Y. H.
Tainer, John A.
Yeates, Todd O.
TI Designing and defining dynamic protein cage nanoassemblies in solution
SO SCIENCE ADVANCES
LA English
DT Article
ID X-RAY-SCATTERING; BIOLOGICAL MACROMOLECULES; SAXS; ASSEMBLIES;
CONFORMATIONS; SYSTEM; FLEXIBILITY; ACQUISITION; COMPUTATION; SOFTWARE
AB Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. We created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage. The monomeric unit is composed of a trimerizing apex-forming domain genetically linked to an edge-forming dimerizing domain. Enhancing the crystallographic results, high-throughput small-angle x-ray scattering (SAXS) comprehensively contrasted our modifications under diverse solution conditions. To generate a phase diagram associating structure and assembly, we developed force plots that measure dissimilarity among multiple SAXS data sets. These new tools, which provided effective feedback on experimental constructs relative to design, have general applicability in analyzing the solution behavior of heterogeneous nanosystems and have been made available as a web-based application. Specifically, our results probed the influence of solution conditions and symmetry on stability and structural adaptability, identifying the dimeric interface as the weak point in the assembly. Force plots comparing SAXS data sets further reveal more complex and controllable behavior in solution than captured by our crystal structures. These methods for objectively and comprehensively comparing SAXS profiles for systems critically affected by solvent conditions and structural heterogeneity provide an enabling technology for advancing the design and bioengineering of nanoscale biological materials.
C1 [Lai, Yen-Ting; Yeates, Todd O.] Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Los Angeles, CA 90095 USA.
[Hura, Greg L.; Dyer, Kevin N.; Tang, Henry Y. H.; Tainer, John A.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
[Hura, Greg L.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
[Tainer, John A.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
[Yeates, Todd O.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Yeates, Todd O.] Univ Calif Los Angeles, California NanoSyst Inst, Los Angeles, CA 90095 USA.
[Lai, Yen-Ting] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Yeates, TO (reprint author), Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Los Angeles, CA 90095 USA.; Tainer, JA (reprint author), Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.; Tainer, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.; Yeates, TO (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.; Yeates, TO (reprint author), Univ Calif Los Angeles, California NanoSyst Inst, Los Angeles, CA 90095 USA.
EM jatainer@lbl.gov; yeates@mbi.ucla.edu
FU NSF [CHE-1332907]; BER program of the DOE Office of Science
[DE-FC02-02ER63421]; Robert A. Welch Distinguished Chair in Chemistry;
Cancer Prevention and Research Institute of Texas; University of Texas
FX This work was supported by NSF grant CHE-1332907 (T.O.Y.) and by the BER
program of the DOE Office of Science (DE-FC02-02ER63421). J.A.T. is
supported by the Robert A. Welch Distinguished Chair in Chemistry.
J.A.T. acknowledges startup funds from the Cancer Prevention and
Research Institute of Texas, and the University of Texas STARs program.
NR 48
TC 0
Z9 0
U1 6
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 2375-2548
J9 SCI ADV
JI Sci. Adv.
PD DEC
PY 2016
VL 2
IS 12
AR e1501855
DI 10.1126/sciadv.1501855
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG7XC
UT WOS:000391268800001
PM 27990489
ER
PT J
AU Morgan, SJ
Neumann, S
Marcus-Samuels, B
Gershengorn, MC
AF Morgan, Sarah J.
Neumann, Susanne
Marcus-Samuels, Bernice
Gershengorn, Marvin C.
TI Thyrotropin and Insulin-Like Growth Factor 1 Receptor Crosstalk
Upregulates Sodium-Iodide Symporter Expression in Primary Cultures of
Human Thyrocytes
SO THYROID
LA English
DT Article
DE cAMP; sodium-iodide symporter; TSHR; IGF-1R
ID RAT-THYROID CELLS; AIRWAY SMOOTH-MUSCLE; VASODILATOR-STIMULATED
PHOSPHOPROTEIN; THYROGLOBULIN GENE-EXPRESSION; PROTEIN-COUPLED RECEPTOR;
INTACT HUMAN PLATELETS; FACTOR-I RECEPTORS; SODIUM/IODIDE SYMPORTER;
FRTL-5 CELLS; SIGNALING PATHWAYS
AB Background: Major regulation of thyroid gland function is mediated by thyrotropin (TSH) activating the TSH receptor (TSHR) and inducing upregulation of genes involved in thyroid hormone synthesis. Evidence suggests that the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) may play a role in regulating TSHR functional effects. This study examined the potential role of TSHR/IGF-1R crosstalk in primary cultures of human thyrocytes. Results: TSH/IGF-1 co-treatment elicited additive effects on thyroglobulin (TG), thyroperoxidase (TPO), and deiodinase type 2 (DIO2) mRNA levels but synergistic effects on sodium-iodide symporter (NIS) mRNA. Similar cooperativity was seen on the level of TG protein secretion (additive) and NIS protein expression (synergistic). The IGF-1R tyrosine kinase inhibitor linsitinib inhibited TSH-stimulated upregulation of NIS but not TG, indicating that NIS regulation is in part IGF-1R dependent and occurs via receptor crosstalk. Cooperativity was not seen at the level of cAMP/protein kinase A (PKA) signaling, IGF-1R phosphorylation, or Akt activation. However, TSH and IGF-1 synergistically activated ERK1/2. Pharmacological inhibition of ERK1/2 by the MEK1/2 inhibitor U0126 and of Akt by MK-2206 virtually abolished NIS stimulation by TSH and the synergistic effect of IGF-1. Conclusion: As linsitinib inhibited upregulation of NIS stimulated by TSH alone, it is concluded that crosstalk between TSHR and IGF-1R, without agonist activation of IGF-1R, plays a role in NIS regulation in human thyrocytes via a mechanism involving ERK1/2 and/or Akt. Fully understanding the nature of this crosstalk has clinical implications for the treatment of thyroid diseases, including thyroid cancer.
C1 [Morgan, Sarah J.; Neumann, Susanne; Marcus-Samuels, Bernice; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD USA.
RP Gershengorn, MC (reprint author), NIDDK, Bldg SO,Room 4134 50 South Dr, Bethesda, MD 20892 USA.
EM marving@mail.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health [Z01
DK011006]
FX We thank Monica Skarulis and Brent Abel from the Diabetes,
Endocrinology, and Obesity Branch for providing human thyroid tissue.
This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (Z01 DK011006).
NR 46
TC 1
Z9 1
U1 4
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD DEC
PY 2016
VL 26
IS 12
BP 1794
EP 1803
DI 10.1089/thy.2016.0323
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG8OF
UT WOS:000391315800018
PM 27638195
ER
PT J
AU Solari, N
Gipponi, M
Franco, DC
Re, F
Sonia, O
Bertoglio, S
Cafiero, F
AF Solari, Nicola
Gipponi, Marco
Franco, Di Somma Carmine
Re, Francesca
Sonia, Olcese
Bertoglio, Sergio
Cafiero, Ferdinando
TI Videoscopic Inguinal-iliac-obturator Lymph-node Dissection: New
Videoscopic Technique for Regional Lymphadenectomy in Patients with
Melanoma
SO ANTICANCER RESEARCH
LA English
DT Article
ID BLADDER-CANCER; PELVIC LYMPHADENECTOMY; MALIGNANT-MELANOMA; SENTINEL;
IMPACT; RATIO; SURVIVAL; EXTENT; GROIN
AB Aim: The feasibility of videoscopic inguinal-iliacobturator lymphadenectomy (VIIOL) was assessed in 20 patients with melanoma and compared with a retrospective sample of 24 patients undergoing standard 'open' technique (HOL). Results: No postoperative death occurred; the mean operative time was lower in the IIOL series (190 min vs. 302 min) but the quality of life was greatly improved in the VIIOL group thanks to earlier bladder catheter removal, no nasogastric suction, less pain, earlier mobilization, lower in hospital stay, and earlier resumption of daily activities (27.6 vs. 83.2 days, p<0.001). Six out of 20 patients in the IIOL series had wound complications (30%) as compared to one in the VIIOL series (4%) (p=0.035). Conclusion: Staging and therapeutic efficacy of VIIOL were similar to the standard technique; the longer operative time of VIIOL was greatly compensated by less pain, lower wound complication rate, and earlier discharge from hospital and recovery of daily activities.
C1 [Solari, Nicola; Franco, Di Somma Carmine; Re, Francesca; Sonia, Olcese; Bertoglio, Sergio; Cafiero, Ferdinando] San Martino Hosp, Surg Unit 1, Genoa, Italy.
[Solari, Nicola; Gipponi, Marco; Franco, Di Somma Carmine; Re, Francesca; Sonia, Olcese; Bertoglio, Sergio; Cafiero, Ferdinando] Natl Canc Inst, Genoa, Italy.
[Gipponi, Marco] Univ Genoa, San Martino Hosp, Breast Unit, Sch Med, Genoa, Italy.
[Bertoglio, Sergio] Univ Genoa, Dept Surg Sci DISC, Sch Med, Genoa, Italy.
RP Gipponi, M (reprint author), IRCCS San Martino IST, Breast Unit, Lgo R Benzi 10, I-16132 Genoa, Italy.
EM marco.gipponi@hsanmartino.it
NR 21
TC 0
Z9 0
U1 1
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD DEC
PY 2016
VL 36
IS 12
BP 6579
EP 6583
DI 10.21873/anticanres.11262
PG 5
WC Oncology
SC Oncology
GA EG3LW
UT WOS:000390946700048
PM 27919986
ER
PT J
AU Miller, BF
Sanchez-Vega, F
Elnitski, L
AF Miller, Brendan F.
Sanchez-Vega, Francisco
Elnitski, Laura
TI The Emergence of Pan-Cancer CIMP and Its Elusive Interpretation
SO BIOMOLECULES
LA English
DT Review
DE pan-cancer; CpG island methylator phenotype; DNA methylation
ID ISLAND METHYLATOR PHENOTYPE; ACUTE LYMPHOBLASTIC-LEUKEMIA;
TUMOR-SUPPRESSOR GENES; CELL LUNG-CANCER; DNA METHYLATION;
CLINICOPATHOLOGICAL FEATURES; MICROSATELLITE INSTABILITY;
HEPATOCELLULAR-CARCINOMA; PROMOTER METHYLATION; COLORECTAL-CANCER
AB Epigenetic dysregulation is recognized as a hallmark of cancer. In the last 16 years, a CpG island methylator phenotype (CIMP) has been documented in tumors originating from different tissues. However, a looming question in the field is whether or not CIMP is a pan-cancer phenomenon or a tissue-specific event. Here, we give a synopsis of the history of CIMP and describe the pattern of DNA methylation that defines the CIMP phenotype in different cancer types. We highlight new conceptual approaches of classifying tumors based on CIMP in a cancer type-agnostic way that reveal the presence of distinct CIMP tumors in a multitude of The Cancer Genome Atlas (TCGA) datasets, suggesting that this phenotype may transcend tissue-type specificity. Lastly, we show evidence supporting the clinical relevance of CIMP-positive tumors and suggest that a common CIMP etiology may define new mechanistic targets in cancer treatment.
C1 [Miller, Brendan F.; Elnitski, Laura] NHGRI, Rockville, MD 20852 USA.
[Sanchez-Vega, Francisco] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
RP Elnitski, L (reprint author), NHGRI, Rockville, MD 20852 USA.
EM millerbf2@mail.nih.gov; sanchezf@cbio.mskcc.org; elnitski@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute
FX We would like to thank Kristin Harper and Yun-Ching Chen for helpful
discussions, edits, and useful feedback during the writing of this
piece. This work was supported by the Intramural Research Program of the
National Human Genome Research Institute.
NR 91
TC 0
Z9 0
U1 0
U2 0
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD DEC
PY 2016
VL 6
IS 4
AR 45
DI 10.3390/biom6040045
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EG4BZ
UT WOS:000390989700007
ER
PT J
AU Anandi, P
Tian, X
Chinian, F
Cantilena, CR
Dunavin, N
Hensel, N
Draper, D
Koklanaris, E
Maxwell, S
Superata, J
Muranski, P
Battiwalla, M
Paczesny, S
Barrett, AJ
Ito, S
AF Anandi, P.
Tian, X.
Chinian, F.
Cantilena, C. R.
Dunavin, N.
Hensel, N.
Draper, D.
Koklanaris, E.
Maxwell, S.
Superata, J.
Muranski, P.
Battiwalla, M.
Paczesny, S.
Barrett, A. J.
Ito, S.
TI Improved reproducibility and quality of GvHD biomarker assay:
application of multiplex microfluidic channel system
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID VERSUS-HOST-DISEASE; CELL TRANSPLANTATION
C1 [Anandi, P.; Chinian, F.; Cantilena, C. R.; Dunavin, N.; Hensel, N.; Draper, D.; Koklanaris, E.; Maxwell, S.; Superata, J.; Muranski, P.; Battiwalla, M.; Barrett, A. J.; Ito, S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, X.] NHLBI, Off Biostat Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Paczesny, S.] Indiana Univ Sch Med, Dept Pediat, Herman B Wells Ctr Pediat, Indianapolis, IN 46202 USA.
RP Ito, S (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM itos2@nhlbi.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD DEC
PY 2016
VL 51
IS 12
BP 1615
EP 1616
DI 10.1038/bmt.2016.226
PG 2
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA EG0YY
UT WOS:000390759600016
PM 27595279
ER
PT J
AU Gatti-Mays, ME
Manion, M
Bowen, LN
Brown, GT
Danner, RL
Khan, O
Nath, A
Battiwalla, M
Barrett, AJ
Ito, S
AF Gatti-Mays, M. E.
Manion, M.
Bowen, L. N.
Brown, G. T.
Danner, R. L.
Khan, O.
Nath, A.
Battiwalla, M.
Barrett, A. J.
Ito, S.
TI Toxoplasmosis encephalitis with immune-reconstitution inflammatory
syndrome in an allogeneic stem cell transplant patient: a case report
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID BONE-MARROW-TRANSPLANTATION; OF-THE-LITERATURE; INFECTION;
INTERLEUKIN-2; THERAPY; TRIAL
C1 [Gatti-Mays, M. E.; Brown, G. T.] NCI, NIH, Bethesda, MD 20892 USA.
[Manion, M.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bowen, L. N.; Khan, O.; Nath, A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Danner, R. L.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Battiwalla, M.; Barrett, A. J.; Ito, S.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Gatti-Mays, ME (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM Margaret.gatti-mays@nih.gov
NR 15
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD DEC
PY 2016
VL 51
IS 12
BP 1622
EP 1624
DI 10.1038/bmt.2016.230
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA EG0YY
UT WOS:000390759600019
PM 27643867
ER
PT J
AU Ramamurthi, KS
AF Ramamurthi, Kumaran S.
TI Editorial overview: Growth and development: prokaryotes
SO CURRENT OPINION IN MICROBIOLOGY
LA English
DT Editorial Material
C1 [Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NCI, Bldg 37, Bethesda, MD 20892 USA.
RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, NCI, Bldg 37, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1369-5274
EI 1879-0364
J9 CURR OPIN MICROBIOL
JI Curr. Opin. Microbiol.
PD DEC
PY 2016
VL 34
BP VII
EP VIII
DI 10.1016/j.mib.2016.159.001
PG 2
WC Microbiology
SC Microbiology
GA EG3TM
UT WOS:000390967600002
PM 27720364
ER
PT J
AU Orr, MW
Galperin, MY
Lee, VT
AF Orr, Mona W.
Galperin, Michael Y.
Lee, Vincent T.
TI Sustained sensing as an emerging principle in second messenger signaling
systems
SO CURRENT OPINION IN MICROBIOLOGY
LA English
DT Review
ID CYCLIC-DI-GMP; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI;
BINDING-PROTEIN; VIBRIO-CHOLERAE; BACTERIAL 2ND-MESSENGER; DIGUANYLATE
CYCLASE; PILZ DOMAIN; EXOPOLYSACCHARIDE PRODUCTION;
CLOSTRIDIUM-DIFFICILE
AB Bacteria utilize a diverse set of nucleotide second messengers to regulate cellular responses by binding macromolecular receptors (RNAs and proteins). Recent studies on cyclic di-GMP (c-di-GMP) have shown that this signaling molecule binds multiple receptors to regulate different steps in the same biological process. We propose this property of the same molecule regulating multiple steps in the same process is biologically meaningful and have termed this phenomenon `sustained sensing'. Here, we discuss the recent findings that support the concept of sustained sensing of c-di-GMP levels and provide additional examples that support the utilization of sustained sensing by other second messengers. Sustained sensing may be widespread in bacteria and provides an additional level of complexity in prokaryotic signal transduction networks.
C1 [Orr, Mona W.; Lee, Vincent T.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Orr, Mona W.; Lee, Vincent T.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
[Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Lee, VT (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
EM vtlee@umd.edu
OI Lee, Vincent T./0000-0002-3593-0318
FU NIH Intramural Research Program at the National Library of Medicine; NIH
[R01 AI110740]
FX M.Y.G. was supported by the NIH Intramural Research Program at the
National Library of Medicine. V.T.L. was supported by a grant from the
NIH (R01 AI110740). We thank Dr. Richard Stewart for critical reading of
the manuscript.
NR 65
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U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1369-5274
EI 1879-0364
J9 CURR OPIN MICROBIOL
JI Curr. Opin. Microbiol.
PD DEC
PY 2016
VL 34
BP 119
EP 126
DI 10.1016/j.mib.2016.08.010
PG 8
WC Microbiology
SC Microbiology
GA EG3TM
UT WOS:000390967600020
PM 27700990
ER
PT J
AU Mayer, ML
AF Mayer, Mark L.
TI Structural biology of glutamate receptor ion channel complexes
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID N-TERMINAL DOMAIN; MEMBRANE-PROTEINS; CRYO-EM; KAINATE RECEPTORS;
CRYSTAL-STRUCTURE; AMPA; MECHANISM; ACTIVATION; DESENSITIZATION; LIGAND
AB Chemical transmission at excitatory synapses in the brain is mediated by a diverse family of glutamate receptor ion channels (iGluRs), tetrameric membrane protein assemblies of molecular weight 400-600 kDa. Until recently, structural information for intact iGluRs was limited to biochemically tractable homomeric receptors trapped in different conformational states. These provided key insights into the mechanisms of iGluR activation and desensitization. Structures of heteromeric AMPA and NMDA receptors, the major iGluR families in the brain, together with long awaited cryo-EM structures of an AMPA receptor TARP complex, expand this picture and reveal surprising conformational diversity, raising many fundamental and controversial questions.
C1 [Mayer, Mark L.] NINDS, Porter Neurosci Res Ctr, DHHS, NIH, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NINDS, Porter Neurosci Res Ctr, DHHS, NIH, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov
FU Intramural Research Program of NINDS
FX I thank Eric Gouaux and Hiro Furukawa and for sharing coordinates, maps
and manuscripts prior to publication, and the Intramural Research
Program of NINDS for proving support.
NR 42
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Z9 2
U1 4
U2 4
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD DEC
PY 2016
VL 41
BP 119
EP 127
DI 10.1016/j.sbi.2016.07.002
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EG3TJ
UT WOS:000390967300016
PM 27454049
ER
PT J
AU Subramaniam, S
Earl, LA
Falconieri, V
Milne, JLS
Egelman, EH
AF Subramaniam, Sriram
Earl, Lesley A.
Falconieri, Veronica
Milne, Jacqueline L. S.
Egelman, Edward H.
TI Resolution advances in cryo-EM enable application to drug discovery
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID U4/U6.U5 TRI-SNRNP; ANGSTROM RESOLUTION; ELECTRON CRYOMICROSCOPY;
CRYOELECTRON MICROSCOPY; ATOMIC-STRUCTURE; TRPV1 STRUCTURES; MECHANISM;
ACTIVATION; INHIBITION; REVEALS
AB The prospect that the structures of protein assemblies, small and large, can be determined using cryo-electron microscopy (cryo-EM) is beginning to transform the landscape of structural biology and cell biology. Great progress is being made in determining 3D structures of biological assemblies ranging from icosahedral viruses and helical arrays to small membrane proteins and protein complexes. Here, we review recent advances in this field, focusing especially on the emerging use of cryo-EM in mapping the binding of drugs and inhibitors to protein targets, an application that requires structure determination at the highest possible resolutions. We discuss methods used to evaluate the information contained in cryoEM density maps and consider strengths and weaknesses of approaches currently used to measure map resolution.
C1 [Subramaniam, Sriram; Earl, Lesley A.; Falconieri, Veronica; Milne, Jacqueline L. S.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Egelman, Edward H.] Univ Virginia, Charlottesville, VA 22908 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health (NIH); NIH [GM035269]
FX We would like to thank Ardan Patwardhan from the Electron Microscopy
Data Bank for assistance with collating EMDB data. This work was
supported by the intramural program of the Center for Cancer Research,
National Cancer Institute, National Institutes of Health (NIH) and by
NIH GM035269 (to E.H.E.).
NR 58
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U1 10
U2 10
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD DEC
PY 2016
VL 41
BP 194
EP 202
DI 10.1016/j.sbi.2016.07.009
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EG3TJ
UT WOS:000390967300025
PM 27552081
ER
PT J
AU Liao, TJ
Tsai, CJ
Jang, H
Fushman, D
Nussinov, R
AF Liao, Tsung-Jen
Tsai, Chung-Jung
Jang, Hyunbum
Fushman, David
Nussinov, Ruth
TI RASSF5: An MST activator and tumor suppressor in vivo but opposite in
vitro
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID REGULATES C-MYC; K-RAS; SARAH DOMAINS; HIPPO PATHWAY; THERAPEUTIC
TARGET; CELL-PROLIFERATION; PANCREATIC-CANCER; SIGNALING PATHWAY;
STRUCTURAL BASIS; PROTEIN-KINASE
AB Is RASSF5 a tumor suppressor or activator? RASSF5 links K Ras and the Hippo pathway. Hippo's signaling promotes YAP1 phosphorylation and degradation. YAP1 overexpression promotes cancer. Most reports point to RASSF5 suppressing cancer; however, some point to its promoting cancer. Our mechanistic view explains how RASSF5 can activate MST1/2 and suppress cancer in vivo; but inhibits MST1/2 in vitro. We propose that both activation and inhibition of MST1/2 can take place via SARAH heterodimerization. Our thesis in vivo, membrane-anchored Ras dimers (or nanoclusters) can promote SARAH domain heterodimerization, Raf-like MST1/2 kinase domain homodimerization and transautophosphorylation. In contrast, in vitro, K-Ras binding also releases the RASSF5 SARAH stimulating MST1/2's SARAH heterodimerization; however, without membrane, no MST1/2 kinase domain homodimerization/trans-autophosphorylation.
C1 [Liao, Tsung-Jen; Tsai, Chung-Jung; Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Liao, Tsung-Jen; Fushman, David] Univ Maryland, Biophys Program, College Pk, MD 20742 USA.
[Fushman, David] Univ Maryland, Ctr Biomol Struct & Org, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
EM nussinor@helix.nih.gov
FU NIH [GM065334]; Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]; Intramural Research
Program of NIH, Frederick National Lab, Center for Cancer Research
FX This work has been supported by NIH grant GM065334 (to DF). This project
has been funded in whole or in part with Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN261200800001E. This research was supported
(in part) by the Intramural Research Program of NIH, Frederick National
Lab, Center for Cancer Research. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the US Government.
NR 69
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U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD DEC
PY 2016
VL 41
BP 217
EP 224
DI 10.1016/j.sbi.2016.09.001
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EG3TJ
UT WOS:000390967300028
PM 27643882
ER
PT J
AU Yun, JS
Lim, TS
Cha, SA
Ahn, YB
Song, KH
Choi, JA
Kwon, J
Jee, D
Cho, YK
Park, YM
Ko, SH
AF Yun, Jae-Seung
Lim, Tae-Seok
Cha, Seon-Ah
Ahn, Yu-Bae
Song, Ki-Ho
Choi, Jin A.
Kwon, Jinwoo
Jee, Donghyun
Cho, Yang Kyung
Park, Yong-Moon
Ko, Seung-Hyun
TI Clinical Course and Risk Factors of Diabetic Retinopathy in Patients
with Type 2 Diabetes Mellitus in Korea
SO DIABETES & METABOLISM JOURNAL
LA English
DT Article
DE Diabetes mellitus, type 2; Diabetic retinopathy; Risk factors
ID CARDIOVASCULAR-DISEASE; GLYCEMIC VARIABILITY; SERUM-CHOLESTEROL;
CONTROLLED-TRIAL; MACULAR EDEMA; PROGRESSION; ASSOCIATION; PREVALENCE;
COMPLICATIONS; EYE
AB Background: We investigated clinical course and risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
Methods: A total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales.
Results: Of the 759 patients, 523 patients (68.9%) completed the follow-up evaluation. During the follow-up period, 235 patients (44.9%) developed DR, and 32 patients (13.6%) progressed to severe nonproliferative DR (NPDR) or proliferative DR (PDR). The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c), and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P= 0.005).
Conclusion: This prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.
C1 [Yun, Jae-Seung; Lim, Tae-Seok; Cha, Seon-Ah; Ahn, Yu-Bae; Ko, Seung-Hyun] Catholic Univ Korea, St Vincents Hosp, Div Endocrinol & Metab, Dept Internal Med,Coll Med, 93 Jungbu Daero, Suwon 16247, South Korea.
[Song, Ki-Ho] Catholic Univ Korea, Yeouido St Marys Hosp, Div Endocrinol & Metab, Dept Internal Med,Coll Med, Seoul, South Korea.
[Choi, Jin A.; Kwon, Jinwoo; Jee, Donghyun; Cho, Yang Kyung] Catholic Univ Korea, St Vincents Hosp, Dept Ophthalmol, Coll Med, Suwon, South Korea.
[Park, Yong-Moon] NIEHS, Epidemiol Branch, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Ko, SH (reprint author), Catholic Univ Korea, St Vincents Hosp, Div Endocrinol & Metab, Dept Internal Med,Coll Med, 93 Jungbu Daero, Suwon 16247, South Korea.
EM kosh@catholic.ac.kr
NR 45
TC 0
Z9 0
U1 1
U2 1
PU KOREAN DIABETES ASSOC
PI SEOUL
PA 1010 RENAISSANCE TOWER BLDG, 14 MANRIJAE-RO, MAPO-GUO, SEOUL, 121-706,
SOUTH KOREA
SN 2233-6079
EI 2233-6087
J9 DIABETES METAB J
JI Diabetes Metab. J.
PD DEC
PY 2016
VL 40
IS 6
BP 482
EP 492
DI 10.4093/dmj.2016.40.6.482
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3GF
UT WOS:000390931100008
PM 27766793
ER
PT J
AU Bogoslovsky, T
Gill, J
Jeromin, A
Davis, C
Diaz-Arrastia, R
AF Bogoslovsky, Tanya
Gill, Jessica
Jeromin, Andreas
Davis, Cora
Diaz-Arrastia, Ramon
TI Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use
SO DIAGNOSTICS
LA English
DT Review
DE traumatic brain injury (TBI); biomarkers; TBI management
ID FIBRILLARY ACIDIC PROTEIN; C-TERMINAL HYDROLASE-L1; DIFFUSE AXONAL
INJURY; GLASGOW COMA SCALE; NEURON-SPECIFIC ENOLASE; SURROGATE
END-POINTS; ICE HOCKEY PLAYERS; MINOR HEAD-INJURY; CEREBROSPINAL-FLUID;
POSTCONCUSSION SYNDROME
AB Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind.
C1 [Bogoslovsky, Tanya; Davis, Cora] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Rockville, MD 20856 USA.
[Gill, Jessica] NINR, NIH, Bethesda, MD 20814 USA.
[Jeromin, Andreas] Quanterix Inc, Lexington, MA 02421 USA.
[Diaz-Arrastia, Ramon] Univ Penn, Dept Neurol, Traumat Brain Injury Clin Res Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Bogoslovsky, T (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Rockville, MD 20856 USA.
EM tanya.bogoslovsky.ctr@usuhs.edu; jessica.gill@nih.gov;
ajeromin@quanterix.com; cora.davis.ctr@usuhs.edu;
ramondia@mail.med.upenn.edu
FU Center for Neuroscience and Regenerative Medicine (CNRM)
FX This work was supported by the Center for Neuroscience and Regenerative
Medicine (CNRM).
NR 123
TC 0
Z9 0
U1 4
U2 4
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2075-4418
J9 DIAGNOSTICS
JI Diagnostics
PD DEC
PY 2016
VL 6
IS 4
AR 37
DI 10.3390/diagnostics6040037
PG 22
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG3HY
UT WOS:000390935700002
ER
PT J
AU Luk, JW
Worley, MJ
Winiger, E
Trim, RS
Hopfer, CJ
Hewitt, JK
Brown, SA
Wall, TL
AF Luk, Jeremy W.
Worley, Matthew J.
Winiger, Evan
Trim, Ryan S.
Hopfer, Christian J.
Hewitt, John K.
Brown, Sandra A.
Wall, Tamara L.
TI Risky driving and sexual behaviors as developmental outcomes of
co-occurring substance use and antisocial behavior
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Substance use; Antisocial behavior; Risky driving; Sexual transmitted
infections; Injection drug use
ID DIAGNOSTIC INTERVIEW SCHEDULE; YOUNG ADULTHOOD; UNITED-STATES;
EXTERNALIZING SPECTRUM; PSYCHIATRIC-DISORDERS; ALCOHOL-USE; DRUG-USE;
ADOLESCENT; ASSOCIATION; PERSONALITY
AB Purpose: To examine the associations between substance use and antisocial behavior trajectories and seven risky behaviors over time.
Method: Data were collected from a high-risk sample of adolescents followed into young adulthood. Five trajectory classes, identified based on dual development of substance use and antisocial behavior symptoms, were used to predict three risky driving and four risky sexual behaviors.
Results: In this high-risk sample (n = 530), participants reported notably high overall rates of reckless driving (55.5%) and unprotected sex under the influence (44.8%) in the past year. Risky behaviors that are typically of low base rates in population-based studies were also elevated, with 8.8% reporting past-year driving under the influence (DUI) charge, 17.6% reporting lifetime sexually transmitted infection (STI), and 10.4% reporting lifetime injection drug use. The Dual Chronic class had the highest levels of all seven risky behaviors, and were 3-4 times more likely to report risky driving, lifetime STI, and injection drug use than the Relatively Resolved class. Rates of past-year reckless driving and DUI were elevated among classes with persistent antisocial behavior, whereas rates of DUI, DUI charge, and unprotected sex under the influence were elevated among classes with persistent substance use.
Conclusions: Young adults with persistent co-occurring substance use and antisocial behavior engage in multiple very costly risky behaviors. Differential associations between risky behaviors and trajectory classes highlight the need for targeted interventions. Published by Elsevier Ireland Ltd.
C1 [Luk, Jeremy W.; Worley, Matthew J.; Winiger, Evan; Trim, Ryan S.; Brown, Sandra A.; Wall, Tamara L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Worley, Matthew J.; Trim, Ryan S.; Wall, Tamara L.] VA San Diego Hlth Syst, La Jolla, CA USA.
[Hopfer, Christian J.] Univ Colorado, Dept Psychiat, Denver, CO 80202 USA.
[Hewitt, John K.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Luk, Jeremy W.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Bethesda, MD 20817 USA.
[Luk, Jeremy W.] 6710B Rockledge Dr,Room 3155A,MSC 7004, Bethesda, MD 20817 USA.
RP Wall, TL (reprint author), Univ Calif San Diego, 3350 La Jolla Village Dr 116B, San Diego, CA 92161 USA.
EM j2luk@ucsd.edu; twall@ucsd.edu
FU National Institute of Drug Abuse [R01 DA035804, R01 DA021905, R01
DA012845, F31 DA030861, P60 DA011015, R01 DA021913, R01 DA015522];
National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R37 AA07033,
T32 AA013525]; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development
FX This research was supported by National Institute of Drug Abuse grants
R01 DA035804 (PIs: Hopfer, Stallings, & Wall), R01 DA021905 (PIs: Brown
& Wall), R01 DA012845 (PI: Hewitt), F31 DA030861 (PI: Worley), P60
DA011015 (PI: Hewitt), R01 DA021913 (PI: Hopfer), R01 DA015522 (PI:
Hopfer), and National Institute on Alcohol Abuse and Alcoholism (NIAAA)
grants R37 AA07033 (PI: Brown) and T32 AA013525 (PI: Riley). This work
was also supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development. The content of this manuscript is solely the responsibility
of the authors. The sponsoring agencies had no role in the design,
analyses, or writing of this paper, or the decision to submit this paper
for publication.
NR 40
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD DEC 1
PY 2016
VL 169
BP 19
EP 25
DI 10.1016/j.drugalcdep.2016.10.006
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA EG3SO
UT WOS:000390965200004
PM 27750183
ER
PT J
AU Feaster, DJ
Parish, CL
Gooden, L
Matheson, T
Castellon, PC
Duan, R
Pan, Y
Haynes, LF
Schackman, BR
Malotte, CK
Mandler, RN
Colfax, GN
Metsch, LR
AF Feaster, Daniel J.
Parish, Carrigan L.
Gooden, Lauren
Matheson, Tim
Castellon, Pedro C.
Duan, Rui
Pan, Yue
Haynes, Louise F.
Schackman, Bruce R.
Malotte, C. Kevin
Mandler, Raul N.
Colfax, Grant N.
Metsch, Lisa R.
TI Substance use and STI acquisition: Secondary analysis from the AWARE
study
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Sexually transmitted infections; Substance use; Substance use treatment;
Gender differences
ID SEXUALLY-TRANSMITTED INFECTIONS; NEW-YORK-CITY; HETEROSEXUAL
METHAMPHETAMINE USERS; NATIONAL EPIDEMIOLOGIC SURVEY; RANDOMIZED
CLINICAL-TRIAL; RISK REDUCTION GROUPS; LOS-ANGELES-COUNTY; HIV-POSITIVE
GAY; DRUG-USE; UNITED-STATES
AB Objectives: Sexually transmitted infections (STIs) are significant public health and financial burdens in the United States. This manuscript examines the relationship between substance use and prevalent and incident ST1s in HIV-negative adult patients at STI clinics.
Methods: A secondary analysis of Project AWARE was performed based on 5012 patients from 9 STI clinics. STIs were assessed by laboratory assay and substance use by self-report. Patterns of substance use were assessed using latent class analysis. The relationship of latent class to STI rates was investigated using Poisson regression by population groups at high risk for STIs defined by participant's and partner's gender.
Results: Drug use patterns differed by risk group and substance use was related to STI rates with the relationships varying by risk behavior group. Substance use treatment participation was associated with increased STI rates.
Conclusions: Substance use focused interventions may be useful in STI clinics to reduce morbidity associated with substance use. Conversely, gender-specific sexual health interventions may be useful in substance use treatment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Feaster, Daniel J.; Duan, Rui; Pan, Yue] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, 1120 NW 14th St, Miami, FL 33136 USA.
[Parish, Carrigan L.; Gooden, Lauren; Castellon, Pedro C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, Miami Res Ctr, 1120 NW 14th St, Miami, FL 33136 USA.
[Matheson, Tim; Colfax, Grant N.] San Francisco Dept Publ Hlth, HIV Prevent Sect, 25 Van Ness Ave, San Francisco, CA 94102 USA.
[Haynes, Louise F.] Med Univ South Carolina, Addict Sci Div, 67 President St, Charleston, SC 29425 USA.
[Schackman, Bruce R.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, 425 East 61st St, New York, NY USA.
[Malotte, C. Kevin] Calif State Univ Long Beach, Dept Hlth Sci, Ctr Hlth Care Innovat, 5500 Atherton St, Long Beach, CA USA.
[Mandler, Raul N.] NIDA, NIH, 6000 Execut Blvd, Rockville, MD 20852 USA.
[Metsch, Lisa R.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, 722 W 168th St,9th Floor, New York, NY 10032 USA.
RP Feaster, DJ (reprint author), Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, 1120 NW 14th St, Miami, FL 33136 USA.
EM dfeaster@med.miami.edu; cp2695@columbia.edu; lkg2129@columbia.edu;
Tim.Matheson@sfdph.org; pc2594@columbia.edu; rduan@med.miami.edu;
panyue@med.miami.edu; hayneslf@musc.edu; brs2006@med.cornell.edu;
kmalotte@csulb.edu; mandlerr@nida.nih.gov; grant.colfax@sfdph.org;
lm2892@columbia.edu
FU Office of the Director, National Institutes of Health (OD)
[RC2DA028973]; National Institute on Drug Abuse [R21DA038641,
R01DA027379]; University of Miami Center for AIDS Research (CFAR) [P30
AI073961]
FX This work was supported by the Office of the Director, National
Institutes of Health (OD) (RC2DA028973), and the National Institute on
Drug Abuse (R21DA038641 and R01DA027379). The infrastructure of the
National Drug Abuse Treatment Clinical Trials Network was used as a
platform in conducting the Project AWARE trial (U10DA13720). Support
from the University of Miami Center for AIDS Research (CFAR) is also
acknowledged (P30 AI073961). The NIH had no further role in study
design, in the collection, analysis and interpretation of data; in the
writing of the report; or in the decision to submit the paper for
publication.
NR 80
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD DEC 1
PY 2016
VL 169
BP 171
EP 179
DI 10.1016/j.drugalcdep.2016.10.027
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA EG3SO
UT WOS:000390965200025
PM 27837708
ER
PT J
AU Liang, TJ
AF Liang, T. Jake
TI Hepatitis C Virus: From Obscurity to the Lasker
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID INHIBITOR
C1 [Liang, T. Jake] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD DEC
PY 2016
VL 151
IS 6
BP 1052
EP 1053
DI 10.1053/j.gastro.2016.10.011
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EG3OV
UT WOS:000390955500009
PM 27765691
ER
PT J
AU Schwimmer, JB
Lavine, JE
Wilson, LA
Neuschwander-Tetri, BA
Xanthakos, SA
Kohli, R
Barlow, SE
Vos, MB
Karpen, SJ
Molleston, JP
Whitington, PF
Rosenthal, P
Jain, AK
Murray, KF
Brunt, EM
Kleiner, DE
Van Natta, ML
Clark, JM
Tonascia, J
Doo, E
AF Schwimmer, Jeffrey B.
Lavine, Joel E.
Wilson, Laura A.
Neuschwander-Tetri, Brent A.
Xanthakos, Stavra A.
Kohli, Rohit
Barlow, Sarah E.
Vos, Miriam B.
Karpen, Saul J.
Molleston, Jean P.
Whitington, Peter F.
Rosenthal, Philip
Jain, Ajay K.
Murray, Karen F.
Brunt, Elizabeth M.
Kleiner, David E.
Van Natta, Mark L.
Clark, Jeanne M.
Tonascia, James
Doo, Edward
CA NASH CRN
TI In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate
Delayed Release Improves Liver Enzymes but Does Not Reduce Disease
Activity Scores
SO GASTROENTEROLOGY
LA English
DT Article
DE Pediatrics; ALT; AST; Obesity
ID RANDOMIZED CONTROLLED-TRIAL; ENTERIC-COATED CYSTEAMINE; QUALITY-OF-LIFE;
METABOLIC SYNDROME; OBESE CHILDREN; HEALTHY-ADULTS; RISK-FACTORS;
ADOLESCENTS; PHARMACOKINETICS; ASSOCIATION
AB BACKGROUND & AIMS: No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. METHODS: We performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing <= 65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran-Mantel-Haenszel analysis. RESULTS: There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8-2.1; P = .34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 +/- 88 U/L vs 8 +/- 77 U/L in the placebo group; P = .02) and aspartate aminotransferase (reduction, 31 +/- 52 vs 4 +/- 36 U/L in the placebo group; P = .008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P = .03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P = .005). CONCLUSIONS: In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR, however, had significant reductions in serum aminotransferase levels and lobular inflammation.
C1 [Schwimmer, Jeffrey B.] Univ Calif San Diego, Sch Med, Dept Pediat, Div Gastroenterol Hepatol & Nutr, La Jolla, CA 92093 USA.
[Schwimmer, Jeffrey B.] Rady Childrens Hosp, Dept Gastroenterol, San Diego, CA USA.
[Lavine, Joel E.] Columbia Univ, Dept Pediat, Div Gastroenterol Hepatol & Nutr, New York, NY 10027 USA.
[Lavine, Joel E.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Wilson, Laura A.; Van Natta, Mark L.; Clark, Jeanne M.; Tonascia, James] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Neuschwander-Tetri, Brent A.] St Louis Univ, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA.
[Jain, Ajay K.] St Louis Univ, Dept Pediat, St Louis, MO 63103 USA.
[Xanthakos, Stavra A.; Kohli, Rohit] Cincinnati Childrens Hosp Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.
[Barlow, Sarah E.] Baylor Coll Med, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Barlow, Sarah E.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Vos, Miriam B.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Dept Pediat,Div Gastroenterol Hepatol & Nutr, Atlanta, GA USA.
[Karpen, Saul J.] Emory Univ, Sch Med, Childrens Hlthcare Atlanta, Div Pediat Gastroenterol Hepatol & Nutr,Dept Pedi, Atlanta, GA USA.
[Molleston, Jean P.] Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA.
[Whitington, Peter F.] Northwestern Univ, Feinberg Med Sch, Dept Pediat, Chicago, IL USA.
[Whitington, Peter F.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Rosenthal, Philip] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, Div Gastroenterol Hepatol & Nutr, San Francisco, CA USA.
[Murray, Karen F.] Univ Washington, Sch Med, Dept Pediat, Div Gastroenterol & Hepatol, Seattle, WA 98195 USA.
[Murray, Karen F.] Seattle Childrens, Seattle, WA USA.
[Brunt, Elizabeth M.] Washington Univ St Louis, Dept Pathol, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Bethesda, MD 20892 USA.
[Doo, Edward] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA.
RP Schwimmer, JB (reprint author), Univ Calif San Diego, Div Gastroenterol Hepatol & Nutr, Dept Pediat, 3020 Childrens Way,MC 5030, San Diego, CA 92123 USA.
EM jschwimmer@ucsd.edu
OI kohli, Rohit/0000-0002-0198-7703; Towbin, Alexander/0000-0003-1729-5071;
Cecil, Kim/0000-0001-8233-5485
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Center for
Advancing Translational Sciences [UL1TR000077, UL1TR000150, UL1TR000424,
UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004,
UL1TR000423, UL1TR000454]; Intramural Research Program of the National
Institutes of Health, National Cancer Institute; Raptor Pharmaceuticals;
National Institute of Diabetes and Digestive and Kidney Diseases
FX The Nonalcoholic Steatohepatitis Clinical Research Network is supported
by the National Institute of Diabetes and Digestive and Kidney Diseases
(U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, and U01DK061713). Additional
support was received from the National Center for Advancing
Translational Sciences (UL1TR000077, UL1TR000150, UL1TR000424,
UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004,
UL1TR000423, and UL1TR000454). This research was supported in part by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute. This study also was funded in part by Raptor
Pharmaceuticals via a Collaborative Research and Development Agreement
with the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 35
TC 1
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U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD DEC
PY 2016
VL 151
IS 6
BP 1141
EP +
DI 10.1053/j.gastro.2016.08.027
PG 23
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EG3OV
UT WOS:000390955500029
PM 27569726
ER
PT J
AU Jaramillo-Lambert, A
Fabritius, AS
Hansen, TJ
Smith, HE
Golden, A
AF Jaramillo-Lambert, Aimee
Fabritius, Amy S.
Hansen, Tyler J.
Smith, Harold E.
Golden, Andy
TI The Identification of a Novel Mutant Allele of topoisomerase II in
Caenorhabditis elegans Reveals a Unique Role in Chromosome Segregation
During Spermatogenesis
SO GENETICS
LA English
DT Article
DE top-2; Caenorhabditis elegans; meiosis; spermatogenesis; topoisomerase
II
ID MEIOTIC PROPHASE; COHESIN REMOVAL; GERM-CELLS; MEIOSIS; CONDENSATION;
RECOMBINATION; SYNAPSIS; OOCYTES; SPERMATIDS; SEPARATION
AB Topoisomerase II alleviates DNA entanglements that are generated during mitotic DNA replication, transcription, and sister chromatid separation. In contrast to mitosis, meiosis has two rounds of chromosome segregation following one round of DNA replication. In meiosis II, sister chromatids segregate from each other, similar to mitosis. Meiosis I, on the other hand, segregates homologs, which requires pairing, synapsis, and recombination. The exact role that topoisomerase II plays during meiosis is unknown. In a screen reexamining Caenorhabditis elegans legacy mutants isolated 30 years ago, we identified a novel allele of the gene encoding topoisomerase II, top-2(it7). In this study, we demonstrate that top-2(it7) males produce dead embryos, even when fertilizing wild-type oocytes. Characterization of early embryonic events indicates that fertilization is successful and sperm components are transmitted to the embryo. However, sperm chromatin is not detected in these fertilized embryos. Examination of top-2(it7) spermatogenic germ lines reveals that the sperm DNA fails to segregate properly during anaphase I of meiosis, resulting in anucleate sperm. top-2(it7) chromosome-segregation defects observed during anaphase I are not due to residual entanglements incurred during meiotic DNA replication and are not dependent on SPO-11-induced double-strand DNA breaks. Finally, we show that TOP-2 associates with chromosomes in meiotic prophase and that chromosome association is disrupted in the germ lines of top-2(it7) mutants.
C1 [Jaramillo-Lambert, Aimee; Fabritius, Amy S.; Hansen, Tyler J.; Smith, Harold E.; Golden, Andy] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Jaramillo-Lambert, A (reprint author), NIDDK, Lab Biochem & Genet, NIH, Room 323,Bldg 8,8 Ctr Dr, Bethesda, MD 20892 USA.
EM jaramillolamban@mail.nih.gov
FU National Institutes of Health Office of Research Infrastructure Programs
[P40 OD-010440]; Intramural Research Program of the National Institutes
of Health, National Institute of Diabetes and Digestive and Kidney
Diseases
FX We thank K. Stein for genetic mapping of mel-15(it7ts); A. Chandra for
helping with the mel- 15(it7ts) complementation tests; James Berger for
analysis of TOP-2 protein structure; N. Devaul, R. Meseroll, and A.
Walters for comments on the manuscript; and members of the Baltimore
Worm Club for helpful discussions. We are grateful to Ken Kemphues for
the original isolation and characterization of the mel-15(it7ts) allele,
which inspired this project. Some nematode strains used in this work
were provided by the Caenorhabditis Genetics Center, which is funded by
National Institutes of Health Office of Research Infrastructure Programs
(P40 OD-010440). Some deletion allele strains were generated by the C.
elegans Gene Knockout Consortium at the University of British Columbia
led by D. Moerman. This research was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 62
TC 0
Z9 0
U1 2
U2 2
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD DEC
PY 2016
VL 204
IS 4
BP 1407
EP +
DI 10.1534/genetics.116.195099
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA EG1BD
UT WOS:000390765500012
PM 27707787
ER
PT J
AU Dunleavy, K
Little, RF
Wilson, WH
AF Dunleavy, Kieron
Little, Richard F.
Wilson, Wyndham H.
TI Update on Burkitt Lymphoma
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Burkitt lymphoma; MYC; TCF3; CCND3; ID3; Risk-adapted; Endemic; Sporadic
ID B-CELL LYMPHOMA; PROMOTES GENOMIC INSTABILITY; ACUTE
LYMPHOBLASTIC-LEUKEMIA; MODIFIED CODOX-M/IVAC; NON-HODGKINS-LYMPHOMA;
DOSE-ADJUSTED EPOCH; ADULT BURKITT; LINE AKATA; CHEMOTHERAPY; RITUXIMAB
AB Because of its rarity and high curability, progress in advancing therapeutics in Burkitt lymphoma (BL) has been difficult. Over recent years, several new mutations that cooperate with MYC have been identified, and this has paved the way for testing novel agents in the disease. One of the challenges of most standard approaches typically used is severe treatment related toxicity that often leads to discontinuation of therapy. To that point, there has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting.
C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Little, Richard F.] NCI, HIV & Stem Cell Therapeut, CTEP, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), Lymphoid Malignancies Branch, Bldg 10,Room 12N4114,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
FU NIH HHS [NIH0010513932]
NR 41
TC 0
Z9 0
U1 4
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
EI 1558-1977
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD DEC
PY 2016
VL 30
IS 6
BP 1333
EP +
DI 10.1016/j.hoc.2016.07.009
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA EG3UW
UT WOS:000390971200014
PM 27888884
ER
PT J
AU Pu, J
Guardia, CM
Keren-Kaplan, T
Bonifacino, JS
AF Pu, Jing
Guardia, Carlos M.
Keren-Kaplan, Tal
Bonifacino, Juan S.
TI Mechanisms and functions of lysosome positioning
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Lysosome; Late endosome; Organelle positioning; Organelle motility;
Kinesin; Dynein
ID GTPASE-ACTIVATING PROTEIN; PLASMA-MEMBRANE REPAIR; KINESIN HEAVY-CHAIN;
BREAST-CANCER CELLS; ARF-LIKE GTPASE; LATE ENDOSOMES; PREFERENTIAL
BINDING; CYTOPLASMIC DYNEIN; SECRETORY GRANULES; NONNEURONAL CELLS
AB Lysosomes have been classically considered terminal degradative organelles, but in recent years they have been found to participate in many other cellular processes, including killing of intracellular pathogens, antigen presentation, plasma membrane repair, cell adhesion and migration, tumor invasion and metastasis, apoptotic cell death, metabolic signaling and gene regulation. In addition, lysosome dysfunction has been shown to underlie not only rare lysosome storage disorders but also more common diseases, such as cancer and neurodegeneration. The involvement of lysosomes in most of these processes is now known to depend on the ability of lysosomes to move throughout the cytoplasm. Here, we review recent findings on the mechanisms that mediate the motility and positioning of lysosomes, and the importance of lysosome dynamics for cell physiology and pathology.
C1 [Pu, Jing; Guardia, Carlos M.; Keren-Kaplan, Tal; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
EM bonifacinoj@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU intramural program of National Institute of Child Health and Human
Development (NICHD) [ZIA HD001607]
FX Work in the authors' laboratory is funded by the intramural program of
National Institute of Child Health and Human Development (NICHD) (ZIA
HD001607). Deposited in PMC for release after 12 months.
NR 147
TC 2
Z9 2
U1 7
U2 7
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD DEC 1
PY 2016
VL 129
IS 23
BP 4329
EP 4339
DI 10.1242/jcs.196287
PG 11
WC Cell Biology
SC Cell Biology
GA EG5RS
UT WOS:000391102600003
PM 27799357
ER
PT J
AU Brown, RJ
Araujo-Vilar, D
Cheung, PT
Dunger, D
Garg, A
Jack, M
Mungai, L
Oral, EA
Patni, N
Rother, KI
von Schnurbein, J
Sorkina, E
Stanley, T
Vigouroux, C
Wabitsch, M
Williams, R
Yorifuji, T
AF Brown, Rebecca J.
Araujo-Vilar, David
Cheung, Pik To
Dunger, David
Garg, Abhimanyu
Jack, Michelle
Mungai, Lucy
Oral, Elif A.
Patni, Nivedita
Rother, Kristina I.
von Schnurbein, Julia
Sorkina, Ekaterina
Stanley, Takara
Vigouroux, Corinne
Wabitsch, Martin
Williams, Rachel
Yorifuji, Tohru
TI The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society
Practice Guideline
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID FAMILIAL PARTIAL LIPODYSTROPHY; CONGENITAL GENERALIZED LIPODYSTROPHY;
LEPTIN-REPLACEMENT THERAPY; SEVERE INSULIN-RESISTANCE; FATTY
LIVER-DISEASE; HUTCHINSON-GILFORD PROGERIA; BASE-LINE CHARACTERISTICS;
ENCODING LAMIN A/C; OF-THE-LITERATURE; NONALCOHOLIC STEATOHEPATITIS
AB Objective: Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs.
Participants: Seventeen participants were nominated by worldwide endocrine societies or selected by the committee as content experts. Funding was via an unrestricted educational grant from Astra Zeneca to the Pediatric Endocrine Society. Meetings were not open to the general public.
Evidence: A literature review was conducted by the committee. Recommendations of the committee were graded using the system of the American Heart Association. Expert opinion was used when published data were unavailable or scarce.
Consensus Process: The guideline was drafted by committee members and reviewed, revised, and approved by the entire committee during group meetings. Contributing societies reviewed the document and provided approval.
Conclusions: Lipodystrophy syndromes are heterogeneous and are diagnosed by clinical phenotype, supplemented by genetic testing in certain forms. Patients with most lipodystrophy syndromes should be screened for diabetes, dyslipidemia, and liver, kidney, and heart disease annually. Diet is essential for the management of metabolic complications of lipodystrophy. Metreleptin therapy is effective for metabolic complications in hypoleptinemic patients with generalized lipodystrophy and selected patients with partial lipodystrophy. Other treatments not specific for lipodystrophy may be helpful as well (eg, metformin for diabetes, and statins or fibrates for hyperlipidemia). Oral estrogens are contraindicated.
C1 [Brown, Rebecca J.; Rother, Kristina I.] NIDDK, NIH, Bldg 10 CRC,Room 6-5942,10 Ctr Dr, Bethesda, MD 20892 USA.
[Araujo-Vilar, David] Univ Santiago de Compostela, Dept Med, Santiago De Compostela 15782, Spain.
[Cheung, Pik To] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China.
[Dunger, David] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England.
[Dunger, David] Univ Cambridge, Metab Res Labs Wellcome Trust, Med Res Council,Inst Metab Sci,MRC Epidemiol Unit, Natl Inst Hlth Res,Cambridge Comprehens Biomed Re, Cambridge CB2 0QQ, England.
[Garg, Abhimanyu] UT Southwestern Med Ctr, Div Nutr & Metab Dis, Dept Internal Med, Dallas, TX 75390 USA.
[Garg, Abhimanyu] UT Southwestern Med Ctr, Ctr Human Nutr, Dallas, TX 75390 USA.
[Jack, Michelle] Univ Sydney, Northern Clin Sch, Royal North Shore Hosp, St Leonards, NSW 2126, Australia.
[Mungai, Lucy] Univ Nairobi, Dept Paediat & Child Hlth, Nairobi 00100, Kenya.
[Oral, Elif A.] Univ Michigan Med Sch & Hlth Syst, Brehm Ctr Diabet, Ann Arbor, MI 48109 USA.
[Oral, Elif A.] Univ Michigan Med Sch & Hlth Syst, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
[Patni, Nivedita] UT Southwestern Med Ctr, Div Pediat Endocrinol, Dept Pediat, Dallas, TX 75390 USA.
[von Schnurbein, Julia; Wabitsch, Martin] Univ Ulm, Dept Pediat & Adolescent Med, Div Pediat Endocrinol & Diabet, D-89075 Ulm, Germany.
[Sorkina, Ekaterina] Moscow MV Lomonosov State Univ, Endocrinol Res Ctr, Clamp Technol Lab, Moscow 119991, Russia.
[Sorkina, Ekaterina] Moscow MV Lomonosov State Univ, Med Sci Educ Ctr Lomonosov, Mol Endocrinol Lab, Moscow 119991, Russia.
[Stanley, Takara] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02115 USA.
[Stanley, Takara] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02115 USA.
[Stanley, Takara] Harvard Med Sch, Boston, MA 02115 USA.
[Vigouroux, Corinne] Univ Paris 06, Univ Pierre & Marie Curie,St Antoine Hosp, Sorbonne Univ,Inst Cardiometab & Nutr,AP HP,Mol B, Inserm Unite Mixte Rech Sante 938,St Antoine Res, F-75012 Paris, France.
[Williams, Rachel] Cambridge Univ Hosp NHS Trust, Dept Paediat Endocrinol, Cambridge CB2 0QQ, England.
[Yorifuji, Tohru] Osaka City Gen Hosp, Childrens Med Ctr, Div Pediat Endocrinol & Metab, Osaka 5340021, Japan.
RP Brown, RJ (reprint author), NIDDK, NIH, Bldg 10 CRC,Room 6-5942,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brownrebecca@niddk.nih.gov
OI Sorkina, Ekaterina/0000-0001-7006-0664
FU Pediatric Endocrine Society from AstraZeneca; intramural research
program of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health [RO1-DK088114, RO1-DK105448,
RO1-DK101941]; Sopha Fund for Lipodystrophy Research at the University
of Michigan; Russian Science Foundation [14-35-00026]
FX This practice guideline was sponsored and organized by the Pediatric
Endocrine Society via au unrestricted education grant from AstraZeneca.
Individual authors were supported by the intramural research program of
the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health Grants RO1-DK088114, RO1-DK105448, and
RO1-DK101941; the Sopha Fund for Lipodystrophy Research at the
University of Michigan, and Grant 14-35-00026 of the Russian Science
Foundation.
NR 114
TC 1
Z9 1
U1 2
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD DEC
PY 2016
VL 101
IS 12
BP 4500
EP 4511
DI 10.1210/jc.2016-2466
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3NE
UT WOS:000390951000002
PM 27710244
ER
PT J
AU Nella, AA
Mallappa, A
Perritt, AF
Gounden, V
Kumar, P
Sinaii, N
Daley, LA
Ling, A
Liu, CY
Soldin, SJ
Merke, DP
AF Nella, Aikaterini A.
Mallappa, Ashwini
Perritt, Ashley F.
Gounden, Verena
Kumar, Parag
Sinaii, Ninet
Daley, Lori-Ann
Ling, Alexander
Liu, Chia-Ying
Soldin, Steven J.
Merke, Deborah P.
TI A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in
Adults With Congenital Adrenal Hyperplasia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID QUALITY-OF-LIFE; 21-HYDROXYLASE DEFICIENCY; ADDISONS-DISEASE;
CLINICAL-TRIAL; INSUFFICIENCY; PHARMACOKINETICS; REPLACEMENT; PROFILES;
THERAPY; COHORT
AB Context: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction.
Objective: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH.
Design: Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires.
Main Outcome Measures: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) <= 1200 ng/dL was measured.
Results: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue.
Conclusions: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.
C1 [Nella, Aikaterini A.; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Nella, Aikaterini A.; Mallappa, Ashwini; Perritt, Ashley F.; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J.; Merke, Deborah P.] Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA.
RP Nella, AA (reprint author), Univ Texas Med Branch, Div Pediat Endocrinol, Dept Pediat, Res Bldg 6,Suite 3-270C,301 Univ Blvd, Galveston, TX 77555 USA.
EM ainella@utmb.edu
FU Intramural programs of the National Institutes of Health (NIH) Clinical
Center; Eunice Kennedy Shriver National Institute of Child Health &
Human Development; Diurnal Limited, Ltd. through an NIH Cooperative
Research and Development Agreement
FX This work was supported by the Intramural programs of the National
Institutes of Health (NIH) Clinical Center and the Eunice Kennedy
Shriver National Institute of Child Health & Human Development.
Medtronic Diabetes Company provided the insulin pumpsand supplies
(reservoirs, infusion sets), and also training and technical support
without charge, upon approval of the study by the Institutional Review
Board Committee. D.P.M. received unrelated research funds from Diurnal
Limited, Ltd. through an NIH Cooperative Research and Development
Agreement.
NR 30
TC 0
Z9 0
U1 4
U2 4
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD DEC
PY 2016
VL 101
IS 12
BP 4690
EP 4698
DI 10.1210/jc.2016-1916
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG3NE
UT WOS:000390951000022
PM 27680873
ER
PT J
AU Hayakawa, K
Formica, AM
Brill-Dashoff, J
Shinton, SA
Ichikawa, D
Zhou, Y
Morse, HC
Hardy, RR
AF Hayakawa, Kyoko
Formica, Anthony M.
Brill-Dashoff, Joni
Shinton, Susan A.
Ichikawa, Daiju
Zhou, Yan
Morse, Herbert C., III
Hardy, Richard R.
TI Early generated B1 B cells with restricted BCRs become chronic
lymphocytic leukemia with continued c-Myc and low Bmf expression
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID FAMILY-MEMBER BIM; BH3-ONLY PROTEINS BIM; POSITIVE SELECTION; TRANSGENIC
MICE; AUTOANTIBODY PRODUCTION; B-1 CELLS; CYCLIN D2; V-REGION; MOUSE;
RECEPTOR
AB In mice, generation of autoreactive CD5(+) B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from E mu-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging. Increased anti-thymocyte/Thy-1 autoreactive (ATA) BCR cells in the B1 B cell subset by transgenic expression yielded spontaneous ATA B-CLL/lymphoma incidence, enhanced by TCL1 transgenesis. In contrast, ATA B-CLL did not develop from other B cell subsets, even when the identical ATA BCR was expressed on a Thy-1 low/null background. Thus, both a specific BCR and B1 B cell context were important for CLL progression. Neonatal B1 B cells and their CLL progeny in aged mice continued to express moderately up-regulated c-Myc and down-regulated proapoptotic Bmf, unlike most mature B cells in the adult. Thus, there is a genetic predisposition inherent in B-1 development generating restricted BCRs and self-renewal capacity, with both features contributing to potential for progression to CLL.
C1 [Hayakawa, Kyoko; Formica, Anthony M.; Brill-Dashoff, Joni; Shinton, Susan A.; Ichikawa, Daiju; Zhou, Yan; Hardy, Richard R.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Ichikawa, Daiju] Keio Univ, Div Clin Physiol & Therapeut, Fac Pharm, Tokyo 105, Japan.
RP Hayakawa, K (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
EM Kyoko.Hayakawa@fccc.edu
FU National Institutes of Health (NIH) [R01 CA129330, R01 AI049335, R01
AI11320]; FCCC Blood Cell Development and Cancer Keystone program;
Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases
FX This work was supported by National Institutes of Health (NIH) grants
R01 CA129330 (K. Hayakawa), R01 AI049335 (K.H. Hayakawa), and R01
AI11320 (R.R. Hardy), and the FCCC Blood Cell Development and Cancer
Keystone program, and in part by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases.
NR 72
TC 0
Z9 0
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD DEC
PY 2016
VL 213
IS 13
BP 3007
EP 3023
DI 10.1084/jem.20160712
PG 17
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EG5ZG
UT WOS:000391122900014
PM 27899442
ER
PT J
AU Kugler, DG
Flomerfelt, FA
Costa, DL
Laky, K
Kamenyeva, O
Mittelstadt, PR
Gress, RE
Rosshart, SP
Rehermann, B
Ashwell, JD
Sher, A
Jankovic, D
AF Kugler, David G.
Flomerfelt, Francis A.
Costa, Diego L.
Laky, Karen
Kamenyeva, Olena
Mittelstadt, Paul R.
Gress, Ronald E.
Rosshart, Stephan P.
Rehermann, Barbara
Ashwell, Jonathan D.
Sher, Alan
Jankovic, Dragana
TI Systemic toxoplasma infection triggers a long-term defect in the
generation and function of naive T lymphocytes
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID THYMIC EPITHELIAL-CELLS; SCID-HU MOUSE; CYTOMEGALOVIRUS-INFECTION;
THYMOCYTE APOPTOSIS; PATHOGEN CHALLENGE; INTERFERON-GAMMA;
IMMUNE-RESPONSE; VIRAL-INFECTION; VIRUS-INFECTION; MEASLES-VIRUS
AB Because antigen-stimulated naive T cells either die as effectors or enter the activated/memory pool, continuous egress of new T lymphocytes from thymus is essential for maintenance of peripheral immune homeostasis. Unexpectedly, we found that systemic infection with the protozoan Toxoplasma gondii triggers not only a transient increase in activated CD4(+) Th1 cells but also a persistent decrease in the size of the naive CD4(+) T lymphocyte pool. This immune defect is associated with decreased thymic output and parasite-induced destruction of the thymic epithelium, as well as disruption of the overall architecture of that primary lymphoid organ. Importantly, the resulting quantitative and qualitative deficiency in naive CD4(+) T cells leads to an immunocompromised state that both promotes chronic toxoplasma infection and leads to decreased resistance to challenge with an unrelated pathogen. These findings reveal that systemic infectious agents, such as T. gondii, can induce long-term immune alterations associated with impaired thymic function. When accumulated during the lifetime of the host, such events, even when occurring at low magnitude, could be a contributing factor in immunological senescence.
C1 [Kugler, David G.; Costa, Diego L.; Sher, Alan; Jankovic, Dragana] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Laky, Karen] NIAID, Cell Dev Sect T, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kamenyeva, Olena] NIAID, Biol Imaging, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Flomerfelt, Francis A.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Mittelstadt, Paul R.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Rosshart, Stephan P.; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kugler, David G.] Juno Therapeut, Seattle, WA 98109 USA.
RP Sher, A; Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ASher@niaid.nih.gov; DJankovic@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Intramural Research
Program of the National Institute for Diabetes and Digestive and Kidney
Diseases, National Institutes of Health; Intramural AIDS Research
Fellowship
FX This work was supported by the Intramural Research Programs of the
National Institute of Allergy and Infectious Diseases and National
Institute for Diabetes and Digestive and Kidney Diseases, National
Institutes of Health and by an Intramural AIDS Research Fellowship (to
D.G. Kugler).
NR 78
TC 0
Z9 0
U1 2
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD DEC
PY 2016
VL 213
IS 13
BP 3041
EP 3056
DI 10.1084/jem.20151636
PG 16
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EG5ZG
UT WOS:000391122900016
PM 27849554
ER
PT J
AU Leone, V
Faraldo-Gomez, JD
AF Leone, Vanessa
Faraldo-Gomez, Jose D.
TI Structure and mechanism of the ATP synthase membrane motor inferred from
quantitative integrative modeling
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID PROTEIN-STRUCTURE PREDICTION; HIGH-RESOLUTION STRUCTURE; AMINO-ACID
SUBSTITUTIONS; ESCHERICHIA-COLI; PROTON TRANSLOCATION; ALPHA-SUBUNIT;
ROTOR RING; F0F1-ATP SYNTHASE; AQUEOUS ACCESS; CROSS-LINKING
AB Two subunits within the transmembrane domain of the ATP synthase-the c-ring and subunit a-energize the production of 90% of cellular ATP by transducing an electrochemical gradient of H+ or Na+ into rotational motion. The nature of this turbine-like energy conversion mechanism has been elusive for decades, owing to the lack of definitive structural information on subunit a or its c-ring interface. In a recent breakthrough, several structures of this complex were resolved by cryo-electron microscopy (cryo-EM), but the modest resolution of the data has led to divergent interpretations. Moreover, the unexpected architecture of the complex has cast doubts on a wealth of earlier biochemical analyses conducted to probe this structure. Here, we use quantitative molecular-modeling methods to derive a structure of the a-c complex that is not only objectively consistent with the cryo-EM data, but also with correlated mutation analyses of both subunits and with prior cross-linking and cysteine accessibility measurements. This systematic, integrative approach reveals unambiguously the topology of subunit a and its relationship with the c-ring. Mapping of known Cd2+ block sites and conserved protonatable residues onto the structure delineates two noncontiguous pathways across the complex, connecting two adjacent proton-binding sites in the c-ring to the space on either side of the membrane. The location of these binding sites and of a strictly conserved arginine on subunit a, which serves to prevent protons from hopping between them, explains the directionality of the rotary mechanism and its strict coupling to the proton-motive force. Additionally, mapping of mutations conferring resistance to oligomycin unexpectedly reveals that this prototypical inhibitor may bind to two distinct sites at the a-c interface, explaining its ability to block the mechanism of the enzyme irrespective of the direction of rotation of the c-ring. In summary, this study is a stepping stone toward establishing the mechanism of the ATP synthase at the atomic level.
C1 [Leone, Vanessa; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Leone, V; Faraldo-Gomez, JD (reprint author), NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM vanessa.leonealvarez@nih.gov; jose.faraldo@nih.gov
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute, National Institutes of Health; Max Planck Society
FX This study was funded by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute, National Institutes of Health
and previously by the Max Planck Society.
NR 82
TC 2
Z9 2
U1 7
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1295
EI 1540-7748
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD DEC
PY 2016
VL 148
IS 6
BP 441
EP 457
DI 10.1085/jgp.201611679
PG 17
WC Physiology
SC Physiology
GA EG6BK
UT WOS:000391128600001
PM 27821609
ER
PT J
AU Al-Naamani, N
Chirinos, JA
Zamani, P
Ruthazer, R
Paulus, JK
Roberts, KE
Barr, RG
Lima, JA
Bluemke, DA
Kronmal, R
Kawut, SM
AF Al-Naamani, Nadine
Chirinos, Julio A.
Zamani, Payman
Ruthazer, Robin
Paulus, Jessica K.
Roberts, Kari E.
Barr, R. Graham
Lima, Joao A.
Bluemke, David A.
Kronmal, Richard
Kawut, Steven M.
TI Association of Systemic Arterial Properties With Right Ventricular
Morphology: The Multi-Ethnic Study of Atherosclerosis (MESA)-Right
Ventricle Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE arterial stiffness; artery; magnetic resonance imaging; right ventricle;
ventricle
ID PRESERVED EJECTION FRACTION; INCIDENT CARDIOVASCULAR EVENTS;
CONGESTIVE-HEART-FAILURE; MESA-RIGHT VENTRICLE; ENDOTHELIAL DYSFUNCTION;
NONINVASIVE EVALUATION; VASCULAR-RESPONSE; AORTIC STIFFNESS; OXIDATIVE
STRESS; DISTURBED FLOW
AB Background-Systemic arterial stiffness is recognized as a major contributor to development of left ventricular dysfunction and failure; however, the relationship of systemic arterial properties and the right ventricle (RV) is unknown.
Methods and Results-The associations between systemic arterial measures (total arterial compliance [TAC], systemic vascular resistance [SVR], and aortic augmentation index [AI]) and RV morphology (mass, end-systolic [RVESV] and end-diastolic volume [RVEDV], and ejection fraction [RVEF]) were examined using data from the Multi-Ethnic Study of Atherosclerosis. All analyses were adjusted for anthropometric, demographic, and clinical variables and the corresponding left ventricular parameter. A total of 3842 subjects without clinical cardiovascular disease were included with a mean age of 61 years, 48% male, 39% non-Hispanic white, 25% Chinese-American, 23% Hispanic, and 13% black. RV measures were within normal range for age and sex. A 1-mL/mm Hg decrease in TAC was associated with 3.9-mL smaller RVESV, 7.6-mL smaller RVEDV, and 2.4-g lower RV mass. A 5-Wood-unit increase in SVR was associated with 0.6-mL decrease in RVESV, 1.7-mL decrease in RVEDV, and 0.4-g decrease in RV mass. A 1% increase in AI was associated with 0.2-mL decrease in RVEDV. We found significant effect modification by age, sex, and race for some of these relationships, with males, whites, and younger individuals having greater decreases in RV volumes and mass.
Conclusions-Markers of increased systemic arterial load were associated with smaller RV volumes and lower RV mass in a population of adults without clinical cardiovascular disease.
C1 [Al-Naamani, Nadine; Roberts, Kari E.] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Al-Naamani, Nadine; Ruthazer, Robin; Paulus, Jessica K.] Tufts Med Ctr, Clin & Translat Sci Inst, Boston, MA USA.
[Chirinos, Julio A.; Zamani, Payman; Kawut, Steven M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Barr, R. Graham] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA.
[Barr, R. Graham] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Lima, Joao A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Bluemke, David A.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Kawut, SM (reprint author), Univ Penn, Perelman Sch Med, 727 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM kawut@exchange.upenn.edu
FU National Center for Advancing Translational Sciences (NCATS); National
Institutes of Health (NIH) [R01-HL086719, R01-HL098382-01A1,
K24-HL103844, N01-HC95159, N01-HC95167, UL1-TR001064, TL1-TR001062,
N01-HC95160, N01-HC95161, N01-HC95162, N01-HC95163, N01-HC95164,
N01-HC95165]
FX This research was supported by the National Center for Advancing
Translational Sciences (NCATS) and the National Institutes of Health
(NIH; R01-HL086719, R01-HL098382-01A1, K24-HL103844, N01-HC95159 through
HC95165, N01-HC95167, UL1-TR001064, and TL1-TR001062). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH.
NR 54
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD DEC
PY 2016
VL 5
IS 12
AR e004162
DI 10.1161/JAHA.116.004162
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EG1JF
UT WOS:000390787700017
ER
PT J
AU Jackson, JD
Moy, B
Evans, MK
AF Jackson, Jonathan D.
Moy, Beverly
Evans, Michele K.
TI The Elimination of Cancer Health Disparities: Are We Ready to Do the
Heavy Lifting?
SO ONCOLOGIST
LA English
DT Editorial Material
ID AFRICAN-AMERICAN MEN; CLINICAL-TRIALS; RACE; WILLINGNESS; PARTICIPATE;
BARRIERS; RISK
C1 [Jackson, Jonathan D.; Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
RP Jackson, JD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM jjackson31@partners.org
NR 21
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD DEC
PY 2016
VL 21
IS 12
BP 1411
EP 1413
DI 10.1634/theoncologist.2016-0327
PG 3
WC Oncology
SC Oncology
GA EG6DZ
UT WOS:000391135800004
PM 27821795
ER
PT J
AU Hopfner, F
Haubenberger, D
Galpern, WR
Gwinn, K
Van't Veer, A
White, S
Bhatia, K
Adler, CH
Eidelberg, D
Ondo, W
Stebbins, GT
Tanner, CM
Helmich, RC
Lenz, FA
Sillitoe, RV
Vaillancourt, D
Vitek, JL
Louis, ED
Shill, HA
Frosch, MP
Foroud, T
Kuhlenbaumer, G
Singleton, A
Testa, CM
Hallett, M
Elble, R
Deuschl, G
AF Hopfner, Franziska
Haubenberger, Dietrich
Galpern, Wendy R.
Gwinn, Katrina
Van't Veer, Ashlee
White, Samantha
Bhatia, Kailash
Adler, Charles H.
Eidelberg, David
Ondo, William
Stebbins, Glenn T.
Tanner, Caroline M.
Helmich, Rick C.
Lenz, Fred A.
Sillitoe, Roy V.
Vaillancourt, David
Vitek, Jerrold L.
Louis, Elan D.
Shill, Holly A.
Frosch, Matthew P.
Foroud, Tatiana
Kuhlenbaeumer, Gregor
Singleton, Andrew
Testa, Claudia M.
Hallett, Mark
Elble, Rodger
Deuschl, Guenther
TI Knowledge gaps and research recommendations for essential tremor
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Review
DE Essential tremor; Common data elements; Genetic association studies;
Neuropathology
ID PURKINJE-CELL LOSS; PARKINSONS-DISEASE; HEARING IMPAIRMENT; INCREASED
NUMBER; CEREBELLUM; LINGO-1; MOTOR; BRAIN; GENE; MUTATIONS
AB Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics. Across all areas, the need for collaborative and coordinated research on a multinational level was expressed. Standardized data collection using common data elements for genetic, clinical, neurophysiological, and pathological studies was recommended. Large cohorts of patients should be studied prospectively to collect bio-samples, characterize the natural history of the clinical syndrome including patient-oriented outcomes, investigate potential etiologies of various phenotypes, and identify pathophysiological mechanisms. In particular, cellular and system-level mechanisms of tremor oscillations should be elucidated because they may yield effective therapeutic targets and biomarkers. A neuropathology consortium was recommended to standardize postmortem analysis and further characterize neuropathological observations in the cerebellum and elsewhere. Furthermore, genome-wide association studies on large patient cohorts (>10,000 patients) may allow the identification of common genes contributing to risk, and whole exome or genome sequencing may enable the identification of genetic risk and causal mutations in cohorts and well-characterized families. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Hopfner, Franziska; Kuhlenbaeumer, Gregor; Deuschl, Guenther] Univ Hosp Schleswig Holstein, Dept Neurol, Kiel, Germany.
[Haubenberger, Dietrich; Galpern, Wendy R.; Gwinn, Katrina; Van't Veer, Ashlee; White, Samantha; Hallett, Mark] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bhatia, Kailash] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1E 6BT, England.
[Adler, Charles H.] Mayo Clin, Coll Med, Scottsdale, AZ USA.
[Eidelberg, David] Feinstein Inst Med Res, Manhasset, NY USA.
[Ondo, William] Methodist Neurol Inst, Houston, TX USA.
[Stebbins, Glenn T.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA.
[Tanner, Caroline M.] Univ Calif San Francisco, Parkinsons Dis Res Educ & Clin Ctr, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Helmich, Rick C.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands.
[Lenz, Fred A.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Hopkins Hosp, Baltimore, MD 21205 USA.
[Sillitoe, Roy V.] Baylor Coll Med, Dept Pathol & Immunol, Dept Neurosci, Program Dev Biol, Houston, TX 77030 USA.
[Vaillancourt, David] Univ Florida, Dept Biomed Engn, Ctr Movement Disorders & Neurorestorat, Dept Appl Physiol & Kinesiol, Gainesville, FL USA.
[Vitek, Jerrold L.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA.
[Louis, Elan D.] Yale Univ, Dept Neurol, Dept Chron Dis Epidemiol, Ctr Neuroepidemiol & Clin Neurol Res,Yale Sch Med, New Haven, CT USA.
[Shill, Holly A.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Testa, Claudia M.] Virginia Commonwealth Univ, Parkinsons & Movement Disorders Ctr, Richmond, VA USA.
[Testa, Claudia M.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA.
[Elble, Rodger] Southern Illinois Univ, Sch Med, Dept Neurol, Springfield, IL USA.
RP Haubenberger, D (reprint author), NINDS, Intramural Res Program, NIH, 9000 Rockville Pike,Bldg 10,Rm 6-5700, Bethesda, MD 20892 USA.
EM dietrich.haubenberger@nih.gov
RI Helmich, Rick/R-6333-2016;
OI Helmich, Rick/0000-0003-4035-6573; Gwinn, Katrina/0000-0002-8277-651X
FU National Institute of Neurological Disorders and Stroke
FX National Institute of Neurological Disorders and Stroke
NR 91
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD DEC
PY 2016
VL 33
BP 27
EP 35
DI 10.1016/j.parkreldis.2016.10.002
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA EG0SR
UT WOS:000390743000004
PM 27769649
ER
PT J
AU McCrea, E
Sissung, TM
Price, DK
Chau, CH
Figg, WD
AF McCrea, Edel
Sissung, Tristan M.
Price, Douglas K.
Chau, Cindy H.
Figg, William D.
TI Androgen receptor variation affects prostate cancer progression and drug
resistance
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE Androgen receptor; Prostate cancer; AR-V7; Pharmacology; Mutation
ID LIGAND-BINDING DOMAIN; MOLECULAR-DYNAMICS SIMULATIONS; GROWTH-FACTOR-I;
SPLICE VARIANTS; ANTITUMOR-ACTIVITY; ENZALUTAMIDE RESISTANCE;
ABIRATERONE ACETATE; BIOLOGICAL-ACTIVITY; CYP17A1 INHIBITOR; XENOGRAFT
MODEL
AB Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients. Published by Elsevier Ltd.
C1 [McCrea, Edel; Price, Douglas K.; Chau, Cindy H.; Figg, William D.] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
[Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Off Clin Director, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
FU Intramural Research Program of National Institutes of Health, National
Cancer Institute, Bethesda, MD, USA
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Bethesda,
MD, USA.
NR 93
TC 1
Z9 1
U1 2
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD DEC
PY 2016
VL 114
BP 152
EP 162
DI 10.1016/j.phrs.2016.10.001
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EG5HQ
UT WOS:000391075300017
PM 27725309
ER
PT J
AU Mertan, F
Turkbey, B
AF Mertan, Francesca
Turkbey, Baris
TI Incorporating imaging into personalized medicine for the detection of
prostate cancer Pharmacological research-Urogenital pharmacology
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE Prostate; Prostate cancer; MRI; mpMRI; Personalized medicine; Imaging
ID ULTRASOUND-GUIDED BIOPSY; LOCALIZATION; MRI
AB Imaging has played an important role in the administration of personalized medicine. From diagnosing diseases to guiding therapies, imaging has become an all-encompassing modality. With respect to prostate cancer, personalized management of the disease has been transformed by imaging. Specifically, multiparametric magnetic resonance imaging has emerged as a vital player in the detection, characterization, and localization of the disease thus making the incorporation of imaging in personalized prostate cancer management integral. In this review, the current role of imaging in personalized medicine for the management of prostate cancer is discussed. (C) 2016 Published by Elsevier Ltd.
C1 [Mertan, Francesca; Turkbey, Baris] NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
NR 16
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD DEC
PY 2016
VL 114
BP 163
EP 165
DI 10.1016/j.phrs.2016.10.020
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EG5HQ
UT WOS:000391075300018
PM 27777131
ER
PT J
AU Shah, J
Sikdar, S
Gerber, L
AF Shah, Jay
Sikdar, Siddhartha
Gerber, Lynn
TI Re: "Dry Needling Alters Trigger Points in the Upper Trapezius Muscle
and Reduces Pain in Subjects with Chronic Myofascial Pain" Reply
SO PM&R
LA English
DT Letter
C1 [Shah, Jay] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA.
[Sikdar, Siddhartha] George Mason Univ, Bioengn Dept, Fairfax, VA 22030 USA.
[Gerber, Lynn] George Mason Univ, Ctr Chron Illness & Disabil, Fairfax, VA 22030 USA.
RP Shah, J (reprint author), NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
EI 1934-1563
J9 PM&R
JI PM&R
PD DEC
PY 2016
VL 8
IS 12
BP 1226
EP 1227
DI 10.1016/j.pmrj.2016.08.003
PG 2
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA EG5LS
UT WOS:000391085900014
PM 27989420
ER
PT J
AU Wolfe, F
Clauw, DJ
Fitzcharles, MA
Goldenberg, DL
Hauser, W
Katz, RL
Mease, PJ
Russell, AS
Russell, IJ
Walitt, B
AF Wolfe, Frederick
Clauw, Daniel J.
Fitzcharles, Mary-Ann
Goldenberg, Don L.
Haeuser, Winfried
Katz, Robert L.
Mease, Philip J.
Russell, Anthony S.
Russell, Irwin Jon
Walitt, Brian
TI 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria
SO SEMINARS IN ARTHRITIS AND RHEUMATISM
LA English
DT Review
DE Fibromyalgia; Criteria; Diagnosis; Classification
ID OF-RHEUMATOLOGY CRITERIA; SYMPTOM SEVERITY SCALE; GENERAL-POPULATION;
WIDESPREAD PAIN; CLASSIFICATION CRITERIA; TENDER POINTS; PREVALENCE;
RELIABILITY; VALIDATION; VERSION
AB Objectives: The provisional criteria of the American College of Rheumatology (ACR) 2010 and the 2011 self-report modification for survey and clinical research are widely used for fibromyalgia diagnosis. To determine the validity, usefulness, potential problems, and modifications required for the criteria, we assessed multiple research reports published in 2010-2016 in order to provide a 2016 update to the criteria.
Methods: We reviewed 14 validation studies that compared 2010/2011 criteria with ACR 1990 classification and clinical criteria, as well as epidemiology, clinical, and databank studies that addressed important criteria-level variables. Based on definitional differences between 1990 and 2010/2011 criteria, we interpreted 85% sensitivity and 90% specificity as excellent agreement.
Results: Against 1990 and clinical criteria, the median sensitivity and specificity of the 2010/2011 criteria were 86% and 90%, respectively. The 2010/2011 criteria led to misclassification when applied to regional pain syndromes, but when a modified widespread pain criterion (the "generalized pain criterion") was added misclassification was eliminated. Based on the above data and clinic usage data, we developed a (2016) revision to the 2010/2011 fibromyalgia criteria. Fibromyalgia may now be diagnosed in adults when all of the following criteria are met:
(1) Generalized pain, defined as pain in at least 4 of 5 regions, is present.
(2) Symptoms have been present at a similar level for at least 3 months.
(3) Widespread pain index (WPI) >= 7 and symptom severity scale (SSS) score >= 5 OR WPI of 4-6 and SSS score >= 9.
(4) A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.
Conclusions: The fibromyalgia criteria have good sensitivity and specificity. This revision combines physician and questionnaire criteria, minimizes misclassification of regional pain disorders, and eliminates the previously confusing recommendation regarding diagnostic exclusions. The physician based criteria are valid for individual patient diagnosis. The self-report version of the criteria is not valid for clinical diagnosis in individual patients but is valid for research studies. These changes allow the criteria to function as diagnostic criteria, while still being useful for classification. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Wolfe, Frederick] Natl Data Bank Rheumat Dis, 1035 N Emporia,Ste 288, Wichita, KS 67214 USA.
[Wolfe, Frederick] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[Clauw, Daniel J.] Univ Michigan, Sch Med, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI USA.
[Fitzcharles, Mary-Ann] McGill Univ, Div Rheumatol, Ctr Hlth, Montreal, PQ, Canada.
[Goldenberg, Don L.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Goldenberg, Don L.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Haeuser, Winfried] Dept Internal Med 1, Saarbrucken, Germany.
[Haeuser, Winfried] Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, Munich, Germany.
[Katz, Robert L.] Rush Med Coll, Rheumatol, Chicago, IL USA.
[Mease, Philip J.] Swedish Med Ctr, Seattle, WA USA.
[Mease, Philip J.] Univ Washington, Seattle, WA 98195 USA.
[Russell, Anthony S.] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Russell, Irwin Jon] Fibromyalgia Res & Consulting, San Antonio, TX USA.
[Walitt, Brian] NINR, NIH, Bethesda, MD 20892 USA.
RP Wolfe, F (reprint author), Natl Data Bank Rheumat Dis, 1035 N Emporia,Ste 288, Wichita, KS 67214 USA.; Wolfe, F (reprint author), Univ Kansas, Sch Med, Wichita, KS 67214 USA.
EM fwolfe@arthritis-research.org
NR 49
TC 1
Z9 1
U1 10
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0049-0172
EI 1532-866X
J9 SEMIN ARTHRITIS RHEU
JI Semin. Arthritis Rheum.
PD DEC
PY 2016
VL 46
IS 3
BP 319
EP 329
DI 10.1016/j.semarthrit.2016.08.012
PG 11
WC Rheumatology
SC Rheumatology
GA EG3XY
UT WOS:000390979200009
PM 27916278
ER
PT J
AU Podbilewicz, B
Chernomordik, LV
AF Podbilewicz, Benjamin
Chernomordik, Leonid V.
TI Membrane fusion: Conserved and diverse
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Editorial Material
C1 [Podbilewicz, Benjamin] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Rockville, MD 20847 USA.
RP Podbilewicz, B (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.; Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Rockville, MD 20847 USA.
EM podbilew@tx.technion.ac.il; chernoml@mail.nih.gov
OI Podbilewicz, Benjamin/0000-0002-0411-4182
NR 0
TC 0
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U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD DEC
PY 2016
VL 60
BP 63
EP 64
DI 10.1016/j.semcdb.2016.11.009
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA EG5IJ
UT WOS:000391077200009
PM 27979329
ER
PT J
AU Moss, B
AF Moss, Bernard
TI Membrane fusion during poxvirus entry
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE Vaccinia virus; Membrane fusion; Virus entry; Hemifusion; Endocytosis
ID VACCINIA-VIRUS ENTRY; INTRACELLULAR MATURE VIRION; CELL-CELL-FUSION;
SERINE-PROTEASE INHIBITOR; SURFACE HEPARAN-SULFATE; OPEN READING FRAME;
L1 PROTEIN; ENVELOPE PROTEIN; NEUTRALIZING ANTIBODY; ENTRY/FUSION
COMPLEX
AB Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism. Published by Elsevier Ltd.
C1 [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
OI Moss, Bernard/0000-0002-2154-8564
FU Division of Intramural Research, NIAID, NIH
FX I thank Jason Laliberte and Andrea Weisberg for help with illustrations.
This work was supported by the Division of Intramural Research, NIAID,
NIH.
NR 94
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U1 4
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD DEC
PY 2016
VL 60
BP 89
EP 96
DI 10.1016/j.semcdb.2016.07.015
PG 8
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA EG5IJ
UT WOS:000391077200012
PM 27423915
ER
PT J
AU Dodd, KW
Berman, A
Brown, J
Carr, BG
Dunn, P
Escobedo, M
Gayer, C
Grieser, M
Carpenter, CR
Hess, EP
Grudzen, CR
AF Dodd, Kenneth W.
Berman, Amy
Brown, Jeremy
Carr, Brendan G.
Dunn, Patrick
Escobedo, Marcus
Gayer, Christopher
Grieser, Mira
Carpenter, Christopher R.
Hess, Erik P.
Grudzen, Corita R.
TI Funding Research in Emergency Department Shared Decision Making: A
Summary of the 2016 Academic Emergency Medicine Consensus Conference
Panel Discussion
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Academic Emergency Medicine Consensus Conference on Shared Decision
Making in the Emergency Department - Development of a Policy-Relevant
Patient-Centered Research Agenda
CY MAY 10, 2016
CL New Orleans, LA
AB As part of the 2016 Academic Emergency Medicine Consensus Conference, Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient-centered Research Agenda, a panel of representatives from the Office of Emergency Care Research, the Patient-Centered Outcomes Research Institute, the American Heart Association, the John A. Hartford Foundation, and the Emergency Care Coordination Center were assembled to discuss funding opportunities for future research in this field. This article summarizes their discussion of funding priorities and examples of successfully funded projects related to shared decision making in emergency medicine. (C) 2016 by the Society for Academic Emergency Medicine
C1 [Dodd, Kenneth W.] Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA.
[Berman, Amy; Escobedo, Marcus] John A Hartford Fdn, New York, NY USA.
[Brown, Jeremy] NIH, Off Emergency Care Res, Bldg 10, Bethesda, MD 20892 USA.
[Carr, Brendan G.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA.
[Carr, Brendan G.] US Dept HHS, Emergency Care Coordinat Ctr, Washington, DC 20201 USA.
[Dunn, Patrick] Amer Heart Assoc, Dallas, TX USA.
[Gayer, Christopher; Grieser, Mira] Patient Ctr Outcomes Res Inst, Washington, DC USA.
[Carpenter, Christopher R.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA.
[Hess, Erik P.] Mayo Clin, Rochester, MN USA.
[Grudzen, Corita R.] NYU, Sch Med, Ronald O Perelman Dept Emergency Med, New York, NY USA.
[Grudzen, Corita R.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
RP Grudzen, CR (reprint author), NYU, Sch Med, Ronald O Perelman Dept Emergency Med, New York, NY USA.; Grudzen, CR (reprint author), NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
EM corita.grudzen@nyumc.org
OI Grudzen, Corita/0000-0003-3039-8497
FU Agency for Healthcare Research and Quality [1R13HS024172-01]; NIMHD NIH
HHS [1R13MD010171-01]
NR 13
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2016
VL 23
IS 12
BP 1340
EP 1345
DI 10.1111/acem.13063
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA EF8ES
UT WOS:000390562300006
PM 27474887
ER
PT J
AU Eitan, E
Suire, C
Zhang, S
Mattson, MP
AF Eitan, Erez
Suire, Caitlin
Zhang, Shi
Mattson, Mark P.
TI Impact of lysosome status on extracellular vesicle content and release
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Alzheimer's disease; HIV AIDS; Niemann pick disease; Parkinson's disease
ID CHEDIAK-HIGASHI-SYNDROME; OUTER-MEMBRANE VESICLES; HEPATITIS-C VIRUS;
ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; MULTIVESICULAR BODIES;
PARKINSONS-DISEASE; EXOSOME SECRETION; CARCINOMA CELLS; ESCRT FUNCTIONS
AB Extracellular vesicles (EVs) are nanoscale size bubble-like membranous structures released from cells. EVs contain RNA, lipids and proteins and are thought to serve various roles including intercellular communication and removal of misfolded proteins. The secretion of misfolded and aggregated proteins in EVs may be a cargo disposal alternative to the autophagy-lysosomal and ubiquitin-proteasome pathways. In this review we will discuss the importance of lysosome functionality for the regulation of EV secretion and content. Exosomes are a subtype of EVs that are released by the fusion of multivesicular bodies (MVB) with the plasma membrane. MVBs can also fuse with lysosomes, and the trafficking pathway of MVBs can therefore determine whether or not exosomes are released from cells. Here we summarize data from studies of the effects of lysosome inhibition on the secretion of EVs and on the possibility that cells compensate for lysosome malfunction by disposal of potentially toxic cargos in EVs. A better understanding of the molecular mechanisms that regulate trafficking of MVBs to lysosomes and the plasma membrane may advance an understanding of diseases in which pathogenic proteins, lipids or infectious agents accumulate within or outside of cells. (C) 2016 Published by Elsevier B.V.
C1 [Eitan, Erez; Suire, Caitlin; Zhang, Shi; Mattson, Mark P.] NIA, Lab Neurosci, Baltimore, MD 21224 USA.
RP Eitan, E (reprint author), NIA, Lab Neurosci, Baltimore, MD 21224 USA.
EM erez.eitan@nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging.
NR 122
TC 3
Z9 3
U1 8
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD DEC
PY 2016
VL 32
SI SI
BP 65
EP 74
DI 10.1016/j.arr.2016.05.001
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA EF9AP
UT WOS:000390623400007
PM 27238186
ER
PT J
AU Fink, E
Fuller, K
Agan, B
Berger, EA
Saphire, A
Quinnan, GV
Elder, JH
AF Fink, Elizabeth
Fuller, Katherine
Agan, Brian
Berger, Edward A.
Saphire, Andrew
Quinnan, Gerald V.
Elder, John H.
TI Humoral Antibody Responses to HIV Viral Proteins and to CD4 Among HIV
Controllers, Rapid and Typical Progressors in an HIV-Positive Patient
Cohort
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
DE HIV; envelope; ADCC; HIV clinical outcomes research
ID IMMUNODEFICIENCY-VIRUS-INFECTION; CELL-MEDIATED CYTOTOXICITY; PBL-SCID
MICE; MONOCLONAL-ANTIBODIES; DISEASE PROGRESSION; ANTIIDIOTYPIC
ANTIBODIES; ANTI-CD4 AUTOANTIBODIES; NEUTRALIZING ANTIBODY;
PASSIVE-IMMUNIZATION; ENVELOPE
AB The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV+ cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV+ subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC. All of the HIV+ patient samples were positive for antibodies to HIV gp120 and p24 and 80% showed evidence of hypergammaglobulinemia. Approximately 10% of cohort members were positive for antibodies to CD4, but we noted no significant correlation relevant to DP. There were statistically significant differences between the groups concerning the level of humoral response to gp120 and Gag. However, we observed no distinction in ability of anti-gp120 antibodies purified from each group to neutralize infection. In addition, there was a statistically significant difference in ADCC, with elite controllers exhibiting significantly lower levels of ADCC than the other five groups. We detected IgA anti-gp120 antibodies, but did not correlate their presence with either DP or ADCC levels. The results are consistent with the interpretation that the humoral antibody response to the antigens assessed here represents a signature of the level of viremia but does not correlate with clinical status of HIV infection.
C1 [Fink, Elizabeth; Fuller, Katherine; Saphire, Andrew; Elder, John H.] Scripps Res Inst, Dept Immunol & Microbial Sci, 10466 North Torrey Pines Rd IMM215, La Jolla, CA 92037 USA.
[Agan, Brian] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
[Agan, Brian] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Quinnan, Gerald V.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biostat, Bethesda, MD 20814 USA.
RP Elder, JH (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10466 North Torrey Pines Rd IMM215, La Jolla, CA 92037 USA.
EM jelder@scripps.edu
NR 48
TC 0
Z9 0
U1 5
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD DEC
PY 2016
VL 32
IS 12
BP 1187
EP 1197
DI 10.1089/aid.2016.0182
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA EF8PZ
UT WOS:000390592600007
PM 27771962
ER
PT J
AU Lovell, JP
Zerbe, CS
Olivier, KN
Claypool, RJ
Frein, C
Anderson, VL
Freeman, AF
Holland, SM
AF Lovell, Jana P.
Zerbe, Christa S.
Olivier, Kenneth N.
Claypool, Reginald J.
Frein, Cathleen
Anderson, Victoria L.
Freeman, Alexandra F.
Holland, Steven M.
TI Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2
Deficiency
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Rationale: Mycobacterium kansasii usually causes chronic pulmonary infections in immunocompetent patients. In contrast, disseminated M. kansasii disease is commonly associated with advanced human immunodeficiency virus infection, but is reported infrequently in other immunocompromised patients.
Objectives: To identify common clinical manifestations and potential risk factors for M. kansasii infection in patients with GATA2 deficiency.
Methods: We reviewed M. kansasii disease associated with GATA2 deficiency at one institution and disease associated with primary and other immunodeficiencies reported in the literature.
Measurements and Main Results: Nine patients with GATA2 deficiency developed M. kansasii infections. Six patients developed disseminated disease. All patients presented with significant mediastinal lymphadenopathy or abscesses. Seven patients had pulmonary risk factors, including six smokers. The majority of patients had low numbers of neutrophils, monocytes, B cells, CD4(+) T cells, and natural killer cells. Other conditions associated with disseminated M. kansasii disease were thymic disorders and IFN-gamma/IL-12 defects.
Conclusions: Disseminated M. kansasii disease involving mediastinal lymph nodes is surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-gamma synthesis and response. Disseminated M. kansasii should be considered a marker indicating a need to evaluate for immunodeficiency syndromes.
C1 [Lovell, Jana P.; Zerbe, Christa S.; Claypool, Reginald J.; Anderson, Victoria L.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NHLBI, Pulm Clin Med Sect, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Frein, Cathleen] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Holland, SM (reprint author), Bldg 10-11N248,MSC 1960, Bethesda, MD 20892 USA.
EM smh@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, National Institutes of Health (NIH); National Cancer
Institute, NIH [HHSN261200800001E]; NIH Medical Research Scholars
Program - NIH
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Disease, National Institutes of Health (NIH).
This project was also funded in part with federal funds from the
National Cancer Institute, NIH, under Contract No. HHSN261200800001E.
J.P.L. was funded through the NIH Medical Research Scholars Program, a
public-private partnership supported by the NIH, and by generous
contributions to the Foundation for the NIH from the Doris Duke
Charitable Foundation, American Association for Dental Research, Howard
Hughes Medical Institute, and Colgate-Palmolive Co., as well as alumni
of student research programs and other individual sources of support.
For a complete list, please visit the Foundation website at
http://www.fnih.org/education-training-0/medical-research-scholars-progr
am. The views expressed in this article are those of the authors and do
not reflect the official policy of the U.S. government.
NR 0
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U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD DEC
PY 2016
VL 13
IS 12
BP 2169
EP 2173
DI 10.1513/AnnalsATS.201603-207BC
PG 5
WC Respiratory System
SC Respiratory System
GA EF9OF
UT WOS:000390658800013
PM 27607353
ER
PT J
AU Young, LR
Trapnell, BC
Mandl, KD
Swarr, DT
Wambach, JA
Blaisdell, CJ
AF Young, Lisa R.
Trapnell, Bruce C.
Mandl, Kenneth D.
Swarr, Daniel T.
Wambach, Jennifer A.
Blaisdell, Carol J.
TI Accelerating Scientific Advancement for Pediatric Rare Lung Disease
Research Report from a National Institutes of Health-NHLBI Workshop,
September 3 and 4, 2015
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD.
C1 [Young, Lisa R.] Vanderbilt Univ, Dept Pediat Med & Cell & Dev Biol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Trapnell, Bruce C.] Univ Cincinnati, Sch Med, Dept Med, Cincinnati, OH USA.
[Trapnell, Bruce C.] Univ Cincinnati, Dept Pediat, Sch Med, Cincinnati, OH USA.
[Mandl, Kenneth D.] Harvard Med Sch, Computat Hlth Informat Program, Boston Childrens Hosp, Dept Pediat, Boston, MA USA.
[Mandl, Kenneth D.] Harvard Med Sch, Computat Hlth Informat Program, Boston Childrens Hosp, Dept Biomed Informat, Boston, MA USA.
[Swarr, Daniel T.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Wambach, Jennifer A.] Washington Univ, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA.
[Blaisdell, Carol J.] NHLBI, Div Lung Dis, Bldg 10, Bethesda, MD 20892 USA.
RP Blaisdell, CJ (reprint author), NHLBI, Div Lung Dis, NIH, Two Rockledge Ctr, Suite 10042,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM carol.blaisdell@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD DEC
PY 2016
VL 13
IS 12
BP S385
EP S393
DI 10.1513/AnnalsATS.201605-402OT
PG 9
WC Respiratory System
SC Respiratory System
GA EF9OF
UT WOS:000390658800001
ER
PT J
AU Masuda, J
Kawamoto, H
Strober, W
Takayama, E
Mizutani, A
Murakami, H
Ikawa, T
Kitani, A
Maeno, N
Shigehiro, T
Satoh, A
Seno, A
Arun, V
Kasai, T
Fuss, IJ
Katsura, Y
Seno, M
AF Masuda, Junko
Kawamoto, Hiroshi
Strober, Warren
Takayama, Eiji
Mizutani, Akifumi
Murakami, Hiroshi
Ikawa, Tomokatsu
Kitani, Atsushi
Maeno, Narumi
Shigehiro, Tsukasa
Satoh, Ayano
Seno, Akimasa
Arun, Vaidyanath
Kasai, Tomonari
Fuss, Ivan J.
Katsura, Yoshimoto
Seno, Masaharu
TI Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting
SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
LA English
DT Article
DE TCF3 (E2A); Artificial transcription factor; TALE technology
ID PLURIPOTENT STEM-CELLS; ZINC-FINGER PROTEINS; UMBILICAL-CORD BLOOD;
EX-VIVO EXPANSION; HEMATOPOIETIC STEM; LYMPHOCYTE DEVELOPMENT;
PROGENITOR CELLS; LENTIVIRAL VECTORS; DNA; EXPRESSION
AB Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Kruppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.
C1 [Masuda, Junko; Mizutani, Akifumi; Murakami, Hiroshi; Maeno, Narumi; Shigehiro, Tsukasa; Satoh, Ayano; Seno, Akimasa; Arun, Vaidyanath; Kasai, Tomonari; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Div Med Bioengn, Okayama 7008530, Japan.
[Masuda, Junko; Strober, Warren; Kitani, Atsushi; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Kawamoto, Hiroshi; Ikawa, Tomokatsu; Katsura, Yoshimoto] RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Dev, Yokohama, Kanagawa 2300045, Japan.
[Kawamoto, Hiroshi] Kyoto Univ, Inst Frontier Med Sci, Dept Immunol, Kyoto 6068507, Japan.
[Takayama, Eiji] Asahi Univ, Sch Dent, Dept Oral Biochem, Hozumi 1851, Gifu 5010296, Japan.
[Ikawa, Tomokatsu] RIKEN Ctr Integrat Med Sci, Lab Immune Regenerat, Yokohama, Kanagawa 2300045, Japan.
[Katsura, Yoshimoto] Nihon Univ, Sch Med, Adv Med Res Ctr, Div Cell Regenerat & Transplantat, Tokyo 1738610, Japan.
RP Masuda, J (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Div Med Bioengn, Okayama 7008530, Japan.; Masuda, J (reprint author), NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA.
EM junkomasuda@okayama-u.ac.jp
OI SATOH, Ayano/0000-0003-3736-1283
FU Japan Society for the Promotion of Science (JSPS) KAKENHI [25860797];
Okayama Foundation for Science and Technology
FX This work was supported in part by Japan Society for the Promotion of
Science (JSPS) KAKENHI, grant numbers 25860797, and Okayama Foundation
for Science and Technology.
NR 60
TC 0
Z9 0
U1 5
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0273-2289
EI 1559-0291
J9 APPL BIOCHEM BIOTECH
JI Appl. Biochem. Biotechnol.
PD DEC
PY 2016
VL 180
IS 8
BP 1559
EP 1573
DI 10.1007/s12010-016-2187-4
PG 15
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA EE8RA
UT WOS:000389892200008
PM 27406037
ER
PT J
AU Plazyo, O
Romero, R
Unkel, R
Balancio, A
Mial, TN
Xu, Y
Dong, Z
Hassan, SS
Gomez-Lopez, N
AF Plazyo, Olesya
Romero, Roberto
Unkel, Ronald
Balancio, Amapola
Mial, Tara N.
Xu, Yi
Dong, Zhong
Hassan, Sonia S.
Gomez-Lopez, Nardhy
TI HMGB1 Induces an Inflammatory Response in the Chorioamniotic Membranes
That Is Partially Mediated by the Inflammasome
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE AIM2; alarmins; caspase-1; DAMPs; interleukin-1 beta; interleukin-6;
MMP-9; NLRP3; NOD2; parturition; pregnancy; preterm birth; preterm
labor; RAGE; sterile inflammation; sterile intra-amniotic inflammation;
TLR-2
ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; HUMAN MYOMETRIAL CELLS;
NECROSIS-FACTOR-ALPHA; GROUP BOX-1 PROTEIN; TOLL-LIKE RECEPTOR; NOD-LIKE
RECEPTORS; PRETERM PREMATURE RUPTURE; PLASMA CYTOKINE PROFILE; HUMAN
FETAL MEMBRANES; INNATE IMMUNE-SYSTEM
AB Spontaneous preterm labor occurs in two subsets of patients with sterile intra-amniotic inflammation, a process induced by alarmins such as high-mobility group box-1 (HMGB1). Inflammasomes are implicated in the process of spontaneous preterm labor. Therefore, we investigated whether HMGB1 initiates an inflammasome-associated inflammatory response in the chorioamniotic membranes. Incubation of the chorioamniotic membranes with HMGB1 1) induced the release of mature IL-1beta and IL-6; 2) upregulated the mRNA expression of the pro-inflammatory mediators NFKB1, IL6, TNF, IL1A, IFNG, and HMGB1 receptors RAGE and TLR2; 3) upregulated the mRNA expression of the inflammasome components NLRP3 and AIM2 as well as NOD proteins (NOD1 and NOD2); 4) increased the protein concentrations of NLRP3 and NOD2; 5) increased the concentration of caspase-1 and the quantity of its active form (p20); and 6) upregulated the mRNA expression and active form of MMP-9. In addition, HMGB1 concentrations in chorioamniotic membrane extracts from women who underwent spontaneous preterm labor were greater than in those from women who had undergone spontaneous labor at term. Collectively, these results show that HMGB1 can induce an inflammatory response in the chorioamniotic membranes, which is partially mediated by the inflammasome. These results provide insight into the mechanisms whereby HMGB1 induces preterm labor and birth in mice and explain why the concentration of this alarmin is increased in women who undergo spontaneous preterm labor.
C1 [Plazyo, Olesya; Romero, Roberto; Unkel, Ronald; Balancio, Amapola; Mial, Tara N.; Xu, Yi; Dong, Zhong; Hassan, Sonia S.; Gomez-Lopez, Nardhy] NICHD, Perinatol Res Branch,Program Perinatal Res & Obst, Div Intramural Res,Eunice Kennedy Shriver Natl In, NIH,DHHS, Bethesda, MD USA.
[Plazyo, Olesya; Romero, Roberto; Unkel, Ronald; Balancio, Amapola; Mial, Tara N.; Xu, Yi; Dong, Zhong; Hassan, Sonia S.; Gomez-Lopez, Nardhy] NICHD, Perinatol Res Branch,Program Perinatal Res & Obst, Div Intramural Res,Eunice Kennedy Shriver Natl In, NIH,DHHS, Detroit, MI USA.
[Plazyo, Olesya; Unkel, Ronald; Balancio, Amapola; Mial, Tara N.; Xu, Yi; Dong, Zhong; Hassan, Sonia S.; Gomez-Lopez, Nardhy] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Gomez-Lopez, Nardhy] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA.
RP Gomez-Lopez, N (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Sch Med,Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
EM ngomezlo@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, U.S. Department of Health
and Human Services (NICHD/NIH/DHHS); NICHD/NIH/DHHS [HHSN275201300006C];
Wayne State University Perinatal Initiative in Maternal, Perinatal and
Child Health
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS),
and, in part, with federal funds from the NICHD/NIH/DHHS under Contract
No. HHSN275201300006C. This research was also supported by the Wayne
State University Perinatal Initiative in Maternal, Perinatal and Child
Health. Presented, in part, at the 63rd Annual Scientific Meeting of the
Society for Reproductive Investigation, March 16-19, 2016, Montreal, QC,
Canada.
NR 152
TC 1
Z9 1
U1 0
U2 0
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD DEC 1
PY 2016
VL 95
IS 6
AR 130
DI 10.1095/biolreprod.116.144139
PG 14
WC Reproductive Biology
SC Reproductive Biology
GA EG1PJ
UT WOS:000390804400017
PM 27806943
ER
PT J
AU Ramnarayanan, S
Kyathanahalli, C
Ingles, J
Park-York, M
Jeyasuria, P
Condon, JC
AF Ramnarayanan, Saiprasad
Kyathanahalli, Chandrashekara
Ingles, Judith
Park-York, MieJung
Jeyasuria, Pancharatnam
Condon, Jennifer C.
TI The Unfolded Protein Response Regulates Uterine Myocyte Antioxidant
Responsiveness During Pregnancy
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE oxidative stress; pregnancy; unfolded protein response; uterus
ID ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE STRESS; VITAMINS C; CELL-DEATH;
ER STRESS; SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; PREECLAMPSIA;
APOPTOSIS; NRF2
AB There is considerable evidence that implicates oxidative stress in the pathophysiology of human pregnancy complications. However, the role and the mechanism of maintaining an antioxidant prosurvival uterine environment during normal pregnancy is largely unresolved. Herein we report that the highly active uterine unfolded protein response plays a key role in promoting antioxidant activity in the uterine myocyte across gestation. The unfolded protein response (UPR) senses the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and activates a signaling network that consists of the transmembrane protein kinase eukaryotic translation initiation factor 2 alpha kinase 3/PKR-like-ER kinase (EIF2AK3), which acts to decrease protein translation levels, allowing for a lowered need for protein folding during periods of ER stress. However, independent of its translational regulatory capacity, EIF2AK3dependent signals elicit the activation of the transcription factor, nuclear factor erythroid 2-like 2 (NFE2L2) in response to oxidative stress. NFE2L2 binds to antioxidant response elements in the promoters of a variety of antioxidant genes that minimize the opportunities for generation of reactive oxygen intermediates. Our analysis demonstrates that in the absence of EIF2AK3, the uterine myocyte experiences increased levels of reactive oxygen species due to decreased NFE2L2 activation. Elevated levels of intracellular reactive oxygen species were observed in the EIF2AK3 null cells, and this was associated with the onset of apoptotic cell death. These findings confirm the prosurvival and antioxidant role of UPR-mediated EIF2AK3 activation in the context of the human uterine myocyte.
C1 [Ramnarayanan, Saiprasad; Kyathanahalli, Chandrashekara; Park-York, MieJung; Jeyasuria, Pancharatnam; Condon, Jennifer C.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, 275 East Hancock St, Detroit, MI 48201 USA.
[Ingles, Judith; Jeyasuria, Pancharatnam; Condon, Jennifer C.] Wayne State Univ, Sch Med, Dept Physiol, 275 East Hancock St, Detroit, MI 48201 USA.
[Jeyasuria, Pancharatnam; Condon, Jennifer C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Bethesda, MD USA.
RP Condon, JC (reprint author), Wayne State Univ, CS Mott Ctr, 275 East Hancock St, Detroit, MI 48201 USA.
EM jcondon@med.wayne.edu
FU March of Dimes [21 FY2012-152]; NICHD [1R01HD065011]
FX This work was supported by the March of Dimes #21 FY2012-152 and the
NICHD 1R01HD065011.
NR 46
TC 0
Z9 0
U1 1
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD DEC 1
PY 2016
VL 95
IS 6
AR 120
DI 10.1095/biolreprod.116.141804
PG 9
WC Reproductive Biology
SC Reproductive Biology
GA EG1PJ
UT WOS:000390804400007
PM 27733380
ER
PT J
AU Chen, SC
Kim, SYH
AF Chen, Stephanie C.
Kim, Scott Y. H.
TI A framework for analysis of research risks and benefits to participants
in standard of care pragmatic clinical trials
SO CLINICAL TRIALS
LA English
DT Article
DE Comparative effectiveness randomized control trials; pragmatic
randomized control trials; informed consent; research risk analysis;
research ethics
ID RECURRENT ERYSIPELAS; SESSION LENGTH; BREAST-CANCER; MORTALITY;
HEMODIALYSIS; ETHICS; ASSOCIATIONS; PROPHYLAXIS; PENICILLIN; CONSENT
AB Background/Aims: Standard of care pragmatic clinical trials that compare treatments already in use could improve care and reduce costs, but there is considerable debate about the research risks of standard of care pragmatic clinical trials and how to apply informed consent regulations to such trials. We sought to develop a framework integrating the insights from opposing sides of the debate.
Methods: We developed a formal risk benefit analysis framework for standard of care pragmatic clinical trials and then applied it to key provisions of the US federal regulations.
Results: Our formal framework for standard of care pragmatic clinical trial risk benefit analysis takes into account three key considerations: the ex ante estimates of risks and benefits of the treatments to be compared in a standard of care pragmatic clinical trial, the allocation ratios of treatments inside and outside such a trial, and the significance of some participants receiving a different treatment inside a trial than outside the trial. The framework provides practical guidance on how the research ethics regulations on informed consent should be applied to standard of care pragmatic clinical trials.
Conclusion: Our proposed formal model makes explicit the relationship between the concepts used by opposing sides of the debate about the research risks of standard of care pragmatic clinical trials and can be used to clarify the implications for informed consent.
C1 [Chen, Stephanie C.; Kim, Scott Y. H.] NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,IC118, Bethesda, MD 20892 USA.
[Kim, Scott Y. H.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,IC118, Bethesda, MD 20892 USA.
EM scott.kim@nih.gov
FU Intramural Research Program at the National Institutes of Health
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported by the Intramural Research Program at the
National Institutes of Health.
NR 31
TC 1
Z9 1
U1 1
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2016
VL 13
IS 6
BP 605
EP 611
DI 10.1177/1740774516656945
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EG0KZ
UT WOS:000390723000007
PM 27365010
ER
PT J
AU Fay, MP
Follmann, DA
AF Fay, Michael P.
Follmann, Dean A.
TI Non-inferiority tests for anti-infective drugs using control group
quantiles
SO CLINICAL TRIALS
LA English
DT Article
DE Difference in proportions; exact test; non-inferiority margin; variable
margin
ID PROPORTIONS; PNEUMONIA
AB Background/Aims: In testing for non-inferiority of anti-infective drugs, the primary endpoint is often the difference in the proportion of failures between the test and control group at a landmark time. The landmark time is chosen to approximately correspond to the qth historic quantile of the control group, and the non-inferiority margin is selected to be reasonable for the target level q. For designing these studies, a troubling issue is that the landmark time must be pre-specified, but there is no guarantee that the proportion of control failures at the landmark time will be close to the target level q. If the landmark time is far from the target control quantile, then the pre-specified non-inferiority margin may not longer be reasonable. Exact variable margin tests have been developed by Rohmel and Kieser to address this problem, but these tests can have poor power if the observed control failure rate at the landmark time is far from its historic value.
Methods: We develop a new variable margin non-inferiority test where we continue sampling until a pre-specified proportion of failures, q, have occurred in the control group, where q is the target quantile level. The test does not require any assumptions on the failure time distributions, and hence, no knowledge of the true qth control quantile for the study is needed.
Results: Our new test is exact and has power comparable to (or greater than) its competitors when the true control quantile from the study equals (or differs moderately from) its historic value. Our nivm R package performs the test and gives confidence intervals on the difference in failure rates at the true target control quantile. The tests can be applied to time to cure or other numeric variables as well.
Conclusion: A substantial proportion of new anti-infective drugs being developed use non-inferiority tests in their development, and typically, a pre-specified landmark time and its associated difference margin are set at the design stage to match a specific target control quantile. If through changing standard of care or selection of a different population the target quantile for the control group changes from its historic value, then the appropriateness of the pre-specified margin at the landmark time may be questionable. Our proposed test avoids this problem by sampling until a pre-specified proportion of the controls have failed.
C1 [Fay, Michael P.; Follmann, Dean A.] NIAID, Biostat Res Branch, 5601 Fishers Lane,MSC 9820, Rockville, MD 20892 USA.
RP Fay, MP (reprint author), NIAID, Biostat Res Branch, 5601 Fishers Lane,MSC 9820, Rockville, MD 20892 USA.
EM mfay@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 11
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2016
VL 13
IS 6
BP 632
EP 640
DI 10.1177/1740774516654861
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EG0KZ
UT WOS:000390723000010
PM 27430709
ER
PT J
AU Korn, EL
Freidlin, B
AF Korn, Edward L.
Freidlin, Boris
TI Non-factorial analyses of two-by-two factorial trial designs
SO CLINICAL TRIALS
LA English
DT Article
DE Factorial design; factorial analysis; Hochberg procedure; interaction;
multiple comparisons; 2 x 2 trial design
ID ASSESS CHELATION-THERAPY; HIGH-DOSE MULTIVITAMINS; CLINICAL-TRIALS;
MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; COMBINATION; TESTS; MINERALS;
TACT
AB Background/aims Factorial analyses of 2 x 2 trial designs are known to be problematic unless one can be sure that there is no interaction between the treatments (A and B). Instead, we consider non-factorial analyses of a factorial trial design that addresses clinically relevant questions of interest without any assumptions on the interaction. Primary questions of interest are as follows: (1) is A better than the control treatment C, (2) is B better than C, (3) is the combination of A and B (AB) better than C, and (4) is AB better than A, B, and C.
Methods A simple three-step procedure that tests the first three primary questions of interest using a Bonferroni adjustment at the first step is proposed. A Hochberg procedure on the four primary questions is also considered. The two procedures are evaluated and compared in limited simulations. Published results from three completed trials with factorial designs are re-evaluated using the two procedures.
Results Both suggested procedures (that answer multiple questions) require a 50%-60% increase in per arm sample size over a two-arm design asking a single question. The simulations suggest a slight advantage to the three-step procedure in terms of power (for the primary and secondary questions). The proposed procedures would have formally addressed the questions arising in the highlighted published trials arguably more simply than the pre-specified factorial analyses used.
Conclusion Factorial trial designs are an efficient way to evaluate two treatments, alone and in combination. In situations where a statistical interaction between the treatment effects cannot be assumed to be 0, simple non-factorial analyses are possible that directly assess the questions of interest without the zero interaction assumption.
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Program, MSC 9735, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Program, MSC 9735, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 27
TC 0
Z9 0
U1 3
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2016
VL 13
IS 6
BP 651
EP 659
DI 10.1177/1740774516659472
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EG0KZ
UT WOS:000390723000012
PM 27439306
ER
PT J
AU Sheehan, J
Hirschfeld, S
Foster, E
Ghitza, U
Goetz, K
Karpinski, J
Lang, L
Moser, RP
Odenkirchen, J
Reeves, D
Rubinstein, Y
Werner, E
Huerta, M
AF Sheehan, Jerry
Hirschfeld, Steven
Foster, Erin
Ghitza, Udi
Goetz, Kerry
Karpinski, Joanna
Lang, Lisa
Moser, Richard P.
Odenkirchen, Joanne
Reeves, Dianne
Rubinstein, Yaffa
Werner, Ellen
Huerta, Michael
TI Improving the value of clinical research through the use of Common Data
Elements
SO CLINICAL TRIALS
LA English
DT Article
DE Common Data Elements; data collection; data sharing; interoperability;
data standards
ID TRIALS
AB The use of Common Data Elements can facilitate cross-study comparisons, data aggregation, and meta-analyses; simplify training and operations; improve overall efficiency; promote interoperability between different systems; and improve the quality of data collection. A Common Data Element is a combination of a precisely defined question (variable) paired with a specified set of responses to the question that is common to multiple datasets or used across different studies. Common Data Elements, especially when they conform to accepted standards, are identified by research communities from variable sets currently in use or are newly developed to address a designated data need. There are no formal international specifications governing the construction or use of Common Data Elements. Consequently, Common Data Elements tend to be made available by research communities on an empiric basis. Some limitations of Common Data Elements are that there may still be differences across studies in the interpretation and implementation of the Common Data Elements, variable validity in different populations, and inhibition by some existing research practices and the use of legacy data systems. Current National Institutes of Health efforts to support Common Data Element use are linked to the strengthening of National Institutes of Health Data Sharing policies and the investments in data repositories. Initiatives include cross-domain and domain-specific resources, construction of a Common Data Element Portal, and establishment of trans-National Institutes of Health working groups to address technical and implementation topics. The National Institutes of Health is seeking to lower the barriers to Common Data Element use through greater awareness and encourage the culture change necessary for their uptake and use. As National Institutes of Health, other agencies, professional societies, patient registries, and advocacy groups continue efforts to develop and promote the responsible use of Common Data Elements, particularly if linked to accepted data standards and terminologies, continued engagement with and feedback from the research community will remain important.
C1 [Sheehan, Jerry; Foster, Erin; Karpinski, Joanna; Lang, Lisa; Huerta, Michael] NIH, Natl Lib Med, 38 Ctr Dr,Rm 2S20,MSC 3811, Bethesda, MD 20894 USA.
[Hirschfeld, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Ghitza, Udi] NIDA, NIH, Bethesda, MD 20892 USA.
[Goetz, Kerry] NEI, NIH, Bethesda, MD 20892 USA.
[Moser, Richard P.; Reeves, Dianne] NCI, NIH, Bethesda, MD 20892 USA.
[Odenkirchen, Joanne] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Rubinstein, Yaffa] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Werner, Ellen] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Huerta, M (reprint author), NIH, Natl Lib Med, 38 Ctr Dr,Rm 2S20,MSC 3811, Bethesda, MD 20894 USA.
EM mike.huerta@nih.hhs.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 11
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2016
VL 13
IS 6
BP 671
EP 676
DI 10.1177/1740774516653238
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EG0KZ
UT WOS:000390723000015
PM 27311638
ER
PT J
AU Szczesna, E
Kasprzak, AA
AF Szczesna, Ewa
Kasprzak, Andrzej A.
TI Insights into the process of EB1-dependent tip-tracking of kinesin-14
Ncd. The role of the microtubule
SO EUROPEAN JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE EB1; Kinesin-14; Ncd; Tip-tracking; Microtubule plus end; +TIPs
ID PLUS-END-TRACKING; IN-VITRO; LOCALIZATION SIGNAL; EB1; PROTEIN;
RECONSTITUTION; MICROSCOPY; DYNAMICS; CLIP-170; CAP
AB End-binding proteins are capable of tracking the plus-ends of growing microtubules (MTs). The motor protein Ncd, a member of the kinesin-14 family, interacts with EB1 protein and becomes a non-autonomous tip-tracker. Here, we attempted to find out whether at least for Ncd, the efficient EB1-ediated tip-tracking involves the interaction of the kinesin with the MT surface. We prepared a series of Ncd tail mutants in which the MT-binding sites were altered or eliminated. Using TIRF microscopy, we characterized their behavior as tip-trackers and measured the dwell times of single molecules of EB1 and Ncd tail or its mutated forms.
The mutated forms of Ncd tail exhibited tip-tracking in the presence of EB1 and the effectiveness of this process was proportional to the affinity of the mutant's tail to MT. Even though the interaction of Ncd with EB1 was weak (K-d similar to 9 mu M) the half saturating concentration of EB1 for tip-tracking was 7 nM. The dwell time of Ncd tail in the presence of EB1 was similar to 1 s. The dwell time of EB1 alone was shorter (similar to 0.3 s) and increased considerably in the presence of a large excess of Ncd tail. We demonstrated that tip-tracking of kinesin-14 occurs through several concurrent mechanisms: binding of kinesin only to EB1 located at the MT end, interaction of the kinesin molecules with a composite site formed by EB1 and the MT tip, and probably surface diffusion of the tail along MT. The second mechanism seems to play a crucial role in efficient tip-tracking. (C) 2016 Elsevier GmbH. All rights reserved.
C1 [Szczesna, Ewa; Kasprzak, Andrzej A.] Polish Acad Sci, Nencki Inst Expt Biol, Dept Biochem, 3 Pasteur St, PL-02093 Warsaw, Poland.
[Szczesna, Ewa] NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Kasprzak, AA (reprint author), Polish Acad Sci, Nencki Inst Expt Biol, Dept Biochem, 3 Pasteur St, PL-02093 Warsaw, Poland.
EM e.szczesna@nencki.gov.pl; a.kasprzak@nencki.gov.pl
RI Kasprzak, Andrzej/R-4476-2016
FU National Science Centre [DEC-2012/05/N/NZ1/00020]
FX We thank Krzysztof Skowronek and Seweryn Bajer for reagents and helpful
discussions and Michal Szkop and Beata Kliszcz for critically reading
the manuscript. The study was supported in part by National Science
Centre grant DEC-2012/05/N/NZ1/00020.
NR 40
TC 0
Z9 0
U1 6
U2 6
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-9335
EI 1618-1298
J9 EUR J CELL BIOL
JI Eur. J. Cell Biol.
PD DEC
PY 2016
VL 95
IS 12
BP 521
EP 530
DI 10.1016/j.ejcb.2016.08.004
PG 10
WC Cell Biology
SC Cell Biology
GA EF9CU
UT WOS:000390629100001
PM 27608966
ER
PT J
AU Price, AJ
Travis, RC
Appleby, PN
Albanes, D
Gurrea, AB
Bjorge, T
Bueno-de-Mesquita, HB
Chen, C
Donovan, J
Gislefoss, R
Goodman, G
Gunter, M
Hamdy, FC
Johansson, M
King, IB
Kuhn, T
Mannisto, S
Martin, RM
Meyer, K
Neal, DE
Neuhouser, ML
Nygard, O
Stattin, P
Tell, GS
Trichopoulou, A
Tumino, R
Ueland, PM
Ulvik, A
de Vogel, S
Vollset, SE
Weinstein, SJ
Key, TJ
Allen, NE
AF Price, Alison J.
Travis, Ruth C.
Appleby, Paul N.
Albanes, Demetrius
Gurrea, Aurelio Barricarte
Bjorge, Tone
Bueno-de-Mesquita, H. Bas
Chen, Chu
Donovan, Jenny
Gislefoss, Randi
Goodman, Gary
Gunter, Marc
Hamdy, Freddie C.
Johansson, Mattias
King, Irena B.
Kuehn, Tilman
Mannisto, Satu
Martin, Richard M.
Meyer, Klaus
Neal, David E.
Neuhouser, Marian L.
Nygard, Ottar
Stattin, Par
Tell, Grethe S.
Trichopoulou, Antonia
Tumino, Rosario
Ueland, Per Magne
Ulvik, Arve
de Vogel, Stefan
Vollset, Stein Emil
Weinstein, Stephanie J.
Key, Timothy J.
Allen, Naomi E.
TI Circulating Folate and Vitamin B-12 and Risk of Prostate Cancer: A
Collaborative Analysis of Individual Participant Data from Six Cohorts
Including 6875 Cases and 8104 Controls
SO EUROPEAN UROLOGY
LA English
DT Article
DE Folate; Vitamin B-12; Prostate cancer; High grade; Prospective cohort;
Pooled data meta-analysis
ID ONE-CARBON METABOLISM; FOLIC-ACID; SERUM FOLATE; CLOT CONTACT;
HOMOCYSTEINE; BIOMARKERS; ASSOCIATION; POPULATION; STABILITY; NUTRITION
AB Background: Folate and vitamin B-12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.
Objective: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.
Design, setting, and participants: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.
Outcome measurements and statistical analysis: Incident PCa and subtype by stage and grade.
Results and limitations: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], p(trend) = 0.018, for folate and 1.12 [95% CI, 1.01-1.25], p(trend) = 0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (p(heterogeneity) < 0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend = 0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (p(heterogeneity) > 0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.
Conclusions: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.
Patient summary: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease. (C) 2016 European Association of Urology. Published by Elsevier B.V.
C1 [Price, Alison J.; Travis, Ruth C.; Appleby, Paul N.; Key, Timothy J.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
[Price, Alison J.] London Sch Hyg & Trop Med, London, England.
[Albanes, Demetrius; Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gurrea, Aurelio Barricarte] Navarra Publ Hlth Inst, Pamplona, Spain.
[Gurrea, Aurelio Barricarte] Navarra Inst Hlth Res IdiSNA, Pamplona, Spain.
[Gurrea, Aurelio Barricarte] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.
[Bjorge, Tone; Tell, Grethe S.; de Vogel, Stefan; Vollset, Stein Emil] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Bjorge, Tone; Gislefoss, Randi] Canc Registry Norway, Oslo, Norway.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas; Gunter, Marc] Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Dept Social & Prevent Med, Fac Med, Kuala Lumpur, Malaysia.
[Chen, Chu; Goodman, Gary; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Donovan, Jenny; Martin, Richard M.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Oxford, England.
[Johansson, Mattias] Int Agcy Res Canc, Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Biobank Res, Umea, Sweden.
[King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Kuehn, Tilman] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
[Martin, Richard M.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England.
[Martin, Richard M.] Natl Inst Hlth Res, Bristol Biomed Res Unit Nutr, Bristol, Avon, England.
[Meyer, Klaus; Ulvik, Arve] Bevital AS, Bergen, Norway.
[Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge, England.
[Nygard, Ottar; Ueland, Per Magne] Univ Bergen, Dept Clin Sci, Bergen, Norway.
[Nygard, Ottar] Haukeland Hosp, Dept Heart Dis, Bergen, Norway.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Trichopoulou, Antonia] Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat, Athens, Greece.
[Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece.
[Tumino, Rosario] ASP Ragusa, Canc Registry & Histopathol Unit, Civ MP Arezzo Hosp, Ragusa, Italy.
[Vollset, Stein Emil] Norwegian Inst Publ Hlth, Bergen, Norway.
[Gislefoss, Randi] Inst Populat Based Res, Oslo, Norway.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Clin Trial Serv Unit, Oxford, England.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Epidemiol Studies Unit, Oxford, England.
RP Price, AJ (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
EM alison.price@ceu.ox.ac.uk
OI Price, Alison/0000-0002-3891-3337
FU Cancer Research UK [C570/ A16491, C8221/A19170, 14136]; Intramural
Research Program of the U.S. National Cancer Institute, National
Institutes of Health; U.S. Public Health Service from the National
Cancer Institute [HHSN261201500005C]; Department of Health and Human
Services; CARET: NIH [UM1CA167462, U01CA63673, R01CA96789]; European
Commission (DG-SANCO); International Agency for Research on Cancer;
Danish Cancer Society (Denmark); German Cancer Aid; German Cancer
Research Center (DKFZ); Federal Ministry of Education and Research
(BMBF); Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; Federal
Ministry of Education and Research (Germany); Hellenic Health Foundation
(Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy;
National Research Council (Italy); Dutch Ministry of Public Health,
Welfare and Sports; Netherlands Cancer Registry; LK Research Funds;
Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World
Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands);
Health Research Fund (FIS) [PI13/01162, PI13/00061]; Regional
Governments of Andalucia, Asturias; Basque Country; Murcia and Navarra;
ISCIII RETIC (Spain) [RD06/0020]; Swedish Cancer Society; Swedish
Research Council; County Council of Skane (Sweden); County Council of
Vasterbotten (Sweden); Medical Research Council [1000143, MR/M012190/1];
Norwegian Cancer Society [107335-PR-2007-0153]; Swedish Cancer Society
[4620]; Lions Research Foundation, Umea, Sweden; Medical Faculty, Umea
University; World Cancer Research Fund UK [2007/07]; National Cancer
Research Institute; UK NIHR Health Technology Assessment Programme
[96/20/06, 96/20/99]; NIHR through the Biomedical Research Centre; CRUK
programme grant (the Integrative Cancer Epidemiology Programme)
[C18281/A19169]; National Institute for Health Research (NIHR) Bristol
Nutritional Biomedical Research Unit based at University Hospitals
Bristol NHS Foundation Trust; University of Bristol
FX This work was supported by Cancer Research UK (grant numbers C570/
A16491 and C8221/A19170). The funders of the study had no role in the
study design, data collection, data analysis, data interpretation or
writing of the report. The authors in the writing team had full access
to the all data in the study. The corresponding author had the final
responsibility for the decision to submit for publication. Funding for
the collaborating studies was as follows: ATBC: The ATBC Study is
supported by the Intramural Research Program of the U.S. National Cancer
Institute, National Institutes of Health, and by U.S. Public Health
Service contract HHSN261201500005C from the National Cancer Institute,
Department of Health and Human Services. CARET: NIH grants UM1CA167462,
U01CA63673, and R01CA96789. EPIC: The coordination of EPIC is
financially supported by the European Commission (DG-SANCO) and the
International Agency for Research on Cancer. The national cohorts are
supported by Danish Cancer Society (Denmark); German Cancer Aid, German
Cancer Research Center (DKFZ), Federal Ministry of Education and
Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum
and Federal Ministry of Education and Research (Germany); the Hellenic
Health Foundation (Greece); Associazione Italiana per la Ricerca sul
Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry
of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry
(NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg
Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics
Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to
Granada;, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucia,
Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020)
(Spain); Swedish Cancer Society, Swedish Research Council and County
Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136
to EPIC-Norfolk; C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical
Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford)
(United Kingdom). Janus: Norwegian Cancer Society (Grant Number
107335-PR-2007-0153). NSHDC: The Swedish Cancer Society (Grant Number
4620), the Lions Research Foundation, Umea, Sweden and Medical Faculty,
Umea University. ProtecT: funded through the World Cancer Research Fund
UK (grant number: 2007/07). The National Cancer Research Institute
(administered by the Medical Research Council) provided support for the
development of the ProtecT epidemiologic database through the Prostate
Mechanisms of Progression and Treatment collaborative. The ProtecT study
is supported by the UK NIHR Health Technology Assessment Programme
(projects 96/20/06, 96/20/99). Support for the ProtecT bio-repository in
Cambridge is provided by NIHR through the Biomedical Research Centre.
Richard Martin is supported by a CRUK programme grant, number
C18281/A19169 (the Integrative Cancer Epidemiology Programme) and by the
National Institute for Health Research (NIHR) Bristol Nutritional
Biomedical Research Unit based at University Hospitals Bristol NHS
Foundation Trust and the University of Bristol. The views expressed are
those of the authors and not necessarily those of the NHS, the NIHR, or
the Department of Health.
NR 36
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD DEC
PY 2016
VL 70
IS 6
BP 941
EP 951
DI 10.1016/j.eururo.2016.03.029
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA EF8FA
UT WOS:000390563100020
PM 27061263
ER
PT J
AU Velho, RV
De Pace, R
Tidow, H
Braulke, T
Pohl, S
AF Velho, Renata Voltolini
De Pace, Raffaella
Tidow, Henning
Braulke, Thomas
Pohl, Sandra
TI Identification of the interaction domains between alpha- and
gamma-subunits of GlcNAc-1-phosphotransferase
SO FEBS LETTERS
LA English
DT Article
DE hexameric GlcNAc-1-phosphotransferase complex; lysosomal enzymes;
mannose 6-phosphate; MRH domain; mucolipidosis II and III; pull-down
interaction approach
ID GLCNACLYSOSOMAL ENZYME N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE;
LYSOSOMAL-ENZYMES; PROTEIN; MUTATIONS; RECOGNITION; REGIONS
AB The disease-associated hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex ((222)) catalyzes the formation of mannose 6-phosphate residues on lysosomal enzymes required for efficient targeting to lysosomes. Using pull-down experiments and mutant subunits, we identified a potential loop-like region in the -subunits comprising residues 535-588 and 645-698 involved in the binding to -subunits. The interaction is independent of the mannose 6-phosphate receptor homology domain but requires the N-terminal unstructured part of the -subunit consisting of residues 26-69. These studies provide new insights into structural requirements for the assembly of the GlcNAc-1-phosphotransferase complex, and the functions of distinct domains of the - and -subunits.
C1 [Velho, Renata Voltolini; De Pace, Raffaella; Braulke, Thomas; Pohl, Sandra] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Biochem Sect, Martinistr 52, D-20246 Hamburg, Germany.
[Tidow, Henning] Univ Hamburg, Inst Biochem & Mol Biol, Hamburg, Germany.
[De Pace, Raffaella] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD USA.
RP Pohl, S (reprint author), Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Biochem Sect, Martinistr 52, D-20246 Hamburg, Germany.
EM s.pohl@uke.de
FU Deutsche Forschungsgemeinschaft [GRK1459, SFB877-B3]
FX This study was supported by Deutsche Forschungsgemeinschaft (GRK1459 and
SFB877-B3).
NR 26
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD DEC
PY 2016
VL 590
IS 23
BP 4287
EP 4295
DI 10.1002/1873-3468.12456
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA EF5ST
UT WOS:000390390600014
PM 27736005
ER
PT J
AU Sarrel, PM
Sullivan, SD
Nelson, LM
AF Sarrel, Philip M.
Sullivan, Shannon D.
Nelson, Lawrence M.
TI Hormone replacement therapy in young women with surgical primary ovarian
insufficiency
SO FERTILITY AND STERILITY
LA English
DT Review
DE Premenopausal oophorectomy; ovarian insufficiency; surgical menopause;
estrogen therapy
ID BILATERAL SALPINGO-OOPHORECTOMY; RECENTLY POSTMENOPAUSAL WOMEN; TERM
HEALTH CONSEQUENCES; LONG-TERM; EARLY MENOPAUSE; CARDIOVASCULAR-DISEASE;
VASOMOTOR SYMPTOMS; BREAST-CANCER; HOT FLASHES; PROPHYLACTIC
OOPHORECTOMY
AB Bilateral oophorectomy performed in women before they are menopausal induces surgical primary ovarian insufficiency, an acute and chronic deficiency of the hormones normally produced by the ovaries. Without hormone replacement therapy (HRT) most of these women develop severe symptoms of estrogen (E) deficiency and are at increased risk for osteoporosis, cardiovascular disease, cognitive decline, dementia, and the associated increases in morbidity and mortality. In cases in which a hysterectomy has been performed at the time of bilateral oophorectomy transdermal or transvaginal E-2 replacement therapy without cyclic progestin replacement is the optimum hormonal management for these women. There is substantial evidence this approach even reduces the risk for breast cancer. Unfortunately, unwarranted fear of all menopausal HRTs has become widespread following the reports of the Women's Health Initiative studies. This fear has led to a steep decline in use of E therapy, even in women in whom HRT is clearly indicated. Discussion of possible ovarian conservation in women who are premenopausal is an integral part of the preoperative planning for any women undergoing hysterectomy. Timely and effective HRT for women who will experience surgical primary ovarian insufficiency is clearly indicated. (C) 2016 by American Society for Reproductive Medicine.
C1 [Sarrel, Philip M.] Yale Univ, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Sarrel, Philip M.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Sullivan, Shannon D.] US FDA, Silver Spring, MD USA.
[Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, CAPT US Publ Hlth Serv, Intramural Res Program, NIH, Bethesda, MD USA.
RP Nelson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, CAPT US Publ Hlth Serv, Intramural Res Program, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM Lawrence_Nelson@nih.gov
FU Intramural Research Program, National Institutes of Health, Bethesda, MD
FX Supported in part by the Intramural Research Program, National
Institutes of Health, Bethesda, MD.
NR 76
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U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2016
VL 106
IS 7
BP 1580
EP 1587
DI 10.1016/j.fertnstert.2016.09.018
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA EF9RU
UT WOS:000390668400007
PM 27793381
ER
PT J
AU Sullivan, SD
Sarrel, PM
Nelson, LM
AF Sullivan, Shannon D.
Sarrel, Philip M.
Nelson, Lawrence M.
TI Hormone replacement therapy in young women with primary ovarian
insufficiency and early menopause
SO FERTILITY AND STERILITY
LA English
DT Review
DE Primary ovarian insufficiency; premature ovarian failure; premature
menopause; early menopause; estrogen; progestin; androgen; hormone
replacement therapy; menopausal hormone therapy; management; morbidity;
mortality
ID BONE-MINERAL DENSITY; CLINICAL-PRACTICE GUIDELINE; PLACEBO-CONTROLLED
TRIAL; RANDOMIZED CONTROLLED-TRIAL; MEIBOMIAN GLAND SECRETIONS; SEX
STEROID REPLACEMENT; ISCHEMIC-HEART-DISEASE; POSTMENOPAUSAL WOMEN;
ESTROGEN-REPLACEMENT; TURNER-SYNDROME
AB Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, similar to 50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women. (C) 2016 by American Society for Reproductive Medicine.
C1 [Sullivan, Shannon D.] US FDA, Silver Spring, MD USA.
[Sarrel, Philip M.] Yale Univ, Obstet Gynecol & Reprod Sci & Psychiat, New Haven, CT USA.
[Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA.
RP Nelson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Publ Hlth Serv, Intramural Res Program, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM lawrence_nelson@nih.gov
FU Intramural Research Program, National Institute of Child Health and
Human Development, National Institutes of Health, Bethesda, Maryland
FX Supported in part by the Intramural Research Program, National Institute
of Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland (L.M.N.).
NR 116
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Z9 1
U1 14
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2016
VL 106
IS 7
BP 1588
EP 1599
DI 10.1016/j.fertnstert.2016.09.046
PG 12
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA EF9RU
UT WOS:000390668400008
PM 27912889
ER
PT J
AU Chin, HB
Howards, PP
Kramer, MR
Mertens, AC
Spencer, JB
AF Chin, Helen B.
Howards, Penelope P.
Kramer, Michael R.
Mertens, Ann C.
Spencer, Jessica B.
TI Which female cancer patients fail to receive fertility counseling before
treatment in the state of Georgia?
SO FERTILITY AND STERILITY
LA English
DT Article
DE Cancer survivors; fertility counseling; female fertility
ID BREAST-CANCER; YOUNG-WOMEN; AMERICAN-SOCIETY; PRESERVATION;
CHEMOTHERAPY; PREGNANCY; SURVIVORS; DISPARITIES; PARENTHOOD; ADOLESCENT
AB Objective: To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer.
Design: Population-based cohort study.
Setting: Not applicable.
Patient(s): A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis.
Intervention(s): None.
Main Outcome Measure(s): The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant.
Result(s): Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types.
Conclusion(s): Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access. (C) 2016 by American Society for Reproductive Medicine.
C1 [Chin, Helen B.; Howards, Penelope P.; Kramer, Michael R.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
Emory Univ, Sch Med, Dept Pediat, Aflac Canc Ctr, Atlanta, GA USA.
Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA.
RP Chin, HB (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,Mailstop A3-05, Res Triangle Pk, NC 27709 USA.
EM helen.chin@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development grant [1R01HD066059]; Reproductive, Perinatal, and Pediatric
Training Grant [T32HD052460]; Health Resources, and Service
Administration Training Grant [T03MC07651-06]; Intramural Research
Program of the National Institute of Environmental Health Sciences,
National Institutes of Health
FX Supported by Eunice Kennedy Shriver National Institute of Child Health
and Human Development grant 1R01HD066059, Reproductive, Perinatal, and
Pediatric Training Grant T32HD052460, Health Resources, and Service
Administration Training Grant T03MC07651-06, and in part by the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health.
NR 41
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2016
VL 106
IS 7
BP 1763
EP +
DI 10.1016/j.fertnstert.2016.08.034
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA EF9RU
UT WOS:000390668400033
PM 27678034
ER
PT J
AU Duan, LQ
Davis, JS
Woolbright, BL
Du, K
Cahkraborty, M
Weemhoff, J
Jaeschke, H
Bourdi, M
AF Duan, Luqi
Davis, John S.
Woolbright, Benjamin L.
Du, Kuo
Cahkraborty, Mala
Weemhoff, James
Jaeschke, Hartmut
Bourdi, Mohammed
TI Differential susceptibility to acetaminophen-induced liver injury in
sub-strains of C57BL/6 mice: 6N versus 6J
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Acetaminophen hepatotoxicity; C57BL/6 sub-strains; Mitochondrial
dysfunction; Protein adducts; DNA fragmentation
ID INDUCED HEPATIC-NECROSIS; CULTURED MOUSE HEPATOCYTES; PARA-BENZOQUINONE
IMINE; INDUCED OXIDANT STRESS; INDUCED HEPATOTOXICITY; TERMINAL KINASE;
CELL-DEATH; PROTEIN ADDUCTS; MITOCHONDRIAL DYSFUNCTION; PERMEABILITY
TRANSITION
AB Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the literature may have ben caused by sub-strain mismatches, e.g. C57BL/6J and C57BL/6N. This study was initiated to determine the mechanism behind the sub-strain susceptibility to APAP toxicity. C57BL/6N and C57BL/6J mice were dosed with 200 mg/kg APAP and sacrificed at different time points. C57BL/6N mice developed significantly more liver injury as measured by plasma ALT activities and histology. Although there was no difference in glutathione depletion or cytochrome P450 activity between groups, C57BL/6N had a higher glutathione disulfide-to-glutathione ratio and more APAP protein adducts. C57BL/6N showed more mitochondrial translocation of phospho-JNK and BAX, and more release of mitochondrial intermembrane proteins apoptosis-inducing factor (AIF), second mitochondria-derived activator of caspases (SMAC), which caused more DNA fragmentation. The increased mitochondrial dysfunction was confirmed in vitro as C57BL/6N hepatocytes had a more precipitous drop in JC-1 fluorescence after APAP exposure. Conclusion: C57BL/6N mice are more susceptible to APAP-induced hepatotoxicity, likely due to increased formation of APAP-protein adducts and a subsequent enhancement of mitochondrial dysfunction associated with aggravated nuclear DNA fragmentation. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Duan, Luqi; Woolbright, Benjamin L.; Du, Kuo; Weemhoff, James; Jaeschke, Hartmut] Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
[Davis, John S.; Cahkraborty, Mala; Bourdi, Mohammed] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD USA.
[Davis, John S.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Cahkraborty, Mala] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Bourdi, Mohammed] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Jaeschke, H (reprint author), Univ Kansas, Dept Pharmacol Toxicol & Therapeut, Med Ctr, 3901 Rainbow Blvd,MS 1018, Kansas City, KS 66160 USA.
EM lduan@kumc.edu; John.Davis@nih.gov; bwoolbright@kmc.edu; kdu@kumc.edu;
cahkraborty@nih.gov; jweemhoff@kumc.edu; hjaeschke@kumc.edu;
mohammed.bourdi@nih.gov
FU National Institutes of Health [R01 AA12916, R01 DK102142]; National
Center for Research Resources of the National Institutes of Health
[5P20RR021940-07]; National Institute of General Medical Sciences of the
National Institutes of Health [8 P20 GM103549-07]; National Institute of
Environmental Health Sciences [T32 ES007079-26A2]
FX This work was supported in part by the National Institutes of Health
grants R01 AA12916, and R01 DK102142 and by grants from the National
Center for Research Resources (5P20RR021940-07) and the National
Institute of General Medical Sciences (8 P20 GM103549-07) of the
National Institutes of Health. Additional support came from the
"Training Program in Environmental Toxicology" T32 ES007079-26A2 (to
B.L.W.) from the National Institute of Environmental Health Sciences.
NR 60
TC 0
Z9 0
U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD DEC
PY 2016
VL 98
BP 107
EP 118
DI 10.1016/j.fct.2016.10.021
PN B
PG 12
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA EF7JH
UT WOS:000390505400003
PM 27773698
ER
PT J
AU Catlin, NR
Herbert, R
Janardhan, K
Hejtmancik, MR
Fomby, LM
Vallant, M
Kissling, GE
DeVito, MJ
AF Catlin, Natasha R.
Herbert, Ron
Janardhan, Kyathanahalli
Hejtmancik, Milton R.
Fomby, Laurene M.
Vallant, Molly
Kissling, Grace E.
DeVito, Michael J.
TI Dose-response assessment of the dermal toxicity of Virginia cedarwood
oil in F344/N rats and B6C3F1/N mice
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Cedarwood oil; Benchmark dose; Skin
ID ALPHA-CEDRENE; ANIMAL-MODELS; IN-VIVO; SKIN; DERMATITIS; ABSORPTION;
PERFUMES
AB Virginia cedarwood oil is widely used as a fragrance material in household and personal products and as a naturally derived pesticide alternative. Due to conflicting literature on dermal exposures in animals and humans, concern for safe levels of human exposure remains. The present study evaluated the toxicity of cedarwood oil applied dermally to F344/N rats and B6C3F1/N mice for 13 weeks. Groups of 10 male and female rats and mice received no treatment (untreated control) or were administered cedarwood oil in 95% aqueous ethanol dermally at concentrations ranging from 0% (vehicle control), 6.25%, 12.5%, 25%, 50%, and 100% (undiluted). Rats and mice developed extensive skin lesions at the site of application. Benchmark dose modeling (BMD) was performed for the significantly increased skin lesions observed in the rat, to provide perspective for risk assessment applications. Benchmark dose modeling levels (BMDL) of 0.65 to 2.1% and 1.2 to 4.4% (equivalent to 13 to 42 mg/Kg and 24 to 48 mg/kg, respectively) cedarwood oil were calculated for the most sensitive endpoint of epidermal hyperplasia in female rats and chronic active inflammation in male rats, respectively. These BMDL levels coincide with reported use levels in cosmetics and pesticides, raising the concern for human exposure. Published by Elsevier Ltd.
C1 [Catlin, Natasha R.; Herbert, Ron; Vallant, Molly; Kissling, Grace E.; DeVito, Michael J.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli] Integrated Lab Syst Inc, Morrisville, NC 27560 USA.
[Hejtmancik, Milton R.; Fomby, Laurene M.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Catlin, NR (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM natasha.catlin@nih.gov
FU National Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, United States Department of
Health and Human Services [N01-ES-65406]
FX This work was performed for the National Toxicology Program, National
Institute of Environmental Health Sciences, National Institutes of
Health, United States Department of Health and Human Services, under
contract No. N01-ES-65406. Prior to submission this work was reviewed by
Drs. Vicki Sutherland and Matthew Stout.
NR 32
TC 0
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U1 4
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD DEC
PY 2016
VL 98
BP 159
EP 168
DI 10.1016/j.fct.2016.10.016
PN B
PG 10
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA EF7JH
UT WOS:000390505400008
PM 27769849
ER
PT J
AU Nagababu, E
AF Nagababu, Enika
TI Ferriheme catalyzes nitric oxide reaction with glutathione to form
S-nitrosoglutathione: A novel mechanism for formation of S-nitrosothiols
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE S-nitrosothiols; S-nitrosoglutathione; Nitric oxide; Ferriheme;
Glutathione
ID RED-CELL MEMBRANE; REDUCTIVE NITROSYLATION; HEME; PROTEIN; NITROSATION;
KINETICS; OXYGEN; IRON; DEOXYHEMOGLOBIN; DEGRADATION
AB S-nitrosothiols (SNO) perform many important functions in biological systems, but the mechanism by which they are generated in vivo remains a contentious issue. Nitric oxide (NO) reacts with thiols to form SNO only in the presence of a molecule that will accept an electron from either NO or the thiol. In this study, we present evidence that ferriheme accepts an electron from NO or glutathione (GSH) to generate S-nitrosoglutathione (GSNO) in vitro under anaerobic or hypoxic (2% O-2) conditions. Ferriheme formed charge transfer-stable complexes with NO to form ferriheme-NO (heme-Fe(II)-NO+) and with GSH to form ferriheme-GS (heme-Fe(II)-GS(center dot))under anaerobic conditions. The reaction between GSH and the heme-Fe(II)-NO+ complex or between NO and the heme-Fe(II)-GS(center dot) complex resulted in simultaneous reductive ferriheme nitrosylation (heme-Fe(II) NO) and the generation of GSNO. Thus, ferriheme is readily reduced to ferroheme in the presence of NO and GSH together, but not with either individually. The reaction between NO and the heme-Fe(II)-GS(center dot) complex to generate GSNO occurred more rapidly than NO was consumed by endothelial cells, but not red blood cells. In addition, pretreatment of endothelial cells with ferriheme or the ferriheme-GS complex generated SNO upon addition of NO under hypoxic conditions. The results of this study raise the possibility that in vivo, ferriheme can complex with GSH to form ferriheme-GS complex (heme-Fe(II)-GS(center dot)), which rapidly reacts with NO to generate GSNO under intracellular oxygen levels. The GSNO formation by this mechanism is more efficient than any other in vitro mechanism(s) reported so far.
C1 [Nagababu, Enika] Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Integrated Vasc Biol Lab, 720 Rutland Ave,Ross 1150, Baltimore, MD 21205 USA.
[Nagababu, Enika] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA.
RP Nagababu, E (reprint author), Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Integrated Vasc Biol Lab, 720 Rutland Ave,Ross 1150, Baltimore, MD 21205 USA.; Nagababu, E (reprint author), NIA, Baltimore, MD 21224 USA.
EM nenika1@JHMI.edu
FU Department of Anesthesiology and Critical Care Medicine, Johns Hopkins
Medical Institutions, Baltimore, Maryland; Intramural Research Program
of The National Institute on Aging, National Institutes of Health, USA
FX This research was supported by the Department of Anesthesiology and
Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore,
Maryland and the Intramural Research Program of The National Institute
on Aging, National Institutes of Health, USA.
NR 51
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U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD DEC
PY 2016
VL 101
BP 296
EP 304
DI 10.1016/j.freeradbiomed.2016.09.015
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA EG0DN
UT WOS:000390701300026
PM 27693379
ER
PT J
AU Fernandez Nunez, L
Ocampo, J
Gottlieb, AM
Rossi, S
Moreno, S
AF Fernandez Nunez, Lucas
Ocampo, Josefina
Gottlieb, Alexandra M.
Rossi, Silvia
Moreno, Silvia
TI Multiple isoforms for the catalytic subunit of PICA in the basal fungal
lineage Mucor circinelloides
SO FUNGAL BIOLOGY
LA English
DT Article
DE cAMP; Differentiation; Orthologs; Paralogs; Pseudokinase; Zygomycetes
ID PROTEIN-KINASE-A; ROUXII SPORANGIOSPORES; ASPERGILLUS-NIDULANS;
REGULATORY SUBUNIT; SIGNALING PATHWAY; CAMP; VIRULENCE; GROWTH; GENES;
EXPRESSION
AB Protein kinase A (PICA) activity is involved in dimorphism of the basal fungal lineage Mucor. From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic subunits of PKA. From sequence alignment and structural prediction we conclude that the catalytic core of the isoforms is conserved, and the difference between them resides in their amino termini. This high number of isoforms is maintained in the subdivision Mucoromycotina. Each paralogue, when compared to the ones form other fungi is more homologous to one of its orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II in which fungal protein kinases have been classified. mRNA levels for each isoform were measured during aerobic and anaerobic growth. The expression of each isoform is differential and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944), the only cloned sequence available until now for a catalytic subunit of M. circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be measured for this protein nor predicted bioinformatically. It can thus be classified as a pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level in different stages of growth, and its deletion is lethal. (C) 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.
C1 [Fernandez Nunez, Lucas; Ocampo, Josefina; Rossi, Silvia; Moreno, Silvia] Univ Buenos Aires, Facu Ciencias Exactas & Nat, Dept Quim Biol, IQUIBICEN CONICET, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina.
[Gottlieb, Alexandra M.] Univ Buenos Aires, Facu Ciencias Exactas & Nat, Dept Ecol Genet & Evolut, IEGEBA CONICET, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina.
[Ocampo, Josefina] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD USA.
RP Moreno, S (reprint author), Univ Buenos Aires, Facu Ciencias Exactas & Nat, Intendente Guiraldes 2160,Ciudad Univ,C1428EGA, Buenos Aires, DF, Argentina.
EM smoreno@qb.fcen.uba.ar
FU Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2010-0128];
Universidad de Buenos Aires [X461]; Consejo Nacional de Investigaciones
Cientificas y Tecnicas (PIP) [11220110100826]
FX This study was supported by the following grants: PICT 2010-0128 Agencia
Nacional de Promocion Cientifica y Tecnologica, Universidad de Buenos
Aires (X461) and Consejo Nacional de Investigaciones Cientificas y
Tecnicas (PIP-2012-2014, 11220110100826). LFN and JO were at the time
doctoral and postdoctoral fellows from CONICET.
NR 61
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U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-6146
EI 1878-6162
J9 FUNGAL BIOL-UK
JI Fungal Biol.
PD DEC
PY 2016
VL 120
IS 12
BP 1493
EP 1508
DI 10.1016/j.funbio.2016.07.013
PG 16
WC Mycology
SC Mycology
GA EG0KG
UT WOS:000390721100002
PM 27890086
ER
PT J
AU Wei, YH
Reveal, B
Cai, WL
Lilly, MA
AF Wei, Youheng
Reveal, Brad
Cai, Weili
Lilly, Mary A.
TI The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to
Nutrient Stress in Drosophila melanogaster
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE TORC1; Nprl2; Nprl3; Iml1; metabolism
ID AMINO-ACID SUFFICIENCY; RAG GTPASES; FAT-BODY; GROWTH-CONTROL;
CELL-GROWTH; AUTOPHAGY; MTOR; RAPAMYCIN; TORC1; DISEASE
AB TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster. We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila.
C1 [Wei, Youheng; Reveal, Brad; Cai, Weili; Lilly, Mary A.] NICHHD, Cell Biol & Neurobiol Branch, NIH, Bldg 35 1C-917, Bethesda, MD 20892 USA.
RP Lilly, MA (reprint author), NICHHD, Cell Biol & Neurobiol Branch, NIH, Bldg 35 1C-917, Bethesda, MD 20892 USA.
EM lillym@helix.nih.gov
FU Intramural Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health [ZIA
HD001613 16]
FX We thank members of the Lilly laboratory for comments on the manuscript.
Multiple stocks used in this study were obtained from the Bloomington
Stock Center. We thank Thomas Neufeld (University of Minnesota) for
providing the TorA948V/CyO stock. This work was supported by
grant ZIA HD001613 16 from the Intramural Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health.
NR 62
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U1 2
U2 2
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD DEC
PY 2016
VL 6
IS 12
BP 3859
EP 3867
DI 10.1534/g3.116.035337
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA EF8PN
UT WOS:000390591400008
PM 27672113
ER
PT J
AU McClendon, TB
Mainpal, R
Amrit, FRG
Krause, MW
Ghazi, A
Yanowitz, JL
AF McClendon, T. Brooke
Mainpal, Rana
Amrit, Francis R. G.
Krause, Michael W.
Ghazi, Arjumand
Yanowitz, Judith L.
TI X Chromosome Crossover Formation and Genome Stability in Caenorhabditis
elegans Are Independently Regulated by xnd-1
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE meiosis; ATM; Tip60; ionizing radiation; genome instability
ID DAMAGE-INDUCED APOPTOSIS; DOUBLE-STRAND BREAKS; HISTONE H3 METHYLATION;
DNA-DAMAGE; C-ELEGANS; MEIOTIC RECOMBINATION; CHECKPOINT PROTEIN;
GENE-EXPRESSION; GERMLINE IMMORTALITY; TUMOR-SUPPRESSOR
AB The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1. Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability.
C1 [McClendon, T. Brooke; Yanowitz, Judith L.] Univ Pittsburgh, Sch Med, Mol Genet & Dev Biol Grad Program, Pittsburgh, PA 15224 USA.
[Amrit, Francis R. G.; Ghazi, Arjumand] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15224 USA.
[McClendon, T. Brooke; Mainpal, Rana; Yanowitz, Judith L.] Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Serv, Pittsburgh, PA 15213 USA.
[Krause, Michael W.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Yanowitz, JL (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, 204 Craft Ave, Pittsburgh, PA 15213 USA.
EM jly@alum.mit.edu
RI Ghazi, Arjumand/D-9373-2017; Rana, Mainpal/Q-7646-2016
OI Ghazi, Arjumand/0000-0002-5859-4206; Rana, Mainpal/0000-0003-2458-7259
FU National Institutes of Health (NIH) Office of Research Infrastructure
Programs [P40 OD010440]; Ellison Medical Foundation [AG-NS-0879-12];
State of Pennsylvania Formula Funds; National Institute of General
Medical Sciences [R01GM104007]
FX We thank Cynthia Wagner and Zebulin Kessler for their assistance in the
construction and bombardment of the Ppie-1::him-5::gfp trans-gene, and
Tetsu Fukushige and Weiping Chen for assistance with the microarrays.
Some strains were provided by the Caenorhabditis Genetics Center, which
is funded by the National Institutes of Health (NIH) Office of Research
Infrastructure Programs (P40 OD010440). The anti-E7 tubulin antibody
developed by M. McCutcheon and S. Carroll and was obtained from the
Developmental Studies Hybridoma Bank, created by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development of the
NIH and maintained at the Department of Biology The University of Iowa.
Sequencing of trans genic constructs and the ced-3(n717) allele was
performed in the Genomics Research Core at the University of Pittsburgh.
Funding for these studies was provided by A New Scholar in Aging award
from the Ellison Medical Foundation (AG-NS-0879-12) to A.G., State of
Pennsylvania Formula Funds to J.L.Y., and an R01 from the National
Institute of General Medical Sciences (R01GM104007) to J.L.Y.
NR 65
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U1 3
U2 3
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD DEC
PY 2016
VL 6
IS 12
BP 3913
EP 3925
DI 10.1534/g3.116.035725
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA EF8PN
UT WOS:000390591400013
PM 27678523
ER
PT J
AU Lin, YZ
Chen, ZX
Oliver, B
Harbison, ST
AF Lin, Yanzhu
Chen, Zhen-Xia
Oliver, Brian
Harbison, Susan T.
TI Microenvironmental Gene Expression Plasticity Among Individual
Drosophila melanogaster
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE microenvironmental plasticity; plasticity; Drosophila; interindividual
variation; RNA-Seq
ID MONOZYGOTIC TWINS DISCORDANT; ODOR-GUIDED BEHAVIOR; DEVELOPMENTAL
STABILITY; ENVIRONMENTAL VARIATION; PHENOTYPIC PLASTICITY; VARIANCE
HETEROGENEITY; RESIDUAL VARIANCE; BIPOLAR DISORDER; IDENTICAL-TWINS;
REFERENCE PANEL
AB Differences in phenotype among genetically identical individuals exposed to the same environmental condition are often noted in genetic studies. Despite this commonplace observation, little is known about the causes of this variability, which has been termed microenvironmental plasticity. One possibility is that stochastic or technical sources of variance produce these differences. A second possibility is that this variation has a genetic component. We have explored gene expression robustness in the transcriptomes of 730 individual Drosophila melanogaster of 16 fixed genotypes, nine of which are infected with Wolbachia. Three replicates of flies were grown, controlling for food, day/night cycles, humidity, temperature, sex, mating status, social exposure, and circadian timing of RNA extraction. Despite the use of inbred genotypes, and carefully controlled experimental conditions, thousands of genes were differentially expressed, revealing a unique and dynamic transcriptional signature for each individual fly. We found that 23% of the transcriptome was differentially expressed among individuals, and that the variability in gene expression among individuals is influenced by genotype. This transcriptional variation originated from specific gene pathways, suggesting a plastic response to the microenvironment; but there was also evidence of gene expression differences due to stochastic fluctuations. These observations reveal previously unappreciated genetic sources of variability in gene expression among individuals, which has implications for complex trait genetics and precision medicine.
C1 [Lin, Yanzhu; Harbison, Susan T.] NHLBI, Lab Syst Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Zhen-Xia; Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Harbison, ST (reprint author), NHLBI, Lab Syst Genet, Bldg 10,Room 7D13,10 Ctr Dr, Bethesda, MD 20892 USA.
EM susan.harbison@nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Heart Lung and Blood Institute; National Institute of Diabetes
and Digestive and Kidney Diseases
FX The authors H. Yang for technical assistance. This work utilized the
computational resources of the National Institutes of Health High
Performance Computing Biowulf cluster (http://hpc.nih.gov). This
research was supported by the Intramural Research Program of the
National Institutes of Health, The National Heart Lung and Blood
Institute, and The National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 99
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U1 9
U2 9
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD DEC
PY 2016
VL 6
IS 12
BP 4197
EP 4210
DI 10.1534/g3.116.035444
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA EF8PN
UT WOS:000390591400038
PM 27770026
ER
PT J
AU Morgan, AP
Didion, JP
Doran, AG
Holt, JM
McMillan, L
Keane, TM
de Villena, FPM
AF Morgan, Andrew P.
Didion, John P.
Doran, Anthony G.
Holt, James M.
McMillan, Leonard
Keane, Thomas M.
de Villena, Fernando Pardo-Manuel
TI Whole Genome Sequence of Two Wild-Derived Mus musculus domesticus Inbred
Strains, LEWES/EiJ and ZALENDE/EiJ, with Different Diploid Numbers
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE inbred mouse strains; wild-derived mouse strains; Robertsonian
translocations; karyotype evolution
ID HOUSE MOUSE; HAPLOTYPE DIVERSITY; LABORATORY MOUSE; CONSOMIC STRAINS;
COMPLEX TRAITS; MICE; GENE; DUPLICATION; SPECIATION; KARYOTYPE
AB Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14x and 18x coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format) and alignments (BAM format) are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction.
C1 [Morgan, Andrew P.; Didion, John P.; de Villena, Fernando Pardo-Manuel] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
[Holt, James M.; McMillan, Leonard] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA.
[Doran, Anthony G.; Keane, Thomas M.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Didion, John P.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP de Villena, FPM (reprint author), Univ N Carolina, Dept Genet, 120 Mason Farm Rd,CB 7264, Chapel Hill, NC 27599 USA.
EM fernando@med.unc.edu
OI Doran, Anthony/0000-0003-3061-4102
FU National Institutes of Health (NIH) [F30MH103925, T32GM067553,
P50GM076468, U19AI100625]; Medical Research Council [MR/L007428/1];
Biotechnology and Biological Sciences Research Council [BB/M000281/1];
Wellcome Trust
FX We wish to thank Timothy A. Bell for help preparing the DNA. This work
was supported in part by National Institutes of Health (NIH) grants
F30MH103925 (A.P.M.), T32GM067553 (A.P.M. and J.P.D.), P50GM076468, and
U19AI100625 (F.P.-M.dV.). T.M.K. and A.G.D. are supported by the Medical
Research Council (MR/L007428/1), the Biotechnology and Biological
Sciences Research Council (BB/M000281/1), and the Wellcome Trust.
NR 41
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U1 5
U2 5
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD DEC
PY 2016
VL 6
IS 12
BP 4211
EP 4216
DI 10.1534/g3.116.034751
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA EF8PN
UT WOS:000390591400039
PM 27765810
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI New Partnerships to Advance Global Health Research for NCD
SO GLOBAL HEART
LA English
DT Editorial Material
ID AFRICA; WORLD; FUND
C1 [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Mensah, George A.] NHLBI, Div Cardiovasc Dis, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.; Mensah, GA (reprint author), NHLBI, Div Cardiovasc Dis, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
NR 18
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Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2211-8160
EI 2211-8179
J9 GLOB HEART
JI Glob. Heart
PD DEC
PY 2016
VL 11
IS 4
BP 473
EP 478
DI 10.1016/j.gheart.2016.10.022
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EF6PT
UT WOS:000390453700028
PM 27938846
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI NCD Research in the Post-2015 Global Health Agenda Perspectives from the
NHLBI Strategic Vision
SO GLOBAL HEART
LA English
DT Editorial Material
ID INEQUITIES; DIVERSITY; PROGRAM; NETWORK; OBESITY; HEART
C1 [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM George.Mensah@nih.gov
NR 46
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2211-8160
EI 2211-8179
J9 GLOB HEART
JI Glob. Heart
PD DEC
PY 2016
VL 11
IS 4
BP 479
EP 483
DI 10.1016/j.gheart.2016.11.002
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EF6PT
UT WOS:000390453700029
PM 27938847
ER
PT J
AU Wang, XM
Bassig, BA
Wen, JJ
Li, GD
Liu, ZB
Yao, WX
Hu, W
Wang, Y
Li, JM
Wang, XD
Gan, MZ
Wang, CS
Xu, G
Rothman, N
Lan, Q
Xu, CG
AF Wang, Xue-mei
Bassig, Bryan A.
Wen, Jing-jing
Li, Gan-di
Liu, Zhi-bin
Yao, Wen-xiu
Hu, Wei
Wang, Ying
Li, Ji-man
Wang, Xiao-dong
Gan, Mao-zhou
Wang, Chun-sen
Xu, Gang
Rothman, Nathaniel
Lan, Qing
Xu, Cai-gang
TI Clinical analysis of 1629 newly diagnosed malignant lymphomas in current
residents of Sichuan province, China
SO HEMATOLOGICAL ONCOLOGY
LA English
DT Article
DE lymphoma; China; geographical variation; descriptive epidemiology
ID B-CELL LYMPHOMA; UNITED-STATES; SUBTYPE; CLASSIFICATION; SHANGHAI
AB Previous studies in other provinces of China (Beijing, Xinjiang, Shanxi, Jiangxi, Shanghai, Guangdong, and Taiwan) suggest that the distributions of lymphoma subtypes differ compared with Western populations. In order to evaluate the characteristics of malignant lymphoma in Sichuan, China, we analyzed case series data from incident lymphoma patients diagnosed in 2008 from three hospitals, including a total of 1629 cases and including only current residents of Sichuan. The median age of diagnosis for cases was 54years, with a higher proportion of male cases compared with female cases. The most commonly diagnosed subtypes included diffuse large B-cell lymphoma (40.4%), NK/T-cell lymphoma (NKTCL; 11.8%), mixed cellularity Hodgkin lymphoma (7.0%), mantle cell lymphoma (4.8%), and marginal zone B-cell lymphoma (3.9%). Differences in demographic characteristics between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases were apparent for median age at diagnosis (HL: 34years; NHL: 57years), and NHLs accounted for nearly all (99.3%) of the 931 cases of extranodal lymphoma. These findings indicate a higher proportion of NKTCL cases and a lower proportion of follicular lymphoma cases (2.3%) in these hospitals in Sichuan, relative to reports from some other provinces within China (e.g., Shanghai and Shanxi) and the USA. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Wang, Xue-mei; Wen, Jing-jing; Li, Gan-di; Liu, Zhi-bin; Xu, Cai-gang] Sichuan Univ, Dept Hematol, Hematol Res Lab & Pathol, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.
[Bassig, Bryan A.; Hu, Wei; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Yao, Wen-xiu; Wang, Ying; Li, Ji-man] Sichuan Prov Tumour Hosp, Dept Internal Med & Pathol, Chengdu, Sichuan, Peoples R China.
[Wang, Xiao-dong; Gan, Mao-zhou; Wang, Chun-sen; Xu, Gang] Sichuan Prov Peoples Hosp, Dept Hematol & Pathol, Chengdu, Sichuan, Peoples R China.
[Wang, Xue-mei] Luzhou Med Coll, Affiliated Hosp, Dept Hematol, Luzhou, Peoples R China.
RP Xu, CG (reprint author), Sichuan Univ, Dept Hematol, Hematol Res Lab & Pathol, West China Hosp, Chengdu 610041, Sichuan, Peoples R China.
EM xucg@cd120.com
NR 30
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0278-0232
EI 1099-1069
J9 HEMATOL ONCOL
JI Hematol. Oncol.
PD DEC
PY 2016
VL 34
IS 4
BP 193
EP 199
DI 10.1002/hon.2202
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA EF8RC
UT WOS:000390595800003
PM 25824105
ER
PT J
AU Makowsky, R
Lhaki, P
Wiener, HW
Bhatta, MP
Cullene, M
Johnson, DC
Perry, RT
Lama, M
Boland, JF
Yeager, M
Ghimire, S
Broker, TR
Shrestha, S
AF Makowsky, Robert
Lhaki, Pema
Wiener, Howard W.
Bhatta, Madhav P.
Cullene, Michael
Johnson, Derek C.
Perry, Rodney T.
Lama, Mingma
Boland, Joseph F.
Yeager, Meredith
Ghimire, Sarita
Broker, Thomas R.
Shrestha, Sadeep
TI Genomic diversity and phylogenetic relationships of human papillomavirus
16 (HPV16) in Nepal
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE HPV16 sequence; Nepal; Phylogenetic tree; HSIL; HPV16 lineage
ID CERVICAL-CANCER; E6; VARIANTS; CLASSIFICATION; PERSISTENCE; NEOPLASIA;
SEQUENCE; LESIONS; WOMEN
AB Objectives/Background: Sequence variants in HPV16 confer differences in oncogenic potential; however, to date there have not been any HPV sequence studies performed in Nepal. The objective of this study was to characterize HPV16 viral genome sequences from Nepal compared to a reference sequence in order to determine their lineages. Additionally, we sought to determine if five High-grade Squamous Intraepithelial Lesion (HSIL) subjects were genetically distinct from the non-HSIL subjects.
Methods: DNA was isolated from exfoliated cervical cells from 17 individuals in Nepal who were previously identified to be HPV16-positive. A custom HPV16 Ion Ampliseq panel of multiplexed degenerate primers was designed that generated 47 overlapping amplicons and covered 99% of the viral genome for all known HPV16 variant lineages. All sequence data were processed through a custom quality control and analysis pipeline of sequence comparisons and phylogenetic analysis.
Results: There were high similarities across the genomes, with two major indels observed in the non-coding region between E5 and L2. Compared to the PAVE reference HPV16 genome, there were up to 9, 4, 38, 27, 8, 7, 52, and 32 nucleotide variants in the E6, E7, E1, E2, E4, E5, L2, and L1 genes in the Nepalese samples, respectively. Based on sequence variation, HPV16 from Nepal falls across the A, C, and D lineages in this study. We found no evidence of genetic distinctness between HSIL and non-HSIL subjects.
Conclusions: The evolutionary and pathological characteristics of the representative HPV16 genomes from Nepal seem similar to results from other parts of the world and provide the basis for further studies. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Makowsky, Robert] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL USA.
[Lhaki, Pema; Lama, Mingma] NFCC Int, Kathmandu, Nepal.
[Wiener, Howard W.; Johnson, Derek C.; Perry, Rodney T.; Shrestha, Sadeep] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Ryals Rm217L,1720 2nd Ave S, Birmingham, AL 35294 USA.
[Bhatta, Madhav P.] Kent State Univ, Coll Publ Hlth, Dept Biostat Environm Hlth Sci & Epidemiol, Kent, OH 44242 USA.
[Cullene, Michael; Boland, Joseph F.; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Cullene, Michael; Boland, Joseph F.; Yeager, Meredith] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Gaithersburg, MD USA.
[Ghimire, Sarita] Nepal Canc Care Fdn, Canc Screening Ctr, Lalitpur, Nepal.
[Broker, Thomas R.] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL USA.
RP Shrestha, S (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Ryals Rm217L,1720 2nd Ave S, Birmingham, AL 35294 USA.
EM sshrestha@uab.edu
FU Department of Epidemiology, School of Public Health, University of
Alabama at Birmingham; College of Public Health, Kent State University;
National Institutes of Health Cancer Prevention and Control Training
Grant [R25CA47888]
FX We thank the study participants and the staff at Nepal Fertility Care
Center (NFCC) who helped with the sample collection, particularly Pankaj
Bhattarai who was instrumental in the health camps. The Family Health
Division, within the Nepal ministry of health also assisted with the
logistics of the health camp and data collection. The study was
supported in part by the pilot fund from the Department of Epidemiology,
School of Public Health, University of Alabama at Birmingham and College
of Public Health, Kent State University. Derek Johnson was supported by
a National Institutes of Health Cancer Prevention and Control Training
Grant (R25CA47888).
NR 27
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U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
EI 1567-7257
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD DEC
PY 2016
VL 46
BP 7
EP 11
DI 10.1016/j.meegid.2016.10.004
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA EF6QP
UT WOS:000390456000002
PM 27725301
ER
PT J
AU Pereira, TA
Syn, WK
Pereira, FEL
Lambertucci, JR
Secor, WE
Diehl, AM
AF Pereira, Thiago Almeida
Syn, Wing-Kin
Pereira, Fausto E. L.
Lambertucci, Jose Roberto
Secor, William Evan
Diehl, Anna Mae
TI Serum osteopontin is a biomarker of severe fibrosis and portal
hypertension in human and murine schistosomiasis mansoni
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Osteopontin; Schistosomiasis mansoni; Liver fibrosis; Portal
hypertension; Biomarker
ID IMMUNE-RESPONSES; PATHOLOGICAL SYNDROMES; CBA/J MICE; INFECTIONS;
IMMUNOPATHOGENESIS; IMMUNOREGULATION; ACTIVATION; CELLS
AB Schistosomiasis is a major cause of fibrosis and portal hypertension. The reason 4-10% of infected subjects develops hepatosplenic schistosomiasis remains unclear. Chronically infected male CBA/J mice reproduce the dichotomic forms of human schistosomiasis. Most mice (80%) develop moderate splenomegaly syndrome (similar to hepatointestinal disease in humans) and 20% present severe hypersplenomegaly syndrome (analogous to human hepatosplenic disease). We demonstrated that the profibrogenic molecule osteopontin discriminates between mice with severe and mild disease and could be a novel morbidity biomarker in murine and human schistosomiasis. Failure to downregulate osteopontin during the chronic phase may explain why hepatosplenic subjects develop severe fibrosis. (C) 2016 Published by Elsevier Ltd on behalf of Australian Society for Parasitology.
C1 [Pereira, Thiago Almeida; Diehl, Anna Mae] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA.
[Pereira, Thiago Almeida; Lambertucci, Jose Roberto] Univ Fed Minas Gerais, Fac Med, Lab Doencas Infecciosas & Parasitarias, Dept Clin Med, Belo Horizonte, MG, Brazil.
[Pereira, Thiago Almeida] NIAID, Immunopathogesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Syn, Wing-Kin] Fdn Liver Res, Inst Hepatol, Liver Regenerat & Repair Res Grp, London, England.
[Syn, Wing-Kin] Med Univ South Carolina, Div Gastroenterol & Hepatol, Charleston, SC 29425 USA.
[Syn, Wing-Kin] Ralph H Johnson Vet Affairs Med Ctr, Gastroenterol Sect, Charleston, SC USA.
[Pereira, Fausto E. L.] Univ Fed Espirito Santo, Nucleo Doengas Infecciosas, Vitoria, ES, Spain.
[Secor, William Evan] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Diehl, AM (reprint author), Duke Univ, Med Ctr, Dept Med, Duke Liver Ctr,Div Gastroenterol, 905 S LaSalle St,GSRB1 Snyderman Bldg,Suite 1073, Durham, NC 27710 USA.
EM diehl004@mc.duke.edu
FU National Institutes of Health (NIH), USA [R01-DK-077794]; Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases (NIAID), USA; Duke University Endowment, USA; Conselho Nacional
de Desenvolvimento Cientifico e Tecnologico, Ministry of Science,
Technology and Innovation of Brazil (CNPq); Fundacao de Amparo a
Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil
FX We thank Mr Carl Stone for administrative support. This work was
supported by: National Institutes of Health (NIH), USA (grant number
R01-DK-077794 (to AMD); Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (NIAID), USA (to TAP)); the
Duke University Endowment, USA (the Florence McAlister Professorship)
(to AMD), the Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico, Ministry of Science, Technology and Innovation of Brazil
(CNPq) (to TAP, FEP and JRL); and Fundacao de Amparo a Pesquisa do
Estado de Minas Gerais (FAPEMIG), Brazil (to JRL).
NR 25
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
EI 1879-0135
J9 INT J PARASITOL
JI Int. J. Parasit.
PD DEC
PY 2016
VL 46
IS 13-14
BP 829
EP 832
DI 10.1016/j.ijpara.2016.08.004
PG 4
WC Parasitology
SC Parasitology
GA EG0ML
UT WOS:000390726800001
PM 27729270
ER
PT J
AU Kaur, S
Roberts, DD
AF Kaur, Sukhbir
Roberts, David D.
TI Divergent modulation of normal and neoplastic stem cells by
thrombospondin-1 and CD47 signaling
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Review
DE Self-renewal; c-Myc; Tumor initiating cells; Cancer; Extracellular
matrix; Matricellular proteins
ID REGULATORY PROTEIN-ALPHA; HEMATOPOIETIC PROGENITOR CELLS;
LEUKEMIA-INITIATING CELLS; ADVERSE PROGNOSTIC-FACTOR; ISCHEMIC TISSUE
SURVIVAL; SIRP-ALPHA; THERAPEUTIC TARGET; BREAST-CANCER; NEUTROPHIL
TRANSMIGRATION; HEPATOCELLULAR-CARCINOMA
AB Thrombospondin-1 is a secreted matricellular protein that regulates the differentiation and function of many cell types. Thrombospondin-1 is not required for embryonic development, but studies using lineage-committed adult stem cells have identified positive and negative effects of thrombospondin-1 on stem cell differentiation and self-renewal and identified several thrombospondin-1 receptors that mediate these responses. Genetic studies in mice reveal a broad inhibitory role of thrombospondin-1 mediated by its receptor CD47. Cells and tissues lacking thrombospondin-1 or CD47 exhibit an increased capacity for self-renewal associated with increased expression of the stem cell transcription factors c-Myc, Sox2, Klf4, and Oct4. Thrombospondin-1 inhibits expression of these transcription factors in a CD47dependent manner. However, this regulation differs in some neoplastic cells. Tumor initiating/cancer stem cells express high levels of CD47, but in contrast to nontransformed stem cells CD47 signaling supports cancer stem cells. Suppression of CD47 expression in cancer stem cells or ligation of CD47 by function blocking antibodies or thrombospondin-1 results in loss of self-renewal. Therefore, the therapeutic CD47 antagonists that are in clinical development for stimulating innate anti-tumor immunity may also inhibit tumor growth by suppressing cancer stem cells. These and other therapeutic modulators of thrombospondin-1 and CD47 signaling may also have applications in regenerative medicine to enhance the function of normal stem cells. Published by Elsevier Ltd.
C1 [Kaur, Sukhbir; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 119
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U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
EI 1878-5875
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD DEC
PY 2016
VL 81
BP 184
EP 194
DI 10.1016/j.biocel.2016.05.005
PN A
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EF9HO
UT WOS:000390641500024
PM 27163531
ER
PT J
AU Sun, C
Gao, J
Couzens, L
Tian, X
Farooqui, MZ
Eichelberger, MC
Wiestner, A
AF Sun, Clare
Gao, Jin
Couzens, Laura
Tian, Xin
Farooqui, Mohammed Z.
Eichelberger, Maryna C.
Wiestner, Adrian
TI Seasonal Influenza Vaccination in Patients With Chronic Lymphocytic
Leukemia Treated With Ibrutinib
SO JAMA ONCOLOGY
LA English
DT Letter
ID INFECTIONS
C1 [Sun, Clare; Farooqui, Mohammed Z.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC Room 3-5140, Bethesda, MD 20892 USA.
[Gao, Jin; Couzens, Laura; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, 10 Ctr Dr,Bldg 10,CRC Room 3-5140, Bethesda, MD 20892 USA.
RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC Room 3-5140, Bethesda, MD 20892 USA.
EM wiestnea@nhlbi.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD DEC 1
PY 2016
VL 2
IS 12
BP 1656
EP 1657
DI 10.1001/jamaoncol.2016.2437
PG 2
WC Oncology
SC Oncology
GA EF8TG
UT WOS:000390601900028
PM 27533065
ER
PT J
AU Blake, KD
Portnoy, DB
Kaufman, AR
Lin, CTJ
Lo, SC
Backlund, E
Cantor, D
Hicks, L
Lin, A
Caporaso, A
Davis, T
Moser, RP
Hesse, BW
AF Blake, Kelly D.
Portnoy, David B.
Kaufman, Annette R.
Lin, Chung-Tung Jordan
Lo, Serena C.
Backlund, Eric
Cantor, David
Hicks, Lloyd
Lin, Amy
Caporaso, Andrew
Davis, Terisa
Moser, Richard P.
Hesse, Bradford W.
TI Rationale, Procedures, and Response Rates for the 2015 Administration of
NCI's Health Information National Trends Survey: HINTS-FDA 2015
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID TOBACCO PRODUCTS; FOOD
AB The National Cancer Institute (NCI) developed the Health Information National Trends Survey (HINTS) to monitor population trends in cancer communication practices, information preferences, health risk behaviors, attitudes, and cancer knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a unique data resource for informing its health communication endeavors and partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self-administered paper instrument sent by mail May 29 to September 8, 2015, using a random probability-based sample of U.S. postal addresses stratified by county-level smoking rates, with an oversampling of high and medium-high smoking strata to increase the yield of current smokers responding to the survey. The response rate for HINTS-FDA 2015 was 33% (N=3,738). The yield of current smokers (n=495) was lower than expected, but the sampling strategy achieved the goal of obtaining more former smokers (n=1,132). Public-use HINTS-FDA 2015 data and supporting documentation have been available for download and secondary data analyses since June 2016 at http://hints.cancer.gov. NCI and FDA encourage the use of HINTS-FDA for health communication research and practice related to tobacco-related communications, public knowledge, and behaviors as well as beliefs and actions related to medical products and dietary supplements.
C1 [Blake, Kelly D.; Hesse, Bradford W.] NCI, NIH, Hlth Commun & Informat Res Branch, Behav Res Program,Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E222,MSC 9671, Bethesda, MD 20892 USA.
[Portnoy, David B.; Backlund, Eric] US FDA, Off Sci, Ctr Tobacco Prod, Silver Spring, MD USA.
[Kaufman, Annette R.] NCI, NIH, Tobacco Control Res Branch, Behav Res Program,Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Lin, Chung-Tung Jordan; Lo, Serena C.] US FDA, Off Analyt & Outreach, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Cantor, David; Hicks, Lloyd; Lin, Amy; Caporaso, Andrew; Davis, Terisa] Westat Corp, Rockville, MD USA.
[Moser, Richard P.] NCI, NIH, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Blake, KD (reprint author), NCI, NIH, Hlth Commun & Informat Res Branch, Behav Res Program,Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E222,MSC 9671, Bethesda, MD 20892 USA.
EM kelly.blake@nih.gov
FU National Cancer Institute (NCI); U.S. Food and Drug Administration's
Center for Tobacco Products, Office of the Commissioner; Center for Food
Safety and Applied Nutrition; NCI [HHSN261201000064C]
FX HINTS-FDA (Health Information National Trends Survey-U.S. Food and Drug
Administration) was funded by the National Cancer Institute (NCI) and
the U.S. Food and Drug Administration's Center for Tobacco Products,
Office of the Commissioner, and Center for Food Safety and Applied
Nutrition via interagency agreements with NCI and by contract from NCI
to Westat, Inc. (HHSN261201000064C).
NR 17
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Z9 1
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD DEC
PY 2016
VL 21
IS 12
BP 1269
EP 1275
DI 10.1080/10810730.2016.1242672
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA EF6BQ
UT WOS:000390415100008
PM 27892827
ER
PT J
AU Bedda, M
Chattopadhyay, PK
Kao, SF
Foulds, K
Roederer, M
AF Bedda, Margaret
Chattopadhyay, Pratip K.
Kao, Shing-Fen
Foulds, Kathy
Roederer, Mario
TI A simple tube adapter to expedite and automate thawing of viably frozen
cells
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Immunoassay; T-cells; flow cytometry; Cryopreservation
ID BIOBANKING
AB Although cryopreserved cell specimens are used throughout biomedical research, the process for thawing samples is labor-intensive and prone to error. Here we describe a small laboratory device that couples an uncapped vial of frozen cells to a conical tube containing warm cell culture media. The entire complex is loaded directly into a centrifuge; within 5 min, cells are thawed and diluted out of toxic cryopreservation medium. The recovery and viability of cells are slightly reduced compared to the common (traditional) method. However, antigen-specific T-cell function is not affected. Since no technician time is required (beyond uncapping of vials), our device allows the parallel processing of as many samples as a centrifuge can hold (up to 96, in some models). Moreover, since the samples are not thawed manually in a water bath, the problems associated with technician-to-technician differences in sample handling are minimized, as is the potential for contamination. Importantly, the elimination of substantial labor involving subjective decisions standardizes this process and can reduce variability in results from cryopreserved specimens. (C) 2016 Published by Elsevier B.V.
C1 [Bedda, Margaret; Chattopadhyay, Pratip K.; Kao, Shing-Fen; Foulds, Kathy; Roederer, Mario] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, 40 Convent Dr, Bethesda, MD 20892 USA.
RP Chattopadhyay, PK (reprint author), NIH, ImmunoTechnol Sect, Vaccine Res Ctr, 40 Convent Dr, Bethesda, MD 20892 USA.
EM pchattop@mail.nih.gov
OI Chattopadhyay, Pratip/0000-0002-5457-9666
FU Intramural Research Program of the Vaccine Research Center, NIH
FX The authors wish to acknowledge Robert Clary and Howard Metger at the
NIH Mechanical Instrument Design and Fabrication Service for making
initial variations of the device. PC is a Marylou Ingram Scholar in the
International Society for the Advancement of Cytometry. This work was
supported by the Intramural Research Program of the Vaccine Research
Center, NIH.
NR 8
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD DEC
PY 2016
VL 439
BP 74
EP 78
DI 10.1016/j.jim.2016.08.009
PG 5
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA EF7IC
UT WOS:000390502300011
PM 27594593
ER
PT J
AU Heldreth, CM
Guardino, CM
Wong, LH
Schetter, CD
Shapiro, JR
Schafer, P
Shalowitz, M
Lanzi, RG
Thorp, J
Raju, T
AF Heldreth, Courtney M.
Guardino, Christine M.
Wong, Lauren H.
Schetter, Christine Dunkel
Shapiro, Jenessa R.
Schafer, Peter
Shalowitz, Madeleine
Lanzi, Robin Gaines
Thorp, John, Jr.
Raju, Tonse
CA CCHN
TI CHILDHOOD RACISM EXPERIENCES AND POSTPARTUM DEPRESSIVE SYMPTOMS IN
AFRICAN AMERICAN MOTHERS
SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE Racial discrimination; childhood racism; early adversity; mental health
ID LOW-BIRTH-WEIGHT; MENTAL-HEALTH; BLOOD-PRESSURE; PERCEIVED
DISCRIMINATION; POSTNATAL DEPRESSION; PHYSICAL HEALTH; SEXUAL-ABUSE;
RISK-FACTORS; STRESS; DISPARITIES
AB In the present research, we examined the effects of childhood experiences of racism-both directly and vicariously experienced when directed at family members or close others-on postpartum depressive symptoms one month after the birth of a child. The sample included 1,349 African American women, who were predominantly low-income. Data were collected by an NIH network in five different regions of the United States using community-based participatory research methods. Participants completed interview measures of childhood experiences of racism, current everyday experiences of discrimination, and postpartum depressive symptoms at one month after birth. We also assessed adult everyday experiences of discrimination as a potential mediator of the association between childhood racism and depressive symptoms. Direct and vicarious childhood racism experiences were each independently associated with greater postpartum depressive symptoms. Furthermore, when adult everyday experiences of racism were included in the models, the effects of childhood racism were no longer significant, suggesting mediation. Consistent with this hypothesis, associations between both childhood direct and indirect racism experiences and postpartum depressive symptoms were partially mediated by the participant's everyday experiences of racism as an adult. Our findings suggest that childhood racism experiences, even those that are observed rather than directly experienced, may have implications for future mental health.
C1 [Heldreth, Courtney M.; Guardino, Christine M.; Schetter, Christine Dunkel; Shapiro, Jenessa R.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Wong, Lauren H.] St Louis Coll Pharm, St Louis, MO USA.
[Schafer, Peter] New York Acad Med, New York, NY USA.
[Shalowitz, Madeleine] North Shore Univ Hlth Syst, Evanston, IL USA.
[Shalowitz, Madeleine] Univ Chicago, Chicago, IL 60637 USA.
[Lanzi, Robin Gaines] Univ Alabama Birmingham, Birmingham, AL USA.
[Thorp, John, Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Raju, Tonse; CCHN] Eunice Kennedy Shriver Natl Inst Child & Hlth Dev, Rockville, MD USA.
RP Heldreth, CM; Schetter, CD (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
EM courtneymariel.h@gmail.com; dunkel@psych.ucla.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [U HD44207, U HD44219, U HD44226, U HD44245, U
HD44253, U HD54791, U HD54019, U HD44226-o5S1, U HD44245-06S1, R03
HD59584]; National Institute for Nursing Research (NINR) [U NR008929]
FX The Community Child Health Network (CCHN) is supported through
cooperative agreements with the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD; U HD44207, U
HD44219, U HD44226, U HD44245, U HD44253, U HD54791, U HD54019, U
HD44226-o5S1, U HD44245-06S1, R03 HD59584) and the National Institute
for Nursing Research (NINR; U NR008929).
NR 83
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PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA
SN 0736-7236
J9 J SOC CLIN PSYCHOL
JI J. Soc. Clin. Psychol.
PD DEC
PY 2016
VL 35
IS 10
BP 840
EP 864
PG 25
WC Psychology, Clinical; Psychology, Social
SC Psychology
GA EF8EC
UT WOS:000390560500003
ER
PT J
AU Braun, LM
Rodriguez, DA
Song, Y
Meyer, KA
Lewis, CE
Reis, JP
Gordon-Larsen, P
AF Braun, Lindsay M.
Rodriguez, Daniel A.
Song, Yan
Meyer, Katie A.
Lewis, Cora E.
Reis, Jared P.
Gordon-Larsen, Penny
TI Changes in walking, body mass index, and cardiometabolic risk factors
following residential relocation: Longitudinal results from the CARDIA
study
SO JOURNAL OF TRANSPORT & HEALTH
LA English
DT Article
DE Built environment; Walkability; Walking; fixed effects; Residential
self-selection
ID YOUNG-ADULTS CARDIA; PHYSICAL-ACTIVITY; BUILT ENVIRONMENT; NEIGHBORHOOD
WALKABILITY; CARDIORESPIRATORY FITNESS; AUSTRALIAN ADULTS;
BLOOD-PRESSURE; LAND-USE; ASSOCIATION; BEHAVIOR
AB Background: While many studies have found the built environment to be associated with walking, most have used cross-sectional research designs and few have examined more distal cardiometabolic outcomes. This study contributes longitudinal evidence based on changes in walking, body mass index (BMI), and cardiometabolic risk following residential relocation.
Methods: We examined 1079 participants in the CARDIA study who moved residential locations between 2000 and 2006 (ages 32-46 in 2000, 49% white/51% black, 55% female). We created a walkability index from measures of population density, street connectivity, and food and physical activity resources, measured at participants' pre- and post-move residential locations. Outcomes measured before and after the move included walking, BMI, waist circumference, blood pressure, insulin resistance, triglycerides, cholesterol, atherogenic dyslipidemia, and C-reactive protein. Fixed effects (FE) models were used to estimate associations between within-person change in walkability and within-person change in each outcome. These estimates were compared to those from random effects (RE) models to assess the implications of unmeasured confounding.
Results: In FE models, a one-SD increase in walkability was associated with a 0.81 mmHg decrease in systolic blood pressure [95% CI: ( 1.55, 0.07)] and a 7.36 percent increase in C-reactive protein [95% CI: (0.60,14.57)]. Although several significant associations were observed in the RE models, Hausman tests suggested that these estimates were biased for most outcomes. RE estimates were most commonly biased away from the null or in the opposite direction of effect as the FE estimates.
Conclusions: Greater walkability was associated with lower blood pressure and higher C-reactive protein in FE models, potentially reflecting competing health risks and benefits in dense, walkable environments. RE models tended to overstate or otherwise misrepresent the relationship between walkability and health. Approaches that base estimates on variation between individuals may be subject to bias from unmeasured confounding, such as residential self-selection. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Braun, Lindsay M.; Song, Yan] Univ North Carolina Chapel Hill, Dept City & Reg Planning, Campus Box 3140,New East Bldg, Chapel Hill, NC 27599 USA.
[Rodriguez, Daniel A.] Univ Calif Berkeley, Dept City & Reg Planning, Berkeley, CA 94720 USA.
[Meyer, Katie A.; Gordon-Larsen, Penny] Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA.
[Reis, Jared P.] NHLBI, Prevent & Populat Sci Program, Bldg 10, Bethesda, MD 20892 USA.
[Gordon-Larsen, Penny] Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC USA.
RP Braun, LM (reprint author), Univ North Carolina Chapel Hill, Dept City & Reg Planning, Campus Box 3140,New East Bldg, Chapel Hill, NC 27599 USA.
EM maurerbraun@unc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [R01HL104580,
R01HL114091]; Intramural Research Program of the National Institute on
Aging (NIA); NIA [AG0005]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [NICHD] [P2C HD050924]; National
Institute for Diabetes and Digestive and Kidney Diseases [NIDDK]
[P30DK56350]; National Institute of Environmental Health Sciences
[NIEHS] [P30ES010126]; NHLBI [AG0005, HHSN268201300025C,
HHSN268201300026C, HHSN268201300027C, HHSN268201300028C,
HHSN268201300029C, HHSN268200900041C]
FX The authors have no financial or other conflicts of interest to
disclose. L.M. Braun had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy of
data analysis. We are grateful to Mr. Marc Peterson of the Carolina
Population Center Spatial Analysis Unit for the underlying Geographic
Information Systems data. This work was funded by the National Heart,
Lung, and Blood Institute (NHLBI) grants R01HL104580 and R01HL114091.
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is
supported by contracts HHSN268201300025C, HHSN268201300026C,
HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and
HHSN268200900041C from the NHLBI, the Intramural Research Program of the
National Institute on Aging (NIA), and an intra-agency agreement between
NIA and NHLBI (AG0005). For general support, the authors are grateful to
the Carolina Population Center, University of North Carolina at Chapel
Hill (grant P2C HD050924 from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [NICHD]), the Nutrition
Obesity Research Center (NORC), University of North Carolina (grant
P30DK56350 from the National Institute for Diabetes and Digestive and
Kidney Diseases [NIDDK]), and the UNC Center for Environmental Health
and Susceptibility (CEHS), University of North Carolina (grant
P30ES010126 from the National Institute of Environmental Health Sciences
[NIEHS]). The National Heart, Lung, and Blood Institute had input into
design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation of the manuscript, and decision
to submit the manuscript for publication.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-1405
J9 J TRANSP HEALTH
JI J. Transp. Health
PD DEC
PY 2016
VL 3
IS 4
SI SI
BP 426
EP 439
DI 10.1016/j.jth.2016.08.006
PG 14
WC Public, Environmental & Occupational Health; Transportation
SC Public, Environmental & Occupational Health; Transportation
GA EG0SP
UT WOS:000390742800002
PM 28163997
ER
PT J
AU Beigi, M
Wilkinson, L
Gobet, F
Parton, A
Jahanshahi, M
AF Beigi, M.
Wilkinson, L.
Gobet, F.
Parton, A.
Jahanshahi, M.
TI Levodopa medication improves incidental sequence learning in Parkinson's
disease
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Parkinson's disease; Incidental sequence learning; Serial reaction time;
Levodopa medication; Striatum; Basal ganglia
ID BASAL GANGLIA; COGNITIVE FUNCTION; IMPLICIT; STRIATUM; MEMORY;
MODULATION; ATTENTION; TASK; PET
AB Empirical evidence suggests that levodopa medication used to treat the motor symptoms of Parkinson's disease (PD) may either improve, impair or not affect specific cognitive processes. This evidence led to the 'dopamine overdose' hypothesis that levodopa medication impairs performance on cognitive tasks if they recruit fronto-striatal circuits which are not yet dopamine-depleted in early PD and as a result the medication leads to an excess of dopamine. This hypothesis has been supported for various learning tasks including conditional associative learning, reversal learning, classification learning and intentional deterministic sequence learning, on all of which PD patients demonstrated significantly worse performance when tested on relative to off dopamine medication. Incidental sequence learning is impaired in PD, but how such learning is affected by dopaminergic therapy remains undetermined. The aim of the current study was to investigate the effect of dopaminergic medication on incidental sequence learning in PD. We used a probabilistic serial reaction time task (SRTT), a sequence learning paradigm considered to make the sequence less apparent and more likely to be learned incidentally rather than intentionally. We compared learning by the same group of PD patients (n=15) on two separate occasions following oral administration of levodopa medication (on state) and after overnight withdrawal of medication (off state). Our results demonstrate for the first time that levodopa medication enhances incidental learning of a probabilistic sequence on the serial reaction time task in PD. However, neither group significantly differed from performance of a control group without a neurological disease, which indicates the importance of within group comparisons for identifying deficits. Levodopa medication enhanced incidental learning by patients with PD on a probabilistic sequence learning paradigm even though the patients were not aware of the existence of the sequence or their acquired knowledge. The results suggest a role in acquiring incidental motor sequence learning for dorsal striatal areas strongly affected by dopamine depletion in early PD.
C1 [Beigi, M.; Wilkinson, L.; Jahanshahi, M.] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Queen Sq, London WC1N 3BG, England.
[Beigi, M.; Parton, A.] Brunel Univ, Div Psychol, Dept Life Sci, Uxbridge UB8 3PH, Middx, England.
[Wilkinson, L.] NINDS, Behav Neurol Unit, 10 Ctr Dr, Bethesda, MD USA.
[Gobet, F.] Univ Liverpool, Dept Psychol Sci, Liverpool L69 7ZA, Merseyside, England.
RP Jahanshahi, M (reprint author), UCL Inst Neurol, 33 Queen Sq, London WC1N 3BG, England.
EM m.jahanshahi@ucl.ac.uk
OI Gobet, Fernand/0000-0002-9317-6886
FU ESRC [R84003]; Parkinson's UK
FX This work was funded by the ESRC (R84003) and Parkinson's UK.
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD DEC
PY 2016
VL 93
BP 53
EP 60
DI 10.1016/j.neuropsychologia.2016.09.019
PN A
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA EG0LC
UT WOS:000390723300006
PM 27686948
ER
PT J
AU Giles, AJ
Chien, CD
Reid, CM
Fry, TJ
Park, DM
Kaplan, RN
Gilbert, MR
AF Giles, Amber J.
Chien, Christopher D.
Reid, Caitlin M.
Fry, Terry J.
Park, Deric M.
Kaplan, Rosandra N.
Gilbert, Mark R.
TI The functional interplay between systemic cancer and the hematopoietic
stem cell niche
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Stem cell niche; Hematopoiesis; Microenvironment; Cancer
ID COLONY-STIMULATING FACTOR; BONE-MARROW MICROENVIRONMENT; CHRONIC
MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROGENITOR CELLS;
ENDOTHELIAL-CELLS; SELF-RENEWAL; OSTEOBLASTIC CELLS; STEM/PROGENITOR
CELLS; RAPID MOBILIZATION
AB Hematopoietic cells are increasingly recognized as playing key roles in tumor growth and metastatic progression. Although many studies have focused on the functional interaction of hematopoietic cells with tumor cells, few have examined the regulation of hematopoiesis by the hematopoietic stem cell (HSC) niche in the setting of cancer. Hematopoiesis occurs primarily in the bone marrow, and processes including expansion, mobilization, and differentiation of hematopoietic progenitors are tightly regulated by the specialized stem cell niche. Loss of niche components or the ability of stem cells to localize to the stem cell niche relieves HSCs of the restrictions imposed under normal homeostasis. In this review, we discuss how tumor-derived factors and therapeutic interventions disrupt structural and regulatory properties of the stem cell niche, resulting in niche invasion by hematopoietic malignancies, extramedullary hematopoiesis, myeloid skewing by peripheral tissue microenvironments, and lymphopenia. The key regulatory roles played by the bone marrow niche in hematopoiesis has implications for therapy-related toxicity and the successful development of immune-based therapies for cancer. Published by Elsevier Inc.
C1 [Giles, Amber J.; Reid, Caitlin M.; Park, Deric M.; Gilbert, Mark R.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Chien, Christopher D.; Fry, Terry J.; Kaplan, Rosandra N.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Giles, AJ (reprint author), 37 Convent Dr,Bldg 37 Rm 1142B, Bethesda, MD 20892 USA.
EM amber.giles@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD DEC
PY 2016
VL 168
BP 53
EP 60
DI 10.1016/j.pharmthera.2016.09.006
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EF9FE
UT WOS:000390635300006
PM 27595927
ER
PT J
AU Baseler, WA
Davies, LC
Quigley, L
Ridnour, LA
Weiss, JM
Hussain, SP
Wink, DA
McVicar, DW
AF Baseler, Walter A.
Davies, Luke C.
Quigley, Laura
Ridnour, Lisa A.
Weiss, Jonathan M.
Hussain, S. Perwez
Wink, David A.
McVicar, Daniel W.
TI Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic
commitment by tuning nitric oxide production
SO REDOX BIOLOGY
LA English
DT Article
ID DENDRITIC CELL ACTIVATION; ALTERNATIVE ACTIVATION; METABOLIC-REGULATION;
INHIBITION; INTERLEUKIN-10; BIOSYNTHESIS; INFLAMMATION; HIF-1-ALPHA;
RESPONSES; SYNTHASE
AB Inflammatory maturation of M1 macrophages by proinflammatory stimuli such as toll like receptor ligands results in profound metabolic reprogramming resulting in commitment to aerobic glycolysis as evidenced by repression of mitochondrial oxidative phosphorylation (OXPHOS) and enhanced glucose utilization. In contrast, "alternatively activated" macrophages adopt a metabolic program dominated by fatty acid-fueled OXPHOS. Despite the known importance of these developmental stages on the qualitative aspects of an inflammatory response, relatively little is know regarding the regulation of these metabolic adjustments. Here we provide evidence that the immunosuppressive cytokine IL-10 defines a metabolic regulatory loop. Our data show for the first time that lipopolysaccharide (LPS)-induced glycolytic flux controls IL-10-production via regulation of mammalian target of rapamycin (mTOR) and that autocrine IL-10 in turn regulates macrophage nitric oxide (NO) production. Genetic and pharmacological manipulation of IL-10 and nitric oxide (NO) establish that metabolically regulated autocrine IL-10 controls glycolytic commitment by limiting NO-mediated suppression of OXPHOS. Together these data support a model where autocine IL-10 production is controlled by glycolytic flux in turn regulating glycolytic commitment by preserving OXPHOS via suppression of NO. We propose that this IL-10-driven metabolic rheostat maintains metabolic equilibrium during M1 macrophage differentiation and that perturbation of this regulatory loop, either directly by exogenous cellular sources of IL-10 or indirectly via limitations in glucose availability, skews the cellular metabolic program altering the balance between inflammatory and immunosuppressive phenotypes. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
C1 [Baseler, Walter A.; Davies, Luke C.; Quigley, Laura; Ridnour, Lisa A.; Weiss, Jonathan M.; Wink, David A.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Davies, Luke C.] Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff, S Glam, Wales.
[Hussain, S. Perwez] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.
RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM mcvicard@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute; Welcome
Trust, UK
FX This work was funded in part by the Intramural Research Program of the
National Cancer Institute. LCD is funded in part by the Welcome Trust,
UK.
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD DEC
PY 2016
VL 10
BP 12
EP 23
DI 10.1016/j.redox.2016.09.005
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EF8SD
UT WOS:000390598800002
PM 27676159
ER
PT J
AU Salmon, AB
Kim, G
Liu, C
Wren, JD
Georgescu, C
Richardson, A
Levine, RL
AF Salmon, Adam B.
Kim, Geumsoo
Liu, Chengyu
Wren, Jonathan D.
Georgescu, Constantin
Richardson, Arlan
Levine, Rodney L.
TI Effects of transgenic methionine sulfoxide reductase A (MsrA) expression
on lifespan and age-dependent changes in metabolic function in mice
SO REDOX BIOLOGY
LA English
DT Article
DE Redox; Oxidative stress; Longevity; Metabolism; Proteostasis
ID PROTEINS; DISEASE; CELLS; OVEREXPRESSION; LOCALIZATION; PROTEOSTASIS;
OXIDATION; RESIDUES; MAMMALS
AB Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA) repairs oxidation of free-and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria. Previous studies in Drosophila have shown that increasing expression of MsrA can extend longevity. Here we test the effects of increasing MsrA on longevity and healthy aging in two transgenic mouse models. We show that elevated expression of MsrA targeted specifically to the cytosol reduces the rate of age-related death in female mice when assessed by Gompertz analysis. However, neither cytosolic nor mitochondrial MsrA overexpression extends lifespan when measured by log-rank analysis. In mice with MsrA overexpression targeted to the mitochondria, we see evidence for improved insulin sensitivity in aged female mice. With these and our previous data, we conclude that the increasing MsrA expression in mice has differential effects on aging and healthy aging that are dependent on the target of its subcellular localization.
C1 [Salmon, Adam B.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA.
[Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA.
[Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core, Bldg 10, Bethesda, MD 20892 USA.
[Wren, Jonathan D.; Georgescu, Constantin] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[Richardson, Arlan] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA.
[Richardson, Arlan] Oklahoma City VA Med Ctr, Oklahoma City, OK USA.
RP Salmon, AB (reprint author), UTHSCSA, 15355 Lambda Dr, San Antonio, TX 78245 USA.; Levine, RL (reprint author), NIH, Bldg 50 Room 2351, Bethesda, MD 20892 USA.
EM salmona@uthscsa.edu; rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU National Institute of Health [R01AG050797]; American Federation of Aging
Research; American Heart Association [15BGIA23220016]; Geriatric
Research, Education and Clinical Center of the South Texas Veterans
Health Care System; Intramural Research Program of the National, Heart,
Lung, and Blood Institute
FX The authors have no potential conflicts of interest to disclose. The
laboratory of ABS is supported by a grant from the National Institute of
Health (R01AG050797), a grant from the American Federation of Aging
Research, a grant from the American Heart Association (15BGIA23220016)
and the Geriatric Research, Education and Clinical Center of the South
Texas Veterans Health Care System. Body composition was measured through
the San Antonio Nathan Shock Center Healthspan and Functional Assessment
core facility (P30AG013319). Statistical analysis of lifespan was
performed by the Discovery Bioinformatics Core of the Oklahoma Nathan
Shock Center (P30AG050911). The work of KM, CL, and RLL was supported by
the Intramural Research Program of the National, Heart, Lung, and Blood
Institute. This material is the result of work supported with resources
and the use of facilities at South Texas Veterans Health Care System,
San Antonio, Texas. The contents do not necessarily represent the views
of the U.S. Department of Veterans Affairs or the United States
Government.
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD DEC
PY 2016
VL 10
BP 251
EP 256
DI 10.1016/j.redox.2016.10.012
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EF8SD
UT WOS:000390598800026
PM 27821326
ER
PT J
AU Proctor, LM
AF Proctor, Lita M.
TI The National Institutes of Health Human Microbiome Project
SO SEMINARS IN FETAL & NEONATAL MEDICINE
LA English
DT Review
DE Microbiome; DNA sequence; Metagenomics; Metabolomics;
Metatranscriptomics; Resources
ID DIVERSITY; GUT; PERIODONTITIS; BACTERIA
AB This overview describes the impetus for and the goals of the National Institutes of Health (NIH)'s Human Microbiome Project (HMP) and the research resources available through the HMI? As the HMP also serves as a catalyst for human microbiome research at the NIH, NIH Institutes and Centers support for this field is also briefly addressed. Published by Elsevier Ltd.
C1 [Proctor, Lita M.] NHGRI, Human Microbiome Project, NIH, 5635 Fisher Lane,Suite 4076, Bethesda, MD 20852 USA.
RP Proctor, LM (reprint author), NHGRI, Human Microbiome Project, NIH, 5635 Fisher Lane,Suite 4076, Bethesda, MD 20852 USA.
EM lita.proctor@nih.gov
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1744-165X
EI 1878-0946
J9 SEMIN FETAL NEONAT M
JI Semin. Fetal Neonatal Med.
PD DEC
PY 2016
VL 21
IS 6
BP 368
EP 372
DI 10.1016/j.siny.2016.05.002
PG 5
WC Pediatrics
SC Pediatrics
GA EF7LA
UT WOS:000390509900002
PM 27350143
ER
PT J
AU Burks, S
Nagle, M
Kim, S
Milo, B
Frank, J
AF Burks, S.
Nagle, M.
Kim, S.
Milo, B.
Frank, J.
TI Pulsed Focused Ultrasound Preconditions Tissues To Increase Potency Of
Intravenously-infused Mesenchymal Stem Cells
SO TISSUE ENGINEERING PART A
LA English
DT Meeting Abstract
CT TERMIS - Americas Conference and Exhibition
CY DEC 11-14, 2016
CL San Diego, CA
SP TERMIS
C1 [Burks, S.; Nagle, M.; Kim, S.; Milo, B.; Frank, J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
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PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD DEC
PY 2016
VL 22
SU 1
MA 355
BP S93
EP S93
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA EF8HF
UT WOS:000390569200350
ER
PT J
AU Burks, SR
Nagle, ME
Kim, S
Milo, B
Frank, J
AF Burks, S. R.
Nagle, M. E.
Kim, S.
Milo, B.
Frank, J.
TI Low Intensity Ultrasound Prolongs Lifetimes Of Transplanted Mesenchymal
Stem Cells In Situ
SO TISSUE ENGINEERING PART A
LA English
DT Meeting Abstract
CT TERMIS - Americas Conference and Exhibition
CY DEC 11-14, 2016
CL San Diego, CA
SP TERMIS
C1 [Burks, S. R.; Nagle, M. E.; Kim, S.; Milo, B.; Frank, J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD DEC
PY 2016
VL 22
SU 1
MA 356
BP S93
EP S94
PG 2
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA EF8HF
UT WOS:000390569200351
ER
PT J
AU Burks, SR
Nagle, ME
Kim, S
Milo, B
Frank, J
AF Burks, S. R.
Nagle, M. E.
Kim, S.
Milo, B.
Frank, J.
TI Pulsed Focused Ultrasound Mechanically Activates Trpc1 Channels To
Enhance Local Stem Cell Homing
SO TISSUE ENGINEERING PART A
LA English
DT Meeting Abstract
CT TERMIS - Americas Conference and Exhibition
CY DEC 11-14, 2016
CL San Diego, CA
SP TERMIS
C1 [Burks, S. R.; Nagle, M. E.; Kim, S.; Milo, B.; Frank, J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD DEC
PY 2016
VL 22
SU 1
MA 279
BP S74
EP S74
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA EF8HF
UT WOS:000390569200275
ER
PT J
AU Frank, JA
Burks, SR
Kim, S
AF Frank, J. A.
Burks, S. R.
Kim, S.
TI Restoring Perfusion In Critical Hindlimb Ischemia Model Using Pulsed
Focused Ultrasound And Mesenchymal Stromal Cells (MSC) In An Aged Mouse
Model
SO TISSUE ENGINEERING PART A
LA English
DT Meeting Abstract
CT TERMIS - Americas Conference and Exhibition
CY DEC 11-14, 2016
CL San Diego, CA
SP TERMIS
C1 [Frank, J. A.; Burks, S. R.; Kim, S.] NIH, Frank Lab, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD DEC
PY 2016
VL 22
SU 1
MA 98
BP S27
EP S27
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA EF8HF
UT WOS:000390569200097
ER
PT J
AU Kim, SJ
Lin, Y
Milo, B
Burks, S
Nagel, M
Frank, JA
AF Kim, S. J.
Lin, Y.
Milo, B.
Burks, S.
Nagel, M.
Frank, J. A.
TI Investigating Cellular Response of Mesenchymal Stromal Cells to
Therapeutic Ultrasound in 3D Scaffold
SO TISSUE ENGINEERING PART A
LA English
DT Meeting Abstract
CT TERMIS - Americas Conference and Exhibition
CY DEC 11-14, 2016
CL San Diego, CA
SP TERMIS
C1 [Kim, S. J.; Milo, B.; Burks, S.; Nagel, M.; Frank, J. A.] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Lin, Y.] Georgetown Univ, Radiol & Imaging Sci, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD DEC
PY 2016
VL 22
SU 1
MA 572
BP S149
EP S149
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA EF8HF
UT WOS:000390569200558
ER
PT J
AU West, KA
Eder, AF
AF West, Kamille A.
Eder, Anne F.
TI Accepting hereditary hemochromatosis blood donors: ask not why, ask why
not
SO TRANSFUSION
LA English
DT Editorial Material
ID DONATION
C1 [West, Kamille A.; Eder, Anne F.] NIH, Dept Transfus Med, Blood Serv Sect, Ctr Clin, Bethesda, MD 20892 USA.
RP West, KA (reprint author), NIH, Dept Transfus Med, Blood Serv Sect, Ctr Clin, Bethesda, MD 20892 USA.
EM kamille.west@nih.gov
NR 9
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2016
VL 56
IS 12
BP 2907
EP 2909
DI 10.1111/trf.13919
PG 3
WC Hematology
SC Hematology
GA EF8KS
UT WOS:000390578300001
PM 27933629
ER
PT J
AU Srivastava, K
Lee, E
Owens, E
Rujirojindakul, P
Flegel, WA
AF Srivastava, Kshitij
Lee, Eunah
Owens, Eric
Rujirojindakul, Pairaya
Flegel, Willy A.
TI Full-length nucleotide sequence of ERMAP alleles encoding Scianna (SC)
antigens
SO TRANSFUSION
LA English
DT Article
ID BLOOD-GROUP SYSTEM; AFRICAN-AMERICANS; GENETIC-VARIATION; ANTIBODY;
PROTEIN; HAPLOTYPES; PHENOTYPES
AB BACKGROUNDScianna (SC) blood group system comprises two antithetical antigens, Sc1 and Sc2, and five additional antigens. The antigens reside on a glycoprotein encoded by the erythroblast membrane-associated protein (ERMAP) gene. For the common ERMAP alleles, we determined the full-length nucleotide sequence that encodes the Scianna glycoprotein.
STUDY DESIGN AND METHODSBlood donor samples from five populations were analyzed including 20 African Americans, 10 Caucasians, 10 Thai, five Asians, and five Hispanics for a total of 100 chromosomes. An assay was devised to determine the genomic sequence of the ERMAP gene in one amplicon, spanning 21.4 kb and covering Exons 2 to 12 and the intervening sequence (IVS). All alleles (confirmed haplotypes) were resolved without ambiguity.
RESULTSAmong 50 blood donors, we found 80 single-nucleotide polymorphisms (SNPs), including six novel SNPs, in 21,308 nucleotides covering the coding sequence of the ERMAP gene and including the introns. The noncoding sequences harbored 75 SNPs (68 in the introns and seven in the 3-UTR). No SNP indicative of a nonfunctional allele was detected. The nucleotide sequences for 48 ERMAP alleles (confirmed haplotypes) were determined by allele-specific polymerase chain reaction and sequencing in 100 chromosomes.
CONCLUSIONSWe documented 48 ERMAP alleles of 21,308 nucleotides each. The two nucleotide sequences available in GenBank for ERMAP alleles of similar length have not been found in our 100 chromosomes. Alleles determined without ambiguity can be used as templates to analyze next generation sequencing data, which will enhance the reliability in clinical diagnostics.
C1 [Srivastava, Kshitij; Lee, Eunah; Owens, Eric; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Rujirojindakul, Pairaya] Prince Songkla Univ, Dept Pathol, Fac Med, Hat Yai, Thailand.
RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
EM waf@nih.gov
FU NIH Clinical Center [Z99 CL999999]
FX This work was supported by the Intramural Research Program (project ID
Z99 CL999999) of the NIH Clinical Center.
NR 28
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2016
VL 56
IS 12
BP 3047
EP 3054
DI 10.1111/trf.13801
PG 8
WC Hematology
SC Hematology
GA EF8KS
UT WOS:000390578300022
PM 27612015
ER
PT J
AU Strengers, PFW
Klein, HG
AF Strengers, Paul F. W.
Klein, Harvey G.
TI Plasma is a strategic resource
SO TRANSFUSION
LA English
DT Editorial Material
ID FACTOR-VIII; BLOOD
AB Plasma-derived medicinal products (PDMPs) such as immunoglobulins and clotting factors are listed by the World Health Organization as essential medicines. These and other PDMPs are crucial for the prophylaxis and treatment of patients with bleeding disorders, immune deficiencies, autoimmune and inflammatory diseases, and a variety of congenital deficiency disorders. While changes in clinical practice in developed countries have reduced the need for red blood cell transfusions thereby significantly reducing the collection volumes of whole blood and recovered plasma suitable for fractionation, the need for PDMPs worldwide continues to increase. The majority of plasma supplies for the manufacture of PDMPs is met by the US commercial plasma industry. However, geographic imbalance in the collection of plasma raises concerns that local disruptions of plasma supplies could result in regional and global shortages of essential PDMPs. Plasma, which fits the definition of a strategic resource, that is, an economically important raw material which is subject to a higher risk of supply interruption, should be considered a strategic resource comparable to energy and drinking water. Plasma collections should be increased outside the United States, including in low- and middle-income countries. The need for capacity building in these countries is an essential part to strengthen quality plasma collection. This will require changes in national and regional policies. We advocate the need for the restoration of an equitable balance of the international plasma supply to reduce the risk of supply shortages worldwide. Strategic independence of plasma should be endorsed on a global level.
C1 [Strengers, Paul F. W.] Sanquin Plasma Prod, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands.
[Strengers, Paul F. W.] Int Plasma Fractionat Assoc, Amsterdam, Netherlands.
[Klein, Harvey G.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Strengers, PFW (reprint author), Sanquin Plasma Prod, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands.
EM p.strengers@sanquin.nl
NR 24
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2016
VL 56
IS 12
BP 3133
EP 3137
DI 10.1111/trf.13913
PG 5
WC Hematology
SC Hematology
GA EF8KS
UT WOS:000390578300032
PM 27861951
ER
PT J
AU Yao, PJ
Petralia, RS
Mattson, MP
AF Yao, Pamela J.
Petralia, Ronald S.
Mattson, Mark P.
TI Sonic Hedgehog Signaling and Hippocampal Neuroplasticity
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID NEURAL STEM-CELLS; DOWN-SYNDROME; ALZHEIMERS-DISEASE; DENTATE GYRUS;
UP-REGULATION; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR;
CEREBRAL-ISCHEMIA; BRAIN PLASTICITY; MEMORY DEFICITS
AB Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural progenitor cells, and their neuronal and glial progeny, during development. Emerging findings suggest that Shh also has important roles in the formation and plasticity of neuronal circuits in the hippocampus, a brain region of fundamental importance in learning and memory. Shh mediates activity-dependent and injury-induced hippocampal neurogenesis. Activation of Shh receptors in the dendrites of hippocampal neurons engages a trans-neuronal signaling pathway that accelerates axon outgrowth and enhances glutamate release from presynaptic terminals. Impaired Shh signaling may contribute to the pathogenesis of several developmental and adult-onset neurological disorders that affect the hippocampus, suggesting a potential for therapeutic interventions that target Shh pathways.
C1 [Yao, Pamela J.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Yao, PJ; Mattson, MP (reprint author), NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.; Mattson, MP (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
EM yaopa@grc.nia.nih.gov; mark.mattson@nih.gov
FU National Institutes of Health/National Institute on Aging; National
Institutes of Health/National Institute on Deafness and Other
Communication Disorders
FX This work was supported by the Intramural Research Programs of the
National Institutes of Health/National Institute on Aging and the
National Institutes of Health/National Institute on Deafness and Other
Communication Disorders. The code for the Advanced Imaging Core is ZIC
DC000081. We thank Kristen Alexander for help with the preparation of
illustrations.
NR 80
TC 2
Z9 2
U1 9
U2 9
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD DEC
PY 2016
VL 39
IS 12
BP 840
EP 850
DI 10.1016/j.tins.2016.10.001
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA EF9DW
UT WOS:000390631900005
PM 27865563
ER
PT J
AU Bonhoeffer, J
Kochhar, S
Hirschfeld, S
Heath, PT
Jones, CE
Bauwens, J
Honrado, A
Heininger, U
Munoz, FM
Eckert, L
Steinhoff, M
Black, S
Padula, M
Sturkenboom, M
Buttery, J
Pless, R
Zuber, P
AF Bonhoeffer, Jan
Kochhar, Sonali
Hirschfeld, Steven
Heath, Paul T.
Jones, Christine E.
Bauwens, Jorgen
Honrado, Angel
Heininger, Ulrich
Munoz, Flor M.
Eckert, Linda
Steinhoff, Mark
Black, Steven
Padula, Michael
Sturkenboom, Miriam
Buttery, Jim
Pless, Robert
Zuber, Patrick
CA GAIA Project Participants
TI Global alignment of immunization safety assessment in pregnancy - The
GAIA project
SO VACCINE
LA English
DT Article
ID EVENTS FOLLOWING IMMUNIZATION; VACCINES
AB Immunization in pregnancy provides a promising contribution to globally reducing neonatal and under five childhood mortality and morbidity. Thorough assessment of benefits and risks for the primarily healthy pregnant women and their unborn babies is required. The GAIA project was formed in response to the call of the World Health Organization for a globally concerted approach to actively monitor the safety of vaccines and immunization in pregnancy programs. GAIA aims to improve the quality of outcome data from clinical vaccine trials in pregnant women with a specific focus on the needs and requirements for safety monitoring in LMIC.
In the first year of the project, a large and functional network of experts was created. The first outputs include a guidance document for clinical trials of immunization in pregnancy, a basic data collection guide, ten case definitions of key obstetric and neonatal health outcomes, an ontology of key terms and a map of pertinent disease codes.
The GAIA Network is designed as an open and growing forum for professionals sharing the GAIA vision and aim. Based on the initial achievements, tools and services are developed to support investigators and strengthen immunization in pregnancy programs with specific focus on LMIC. (C) 2016 Published by Elsevier Ltd.
C1 [Bonhoeffer, Jan; Bauwens, Jorgen] Brighton Collaborat Fdn, Spitalstr 33, CH-4056 Basel, Switzerland.
[Bonhoeffer, Jan; Heininger, Ulrich] Univ Basel, Childrens Hosp, Basel, Switzerland.
[Kochhar, Sonali] Global Healthcare Consulting, Delhi, India.
[Hirschfeld, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Heath, Paul T.; Jones, Christine E.] St Georges Univ London, London, England.
[Honrado, Angel] Synapse Res Management Partners, Barcelona, Spain.
[Munoz, Flor M.] Baylor Coll Med, Houston, TX 77030 USA.
[Eckert, Linda] Univ Washington, Seattle, WA 98195 USA.
[Steinhoff, Mark; Black, Steven] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Padula, Michael] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Sturkenboom, Miriam] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Buttery, Jim] Monash Univ, Melbourne, Vic, Australia.
[Pless, Robert] Publ Hlth Agcy Canada, Ottawa, ON, Canada.
[Zuber, Patrick] WHO, Geneva, Switzerland.
RP Bonhoeffer, J (reprint author), Brighton Collaborat Fdn, Spitalstr 33, CH-4056 Basel, Switzerland.
EM contact@brightoncollaboration.org
FU Bill & Melinda Gates Foundation [OPP1119788]
FX The GAIA project is supported by the Bill & Melinda Gates Foundation,
Grant Number OPP1119788. The authors are grateful for the extraordinary
effort by the many volunteering professional colleagues in the various
working groups and the many additional participants providing excellent
contributions, peer review or in person consultations. An updated list
of GAIA Network partners and participants is available at:
http://gaia-consortium.net.
NR 10
TC 0
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD DEC 1
PY 2016
VL 34
IS 49
SI SI
BP 5993
EP 5997
DI 10.1016/j.vaccine.2016.07.006
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EF7MP
UT WOS:000390514000002
PM 27751641
ER
PT J
AU Jones, CE
Munoz, FM
Spiegel, HML
Heininger, U
Zuber, PLF
Edwards, KM
Lambach, P
Neels, P
Kohl, KS
Gidudu, J
Hirschfeld, S
Oleske, JM
Khuri-Bulos, N
Bauwens, J
Eckert, LO
Kochhar, S
Bonhoeffer, J
Heath, PT
AF Jones, Christine E.
Munoz, Flor M.
Spiegel, Hans M. L.
Heininger, Ulrich
Zuber, Patrick L. F.
Edwards, Kathryn M.
Lambach, Philipp
Neels, Pieter
Kohl, Katrin S.
Gidudu, Jane
Hirschfeld, Steven
Oleske, James M.
Khuri-Bulos, Najwa
Bauwens, Jorgen
Eckert, Linda O.
Kochhar, Sonali
Bonhoeffer, Jan
Heath, Paul T.
CA Brighton Collaboration Immunizatio
TI Guideline for collection, analysis and presentation of safety data in
clinical trials of vaccines in pregnant women
SO VACCINE
LA English
DT Article
DE Adverse event; Immunization; Pregnancy; Guidelines; Clinical trials;
Vaccines; Safety
ID INFLUENZA VACCINATION; STATEMENT; INFANTS; QUALITY; RECOMMENDATIONS;
EPIDEMIOLOGY; PREVENTION; PROTOCOL
AB Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies.
The guidelines proposed in this document have been developed to harmonize safety data collection in all phases of clinical trials of vaccines in pregnant women and apply to data from the mother, fetus and infant. Guidelines on the prioritization of the data to be collected is also provided to allow applicability in various geographic, cultural and resource settings, including high, middle and low-income countries. (C) 2016 Published by Elsevier Ltd.
C1 [Jones, Christine E.; Heath, Paul T.] St Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, Jenner Wing,Level 2,Room 2-213, London SW17 0RE, England.
[Munoz, Flor M.] Baylor Coll Med, Houston, TX 77030 USA.
[Spiegel, Hans M. L.] Henry Jackson Fdn, Bethesda, MD USA.
[Heininger, Ulrich; Bonhoeffer, Jan] Univ Basel, Childrens Hosp, Basel, Switzerland.
[Zuber, Patrick L. F.] WHO, SAV, Regulat Med & Other Hlth Technol RHT, Dept Essential Med & Hlth Prod EMP,Hlth Syst & In, Geneva, Switzerland.
[Edwards, Kathryn M.] Vanderbilt Univ, Dept Pediat, Vanderbilt Vaccine Res Program, Nashville, TN USA.
[Lambach, Philipp] WHO, Initiat Vaccine Res, Geneva, Switzerland.
[Neels, Pieter] IABS EU, Int Alliance Biol Standardizat, Lyon, France.
[Kohl, Katrin S.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Gidudu, Jane] CDC, Global Immunizat Div, Ctr Global Hlth, Atlanta, GA 30333 USA.
[Hirschfeld, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Oleske, James M.] Rutgers New Jersey Med Sch, Div Pediat Allergy Immunol & Infect Dis, Newark, NJ USA.
[Khuri-Bulos, Najwa] Univ Jordan, Infect Dis & Vaccine Ctr, Amman, Jordan.
[Bauwens, Jorgen] Brighton Collaborat Fdn, Basel, Switzerland.
[Eckert, Linda O.] Univ Washington, Seattle, WA 98195 USA.
[Kochhar, Sonali] Global Healthcare Consulting, Delhi, India.
RP Heath, PT (reprint author), St Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, Jenner Wing,Level 2,Room 2-213, London SW17 0RE, England.
EM contact@brightoncollaboration.org
FU Bill & Melinda Gates Foundation [OPP1119788]
FX This work has been supported by the Bill & Melinda Gates Foundation
Grant OPP1119788, Global Alignment of Immunization Safety Assessment in
pregnancy (GAIA).
NR 54
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD DEC 1
PY 2016
VL 34
IS 49
SI SI
BP 5998
EP 6006
DI 10.1016/j.vaccine.2016.07.032
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA EF7MP
UT WOS:000390514000003
PM 27481360
ER
PT J
AU Simonsick, EM
Meier, HCS
Shaffer, NC
Studenski, SA
Ferrucci, L
AF Simonsick, Eleanor M.
Meier, Helen C. S.
Shaffer, Nancy Chiles
Studenski, Stephanie A.
Ferrucci, Luigi
TI Basal body temperature as a biomarker of healthy aging
SO AGE
LA English
DT Article
DE Aging; Body temperature; Functional performance; Excessive adiposity
ID DISTANCE CORRIDOR WALK; INTACT OLDER-ADULTS; ALL-CAUSE MORTALITY;
CALORIE RESTRICTION; METABOLIC-RATE; CORE TEMPERATURE; MUSCLE STRENGTH;
GAIT SPEED; LONGEVITY; AGE
AB Scattered evidence indicates that a lower basal body temperature may be associated with prolonged health span, yet few studies have directly evaluated this relationship. We examined cross-sectional and longitudinal associations between early morning oral temperature (95.0-98.6 A degrees F) and usual gait speed, endurance walk performance, fatigability, and grip strength in 762 non-frail men (52 %) and women aged 65-89 years participating in the Baltimore Longitudinal Study of Aging. Since excessive adiposity (body mass index ae35 kg/m(2) or waist-to-height ratio ae0.62) may alter temperature set point, associations were also examined within adiposity strata. Overall, controlling for age, race, sex, height, exercise, and adiposity, lower temperature was associated with faster gait speed, less time to walk 400 m quickly, and lower perceived exertion following 5-min of walking at 0.67 m/s (all p ae 0.02). In the non-adipose (N = 662), these associations were more robust (all p ae 0.006). Direction of association was reversed in the adipose (N = 100), but none attained significance (all p > 0.22). Over 2.2 years, basal temperature was not associated with functional change in the overall population or non-adipose. Among the adipose, lower baseline temperature was associated with greater decline in endurance walking performance (p = 0.006). In longitudinal analyses predicting future functional performance, low temperature in the non-adipose was associated with faster gait speed (p = 0.021) and less time to walk 400 m quickly (p = 0.003), whereas in the adipose, lower temperature was associated with slower gait speed (p = 0.05) and more time to walk 400 m (p = 0.008). In older adults, lower basal body temperature appears to be associated with healthy aging in the absence of excessive adiposity.
C1 [Simonsick, Eleanor M.; Shaffer, Nancy Chiles; Studenski, Stephanie A.; Ferrucci, Luigi] NIA, Intramural Res Program, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA.
[Meier, Helen C. S.] Univ Wisconsin Madison, Joseph J Zilber Sch Publ Hlth, Wilwaukee, WI USA.
RP Simonsick, EM (reprint author), NIA, Intramural Res Program, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA.
EM simonsickel@mail.nih.gov
FU Intramural Research Program, National Institute on Aging, and National
Institutes of Health; Intramural Research Program of the National
Institute on Aging
FX Funded by the Intramural Research Program, National Institute on Aging,
and National Institutes of Health. The Baltimore Longitudinal Study of
Aging is supported by the Intramural Research Program of the National
Institute on Aging.
NR 40
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U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD DEC
PY 2016
VL 38
IS 5-6
BP 445
EP 454
DI 10.1007/s11357-016-9952-8
PG 10
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA EF1CK
UT WOS:000390062500007
PM 27785691
ER
PT J
AU Lamb, RJ
Ginsburg, BC
Schindler, CW
AF Lamb, R. J.
Ginsburg, Brett C.
Schindler, Charles W.
TI Effects of an ethanol-paired CS on responding for ethanol and food:
Comparisons with a stimulus in a Truly-Random-Control group and to a
food-paired CS on responding for food
SO ALCOHOL
LA English
DT Article
DE Pavlovian conditioning; Pavlovian-Instrumental-Transfer; Ethanol
self-administration; Rat; Truly-Random-Control; Associative learning;
Addiction; Alcoholism; Craving
ID PAVLOVIAN-INSTRUMENTAL-TRANSFER; DRUG-SEEKING BEHAVIOR; CONDITIONED
APPROACH; INCENTIVE SALIENCE; SIGN-TRACKING; COCAINE; RATS; ADDICTION;
ALCOHOL; CUES
AB Motivational increases due to exposure to alcohol-paired Conditioned Stimuli (CS) are central to some accounts of alcoholism. However, few studies isolate a stimulus's function as a CS from its other potential functions. Pavlovian-Instrumental-Transfer (PIT) procedures isolate a stimulus's function as a CS from its other functions. Though there are several relevant studies using PIT, knowledge gaps exist. Particularly, it is not clear that an alcohol-paired CS will increase alcohol seeking compared to the same stimulus in a Truly-Random-Control group, nor whether such increases are specific to alcohol seeking. To address these knowledge gaps in Experiment 1, rats responded for ethanol (0.1 ml 8% w/v) under an RI 30-sec schedule, then the lever was removed and half the rats had ethanol delivered during occasional 120 sec light presentations, while the remainder had ethanol and the light presented under independent RT schedules. Later the lever was returned and the light was presented during responding in extinction (PIT test). Following this test, levers were again removed and the light was presented without ethanol (light extinction), following again by a PIT test. Responding in the two groups during light presentations did not differ in either PIT test. Experiment 2 repeated Experiment 1 using food instead of ethanol. In Experiment 2, responding during light presentations increased in the paired group. In Experiment 3, rats were trained on a concurrent FR schedule of food and ethanol delivery. Ethanol was delivered following 5 responses and the response requirement for food adjusted so that similar numbers of food and ethanol deliveries were obtained. Subsequently, rats underwent conditioning, control and testing procedures identical to those in Experiment 1. In Experiment 3, the ethanol-paired CS increased ethanol-responding, but not food-responding. These results are most easily interpreted as changes in responding resulting from CS-elicited behavior rather than motivational changes. This interpretation is more compatible with some descriptions of the role of an alcohol-paired CS in alcoholism than others. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lamb, R. J.; Ginsburg, Brett C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Lamb, R. J.; Ginsburg, Brett C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Schindler, Charles W.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Lamb, RJ (reprint author), UTHSCSA, Psychiat, MC 7792,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM lamb@uthscsa.edu
FU NIH [AA12337]; NIH/NIDA Intramural Research Program
FX This work was supported by NIH grant AA12337. CWS was supported by the
NIH/NIDA Intramural Research Program. The excellent technical assistance
of Jonathan Chemello was instrumental in the accomplishment of this
work.
NR 32
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD DEC
PY 2016
VL 57
BP 15
EP 27
DI 10.1016/j.alcohol.2016.10.009
PG 13
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA EF4KP
UT WOS:000390294500003
PM 27916139
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI Moral Distress in Scientific Research
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
ID WHISTLEBLOWER
C1 [Resnik, David B.] NIH, Res Triangle Pk, NC USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural Program of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH)
FX This research was supported by the Intramural Program of the National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH). It does not represent the views of the NIEHS, NIH, or
the U.S. government. I am grateful to Andrew Jameton for useful comments
and for encouraging me to write about moral distress in scientific
research.
NR 10
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U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD DEC
PY 2016
VL 16
IS 12
BP 13
EP 15
DI 10.1080/15265161.2016.1239784
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EF1WN
UT WOS:000390115900012
PM 27901443
ER
PT J
AU Campbell, SM
Ulrich, CM
Grady, C
AF Campbell, Stephen M.
Ulrich, Connie M.
Grady, Christine
TI Response to Open Peer Commentaries on "A Broader Understanding of Moral
Distress"
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Letter
C1 [Campbell, Stephen M.] Bentley Univ, Waltham, MA USA.
[Ulrich, Connie M.] Univ Penn, Philadelphia, PA 19104 USA.
[Grady, Christine] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Campbell, SM (reprint author), Bentley Univ, Dept Philosophy, 175 Forest St, Waltham, MA 02452 USA.
EM scampbell@bentley.edu
NR 14
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Z9 0
U1 1
U2 1
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD DEC
PY 2016
VL 16
IS 12
BP W1
EP W3
DI 10.1080/15265161.2016.1248579
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA EF1WN
UT WOS:000390115900001
ER
PT J
AU Keppler-Noreuil, KM
Parker, VER
Darling, TN
Martinez-Agosto, JA
AF Keppler-Noreuil, Kim M.
Parker, Victoria E. R.
Darling, Thomas N.
Martinez-Agosto, Julian A.
TI Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic
strategies
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Review
DE somatic mosaicism; segmental overgrowth; therapy; PI3K; AKT; mTOR
pathway
ID TUBEROUS SCLEROSIS COMPLEX; FOCAL CORTICAL DYSPLASIA; DEVELOPMENTAL
BRAIN MALFORMATIONS; MAMMALIAN TARGET; MTOR INHIBITORS; ACTIVATING
MUTATIONS; CONSENSUS CONFERENCE; PULMONARY-EMBOLISM; RAPAMYCIN PATHWAY;
CLOVES SYNDROME
AB The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis. Key negative regulators of the PI3K-AKT signaling pathway include PTEN and TSC1/TSC2 and germline loss-of function mutations of these genes are established to cause PTEN Hamartoma Tumor Syndrome and Tuberous Sclerosis Complex. Mosaic forms of these conditions lead to increased activation of PI3K and mTOR at affected sites and there is phenotypic overlap between these conditions. All are associated with significant morbidity with limited options for treatment other than symptomatic therapies and surgeries. As dysregulation of the PI3K/AKT/mTOR pathway has been implicated in cancer, several small molecule inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are under clinical investigation. The development of these therapies brings closer the prospect of targeting treatment for somatic PI3K/AKT/mTOR-related overgrowth syndromes. This review describes the clinical findings, gene function and pathogenesis of these mosaic overgrowth syndromes, and presents existing and future treatment strategies to reduce or prevent associated complications of these disorders. (c) 2016 Wiley Periodicals, Inc.
C1 [Keppler-Noreuil, Kim M.] NHGRI, NIH, 49 Convent Dr 4A68, Bethesda, MD 20892 USA.
[Keppler-Noreuil, Kim M.] Univ Iowa, Iowa City, IA 52242 USA.
[Parker, Victoria E. R.] MedImmune Ltd, Gaithersburg, MD USA.
[Parker, Victoria E. R.] Cambridge Univ Hosp NHS Trust, Cambridge, MA USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dermatol, Bethesda, MD 20814 USA.
[Martinez-Agosto, Julian A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA.
[Martinez-Agosto, Julian A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Med Genet, Dept Pediat, Los Angeles, CA 90024 USA.
RP Keppler-Noreuil, KM (reprint author), NHGRI, NIH, 49 Convent Dr 4A68, Bethesda, MD 20892 USA.
EM kim.keppler-noreuil@nih.gov
OI Darling, Thomas/0000-0002-5161-1974
FU National Human Genome Research Institute; UK National Institute for
Health Research (NIHR) Cambridge Biomedical Research Centre; March of
Dimes Birth Defects Foundation [6-FY12-324]; NINDS [U54-NS092090];
NIH/NICHD [P50-HD-055784]; NIH/NCATS [UL1TR000124]
FX The authors are grateful to the patients and their families who have
participated in this research review. KKN is supported by intramural
funding of the National Human Genome Research Institute. VERP is
supported by the UK National Institute for Health Research (NIHR)
Cambridge Biomedical Research Centre. JAMA is supported by the March of
Dimes Birth Defects Foundation (6-FY12-324), NINDS (U54-NS092090),
NIH/NICHD (P50-HD-055784), and NIH/NCATS (UL1TR000124).
NR 131
TC 1
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U1 9
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4868
EI 1552-4876
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD DEC
PY 2016
VL 172
IS 4
BP 402
EP 421
DI 10.1002/ajmg.c.31531
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA EF5SO
UT WOS:000390390100007
PM 27860216
ER
PT J
AU Gaur, L
Hanna, A
Bandettini, WP
Fischbeck, KH
Arai, AE
Mankodi, A
AF Gaur, Lasya
Hanna, Alexander
Bandettini, W. Patricia
Fischbeck, Kenneth H.
Arai, Andrew E.
Mankodi, Ami
TI Upper arm and cardiac magnetic resonance imaging in Duchenne muscular
dystrophy
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID LATE-GADOLINIUM-ENHANCEMENT; VENTRICULAR SYSTOLIC FUNCTION;
EXTRACELLULAR VOLUME; CARDIOMYOPATHY; MUSCLE; QUANTIFICATION; BOYS; MRI;
FAT; T1
AB We analyzed quantitative maps of T-1 and T-2 relaxation times and muscle fat fraction measurements in magnetic resonance imaging of the upper arm skeletal muscles and heart in ambulatory boys with Duchenne muscular dystrophy and age-range-matched healthy volunteer boys. The cardiac-optimized sequences detected fatty infiltration and edema in the upper arm skeletal muscles but not the myocardium in these Duchenne muscular dystrophy boys who had normal ejection fraction. Imaging the heart and skeletal muscle using the same magnetic resonance imaging methods during a single scan may be useful in assessing relative disease status and therapeutic response in clinical trials of Duchenne muscular dystrophy.
C1 [Gaur, Lasya; Hanna, Alexander; Bandettini, W. Patricia; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging, Bldg 10, Bethesda, MD 20892 USA.
[Fischbeck, Kenneth H.; Mankodi, Ami] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA.
[Gaur, Lasya] Johns Hopkins Univ Hosp, Pediat Cardiol, Baltimore, MD 21287 USA.
RP Mankodi, A (reprint author), NINDS, Hereditary Muscle Dis Unit, Neurogenet Branch, NIH, 35 Convent Dr,Bldg 35,Room 2A-1002, Bethesda, MD 20892 USA.
EM ami.mankodi@nih.gov
FU National Institute of Neurological Disorders and Stroke
FX This work was supported by National Institute of Neurological Disorders
and Stroke.
NR 29
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD DEC
PY 2016
VL 3
IS 12
BP 948
EP 955
DI 10.1002/acn3.367
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA EF8GH
UT WOS:000390566700006
PM 28097207
ER
PT J
AU Scuteri, A
Franco, OH
Volzke, H
Shin, MH
Kweon, SS
Rietzschel, E
Ryliskyte, L
Strazhesko, I
Chen, CH
Lakatta, EG
Nilsson, PM
AF Scuteri, Angelo
Franco, Oscar H.
Volzke, Henry
Shin, Min-Ho
Kweon, Sun-Seog
Rietzschel, Ernst
Ryliskyte, Ligita
Strazhesko, Irina
Chen, Chen-Huan
Lakatta, Edward G.
Nilsson, Peter M.
CA Metabolic Syndrome Arteries Res
TI The relationship between the metabolic syndrome and arterial wall
thickness: A mosaic still to be interpreted
SO ATHEROSCLEROSIS
LA English
DT Article
DE Arteries; Arterial ageing; Carotid intima-media thickness; Metabolic
syndrome
ID INTIMA-MEDIA THICKNESS; MYOCARDIAL-INFARCTION; CAROTID-ARTERY;
BLOOD-PRESSURE; RISK-FACTOR; STIFFNESS; ULTRASOUND; STATEMENT; STROKE;
WOMEN
AB Background and aims: We aimed to identify clusters of metabolic syndrome (MetS) components, risky for extremely high intima-media thickness.
Methods: We studied 41,513 volunteers (men and women) from eleven cohorts worldwide, participating in the MARE (Metabolic syndrome and Artery REsearch) Consortium.
Results: Specific clusters of MetS components - high triglycerides-high blood pressure-abdominal obesity (TBW), low HDL cholesterol-high blood pressure-abdominal obesity (HBW), high glucose-high blood pressure-abdominal obesity (GBW) - were accompanied by a 50-90% significantly greater likelihood of presenting extremely high intima-media thickness (via ultrasound of carotid artery, CCA IMT), after controlling for age, sex, smoking, non-HDL cholesterol, and presence of diabetes mellitus. This likelihood is comparable to the effect of being 7-8 years older or of being a cigarette smoker or of having non-HDL cholesterol 50 mg/dl higher.
Conclusions: The consistent association of specific clusters of MetS components with extremely thick (older) large artery cross-culturally suggests that identification of those clusters in clinical practice will facilitate a personalized health care and a better - i.e. more healthy and cost-effective - prevention of major cardiovascular (CV) events. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Scuteri, Angelo] Policlin Tor Vergata, UOC Hypertens & Nephrol, Dept Med, Rome, Italy.
[Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Shin, Min-Ho; Kweon, Sun-Seog] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju, South Korea.
[Rietzschel, Ernst] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium.
[Rietzschel, Ernst] Univ Ghent, Ghent, Belgium.
[Ryliskyte, Ligita] Vilnius Univ Hosp Santariskiu Klin, Ctr Cardiol & Angiol, Vilnius, Lithuania.
[Strazhesko, Irina] Natl Res Ctr Prevent Med, Dept Aging & Age Associated Dis Prevent, Moscow, Russia.
[Chen, Chen-Huan] Natl Yang Ming Univ, Cardiovasc Res Ctr, Dept Publ Hlth, Taipei, Taiwan.
[Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Programme, NIH, Baltimore, MD 21224 USA.
[Nilsson, Peter M.] Lund Univ, Univ Hosp, Dept Clin Sci, Malmo, Sweden.
RP Scuteri, A (reprint author), Policlin Tor Vergata, UOC Hypertens & Nephrol, Dept Med, Rome, Italy.
EM angeloelefante@interfree.it
FU Fund for Scientific Research - Flanders (FWO) [G042703, G083810N];
Erasmus Medical Center and Erasmus University Rotterdam; Netherlands
Organization for Scientific Research; Netherlands Organization for
Health Research and Development (ZonMw); Research Institute for Diseases
in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of
Education, Culture and Science; Ministry of Health Welfare and Sports;
European Commission; Municipality of Rotterdam; NIA [NO1-AG-1-2109];
Intramural Research Program of the NIH, National Institute on Aging
(USA); Federal Ministry of Education and Research; Federal State of
Mecklenburg-West Pomerania; Research Institute of Medical Sciences,
Chonnam National University; Intramural Research Program of the NIH,
National Institute on Aging; National Science Council (NSC)
[99-2314-B-010-034-MY3]; Taipei Veterans General Hospital [V102C-119];
Intramural Research Program of the National Institute on Aging, National
Institutes of Health; Swedish Research Council [K2008-65X-20752-01-3,
K2011-65X-20752-04-6]; Lundstroms Foundation; Swedish Heart-Lung
Foundation [2010-0244, 2013-0249]; ALF government grants [2012/1789];
[NO1-AG-1-2118]
FX The Asklepios Study is supported by the Fund for Scientific Research -
Flanders (FWO research grants G042703 and G083810N).; The Rotterdam
Study is supported by the Erasmus Medical Center and Erasmus University
Rotterdam; the Netherlands Organization for Scientific Research; the
Netherlands Organization for Health Research and Development (ZonMw);
the Research Institute for Diseases in the Elderly (RIDE); the
Netherlands Heart Foundation; the Ministry of Education, Culture and
Science; the Ministry of Health Welfare and Sports; the European
Commission; and the Municipality of Rotterdam.; The SardiNIA team was
supported by Contract NO1-AG-1-2109 from the NIA. This research was
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging (USA). SHIP is part of the Community
Medicine Network of the University Medicine Greifswald. The network was
initially funded by the Federal Ministry of Education and Research as
well as the Federal State of Mecklenburg-West Pomerania.; The Dong-gu
Study and the Namwon Study were supported by Research Institute of
Medical Sciences, Chonnam National University.; The Baltimore
Longitudinal Study of Aging (BLSA) is supported in part by the
Intramural Research Program of the NIH, National Institute on Aging.;
The Kingmen Aging study was supported, in part, by a grant from the
National Science Council (NSC 99-2314-B-010-034-MY3), an intramural
grant from the Taipei Veterans General Hospital (grant V102C-119),
Research and Development contract NO1-AG-1-2118, and the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health.; The Malmoe Diet Cancer - Cardiovascular Study was supported
by grants from the Swedish Research Council (K2008-65X-20752-01-3,
K2011-65X-20752-04-6), the Lundstroms Foundation, the Swedish Heart-Lung
Foundation (2010-0244; 2013-0249) and ALF government grants (Dnr:
2012/1789).
NR 22
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U1 4
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD DEC
PY 2016
VL 255
BP 11
EP 16
DI 10.1016/j.atherosclerosis.2016.10.032
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EE3QL
UT WOS:000389509700026
PM 27794213
ER
PT J
AU Forbang, NI
McClelland, RL
Remigio-Baker, RA
Allison, MA
Sandfort, V
Michos, ED
Thomas, I
Rifkin, DE
Criqui, MH
AF Forbang, Nketi I.
McClelland, Robyn L.
Remigio-Baker, Rosemay A.
Allison, Matthew A.
Sandfort, Veit
Michos, Erin D.
Thomas, Isac
Rifkin, Dena E.
Criqui, Michael H.
TI Associations of cardiovascular disease risk factors with abdominal
aortic calcium volume and density: The Multi-Ethnic Study of
Atherosclerosis (MESA)
SO ATHEROSCLEROSIS
LA English
DT Article
DE Abdominal aortic calcium; Agatston calcium score; Cardiovascular disease
risk factors; Coronary artery calcium; Density calcium score; Volume
calcium score
ID CORONARY-ARTERY CALCIUM; COMPUTED-TOMOGRAPHY; ETHNIC-DIFFERENCES;
MORTALITY; CALCIFICATION; ANGIOGRAPHY; MORBIDITY; EVENTS
AB Background and aims: Abdominal aortic calcium (AAC) predicts future cardiovascular disease (CVD) events and all-cause mortality independent of CVD risk factors. The standard AAC score, the Agatston, up-weights for greater calcium density, and thus models higher calcium density as associated with increased CVD risk. We determined associations of CVD risk factors with AAC volume and density (separately).
Methods: In a multi-ethnic cohort of community living adults, we used abdominal computed tomography scans to measure AAC volume and density. Multivariable linear regression was used to determine the period cross-sectional independent associations of CVD risk factors with AAC volume and AAC density in participants with prevalent AAC.
Results: Among 1413 participants with non-zero AAC scores, the mean age was 65 +/- 9 years, 52% were men, 44% were European-, 24% were Hispanic-, 18% were African-, and 14% were Chinese Americans (EA, HA, AA, and CA respectively). Median (interquartile range, IQR) for AAC volume was 628 mm(3) (157 -1939 mm(3)), and mean AAC density was 3.0 +/- 0.6. Compared to EA, each of HA, AA, and CA had lower natural log (ln) AAC volume, but higher AAC density. After adjustments for AAC density, older age, ever smoking history, higher systolic blood pressure, elevated total cholesterol, reduced HDL cholesterol, statin and anti-hypertensive medication use, family history of myocardial infarction, and alcohol consumption were significantly associated with higher ln(AAC volume). In contrast, after adjustments for ln(AAC volume), older age, ever smoking history, higher BMI, and lower HDL cholesterol were significantly associated with lower AAC density.
Conclusions: Several CVD risk factors were associated with higher AAC volume, but lower AAC density. Future studies should investigate the impact of calcium density of aortic plaques in CVD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Forbang, Nketi I.; Remigio-Baker, Rosemay A.; Allison, Matthew A.; Thomas, Isac; Rifkin, Dena E.; Criqui, Michael H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
[McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Allison, Matthew A.; Rifkin, Dena E.] Vet Adm San Diego Healthcare Syst, La Jolla, CA USA.
[Sandfort, Veit] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Michos, Erin D.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
RP Forbang, NI (reprint author), 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM nforbang@gmail.com
OI Allison, Matthew/0000-0003-0777-8272; Michos, Erin/0000-0002-5547-5084
FU National Heart, Lung, and Blood Institute [HL072403, N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169];
NCRR [UL1-TR-000040, UL1-TR-001079]
FX This study was supported by grant HL072403 and contracts N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169
from the National Heart, Lung, and Blood Institute and by grants
UL1-TR-000040 and UL1-TR-001079 from NCRR. The authors thank the other
investigators, the staff, and the participants of the MESA study for
their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
http://www.mesa-nhlbi.org.
NR 12
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD DEC
PY 2016
VL 255
BP 54
EP 58
DI 10.1016/j.atherosclerosis.2016.10.036
PG 5
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EE3QL
UT WOS:000389509700032
PM 27816809
ER
PT J
AU Slominski, AT
Zmijewski, MA
Jetten, AM
AF Slominski, Andrzej T.
Zmijewski, Michal A.
Jetten, Anton M.
TI ROR alpha is not a receptor for melatonin
SO BIOESSAYS
LA English
DT Editorial Material
C1 [Slominski, Andrzej T.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Slominski, Andrzej T.] Univ Alabama Birmingham, Ctr Comprehens Canc, Canc Chemoprevent Program, Birmingham, AL 35294 USA.
[Slominski, Andrzej T.] VA Med Ctr, Birmingham, AL 35233 USA.
[Zmijewski, Michal A.] Med Univ Gdansk, Dept Histol, Gdansk, Poland.
[Jetten, Anton M.] NIEHS, Immun Inflammat & Dis Lab, NIH, Durham, NC USA.
RP Slominski, AT (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.; Slominski, AT (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, Canc Chemoprevent Program, Birmingham, AL 35294 USA.; Slominski, AT (reprint author), VA Med Ctr, Birmingham, AL 35233 USA.
EM aslominski@uabmc.edu
FU NIAMS NIH HHS [R21 AR066505, R01 AR052190, R01 AR056666]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD DEC
PY 2016
VL 38
IS 12
BP 1193
EP 1194
DI 10.1002/bies.201600204
PG 2
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EF0AL
UT WOS:000389987700005
PM 27739090
ER
PT J
AU Sawyer, IA
Sturgill, D
Sung, MH
Hager, GL
Dundr, M
AF Sawyer, Iain A.
Sturgill, David
Sung, Myong-Hee
Hager, Gordon L.
Dundr, Miroslav
TI Cajal body function in genome organization and transcriptome diversity
SO BIOESSAYS
LA English
DT Article
DE Cajal bodies; chromatin; genome organization; nuclear bodies; RNA
splicing; snRNPs; transcription
ID RNA-POLYMERASE-II; WIDESPREAD INTRON RETENTION; HUMAN SNRNA GENES; 3'
END FORMATION; NUCLEAR-BODIES; COILED BODIES; MESSENGER-RNA; INTEGRATOR
COMPLEX; NONCODING RNAS; HUMAN-CELLS
AB Nuclear bodies contribute to non-random organization of the human genome and nuclear function. Using a major prototypical nuclear body, the Cajal body, as an example, we suggest that these structures assemble at specific gene loci located across the genome as a result of high transcriptional activity. Subsequently, target genes are physically clustered in close proximity in Cajal body-containing cells. However, Cajal bodies are observed in only a limited number of human cell types, including neuronal and cancer cells. Ultimately, Cajal body depletion perturbs splicing kinetics by reducing target small nuclear RNA (snRNA) transcription and limiting the levels of spliceosomal snRNPs, including their modification and turnover following each round of RNA splicing. As such, Cajal bodies are capable of shaping the chromatin interaction landscape and the transcriptome by influencing spliceosome kinetics. Future studies should concentrate on characterizing the direct influence of Cajal bodies upon snRNA gene transcriptional dynamics.
C1 [Sawyer, Iain A.; Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.
[Sawyer, Iain A.; Sturgill, David; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Sung, Myong-Hee] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Dundr, M (reprint author), Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.; Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM hagerg@dce41.nci.nih.gov; mirek.dundr@rosalindfranklin.edu
FU National Institutes of Health, National Institute of General Medical
Sciences [R01GM090156]; Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research; National Institute on Aging
FX The authors are supported by a National Institutes of Health, National
Institute of General Medical Sciences grant (R01GM090156, awarded to
M.D.), the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research (G.L.H.),
and the National Institute on Aging (M-H.S.). We thank Dr. Eric Wagner
and Dr. Karen Meaburn for stimulating conversations. The authors declare
no competing financial interests. Super-resolution structured
illumination microscopy (SIM) images were acquired at the NCI Core
Fluorescence Imaging Facility in Building 41, National Institutes of
Health(Bethesda, MD) with the assistance of Dr. Tatiana Karpova.
NR 134
TC 1
Z9 1
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD DEC
PY 2016
VL 38
IS 12
BP 1197
EP 1208
DI 10.1002/bies.201600144
PG 12
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA EF0AL
UT WOS:000389987700007
PM 27767214
ER
PT J
AU Zhai, HC
Yu, Y
Zhang, W
Chen, G
Jia, FC
AF Zhai, Hongchang
Yu, Yuan
Zhang, Wei
Chen, Gang
Jia, Fucang
TI ACC and IPL networks in the perception of the faces of parents during
selective tasks
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Face perception; Mother/father's face; Functional connectivity; fMRI;
Brain network
ID EVENT-RELATED FMRI; SUPERIOR TEMPORAL SULCUS; PERSONALLY FAMILIAR FACES;
SELF-FACE; ROMANTIC LOVE; BRAIN RESPONSES; VISUAL-CORTEX; NEURAL BASIS;
RECOGNITION; MOTHERS
AB The perception of the faces of parents is different from that of other faces. Mother's face perception is associated with childbearing and parenting and has specific cognitive processing properties. Yet, the underlying mechanism remains unknown. We investigated the neural network that is involved in the perception of parent's face based upon parental face selective tasks that were completed by 23 normal adults. Resting state functional magnetic resonance imaging (fMRI) and a task block design with fixation cross sign control fMRI were used. The faces activated the right inferior frontal gyrus, the left and right middle frontal gyri, and the left and right inferior parietal lobule. In addition, the parental faces task resulted in more activation than the control tasks in the left and right anterior cingulate, left middle (superior) temporal gyrus, right and left inferior frontal gyrus. The anterior cingulate cortex (ACC) and the inferior parietal lobe (IPL) are central nodes of the brain network, while the parental face perception network includes the anterior cingulate cortex and superior temporal gyrus (ACC-STG)/parahippocampal network as well as the inferior frontal and inferior parietal lobule (IFG-IPL) network. The network of father's face perception involves the left inferior parietal lobule and left middle frontal gyrus/right middle frontal gyrus/right inferior frontal gyrus, while mother's face perception involves the right inferior parietal lobe and frontal network (MFG.L/IFG.R). The experiments showed that the ACC-STG/parahippocampal network and IFG-IPL network are neural networks used in parental face perception, and the ACC and IPL are central nodes in the network. The neural pathway of parental face perception is similar to the perception of a stranger's face, as both include the STG, but is different in that the perception of the stranger's face involves a connected STG and IPL as a specific neural pathway.
C1 [Zhai, Hongchang; Yu, Yuan] Guangzhou Univ, Coll Educ, Higher Educ Mega Ctr, 230 Waihuan West Rd, Guangzhou 510006, Guangdong, Peoples R China.
[Zhang, Wei] South China Normal Univ, Sch Psychol, Guangzhou 510631, Guangdong, Peoples R China.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA.
[Jia, Fucang] Chinese Acad Sci, Shenzhen Inst Adv Technol, 1068 Xueyuan Ave, Shenzhen 518055, Peoples R China.
RP Zhai, HC (reprint author), Guangzhou Univ, Coll Educ, Higher Educ Mega Ctr, 230 Waihuan West Rd, Guangzhou 510006, Guangdong, Peoples R China.; Jia, FC (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, 1068 Xueyuan Ave, Shenzhen 518055, Peoples R China.
EM zhaihongchang@126.com; fc.jia@siat.ac.cn
FU NSFC-Guangdong Union Foundation [U1201257]; Shenzhen Basic Research
Project [JCYJ20150630114942306]
FX This study was supported by grants from the following sources: the
NSFC-Guangdong Union Foundation (Grant No. U1201257) and the Shenzhen
Basic Research Project (Grant No. JCYJ20150630114942306).
NR 69
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
EI 1931-7565
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD DEC
PY 2016
VL 10
IS 4
BP 1172
EP 1183
DI 10.1007/s11682-015-9486-1
PG 12
WC Neuroimaging
SC Neurosciences & Neurology
GA EF0LC
UT WOS:000390015900023
PM 26613720
ER
PT J
AU Shin, JM
Lee, B
Cho, KH
AF Shin, Jae-Min
Lee, Byungkook
Cho, Kwang-Hwi
TI A New Efficient Conformational Search Method for ab initio Protein
Folding Study: Window Growth Evolutionary Algorithm
SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY
LA English
DT Article
DE Protein folding; Window growth evolutionary algorithm; Window growth;
Evolutionary algorithm
ID GENETIC ALGORITHMS; SIMULATIONS; BACKBONE; ENERGY; MINIMIZATION;
NUCLEATION; BUILDUP; PROGRAM; MODEL; CHAIN
AB A new conformational search method, WGEA (window growth evolutionary algorithm), is described. In this method, a trial conformation is selected or rejected on the basis of the energy of a selected window of w consecutive residues only; interactions between residues beyond the selected window are ignored. The position of the window is selected randomly in a Monte-Carlo procedure. The window size w is changed slowly, from a minimum of 6 to the full length of the protein. An ensemble of structures is generated at each window size from which a fixed number of conformations are selected to be used as seed conformations for the next window size. When the root-mean-square (RMS) deviation from the experimental structure is used as the energy function and six discrete dihedral angle states are used for each residue to describe the protein conformation, WGEA efficiently refolds 14 model proteins within C RMS deviation of 1.2-2.8 angstrom.
C1 [Shin, Jae-Min; Cho, Kwang-Hwi] Soongsil Univ, Sch Syst Biomed Sci, Seoul 156743, South Korea.
[Lee, Byungkook] NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Cho, KH (reprint author), Soongsil Univ, Sch Syst Biomed Sci, Seoul 156743, South Korea.
EM chokh@ssu.ac.kr
FU KREONET (Korea Research Environment Open NETwork); National Research
Foundation of Korea (NRF) - Ministry of Science, ICT Future
[NRF-2012M3A9D1054705]
FX This work was supported by KREONET (Korea Research Environment Open
NETwork) which is managed and operated by KISTI (Korea Institute of
Science and Technology Information) and Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by
Ministry of Science, ICT & Future (NRF-2012M3A9D1054705).
NR 39
TC 0
Z9 0
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0253-2964
EI 1229-5949
J9 B KOREAN CHEM SOC
JI Bull. Korean Chem. Soc.
PD DEC
PY 2016
VL 37
IS 12
BP 1971
EP 1976
DI 10.1002/bkcs.11006
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA EF4BT
UT WOS:000390270200014
ER
PT J
AU Lam, S
Mandrekar, SJ
Gesthalter, Y
Ziegler, KLA
Seisler, DK
Midthun, DE
Mao, JT
Aubry, MC
McWilliams, A
Sin, DD
Shaipanich, T
Liu, G
Johnson, E
Bild, A
Lenburg, ME
Ionescu, DN
Mayo, J
Yi, J
Tazelaar, H
Harmsen, WS
Smith, J
Spira, AE
Beane, J
Limburg, PJ
Szabo, E
AF Lam, Stephen
Mandrekar, Sumithra J.
Gesthalter, Yaron
Ziegler, Katie L. Allen
Seisler, Drew K.
Midthun, David E.
Mao, Jenny T.
Aubry, Marie Christine
McWilliams, Annette
Sin, Don D.
Shaipanich, Tawimas
Liu, Gang
Johnson, Evan
Bild, Andrea
Lenburg, Marc E.
Ionescu, Diana N.
Mayo, John
Yi, Joanne (Eunhee)
Tazelaar, Henry
Harmsen, William S.
Smith, Judith
Spira, Avrum E.
Beane, Jennifer
Limburg, Paul J.
Szabo, Eva
CA Canc Prevention Network
TI A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial
Dysplasia
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID PREVENT COLORECTAL ADENOMAS; FEMALE A/J MICE; LUNG-CANCER; FORMER
SMOKERS; LESIONS; CHEMOPREVENTION; BRONCHOSCOPY; STATISTICS; ASPIRIN;
GENOME
AB Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with >= 1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myoinositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent.
C1 [Lam, Stephen; Shaipanich, Tawimas; Ionescu, Diana N.] British Columbia Canc Agcy, 10-111 675 West 10th Ave, Vancouver, BC V5Z 4E6, Canada.
[Mandrekar, Sumithra J.; Ziegler, Katie L. Allen; Seisler, Drew K.; Midthun, David E.; Aubry, Marie Christine; Yi, Joanne (Eunhee); Harmsen, William S.; Limburg, Paul J.] Mayo Clin, Rochester, MN USA.
[Gesthalter, Yaron; Liu, Gang; Johnson, Evan; Lenburg, Marc E.; Spira, Avrum E.; Beane, Jennifer] Boston Univ, Med Ctr, Boston, MA 02215 USA.
[Mao, Jenny T.] New Mexico Vet Hlth Care Syst, Albuquerque, NM USA.
[McWilliams, Annette] Fiona Stanley Hosp, Palmyra Dc, WA, Australia.
[Sin, Don D.] St Pauls Hosp, Vancouver, BC, Canada.
[Bild, Andrea] Univ Utah, Salt Lake City, UT USA.
[Mayo, John] Vancouver Gen Hosp, Vancouver, BC, Canada.
[Tazelaar, Henry] Mayo Clin, Scottsdale, AZ USA.
[Smith, Judith] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Lam, S (reprint author), British Columbia Canc Agcy, 10-111 675 West 10th Ave, Vancouver, BC V5Z 4E6, Canada.
EM slam2@bccancer.bc.ca
FU National Cancer Institute [N01CN35000]
FX The study was supported by a contract from the National Cancer Institute
(N01CN35000).
NR 36
TC 1
Z9 1
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD DEC
PY 2016
VL 9
IS 12
BP 906
EP 914
DI 10.1158/1940-6207.CAPR-15-0254
PG 9
WC Oncology
SC Oncology
GA EF1NS
UT WOS:000390092200003
PM 27658890
ER
PT J
AU McDermott, TJ
Badura-Brack, AS
Becker, KM
Ryan, TJ
Bar-Haim, Y
Pine, DS
Khanna, MM
Heinrichs-Graham, E
Wilson, TW
AF McDermott, Timothy J.
Badura-Brack, Amy S.
Becker, Katherine M.
Ryan, Tara J.
Bar-Haim, Yair
Pine, Daniel S.
Khanna, Maya M.
Heinrichs-Graham, Elizabeth
Wilson, Tony W.
TI Attention training improves aberrant neural dynamics during working
memory processing in veterans with PTSD
SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE Working memory; Prefrontal cortex; Attention; Cognitive control
ID POSTTRAUMATIC-STRESS-DISORDER; RESTING-STATE MAGNETOENCEPHALOGRAPHY;
SPACE SEPARATION METHOD; TEST-RETEST RELIABILITY; BIAS MODIFICATION;
OSCILLATORY DYNAMICS; ALPHA-ACTIVITY; MEG; MAINTENANCE; TASK
AB Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory (WM). Recent studies suggest that attention training reduces PTSD symptomatology, but the underlying neural mechanisms are unknown. We used high-density magnetoencephalography (MEG) to evaluate whether attention training modulates brain regions serving WM processing in PTSD. Fourteen veterans with PTSD completed a WM task during a 306-sensor MEG recording before and after 8 sessions of attention training treatment. A matched comparison sample of 12 combat-exposed veterans without PTSD completed the same WM task during a single MEG session. To identify the spatiotemporal dynamics, each group's data were transformed into the time-frequency domain, and significant oscillatory brain responses were imaged using a beamforming approach. All participants exhibited activity in left hemispheric language areas consistent with a verbal WM task. Additionally, veterans with PTSD and combat-exposed healthy controls each exhibited oscillatory responses in right hemispheric homologue regions (e.g., right Broca's area); however, these responses were in opposite directions. Group differences in oscillatory activity emerged in the theta band (4-8 Hz) during encoding and in the alpha band (9-12 Hz) during maintenance and were significant in right prefrontal and right supramarginal and inferior parietal regions. Importantly, following attention training, these significant group differences were reduced or eliminated. This study provides initial evidence that attention training improves aberrant neural activity in brain networks serving WM processing.
C1 [McDermott, Timothy J.; Badura-Brack, Amy S.; Ryan, Tara J.; Khanna, Maya M.] Creighton Univ, Dept Psychol, 2500 Calif Plaza, Omaha, NE 68178 USA.
[Becker, Katherine M.; Heinrichs-Graham, Elizabeth; Wilson, Tony W.] UNMC, Ctr Magnetoencephalog, Omaha, NE USA.
[Becker, Katherine M.] Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA.
[Ryan, Tara J.] Simon Fraser Univ, Dept Psychol, Burnaby, BC, Canada.
[Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, Tel Aviv, Israel.
[Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Heinrichs-Graham, Elizabeth; Wilson, Tony W.] UNMC, Dept Neurol Sci, Omaha, NE USA.
RP Badura-Brack, AS (reprint author), Creighton Univ, Dept Psychol, 2500 Calif Plaza, Omaha, NE 68178 USA.
EM abadura@creighton.edu
OI Wilson, Tony W/0000-0002-5053-8306
FU At Ease, USA; Creighton University College of Arts and Science Summer
Undergraduate Research Fellowship; National Institutes of Health
[R01-MH103220]; National Science Foundation [1539067]
FX This research was supported by a grant from the nonprofit organization
At Ease, USA (ABB), by a Creighton University College of Arts and
Science Summer Undergraduate Research Fellowship (TJM), and Grants
R01-MH103220 from the National Institutes of Health (TWW) and #1539067
from the National Science Foundation (TWW). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
TC 1
Z9 1
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-7026
EI 1531-135X
J9 COGN AFFECT BEHAV NE
JI Cogn. Affect. Behav. Neurosci.
PD DEC
PY 2016
VL 16
IS 6
BP 1140
EP 1149
DI 10.3758/s13415-016-0459-7
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA EF0MJ
UT WOS:000390019200014
PM 27722837
ER
PT J
AU Rotimi, CN
Tekola-Ayele, F
Baker, JL
Shriner, D
AF Rotimi, Charles N.
Tekola-Ayele, Fasil
Baker, Jennifer L.
Shriner, Daniel
TI The African diaspora: history, adaptation and health
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID DUFFY-BLOOD-GROUP; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-ASSOCIATED
NEPHROPATHY; LACTASE PERSISTENCE; PLASMODIUM-VIVAX; KIDNEY-DISEASE;
ETHIOPIAN POPULATION; MALARIAL INFECTION; SEQUENCING DATA; APOL1
VARIANTS
AB The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities.
C1 [Rotimi, Charles N.; Tekola-Ayele, Fasil; Baker, Jennifer L.; Shriner, Daniel] Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047 12 South Dr, Bethesda, MD 20892 USA.
RP Rotimi, CN (reprint author), Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047 12 South Dr, Bethesda, MD 20892 USA.
EM rotimic@mail.nih.gov
OI Tekola-Ayele, Fasil/0000-0003-4194-9370
FU Intramural Research Program of the National Institutes of Health (NIH)
in the Center for Research on Genomics and Global Health (CRGGH);
National Human Genome Research Institute (NHGRI); National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK); Center for
Information Technology (CIT); Office of the Director at the NIH
[1ZIAHG200362]
FX The study was supported by the Intramural Research Program of the
National Institutes of Health (NIH) in the Center for Research on
Genomics and Global Health (CRGGH). The CRGGH is supported by the
National Human Genome Research Institute (NHGRI), the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), the Center for
Information Technology (CIT), and the Office of the Director at the NIH
(1ZIAHG200362).
NR 77
TC 0
Z9 0
U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD DEC
PY 2016
VL 41
BP 77
EP 84
DI 10.1016/j.gde.2016.08.005
PG 8
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA EE8ZQ
UT WOS:000389915800011
PM 27644073
ER
PT J
AU Leung, JM
Olivier, KN
AF Leung, Janice M.
Olivier, Kenneth N.
TI Bronchiectasis and connective tissue diseases
SO CURRENT PULMONOLOGY REPORTS
LA English
DT Article
DE Bronchiectasis; Connective tissue disease; Rheumatoid arthritis;
Sjogren's syndrome; Marfan syndrome; Ehlers-Danlos syndrome
ID RESOLUTION COMPUTED-TOMOGRAPHY; EHLERS-DANLOS-SYNDROME; EARLY
RHEUMATOID-ARTHRITIS; PRIMARY SJOGRENS-SYNDROME; NONTUBERCULOUS
MYCOBACTERIAL INFECTION; PULMONARY-FUNCTION TESTS; MARFAN-SYNDROME;
LUNG-DISEASE; MATRIX METALLOPROTEINASES; SYSTEMIC-SCLEROSIS
AB Connective tissue diseases (CTD) encompass a range of heritable and autoimmune conditions that are well known for their systemic effects. While these conditions have been observed to impact the lung in myriad fashion, bronchiectasis remains an often overlooked pulmonary complication, despite the fact that the prevalence of bronchiectasis can be as high as 60 % in patients with rheumatoid arthritis. In this review, we cover the epidemiology and clinical findings of bronchiectasis in autoimmune CTDs such as rheumatoid arthritis and Sjogren's syndrome and heritable CTDs such as Marfan syndrome and Ehlers-Danlos syndrome. We propose that changes in the oral, gut, and lung microbiome may influence autoimmunity and the structural integrity of the airway, thus leading to bronchiectasis.
C1 [Leung, Janice M.] Univ British Columbia, Div Resp Med, Dept Med, St Pauls Hosp, Room 166,1088 Burrard St, Vancouver, BC V6Z 1Y6, Canada.
[Leung, Janice M.] Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Room 166,1088 Burrard St, Vancouver, BC V6Z 1Y6, Canada.
[Olivier, Kenneth N.] NHLBI, Pulm Clin Med Sect, NIH, 10 Ctr Dr,MSC 1454,Bldg 10-CRC,Room 6-3130, Bethesda, MD 20892 USA.
RP Leung, JM (reprint author), Univ British Columbia, Div Resp Med, Dept Med, St Pauls Hosp, Room 166,1088 Burrard St, Vancouver, BC V6Z 1Y6, Canada.; Leung, JM (reprint author), Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Room 166,1088 Burrard St, Vancouver, BC V6Z 1Y6, Canada.; Olivier, KN (reprint author), NHLBI, Pulm Clin Med Sect, NIH, 10 Ctr Dr,MSC 1454,Bldg 10-CRC,Room 6-3130, Bethesda, MD 20892 USA.
EM Janice.Leung@hli.ubc.ca; Kenneth.olivier@nih.gov
FU Intramural Research Program of the NIH, National Heart, Lung, and Blood
Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, National Heart, Lung, and Blood Institute.
NR 107
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
EI 2199-2428
J9 CURR PULMONOL REP
JI Curr. Pulmonol. Rep.
PD DEC
PY 2016
VL 5
IS 4
BP 169
EP 176
DI 10.1007/s13665-016-0154-8
PG 8
WC Respiratory System
SC Respiratory System
GA EF7XT
UT WOS:000390543400001
ER
PT J
AU Young-Hyman, D
de Groot, M
Hill-Briggs, F
Gonzalez, JS
Hood, K
Peyrot, M
AF Young-Hyman, Deborah
de Groot, Mary
Hill-Briggs, Felicia
Gonzalez, Jeffrey S.
Hood, Korey
Peyrot, Mark
TI Psychosocial Care for People With Diabetes: A Position Statement of the
American Diabetes Association
SO DIABETES CARE
LA English
DT Article
ID SELF-MANAGEMENT BEHAVIORS; POOR GLYCEMIC CONTROL; BARIATRIC SURGERY;
WEIGHT-LOSS; TREATMENT ADHERENCE; COLLABORATIVE CARE; METABOLIC-CONTROL;
CLINICAL DEPRESSION; EATING-DISORDERS; RANDOMIZED-TRIAL
C1 [Young-Hyman, Deborah] NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA.
[de Groot, Mary] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA.
[Hill-Briggs, Felicia] Johns Hopkins Sch Med, Baltimore, MD USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Bronx, NY USA.
[Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Hood, Korey] Stanford Univ, Stanford, CA 94305 USA.
[Peyrot, Mark] Loyola Univ Maryland, Baltimore, MD USA.
RP Young-Hyman, D (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA.
EM younghyd@od.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
[R18-DK-092765]; National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health [R01-DK-104845, R18-DK-098742,
P30-DK-111022]
FX M.d.G. was funded in part by the National Institute of Diabetes and
Digestive and Kidney Diseases (R18-DK-092765). J.S.G. is supported by
grants from the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health (R01-DK-104845, R18-DK-098742,
and P30-DK-111022).
NR 132
TC 7
Z9 7
U1 17
U2 17
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD DEC
PY 2016
VL 39
IS 12
BP 2126
EP 2140
DI 10.2337/dc16-2053
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EG1IF
UT WOS:000390785000017
PM 27879358
ER
PT J
AU Dreger, DL
Rimbault, M
Davis, BW
Bhatnagar, A
Parker, HG
Ostrander, EA
AF Dreger, Dayna L.
Rimbault, Maud
Davis, Brian W.
Bhatnagar, Adrienne
Parker, Heidi G.
Ostrander, Elaine A.
TI Whole-genome sequence, SNP chips and pedigree structure: building
demographic profiles in domestic dog breeds to optimize genetic-trait
mapping
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Population; Homozygosity; Canine; Inbreeding
ID LINKAGE MAP; REVEALS ADAPTATION; CANIS-FAMILIARIS; SELECTIVE SWEEPS;
WIDE SNP; ASSOCIATION; HUMANS; LOCUS; TOOL; DISEQUILIBRIUM
AB In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These datawere coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breedspecific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies.
C1 [Dreger, Dayna L.; Rimbault, Maud; Davis, Brian W.; Bhatnagar, Adrienne; Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Rimbault, Maud] Inst Genet & Dev Rennes, F-35043 Rennes, France.
[Bhatnagar, Adrienne] PIC North Amer, Hendersonville, TN 37075 USA.
RP Ostrander, EA (reprint author), NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural Program of the National Human Genome Research Institute
FX This work was funded by the Intramural Program of the National Human
Genome Research Institute.
NR 61
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U1 37
U2 37
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD DEC 1
PY 2016
VL 9
IS 12
BP 1445
EP 1460
DI 10.1242/dmm.027037
PG 16
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA EF5LS
UT WOS:000390372300003
PM 27874836
ER
PT J
AU Nakano, M
Yahiro, K
Yamasaki, E
Kurazono, H
Akada, J
Yamaoka, Y
Niidome, T
Hatakeyama, M
Suzuki, H
Yamamoto, T
Moss, J
Isomoto, H
Hirayama, T
AF Nakano, Masayuki
Yahiro, Kinnosuke
Yamasaki, Eiki
Kurazono, Hisao
Akada, Junko
Yamaoka, Yoshio
Niidome, Takuro
Hatakeyama, Masanori
Suzuki, Hidekazu
Yamamoto, Taro
Moss, Joel
Isomoto, Hajime
Hirayama, Toshiya
TI Helicobacter pylori VacA, acting through receptor protein tyrosine
phosphatase alpha, is crucial for CagA phosphorylation in human duodenum
carcinoma cell line AZ-521
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Helicobacter pylori; VacA; CagA
ID GASTRIC EPITHELIAL-CELLS; SRC-FAMILY KINASES; VACUOLATING CYTOTOXIN;
PTP-ALPHA; C-SRC; BIOLOGICAL-ACTIVITY; IV SECRETION; RPTP-ALPHA;
IN-VITRO; ACTIVATION
AB Helicobacter pylori, a major cause of gastroduodenal diseases, produces vacuolating cytotoxin (VacA) and cytotoxin-associated gene A (CagA), which seem to be involved in virulence. VacA exhibits pleiotropic actions in gastroduodenal disorders via its specific receptors. Recently, we found that VacA induced the phosphorylation of cellular Src kinase (Src) at Tyr418 in AZ-521 cells. Silencing of receptor protein tyrosine phosphatase (RPTP)alpha, a VacA receptor, reduced VacA-induced Src phosphorylation. Src is responsible for tyrosine phosphorylation of CagA at its Glu-Pro-Ile-Tyr-Ala (EPIYA) variant C (EPIYA-C) motif in Helicobacter pylori-infected gastric epithelial cells, resulting in binding of CagA to SHP-2 phosphatase. Challenging AZ-521 cells with wild-type H. pylori induced phosphorylation of CagA, but this did not occur when challenged with a vacA gene-disrupted mutant strain. CagA phosphorylation was observed in cells infected with a vacA gene-disrupted mutant strain after addition of purified VacA, suggesting that VacA is required for H. pylori-induced CagA phosphorylation. Following siRNA-mediated RPTP alpha knockdown in AZ-521 cells, infection with wild-type H. pylori and treatment with VacA did not induce CagA phosphorylation. Taken together, these results support our conclusion that VacA mediates CagA phosphorylation through RPTP alpha in AZ-521 cells. These data indicate the possibility that Src phosphorylation induced by VacA is mediated through RPTP alpha, resulting in activation of Src, leading to CagA phosphorylation at Tyr972 in AZ-521 cells.
C1 [Nakano, Masayuki; Hirayama, Toshiya] Nagasaki Univ, Inst Trop Med, Dept Bacteriol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
[Nakano, Masayuki; Yamamoto, Taro] Nagasaki Univ, Inst Trop Med, Dept Int Hlth, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
[Yahiro, Kinnosuke] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan.
[Yamasaki, Eiki; Kurazono, Hisao] Obihiro Univ Agr & Vet Med, Div Food Hyg, Dept Anim & Food Hyg, Nishi 2-11,Inada Cho, Obihiro, Hokkaido 0808555, Japan.
[Akada, Junko; Yamaoka, Yoshio] Oita Univ, Fac Med, Dept Environm & Prevent Med, Idaigaoka 1-1, Oita 8795593, Japan.
[Yamaoka, Yoshio] Baylor Coll Med, Dept Med, Gastroenterol & Hepatol Sect, Houston, TX 77030 USA.
[Niidome, Takuro] Kumamoto Univ, Grad Sch Sci & Technol, Dept Appl Chem & Biochem, Chuo Ku, 2-39-1 Kurokami, Kumamoto 8608555, Japan.
[Hatakeyama, Masanori] Univ Tokyo, Grad Sch Med, Div Microbiol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
[Suzuki, Hidekazu] Keio Univ, Sch Med, Med Educ Ctr, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
[Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Isomoto, Hajime] Tottori Univ, Fac Med, Div Med & Clin Sci, 86 Nishi Cho, Yonago, Tottori 6838503, Japan.
RP Nakano, M (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.; Nakano, M (reprint author), Nagasaki Univ, Inst Trop Med, Dept Int Hlth, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
EM manakano@nagasaki-u.ac.jp
RI Suzuki, Hidekazu/J-4396-2013
FU Takeda Science Foundation; Japan Society for the Promotion of Science
(JSPS) KAKENHI Grant [JP16K08778]; Cooperative Research Grant of
Institute of Tropical Medicine, Nagasaki University (NEKKEN);
Improvement of Research Environment for Young Researchers from the Japan
Science and Technology Agency; Intramural Research Program, National
Institutes of Health, National Heart, Lung, and Blood Institute
FX This work was supported by Takeda Science Foundation and by Japan
Society for the Promotion of Science (JSPS) KAKENHI Grant Number
JP16K08778 (to M.N.); by the Cooperative Research Grant of Institute of
Tropical Medicine, Nagasaki University (NEKKEN) (to K.Y. and T.H.); by
Improvement of Research Environment for Young Researchers from the Japan
Science and Technology Agency (to K.Y.); by the Intramural Research
Program, National Institutes of Health, National Heart, Lung, and Blood
Institute (to J.M.).
NR 56
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U1 0
U2 0
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD DEC 1
PY 2016
VL 9
IS 12
BP 1473
EP 1481
DI 10.1242/dmm.025361
PG 9
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA EF5LS
UT WOS:000390372300005
PM 27935824
ER
PT J
AU Zhang, J
Wang, P
Li, JY
Mendola, P
Sherman, S
Ying, Q
AF Zhang, Jie
Wang, Peng
Li, Jingyi
Mendola, Pauline
Sherman, Seth
Ying, Qi
TI Estimating population exposure to ambient polycyclic aromatic
hydrocarbon in the United States - Part II: Source apportionment and
cancer risk assessment
SO ENVIRONMENT INTERNATIONAL
LA English
DT Review
DE Cancer risk assessment; United States; Polycyclic aromatic hydrocarbon;
Source apportionment; Benzo[alpha]pyrene
ID SOURCE IDENTIFICATION; RADIOCARBON ANALYSIS; DIAGNOSTIC RATIOS;
URBAN-ENVIRONMENT; EMISSION SOURCES; PAHS; AIR; ATMOSPHERE; MODEL;
AEROSOLS
AB A revised Community Multiscale Air Quality (CMAQ) model was developed to simulate the emission, reactions, transport, deposition and gas-to-particle partitioning processes of 16 priority polycyclic aromatic hydrocarbons (PAHs), as described in Part I of the two-part series. The updated CMAQ model was applied in this study to quantify the contributions of different emission sources to the predicted PAH concentrations and excess cancer risk in the United States (US) in 2011. The cancer risk in the continental US due to inhalation exposure of outdoor naphthalene (NAPH) and seven larger carcinogenic PAHs (cPAHs) was predicted to be significant. The incremental lifetime cancer risk (ILCR) exceeds 1 x 10(-5) in many urban and industrial areas. Exposure to PAHs was estimated to result in 5704 (608-10,800) excess lifetime cancer cases. Point sources not related with energy generation and the oil and gas processes account for approximately 31% of the excess cancer cases, followed by non-road engines with 18.6% contributions. Contributions of residential wood combustion (16.2%) are similar to that of transportation- related sources (mostly motor vehicles with small contributions from railway and marine vessels; 13.4%). The oil and gas industry emissions, although large contributors to high concentrations of cPAHs regionally, are only responsible of 4.3% of the excess cancer cases, which is similar to the contributions of non-US sources (6.8%) and non-point sources (7.2%). The power generation units pose the most minimal impact on excess cancer risk, with contributions of approximately 2.3%. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Zhang, Jie; Wang, Peng; Li, Jingyi; Ying, Qi] Texas A&M Univ, Zachary Dept Civil Engn, College Stn, TX 77845 USA.
[Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Sherman, Seth] Emmes Corp, Rockville, MD 20850 USA.
[Li, Jingyi] Princeton Univ, Atmospher & Ocean Sci Program, Princeton, NJ 08544 USA.
RP Ying, Q (reprint author), Texas A&M Univ, Zachary Dept Civil Engn, College Stn, TX 77845 USA.
EM qying@civil.tamu.edu
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, through the Air Quality and Reproductive Health
[HHSN275200800002I, HHSN27500008]
FX The project was partially supported by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, through the Air
Quality and Reproductive Health study supported through Contract No.
HHSN275200800002I, Task Order No. HHSN27500008 awarded to The EMMES
Corporation. The authors have no conflicts of interests to disclose. The
authors want to acknowledge the Texas A&M Supercomputing Facility
(http://sc.tamu.edu) and the Texas Advanced Computing Center
(http://www.tacc.utexas.edu/) for providing computing resources
essential for completing the research reported in this paper.
NR 53
TC 1
Z9 1
U1 17
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD DEC
PY 2016
VL 97
BP 163
EP 170
DI 10.1016/j.envint.2016.08.024
PG 8
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA EE8YP
UT WOS:000389912900019
PM 27613001
ER
PT J
AU Taylor, KW
Joubert, BR
Braun, JM
Dilworth, C
Gennings, C
Hauser, R
Heindel, JJ
Rider, CV
Webster, TF
Carlin, DJ
AF Taylor, Kyla W.
Joubert, Bonnie R.
Braun, Joe M.
Dilworth, Caroline
Gennings, Chris
Hauser, Russ
Heindel, Jerry J.
Rider, Cynthia V.
Webster, Thomas F.
Carlin, Danielle J.
TI Statistical Approaches for Assessing Health Effects of Environmental
Chemical Mixtures in Epidemiology: Lessons from an Innovative Workshop
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID EXPOSURE
AB Quantifying the impact of exposure to environmental chemical mixtures is important for identifying risk factors for diseases and developing more targeted public health interventions. The National Institute of Environmental Health Sciences (NIEHS) held a workshop in July 2015 to address the need to develop novel statistical approaches for multi-pollutant epidemiology studies. The primary objective of the workshop was to identify and compare different statistical approaches and methods for analyzing complex chemical mixtures data in both simulated and real-world data sets. At the workshop, participants compared approaches and results and speculated as to why they may have differed. Several themes emerged: a) no one statistical approach appeared to outperform the others, b) many methods included some form of variable reduction or summation of the data before statistical analysis, c) the statistical approach should be selected based upon a specific hypothesis or scientific question, and d) related mixtures data should be shared among researchers to more comprehensively and accurately address methodological questions and statistical approaches. Future efforts should continue to design and optimize statistical approaches to address questions about chemical mixtures in epidemiological studies.
C1 [Taylor, Kyla W.; Joubert, Bonnie R.; Dilworth, Caroline; Heindel, Jerry J.; Rider, Cynthia V.; Carlin, Danielle J.] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
[Braun, Joe M.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Gennings, Chris] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
[Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Webster, Thomas F.] Boston Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA USA.
RP Taylor, KW (reprint author), NIEHS, POB 12233,MD K2-04, Res Triangle Pk, NC 27709 USA.
EM kyla.taylor@niehs.nih.gov
RI Braun, Joseph/H-8649-2014
FU NIEHS [R00 ES020346, R01 ES024381]
FX This work was supported by the following NIEHS grants: R00 ES020346 and
R01 ES024381.
NR 15
TC 0
Z9 0
U1 7
U2 7
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD DEC
PY 2016
VL 124
IS 12
BP A227
EP A229
DI 10.1289/EHP547
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA EF3FX
UT WOS:000390211200004
PM 27905274
ER
PT J
AU Erer, B
Takeuchi, M
Ustek, D
Tugal-Tutkun, I
Seyahi, E
Ozyazgan, Y
Duymaz-Tozkir, J
Gul, A
Kastner, DL
Remmers, EF
Ombrello, MJ
AF Erer, B.
Takeuchi, M.
Ustek, D.
Tugal-Tutkun, I.
Seyahi, E.
Ozyazgan, Y.
Duymaz-Tozkir, J.
Gul, A.
Kastner, D. L.
Remmers, E. F.
Ombrello, M. J.
TI Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behcet's disease
SO GENES AND IMMUNITY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MHC CLASS-I; HLA CLASS-I;
ANKYLOSING-SPONDYLITIS; SUSCEPTIBILITY LOCI; KIR GENES; RECEPTOR;
HLA-B-ASTERISK-51; IL23R-IL12RB2; RECOGNITION
AB The Behcet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, P-dominant = 0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant = 0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.
C1 [Erer, B.; Ombrello, M. J.] NIAMSD, Translat Genet & Genom Unit, 10 Ctr Dr,10C101,MSC 1560, Bethesda, MD 20892 USA.
[Erer, B.; Tugal-Tutkun, I.; Gul, A.] Istanbul Univ, Div Rheumatol, Dept Internal Med, Istanbul Fac Med, Istanbul, Turkey.
[Takeuchi, M.; Kastner, D. L.; Remmers, E. F.] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA.
[Ustek, D.] Istanbul Univ, Inst Expt Med, Dept Genet, Istanbul, Turkey.
[Seyahi, E.] Istanbul Univ, Cerrahpasa Fac Med, Div Rheumatol, Dept Internal Med, Istanbul, Turkey.
[Ozyazgan, Y.] Istanbul Univ, Cerrahpasa Fac Med, Dept Ophthalmol, Istanbul, Turkey.
[Duymaz-Tozkir, J.] Istanbul Univ, Inst Hlth Sci, Dept Immunol, Istanbul, Turkey.
RP Erer, B; Ombrello, MJ (reprint author), NIAMSD, Translat Genet & Genom Unit, 10 Ctr Dr,10C101,MSC 1560, Bethesda, MD 20892 USA.
EM burakerer@yahoo.com; ombrellomj@mail.nih.gov
FU National Institute of Arthritis and Muscuoskeletal and Skin Diseases of
the National Institutes of Health [Z01-AR041198]; National Human Genome
Research Institute of the National Institutes of Health [Z01-HG200370]
FX This work was supported by the Intramural Research Programs of the
National Institute of Arthritis and Muscuoskeletal and Skin Diseases
(Z01-AR041198) and the National Human Genome Research Institute
(Z01-HG200370) of the National Institutes of Health.
NR 34
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
EI 1476-5470
J9 GENES IMMUN
JI Genes Immun.
PD DEC
PY 2016
VL 17
IS 7
BP 396
EP 399
DI 10.1038/gene.2016.36
PG 4
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA EF6EN
UT WOS:000390424000004
PM 27708262
ER
PT J
AU Tian, YY
Yang, Y
Zhang, XW
Nakajima, T
Tanaka, N
Sugiyama, E
Kamijo, Y
Lu, Y
Moriya, K
Koike, K
Gonzalez, FJ
Aoyama, T
AF Tian, Yangyang
Yang, Yang
Zhang, Xiaowei
Nakajima, Takero
Tanaka, Naoki
Sugiyama, Eiko
Kamijo, Yuji
Lu, Yu
Moriya, Kyoji
Koike, Kazuhiko
Gonzalez, Frank J.
Aoyama, Toshifumi
TI Age-dependent PPAR alpha activation induces hepatic sulfatide
accumulation in transgenic mice carrying the hepatitis C virus core gene
SO GLYCOCONJUGATE JOURNAL
LA English
DT Article
DE Cancer; Core protein; HCV; PPAR alpha; Sphingolipid; Sulfatide
ID HEPATOCELLULAR-CARCINOMA CELLS; RECEPTOR-ALPHA; SERINE
PALMITOYLTRANSFERASE; CEREBROSIDE SULFOTRANSFERASE; MASS-SPECTROMETRY;
CANCER-CELLS; METABOLISM; PROTEIN; EXPRESSION; SULFOGLYCOLIPIDS
AB Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is involved in the regulation of sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPAR alpha activation and carcinogenesis in liver. However, the metabolism of sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between sulfatide metabolism, carcinogenesis, HCVcp, and PPAR alpha, age-dependent changes of these factors were examined in HCVcpTg, PPAR alpha inhibitor-treated HCVcpTg, and non-Tg mice. The sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in sulfatide synthesis, the hepatic expression of known sulfatide-transferring protein, oxidative stress, and hepatic PPAR alpha expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of sulfatides and PPAR alpha activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPAR alpha inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPAR alpha activation increases synthesis of sulfatides and the resulting sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic sulfatide content and the modulation of sulfatide generation by intervention using a PPAR alpha inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively.
C1 [Tian, Yangyang; Yang, Yang; Nakajima, Takero; Tanaka, Naoki; Lu, Yu; Aoyama, Toshifumi] Shinshu Univ, Dept Metab Regulat, Grad Sch Med, Matsumoto, Nagano 3908621, Japan.
[Zhang, Xiaowei] HebeiMed Univ, Hosp 2, Dept Neurosurg, Shijiazhuang 050000, Hebei, Peoples R China.
[Sugiyama, Eiko] Prefectural Coll, Dept Nutr Sci, Nagano 3808525, Japan.
[Kamijo, Yuji] Shinshu Univ, Dept Nephrol, Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
[Moriya, Kyoji] Univ Tokyo, Grad Sch Med, Dept Infect Control & Prevent, Tokyo 1130033, Japan.
[Koike, Kazuhiko] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Tokyo 1130033, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kamijo, Y (reprint author), Shinshu Univ, Dept Nephrol, Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
EM yujibeat@shinshu-u.ac.jp
NR 40
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U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0282-0080
EI 1573-4986
J9 GLYCOCONJUGATE J
JI Glycoconjugate J.
PD DEC
PY 2016
VL 33
IS 6
BP 927
EP 936
DI 10.1007/s10719-016-9703-1
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EF0GJ
UT WOS:000390003600008
PM 27318478
ER
PT J
AU Eraso, JM
Olsen, RJ
Beres, SB
Kachroo, P
Porter, AR
Nasser, W
Bernard, PE
DeLeo, FR
Musser, JM
AF Eraso, Jesus M.
Olsen, Randall J.
Beres, Stephen B.
Kachroo, Priyanka
Porter, Adeline R.
Nasser, Waleed
Bernard, Paul E.
DeLeo, Frank R.
Musser, James M.
TI Genomic Landscape of Intrahost Variation in Group A Streptococcus:
Repeated and Abundant Mutational Inactivation of the fabT Gene Encoding
a Regulator of Fatty Acid Synthesis
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CROSS-REACTIVE ANTIGEN; ILLUMINA SEQUENCE DATA; TRANSCRIPTIONAL
REGULATION; STAPHYLOCOCCUS-AUREUS; NECROTIZING FASCIITIS; CELL-WALL;
LIPID-II; VIRULENCE; PYOGENES; BIOSYNTHESIS
AB To obtain new information about Streptococcus pyogenes intrahost genetic variation during invasive infection, we sequenced the genomes of 2,954 serotype M1 strains recovered from a nonhuman primate experimental model of necrotizing fasciitis. A total of 644 strains (21.8%) acquired polymorphisms relative to the input parental strain. The fabT gene, encoding a transcriptional regulator of fatty acid biosynthesis genes, contained 54.5% of these changes. The great majority of polymorphisms were predicted to deleteriously alter FabT function. Transcriptome-sequencing (RNA-seq) analysis of a wild-type strain and an isogenic fabT deletion mutant strain found that between 3.7 and 28.5% of the S. pyogenes transcripts were differentially expressed, depending on the growth temperature (35 degrees C or 40 degrees C) and growth phase (mid-exponential or stationary phase). Genes implicated in fatty acid synthesis and lipid metabolism were significantly upregulated in the fabT deletion mutant strain. FabT also directly or indirectly regulated central carbon metabolism genes, including pyruvate hub enzymes and fermentation pathways and virulence genes. Deletion of fabT decreased virulence in a nonhuman primate model of necrotizing fasciitis. In addition, the fabT deletion strain had significantly decreased survival in human whole blood and during phagocytic interaction with polymorphonuclear leukocytes ex vivo. We conclude that FabT mutant progeny arise during infection, constitute a metabolically distinct subpopulation, and are less virulent in the experimental models used here.
C1 [Eraso, Jesus M.; Olsen, Randall J.; Beres, Stephen B.; Kachroo, Priyanka; Nasser, Waleed; Bernard, Paul E.; Musser, James M.] Houston Methodist Res Inst, Dept Pathol & Genom Med, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA.
[Eraso, Jesus M.; Olsen, Randall J.; Beres, Stephen B.; Kachroo, Priyanka; Nasser, Waleed; Bernard, Paul E.; Musser, James M.] Houston Methodist Hosp, Houston, TX 77030 USA.
[Olsen, Randall J.; Musser, James M.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Porter, Adeline R.; DeLeo, Frank R.] NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Bernard, Paul E.] Texas A&M Hlth Sci Ctr, Bryan, TX USA.
RP Musser, JM (reprint author), Houston Methodist Res Inst, Dept Pathol & Genom Med, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA.; Musser, JM (reprint author), Houston Methodist Hosp, Houston, TX 77030 USA.; Musser, JM (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
EM jmmusser@houstonmethodist.org
OI Kachroo, Priyanka/0000-0002-3563-7832
FU Fondren Foundation; Intramural Research Program of the NIAID, NIH
FX The research was supported in part by the Fondren Foundation and the
Intramural Research Program of the NIAID, NIH. The funders had no role
in study design, data collection and interpretation, or decision to
submit the work for publication.
NR 68
TC 1
Z9 1
U1 5
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD DEC
PY 2016
VL 84
IS 12
BP 3268
EP 3281
DI 10.1128/IAI.00608-16
PG 14
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA EF2BG
UT WOS:000390128700002
PM 27600505
ER
PT J
AU Break, TJ
Witter, AR
Indramohan, M
Mummert, ME
Dory, L
Berg, RE
AF Break, Timothy J.
Witter, Alexandra R.
Indramohan, Mohanalaxmi
Mummert, Mark E.
Dory, Ladislav
Berg, Rance E.
TI Extracellular Superoxide Dismutase Enhances Recruitment of Immature
Neutrophils to the Liver
SO INFECTION AND IMMUNITY
LA English
DT Article
ID HEPARIN-BINDING DOMAIN; LISTERIA-MONOCYTOGENES; LUNG INJURY;
MYELOPEROXIDASE DEFICIENCY; OXIDATIVE FRAGMENTATION;
BACTERIAL-INFECTION; GENE POLYMORPHISM; EC-SOD; INFLAMMATION; MICE
AB Listeria monocytogenes is a Gram-positive intracellular pathogen that causes spontaneous abortion in pregnant women, as well as septicemia, meningitis, and gastroenteritis, primarily in immunocompromised individuals. Although L. monocytogenes can usually be effectively treated with antibiotics, there is still around a 25% mortality rate with individuals who develop clinical listeriosis. Neutrophils are innate immune cells required for the clearance of pathogenic organisms, including L. monocytogenes. The diverse roles of neutrophils during both infectious and noninfectious inflammation have recently gained much attention. However, the impact of reactive oxygen species, and the enzymes that control their production, on neutrophil recruitment and function is not well understood. Using congenic mice with varying levels of extracellular superoxide dismutase (ecSOD) activity, we have recently shown that the presence of ecSOD decreases clearance of L. monocytogenes while increasing the recruitment of neutrophils that are not protective in the liver. The data presented here show that ecSOD activity does not lead to a cell-intrinsic increase in neutrophil-homing potential or a decrease in protection against L. monocytogenes. Instead, ecSOD activity enhances the production of neutrophil-attracting factors and protects hyaluronic acid (HA) from damage. Furthermore, neutrophils from the livers of ecSOD-expressing mice have decreased intracellular and surface-bound myeloperoxidase, are less capable of killing phagocytosed L. monocytogenes, and have decreased oxidative burst. Collectively, our data reveal that ecSOD activity modulates neutrophil recruitment and function in a cell-extrinsic fashion, highlighting the importance of the enzyme in protecting tissues from oxidative damage.
C1 [Break, Timothy J.; Witter, Alexandra R.; Indramohan, Mohanalaxmi; Mummert, Mark E.; Berg, Rance E.] Univ North Texas, Hlth Sci Ctr, Dept Cell Biol & Immunol, Ft Worth, TX 76107 USA.
[Mummert, Mark E.] Univ North Texas, Hlth Sci Ctr, Mental Sci Inst, Ft Worth, TX USA.
[Dory, Ladislav] Univ North Texas, Hlth Sci Ctr, Inst Cardiovasc & Metab Dis, Ft Worth, TX USA.
[Break, Timothy J.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Indramohan, Mohanalaxmi] Northwestern Univ, Dept Med, Div Rheumatol, Chicago, IL 60611 USA.
RP Berg, RE (reprint author), Univ North Texas, Hlth Sci Ctr, Dept Cell Biol & Immunol, Ft Worth, TX 76107 USA.
EM Rance.Berg@unthsc.edu
FU NIH/NIAID [AI109630]; BioLegend grant; UNTHSC; AAI Careers in Immunology
fellowship; Sigma Xi
FX This work was supported by a grant from NIH/NIAID (AI109630) to R.E.B.,
a BioLegend grant to R.E.B. and T.J.B., Intramural seed grants from
UNTHSC to R.E.B. and T.J.B., a Sigma Xi Grant-In-Aid of Research grant
to T.J.B., and an AAI Careers in Immunology fellowship to R.E.B. and
A.R.W.
NR 56
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD DEC
PY 2016
VL 84
IS 12
BP 3302
EP 3312
DI 10.1128/IAI.00603-16
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA EF2BG
UT WOS:000390128700005
PM 27600509
ER
PT J
AU Wrande, M
Andrews-Polymenis, H
Twedt, DJ
Steele-Mortimer, O
Porwollik, S
McClelland, M
Knodler, LA
AF Wrande, Marie
Andrews-Polymenis, Helene
Twedt, Donna J.
Steele-Mortimer, Olivia
Porwollik, Steffen
McClelland, Michael
Knodler, Leigh A.
TI Genetic Determinants of Salmonella enterica Serovar Typhimurium
Proliferation in the Cytosol of Epithelial Cells
SO INFECTION AND IMMUNITY
LA English
DT Article
ID III SECRETION SYSTEM; HORIZONTALLY ACQUIRED GENES;
FRANCISELLA-TULARENSIS; ESCHERICHIA-COLI; EXPRESSION; VIRULENCE;
IDENTIFICATION; MACROPHAGES; INFECTION; AUTOPHAGY
AB Intestinal epithelial cells provide an important colonization niche for Salmonella enterica serovar Typhimurium during gastrointestinal infections. In infected epithelial cells, a subpopulation of S. Typhimurium bacteria damage their internalization vacuole, leading to escape from the Salmonella-containing vacuole (SCV) and extensive proliferation in the cytosol. Little is known about the bacterial determinants of nascent SCV lysis and subsequent survival and replication of Salmonella in the cytosol. To pinpoint S. Typhimurium virulence factors responsible for these steps in the intracellular infectious cycle, we screened a S. Typhimurium multigene deletion library in Caco-2 C2Bbe1 and HeLa epithelial cells for mutants that had an altered proportion of cytosolic bacteria compared to the wild type. We used a gentamicin protection assay in combination with a chloroquine resistance assay to quantify total and cytosolic bacteria, respectively, for each strain. Mutants of three S. Typhimurium genes, STM1461 (ydgT), STM2829 (recA), and STM3952 (corA), had reduced cytosolic proliferation compared to wild-type bacteria, and one gene, STM2120 (asmA), displayed increased cytosolic replication. None of the mutants were affected for lysis of the nascent SCV or vacuolar replication in epithelial cells, indicating that these genes are specifically required for survival and proliferation of S. Typhimurium in the epithelial cell cytosol. These are the first genes identified to contribute to this step of the S. Typhimurium infectious cycle.
C1 [Wrande, Marie; Twedt, Donna J.; Knodler, Leigh A.] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
[Andrews-Polymenis, Helene] Texas A&M Univ, Dept Microbial Pathogenesis & Immunol, Coll Med, Bryan, TX USA.
[Steele-Mortimer, Olivia] NIAID, Bacteriol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Porwollik, Steffen; McClelland, Michael] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
[Wrande, Marie] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
RP Knodler, LA (reprint author), Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
EM lknodler@vetmed.wsu.edu
FU CDMRP [W81XWH-08-1-0720]; USDA [2010-65201-20692, 2011-67017-30127,
2014-67017-21707]; Centre for Produce Safety, Binational Agricultural
Research and Development Fund; North American Meat Institute; NIAID/NIH
[R56 AI077645, R01 AI083646, R21 AI083964, R01 AI052237, R01 075093, R01
AI034829, 1ZIAAI000909]; Paul G. Allen School for Global Animal Health
and Stanley L. Adler Research Fund; Swedish Research Council Formas;
Wenner-Gren Foundation
FX This work, including the efforts of Michael McClelland and Steffen
Porwollik, was funded by CDMRP (W81XWH-08-1-0720), USDA
(2010-65201-20692, 2011-67017-30127, and 2014-67017-21707), Centre for
Produce Safety, Binational Agricultural Research and Development Fund,
and North American Meat Institute. This work, including the efforts of
Helene Andrews-Polymenis, was funded by NIAID/NIH (R56 AI077645, R01
AI083646, R21 AI083964, R01 AI052237, R01 075093, and R01 AI034829).
This work, including the efforts of Leigh A. Knodler, was funded by Paul
G. Allen School for Global Animal Health and Stanley L. Adler Research
Fund. This work, including the efforts of Marie Wrande, was funded by
Swedish Research Council Formas and Wenner-Gren Foundation. This work,
including the efforts of Olivia Steele-Mortimer, was funded by NIAID/NIH
(1ZIAAI000909).
NR 52
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Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD DEC
PY 2016
VL 84
IS 12
BP 3517
EP 3526
DI 10.1128/IAI.00734-16
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA EF2BG
UT WOS:000390128700024
PM 27698022
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Cardiac Dysautonomia and Survival in Hereditary Transthyretin
Amyloidosis
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE amyloidosis; dysautonomia; metaiodobenzylguanidine; sympathetic nervous
system
ID HEART-RATE-VARIABILITY; LIVER-TRANSPLANTATION; POLYNEUROPATHY; DISEASE;
NERVE; ACETYLCHOLINESTERASE; DENERVATION; TRANSPORT; VAGUS
C1 [Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC 1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
NR 31
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD DEC
PY 2016
VL 9
IS 12
BP 1442
EP 1445
DI 10.1016/j.jcmg.2016.08.003
PG 4
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA EF4LC
UT WOS:000390295800012
PM 27838301
ER
PT J
AU Chawla, S
Natarajan, G
Shankaran, S
Pappas, A
Stoll, BJ
Carlo, WA
Saha, S
Das, A
Laptook, AR
Higgins, RD
AF Chawla, Sanjay
Natarajan, Girija
Shankaran, Seethe
Pappas, Athina
Stoll, Barbara J.
Carlo, Waldemar A.
Saha, Shampa
Das, Abhik
Laptook, Abbot R.
Higgins, Rosemary D.
CA Natl Inst Child Hlth
Human Dev Neonatal Res Network
TI Association of Neurodevelopmental Outcomes and Neonatal Morbidities of
Extremely Premature Infants With Differential Exposure to Antenatal
Steroids
SO JAMA PEDIATRICS
LA English
DT Article
ID CHILDREN BORN PRETERM; BIRTH-WEIGHT INFANTS; GROSS MOTOR FUNCTION;
SYSTEM; CORTICOSTEROIDS; DEXAMETHASONE; MULTICENTER; HEMORRHAGE;
PRESSURE; THERAPY
AB IMPORTANCE Many premature infants are born without exposure to antenatal steroids (ANS) or with incomplete courses. This study evaluates the dose-dependent effect of ANS on rates of neonatal morbidities and early childhood neurodevelopmental outcomes of extremely premature infants.
OBJECTIVE To compare rates of neonatal morbidities and 18-to 22-month neurodevelopmental outcomes of extremely premature infants exposed to no ANS or partial or complete courses of ANS.
DESIGN, SETTING, AND PARTICIPANTS In this observational cohort study, participantswere extremely premature infants (birth weight range, 401-1000 g; gestational age, 22-27 weeks) who were born at participating centers of the National Institute of Child Health and Human Development Neonatal Research Network between January 2006 and December 2011. Data were analyzed between October 2013 and May 2016.
MAIN OUTCOMES AND MEASURES Rates of death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined as the presence of any of the following: moderate to severe cerebral palsy, a cognitive score less than 85 on the Bayley Scales of Infant and Toddler Development III, blindness, or deafness.
RESULTS There were 848 infants in the no ANS group, 1581 in the partial ANS group, and 3692 in the complete ANS group; the mean (SD) birth weights were 725 (169), 760 (173), and 753 (170) g, respectively, and the mean (SD) gestational ages were 24.5 (1.4), 24.9 (2), and 25.1 (1.1) weeks. Of 6121 eligible infants, 4284 (70.0%) survived to 18-to 22-month follow-up, and data were available for 3892 of 4284 infants (90.8%). Among the no, partial, and complete ANS groups, there were significant differences in the rates of mortality (43.1%, 29.6%, and 25.2%, respectively), severe intracranial hemorrhage among survivors (23.3%, 19.1%, and 11.7%), death or necrotizing enterocolitis (48.1%, 37.1%, and 32.5%), and death or bronchopulmonary dysplasia (74.9%, 68.9%, and 65.5%). Additionally, death or neurodevelopmental impairment occurred in 68.1%, 54.4%, and 48.1% of patients in the no, partial, and complete ANS groups, respectively. Logistic regression analysis revealed that complete (odds ratio, 0.63; 95% CI, 0.53-0.76) and partial (odds ratio, 0.77; 95% CI, 0.63-0.95) ANS courses were associated with lower rates of death or neurodevelopmental impairment compared with the no ANS group. The reduction in the rate of death or neurodevelopmental impairment associated with exposure to a complete ANS course may be mediated through a reduction in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia in the neonatal period.
CONCLUSIONS AND RELEVANCE Antenatal steroid exposurewas associated with a dose-dependent protective effect against death or neurodevelopmental impairment in extremely preterm infants. The effect was partly mediated by ANS-associated reductions in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia. These results support prompt administration of ANS, with the goal of a complete course prior to delivery.
C1 [Chawla, Sanjay; Natarajan, Girija; Shankaran, Seethe; Pappas, Athina] Wayne State Univ, Dept Pediat, 3901 Beaubien, Detroit, MI 48201 USA.
[Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Saha, Shampa; Das, Abhik] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA.
[Laptook, Abbot R.] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Chawla, S (reprint author), Wayne State Univ, Dept Pediat, 3901 Beaubien, Detroit, MI 48201 USA.
EM schawla@dmc.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health; National Center for Research
Resources; National Center for Advancing Translational Sciences
FX This work was conducted for and supported by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development. The National
Institutes of Health, the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, the National Center for Research
Resources, and the National Center for Advancing Translational Sciences
provided grant support for the 17 generic database and follow-up studies
of the Neonatal Research Network through cooperative agreements.
NR 26
TC 1
Z9 1
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD DEC 1
PY 2016
VL 170
IS 12
BP 1164
EP 1172
DI 10.1001/jamapediatrics.2016.1936
PG 9
WC Pediatrics
SC Pediatrics
GA EF3WZ
UT WOS:000390256900016
PM 27723868
ER
PT J
AU Rosenberg, AR
Wolfe, J
Wiener, L
Lyon, M
Feudtner, C
AF Rosenberg, Abby R.
Wolfe, Joanne
Wiener, Lori
Lyon, Maureen
Feudtner, Chris
TI Ethics, Emotions, and the Skills of Talking About Progressing Disease
With Terminally Ill Adolescents A Review
SO JAMA PEDIATRICS
LA English
DT Review
ID OF-LIFE CARE; PEDIATRIC PALLIATIVE CARE; ADVANCED CANCER; PROGNOSTIC
DISCLOSURE; YOUNG-ADULTS; BAD-NEWS; CHILDREN; PARENTS; END;
COMMUNICATION
AB Importance:For clinicians caring for adolescent patients living with progressive, life-threatening illness, discussions regarding prognosis, goals of care, and treatment options can be extremely challenging. While clinicians should respect and help to facilitate adolescents' emerging autonomy, they often must also work with parents' wishes to protect patients from the emotional distress of hearing bad news.
Observations:We reviewed the ethical justifications for and against truth-telling, and we considered the published ethical and practice guidance, as well as the perspectives of patients, parents, and clinicians involved in these cases. We also explored particular challenges with respect to the cultural context, timing, and content of conversations at the end of adolescents' lives. In most cases, clinicians should gently but persistently engage adolescents directly in conversations about their disease prognosis and corresponding hopes, worries, and goals. These conversations need to occur multiple times, allowing significant time in each discussion for exploration of patient and family values. While truth-telling does not cause the types of harm that parents and clinicians may fear, discussing this kind of difficult news is almost always emotionally distressing. We suggest some "phrases that help" when clinicians strive to deepen understanding and facilitate difficult conversations with adolescents, parents, and other family members.
Conclusions and Relevance:The pediatrician's opportunities to engage in difficult conversations about poor prognosis may be rare, but such conversations can be crucial. These discussions affect how patients live at the end of their lives, how they die, and how their families go on. Improved understanding of basic principles of communication, as well as augmented understanding of patient, family, and clinician perspectives may better enable us to navigate these important conversations.
C1 [Rosenberg, Abby R.] Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB-8-501, Seattle, WA 98145 USA.
[Rosenberg, Abby R.] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA.
[Rosenberg, Abby R.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA.
[Wolfe, Joanne] Harvard Med Sch, Boston, MA USA.
[Wiener, Lori] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lyon, Maureen] Childrens Res Inst, Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA.
[Lyon, Maureen] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
[Feudtner, Chris] Childrens Hosp Philadelphia, Pediat Adv Care Team, Philadelphia, PA 19104 USA.
[Feudtner, Chris] Childrens Hosp Philadelphia, Dept Med Eth, Philadelphia, PA 19104 USA.
[Feudtner, Chris] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Feudtner, Chris] Univ Penn, Dept Med Eth, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Feudtner, Chris] Univ Penn, Dept Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Rosenberg, AR (reprint author), Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB-8-501, Seattle, WA 98145 USA.
EM abby.rosenberg@seattlechildrens.org
FU National Institutes of Health [KL2TR000421, L40 CA170049]; Intramural
Research Program of the National Cancer Institute
FX This work was supported in part by grants KL2TR000421 and L40 CA170049
from the National Institutes of Health (Dr Rosenberg) and the Intramural
Research Program of the National Cancer Institute (Dr Wiener).
NR 68
TC 0
Z9 0
U1 8
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD DEC 1
PY 2016
VL 170
IS 12
BP 1216
EP 1223
DI 10.1001/jamapediatrics.2016.2142
PG 8
WC Pediatrics
SC Pediatrics
GA EF3WZ
UT WOS:000390256900023
PM 27749945
ER
PT J
AU Dersh, D
Yewdell, JW
AF Dersh, Devin
Yewdell, Jonathan W.
TI I've got algorithm: predicting tumor and autoimmune peptide targets for
CD8(+) T cells
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID CLASS-I PATHWAY; MASS-SPECTROMETRY; MESSENGER-RNA; ANTIGEN; TRANSLATION;
COMPLEX; LYMPHOCYTES; PROTEASOME; PATHOGENS
AB CD8(+) T cells play a central role in eradicating intracellular pathogens, but also are important for noninfectious diseases, including cancer and autoimmunity. The ability to clinically manipulate CD8(+) T cells to target cancer and autoimmune disease is limited by our ignorance of relevant self-peptide target antigens. In this issue of the JCI, Pearson et al. describe 25,270 MHC class I-associated peptides presented by a wide range of HLA A and B allomorphs expressed by 18 different B cell lines. Via extensive bioinformatic analysis, the authors make surprising conclusions regarding the selective nature of peptide generation at the level of individual gene products and create a predictive algorithm for disease-relevant self-peptides that will be of immediate use for clinical and basic immunological research.
C1 [Dersh, Devin; Yewdell, Jonathan W.] NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIH, Room 2E13-1C,Bldg 33,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@NIH.gov
NR 25
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC 1
PY 2016
VL 126
IS 12
BP 4399
EP 4401
DI 10.1172/JCI91302
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EF2CK
UT WOS:000390131900004
PM 27841762
ER
PT J
AU Kwak, H
Salvucci, O
Weigert, R
Martinez-Torrecuadrada, JL
Henkemeyer, M
Poulos, MG
Butler, JM
Tosato, G
AF Kwak, Hyeongil
Salvucci, Ombretta
Weigert, Roberto
Martinez-Torrecuadrada, Jorge L.
Henkemeyer, Mark
Poulos, Michael G.
Butler, Jason M.
Tosato, Giovanna
TI Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell
mobilization from bone marrow
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PRE-METASTATIC NICHE; TYROSINE KINASE; TUMOR-GROWTH; STEM-CELLS; G-CSF;
ANGIOGENESIS; MIGRATION; CYCLOPHOSPHAMIDE; MICROENVIRONMENT;
INFLAMMATION
AB Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow. Stress signals from cancer and other conditions promote HSPC mobilization into circulation and subsequent homing to tissue microenvironments. HSPC infiltration into tissue microenvironments can influence disease progression; notably, in cancer, HSPCs encourage tumor growth. Here we have uncovered a mutually exclusive distribution of EPHB4 receptors in bone marrow sinusoids and ephrin B2 ligands in hematopoietic cells. We determined that signaling interactions between EPHB4 and ephrin B2 control HSPC mobilization from the bone marrow. In mice, blockade of the EPHB4/ephrin B2 signaling pathway reduced mobilization of HSPCs and other myeloid cells to the circulation. EPHB4/ephrin B2 blockade also reduced HSPC infiltration into tumors as well as tumor progression in murine models of melanoma and mammary cancer. These results identify EPHB4/ephrin B2 signaling as critical to HSPC mobilization from bone marrow and provide a potential strategy for reducing cancer progression by targeting the bone marrow.
C1 [Kwak, Hyeongil; Salvucci, Ombretta; Tosato, Giovanna] NCI, Cellular Oncol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Weigert, Roberto] NIDCR, NIH, Bethesda, MD USA.
[Weigert, Roberto] NCI, Cellular & Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Martinez-Torrecuadrada, Jorge L.] CNIO, Biotechnol Programme, Prote Unit, Madrid, Spain.
[Henkemeyer, Mark] Univ Texas Southwestern Med Ctr, Dept Dev Biol, Dallas, TX USA.
[Poulos, Michael G.; Butler, Jason M.] Weill Cornell Med Coll, Dept Genet Med, New York, NY USA.
RP Tosato, G (reprint author), NIH, Cellular Oncol Lab, 37 Convent Dr,Bethesda Campus,Bldg 37,Room 4124, Bethesda, MD 20892 USA.
EM Tosatog@mail.nih.gov
FU intramural research program of the CCR/NCI/NIH; Regional Government of
Madrid (Angiobodies Programme) [BIPEDD2 S2011/BMD-2312]; European Social
Fund; Ansary Stem Cell Institute; American Society of Hematology Scholar
Award; American Federation for Aging Research grant; Leukemia and
Lymphoma Society Quest for Cures award
FX We thank E. Pasquale for constructs; D. Soriano, R. Wong, and A.
Acker-Palmer for mice; CCR animal facility personnel; D. Lowy and
members of the Laboratory of Cellular Oncology for help in various
aspects of this work. This work was supported by the intramural research
program of the CCR/NCI/NIH. JLMT is supported by the Regional Government
of Madrid (Angiobodies Programme BIPEDD2 S2011/BMD-2312) and the
European Social Fund; JMB is supported by the Ansary Stem Cell
Institute, an American Society of Hematology Scholar Award, an American
Federation for Aging Research grant, and a Leukemia and Lymphoma Society
Quest for Cures award.
NR 60
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC 1
PY 2016
VL 126
IS 12
BP 4554
EP 4568
DI 10.1172/JCI87848
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EF2CK
UT WOS:000390131900017
PM 27820703
ER
PT J
AU Zhang, LJ
Du, JH
Justus, S
Hsu, CW
Bonet-Ponce, L
Wu, WH
Tsai, YT
Wu, WP
Jia, YD
Duong, JK
Mahajan, VB
Lin, CS
Wang, S
Hurley, JB
Tsang, SH
AF Zhang, Lijuan
Du, Jianhai
Justus, Sally
Hsu, Chun-Wei
Bonet-Ponce, Luis
Wu, Wen-Hsuan
Tsai, Yi-Ting
Wu, Wei-Pu
Jia, Yading
Duong, Jimmy K.
Mahajan, Vinit B.
Lin, Chyuan-Sheng
Wang, Shuang
Hurley, James B.
Tsang, Stephen H.
TI Reprogramming metabolism by targeting sirtuin 6 attenuates retinal
degeneration
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID LEBERS CONGENITAL AMAUROSIS; RECESSIVE RETINITIS-PIGMENTOSA; ROD
CGMP-PHOSPHODIESTERASE; HISTONE DEACETYLASE SIRT6; CONE VIABILITY
FACTOR; GENE-THERAPY; GAMMA-SUBUNIT; OXYGEN DISTRIBUTION; PRECLINICAL
MODEL; CHILDHOOD BLINDNESS
AB Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy-mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders.
C1 [Zhang, Lijuan; Justus, Sally; Hsu, Chun-Wei; Wu, Wen-Hsuan; Tsai, Yi-Ting; Wu, Wei-Pu; Tsang, Stephen H.] Columbia Univ, Dept Ophthalmol, Jonas Childrens Vis Care & Bernard & Shirlee Brow, New York, NY 10027 USA.
[Zhang, Lijuan; Justus, Sally; Hsu, Chun-Wei; Wu, Wen-Hsuan; Tsai, Yi-Ting; Wu, Wei-Pu; Jia, Yading; Tsang, Stephen H.] New York Presbyterian Hosp, Edward S Harkness Eye Inst, New York, NY USA.
[Zhang, Lijuan] Shanxi Med Univ, Shanxi Eye Hosp, Taiyuan, Peoples R China.
[Du, Jianhai; Hurley, James B.] Univ Washington, Dept Biochem & Ophthalmol, Seattle, WA 98195 USA.
[Bonet-Ponce, Luis] NIH, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, Bldg 10, Bethesda, MD 20892 USA.
[Duong, Jimmy K.; Wang, Shuang] Columbia Univ, Med Ctr, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA.
[Mahajan, Vinit B.] Univ Iowa, Omics Lab, Iowa City, IA USA.
[Lin, Chyuan-Sheng] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Dept Pathol & Cell Biol, New York, NY USA.
[Tsang, Stephen H.] Columbia Univ, Coll Phys & Surg, Inst Human Nutr, Dept Pathol, New York, NY USA.
[Tsang, Stephen H.] Columbia Univ, Coll Phys & Surg, Inst Human Nutr, Dept Cell Biol, New York, NY USA.
RP Tsang, SH (reprint author), Columbia Univ, Med Ctr, 635 West 165th St,Box 112, New York, NY 10032 USA.
EM sht2@columbia.edu
FU NIH [5P30EY019007, R01EY018213, R01EY024698, 1R01EY026682, R21AG050437,
1R01EY02602001, 5R21AG050437]; National Cancer Institute Core
[5P30CA013696]; Research to Prevent Blindness (RPB) Physician-Scientist
Award; RPB; Tistou and Charlotte Kerstan Foundation; Schneeweiss Stem
Cell Fund, New York State [C029572]; Foundation Fighting Blindness New
York Regional Research Center Grant [C-NY05-0705-0312]; Gebroe Family
Foundation
FX The Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma
Laboratory are supported by the NIH (5P30EY019007, R01EY018213,
R01EY024698, 1R01EY026682, R21AG050437), National Cancer Institute Core
(5P30CA013696), the Research to Prevent Blindness (RPB)
Physician-Scientist Award, and unrestricted funds from RPB. SHT is a
member of the RD-CURE Consortium and is supported by the Tistou and
Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York
State (C029572), the Foundation Fighting Blindness New York Regional
Research Center Grant (C-NY05-0705-0312), and the Gebroe Family
Foundation. JBH is supported by NIH (1R01EY02602001). VBM is supported
by NIH (1R01EY026682, 5R21AG050437). Special thanks go to Amy Caudy,
Eyal Gottlieb, and Adam Rosebrock for their consultations during the
metabolomics course at Cold Spring Harbor Laboratory.
NR 95
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC 1
PY 2016
VL 126
IS 12
BP 4659
EP 4673
DI 10.1172/JCI86905
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EF2CK
UT WOS:000390131900025
PM 27841758
ER
PT J
AU Szyniszewska, AM
Leppla, NC
Huang, Z
Tatem, AJ
AF Szyniszewska, A. M.
Leppla, N. C.
Huang, Z.
Tatem, A. J.
TI Analysis of Seasonal Risk for Importation of the Mediterranean Fruit
Fly, Ceratitis capitata (Diptera: Tephritidae), via Air Passenger
Traffic Arriving in Florida and California
SO JOURNAL OF ECONOMIC ENTOMOLOGY
LA English
DT Article
DE Ceratitis capitata; Mediterranean fruit fly; risk analysis
ID BIOLOGICAL INVASIONS; INTERNATIONAL-TRADE; NORTHERN GREECE; CARGO
AIRCRAFT; UNITED-STATES; INTERCEPTIONS; PATHWAY; DISEASE; TRAVEL; PESTS
AB The Mediterranean fruit fly, Ceratitis capitata ( Wiedemann), is one of the most economically damaging pests in the world and has repeatedly invaded two major agricultural states in the United States, Florida and California, each time requiring costly eradication. The Mediterranean fruit fly gains entry primarily in infested fruit carried by airline passengers and, since Florida and California each receive about 13 million international passengers annually, the risk of Mediterranean fruit fly entering the United States is potentially very high. The risk of passengers bringing the pest into Florida or California from Mediterranean fruit fly-infested countries was determined with two novel models, one estimated seasonal variation in airline passenger number and the other defined the seasonal and spatial variability in Mediterranean fruit fly abundance. These models elucidated relationships among the risk factors for Mediterranean fruit fly introduction, such as amount of passenger traffic, routes traveled, season of travel, abundance of Mediterranean fruit fly in countries where flights departed, and risk of the pest arriving at destination airports. The risk of Mediterranean fruit fly being introduced into Florida was greatest from Colombia, Brazil, Panama, Venezuela, Argentina, and Ecuador during January-August, whereas primarily the risk to California was from Brazil, Panama, Colombia, and Italy in May-August. About three times more Mediterranean fruit flies were intercepted in passenger baggage at airports in Florida than California, although the data were compromised by a lack of systematic sampling and other limitations. Nevertheless, this study achieved the goal of analyzing available data on seasonal passenger flow and Mediterranean fruit fly population levels to determine when surveillance should be intensified at key airports in Florida and California.
C1 [Szyniszewska, A. M.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Szyniszewska, A. M.; Leppla, N. C.] Univ Florida, Dept Entomol & Nematol, Gainesville, FL 32611 USA.
[Huang, Z.] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China.
[Tatem, A. J.] Univ Southampton, WorldPop Project, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, A. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, A. J.] Flowminder Fdn, Stockholm, Sweden.
RP Leppla, NC (reprint author), Univ Florida, Dept Entomol & Nematol, Gainesville, FL 32611 USA.
EM aniasz@gmail.com; ncleppla@ufl.edu; seenhzj@gmail.com;
Andy.Tatem@gmail.com
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health
FX We thank Daniel Borchert (USDA, APHIS) for accessing the pest
interception records. Kevin Bigsby (North Carolina State University,
Center for Integrated Pest Management), Barney Caton (USDA, APHIS), and
Denys Yemshanov (Natural Resources Canada) provided helpful reviews of
the manuscript. This research was made possible, in part, by Cooperative
Agreements No. 12-8130-0158-CA and 14-8130-0158-CA from the USDA, APHIS.
It may not necessarily express the views of APHIS. Funding support for
A.J.T. was provided by the RAPIDD program of the Science and Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 53
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Z9 0
U1 8
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-0493
EI 1938-291X
J9 J ECON ENTOMOL
JI J. Econ. Entomol.
PD DEC
PY 2016
VL 109
IS 6
BP 2317
EP 2328
DI 10.1093/jee/tow196
PG 12
WC Entomology
SC Entomology
GA EF4WU
UT WOS:000390333500009
ER
PT J
AU Jenewein, J
Erni, J
Moergeli, H
Grillon, C
Schumacher, S
Mueller-Pfeiffer, C
Hassanpour, K
Seiler, A
Wittmann, L
Schnyder, U
Hasler, G
AF Jenewein, Josef
Erni, Jeannine
Moergeli, Hanspeter
Grillon, Christian
Schumacher, Sonja
Mueller-Pfeiffer, Christoph
Hassanpour, Katayun
Seiler, Annina
Wittmann, Lutz
Schnyder, Ulrich
Hasler, Gregor
TI Altered Pain Perception and Fear-Learning Deficits in Subjects With
Posttraumatic Stress Disorder
SO JOURNAL OF PAIN
LA English
DT Article
DE Anxiety; fear; fear-learning; chronic pain; post-traumatic stress
disorder
ID ADMINISTERED PTSD SCALE; MUTUAL MAINTENANCE; ANXIETY; SYMPTOMS;
INHIBITION; AWARENESS; HUMANS; MODELS; CUES
AB There is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age-and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects' hand. A designation of 'CS-' was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of 'CS+' was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS, and a low-temperature stimulus induced less subjective pain after CS than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments.
Perspective: This study provides new insights into the pathogenesis of chronic pain in patients with PTSD. The findings may help to develop new treatment strategies for this highly prevalent co-morbidity in PTSD. (C) 2016 by the American Pain Society
C1 [Jenewein, Josef; Erni, Jeannine; Moergeli, Hanspeter; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Hassanpour, Katayun; Seiler, Annina; Schnyder, Ulrich] Univ Zurich, Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland.
[Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA.
[Wittmann, Lutz] Int Psychoanalyt Univ, Berlin, Germany.
[Hasler, Gregor] Univ Bern, Univ Hosp Psychiat & Psychotherapy, Bern, Switzerland.
RP Jenewein, J (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Ramistr 100, CH-8091 Zurich, Switzerland.
EM josef.jenewein@usz.ch
OI Hasler, Gregor/0000-0002-8311-0138; Jenewein, Josef/0000-0003-4271-918X
FU Hermann Klaus Foundation, Zurich, Switzerland; Werner Alfred Selo
Foundation, Zurich, Switzerland; Kurt and Senta Herrmann Foundation,
Zurich, Switzerland
FX This work was supported by the Hermann Klaus Foundation, Zurich,
Switzerland; Werner Alfred Selo Foundation, Zurich, Switzerland; and the
Kurt and Senta Herrmann Foundation, Zurich, Switzerland.
NR 36
TC 0
Z9 0
U1 7
U2 7
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD DEC
PY 2016
VL 17
IS 12
BP 1325
EP 1333
DI 10.1016/j.jpain.2016.09.002
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA EF4KD
UT WOS:000390293300007
PM 27641312
ER
PT J
AU Mohammad, S
Wolfe, LA
Stobe, P
Biskup, S
Wainwright, MS
Melin-Aldana, H
Malladi, P
Muenke, M
Gahl, WA
Whitington, PF
AF Mohammad, Saeed
Wolfe, Lynne A.
Stoebe, Petra
Biskup, Saskia
Wainwright, Mark S.
Melin-Aldana, Hector
Malladi, Padmini
Muenke, Maximilian
Gahl, William A.
Whitington, Peter F.
TI Infantile Cirrhosis, Growth Impairment, and Neurodevelopmental Anomalies
Associated with Deficiency of PPP1R15B
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID VANISHING WHITE-MATTER; UNDIAGNOSED DISEASES; PROTEIN-SYNTHESIS; SEVERE
VARIANT; SHORT STATURE; TRANSLATION; LEUKOENCEPHALOPATHY; MUTATION;
GENE; APOPTOSIS
AB Objective To assess the utility of whole-exome sequencing (WES) in a sibling pair with undetermined liver disease and describe the phenotype associated with mutations discovered therein.
Study design Next-generation WES was performed on 2 siblings (S1 and S2) who were born to nonconsanguineous parents of European extraction. Both siblings developed cirrhosis of indeterminate etiology and required liver transplantation; S1 at 7 months and S2 at 22 months.
Results Sequencing of germline DNA identified compound heterozygous mutations in PPP1R15B resulting in increased levels of phosphorylated eukaryotic translation initiation factor 2 alpha.
Conclusions The first demonstration of PPP1R15B associated with liver disease expands the phenotypic spectrum of PPP1R15B related diseases. Our findings validate the application of WES in the diagnosis of children with undetermined liver disease. Understanding the genetic basis of liver disease may allow the development of targeted therapies for treatment and adequate counseling of families.
C1 [Mohammad, Saeed; Malladi, Padmini; Whitington, Peter F.] Northwestren Univ, Feinberg Sch Med, Dept Pediat, Div Gastroenterol, Chicago, IL 60208 USA.
[Mohammad, Saeed; Wainwright, Mark S.; Melin-Aldana, Hector] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60208 USA.
[Wolfe, Lynne A.] NIH, Undiagnosed Dis Program, Common Fund, Bethesda, MD USA.
[Stoebe, Petra; Biskup, Saskia] Cent Genom & Transcript, Tubingen, Germany.
[Wainwright, Mark S.] Northwestren Univ, Feinberg Sch Med, Dept Pediat, Div Neurol, Chicago, IL 60208 USA.
[Melin-Aldana, Hector] Northwestren Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60208 USA.
[Muenke, Maximilian] NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD USA.
[Gahl, William A.] NIH, Natl Human Genome Res Inst, Bethesda, MD USA.
RP Mohammad, S (reprint author), Northwestren Univ, Feinberg Sch Med, Dept Pediat, Div Gastroenterol, Chicago, IL 60208 USA.; Mohammad, S (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60208 USA.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD DEC
PY 2016
VL 179
BP 144
EP +
DI 10.1016/j.jpeds.2016.08.043
PG 8
WC Pediatrics
SC Pediatrics
GA EF0PD
UT WOS:000390027100032
PM 27640355
ER
PT J
AU Moore, RA
Choi, YP
Head, MW
Ironside, JW
Faris, R
Ritchie, DL
Zanusso, G
Priola, SA
AF Moore, Roger A.
Choi, Young Pyo
Head, Mark W.
Ironside, James W.
Faris, Robert
Ritchie, Diane L.
Zanusso, Gianluigi
Priola, Suzette A.
TI Relative Abundance of apoE and A beta 1-42 Associated with Abnormal
Prion Protein Differs between Creutzfeldt-Jakob Disease Subtypes
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE prion protein; transmissible spongiform encephalopathies;
Creutzfeld-Jakob disease; mass spectrometry; proteomics; creatine
kinase; apolipoprotein E; amyloid beta
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; SCRAPIE PRION;
MASS-SPECTROMETRY; STATISTICAL-MODEL; DATABASE SEARCH; PURIFICATION;
AGENT; IDENTIFICATION; PROTEOMICS; SIZE
AB Aggregated and protease-resistant mammalian prion protein (PrPsc) is the primary protein component of infectious prions. Enriched PrPsc preparations are often used to study the mechanisms that underly prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrPsc components including various proteins that could confound functional and structural studies. It is thus important to identify these proteins and assess their potential relevance to prion pathogenesis. Following proteinase K treatment and phosphotungstic acid precipitation of brain homogenate, we have used mass spectrometry to analyze the protein content of PrPsc isolated from prion-infected mice, multiple cases of sporadic Creutzfeldt-Jakob disease (sCJD), and human growth hormone associated cases of iatrogenic CJD (iCJD). Creatine kinase was the primary protein contaminant in all PrPsc samples, while many of the other proteins identified were also found in non-CJD controls, which suggests that they are not CJD specific. Interestingly, the Alzheimer's disease associated peptide amyloid beta 1-42 (A beta 1-42) was identified in the majority of the sCJD cases as well as non-CJD age-matched controls, while apoliprotein E was found in greater abundance in the sCJD cases. By contrast, while some of the iCJD cases showed evidence of higher molecular weight A beta oligomers, monomeric A beta 1-42 peptide was not detected by immunoblot, and only one case had significant levels of apolipoprotein E. Our data are consistent with the age-associated deposition of A beta 1-42 in older sporadic CJD and non-CJD patients and suggest that both apolipoprotein E and A beta 1-42 abundance can differ depending upon the type of CJD.
C1 [Moore, Roger A.; Faris, Robert; Priola, Suzette A.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Choi, Young Pyo] Korea Brain Res Inst, Div Res, Lab Anim Ctr, Daegu 41068, South Korea.
[Head, Mark W.; Ironside, James W.; Ritchie, Diane L.] Univ Edinburgh, Sch Clin Sci, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh EH8 9YL, Midlothian, Scotland.
[Zanusso, Gianluigi] Univ Verona, Dept Neurosci Biomed & Movement Sci, I-37129 Verona, Italy.
RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM spriola@nih.gov
FU National Institute of Allergy and Infectious Disease, National
Institutes of Health [1-Z01-AI000752-12]; Fondation Alliance Biosecure
"Multicenter evaluation of improved RT-QuIC diagnostic assays for
Creutzfeldt-Jakob and other human prion diseases"; Medical Research
Council [MRC G0900580]; KBRI Research program of the Ministry of
Science, ICT, and Future Planning [2231-415]
FX The authors would like to thank Dr. Andrew Timmes for generously
providing purified mouse PrPsc and Drs. Byron Caughey, Karin
Peterson, and Brad Groveman for critically evaluating the manuscript.
The authors also thank Anita Mora and Ryan Kissinger for providing
technical assistance in preparation of the figures and the table of
contents illustration. This research was supported by the intramural
research program of the National Institute of Allergy and Infectious
Disease, National Institutes of Health (Project No. 1-Z01-AI000752-12)
and by Fondation Alliance Biosecure "Multicenter evaluation of improved
RT-QuIC diagnostic assays for Creutzfeldt-Jakob and other human prion
diseases". Edinburgh Brain Banks is supported by the Medical Research
Council (MRC G0900580) and Y.P.C. by the KBRI Research program of the
Ministry of Science, ICT, and Future Planning (2231-415).
NR 54
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U1 2
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD DEC
PY 2016
VL 15
IS 12
BP 4518
EP 4531
DI 10.1021/acs.jproteome.6b00633
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA EE2EM
UT WOS:000389396500030
PM 27597180
ER
PT J
AU Oliver, B
Boehm, M
Rosing, DR
Shapiro, LS
Dempsey, DT
Merkel, PA
Lee, CCR
Cowen, EW
AF Oliver, Brittany
Boehm, Manfred
Rosing, Douglas R.
Shapiro, Lee S.
Dempsey, Daniel T.
Merkel, Peter A.
Lee, Chyi-Chia Richard
Cowen, Edward W.
TI Diffuse atrophic papules and plaques, intermittent abdominal pain,
paresthesias, and cardiac abnormalities in a 55-year-old woman
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Editorial Material
DE complement; Degos disease; eculizumab; interferon; malignant atrophic
papulosis; treprostinil; vasculopathy
ID PAPULOSIS DEGOS-DISEASE; FAMILY
C1 [Oliver, Brittany] NIH, Bethesda, MD USA.
[Boehm, Manfred] NHLBI, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA.
[Rosing, Douglas R.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Shapiro, Lee S.] Ctr Rheumatol, Saratoga Springs, NY USA.
[Dempsey, Daniel T.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10 Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10 Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA.
EM cowene@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 18
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD DEC
PY 2016
VL 75
IS 6
BP 1274
EP 1277
DI 10.1016/j.jaad.2016.09.015
PG 4
WC Dermatology
SC Dermatology
GA EF0QX
UT WOS:000390032000055
PM 27717619
ER
PT J
AU Ernst, ME
Davis, BR
Soliman, EZ
Prineas, RJ
Okin, PM
Ghosh, A
Cushman, WC
Einhorn, PT
Oparil, S
Grimm, RH
AF Ernst, Michael E.
Davis, Barry R.
Soliman, Elsayed Z.
Prineas, Ronald J.
Okin, Peter M.
Ghosh, Alokananda
Cushman, William C.
Einhorn, Paula T.
Oparil, Suzanne
Grimm, Richard H., Jr.
CA ALLHAT Collaborative Res Grp
TI Electrocardiographic measures of left ventricular hypertrophy in the
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial
SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION
LA English
DT Article
DE Amlodipine; chlorthalidone; electrocardiography; lisinopril
ID FACTOR INTERVENTION TRIAL; TO-VISIT VARIABILITY; SYSTOLIC
BLOOD-PRESSURE; DRUG-THERAPY; FOLLOW-UP; HYPERTENSION; RISK; MORTALITY;
AMLODIPINE; DISEASE
AB Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = 857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Delta baseline, 2 years = +3 to -27 mu V, analysis of variance P = .8612; 4 years = +10 to -17 mu V, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH. (C) 2016 American Society of Hypertension. All rights reserved.
C1 [Ernst, Michael E.] Univ Iowa, Coll Pharm, Dept Pharm Practice & Sci, Iowa City, IA 52242 USA.
[Ernst, Michael E.] Univ Iowa, Dept Family Med, Carver Coll Med, Iowa City, IA USA.
[Davis, Barry R.; Ghosh, Alokananda] Univ Texas Sch Publ Hlth, Dept Biostat, Coordinating Ctr Clin Trials, Houston, TX USA.
[Soliman, Elsayed Z.; Prineas, Ronald J.] Wake Forest Univ, Epidemiol Cardiol Res Ctr EPICARE, Dept Epidemiol & Prevent, Div Publ Hlth Sci,Sch Med, Winston Salem, NC 27109 USA.
[Okin, Peter M.] Weill Cornell Med Coll, Div Cardiol, New York, NY USA.
[Cushman, William C.] Vet Affairs Med Ctr, Prevent Med Sect, Memphis, TN USA.
[Einhorn, Paula T.] NHLBI, Div Heart & Vasc Dis, Bldg 10, Bethesda, MD 20892 USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL USA.
[Grimm, Richard H., Jr.] Minneapolis Med Res Fdn Inc, Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
[Grimm, Richard H., Jr.] Hennepin Cty Med Ctr, Div Clin Epidemiol, Minneapolis, MN 55415 USA.
[Grimm, Richard H., Jr.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA.
RP Davis, BR (reprint author), Univ Texas Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Pressler St W-916, Houston, TX 77030 USA.
EM barry.r.davis@uth.tmc.edu
OI Prineas, Ronald/0000-0001-7494-0634
FU National Heart, Lung, and Blood Institute [NO1-HC-35130,
HHSN268201100036C]
FX This study was supported by contracts NO1-HC-35130 and HHSN268201100036C
with the National Heart, Lung, and Blood Institute.
NR 29
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-1711
EI 1878-7436
J9 J AM SOC HYPERTENS
JI J. Am. Soc. Hypertens.
PD DEC
PY 2016
VL 10
IS 12
BP 930
EP 938
DI 10.1016/j.jash.2016.10.010
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EF4KA
UT WOS:000390293000005
PM 27938852
ER
PT J
AU Iranzo, J
Koonin, EV
Prangishvili, D
Krupovic, M
AF Iranzo, Jaime
Koonin, Eugene V.
Prangishvili, David
Krupovic, Mart
TI Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary
Connections between Viruses and Capsidless Mobile Elements
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID STRANDED DNA VIRUSES; CRISPR-CAS SYSTEMS; VIRAL GENOMES; SHAPED VIRUS;
HYPERTHERMOPHILIC ARCHAEA; THERMOPHILIC BACTERIA; VIRION ARCHITECTURE;
HALOPHILIC ARCHAEA; TAILED VIRUSES; HOT-SPRINGS
AB Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order Caudovirales and the families Turriviridae and Sphaerolipoviridae that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere.
IMPORTANCE
Viruses infecting archaea are among the most mysterious denizens of the virosphere. Many of these viruses display no genetic or even morphological relationship to viruses of bacteria and eukaryotes, raising questions regarding their origins and position in the global virosphere. Analysis of 5,740 protein sequences from 116 genomes allowed dissection of the archaeal virus network and showed that most groups of archaeal viruses are evolutionarily connected to capsidless mobile genetic elements, including various plasmids and transposons. This finding could reflect actual independent origins of the distinct groups of archaeal viruses from different nonviral elements, providing important insights into the emergence and evolution of the archaeal virome.
C1 [Iranzo, Jaime; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Prangishvili, David; Krupovic, Mart] Inst Pasteur, Unite Biol Mol Gene Chez Extremophiles, Paris, France.
RP Krupovic, M (reprint author), Inst Pasteur, Unite Biol Mol Gene Chez Extremophiles, Paris, France.
EM krupovic@pasteur.fr
OI Krupovic, Mart/0000-0001-5486-0098; Iranzo, Jaime/0000-0002-4538-7726
FU HHS \ National Institutes of Health (NIH) (intramural funds of the US
Department of Health and Human Services); Agence Nationale de la
Recherche (ANR) (program BLANC project EXAVIR)
FX This work, including the efforts of Jaime Iranzo and Eugene V. Koonin,
was funded by HHS vertical bar National Institutes of Health (NIH)
(intramural funds of the US Department of Health and Human Services).
This work, including the efforts of David Prangishvili, was funded by
Agence Nationale de la Recherche (ANR) (program BLANC project EXAVIR).
NR 82
TC 1
Z9 1
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 24
BP 11043
EP 11055
DI 10.1128/JVI.01622-16
PG 13
WC Virology
SC Virology
GA EF2BL
UT WOS:000390129300006
PM 27681128
ER
PT J
AU Chen, CY
Shingai, M
Welbourn, S
Martin, MA
Borrego, P
Taveira, N
Strebel, K
AF Chen, Chia-Yen
Shingai, Masashi
Welbourn, Sarah
Martin, Malcolm A.
Borrego, Pedro
Taveira, Nuno
Strebel, Klaus
TI Antagonism of BST-2/Tetherin Is a Conserved Function of the Env
Glycoprotein of Primary HIV-2 Isolates
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-2 ENVELOPE PROTEIN; VIRAL PARTICLE
RELEASE; VPU PROTEIN; CELL-SURFACE; RETROVIRUS RELEASE; TETHERIN; BST-2;
RESTRICTION; NEF
AB Although HIV-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit.
IMPORTANCE
Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a vpu gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence.
C1 [Chen, Chia-Yen; Shingai, Masashi; Welbourn, Sarah; Martin, Malcolm A.; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Borrego, Pedro; Taveira, Nuno] Univ Lisbon, Fac Pharm, Res Inst Med iMed ULisboa, Lisbon, Portugal.
[Taveira, Nuno] Inst Super Ciencias Saude Egas Moniz, Ctr Invest Interdisciplinar Egas Moniz, Caparica, Portugal.
RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
RI Taveira, Nuno/A-6252-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014;
iMed.ULisboa, EEPHIV /B-4222-2014;
OI Taveira, Nuno/0000-0003-0176-5585; Borrego, Pedro/0000-0002-1949-9484
FU NIH [AI000669]
FX This work, including the efforts of Klaus Strebel, was funded by NIH
Intramural Research Program (AI000669).
NR 55
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 24
BP 11062
EP 11074
DI 10.1128/JVI.01451-16
PG 13
WC Virology
SC Virology
GA EF2BL
UT WOS:000390129300008
PM 27681141
ER
PT J
AU Wu, F
Kirmaier, A
White, E
Ourmanov, I
Whitted, S
Matsuda, K
Riddick, N
Hall, LR
Morgan, JS
Plishka, RJ
Buckler-White, A
Johnson, WE
Hirsch, VM
AF Wu, Fan
Kirmaier, Andrea
White, Ellen
Ourmanov, Ilnour
Whitted, Sonya
Matsuda, Kenta
Riddick, Nadeene
Hall, Laura R.
Morgan, Jennifer S.
Plishka, Ronald J.
Buckler-White, Alicia
Johnson, Welkin E.
Hirsch, Vanessa M.
TI TRIM5 alpha Resistance Escape Mutations in the Capsid Are Transferable
between Simian Immunodeficiency Virus Strains
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RHESUS MACAQUES; INTRARECTAL CHALLENGE; MONKEY TRIM5-ALPHA; INFECTION;
TRIM5; ACQUISITION; SIV; VACCINE; NEUTRALIZATION; REPLICATION
AB TRIM5 alpha polymorphism limits and complicates the use of simian immunodeficiency virus (SIV) for evaluation of human immunodeficiency virus (HIV) vaccine strategies in rhesus macaques. We previously reported that the TRIM5 alpha-sensitive SIV from sooty mangabeys (SIVsm) clone SIVsmE543-3 acquired amino acid substitutions in the capsid that overcame TRIM5 alpha restriction when it was passaged in rhesus macaques expressing restrictive TRIM5 alpha alleles. Here we generated TRIM5 alpha-resistant clones of the related SIVsmE660 strain without animal passage by introducing the same amino acid capsid substitutions. We evaluated one of the variants in rhesus macaques expressing permissive and restrictive TRIM5 alpha alleles. The SIVsmE660 variant infected and replicated in macaques with restrictive TRIM5 alpha genotypes as efficiently as in macaques with permissive TRIM5 alpha genotypes. These results demonstrated that mutations in the SIV capsid can confer SIV resistance to TRIM5 alpha restriction without animal passage, suggesting an applicable method to generate more diverse SIV strains for HIV vaccine studies.
IMPORTANCE
Many strains of SIV from sooty mangabey monkeys are susceptible to resistance by common rhesus macaque TRIM5 alpha alleles and result in reduced virus acquisition and replication in macaques that express these restrictive alleles. We previously observed that spontaneous variations in the capsid gene were associated with improved replication in macaques, and the introduction of two amino acid changes in the capsid transfers this improved replication to the parent clone. In the present study, we introduced these mutations into a related but distinct strain of SIV that is commonly used for challenge studies for vaccine trials. These mutations also improved the replication of this strain in macaques with the restrictive TRIM5 alpha genotype and thus will eliminate the confounding effects of TRIM5 alpha in vaccine studies.
C1 [Wu, Fan; White, Ellen; Ourmanov, Ilnour; Whitted, Sonya; Matsuda, Kenta; Riddick, Nadeene; Plishka, Ronald J.; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Kirmaier, Andrea; Hall, Laura R.; Morgan, Jennifer S.; Johnson, Welkin E.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
RP Wu, F; Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM wuf2@niaid.nih.gov; vhirsch@niaid.nih.gov
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [AI083118]
FX This work, including the efforts of Fan Wu, Ellen White, Ilnour
Ourmanov, Sonya Whitted, Kenta Matsuda, Nadeene Riddick, Ronald J.
Plishka, Alicia Buckler-White, and Vanessa M. Hirsch, was funded by HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) (Intramural program). This work, including
the efforts of Andrea Kirmaier, Laura R. Hall, Jennifer S. Morgan, and
Welkin E. Johnson, was funded by HHS vertical bar NIH vertical bar
National Institute of Allergy and Infectious Diseases (NIAID)
(AI083118).
NR 35
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 24
BP 11087
EP 11095
DI 10.1128/JVI.01620-16
PG 9
WC Virology
SC Virology
GA EF2BL
UT WOS:000390129300010
PM 27681142
ER
PT J
AU Luque, D
Mata, CP
Gonzalez-Camacho, F
Gonzalez, JM
Gomez-Blanco, J
Alfonso, C
Rivas, G
Havens, WM
Kanematsu, S
Suzuki, N
Ghabrial, SA
Trus, BL
Caston, JR
AF Luque, Daniel
Mata, Carlos P.
Gonzalez-Camacho, Fernando
Gonzalez, Jose M.
Gomez-Blanco, Josue
Alfonso, Carlos
Rivas, German
Havens, Wendy M.
Kanematsu, Satoko
Suzuki, Nobuhiro
Ghabrial, Said A.
Trus, Benes L.
Caston, Jose R.
TI Heterodimers as the Structural Unit of the T=1 Capsid of the Fungal
Double-Stranded RNA Rosellinia necatrix Quadrivirus 1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PHYTOPATHOGENIC FILAMENTOUS FUNGUS; PENICILLIUM-CHRYSOGENUM-VIRUS;
BURSAL DISEASE VIRUS; L-A VIRUS; DSRNA VIRUS; STRUCTURE REVEALS;
CRYOELECTRON MICROSCOPY; ATOMIC-STRUCTURE; 3-DIMENSIONAL STRUCTURE;
ANGSTROM RESOLUTION
AB Most double-stranded RNA (dsRNA) viruses are transcribed and replicated in a specialized icosahedral capsid with a T = 1 lattice consisting of 60 asymmetric capsid protein (CP) dimers. These capsids help to organize the viral genome and replicative complex( es). They also act as molecular sieves that isolate the virus genome from host defense mechanisms and allow the passage of nucleotides and viral transcripts. Rosellinia necatrix quadrivirus 1 (RnQV1), the type species of the family Quadriviridae, is a dsRNA fungal virus with a multipartite genome consisting of four monocistronic segments (segments 1 to 4). dsRNA-2 and dsRNA-4 encode two CPs (P2 and P4, respectively), which coassemble into similar to 450-angstrom-diameter capsids. We used three-dimensional cryo-electron microscopy combined with complementary biophysical techniques to determine the structures of RnQV1 virion strains W1075 and W1118. RnQV1 has a quadripartite genome, and the capsid is based on a single-shelled T = 1 lattice built of P2-P4 dimers. Whereas the RnQV1-W1118 capsid is built of full-length CP, P2 and P4 of RnQV1-W1075 are cleaved into several polypeptides, maintaining the capsid structural organization. RnQV1 heterodimers have a quaternary organization similar to that of homodimers of reoviruses and other dsRNA mycoviruses. The RnQV1 capsid is the first T = 1 capsid with a heterodimer as an asymmetric unit reported to date and follows the architectural principle for dsRNA viruses that a 120-subunit capsid is a conserved assembly that supports dsRNA replication and organization.
IMPORTANCE
Given their importance to health, members of the family Reoviridae are the basis of most structural and functional studies and provide much of our knowledge of dsRNA viruses. Analysis of bacterial, protozoal, and fungal dsRNA viruses has improved our understanding of their structure, function, and evolution, as well. Here, we studied a dsRNA virus that infects the fungus Rosellinia necatrix, an ascomycete that is pathogenic to a wide range of plants. Using three-dimensional cryo-electron microscopy and analytical ultracentrifugation analysis, we determined the structure and stoichiometry of Rosellinia necatrix quadrivirus 1 (RnQV1). The RnQV1 capsid is a T = 1 capsid with 60 heterodimers as the asymmetric units. The large amount of genetic information used by RnQV1 to construct a simple T = 1 capsid is probably related to the numerous virus-host and virus-virus interactions that it must face in its life cycle, which lacks an extracellular phase.
C1 [Luque, Daniel; Mata, Carlos P.; Gonzalez, Jose M.; Gomez-Blanco, Josue; Caston, Jose R.] CSIC, CNB, Dept Struct Macromol, Madrid, Spain.
[Luque, Daniel; Gonzalez-Camacho, Fernando] ISCIII, Ctr Nacl Microbiol, Carretera Majadahonda Pozuelo, Madrid, Spain.
[Alfonso, Carlos; Rivas, German] CSIC, Ctr Invest Biol, Madrid, Spain.
[Havens, Wendy M.; Ghabrial, Said A.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA.
[Kanematsu, Satoko] Natl Agr & Food Res Org NARO, Inst Fruit Tree Sci, Morioka, Iwate, Japan.
[Suzuki, Nobuhiro] Inst Plant Sci & Resources, Okayama, Japan.
[Trus, Benes L.] NIH, Imaging Sci Lab, CIT, Bldg 10, Bethesda, MD 20892 USA.
[Gonzalez, Jose M.] Wellcome Trust Sanger Inst, Cambridge, England.
RP Caston, JR (reprint author), CSIC, CNB, Dept Struct Macromol, Madrid, Spain.
EM jrcaston@cnb.csic.es
RI Suzuki, Nobuhiro/B-2517-2011; Alfonso, Carlos/K-1316-2014; Luque,
Daniel/I-6467-2015
OI Alfonso, Carlos/0000-0001-7165-4800; Luque, Daniel/0000-0002-0151-6020
FU Spanish Ministry of Economy and Competitively [BFU2014-52070-C2-2-P];
Spanish Ministry of Economy and Competitivity [BFU2014-55475 R];
Comunidad Autonoma de Madrid [S2013/MIT-2807]; Intramural Research
Program of NIH; Ministry of Education, Culture, Science, Sports and
Technology (MEXT) of Japan [16H06436]
FX This work, including the efforts of Carlos Alfonso and German Rivas, was
funded by Spanish Ministry of Economy and Competitively
(BFU2014-52070-C2-2-P). This work, including the efforts of Jose R.
Caston, was funded by Spanish Ministry of Economy and Competitivity
(BFU2014-55475 R). This work, including the efforts of Jose R. Caston,
was funded by Comunidad Autonoma de Madrid (S2013/MIT-2807). This work,
including the efforts of Benes L. Trus, was funded by Intramural
Research Program of the NIH. This work, including the efforts of
Nobuhiro Suzuki, was funded by Ministry of Education, Culture, Science,
Sports and Technology (MEXT) of Japan (16H06436).
NR 63
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 24
BP 11220
EP 11230
DI 10.1128/JVI.01013-16
PG 11
WC Virology
SC Virology
GA EF2BL
UT WOS:000390129300021
PM 27707923
ER
PT J
AU Bas-Hoogendam, JM
Blackford, JU
Bruhl, AB
Blair, KS
van der Wee, NJA
Westenberg, PM
AF Bas-Hoogendam, Janna Marie
Blackford, Jennifer U.
Bruhl, Annette B.
Blair, Karina S.
van der Wee, Nic J. A.
Westenberg, P. Michiel
TI Neurobiological candidate endophenotypes of social anxiety disorder
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Social anxiety disorder; Genetic vulnerability; Endophenotypes;
Neuroimaging; Amygdala; Medial prefrontal cortex; Connectivity; Uncinate
fasciculus
ID DEFAULT MODE NETWORK; VOXEL-BASED MORPHOMETRY; CEREBRAL BLOOD-FLOW;
COMORBIDITY SURVEY REPLICATION; BRAIN FUNCTIONAL CONNECTIVITY; AVOIDANT
PERSONALITY-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; COGNITIVE-BEHAVIORAL
THERAPY; PREDICTS ANXIOUS TEMPERAMENT; WHITE-MATTER MICROSTRUCTURE
AB Social anxiety disorder (SAD) is a disabling psychiatric disorder with a complex pathogenesis. Studies indicate a genetic component in the development of SAD, but the search for genetic mechanisms underlying this vulnerability is complicated. A focus on endophenotypes instead of the disorder itself may provide a fruitful path forward. Endophenotypes are measurable characteristics related to complex psychiatric disorders and reflective of genetically-based disease mechanisms, and could shed light on the ways by which genes contribute to the development of SAD. We review evidence for candidate MRI endophenotypes of SAD and discuss the extent to which they meet the criteria for an endophenotype, focussing on the amygdala, the medial prefrontal cortex, whole-brain functional connectivity and structural-anatomical changes. Strongest evidence is present for the primary endophenotype criterion of association between the candidate endophenotypes and SAD, while the other criteria, involving trait-stability, heritability and co-segregation of the endophenotype with the disorder within families, warrant further investigation. We highlight the potential of neuroimaging endophenotypes and stress the need for family studies into SAD endophenotypes. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Bas-Hoogendam, Janna Marie; Westenberg, P. Michiel] Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands.
[Bas-Hoogendam, Janna Marie; van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Dept Psychiat, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
[Bas-Hoogendam, Janna Marie; van der Wee, Nic J. A.; Westenberg, P. Michiel] Leiden Inst Brain & Cognit, Leiden, Netherlands.
[Blackford, Jennifer U.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA.
[Blackford, Jennifer U.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
[Bruhl, Annette B.] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England.
[Bruhl, Annette B.] Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland.
[Blair, Karina S.] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bas-Hoogendam, JM (reprint author), Leiden Univ, Inst Psychol, Dev & Educ Psychol, Wassenaarseweg 52,Pieter Court Bldg,Room 3-B43, NL-2333 AK Leiden, Netherlands.
EM j.m.hoogendam@fsw.leidenuniv.nl; jenni.blackford@Vanderbilt.Edu;
abb41@medschl.cam.ac.uk; blair.karina@gmail.com;
N.J.A.van_der_Wee@lumc.nl; westenberg@fsw.leidenuniv.nl
FU Leiden University Research Profile 'Health, Prevention and the Human
Life Cycle'
FX This research has been funded by the Leiden University Research Profile
'Health, Prevention and the Human Life Cycle'. The funding source had no
involvement in writing this review nor in the decision to submit this
review for publication. We thank the Lorentz Center (Leiden, the
Netherlands) for their support in organizing the workshop
'Endophenotypes of Social Anxiety Disorder: Can We Detect Them and Are
They Useful in Clinical Practice?' (14-18 December 2015). This workshop
was of high value for the preparation of the present review.
NR 282
TC 0
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U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
EI 1873-7528
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD DEC
PY 2016
VL 71
BP 362
EP 378
DI 10.1016/j.neubiorev.2016.08.040
PG 17
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA EF7IA
UT WOS:000390502100025
PM 27593443
ER
PT J
AU Radin, RM
Shomaker, LB
Kelly, NR
Pickworth, CK
Thompson, KA
Brady, SM
Demidowich, A
Galescu, O
Altschul, AM
Shank, LM
Yanovski, SZ
Tanofsky-Kraff, M
Yanovski, JA
AF Radin, R. M.
Shomaker, L. B.
Kelly, N. R.
Pickworth, C. K.
Thompson, K. A.
Brady, S. M.
Demidowich, A.
Galescu, O.
Altschul, A. M.
Shank, L. M.
Yanovski, S. Z.
Tanofsky-Kraff, M.
Yanovski, J. A.
TI Cortisol response to an induction of negative affect among adolescents
with and without loss of control eating
SO PEDIATRIC OBESITY
LA English
DT Article
DE binge eating; loss of control eating; cortisol; depressive symptoms;
adolescence
ID DEPRESSIVE SYMPTOMS; INSULIN-RESISTANCE; DIURNAL CORTISOL; ADULT
OBESITY; MEAL INTAKE; BINGE; STRESS; GIRLS; RISK; DISORDERS
AB Background: Adults with binge eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge eating disorder.
Methods: We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at -80, 0, 30 and 50 min relative to film administration, and state mood ratings were reported before and after the film.
Results: Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps>0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps>0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps>0.05).
Conclusions: A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations.
C1 [Radin, R. M.; Shomaker, L. B.; Kelly, N. R.; Pickworth, C. K.; Thompson, K. A.; Brady, S. M.; Demidowich, A.; Galescu, O.; Altschul, A. M.; Shank, L. M.; Yanovski, S. Z.; Tanofsky-Kraff, M.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Radin, R. M.; Kelly, N. R.; Shank, L. M.; Tanofsky-Kraff, M.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Shomaker, L. B.; Kelly, N. R.] Colorado State Univ, Dept Human Dev & Family Studies, 303 Behav Sci Bldg,410 Pitkin St, Ft Collins, CO 80523 USA.
[Yanovski, S. Z.] Natl Inst Diabet Digest & Kidney Dis, Off Obes Res, Div Digest Dis & Nutr, NIH,DHHS, Bethesda, MD 20892 USA.
RP Shomaker, LB (reprint author), Colorado State Univ, Dept Human Dev & Family Studies, 303 Behav Sci Bldg,410 Pitkin St, Ft Collins, CO 80523 USA.
EM Lauren.Shomaker@colostate.edu
OI Shank, Lisa/0000-0002-6922-7946
FU NIH National Research Service [F32HD056762]; NICHD [K99/R00HD069516];
NIH Intramural Research Program Grant from NICHD [1ZIAHD000641]; NIH
Bench to Bedside Program; Office of Behavioral and Social Sciences
Research
FX R.M.R., L.B.S., M.T.K. and J.A.Y. conceived the hypothesis for this
article. R.M.R., L.B.S., M.T.K. and J.A.Y. wrote the first draft of the
manuscript. R.M.R., M.T.K., L.B.S. and J.A.Y. conducted data analysis.
All authors (R.M.R., M.T.K., L.B.S., N.R.K., C.K.P., K.A.T., S.M.B.,
A.D., O.G., A.A., L.M.S., S.Z.Y. and J.A.Y.) participated in data
collection, reviewed and edited the manuscript and approved the final
version of the manuscript. J. Yanovski is a commissioned officer in the
US Public Health Service (PHS). Funding for this study was provided by
the following sources: NIH National Research Service Award F32HD056762
and Pathway to Independence Award K99/R00HD069516 (L. Shomaker) from
NICHD; NIH Intramural Research Program Grant 1ZIAHD000641 (J. Yanovski)
from NICHD with supplemental funding from the NIH Bench to Bedside
Program and the Office of Behavioral and Social Sciences Research. The
aforementioned funding source (NICHD) had no role in the study design,
collection, analysis or interpretation of data, writing of the
manuscript or decision to submit the paper for publication. The opinions
and assertions expressed herein are those of the authors and are not to
be construed as reflecting the views of the PHS, USUHS or the US
Department of Defense. Portions of this study were presented at The
Obesity Society, Boston, MA, November, 2014.
NR 32
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-6310
EI 2047-6302
J9 PEDIATR OBES
JI Pediatr. Obes.
PD DEC
PY 2016
VL 11
IS 6
BP 513
EP 520
DI 10.1111/ijpo.12095
PG 8
WC Pediatrics
SC Pediatrics
GA EF0RF
UT WOS:000390032800015
PM 26667312
ER
PT J
AU Krause, AJ
Cines, B
Pogrebniak, E
Sherafat-Kazemzadeh, R
Demidowich, AP
Galescu, OA
Brady, SM
Reynolds, JC
Hubbard, VS
Yanovski, JA
AF Krause, A. J.
Cines, B.
Pogrebniak, E.
Sherafat-Kazemzadeh, R.
Demidowich, A. P.
Galescu, O. A.
Brady, S. M.
Reynolds, J. C.
Hubbard, V. S.
Yanovski, J. A.
TI Associations between adiposity and indicators of thyroid status in
children and adolescents
SO PEDIATRIC OBESITY
LA English
DT Article
DE Free thyroxine; obesity; paediatric; TSH
ID BODY-MASS INDEX; OBESE CHILDREN; WEIGHT-LOSS; METABOLIC PARAMETERS;
HORMONE-LEVELS; HYPOTHYROIDISM; INSULIN; TSH; THYROTROPIN; EXPRESSION
AB Background: In adults, obesity is associated with abnormalities of thyroid function; there are fewer studies in paediatric cohorts.
Objectives: To examine associations of weight and adiposity with indices of thyroid function and thyroid-related metabolic factors in children.
Design/Methods: A sample of 1203 children without obesity (body mass index [BMI] <95th percentile; N=631) and with obesity (BMI >= 95th percentile; N=572), age 5-18 years, had height and weight measured (to calculate BMI-Z score for age and sex) and had blood collected in the morning for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and leptin. A subset (N=829) also underwent measurement of fat mass by dual-energy X-ray absorptiometry. Analyses examined associations of TSH and FT4 with adiposity and obesity-related conditions accounting for sociodemographic factors.
Results: Thyroid-stimulating hormone was positively related to BMIz and fat mass (both p-values <0.001). FT4 was negatively related to BMIz and fat mass (both p-values <0.001). TSH was positively correlated to leptin (p=0.001) even after accounting for fat mass.
Conclusions: Paediatric obesity is associated with higher TSH and lower FT4 concentrations and with a greater prevalence of abnormally high TSH. Leptin concentrations may in part explain obesity's effects on thyroid status, perhaps through leptin's effects on TSH secretion.
C1 [Krause, A. J.; Cines, B.; Pogrebniak, E.; Sherafat-Kazemzadeh, R.; Demidowich, A. P.; Galescu, O. A.; Brady, S. M.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Krause, A. J.; Hubbard, V. S.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, NIH, Div Nutr Res Coordinat, Bethesda, MD USA.
[Reynolds, J. C.] NIH, Div Nucl Med, Radiol & Imaging Sci Dept, Hatfield Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
FU National Institutes of Child Health and Human Development/NIH Intramural
Research Program Grant from NIMHD [ZIAHD000641]; NIH Division of
Nutrition Research Coordination, NIDDK, NIH
FX J. A. Yanovski was supported by the National Institutes of Child Health
and Human Development/NIH Intramural Research Program Grant ZIAHD000641
with supplemental funding from NIMHD. A. Krause was supported by the NIH
Division of Nutrition Research Coordination, NIDDK, NIH.
NR 30
TC 1
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-6310
EI 2047-6302
J9 PEDIATR OBES
JI Pediatr. Obes.
PD DEC
PY 2016
VL 11
IS 6
BP 551
EP 558
DI 10.1111/ijpo.12112
PG 8
WC Pediatrics
SC Pediatrics
GA EF0RF
UT WOS:000390032800020
PM 26910299
ER
PT J
AU Schwarz, B
Morabito, KM
Ruckwardt, TJ
Patterson, DP
Avera, J
Miettinen, HM
Graham, BS
Douglas, T
AF Schwarz, Benjamin
Morabito, Kaitlyn M.
Ruckwardt, Tracy J.
Patterson, Dustin P.
Avera, John
Miettinen, Heini M.
Graham, Barney S.
Douglas, Trevor
TI Viruslike Particles Encapsidating Respiratory Syncytial Virus M and M2
Proteins Induce Robust T Cell Responses
SO ACS BIOMATERIALS SCIENCE & ENGINEERING
LA English
DT Article
DE subunit vaccine; viruslike particle; respiratory syncytial virus; CD8+T
cell immunity; tissue-resident memory T cells
ID RANDOMIZED CONTROLLED-TRIAL; VACCINE DEVELOPMENT; BACTERIOPHAGE P22;
DENDRITIC CELLS; INFECTION; INFLUENZA; MICE; LYMPHOCYTES; PLATFORM;
MODEL
AB Subunit vaccines provide a safe, focused alternative to conventional vaccines. However, these vaccines often require significant adjuvants and are particularly hard to target toward cytotoxic T lymphocyte (CTL) immunity. Viruslike particles (VLPs) provide biomaterial scaffolds with pathogen-like polyvalent structures making them useful platforms for biomimetic antigen delivery to the immune system. Encapsidation of antigens within VLPs has been shown to enhance antigen availability for CD8 T cell responses. Here, we examine the potential to generate complex responses to multiple subunit antigens localized within the same VLP particle. Two proteins of respiratory syncytial virus (RSV) with well-characterized CD8 T cell responses, the matrix (M) and matrix 2 (M2) proteins, were successfully coencapsidated within the P22 VLP. Upon intranasal administration in mice, the particles stimulated CD8 T cell memory responses against both antigens. In addition, vaccination elicited tissue-resident T cell populations. Upon subsequent RSV challenge, P22-M/M2-treated mice displayed significantly reduced lung viral titers. This demonstrates the utility of the P22 VLP in directing immune responses to multiple encapsidated viral antigens, demonstrating the potential of this technology to facilitate immunity to multiple targets simultaneously.
C1 [Schwarz, Benjamin; Avera, John; Douglas, Trevor] Indiana Univ, Dept Chem, 800 East Kirkwood Ave, Bloomington, IN 47405 USA.
[Morabito, Kaitlyn M.; Ruckwardt, Tracy J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Morabito, Kaitlyn M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA.
[Patterson, Dustin P.] Univ Texas Tyler, Dept Chem & Biochem, 3900 Univ Blvd, Tyler, TX 75799 USA.
[Miettinen, Heini M.] Montana State Univ, Dept Microbiol & Immunol, POB 173400, Bozeman, MT 59717 USA.
RP Douglas, T (reprint author), Indiana Univ, Dept Chem, 800 East Kirkwood Ave, Bloomington, IN 47405 USA.; Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@mail.nih.gov; trevdoug@indiana.edu
RI Douglas, Trevor/F-2748-2011
FU NIH [R01 AI104905, R01 EB012027]; Department of Defense (DoD) Air Force
Office of Sponsored Research through the National Defense Science &
Engineering Graduate Fellowship (NDSEG) Program; Intramural National
Institute of Allergy and Infectious diseases
FX Research supported by NIH grants NIH grants R01 AI104905 and R01
EB012027. B.S. was supported by the Department of Defense (DoD) Air
Force Office of Sponsored Research through the National Defense Science
& Engineering Graduate Fellowship (NDSEG) Program. All animal work was
supported by Intramural National Institute of Allergy and Infectious
diseases.
NR 53
TC 0
Z9 0
U1 6
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-9878
J9 ACS BIOMATER SCI ENG
JI ACS Biomater. Sci. Eng.
PD DEC
PY 2016
VL 2
IS 12
BP 2324
EP 2332
DI 10.1021/acsbiomaterials.6b00532
PG 9
WC Materials Science, Biomaterials
SC Materials Science
GA EE7IN
UT WOS:000389789200022
ER
PT J
AU Jose, GS
Jackson, ER
Haymond, A
Johny, C
Edwards, RL
Wang, X
Brothers, RC
Edelstein, EK
Odom, AR
Boshoff, HI
Couch, RD
Dowd, CS
AF Jose, Geraldine San
Jackson, Emily R.
Haymond, Amanda
Johny, Chinchu
Edwards, Rachel L.
Wang, Xu
Brothers, R. Carl
Edelstein, Emma K.
Odom, Audrey R.
Boshoff, Helena I.
Couch, Robin D.
Dowd, Cynthia S.
TI Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked
Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis
and Yersinia pestis
SO ACS INFECTIOUS DISEASES
LA English
DT Article
DE MEP pathway; antibiotic; phosphonate prodrug; Mycobacterium
tuberculosis; Yersinia pestis
ID 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE; NON-MEVALONATE-PATHWAY;
SUBSTITUTED FOSMIDOMYCIN ANALOGS; ISOPRENOID BIOSYNTHESIS; NONMEVALONATE
PATHWAY; TERPENOID BIOSYNTHESIS; RESISTANCE; ANTIMALARIAL;
ANTIBACTERIAL; DISCOVERY
AB Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar ICso values. In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. The most potent compounds have Mtb MIC values of 3-12 pg/mL. Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development.
C1 [Jose, Geraldine San; Jackson, Emily R.; Wang, Xu; Brothers, R. Carl; Edelstein, Emma K.; Dowd, Cynthia S.] George Washington Univ, Dept Chem, 800 22nd St NW, Washington, DC 20052 USA.
[Haymond, Amanda; Johny, Chinchu; Couch, Robin D.] George Mason Univ, Dept Chem & Biochem, 10900 Univ Blvd, Manassas, VA 20110 USA.
[Edwards, Rachel L.; Odom, Audrey R.] Washington Univ, Sch Med, Dept Pediat, 660 S Euclid Ave, St Louis, MO 63110 USA.
[Boshoff, Helena I.] NIAID, TB Res Sect, LCID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Dowd, CS (reprint author), George Washington Univ, Dept Chem, 800 22nd St NW, Washington, DC 20052 USA.
EM cdowd@gwu.edu
OI Edwards, Rachel/0000-0002-7928-7440
FU George Washington University's Department of Chemistry; University
Facilitating Fund, NIH [AI086453, AI103280, AI123808]; George Mason
University's Department of Chemistry and Biochemistry, the U.S. Army
Medical Research and Materiel Command [W23RYX1291N601]; Division of
Intramural Research, NIAID, NIH
FX We gratefully acknowledge technical assistance from Teresa Hawley (GWU
Medical Center), Joshua Wilhide (UMBC), and Phil Mortimer OHU) for
assistance with HRMS analysis. Financial support was provided by George
Washington University's Department of Chemistry and University
Facilitating Fund, NIH (Grant AI086453 to C.S.D. and Grants AI103280 and
AI123808 to A.R.O.), George Mason University's Department of Chemistry
and Biochemistry, the U.S. Army Medical Research and Materiel Command
(Grant W23RYX1291N601 to R.D.C.), and the Division of Intramural
Research, NIAID, NIH.
NR 47
TC 0
Z9 0
U1 9
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-8227
J9 ACS INFECT DIS
JI ACS Infect. Dis.
PD DEC
PY 2016
VL 2
IS 12
BP 35
EP 47
DI 10.1021/acsinfecdis.6b00125
PG 13
WC Chemistry, Medicinal; Infectious Diseases
SC Pharmacology & Pharmacy; Infectious Diseases
GA EE6QY
UT WOS:000389738500004
ER
PT J
AU Evans, JC
Trujillo, C
Wang, Z
Eoh, H
Ehrt, S
Schnappinger, D
Boshoff, HIM
Rhee, KY
Barry, CE
Mizrahi, V
AF Evans, Joanna C.
Trujillo, Carolina
Wang, Zhe
Eoh, Hyungjin
Ehrt, Sabine
Schnappinger, Dirk
Boshoff, Helena I. M.
Rhee, Kyu Y.
Barry, Clifton E., III
Mizrahi, Valerie
TI Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway
of Mycobacterium tuberculosis
SO ACS INFECTIOUS DISEASES
LA English
DT Article
DE tuberculosis; drug discovery; CoA; pantetheine; CoaBC
ID ACYL CARRIER PROTEIN; MECHANISTICALLY DIVERSE INHIBITORS; MYCOLIC ACID
BIOSYNTHESIS; PANTOTHENATE KINASE; ESCHERICHIA-COLI; PHOSPHOPANTETHEINE
ADENYLYLTRANSFERASE; PYRAZINAMIDE RESISTANCE; ASPARTATE DECARBOXYLASE;
REACTION INTERMEDIATE; GENE-EXPRESSION
AB Mycobacterium tuberculosis relies on its own ability to biosynthesize coenzyme A to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the essential pantothenate and coenzyme A biosynthesis pathways have attracted attention as targets for tuberculosis drug development. To identify the optimal step for coenzyme A pathway disruption in M. tuberculosis, we constructed and characterized a panel of conditional knockdown mutants in coenzyme A pathway genes. Here, we report that silencing of coaBC was bactericidal in vitro, whereas silencing of panB, panC, or coaE was bacteriostatic over the same time course. Silencing of coaBC was likewise bactericidal in vivo, whether initiated at infection or during either the acute or chronic stages of infection, confirming that CoaBC is required for M. tuberculosis to grow and persist in mice and arguing against significant CoaBC bypass via transport and assimilation of host-derived pantetheine in this animal model. These results provide convincing genetic validation of CoaBC as a new bactericidal drug target.
C1 [Evans, Joanna C.; Barry, Clifton E., III; Mizrahi, Valerie] Univ Cape Town, Fac Hlth Sci, MRC NHLS UCT Mol Mycobacteriol Res Unit, Anzio Rd, ZA-7925 Observatory, South Africa.
[Evans, Joanna C.; Barry, Clifton E., III; Mizrahi, Valerie] Univ Cape Town, Fac Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, Inst Infect Dis & Mol Med, Anzio Rd, ZA-7925 Observatory, South Africa.
[Evans, Joanna C.; Barry, Clifton E., III; Mizrahi, Valerie] Univ Cape Town, Fac Hlth Sci, Dept Pathol, Anzio Rd, ZA-7925 Observatory, South Africa.
[Trujillo, Carolina; Wang, Zhe; Eoh, Hyungjin; Ehrt, Sabine; Schnappinger, Dirk; Rhee, Kyu Y.] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA.
[Wang, Zhe; Eoh, Hyungjin; Rhee, Kyu Y.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY 10065 USA.
[Boshoff, Helena I. M.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Eoh, Hyungjin] Univ Southern Calif, Zilkha Neurogenet Inst, Keck Sch Med, Dept Mol Microbiol & Immunol, 1501 San Pablo St, Los Angeles, CA 90033 USA.
RP Mizrahi, V (reprint author), Univ Cape Town, Fac Hlth Sci, MRC NHLS UCT Mol Mycobacteriol Res Unit, Anzio Rd, ZA-7925 Observatory, South Africa.; Mizrahi, V (reprint author), Univ Cape Town, Fac Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, Inst Infect Dis & Mol Med, Anzio Rd, ZA-7925 Observatory, South Africa.; Mizrahi, V (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Pathol, Anzio Rd, ZA-7925 Observatory, South Africa.
EM valerie.mizrahi@uct.ac.za
FU TB Drug Accelerator program of the Bill and Melinda Gates Foundation;
South African Medical Research Council; National Research Foundation of
South Africa; International Research Scholar's grant from the HHMI;
Intramural Research Program of NIAID
FX This work was supported by grants from the TB Drug Accelerator program
of the Bill and Melinda Gates Foundation (to C.E.B. III, K.Y.R, D.S.,
and V.M.); the South African Medical Research Council; the National
Research Foundation of South Africa, and an International Research
Scholar's grant from the HHMI (to V.M.); and, in part, by the Intramural
Research Program of NIAID (H.I.M.B. and C.E.B. HI). We thank Erick
Strauss for valuable discussions and for kindly providing P-PantSH,
Jonathan Blackburn and Nelson Soares for advice and assistance with mass
spectrometry, and Digby Warner for helpful discussions and for
critically reviewing the manuscript.
NR 69
TC 1
Z9 1
U1 4
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-8227
J9 ACS INFECT DIS
JI ACS Infect. Dis.
PD DEC
PY 2016
VL 2
IS 12
BP 70
EP 80
DI 10.1021/acsinfecdis.6b00150
PG 11
WC Chemistry, Medicinal; Infectious Diseases
SC Pharmacology & Pharmacy; Infectious Diseases
GA EE6QY
UT WOS:000389738500007
PM 27676316
ER
PT J
AU Pilotto, A
Gallina, P
Panza, F
Copetti, M
Cella, A
Cruz-Jentoft, A
Daragjati, J
Ferrucci, L
Maggi, S
Mattace-Raso, F
Paccalin, M
Polidori, MC
Topinkova, E
Trifiro, G
Welmer, AK
Strandberg, T
Marchionni, N
AF Pilotto, Alberto
Gallina, Pietro
Panza, Francesco
Copetti, Massimiliano
Cella, Alberto
Cruz-Jentoft, Alfonso
Daragjati, Julia
Ferrucci, Luigi
Maggi, Stefania
Mattace-Raso, Francesco
Paccalin, Marc
Polidori, Maria Cristina
Topinkova, Eva
Trifiro, Gianluca
Welmer, Anna-Karin
Strandberg, Timo
Marchionni, Niccolo
CA MPI AGE Project Investigators
TI Relation of Statin Use and Mortality in Community-Dwelling Frail Older
Patients With Coronary Artery Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID MULTIDIMENSIONAL PROGNOSTIC INDEX; ACUTE MYOCARDIAL-INFARCTION; ADULTS;
VALIDATION; GUIDELINES; THERAPY; CARE; MEN
AB Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged >= 65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1,-2, and-3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and Z85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Pilotto, Alberto; Cella, Alberto] Natl Relevance & High Specializat Hosp, EO Galliera Hosp, Dept Geriatr Care OrthoGeriatr & Rehabil, Frailty Area, Genoa, Italy.
[Pilotto, Alberto; Daragjati, Julia] S Antonio Hosp, Azienda ULSS Padova 16, Geriatr Unit, Padua, Italy.
[Gallina, Pietro] Azienda ULSS 16, Hlth Directorate, Padua, Italy.
[Panza, Francesco] Univ Ban Aldo Moro, Dept Basic Med Neurosci & Sense Organs, Neurodegenerat Dis Unit, Bari, Italy.
[Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Unit Biostat, Foggia, Italy.
[Cruz-Jentoft, Alfonso] Hosp Univ Ramon & Cajal, Madrid, Spain.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Maggi, Stefania] CNR, Neurosci Sect, Padua, Italy.
[Mattace-Raso, Francesco; Trifiro, Gianluca] Erasmus MC, Rotterdam, Netherlands.
[Paccalin, Marc] Univ Hosp Poitiers, Poitiers, France.
[Polidori, Maria Cristina] Univ Cologne, Dept Med 2, Unit Aging Clin Res, Cologne, Germany.
[Topinkova, Eva] Univ Charles I, Prague, Czech Republic.
[Trifiro, Gianluca] Univ Messina, Messina, Italy.
[Welmer, Anna-Karin] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden.
[Strandberg, Timo] Univ Helsinki, Dept Med, Geriatr Clin, Helsinki, Finland.
[Strandberg, Timo] Univ Oulu, Inst Hlth Sci Geriatr, Oulu, Finland.
[Strandberg, Timo] Oulu Univ Hosp, Oulu, Finland.
[Marchionni, Niccolo] Univ Florence, Div Geriatr Cardiol & Med, Florence, Italy.
RP Panza, F (reprint author), Univ Ban Aldo Moro, Dept Basic Med Neurosci & Sense Organs, Neurodegenerat Dis Unit, Bari, Italy.
EM geriat.dot@geriatria.uniba.it
OI strandberg, timo/0000-0001-6299-925X
FU MPI_AGE European project - Consumers, Health, Agriculture and Food
Executive Agency (CHAFEA) in the frame of the European Innovation
Partnership on Active and Healthy Aging Second Health Program
FX This work was supported from the MPI_AGE European project co-funded by
the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA) in
the frame of the European Innovation Partnership on Active and Healthy
Aging Second Health Program 2008-2013.
NR 26
TC 1
Z9 1
U1 4
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD DEC 1
PY 2016
VL 118
IS 11
BP 1624
EP 1630
DI 10.1016/j.amjcard.2016.08.042
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EE5YS
UT WOS:000389686100003
PM 27670793
ER
PT J
AU Borgogna, JL
Roberts, D
Rath, JM
Glover, ED
Ravel, J
Shardell, M
Yeoman, CJ
Brotman, RM
Nelson, TM
AF Borgogna, Joanna-Lynn
Roberts, Dave
Rath, Jessica M.
Glover, Elbert D.
Ravel, Jacques
Shardell, Michelle
Yeoman, Carl J.
Brotman, Rebecca M.
Nelson, Tiffanie M.
TI Cigarette smoking is associated with an altered metabolomic profile of
the vaginal environment
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the
Infectious-Diseases-Society-for-Obstetrics-and-Gynecology (ISDOG)
CY AUG 11-13, 2016
CL Annapolis, MD
SP Infect Dis Soc Obstet & Gynecol
C1 [Borgogna, Joanna-Lynn; Roberts, Dave; Yeoman, Carl J.; Nelson, Tiffanie M.] Montana State Univ, Bozeman, MT 59717 USA.
[Rath, Jessica M.; Glover, Elbert D.; Ravel, Jacques; Brotman, Rebecca M.] Univ Maryland, Baltimore, MD 21201 USA.
[Shardell, Michelle] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD DEC
PY 2016
VL 215
IS 6
MA 3
BP 815
EP 815
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE3RM
UT WOS:000389514400055
ER
PT J
AU Guterman, J
Pawlitz, MD
Pei, B
Goyert, J
Puder, KS
Gonik, B
Chen, K
AF Guterman, J.
Pawlitz, M. D.
Pei, B.
Goyert, J.
Puder, K. S.
Gonik, B.
Chen, K.
TI Maternal immunoglobulin D induced by antepartum vaccination undergoes
placental transfer to the fetus
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the
Infectious-Diseases-Society-for-Obstetrics-and-Gynecology (ISDOG)
CY AUG 11-13, 2016
CL Annapolis, MD
SP Infect Dis Soc Obstet & Gynecol
C1 [Guterman, J.; Pawlitz, M. D.; Pei, B.; Goyert, J.; Puder, K. S.; Gonik, B.; Chen, K.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Pawlitz, M. D.; Pei, B.; Goyert, J.; Chen, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48201 USA.
[Pawlitz, M. D.; Chen, K.] Wayne State Univ, Grad Program Immunol & Microbiol, Dept Immunol & Microbiol, Detroit, MI 48201 USA.
[Chen, K.] Wayne State Univ, Dept Oncol, Detroit, MI 48201 USA.
[Chen, K.] Barbara Ann Karmanos Canc Ctr, Tumor Biol & Microenvironm Program, Detroit, MI 48201 USA.
[Chen, K.] NIAID, Mucosal Immunol Studies Team, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD DEC
PY 2016
VL 215
IS 6
MA 24
BP 825
EP 825
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE3RM
UT WOS:000389514400076
ER
PT J
AU Bressler, LH
Bernardi, LA
De Chavez, PJD
Baird, DD
Carnethon, MR
Marsh, EE
AF Bressler, Leah Hawkins
Bernardi, Lia A.
De Chavez, Peter John D.
Baird, Donna D.
Carnethon, Mercedes R.
Marsh, Erica E.
TI Alcohol, cigarette smoking, and ovarian reserve in reproductive-age
African-American women
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE alcohol; anti-Mullerian hormone; cigarette smoking; ovarian reserve;
second-hand smoke
ID ANTI-MULLERIAN HORMONE; IN-VITRO FERTILIZATION; ANTRAL FOLLICLE COUNT;
ANTIMULLERIAN HORMONE; LIFE-STYLE; ENVIRONMENTAL-FACTORS; RISK-FACTORS;
CONSUMPTION; MENOPAUSE; FECUNDABILITY
AB BACKGROUND: Although alcohol consumption and cigarette smoking are common behaviors in reproductive-age women, little is known about the impact of consumption patterns on ovarian reserve. Even less is known about the effects of smoking and alcohol use in reproductive-age African-American women.
OBJECTIVE: The objective of the study was to examine the impact of the patterns of alcohol intake and cigarette smoking on anti-Mullerian hormone levels as a marker of ovarian reserve in African-American women.
STUDY DESIGN: This was a cross-sectional analysis from the baseline clinical visit and data collection of the Study of Environment, Lifestyle, and Fibroids performed by the National Institute of Environmental Health Sciences. A total of 1654 volunteers, aged 23-34 years, recruited from the Detroit, Michigan community completed questionnaires on alcohol intake and cigarette smoking and provided serum for anti-Mullerian hormone measurement. Multivariable linear and logistic regressions were used as appropriate to estimate the effect of a range of exposure patterns on anti-Mullerian hormone levels while adjusting for potential confounders including age, body mass index, and hormonal contraception.
RESULTS: Most participants were alcohol drinkers (74%). Of those, the majority (74%) engaged in binge drinking at least once in the last year. Women who reported binge drinking twice weekly or more had 26% lower anti-Mullerian hormone levels compared with current drinkers who never binged (95% confidence interval, -44, -2, P < .04). Other alcohol consumption patterns (both past and current) were unrelated to anti-Mullerian hormone. The minority of participants currently (19%) or formerly (7%) smoked, and only 4% of current smokers used a pack a day or more. Neither smoking status nor second-hand smoke exposure in utero, childhood, or adulthood was associated with anti-Mullerian hormone levels.
CONCLUSION: Results suggest that current, frequent binge drinking may have an adverse impact on ovarian reserve. Other drinking and smoking exposures were not associated with anti-Mullerian hormone in this cohort of healthy, young, African-American women. A longitudinal study of how these common lifestyle behaviors have an impact on the variability in age-adjusted anti-Mullerian hormone levels is merited.
C1 [Bressler, Leah Hawkins; Bernardi, Lia A.; Marsh, Erica E.] Northwestern Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA.
[De Chavez, Peter John D.; Carnethon, Mercedes R.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Baird, Donna D.] NIEHS, Dept Epidemiol, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Marsh, EE (reprint author), Northwestern Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA.
EM erica-marsh@northwestern.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institutes of Health [R21HD077479-01, K12HD050121]; Robert Wood
Johnson Foundation; Friends of Prentice; Evergreen Invitational; Woman's
Board; Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences; American Recovery
and Reinvestment Act
FX This study was supported by National Institutes of Health grant
R21HD077479-01; National Institutes of Health Grant
K12HD050121-Northwestern University Women's Reproductive Health scholar
award; Harold Amos Medical Faculty Development Award from the Robert
Wood Johnson Foundation, Friends of Prentice, Evergreen Invitational,
Woman's Board. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences, and in part by funds
allocated for health research by the American Recovery and Reinvestment
Act.
NR 49
TC 0
Z9 0
U1 15
U2 15
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD DEC
PY 2016
VL 215
IS 6
AR 758.e1-9
DI 10.1016/j.ajog.2016.07.012
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE3RM
UT WOS:000389514400018
ER
PT J
AU Knickelbein, JE
Tucker, WR
Bhatt, N
Armbrust, K
Valent, D
Obiyor, D
Nussenblatt, RB
Sen, HN
AF Knickelbein, Jared E.
Tucker, William R.
Bhatt, Nirali
Armbrust, Karen
Valent, David
Obiyor, Dominic
Nussenblatt, Robert B.
Sen, H. Nida
TI Gevokizumab in the Treatment of Autoimmune Non-necrotizing Anterior
Scleritis: Results of a Phase I/II Clinical Trial
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; BEHCETS-DISEASE; RITUXIMAB; EFFICACY; THERAPY
AB PURPOSE: To evaluate the safety and potential efficacy of gevokizumab, an anti-interleukin 1 beta (IL-1 beta) monoclonal antibody, in the treatment of active, noninfectious, non-necrotizing anterior scleritis.
DESIGN: Phase 1/2, open label, nonrandomized, prospective, single-arm pilot trial.
METHODS: Eight patients with active, noninfectious, non-necrotizing anterior scleritis with a scleral inflammatory grade of +1 to +3 in at least 1 eye were enrolled. In 1 patient both eyes were enrolled, for a total of 9 eyes (4 eyes with +1, 1 eye with +2, and 4 eyes with +3). Patients received 1 subcutaneous injection of 60 mg gevokizumab at baseline and then every 4 weeks for 12 weeks. Complete physical and ocular examinations were performed at each visit. The primary outcome was at least a 2-step reduction or reduction to grade 0 in scleral inflammation on a 0 to +4 scale according to a standardized photographic scleritis grading system by 16 weeks in the study eye compared to baseline. Secondary outcomes included changes in visual acuity, intraocular pressure, and trends in scleral grading. Participants who met the primary outcome were eligible to continue in the study for up to 52 weeks and received additional gevokizumab injections every 4 weeks until week 36, followed by 2 safety visits at weeks 40 and 52.
RESULTS: Seven eyes from 7 patients met the primary outcome within a median time of 2 weeks following the first gevokizumab injection. No definitive changes in visual acuity or intraocular pressure were identified. There were no serious adverse events related to the study drug. A total of 43 adverse effects were reported, with 93% described as mild, 95% as nonocular, and only 14% deemed possibly caused by the investigational treatment.
CONCLUSIONS: The results of this small study suggest that blockage of IL-1 beta using gevokizumab may be beneficial in treating active, noninfectious anterior scleritis and that gevokizumab is well tolerated. Larger randomized trials are warranted to assess the true efficacy of gevokizumab in the treatment of non-necrotizing anterior scleritis. Published by Elsevier Inc.
C1 [Knickelbein, Jared E.; Tucker, William R.; Bhatt, Nirali; Armbrust, Karen; Valent, David; Obiyor, Dominic; Nussenblatt, Robert B.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU INTRAMURAL RESEARCH PROGRAM OF THE NIH, NEI
FX THIS RESEARCH WAS SUPPORTED BY THE INTRAMURAL RESEARCH PROGRAM OF THE
NIH, NEI. THE STUDY medication was provided by XOMA Corporation
(Berkeley, California, USA).
NR 21
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2016
VL 172
BP 104
EP 110
DI 10.1016/j.ajo.2016.09.017
PG 7
WC Ophthalmology
SC Ophthalmology
GA EE5AF
UT WOS:000389616400015
PM 27663070
ER
PT J
AU Jung, HJ
Kwon, TH
AF Jung, Hyun Jun
Kwon, Tae-Hwan
TI Molecular mechanisms regulating aquaporin-2 in kidney collecting duct
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Review
DE arginine vasopressin; aquaporin-2; body water balance; intracellular
trafficking
ID NEPHROGENIC DIABETES-INSIPIDUS; RENAL PRINCIPAL CELLS; WATER CHANNEL
AQUAPORIN-2; PROTEIN-KINASE-A; VASOPRESSIN-MEDIATED TRANSLOCATION;
BLADDER EPITHELIAL-CELLS; THICK ASCENDING LIMB; LC-MS/MS ANALYSIS;
RAT-KIDNEY; APICAL MEMBRANE
AB The kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone that induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of the Aqp2 gene to increase AQP2 protein abundance. The signaling pathways, including AQP2 phosphorylation, RhoA phosphorylation, intracellular calcium mobilization, and actin depolymerization, play a key role in the translocation of AQP2. This review summarizes recent data demonstrating the regulation of AQP2 as the underlying molecular mechanism for the homeostasis of water balance in the body.
C1 [Jung, Hyun Jun] NHLBI, Epithelial Syst Biol Lab, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kwon, Tae-Hwan] Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Dongin Dong 101, Taegu 41944, South Korea.
RP Kwon, TH (reprint author), Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Dongin Dong 101, Taegu 41944, South Korea.
EM thkwon@knu.ac.kr
FU National Research Foundation of Korea (NRF) - Ministry of Science, ICT,
and Future Planning, Korea [2014R1A5A2009242, 2016R1A2B4009365]
FX This study was supported by the National Research Foundation of Korea
(NRF) funded by the Ministry of Science, ICT, and Future Planning, Korea
(2014R1A5A2009242 and 2016R1A2B4009365).
NR 161
TC 0
Z9 0
U1 14
U2 14
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD DEC 1
PY 2016
VL 311
IS 6
BP F1318
EP F1328
DI 10.1152/ajprenal.00485.2016
PG 11
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA EE5KW
UT WOS:000389647100026
PM 27760771
ER
PT J
AU Brown, J
Grudzen, C
Kyriacou, DN
Obermeyer, Z
Quest, T
Rivera, D
Stone, S
Wright, J
Shelburne, N
AF Brown, Jeremy
Grudzen, Corita
Kyriacou, Demetrios N.
Obermeyer, Ziad
Quest, Tammie
Rivera, Donna
Stone, Susan
Wright, Jason
Shelburne, Nonniekaye
TI The Emergency Care of Patients With Cancer: Setting the Research Agenda
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID ELEVATION MYOCARDIAL-INFARCTION; CLINICAL-PRACTICE GUIDELINE; RANDOMIZED
CONTROLLED-TRIAL; TO-BALLOON TIME; FEBRILE NEUTROPENIA; PALLIATIVE CARE;
ACUTE-LEUKEMIA; MANAGEMENT; FEVER; ONCOLOGY
AB To identify research priorities and appropriate resources and to establish the infrastructure required to address the emergency care of patients with cancer, the National Institutes of Health's National Cancer Institute and the Office of Emergency Care Research sponsored a one-day workshop, "Cancer and Emergency Medicine: Setting the Research Agenda," in March 2015 in Bethesda, MD. Participants included leading researchers and clinicians in the fields of oncology, emergency medicine, and palliative care, and representatives from the National Institutes of Health. Attendees were charged with identifying research opportunities and priorities to advance the understanding of the emergency care of cancer patients. Recommendations were made in 4 areas: the collection of epidemioiogic data, care of the patient with febrile neutropenia, acute events such as dyspnea, and palliative care in the emergency department setting.
C1 [Brown, Jeremy] NYU, Sch Med, Natl Inst Gen Med Sci, Off Emergency Care Res, New York, NY USA.
[Grudzen, Corita] NYU, Sch Med, Dept Emergency Med, New York, NY USA.
[Kyriacou, Demetrios N.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA.
[Obermeyer, Ziad] Harvard Med Sch, Dept Emergency Med & Hlth Care Policy, Boston, MA USA.
[Quest, Tammie] Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA.
[Quest, Tammie] Emory Univ, Div Geriatr & Gerontol, Atlanta, GA 30322 USA.
[Rivera, Donna; Shelburne, Nonniekaye] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Stone, Susan] Cedars Sinai Med Ctr, Palliat Care Serv, Los Angeles, CA 90048 USA.
[Wright, Jason] Columbia Univ, Coll Phys & Surg, New York, NY USA.
RP Brown, J (reprint author), NYU, Sch Med, Natl Inst Gen Med Sci, Off Emergency Care Res, New York, NY USA.
EM jeremy.brown@nih.gov
OI Grudzen, Corita/0000-0003-3039-8497
NR 40
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD DEC
PY 2016
VL 68
IS 6
BP 706
EP 711
DI 10.1016/j.annemergmed.2016.01.021
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA ED9BJ
UT WOS:000389164800011
ER
PT J
AU Takeuchi, M
Ombrello, MJ
Kirino, Y
Erer, B
Tugal-Tutkun, I
Seyahi, E
Ozyazgan, Y
Watts, NR
Gul, A
Kastner, DL
Remmers, EF
AF Takeuchi, Masaki
Ombrello, Michael J.
Kirino, Yohei
Erer, Burak
Tugal-Tutkun, Ilknur
Seyahi, Emire
Ozyazgan, Yilmaz
Watts, Norman R.
Gul, Ahmet
Kastner, Daniel L.
Remmers, Elaine F.
TI A single endoplasmic reticulum aminopeptidase-1 protein allotype is a
strong risk factor for Behcet's disease in HLA-B(star)51 carriers
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ANKYLOSING-SPONDYLITIS; SUSCEPTIBILITY LOCI;
ERAP1; INDIVIDUALS; HAPLOTYPE; HLA-B27
AB Introduction Endoplasmic reticulum aminopeptidase-1 (ERAP1) protein is highly polymorphic with numerous missense amino acid variants. We sought to determine the naturally occurring ERAP1 protein allotypes and their contribution to Behcet's disease.
Methods Genotypes of all reported missense ERAP1 gene variants with 1000 Genomes Project EUR superpopulation frequency >1% were determined in 1900 Behcet's disease cases and 1779 controls from Turkey. ERAP1 protein allotypes and their contributions to Behcet's disease risk were determined by haplotype identification and disease association analyses.
Results One ERAP1 protein allotype with five nonancestral amino acids was recessively associated with disease (p=3.13x10(-6), OR 2.55, 95% CI 1.70 to 3.82). The ERAP1 association was absent in individuals who lacked HLA-B(star)51. Individuals who carry HLA-B(star)51 and who are also homozygous for the haplotype had an increased disease odds compared with those with neither risk factor (p=4.80x10(-20), OR 10.96, 95% CI 5.91 to 20.32).
Discussion The Behcet's disease-associated ERAP1 protein allotype was previously shown to have poor peptide trimming activity. Combined with its requirement for HLA-B(star)51, these data suggest that a hypoactive ERAP1 allotype contributes to Behcet's disease risk by altering the peptides available for binding to HLA-B(star)51.
C1 [Takeuchi, Masaki; Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, 10 Ctr Dr,MSC 1849,Bldg 10 CRC East,Room B2-5235, Bethesda, MD 20892 USA.
[Takeuchi, Masaki] Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Yokohama, Kanagawa, Japan.
[Ombrello, Michael J.] NIAMSD, Translat Genet & Genom Unit, Bethesda, MD 20892 USA.
[Kirino, Yohei] Yokohama City Univ, Grad Sch Med, Dept Stem Cell & Immune Regulat, Yokohama, Kanagawa 232, Japan.
[Erer, Burak; Tugal-Tutkun, Ilknur; Gul, Ahmet] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Seyahi, Emire; Ozyazgan, Yilmaz] Istanbul Univ, Cerrahpasa Fac Med, Istanbul, Turkey.
[Watts, Norman R.] NIAMSD, Prot Express Lab, Bethesda, MD 20892 USA.
RP Remmers, EF (reprint author), NHGRI, Inflammatory Dis Sect, 10 Ctr Dr,MSC 1849,Bldg 10 CRC East,Room B2-5235, Bethesda, MD 20892 USA.
EM remmerse@mail.nih.gov
RI 桐野, 洋平/B-3701-2009
OI 桐野, 洋平/0000-0002-9488-661X
FU National Human Genome Research Institute; National Institute of
Arthritis and Musculoskeletal and Skin Diseases; Japan Society for the
Promotion of Science [26713036]; Naito Memorial Foundation; Kanae
Foundation for the Promotion of Medical Science; Yokohama Foundation for
Advancement of Medical Science
FX This study was supported by the Intramural Research Programs of the
National Human Genome Research Institute and the National Institute of
Arthritis and Musculoskeletal and Skin Diseases. Dr Kirino is supported
by grants from Japan Society for the Promotion of Science Grant-in-Aid
for Scientific Research (Grant No. 26713036), the Naito Memorial
Foundation, the Kanae Foundation for the Promotion of Medical Science
and Yokohama Foundation for Advancement of Medical Science.
NR 17
TC 1
Z9 1
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD DEC
PY 2016
VL 75
IS 12
BP 2208
EP 2211
DI 10.1136/annrheumdis-2015-209059
PG 4
WC Rheumatology
SC Rheumatology
GA EE1JZ
UT WOS:000389338900032
PM 27217550
ER
PT J
AU Duffy, VB
Rawal, S
Park, J
Brand, MH
Sharafi, M
Bolling, BW
AF Duffy, Valerie B.
Rawal, Shristi
Park, Jeeha
Brand, Mark H.
Sharafi, Mastaneh
Bolling, Bradley W.
TI Characterizing and improving the sensory and hedonic responses to
polyphenol-rich aronia berry juice
SO APPETITE
LA English
DT Article
DE Food preferences; Beverages/*analysis; Psychophysics; Fruit; Surveys and
questionnaires; Polyphenols
ID REPEATED EXPOSURE; FOOD-CONSUMPTION; BITTER TASTE;
CARDIOVASCULAR-DISEASE; CHEMICAL-COMPOSITION; DIETARY QUALITY; LIKING;
CHILDREN; ADULTS; PREFERENCE
AB Interest in nutrient-rich berry juices is growing, but their high polyphenol levels render them sensorily unappealing. Fifty adults, who were assessed for sensory phenotype and dietary behaviors, provided sensory and palatability ratings of juices from 'Viking' aronia berries for each of seven harvest weeks. By peak harvest, juice preference increased two-fold, averaging neither like/dislike. This hedonic shift was associated with: increases in juice sugars paralleling increases in perceived sweetness (maximum = weak); reductions in percent acidity paralleling reductions in sourness (minimum = moderate), astringency (minimum = to just above weak) and bitterness (minimum = just below weak). About 25% of adults'liked the aronia juice, including adults who also liked an aqueous citric acid solution (average rating = moderately sour) or those who reported adventurous eating behaviors. Bitter taste phenotype, measured by propylthiouracil or quinine bitterness, failed to explain significant variation in juice sensation or preference. We also collected sensory and preference ratings from juice collected at peak harvest blended with sugar and/or sweet olfactory flavoring (10 ppm ethyl butyrate). Increasing juice sweetness by adding 5% sucrose decreased sourness and improved preference from weak dislike to weak like. Adding sweet olfactory flavoring decreased juice sourness without changing preference. Adding sweet flavoring and 3% sucrose resulted in reduction of sourness and improvements in preference ratings comparable to 5% added sucrose. Neither added sugar nor flavoring blocked juice astringency. In summary, these findings suggest that aronia juice, even from berries picked at peak harvest, appealed to only a few adults (sour likers or adventurous eaters). Although enhanced sweetness, with added sugar and sweet olfactory flavoring, improved aronia juice preference, broader sensory approaches are required to blunt astringency for greater consumer appeal. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Duffy, Valerie B.; Rawal, Shristi; Park, Jeeha; Sharafi, Mastaneh] Univ Connecticut, Dept Allied Hlth Sci, 358 Mansfield Rd, Storrs, CT 06269 USA.
[Rawal, Shristi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Brand, Mark H.] Univ Connecticut, Dept Plant Sci & Landscape Architecture, Storrs, CT USA.
[Bolling, Bradley W.] Univ Wisconsin Madison, Dept Food Sci, Madison, WI USA.
RP Duffy, VB (reprint author), Univ Connecticut, Dept Allied Hlth Sci, 358 Mansfield Rd, Storrs, CT 06269 USA.
EM valerie.duffy@uconn.edu
OI Bolling, Bradley/0000-0002-4222-2467
FU U.S. Department of Agriculture, Hatch Formula Funds [2015-31200-06009,
1001056]; USDA Northeast Sustainable Agriculture Research Education;
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institute of Food and Agriculture
FX Supported by the National Institute of Food and Agriculture, U.S.
Department of Agriculture, Hatch Formula Funds, under award number
2015-31200-06009, accession number 1001056 and the USDA Northeast
Sustainable Agriculture Research & Education. Also, Dr. S. Rawal was
partially supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD).
NR 71
TC 0
Z9 0
U1 6
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
EI 1095-8304
J9 APPETITE
JI Appetite
PD DEC 1
PY 2016
VL 107
BP 116
EP 125
DI 10.1016/j.appet.2016.07.026
PG 10
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA EE2BP
UT WOS:000389389000014
PM 27457970
ER
PT J
AU Jin, XT
Sviridov, D
Liu, Y
Vaisman, B
Addadi, L
Remaley, AT
Kruth, HS
AF Jin, Xueting
Sviridov, Denis
Liu, Ying
Vaisman, Boris
Addadi, Lia
Remaley, Alan T.
Kruth, Howard S.
TI ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I
(Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of
Extracellular Cholesterol Microdomains Deposited by Macrophages
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE apolipoprotein A-I; atherosclerosis; cholesterol; extracellular matrix;
macrophages
ID HIGH-DENSITY-LIPOPROTEIN; CELLULAR LIPID EFFLUX; SMOOTH-MUSCLE-CELLS;
PLASMA-MEMBRANE MICROSOLUBILIZATION; O-NEGATIVE PARTICLES;
ATHEROSCLEROTIC LESIONS; ANTIBODY RECOGNITION; PHOSPHOLIPID EFFLUX;
HUMAN-COMPLEMENT; MODEL MEMBRANES
AB Objective-We examined the function of ABCA1 (ATP-binding cassette transporter A1) in ApoA-I (apolipoprotein A-I) mobilization of cholesterol microdomains deposited into the extracellular matrix by cholesterol-enriched macrophages. We have also determined whether an ApoA-I mimetic peptide without and with complexing to sphingomyelin can mobilize macrophage-deposited cholesterol microdomains.
Approach and Results-Extracellular cholesterol microdomains deposited by cholesterol-enriched macrophages were detected with a monoclonal antibody, 58B1. ApoA-I and an ApoA-I mimetic peptide 5A mobilized cholesterol microdomains deposited by ABCA1(+/+) macrophages but not by ABCA1(-/-) macrophages. In contrast, ApoA-I mimetic peptide 5A complexed with sphingomyelin could mobilize cholesterol microdomains deposited by ABCA1(-/-) macrophages.
Conclusions-Our findings show that a unique pool of extracellular cholesterol microdomains deposited by macrophages can be mobilized by both ApoA-I and an ApoA-I mimetic peptide but that mobilization depends on macrophage ABCA1. It is known that ABCA1 complexes ApoA-I and ApoA-I mimetic peptide with phospholipid, a cholesterol-solubilizing agent, explaining the requirement for ABCA1 in extracellular cholesterol microdomain mobilization. Importantly, ApoA-I mimetic peptide already complexed with phospholipid can mobilize macrophage-deposited extracellular cholesterol microdomains even in the absence of ABCA1.
C1 [Jin, Xueting; Liu, Ying; Kruth, Howard S.] NHLBI, Expt Atherosclerosis Sect, NIH, Bldg 10,Room 5N-113,10 Ctr Dr MSC 1422, Bethesda, MD 20892 USA.
[Sviridov, Denis; Vaisman, Boris; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Addadi, Lia] Weizmann Inst Sci, Dept Biol Struct, Rehovot, Israel.
RP Kruth, HS (reprint author), NHLBI, Expt Atherosclerosis Sect, NIH, Bldg 10,Room 5N-113,10 Ctr Dr MSC 1422, Bethesda, MD 20892 USA.
EM kruthh@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of
Health; US-Israel Binational Science Foundation [2013045]
FX This work was supported by the Intramural Research Program, National
Heart, Lung, and Blood Institute, National Institutes of Health, and by
the US-Israel Binational Science Foundation (grant 2013045).
NR 63
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD DEC
PY 2016
VL 36
IS 12
BP 2283
EP 2291
DI 10.1161/ATVBAHA.116.308334
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA EE1KO
UT WOS:000389340500005
PM 27758769
ER
PT J
AU Breton-Romero, R
Wang, N
Palmisano, J
Larson, MG
Vasan, RS
Mitchell, GF
Benjamin, EJ
Vita, JA
Hamburg, NM
AF Breton-Romero, Rosa
Wang, Na
Palmisano, Joseph
Larson, Martin G.
Vasan, Ramachandran S.
Mitchell, Gary F.
Benjamin, Emelia J.
Vita, Joseph A.
Hamburg, Naomi M.
TI Cross-Sectional Associations of Flow Reversal, Vascular Function, and
Arterial Stiffness in the Framingham Heart Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE arterial stiffness; endothelium; epidemiology; hyperemia; vascular
function
ID IMPAIR ENDOTHELIAL FUNCTION; LOCAL SHEAR-STRESS; BRACHIAL-ARTERY;
NITRIC-OXIDE; SUPEROXIDE-PRODUCTION; CARDIOVASCULAR RISK; AORTIC
STIFFNESS; RETROGRADE FLOW; IN-VIVO; ATHEROSCLEROSIS
AB Objective-Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined.
Approach and Results-We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47 +/- 13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9 +/- 0.2 versus 5.0 +/- 0.2%; P<0.0001) and reactive hyperemic flow velocity (50 +/- 0.99 versus 57 +/- 0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3 +/- 0.1 versus 8.9 +/- 0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6 +/- 0.1 versus 9.8 +/- 0.1 m/s), and higher forearm vascular resistance (5.32 +/- 0.03 versus 4.66 +/- 0.02 log dyne/s/cm(5); P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal.
Conclusions-In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction.
C1 [Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Hamburg, Naomi M.] Boston Univ, 88 E Newton St C818, Boston, MA 02215 USA.
[Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Boston, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Cardiol, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Prevent Med Sect, Boston, MA 02215 USA.
[Breton-Romero, Rosa; Vasan, Ramachandran S.; Benjamin, Emelia J.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA.
[Wang, Na; Palmisano, Joseph; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Stat, Boston, MA 02215 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
RP Hamburg, NM (reprint author), Boston Univ, 88 E Newton St C818, Boston, MA 02215 USA.
EM nhamburg@bu.edu
FU National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute (NHLBI) [N01-HC25195, HHSN268201500001l]; NIH [R01HL107385,
1R01HL126136-01, 1R01HL60040, HL70100, HL076784, AG028321, HL080124,
2K24-HL4334, HL083781, HL102299]; Donald W. Reynolds Foundation;
American Heart Association [16POST27260178]; Department of Medicine at
Boston University School of Medicine
FX The Framingham Heart Study is funded by National Institutes of Health
(NIH)/National Heart, Lung, and Blood Institute (NHLBI) contract
N01-HC25195 and HHSN268201500001l. The project was supported by NIH
grants R01HL107385, 1R01HL126136-01, 1R01HL60040, HL70100, HL076784,
AG028321, HL080124, 2K24-HL4334, and the Donald W. Reynolds Foundation.
Dr Hamburg is supported by NIH grants HL083781 and HL102299. Dr
Breton-Romero is supported by an American Heart Association Postdoctoral
Fellowship 16POST27260178. Dr Vasan is partly supported by the Evans
Scholar award from the Department of Medicine at Boston University
School of Medicine.
NR 42
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD DEC
PY 2016
VL 36
IS 12
BP 2452
EP 2459
DI 10.1161/ATVBAHA.116.307948
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA EE1KO
UT WOS:000389340500023
PM 27789476
ER
PT J
AU Tchantchaleishvili, V
Phillips, SJ
AF Tchantchaleishvili, Vakhtang
Phillips, Steven J.
TI Update in Artificial Heart Technology: Are We There Yet?
SO ARTIFICIAL ORGANS
LA English
DT Editorial Material
C1 [Tchantchaleishvili, Vakhtang] Mayo Clin, Dept Cardiovasc Surg, Rochester, MN USA.
[Phillips, Steven J.] NIH, US Dept HHS, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Phillips, SJ (reprint author), NIH, US Dept HHS, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM steven_phillips@nlm.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0160-564X
EI 1525-1594
J9 ARTIF ORGANS
JI Artif. Organs
PD DEC
PY 2016
VL 40
IS 12
BP 1099
EP 1100
DI 10.1111/aor.12877
PG 2
WC Engineering, Biomedical; Transplantation
SC Engineering; Transplantation
GA EE3CT
UT WOS:000389465300006
PM 27911029
ER
PT J
AU Nelson, KB
Sartwelle, TP
Rouse, DJ
AF Nelson, Karin B.
Sartwelle, Thomas P.
Rouse, Dwight J.
TI Electronic fetal monitoring, cerebral palsy, and caesarean section:
assumptions versus evidence
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID HEART-RATE; DELIVERY RATE; LITIGATION; MORTALITY; RISK; AUSCULTATION;
HEALTH; TRENDS; TRIALS; INJURY
C1 [Nelson, Karin B.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Sartwelle, Thomas P.] Deans & Lyons, Houston, TX USA.
[Rouse, Dwight J.] Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA.
[Rouse, Dwight J.] Brown Univ, Providence, RI 02912 USA.
RP Nelson, KB (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM nelsonk@ninds.nih.gov
NR 38
TC 1
Z9 1
U1 5
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD DEC 1
PY 2016
VL 355
AR i6405
DI 10.1136/bmj.i6405
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA EE0ZO
UT WOS:000389309800004
PM 27908902
ER
PT J
AU Schindler, CW
Thorndike, EB
Suzuki, M
Rice, KC
Baumann, MH
AF Schindler, Charles W.
Thorndike, Eric B.
Suzuki, Masaki
Rice, Kenner C.
Baumann, Michael H.
TI Pharmacological mechanisms underlying the cardiovascular effects of the
"bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV)
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
ID NEURONAL MONOAMINE UPTAKE; CONSCIOUS RATS; DESIGNER DRUG; CONCISE GUIDE;
COCAINE; TRANSPORTERS; METABOLITES; MEPHEDRONE; MDMA; STIMULATION
AB Background and Purpose3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here, we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats.
Experimental ApproachMale Sprague-Dawley rats had telemetry transmitters surgically implanted for the measurement of BP and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles. Following drug treatment, cardiovascular parameters were monitored for 3h sessions.
Key ResultsRacemic MDPV (0.3-3.0mgkg(-1)) increased BP and HR in a dose-dependent manner. The S(+) enantiomer (0.3-3.0mgkg(-1)) of MDPV produced similar effects, while the R(-) enantiomer (0.3-3.0mgkg(-1)) had no effects. Neither of the hydroxylated phase I metabolites of MDPV altered cardiovascular parameters significantly from baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3mgkg(-1)) antagonized the increases in BP and HR produced by 1mgkg(-1) MDPV. The (1)-adrenoceptor antagonist prazosin (0.3mgkg(-1)) attenuated the increase in BP following MDPV, while the -adrenoceptor antagonists propranolol (1mgkg(-1)) and atenolol (1 and 3mgkg(-1)) attenuated the HR increases.
Conclusions and ImplicationsThe S(+) enantiomer appeared to mediate the cardiovascular effects of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV increased BP and HR through activation of central sympathetic outflow. Mixed-action /-adrenoceptor antagonists may be useful as treatments in counteracting the adverse cardiovascular effects of MDPV.
C1 [Schindler, Charles W.; Thorndike, Eric B.] NIDA, Preclin Pharmacol Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, NIH, Intramural Res Program, Baltimore, MD USA.
[Baumann, Michael H.] NIDA, Designer Drug Res Unit, NIH, Intramural Res Program, Baltimore, MD USA.
RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
EM cschind@helix.nih.gov
FU Intramural Research Programs of the National Institute on Drug Abuse
(NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA),
National Institutes of Health
FX This research was supported by the Intramural Research Programs of the
National Institute on Drug Abuse (NIDA) and National Institute on
Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health.
NR 44
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD DEC
PY 2016
VL 173
IS 24
BP 3492
EP 3501
DI 10.1111/bph.13640
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA ED6SL
UT WOS:000388986200007
PM 27714779
ER
PT J
AU Pinsky, PF
Yu, K
Black, A
Huang, WY
Prorok, PC
AF Pinsky, P. F.
Yu, K.
Black, A.
Huang, W. Y.
Prorok, P. C.
TI Active follow-up versus passive linkage with cancer registries for case
ascertainment in a cohort
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Cancer registries; Linkage; Active-follow-up; Case ascertainment
AB Background: Ascertaining incident cancers is a critical component of cancer-focused epidemiologic cohorts and of cancer prevention trials. Potential methods: for cancer case ascertainment include active follow-up and passive linkage with state cancer registries. Here we compare the two approaches in a large cancer screening trial.
Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial enrolled 154,955 subjects at ten U.S. centers and followed them for all-cancer incidence. Cancers were ascertained by an active follow-up process involving annual questionnaires, retrieval of records and medical record abstracting to ascertain and confirm cancers. For a subset of centers, linkage with state cancer registries was also performed. We assessed the agreement of the two methods in ascertaining incident cancers from 1993 to 2009 in 80,083 subjects from six PLCO centers where cancers were ascertained both by active follow-up and through linkages with 14 state registries.
Results: The ratio (times 100) of confirmed cases ascertained by registry linkage compared to active follow-up was 96.4 (95% CI: 95.1-98.2). Of cancers ascertained by either method, 86.6% and 83.5% were identified by active follow-up and by registry linkage, respectively. Of cancers missed by active follow-up, 30% were after subjects were lost to follow-up and 16% were reported but could not be confirmed. Of cancers missed by the registries, 27% were not sent to the state registry of the subject's current address at the time of linkage.
Conclusion: Linkage with state registries identified a similar number of cancers as active follow-up and can be a cost-effective method to ascertain incident cancers in a large cohort. Published by Elsevier Ltd.
C1 [Pinsky, P. F.; Yu, K.; Prorok, P. C.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Black, A.; Huang, W. Y.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
FU National Cancer Institute [HHSN261201100008C]; Centers for Disease
Control and Prevention, National Program for Central Registries;
National Cancer Institute, Surveillance, Epidemiology, and End Results
Program
FX This research was supported by contract number HHSN261201100008C from
the National Cancer Institute. The funding agency had no role in the
research, other than the fact that the authors were employees of the
funding agency.; Cancer incidence data have been provided by the
following registries: Arizona, California, Colorado, D.C., Hawaii,
Idaho, Maryland, Michigan, Nevada, Ohio, Pennsylvania, Texas, Utah,
Virginia. All are supported in part by funds from the Centers for
Disease Control and Prevention, National Program for Central Registries,
local states or by the National Cancer Institute, Surveillance,
Epidemiology, and End Results Program. The results reported here and the
conclusions derived are the sole responsibility of the authors.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
EI 1877-783X
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD DEC
PY 2016
VL 45
BP 26
EP 31
DI 10.1016/j.canep.2016.09.003
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE3RV
UT WOS:000389515900005
PM 27687075
ER
PT J
AU Jedy-Agba, EE
Dareng, EO
Adebamowo, SN
Odutola, M
Oga, EA
Igbinoba, F
Otu, T
Ezeome, E
Bray, F
Hassan, R
Adebamowo, CA
AF Jedy-Agba, E. E.
Dareng, E. O.
Adebamowo, S. N.
Odutola, M.
Oga, E. A.
Igbinoba, F.
Otu, T.
Ezeome, E.
Bray, F.
Hassan, R.
Adebamowo, C. A.
TI The burden of HPV associated cancers in two regions in Nigeria 2012-2014
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE HPV; HPV associated cancers; Cancer registries; Cancer incidence;
Nigeria
ID SUB-SAHARAN AFRICA; HUMAN-PAPILLOMAVIRUS PREVALENCE; CERVICAL-CANCER;
PENILE CANCER; VAGINAL-CANCER; GLOBAL BURDEN; ORAL-CAVITY; ANAL CANCER;
METAANALYSIS; CARCINOMA
AB Introduction: HPV attributable cancers are the second most common infection-related cancers worldwide, with much higher burden in less developed regions. There are currently no country-specific estimates of the burden of these cancers in Nigeria just like many other low and middle income countries.
Methods: In this study, we quantified the proportion of the cancer burden in Nigeria that is attributable to HPV infection from 2012 to 2014 using HPV prevalence estimated from previous studies and data from two population based cancer registries (PBCR) in Nigeria. We considered cancer sites for which there is strong evidence of an association with HPV infection based on the International Agency for Research on Cancer (IARC) classification. We obtained age and sex-specific estimates of incident cancers and using the World Standard Population, we derived age standardized incidence (ASR) rates for each cancer type by categories of sex, and estimated the population attributable fractions (PAF).
Results: The two PBCR reported 4336 new cancer cases from 2012 to 2014. Of these, 1627 (37.5%) were in males and 2709 (62.5%) in females. Some 11% (488/4336) of these cancers were HPV associated; 2% (38/1627) in men and 17% (450/2709) in women. Of the HPV associated cancers, 7.8% occurred in men and 92.2% in women. The ASRs for HPV associated cancers was 33.5 per 100,000; 2.3 and 31.2 per 100,000 in men and women respectively. The proportion of all cancers attributable to HPV infection ranged from 10.2 to 10.4% (442-453 of 4336) while the proportion of HPV associated cancers attributable to HPV infection ranged from 90.6% to 92.8% (442-453 of the 488 cases). In men, 55.3% to 68.4% of HPV associated cancers were attributable to HPV infection compared to 93.6% to 94.8% in women. The combined ASR for HPV attributable cancers ranged from 31.0 to 31.7 per 100,000. This was 1.4 to 1.7 per 100,000 in men and 29.6 to 30.0 per 100,000 in women. In women, cervical cancer (n = 392, ASR 28.3 per 100,000) was the commonest HPV attributable cancer, while anal cancer (n = 21, ASR 1.2 per 100,000) was the commonest in men.
Conclusions: HPV attributable cancers constitute a substantial cancer burden in Nigerian women, much less so in men. A significant proportion of cancers in Nigerian women would be prevented if strategies such as HPV DNA based screening and HPV vaccination are implemented. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Jedy-Agba, E. E.] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
[Dareng, E. O.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Adebamowo, S. N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Odutola, M.; Adebamowo, C. A.] Inst Human Virol, Abuja, Nigeria.
[Oga, E. A.; Adebamowo, C. A.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Igbinoba, F.] Natl Hosp Abuja, Abuja, Nigeria.
[Otu, T.] Univ Abuja Teaching Hosp Gwagwalada, Abuja, Nigeria.
[Ezeome, E.] Univ Nigeria Teaching Hosp Enugu, Enugu, Nigeria.
[Bray, F.] Int Agcy Res Canc, Lyon, France.
[Hassan, R.] Fed Minist Hlth, Abuja, Nigeria.
[Adebamowo, C. A.] Univ Maryland, Sch Med, Marlene & Stewart Greenbaum Comprehens Canc Ctr, Baltimore, MD 21201 USA.
[Adebamowo, C. A.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
RP Jedy-Agba, EE (reprint author), London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
EM elima.jedyagba@gmail.com
FU IHV-UM Capacity Development for Research into AIDS-Associated
Malignancies (CADRE) [NIH/NCI D43CA153792]; African Collaborative Center
for Microbiome and Genomics Research (ACCME) [NIH/NHGRI U54HG006947]
FX We acknowledge the work in data collection and data entry carried out by
the cancer registrars at the Abuja and Enugu population-based cancer
registries. This work was supported by IHV-UM Capacity Development for
Research into AIDS-Associated Malignancies (CADRE, NIH/NCI D43CA153792)
and the African Collaborative Center for Microbiome and Genomics
Research (ACCME, NIH/NHGRI U54HG006947).
NR 56
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U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
EI 1877-783X
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD DEC
PY 2016
VL 45
BP 91
EP 97
DI 10.1016/j.canep.2016.10.008
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE3RV
UT WOS:000389515900013
PM 27780076
ER
PT J
AU Meier, HCS
Sandler, DP
Simonsick, EM
Parks, CG
AF Meier, Helen C. S.
Sandler, Dale P.
Simonsick, Eleanor M.
Parks, Christine G.
TI Association between Vitamin D Deficiency and Antinuclear Antibodies in
Middle-Aged and Older US Adults
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CIRCULATING 25-HYDROXYVITAMIN D; CANCER;
AUTOANTIBODIES; AUTOIMMUNITY; METAANALYSIS; BIOMARKERS; DISEASE; WOMEN;
SERUM
AB Background: Vitamin D deficiency is associated with cancer and autoimmune diseases, but little is known about the association between vitamin D and antinuclear antibodies (ANA), a biomarker of immune dysfunction in healthy populations. The objective of this study was to determine whether vitamin D deficiency is associated with ANA in middle-aged and older U. S. adults.
Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 2001-2004 was conducted. Data were available for 1,012 adults aged 50 years and older. Serum 25-hydroxyvitamin D levels were measured by radioimmunoassay. ANA was measured in a 1:80 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4+).
Results: Greater vitamin D deficiency was associated with higher ANA prevalence in the unadjusted (P-trend = 0.0002) logistic regression model and after adjustment for sex, age, education, race/ethnicity, season, and NHANES cycle (P-trend-0.04). After adjustment, those with severe vitamin D deficiency (< 10 ng/mL) had 2.99 (95% CI, 1.25-7.15) times the odds of ANA compared with having normal vitamin D levels (>= 30 ng/mL), while deficient and insufficient individuals had twice the odds of ANA.
Conclusions: Among U. S. residents ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. Vitamin D sufficiency may be important for preventing immune dysfunction in older populations.
Impact: Our findings support the growing evidence that vitamin D is an important immune modulator. Vitamin D deficiency in older adults may increase vulnerability to cancer by contributing to immune dysfunction. Cancer Epidemiol Biomarkers Prev; 25(12); 1559-63. (C) 2016 AACR.
C1 [Meier, Helen C. S.] Univ Wisconsin Milwaukee, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI USA.
[Sandler, Dale P.; Parks, Christine G.] NIEHS, NIH, Epidemiol Branch, Res Triangle Pk, NC USA.
[Simonsick, Eleanor M.] Natl Inst Aging, Translat Gerontol Branch, Longitudinal Studies Sect, NIH, Baltimore, MD USA.
RP Sandler, DP (reprint author), NIEHS, NIH, Epidemiol Branch, Res Triangle Pk, NC USA.; Sandler, DP (reprint author), NIEHS, POB 12233 MD A3-05 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM sandler@niehs.nih.gov
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [Z01-ES049028]; National Institute on
Aging [AG000015-57]
FX This work was supported by the Intramural Research Program of the NIH,
the National Institute of Environmental Health Sciences (Z01-ES049028;
to DP Sandler), and the National Institute on Aging (AG000015-57; to EM
Simonsick).
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2016
VL 25
IS 12
BP 1559
EP 1563
DI 10.1158/1055-9965.EPI-16-0339
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE6FL
UT WOS:000389704300003
PM 27543618
ER
PT J
AU Lin, J
McGlynn, KA
Carter, CA
Nations, JA
Anderson, WF
Shriver, CD
Zhu, KM
AF Lin, Jie
McGlynn, Katherine A.
Carter, Corey A.
Nations, Joel A.
Anderson, William F.
Shriver, Craig D.
Zhu, Kangmin
TI The Impact of Preexisting Mental Health Disorders on the Diagnosis,
Treatment, and Survival among Lung Cancer Patients in the US Military
Health System
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; ALL-CAUSE MORTALITY; AUSTRALIAN
PSYCHIATRIC-PATIENTS; PROVIDER COMMUNICATION; AMERICAN SOCIETY; EXCESS
MORTALITY; UNITED-STATES; BREAST-CANCER; COLON-CANCER; CARE-SYSTEM
AB Background: Higher cancer-related mortality has been observed among people with mental health disorders than in the general population. Both delay in diagnosis and inadequate treatment due to health care access have been found to explain the higher mortality. The U.S. Military Health System (MHS), in which all beneficiaries have equal access to health care, provides an ideal system to study this disparity where there are no or minimal barriers to health care access. This study assessed preexisting mental health disorders and stage at diagnosis, receipt of cancer treatment, and overall survival among patients with nonsmall cell lung cancer (NSCLC) in the U.S. MHS.
Methods: The study used data from the linked database from the Department of Defense's Central Cancer Registry and the MHS Data Repository (MDR). The study subjects included 5,054 patients with histologically confirmed primary NSCLC diagnosed
Results: Patients with a preexisting mental disorder did not present with more advanced disease at diagnosis than those without. There were no significant differences in receiving cancer treatments between the two groups. However, patients with a mental health disorder had a higher mortality than those without [adjusted HR, 1.11; 95% confidence interval (CI), 1.03-1.20].
Conclusions: Poor survival in NSCLC in patients with a preexisting mental health disorder is not necessarily associated with delay in diagnosis and/or inadequate cancer treatment.
Impact: This study contributes to the current understanding that health care access may not be sufficient to explain the poor survival among patients with NSCLC with preexisting mental health disorders. Cancer Epidemiol Biomarkers Prev; 25(12); 1564-71. (C) 2016 AACR.
C1 [Lin, Jie; Carter, Corey A.; Nations, Joel A.; Shriver, Craig D.; Zhu, Kangmin] John P Murtha Canc Ctr, Walter Reed Natl Mil Med Ctr, 11300 Rockville Pike Suite 1120, Bethesda, MD 20852 USA.
[McGlynn, Katherine A.; Anderson, William F.] Div Canc Epidemiol & Genet, Natl Canc Inst, Bethesda, MD USA.
[Shriver, Craig D.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA.
[Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biostatist, Bethesda, MD USA.
RP Lin, J (reprint author), John P Murtha Canc Ctr, Walter Reed Natl Mil Med Ctr, 11300 Rockville Pike Suite 1120, Bethesda, MD 20852 USA.
EM jlin@murthacancercenter.org
FU John P. Murtha Cancer Center, Walter Reed National Military Medical
Center via the Uniformed Services University of the Health Sciences
under the auspices of the Henry M. Jackson Foundation for the
Advancement of Military Medicine; National Cancer Institute
FX This project was supported by John P. Murtha Cancer Center, Walter Reed
National Military Medical Center via the Uniformed Services University
of the Health Sciences under the auspices of the Henry M. Jackson
Foundation for the Advancement of Military Medicine and by the
intramural research program of the National Cancer Institute.
NR 57
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U1 4
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2016
VL 25
IS 12
BP 1564
EP 1571
DI 10.1158/1055-9965.EPI-16-0316
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE6FL
UT WOS:000389704300004
PM 27566418
ER
PT J
AU Rand, KA
Song, C
Dean, E
Serie, DJ
Curtin, K
Sheng, X
Hu, DL
Huff, CA
Bernal-Mizrachi, L
Tomasson, MH
Ailawadhi, S
Singhal, S
Pawlish, K
Peters, ES
Bock, CH
Stram, A
Van den Berg, DJ
Edlund, CK
Conti, DV
Zimmerman, T
Hwang, AE
Huntsman, S
Graff, J
Nooka, A
Kong, YF
Pregja, SL
Berndt, SI
Blot, WJ
Carpten, J
Casey, G
Chu, L
Diver, WR
Stevens, VL
Lieber, MR
Goodman, PJ
Hennis, AJM
Hsing, AW
Mehta, J
Kittles, RA
Kolb, S
Klein, EA
Leske, C
Murphy, AB
Nemesure, B
Neslund-Dudas, C
Strom, SS
Vij, R
Rybicki, BA
Stanford, JL
Signorello, LB
Witte, JS
Ambrosone, CB
Bhatti, P
John, EM
Bernstein, L
Zheng, W
Olshan, AF
Hu, JJ
Ziegler, RG
Nyante, SJ
Bandera, EV
Birmann, BM
Ingles, SA
Press, MF
Atanackovic, D
Glenn, MJ
Cannon-Albright, LA
Jones, B
Tricot, G
Martin, TG
Kumar, SK
Wolf, JL
Halverson, SLD
Rothman, N
Brooks-Wilson, AR
Rajkumar, SV
Kolonel, LN
Chanock, SJ
Slager, SL
Severson, RK
Janakiraman, N
Terebelo, HR
Brown, EE
De Roos, AJ
Mohrbacher, AF
Colditz, GA
Giles, GG
Spinelli, JJ
Chiu, BC
Munshi, NC
Anderson, KC
Levy, J
Zonder, JA
Orlowski, RZ
Lonial, S
Camp, NJ
Vachon, CM
Ziv, E
Stram, DO
Hazelett, DJ
Haiman, CA
Cozen, W
AF Rand, Kristin A.
Song, Chi
Dean, Eric
Serie, Daniel J.
Curtin, Karen
Sheng, Xin
Hu, Donglei
Huff, Carol Ann
Bernal-Mizrachi, Leon
Tomasson, Michael H.
Ailawadhi, Sikander
Singhal, Seema
Pawlish, Karen
Peters, Edward S.
Bock, Cathryn H.
Stram, Alex
Van den Berg, David J.
Edlund, Christopher K.
Conti, David V.
Zimmerman, Todd
Hwang, Amie E.
Huntsman, Scott
Graff, John
Nooka, Ajay
Kong, Yinfei
Pregja, Silvana L.
Berndt, Sonja I.
Blot, William J.
Carpten, John
Casey, Graham
Chu, Lisa
Diver, W. Ryan
Stevens, Victoria L.
Lieber, Michael R.
Goodman, Phyllis J.
Hennis, Anselm J. M.
Hsing, Ann W.
Mehta, Jayesh
Kittles, Rick A.
Kolb, Suzanne
Klein, Eric A.
Leske, Cristina
Murphy, Adam B.
Nemesure, Barbara
Neslund-Dudas, Christine
Strom, Sara S.
Vij, Ravi
Rybicki, Benjamin A.
Stanford, Janet L.
Signorello, Lisa B.
Witte, John S.
Ambrosone, Christine B.
Bhatti, Parveen
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Olshan, Andrew F.
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah J.
Bandera, Elisa V.
Birmann, Brenda M.
Ingles, Sue A.
Press, Michael F.
Atanackovic, Djordje
Glenn, Martha J.
Cannon-Albright, Lisa A.
Jones, Brandt
Tricot, Guido
Martin, Thomas G.
Kumar, Shaji K.
Wolf, Jeffrey L.
Halverson, Sandra L. Deming
Rothman, Nathaniel
Brooks-Wilson, Angela R.
Rajkumar, S. Vincent
Kolonel, Laurence N.
Chanock, Stephen J.
Slager, Susan L.
Severson, Richard K.
Janakiraman, Nalini
Terebelo, Howard R.
Brown, Elizabeth E.
De Roos, Anneclaire J.
Mohrbacher, Ann F.
Colditz, Graham A.
Giles, Graham G.
Spinelli, John J.
Chiu, Brian C.
Munshi, Nikhil C.
Anderson, Kenneth C.
Levy, Joan
Zonder, Jeffrey A.
Orlowski, Robert Z.
Lonial, Sagar
Camp, Nicola J.
Vachon, Celine M.
Ziv, Elad
Stram, Daniel O.
Hazelett, Dennis J.
Haiman, Christopher A.
Cozen, Wendy
TI A Meta-analysis of Multiple Myeloma Risk Regions in African and European
Ancestry Populations Identifies Putatively Functional Loci
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; UNDETERMINED SIGNIFICANCE; MONOCLONAL
GAMMOPATHY; LOS-ANGELES; VARIANTS; SITES; GENOTYPES; PATTERNS; 7P15.3;
TARGET
AB Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.
Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.
Results: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 30 end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 x 10(-7)) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-kB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7.
Conclusions: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles.
Impact: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. (C) 2016 AACR.
C1 [Rand, Kristin A.; Song, Chi; Sheng, Xin; Van den Berg, David J.; Edlund, Christopher K.; Conti, David V.; Hwang, Amie E.; Kong, Yinfei; Casey, Graham; Lieber, Michael R.; Ingles, Sue A.; Press, Michael F.; Mohrbacher, Ann F.; Stram, Daniel O.; Haiman, Christopher A.; Cozen, Wendy] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Rand, Kristin A.; Song, Chi; Sheng, Xin; Van den Berg, David J.; Edlund, Christopher K.; Conti, David V.; Hwang, Amie E.; Kong, Yinfei; Casey, Graham; Lieber, Michael R.; Ingles, Sue A.; Press, Michael F.; Mohrbacher, Ann F.; Stram, Daniel O.; Haiman, Christopher A.; Cozen, Wendy] Univ Southern Calif, Norris Comprehens Canc Ctr, Topping Tower,1441 Eastlake Ave,Room 4451A, Los Angeles, CA 90033 USA.
[Dean, Eric] Sutter Hlth, Oakland, CA USA.
[Serie, Daniel J.; Ailawadhi, Sikander] Mayo Clin Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
[Curtin, Karen; Atanackovic, Djordje; Glenn, Martha J.; Cannon-Albright, Lisa A.; Jones, Brandt; Camp, Nicola J.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Hu, Donglei; Huntsman, Scott; Martin, Thomas G.; Wolf, Jeffrey L.; Ziv, Elad] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Huff, Carol Ann] Johns Hopkins Univ, Johns Hopkins Sch Med, Baltimore, MD USA.
[Bernal-Mizrachi, Leon; Nooka, Ajay; Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Tomasson, Michael H.; Vij, Ravi; Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA.
[Singhal, Seema; Mehta, Jayesh; Murphy, Adam B.] Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA.
[Pawlish, Karen] New Jersey Dept Hlth, New Jersey State Canc Registry, Trenton, NJ USA.
[Peters, Edward S.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA.
[Bock, Cathryn H.; Pregja, Silvana L.; Severson, Richard K.; Zonder, Jeffrey A.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Bock, Cathryn H.; Pregja, Silvana L.; Severson, Richard K.; Zonder, Jeffrey A.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA.
[Stram, Alex] Genom Hlth Inc, Redwood City, CA USA.
[Zimmerman, Todd; Chiu, Brian C.] Univ Chicago, Chicago, IL 60637 USA.
[Graff, John; Bandera, Elisa V.] Rutgers State Univ, Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Berndt, Sonja I.; Ziegler, Regina G.; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA.
[Blot, William J.; Zheng, Wei; Halverson, Sandra L. Deming] Int Epidemiol Inst, Rockville, MD USA.
[Blot, William J.] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Nashville, TN 37212 USA.
[Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA.
[Chu, Lisa; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Chu, Lisa; Hsing, Ann W.; John, Esther M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Chu, Lisa; Hsing, Ann W.; John, Esther M.] Stanford Canc Inst, Palo Alto, CA USA.
[Diver, W. Ryan; Stevens, Victoria L.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Goodman, Phyllis J.] SWOG Stat Ctr, Seattle, WA USA.
[Hennis, Anselm J. M.; Leske, Cristina; Nemesure, Barbara] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Hennis, Anselm J. M.] Univ West Indies, Chron Dis Res Ctr, Bridgetown, Barbados.
[Hennis, Anselm J. M.] Univ West Indies, Fac Med Sci, Bridgetown, Barbados.
[Kittles, Rick A.] Univ Arizona, Dept Surg, Tucson, AZ USA.
[Kolb, Suzanne; Stanford, Janet L.; Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Neslund-Dudas, Christine; Rybicki, Benjamin A.; Janakiraman, Nalini] Henry Ford Hosp, Detroit, MI 48202 USA.
[Strom, Sara S.; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Signorello, Lisa B.; Birmann, Brenda M.] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Olshan, Andrew F.; Nyante, Sarah J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Olshan, Andrew F.; Nyante, Sarah J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Hu, Jennifer J.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Hu, Jennifer J.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Tricot, Guido] Univ Iowa, Iowa City, IA USA.
[Kumar, Shaji K.; Rajkumar, S. Vincent; Slager, Susan L.; Vachon, Celine M.] Mayo Clin, Rochester, MN USA.
[Brooks-Wilson, Angela R.; Spinelli, John J.] BC Canc Agcy, Vancouver, BC, Canada.
[Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Terebelo, Howard R.] Providence Hosp, Southfield, MI 48037 USA.
[Brown, Elizabeth E.] Univ Alabama Birmingham, Birmingham, AL USA.
[De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA.
[Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.] Univ Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Giles, Graham G.] Monash Univ, Melbourne, Vic, Australia.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada.
[Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Harvard Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Levy, Joan] Multiple Myeloma Res Fdn, Norwalk, CT USA.
[Hazelett, Dennis J.] Cedars Sinai Med Ctr, Ctr Bioinformat & Computat Biol, Los Angeles, CA 90048 USA.
RP Cozen, W (reprint author), Univ Southern Calif, Norris Comprehens Canc Ctr, Topping Tower,1441 Eastlake Ave,Room 4451A, Los Angeles, CA 90033 USA.; Haiman, CA (reprint author), USC Norris Comprehens Canc Ctr, Harlyne Norris Res Tower,1450 Biggy St,Room 1504, Los Angeles, CA 90033 USA.; Hazelett, DJ (reprint author), Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM Dennis.Hazelett@csmc.edu; haiman@usc.edu; wcozen@usc.edu
RI Brooks-Wilson, Angela/E-9399-2012
OI Brooks-Wilson, Angela/0000-0003-1009-6408
FU National Cancer Institute at the NIH [1R01CA134786, 2P50CA100707,
Myeloma SPORE 2P50CA100707 Project, R01CA152336, R01CA134674, P50
CA142509, R01CA184464, R21CA155951, R25CA76023, R01CA186646,
U54CA118948, P30CA13148, R21CA191896, K24CA169004]; Leukemia Lymphoma
Society [LLS 6067-090]; American Cancer Society [IRG60-001-47]; Steve
and Nancy Grand Multiple Myeloma Translational Initiative; National
Cancer Institute Surveillance Epidemiology and End Results
Population-based Registry Program, NIH, Department of Health and Human
Services [N01-PC-35139]; HHSN [261201300021I, N01PC-2013 00021,
HHSN261201000026C]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention [5U58DP003931-02,
1U58DP000807-01]; Huntsman Cancer Institute (HCI); HCI Cancer Center
Support grant [P30 CA42014]; USC Norris Comprehensive Cancer Center Core
grant from the National Cancer Institute [P30CA014089]; California
Department of Health Services [103885]; NIH [CA63464, CA54281,
CA1326792, CA148085, HG004726, CA056678, CA082664, CA092579, ES011126];
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, NCI, NIH; Cancer Research Fund [99- 00524V10258, 9712013];
University of California [98-00924V]; Department of Health Services
Cancer Research Program; NCI, NIH, Department of Health and Human
Services [N01-PC-35139]; Fred Hutchinson Cancer Research Center;
Intramural Program of the National Human Genome Research Institute;
Public Health Service from the National Cancer Institute [U10 CA37429,
UM1 CA182883]; Vanderbilt-Ingram Cancer Center [CA68485]; Department of
Defense Breast Cancer Research Program Era of Hope Scholar Award
[W81XWH-08-1-0383]; Norris Foundation [P01-CA151135, U19-CA148065]; MEC
(NIH) [R01-CA63464, R37-CA54281, UM1-CA164973]; CARE (National Institute
for Child Health and Development) [NO1-HD-3-3175, K05 CA136967]; WCHS
[U.S. Army Medical Research and Material Command (USAMRMC)]
[DAMD-17-01-0-0334]; WCHS [NIH] [R01-CA100598]; WCHS [Breast Cancer
Research Foundation]; SFBCS (NIH) [R01-CA77305]; SFBCS (United States
Army Medical Research Program) [DAMD17-96-6071]; NC-BCFR (NIH)
[U01-CA69417]; CBCS (NIH Specialized Program of Research Excellence in
Breast Cancer) [P50-CA58223]; Center for Environmental Health and
Susceptibility National Institute of Environmental Health Sciences, NIH
[P30-ES10126]; PLCO (Intramural Research Program, National Cancer
Institute, NIH); NBHS (National Institutes of Health) [R01-CA100374];
WFBC (NIH) [R01-CA73629]; National Cancer Institute, NIH
[RFA-CA-06-503]; [CA68578]; [ES007784]; [DAMD W81XWH-07-1-0645];
[CA140388]; [CA88164]; [CA127298]
FX This study was supported by the National Cancer Institute at the NIH
(1R01CA134786 to W. Cozen and Christopher A. Haiman; 2P50CA100707 to
K.C. Anderson; Myeloma SPORE 2P50CA100707 Project 6 to K.C. Anderson, W.
Cozen, and D.V. Conti; R01CA152336 and R01CA134674 to N. J. Camp; P50
CA142509 and R01CA184464 to R. Z. Orlowski; R21CA155951, R25CA76023,
R01CA186646, U54CA118948 Project 3 and P30CA13148 (seed grant) to E. E.
Brown; and R21CA191896 and K24CA169004 to E. Ziv). The study also
received support from the Leukemia Lymphoma Society (LLS 6067-090) to N.
J. Camp, the American Cancer Society (IRG60-001-47) to E. E. Brown, and
the Steve and Nancy Grand Multiple Myeloma Translational Initiative to
E. Ziv. Data collection from the cancer registries was supported by the
National Cancer Institute Surveillance Epidemiology and End Results
Population-based Registry Program, NIH, Department of Health and Human
Services, under contracts N01-PC-35139 (to USC for Los Angeles County),
HHSN 261201300021I, N01PC-2013 00021 (to the New Jersey State Cancer
Registry), and HHSN261201000026C (to the Utah Cancer Registry).
Additional support for collection of incident multiple myeloma patient
data was obtained from the Utah State Department of Health and the
University of Utah, the Utah Population Database (UPDB) and the Utah
Cancer Registry (UCR), the National Program of Cancer Registries of the
Centers for Disease Control and Prevention (5U58DP003931-02 to the New
Jersey State Cancer Registry and 1U58DP000807-01 to the California
Cancer Registry), the Huntsman Cancer Institute (HCI) and the HCI Cancer
Center Support grant, P30 CA42014 and by the USC Norris Comprehensive
Cancer Center Core grant P30CA014089 from the National Cancer Institute.
The collection of patients used in this publication was supported in
part by the California Department of Health Services as part of the
statewide cancer reporting program mandated by California Health and
Safety Code Section 103885. AAPC studies: The MEC is supported by NIH
grants CA63464, CA54281, CA1326792, CA148085, and HG004726. Genotyping
of the PLCO samples was funded by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, NCI, NIH. LAAPC was funded
by grant 99- 00524V10258 from the Cancer Research Fund, under
Interagency Agreement # 9712013 (University of California contract #
98-00924V) with the Department of Health Services Cancer Research
Program. Cancer incidence data for the MEC and LAAPC studies have been
collected by the Los Angeles Cancer Surveillance Program of the
University of Southern California with Federal funds from the NCI, NIH,
Department of Health and Human Services, under Contract No.
N01-PC-35139, and the California Department of Health Services as part
of the statewide cancer reporting program mandated by California Health
and Safety Code Section 103885, and grant number 1U58DP000807-3 from the
Centers for Disease Control and Prevention. KCPCS was supported by NIH
grants CA056678, CA082664, and CA092579, with additional support from
the Fred Hutchinson Cancer Research Center and the Intramural Program of
the National Human Genome Research Institute. MDA was supported by
grants, CA68578, ES007784, DAMD W81XWH-07-1-0645, and CA140388. CaP
Genes was supported by CA88164 and CA127298. SELECT was funded in part
by Public Health Service grants U10 CA37429 (C.D. Blanke) and UM1
CA182883 (I. M. Thompson/C.M. Tangen) from the National Cancer
Institute. GECAP was supported by NIH grant ES011126.; SCCS sample
preparation was conducted at the Epidemiology Biospecimen Core Lab that
is supported in part by the Vanderbilt-Ingram Cancer Center (CA68485).;
AABC studies: AABC was supported by a Department of Defense Breast
Cancer Research Program Era of Hope Scholar Award to CAH
(W81XWH-08-1-0383), the Norris Foundation, P01-CA151135 and
U19-CA148065. Each of the participating studies was supported by the
following grants: MEC (NIH grants R01-CA63464, R37-CA54281 and
UM1-CA164973); CARE (National Institute for Child Health and Development
grant NO1-HD-3-3175, K05 CA136967); WCHS [U.S. Army Medical Research and
Material Command (USAMRMC) grant DAMD-17-01-0-0334, the NIH grant
R01-CA100598, and the Breast Cancer Research Foundation]; SFBCS (NIH
grant R01-CA77305 and United States Army Medical Research Program grant
DAMD17-96-6071); NC-BCFR (NIH grant U01-CA69417); CBCS (NIH Specialized
Program of Research Excellence in Breast Cancer, grant number
P50-CA58223, and Center for Environmental Health and Susceptibility
National Institute of Environmental Health Sciences, NIH, grant number
P30-ES10126); PLCO (Intramural Research Program, National Cancer
Institute, NIH); NBHS (National Institutes of Health grant
R01-CA100374); WFBC (NIH grant R01-CA73629). The Breast Cancer Family
Registry (BCFR) was supported by the National Cancer Institute, NIH
under RFA-CA-06-503 and through cooperative agreements with members of
the Breast Cancer Family Registry and Principal Investigators.
NR 38
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U2 5
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2016
VL 25
IS 12
BP 1609
EP 1618
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE6FL
UT WOS:000389704300009
PM 27587788
ER
PT J
AU Zhu, CS
Huang, WY
Pinsky, PF
Berg, C
Sherman, M
Yu, KJ
Carrick, DM
Black, A
Hoover, R
Lenz, P
Williams, C
Hawkins, L
Chaloux, M
Yurgalevitch, S
Mathew, S
Miller, A
Olivo, V
Khan, A
Pretzel, SM
Multerer, D
Beckmann, P
Broski, KG
Freedman, ND
AF Zhu, Claire S.
Huang, Wen-Yi
Pinsky, Paulf F.
Berg, Christine D.
Sherman, Mark
Yu, Kelly J.
Carrick, Danielle M.
Black, Amanda
Hoover, Robert
Lenz, Petra
Williams, Craig
Hawkins, Laura
Chaloux, Matthew
Yurgalevitch, Susan
Mathew, Sunitha
Miller, Amy
Olivo, Vanessa
Khan, Asia
Pretzel, Shannon M.
Multerer, Deborah
Beckmann, Patricia
Broski, Karen G.
Freedman, Neal D.
TI The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial
Pathology Tissue Resource
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BREAST-CANCER; EPIDEMIOLOGY
AB Background: Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial.
Methods: Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction.
Results: Pathology tissue specimens were obtained for prostate cancer (n = 1,052), lung cancer (n = 434), colorectal cancer (n = 675) and adenoma (n = 658), ovarian cancer and borderline tumors (n = 212), breast cancer (n = 870), and bladder cancer (n = 204). The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories.
Conclusions: Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis.
Impact: The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25(12); 1635-42. (C) 2016 AACR.
C1 [Zhu, Claire S.; Pinsky, Paulf F.; Sherman, Mark] NCI, Canc Prevent Div, Bethesda, MD USA.
[Huang, Wen-Yi; Berg, Christine D.; Yu, Kelly J.; Black, Amanda; Hoover, Robert; Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Carrick, Danielle M.] Div Canc Control & Populat Sci, NCI, Bethesda, MD USA.
[Lenz, Petra] Leidos Biomedical Res Inc, Clin Res Directorate, Clin Monitoring Res Program, NCI Campus, Frederick, MD USA.
[Williams, Craig; Hawkins, Laura; Chaloux, Matthew] Informat Management Serv Inc, Rockville, MD USA.
[Yurgalevitch, Susan; Mathew, Sunitha; Miller, Amy; Olivo, Vanessa; Khan, Asia] Westat Corp, Rockville, MD USA.
[Pretzel, Shannon M.] Univ Colorado Canc Ctr, Aurora, CO USA.
[Multerer, Deborah] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
[Beckmann, Patricia] Univ Minnesota, Minneapolis, MN USA.
[Broski, Karen G.] Henry Ford Hlth Syst, Detroit, MI USA.
RP Zhu, CS (reprint author), NCI, 9606 Med Ctr Dr,Room 5E106, Rockville, MD 20850 USA.
EM zhucla@mail.nih.gov
FU NCI, NIH; NCI [HHSN261200800001E, N01-CN-25512, HHSN261201300008I]
FX This project has been funded in whole or in part with federal funds from
the NCI, NIH, to 10 PLCO screening centers, a coordinating center, a
data management center, and 2 central tissue microarray construction
laboratories. P. Lenz was supported by NCI contract no.
HHSN261200800001E; K. Broski was supported by NCI contract no.
N01-CN-25512; and M. Chaloux, L. Hawkins, and C. Williams were supported
by NCI contract no. HHSN261201300008I.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2016
VL 25
IS 12
BP 1635
EP 1642
DI 10.1158/1055-9965.EPI-16-0506
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA EE6FL
UT WOS:000389704300012
PM 27635065
ER
PT J
AU Moore, E
Clavijo, PE
Davis, R
Cash, H
Van Waes, C
Kim, Y
Allen, C
AF Moore, Ellen
Clavijo, Paul E.
Davis, Ruth
Cash, Harrison
Van Waes, Carter
Kim, Young
Allen, Clint
TI Established T Cell-Inflamed Tumors Rejected after Adaptive Resistance
Was Reversed by Combination STING Activation and PD-1 Pathway Blockade
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID DENDRITIC CELLS; I INTERFERON; MICROENVIRONMENT; INNATE; CANCER;
ANTITUMOR; REGRESSION; RESPONSES; IMMUNITY; RECOGNITION
AB Patients with head and neck squamous cell carcinoma harbor T cell-inflamed and non-T cell-inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell-inflamed (MOC1), but not non-T cell-inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP, RP dithio-c-di-GMP. Rejection or durable tumor control of MOC1 tumors was dependent upon a functional STING receptor and CD8 T lymphocytes. STING activation resulted in increased tumor microenvironment type 1 and type 2 IFN and greater expression of PD-1 pathway components in vivo. Established MOC1 tumors were rejected and distant tumors abscopally controlled, after adaptive immune resistance had been reversed by the addition of PD-L1 mAb. These findings suggest that PD-1 pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity. (C) 2016 AACR.
C1 [Moore, Ellen; Clavijo, Paul E.; Davis, Ruth; Cash, Harrison; Van Waes, Carter; Allen, Clint] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Kim, Young; Allen, Clint] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
RP Allen, C (reprint author), NIH, Bldg 10,Room 7N240C, Bethesda, MD 20892 USA.
EM clint.allen@nih.gov
OI Davis, Ruth/0000-0001-9592-932X
FU Intramural NIH HHS [ZIA DC000087-01]
NR 34
TC 0
Z9 0
U1 5
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD DEC
PY 2016
VL 4
IS 12
BP 1061
EP 1071
DI 10.1158/2326-6066.CIR-16-0104
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA EE6FA
UT WOS:000389702900008
PM 27821498
ER
PT J
AU Archer, TC
Fertig, EJ
Gosline, SJC
Hafner, M
Hughes, SK
Joughin, BA
Meyer, AS
Piccolo, SR
Shajahan-Haq, AN
AF Archer, Tenley C.
Fertig, Elana J.
Gosline, Sara J. C.
Hafner, Marc
Hughes, Shannon K.
Joughin, Brian A.
Meyer, Aaron S.
Piccolo, Stephen R.
Shajahan-Haq, Ayesha N.
TI Systems Approaches to Cancer Biology
SO CANCER RESEARCH
LA English
DT Editorial Material
ID BREAST-CANCER; REVEALS; SCIENCE
AB Cancer systems biology aims to understand cancer as an integrated system of genes, proteins, networks, and interactions rather than an entity of isolated molecular and cellular components. The inaugural Systems Approaches to Cancer Biology Conference, cosponsored by the Association of Early Career Cancer Systems Biologists and the National Cancer Institute of the NIH, focused on the interdisciplinary field of cancer systems biology and the challenging cancer questions that are best addressed through the combination of experimental and computational analyses. Attendees found that elucidating the many molecular features of cancer inevitably reveals new forms of complexity and concluded that ensuring the reproducibility and impact of cancer systems biology studies will require widespread method and data sharing and, ultimately, the translation of important findings to the clinic. (C) 2016 AACR.
C1 [Archer, Tenley C.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
[Fertig, Elana J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Gosline, Sara J. C.] Sage Bionetworks, Seattle, WA USA.
[Hafner, Marc] Harvard Med Sch, Dept Syst Biol, Boston, MA USA.
[Hughes, Shannon K.] NCI, Div Canc Biol, NIH, Rockville, MD USA.
[Joughin, Brian A.; Meyer, Aaron S.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Piccolo, Stephen R.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Shajahan-Haq, Ayesha N.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Meyer, AS (reprint author), MIT, 77 Massachusetts Ave,Bldg 76-361F, Cambridge, MA 02139 USA.
EM ameyer@asmlab.org
FU NIH HHS [DP5 OD019815]
NR 19
TC 0
Z9 1
U1 8
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 1
PY 2016
VL 76
IS 23
BP 6774
EP 6777
DI 10.1158/0008-5472.CAN-16-1580
PG 4
WC Oncology
SC Oncology
GA EE2SX
UT WOS:000389435800004
PM 27864348
ER
PT J
AU Skau, CT
Fischer, RS
Gurel, P
Thiam, HR
Tubbs, A
Baird, MA
Davidson, MW
Piel, M
Alushin, GM
Nussenzweig, A
Steeg, PS
Waterman, CM
AF Skau, Colleen T.
Fischer, Robert S.
Gurel, Pinar
Thiam, Hawa Racine
Tubbs, Anthony
Baird, Michelle A.
Davidson, Michael W.
Piel, Matthieu
Alushin, Gregory M.
Nussenzweig, Andre
Steeg, Patricia S.
Waterman, Clare M.
TI FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration
and Promote Metastasis
SO CELL
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; CELL-MIGRATION; DNA-DAMAGE; FOCAL ADHESIONS;
INTELLECTUAL DISABILITY; FORCE TRANSMISSION; TUMOR PROGRESSION; FORMIN
2; ENVELOPE; CANCER
AB Cell migration in confined 3D tissue microenvironments is critical for both normal physiological functions and dissemination of tumor cells. We discovered a cytoskeletal structure that prevents damage to the nucleus during migration in confined microenvironments. The formin-family actin filament nucleator FMN2 associates with and generates a perinuclear actin/focal adhesion (FA) system that is distinct from previously characterized actin/FA structures. This system controls nuclear shape and positioning in cells migrating on 2D surfaces. In confined 3D microenvironments, FMN2 promotes cell survival by limiting nuclear envelope damage and DNA double-strand breaks. We found that FMN2 is upregulated in human melanomas and showed that disruption of FMN2 in mouse melanoma cells inhibits their extravasation and metastasis to the lung. Our results indicate a critical role for FMN2 in generating a perinuclear actin/FA system that protects the nucleus and DNA from damage to promote cell survival during confined migration and thus promote cancer metastasis.
C1 [Skau, Colleen T.; Fischer, Robert S.; Gurel, Pinar; Thiam, Hawa Racine; Baird, Michelle A.; Alushin, Gregory M.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Thiam, Hawa Racine; Piel, Matthieu] CNRS UMR 144, Inst Curie, 26 Rue Ulm, F-75005 Paris, France.
[Tubbs, Anthony; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Magnet Lab, Tallahassee, FL 32306 USA.
[Steeg, Patricia S.] NCI, Womens Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM watermancm@nhlbi.nih.gov
FU Intramural Programs of the National Heart, Lung, and Blood Institute;
National Cancer Institute, NIH, Bethesda, MD; NIH Director's Early
Independence Award [1DP5OD17885-1]; ANR "Netoshape"; ANR "Association
pour la Recherche contre le Cancer'' [SFI20101201669]
FX The authors would like to thank Dr. Mary Beckerle (Huntsman Cancer
Institute), Dr. James Anderson (NHLBI), and Dr. Ken Yamada (NICDR) for
reagents, Drs. Margot Quinlan and Alex M.L. Wu (NCI) for technical
advice, William Shin for work on C.M.W.'s lab microscopes, and Schwanna
Thacker for administrative assistance. This work is supported by the
Intramural Programs of the National Heart, Lung, and Blood Institute
(C.T.S., R.S.F., H.R.-T., M.A.B., G.M.A., and C.M.W.) and the National
Cancer Institute (A.T., A.N., and P.S.S.), NIH, Bethesda, MD, an NIH
Director's Early Independence Award (1DP5OD17885-1) (P.G. and G.M.A.),
and ANR "Netoshape'' and "Association pour la Recherche contre le
Cancer'' (no. SFI20101201669; M.P.). Dedicated to the memory of Michael
W. Davidson.
NR 63
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U1 18
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD DEC 1
PY 2016
VL 167
IS 6
BP 1571
EP +
DI 10.1016/j.cell.2016.10.023
PG 33
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE3EN
UT WOS:000389470500018
PM 27839864
ER
PT J
AU Lucas, M
Gershlick, DC
Vidaurrazaga, A
Rojas, AL
Bonifacino, JS
Hierro, A
AF Lucas, Maria
Gershlick, David C.
Vidaurrazaga, Ander
Rojas, Adriana L.
Bonifacino, Juan S.
Hierro, Aitor
TI Structural Mechanism for Cargo Recognition by the Retromer Complex
SO CELL
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; CRYSTAL-STRUCTURE; MAMMALIAN RETROMER;
RETROGRADE TRANSPORT; DOMAIN; ARRESTIN; REVEALS; VPS35; YEAST; FOLD
AB Retromer is a multi-protein complex that recycles transmembrane cargo from endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer impair various cellular processes and underlie some forms of Alzheimer's disease and Parkinson's disease. Although retromer was discovered over 15 years ago, the mechanisms for cargo recognition and recruitment to endosomes have remained elusive. Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycl ing signal from the divalent cation transporter DMT1-II. This analysis identifies a binding site for canonical recycling signals at the interface between VPS26 and SNX3. In addition, the structure highlights a network of cooperative interactions among the VPS subunits, SNX3, and cargo that couple signal-recognition to membrane recruitment.
C1 [Lucas, Maria; Vidaurrazaga, Ander; Rojas, Adriana L.; Hierro, Aitor] CIC BioGUNE, Struct Biol Unit, Bizkaia Technol Pk, Derio 48160, Spain.
[Gershlick, David C.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
[Hierro, Aitor] Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Spain.
RP Hierro, A (reprint author), CIC BioGUNE, Struct Biol Unit, Bizkaia Technol Pk, Derio 48160, Spain.; Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.; Hierro, A (reprint author), Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Spain.
EM bonifacinoj@helix.nih.gov; ahierro@cicbiogune.es
RI Lucas, Maria/G-9788-2012;
OI Lucas, Maria/0000-0002-7854-4249; Rojas, Adriana/0000-0002-7358-3505;
Bonifacino, Juan S./0000-0002-5673-6370
FU Carlos III Health Institute [PI11/00121]; Basque Government [PI2011-26];
Spanish Ministry of Economy and Competitiveness [BFU2014-59759-R];
intramural program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, NIH [ZIA HD001607]; European
Community's Seventh Framework Programme (FP7) [283570]; Horizon 2020
programme iNEXT [653706]
FX We thank Alberto Marina (CIC bioGUNE) for technical assistance. This
work was supported by the Carlos III Health Institute grant PI11/00121,
the Basque Government grant PI2011-26, the Spanish Ministry of Economy
and Competitiveness grant BFU2014-59759-R (to A.H.), and the intramural
program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, NIH (ZIA HD001607) (to J.S.B.). This study made
use of the Diamond Light Source (Oxfordshire, UK), synchrotron SOLEIL
(Gif-sur Yvette, France), the European Synchrotron Radiation Facility
(ESRF, Grenoble, France), and ALBA synchrotron beamline BL13-XALOC,
funded in part by the European Community's Seventh Framework Programme
(FP7/2007-2013) under BioStruct-X (grant agreement no. 283570) and the
Horizon 2020 programme iNEXT (H2020 project #653706). We thank all the
staff from these facilities, and, in particular, to Andrew Thomson from
SOLEIL, for assistance with X-ray data collection and processing, and
Robert Rambo from Diamond for assistance with SAXS data collection. We
also thank Peter Cullen, Carol R. Haft, and Mitsuaki Tabuchi for kind
gifts of reagents and Philip McCoy (NHLBI, NIH) for cell sorting.
NR 59
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U1 15
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD DEC 1
PY 2016
VL 167
IS 6
BP 1623
EP +
DI 10.1016/j.cell.2016.10.056
PG 27
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE3EN
UT WOS:000389470500022
PM 27889239
ER
PT J
AU Murayi, R
Chittiboina, P
AF Murayi, Roger
Chittiboina, Prashant
TI Glucocorticoids in the management of peritumoral brain edema: a review
of molecular mechanisms
SO CHILDS NERVOUS SYSTEM
LA English
DT Review
DE Peritumoral brain edema (PTBE); Glucocorticoids; Blood-brain barrier
ID VASCULAR-PERMEABILITY FACTOR; CENTRAL-NERVOUS-SYSTEM;
MATRIX-METALLOPROTEINASE EXPRESSION; TIGHT JUNCTION PERMEABILITY;
NF-KAPPA-B; AQUAPORIN-4 EXPRESSION; ENDOTHELIAL-CELLS; DEXAMETHASONE
REGULATION; CAPILLARY-PERMEABILITY; BARRIER PERMEABILITY
AB Peritumoral brain edema (PTBE) is mediated by blood-brain barrier breakdown. PTBE results from interstitial vasogenic brain edema due to vascular endothelial growth factor and other inflammatory products of brain tumors. Glucocorticoids (GCs) are the mainstay for treatment of PTBE despite significant systemic side effects. GCs are thought to affect multiple cell types in the edematous brain. Here, we review preclinical studies of GC effects on edematous brain and review mechanisms underlying GC action on tumor cells, endothelial cells, and astrocytes. GCs may reduce tumor cell viability and suppress vascular endothelial growth factor (VEGF) production in tumor cells. Modulation of expression and distribution of tight junction proteins occludin, claudin-5, and ZO-1 in endothelial cells likely plays a central role in GC action on endothelial cells. GCs may also have an effect on astrocyte angiopoietin production and limited effect on astrocyte aquaporin. A better understanding of these molecular mechanisms may lead to the development of novel therapeutics for management of PTBE with a better side effect profile.
C1 [Murayi, Roger; Chittiboina, Prashant] NINDS, Surg Neurol Branch, Neurosurg Unit Pituitary & Inheritable Dis, NIH, 10 Ctr Dr,Room 3D20, Bethesda, MD 20892 USA.
RP Chittiboina, P (reprint author), NINDS, Surg Neurol Branch, Neurosurg Unit Pituitary & Inheritable Dis, NIH, 10 Ctr Dr,Room 3D20, Bethesda, MD 20892 USA.
EM Prashant.Chittiboina@nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health (NIH); NIH
FX The authors would like to thank Marsha Merrill, PhD, for discussions and
historical insights. This study was funded by the intramural research
program of the National Institute of Neurological Disorders and Stroke
at the National Institutes of Health (NIH). This research was also made
possible through the NIH Medical Research Scholars Program, a
public-private partnership supported jointly by the NIH and generous
contributions to the Foundation for the NIH. The authors thank Ethan
Tyler from the Medical Arts Branch of the NIH Clinical Center for the
illustration.
NR 108
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0256-7040
EI 1433-0350
J9 CHILD NERV SYST
JI Childs Nerv. Syst.
PD DEC
PY 2016
VL 32
IS 12
BP 2293
EP 2302
DI 10.1007/s00381-016-3240-x
PG 10
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA EE5GL
UT WOS:000389633500008
PM 27613642
ER
PT J
AU Moxey-Mims, MM
Flessner, MF
Holzman, L
Kaskel, F
Sedor, JR
Smoyer, WE
Thompson, AM
Yao, L
AF Moxey-Mims, Marva M.
Flessner, Michael F.
Holzman, Lawrence
Kaskel, Frederick
Sedor, John R.
Smoyer, William E.
Thompson, Aliza M.
Yao, Lynne
TI Glomerular Diseases: Registries and Clinical Trials
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RANDOMIZED CONTROLLED-TRIALS;
KIDNEY-DISEASE; LUPUS NEPHRITIS; MEMBRANOUS NEPHROPATHY; PATIENT-CARE;
NEPHROLOGY; HEALTH
AB Nephrology has conducted few high quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are over-arching process issues that affect the conduct of all clinical trials, but there are also some specialty specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.
C1 [Moxey-Mims, Marva M.] NIDDK, Div Kidney Urol & Hematol, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
RP Moxey-Mims, MM (reprint author), NIDDK, Div Kidney Urol & Hematol, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM mm726k@nih.gov
FU NIDDK; Genentech (South San Francisco, CA)
FX M.M.M.-M. and M.F.F. have National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK; Bethesda, MD) oversight for the Cure
Glomerulonephropathy (CureGN) and the Nephrotic Syndrome Study Network
(NEPTUNE) studies. L.H. is funded by the NIDDK as a principal
investigator for CureGN, a site principal investigator for NEPTUNE, and
a consultant for GlaxoSmithKline (Brentford, United Kingdom), Pfizer
(New York, NY), and Bristol-Meyers Squibb (Princeton, NJ). F.K. is a
site principal investigator for CureGN and NEPTUNE studies. J.R.S. is
funded by the NIDDK and serves as a site principal investigator for
NEPTUNE and CureGN and a consultant for Bristol-Meyers Squibb,
GlaxoSmithKline, Sanofi-Genzyme (Framingham, MA), and Thrid Rock
Ventures (Boston, MA). J.R.S. is on the Scientific Advisory Board for
the Phase II Treatment Resistant Nephrotic Syndrome Trial with Abatacept
by Bristol-Meyers Squibb. W.E.S. is funded by the NIDDK as a principal
investigator for CureGN, has received funding from Genentech (South San
Francisco, CA) as a principal investigator on the Randomized Trial
Comparing Rituximab Against Mycophenolate Mofetil in Children With
Refractory Nephrotic Syndrome Trial, and is coprincipal investigator of
the Ohio State University Clinical and Translational Science Awards.
A.M.T. and L.Y. have no disclosures.
NR 30
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD DEC
PY 2016
VL 11
IS 12
BP 2234
EP 2243
DI 10.2215/CJN.00540116
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA EE3OF
UT WOS:000389498200020
PM 27672219
ER
PT J
AU Cohen, SD
Cukor, D
Kimmel, PL
AF Cohen, Scott D.
Cukor, Daniel
Kimmel, Paul L.
TI Anxiety in Patients Treated with Hemodialysis
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Review
ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE;
DEPRESSION; DISORDERS; THERAPY; DIALYSIS; HEALTH; IMPAIRMENT; PREVALENCE
AB Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients' perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD.
C1 [Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA.
[Cukor, Daniel] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA.
[Kimmel, Paul L.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
RP Kimmel, PL (reprint author), NIDDK, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM kimmelp@extra.niddk.nih.gov
NR 33
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD DEC
PY 2016
VL 11
IS 12
BP 2250
EP 2255
DI 10.2215/CJN.02590316
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA EE3OF
UT WOS:000389498200022
PM 27660303
ER
PT J
AU Hartz, J
Yingling, L
Powell-Wiley, TM
AF Hartz, Jacob
Yingling, Leah
Powell-Wiley, Tiffany M.
TI Use of Mobile Health Technology in the Prevention and Management of
Diabetes Mellitus
SO CURRENT CARDIOLOGY REPORTS
LA English
DT Review
DE Mobile health technology; Diabetes mellitus; Cardiovascular disease;
Racial/ethnic minorities; Children; Adolescents
ID RANDOMIZED CONTROLLED-TRIAL; GLUCOSE MONITORING-SYSTEM; BEHAVIOR-CHANGE
TECHNIQUES; PHYSICAL-ACTIVITY; SELF-MANAGEMENT; GLYCEMIC CONTROL;
WEIGHT-LOSS; SMARTPHONE TECHNOLOGY; CHRONIC DISEASE; OLDER-ADULTS
AB Cardiovascular disease is the leading cause of morbidity and mortality globally, with diabetes being an independent risk factor. Adequate diabetes management has proven to be resource-intensive, requiring frequent lab work, primary care and specialist visits, and time-consuming record-keeping by the patient and care team. New mobile health (mHealth) technologies have enhanced how diabetes is managed and care is delivered. While more recent work has investigated mHealth devices as complementary tools in behavioral interventions for diabetes prevention and management, little is still known about the effectiveness of mHealth technology as stand-alone intervention tools for reducing diabetes risk. In addition, more work is needed to identify the role of mHealth technology in treating vulnerable populations to ameliorate cardiovascular health disparities. With advances in mobile health technology development for diabetes prevention and management, these modalities will likely play an increasingly prominent role in reducing cardiometabolic risk for the US population.
C1 [Hartz, Jacob] Childrens Natl Med Ctr, Dept Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA.
[Yingling, Leah; Powell-Wiley, Tiffany M.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,5-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Powell-Wiley, TM (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,5-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jhartz@childrensnational.org; leah.lingling@nih.gov;
tiffany.powell-wiley@nih.gov
OI Yingling, Leah/0000-0002-7851-690X
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute (NHLBI) of the National Institutes of Health (NIH)
FX The views expressed in this manuscript are those of the authors and do
not necessarily represent the views of the National Heart, Lung, and
Blood Institute; the National Institutes of Health; or the U.S.
Department of Health and Human Services. Funding for TP-W and LY is
provided through the Division of Intramural Research of the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health (NIH).
NR 91
TC 0
Z9 0
U1 29
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3782
EI 1534-3170
J9 CURR CARDIOL REP
JI Curr. Cardiol. Rep.
PD DEC
PY 2016
VL 18
IS 12
AR 130
DI 10.1007/s11886-016-0796-8
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EE8RM
UT WOS:000389893400014
PM 27826901
ER
PT J
AU Hirahara, K
Schwartz, D
Gadina, M
Kanno, Y
O'Shea, JJ
AF Hirahara, Kiyoshi
Schwartz, Daniella
Gadina, Massimo
Kanno, Yuka
O'Shea, John J.
TI Targeting cytokine signaling in autoimmunity: back to the future and
beyond
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID ACTIVE RHEUMATOID-ARTHRITIS; JANUS KINASE INHIBITOR; TO-SEVERE
PSORIASIS; RANDOMIZED CONTROLLED-TRIAL; CHRONIC PLAQUE PSORIASIS; HAN
CHINESE POPULATION; LONG-TERM EXTENSION; INADEQUATE RESPONSE;
DOUBLE-BLIND; BACKGROUND METHOTREXATE
AB Cytokines represent structurally diverse soluble factors with critical roles in normal immune function and the pathogenesis of autoimmunity. The emergence of many successful biological therapies targeting cytokines and cytokine receptors exemplifies the importance of cytokines in driving human autoimmune disease; unsurprisingly, there is no paucity of reviews on this subject. Nonetheless, many patients with autoimmune disease do not respond to biologicals, and cure remains an unmet goal. Thus, targeting the intracellular pathways employed by cytokines provides new therapeutic opportunities. A subset of cytokines utilizes the Janus kinase-signal transducer of activators of transcription (JAK-STAT) pathway as a mode of signal transduction. First generation JAK inhibitors (jakinibs) are used to treat rheumatologic disease, and second-generation jakinibs are being developed. Simultaneously, rapid advances are being made in our understanding of the genomic and epigenomic impact of cytokines. In this review, we will briefly review the role of JAKSTAT-dependent cytokines in immune-mediated disease, the current status of Jakinibs, and future possibilities for therapeutic intervention using genomic insights.
C1 [Hirahara, Kiyoshi] Chiba Univ, Grad Sch Med, Dept Immunol, 1-8-1 Inohana Chuo Ku, Chiba 2608670, Japan.
[Schwartz, Daniella; Kanno, Yuka; O'Shea, John J.] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Gadina, Massimo] NIAMS, Translat Immunol Sect, Off Sci Technol, NIH, Bethesda, MD 20892 USA.
RP O'Shea, JJ (reprint author), NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM John.Oshea@nih.gov
RI Hirahara, Kiyoshi/E-2460-2017
OI Hirahara, Kiyoshi/0000-0002-9128-9449
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the NIH
FX The work of Y.K., D.S., M.G., J.O.S. is supported by the Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the NIH.
NR 82
TC 1
Z9 1
U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD DEC
PY 2016
VL 43
BP 89
EP 97
DI 10.1016/j.coi.2016.10.001
PG 9
WC Immunology
SC Immunology
GA EE6OX
UT WOS:000389733200014
PM 27821272
ER
PT J
AU Peyre, H
Hoertel, N
Rivollier, F
Landman, B
McMahon, K
Chevance, A
Lemogne, C
Delorme, R
Blanco, C
Limosin, F
AF Peyre, Hugo
Hoertel, Nicolas
Rivollier, Fabrice
Landman, Benjamin
McMahon, Kibby
Chevance, Astrid
Lemogne, Cedric
Delorme, Richard
Blanco, Carlos
Limosin, Frederic
TI Latent class analysis of the feared situations of social anxiety
disorder: A population-based study
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE generalized; latent class analysis; performance only; psychiatric
disorders; social anxiety disorder; social fears; social phobia;
subtypes
ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE-DISORDER; QUALITY-OF-LIFE;
PSYCHIATRIC DIAGNOSTIC MODULES; IV AUDADIS-IV; GENERAL-POPULATION;
COMORBIDITY SURVEY; PHOBIA; RELIABILITY; SUBTYPES
AB BackgroundLittle is known about differences in mental health comorbidity and quality of life in individuals with social anxiety disorder (SAD) according to the number and the types of feared situations.
MethodsUsing a US nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions, we performed latent class analysis to compare the prevalence rates of mental disorders and quality of life measures across classes defined by the number and the types of feared social situations among individuals with SAD.
ResultsAmong the 2,448 participants with a lifetime diagnosis of SAD, we identified three classes of individuals who feared most social situations but differed in the number of feared social situations (generalized severe [N = 378], generalized moderate [N = 1,049] and generalized low [N = 443]) and a class of subjects who feared only performance situations [N = 578]. The magnitude of associations between each class and a wide range of mental disorders and quality of life measures were consistent with a continuum model, supporting that the deleterious effects of SAD on mental health may increase with the number of social situations feared. However, we found that individuals with the performance only specifier may constitute an exception to this model because these participants had significantly better mental health than other participants with SAD.
ConclusionsOur findings give additional support to the recent changes made in the DSM-5, including the introduction of the performance only specifier and the removal of the generalized specifier to promote the dimensional approach of the number of social fears.
C1 [Peyre, Hugo; Landman, Benjamin; Delorme, Richard] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, Paris, France.
[Peyre, Hugo] Ecole Normale Super, Cognit Sci & Psycholinguist Lab, Paris, France.
[Hoertel, Nicolas; Lemogne, Cedric; Limosin, Frederic] Paris Descartes Univ, PRES Sorbonne Paris Cite, Paris, France.
[Hoertel, Nicolas; Chevance, Astrid; Lemogne, Cedric; Limosin, Frederic] Corentin Celton Hosp, AP HP, Dept Psychiat, Issy Les Moulineaux, France.
[Hoertel, Nicolas; Rivollier, Fabrice; Lemogne, Cedric; Limosin, Frederic] Psychiat & Neurosci Ctr, INSERM UMR 894, Paris, France.
[Rivollier, Fabrice] Paris Descartes Univ, Sainte Anne Hosp, Serv Hospitalouniv, Paris, France.
[McMahon, Kibby] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Blanco, Carlos] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
RP Peyre, H (reprint author), Ecole Normale Super, Dept Etud Cognit, LSCP, 29 Rue Ulm, F-75005 Paris, France.
EM peyrehugo@yahoo.fr
OI Lemogne, Cedric/0000-0002-3487-4721
NR 32
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD DEC
PY 2016
VL 33
IS 12
BP 1178
EP 1187
DI 10.1002/da.22547
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA EE9EA
UT WOS:000389927400011
PM 27575056
ER
PT J
AU Chen, BH
Hivert, MF
Peters, MJ
Pilling, LC
Hogan, JD
Pham, LM
Harries, LW
Fox, CS
Bandinelli, S
Dehghan, A
Hernandez, DG
Hofman, A
Hong, J
Joehanes, R
Johnson, AD
Munson, PJ
Rybin, DV
Singleton, AB
Uitterlinden, AG
Ying, S
Melzer, D
Levy, D
van Meurs, JBJ
Ferrucci, L
Florez, JC
Dupuis, J
Meigs, JB
Kolaczyk, ED
AF Chen, Brian H.
Hivert, Marie-France
Peters, Marjolein J.
Pilling, Luke C.
Hogan, John D.
Pham, Lisa M.
Harries, Lorna W.
Fox, Caroline S.
Bandinelli, Stefania
Dehghan, Abbas
Hernandez, Dena G.
Hofman, Albert
Hong, Jaeyoung
Joehanes, Roby
Johnson, Andrew D.
Munson, Peter J.
Rybin, Denis V.
Singleton, Andrew B.
Uitterlinden, Andre G.
Ying, Saixia
Melzer, David
Levy, Daniel
van Meurs, Joyce B. J.
Ferrucci, Luigi
Florez, Jose C.
Dupuis, Josee
Meigs, James B.
Kolaczyk, Eric D.
CA Magic Investigators
TI Peripheral Blood Transcriptomic Signatures of Fasting Glucose and
Insulin Concentrations
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HUMAN SKELETAL-MUSCLE; TYPE-2 DIABETES
SUSCEPTIBILITY; INFLUENCING GLYCEMIC TRAITS; EAST ASIANS; LOCI;
IDENTIFICATION; EXPRESSION; RESISTANCE; VARIANTS
AB Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.
C1 [Chen, Brian H.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Chen, Brian H.; Fox, Caroline S.; Joehanes, Roby; Johnson, Andrew D.; Levy, Daniel; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Chen, Brian H.; Fox, Caroline S.; Joehanes, Roby; Johnson, Andrew D.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Hivert, Marie-France] Harvard Med Sch, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Hivert, Marie-France; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Boston, MA 02114 USA.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada.
[Peters, Marjolein J.; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Erasmus Univ, Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands.
[Peters, Marjolein J.; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Peters, Marjolein J.; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Rotterdam, Netherlands.
[Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Epidemiol & Publ Hlth Grp, Exeter, Devon, England.
[Hogan, John D.; Pham, Lisa M.; Kolaczyk, Eric D.] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
[Harries, Lorna W.] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
[Hernandez, Dena G.; Singleton, Andrew B.] NIA, Lab Neurogenet, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Hong, Jaeyoung; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Joehanes, Roby] Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA.
[Munson, Peter J.; Ying, Saixia] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Rybin, Denis V.] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.; Meigs, James B.] Broad Inst, Metab Program, Cambridge, MA 02142 USA.
[Florez, Jose C.; Meigs, James B.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Florez, Jose C.; Meigs, James B.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Kolaczyk, Eric D.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Kolaczyk, ED (reprint author), Boston Univ, Program Bioinformat, Boston, MA 02215 USA.; Meigs, JB (reprint author), Broad Inst, Metab Program, Cambridge, MA 02142 USA.; Meigs, JB (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Meigs, JB (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.; Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.; Kolaczyk, ED (reprint author), Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
EM jmeigs@partners.org; kolaczyk@bu.edu
FU European Commission [HEALTH-F2-2008-201865, GEFOS, HEALTH-F2-2008 35627,
TREAT-OA 200800]; Netherlands Organisation for Scientific Research
[175.010.2005.011, 911-03-012]; Research Institute for Diseases in the
Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative/Netherlands
Consortium for Healthy Ageing [050-060-810]; Netherlands Organisation
for Scientific Research VIDI grant [917103521]; Erasmus University
Medical Center Rotterdam; Erasmus University; Netherlands Organisation
for Health Research and Development; Research Institute for Diseases in
the Elderly; Netherlands Ministry of Education, Culture and Science;
Netherlands Ministry for Health, Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam
FX This work was funded by the European Commission (HEALTH-F2-2008-201865,
GEFOS, HEALTH-F2-2008 35627, and TREAT-OA 200800), the Netherlands
Organisation for Scientific Research (175.010.2005.011 and 911-03-012),
the Research Institute for Diseases in the Elderly (014-93-015, RIDE2),
the Netherlands Genomics Initiative/Netherlands Consortium for Healthy
Ageing (050-060-810), and Netherlands Organisation for Scientific
Research VIDI grant (917103521). The RS is funded by Erasmus University
Medical Center Rotterdam and Erasmus University; Netherlands
Organisation for Health Research and Development; the Research Institute
for Diseases in the Elderly; the Netherlands Ministry of Education,
Culture and Science; the Netherlands Ministry for Health, Welfare and
Sports; the European Commission (DG XII); and the Municipality of
Rotterdam.; The FHS is funded by the National Institutes of Health (NIH)
contract N01-HC-25195. The laboratory work for this investigation was
funded by the Division of Intramural Research, National Heart, Lung, and
Blood Institute, NIH. The analytical component of this project was
funded by the Division of Intramural Research, National Heart, Lung, and
Blood Institute, and the Center for Information Technology, NIH. This
study utilized the high-performance computational capabilities of the
Biowulf Linux cluster (https://hpc.nih.gov/) and Helix Systems
(http://helix.nih.gov) at the NIH. L.M.P., J.D., J.B.M., and E.D.K. were
partially supported by NIH grant R01 DK078616. J.B.M. is partly
supported by NIH grant K24 DK080140.; This research was supported in
part by the Intramural Research Program, National Institute on Aging,
NIH (Z01-AG000947 and Z01-AG000185). The InCHIANTI study baseline
(1998-2000) was supported as a targeted project (ICS110.1/RF97.71) by
the Italian Ministry of Health and in part by the National Institute on
Aging (contracts 263 MD 9164 and 263 MD 821336). L.W.H. was funded by a
grant from the U.K. Medical Research Council (MR/J006777/1).
NR 42
TC 0
Z9 0
U1 2
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD DEC
PY 2016
VL 65
IS 12
BP 3794
EP 3804
DI 10.2337/db16-0470
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EE0RA
UT WOS:000389285400029
PM 27625022
ER
PT J
AU Geliebter, A
McOuatt, H
Tetreault, CB
Kordunova, D
Rice, K
Zammit, G
Gluck, M
AF Geliebter, Allan
McOuatt, Haley
Tetreault, Cora B.
Kordunova, Dorina
Rice, Kathleen
Zammit, Gary
Gluck, Marci
TI Is night eating syndrome associated with obstructive sleep apnea, BMI,
and depressed mood in patients from a sleep laboratory study?
SO EATING BEHAVIORS
LA English
DT Article
DE OSA; NES; Obesity; Eating disorders; AHI; BMI
ID CLINICAL-SIGNIFICANCE; OBESE-PATIENTS; WEIGHT-LOSS; DISORDERS;
EPIDEMIOLOGY; VALIDATION; STUDENTS; FEATURES; ANXIETY
AB Purpose: The aim of this study was to assess night eating syndrome (NES) in patients referred for polysomnography and its association with obstructive sleep apnea (OSA). We also assessed whether participants with OSA were more likely to get up and eat at night, and whether these behaviors were associated with the apnea-hypopnea sleep index (AHI). We additionally examined whether NES and OSA were associated with BMI, and assessed depressed mood among participants with NES or OSA.
Methods: The Night Eating Diagnostic Questionnaire (NEDQ), Zung Depression Scale, and demographic and medical questionnaires were used to evaluate 84 qualified participants. Polysomnography was used to assess AHI, and therefore OSA.
Results: Thirty individuals met full or sub-threshold NES (NES[St]) criteria, and 54 had no night eating (Normal). Eighty-nine percent of the sample had OSA with AHI >= 5. Neither AHI nor BMI differed between NES(St) and Normal, F(1,82) - 1.67, p - 0.20 and F(1, 82) - 2.2, p - 0.14, respectively. Participants with NES(St) were, however, more likely than Normal to have depressed mood (mild, moderately, or severely depressed), x(2) = 4.47 p = 0.03. There was a positive correlation between AHI and BMI, r = 0.37, p = 0.001. Those with OSA were not more likely to eat at night, F(1,82) = 0.04, p = 0.84, or get out of bed more often, F(1,13) = 0.23, p = 0.64, and there was no correlation between AHI and eating at night (r = -0.11, p = 0.31). However, there was a positive correlation between AHI and the number of times participants got up out of bed (r = 0.81, p < 0.001).
Conclusions: We found that NES was not associated with BMI or AHI severity. The findings show that NES is primarily an eating disorder, rather than a sleep disorder, and that there is an association between NES and depressed mood. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Geliebter, Allan; McOuatt, Haley; Tetreault, Cora B.; Kordunova, Dorina] Mt Sinai St Lukes Hosp, New York, NY USA.
[Geliebter, Allan; Kordunova, Dorina] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Geliebter, Allan] Touro Coll & Univ Syst, Dept Psychol, New York, NY USA.
[Rice, Kathleen; Zammit, Gary] Clinilabs Sleep Disorders Inst, New York, NY 10025 USA.
[Gluck, Marci] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85099 USA.
RP Geliebter, A (reprint author), Mt Sinai St Lukes Hosp, S&R, 11th Flr,Rm 1136, New York, NY 10025 USA.
EM ageliebt@chpnet.org
FU NIH [DK068603, DK074046]
FX Funding for the study was provided in part by NIH grants DK068603 and
DK074046. NIH had no role in the study design, collection, analysis or
interpretation of the data, writing the manuscript, or the decision to
submit the paper for publication.
NR 41
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1471-0153
EI 1873-7358
J9 EAT BEHAV
JI Eat. Behav.
PD DEC
PY 2016
VL 23
BP 115
EP 119
DI 10.1016/j.eatbeh.2016.08.008
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA EF0EZ
UT WOS:000389999800021
PM 27643566
ER
PT J
AU Fan, R
Chiu, CY
Jung, J
Weeks, DE
Wilson, AF
Bailey-Wilson, JE
Amos, CI
Chen, Z
Mills, JL
Xiong, M
AF Fan, Ruzong
Chiu, Chi-yang
Jung, Jeesun
Weeks, Daniel E.
Wilson, Alexander F.
Bailey-Wilson, Joan E.
Amos, Christopher I.
Chen, Zhen
Mills, James L.
Xiong, Momiao
TI A Comparison Study of Fixed and Mixed Effect Models for Gene Level
Association Studies of Complex Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variants; common variants; association mapping;
quantitative/dichotomous trait loci; complex traits; functional data
analysis; multivariate linear models; logistic regressions
ID FUNCTIONAL LINEAR-MODELS; QUANTITATIVE TRAITS; RARE; LOCI; METAANALYSIS;
VARIANTS; DISEASES; LINKAGE
AB In association studies of complex traits, fixed-effect regression models are usually used to test for association between traits and major gene loci. In recent years, variance-component tests based on mixed models were developed for region-based genetic variant association tests. In the mixed models, the association is tested by a null hypothesis of zero variance via a sequence kernel association test (SKAT), its optimal unified test (SKAT-O), and a combined sum test of rare and common variant effect (SKAT-C). Although there are some comparison studies to evaluate the performance of mixed and fixed models, there is no systematic analysis to determine when the mixed models perform better and when the fixed models perform better. Here we evaluated, based on extensive simulations, the performance of the fixed and mixed model statistics, using genetic variants located in 3, 6, 9, 12, and 15 kb simulated regions. We compared the performance of three models: (i) mixed models that lead to SKAT, SKAT-O, and SKAT-C, (ii) traditional fixed-effect additive models, and (iii) fixed-effect functional regression models. To evaluate the type I error rates of the tests of fixed models, we generated genotype data by two methods: (i) using all variants, (ii) using only rare variants. We found that the fixed-effect tests accurately control or have low false positive rates. We performed simulation analyses to compare power for two scenarios: (i) all causal variants are rare, (ii) some causal variants are rare and some are common. Either one or both of the fixed-effect models performed better than or similar to the mixed models except when (1) the region sizes are 12 and 15 kb and (2) effect sizes are small. Therefore, the assumption of mixed models could be satisfied and SKAT/SKAT-O/SKAT-C could perform better if the number of causal variants is large and each causal variant contributes a small amount to the traits (i.e., polygenes). In major gene association studies, we argue that the fixed-effect models perform better or similarly to mixed models in most cases because some variants should affect the traits relatively large. In practice, it makes sense to perform analysis by both the fixed and mixed effect models and to make a comparison, and this can be readily done using our R codes and the SKAT packages. Published 2016 Wiley Periodicals, Inc.
C1 [Fan, Ruzong; Chiu, Chi-yang; Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Jung, Jeesun] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD USA.
[Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Wilson, Alexander F.; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Amos, Christopher I.] Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Lebanon, NH USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Xiong, Momiao] Univ Texas Houston, Ctr Human Genet, Houston, TX USA.
RP Fan, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
EM fanr@mail.nih.gov
OI Weeks, Daniel/0000-0001-9410-7228
NR 32
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2016
VL 40
IS 8
BP 702
EP 721
DI 10.1002/gepi.21984
PG 20
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA EE5GO
UT WOS:000389633800003
PM 27374056
ER
PT J
AU He, QC
Cai, TX
Liu, Y
Zhao, N
Harmon, QE
Almli, LM
Binder, EB
Engel, SM
Ressler, KJ
Conneely, KN
Lin, XH
Wu, MC
AF He, Qianchuan
Cai, Tianxi
Liu, Yang
Zhao, Ni
Harmon, Quaker E.
Almli, Lynn M.
Binder, Elisabeth B.
Engel, Stephanie M.
Ressler, Kerry J.
Conneely, Karen N.
Lin, Xihong
Wu, Michael C.
TI Prioritizing individual genetic variants after kernel machine testing
using variable selection
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE genetic association studies; kernel machine methods; KNIFE; set-based;
variable selection
ID GENOME-WIDE ASSOCIATION; REGRESSION; REGULARIZATION; EXPRESSION;
OUTCOMES; STRESS; CANCER; RARE
AB Kernel machine learning methods, such as the SNP-set kernel association test (SKAT), have been widely used to test associations between traits and genetic polymorphisms. In contrast to traditional single-SNP analysis methods, these methods are designed to examine the joint effect of a set of related SNPs (such as a group of SNPs within a gene or a pathway) and are able to identify sets of SNPs that are associated with the trait of interest. However, as with many multi-SNP testing approaches, kernel machine testing can draw conclusion only at the SNP-set level, and does not directly inform on which one(s) of the identified SNP set is actually driving the associations. A recently proposed procedure, KerNel Iterative Feature Extraction (KNIFE), provides a general framework for incorporating variable selection into kernel machine methods. In this article, we focus on quantitative traits and relatively common SNPs, and adapt the KNIFE procedure to genetic association studies and propose an approach to identify driver SNPs after the application of SKAT to gene set analysis. Our approach accommodates several kernels that are widely used in SNP analysis, such as the linear kernel and the Identity by State (IBS) kernel. The proposed approach provides practically useful utilities to prioritize SNPs, and fills the gap between SNP set analysis and biological functional studies. Both simulation studies and real data application are used to demonstrate the proposed approach.
C1 [He, Qianchuan; Liu, Yang; Zhao, Ni; Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Cai, Tianxi; Lin, Xihong] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Harmon, Quaker E.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Almli, Lynn M.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Binder, Elisabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.
[Engel, Stephanie M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Ressler, Kerry J.] McLean Hosp, Div Depress & Anxiety Disorders, 115 Mill St, Belmont, MA 02178 USA.
[Conneely, Karen N.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
RP He, QC; Wu, MC (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
EM qhe@fredhutch.org; mcwu@fredhutch.org
OI Wu, Michael C./0000-0002-3357-6570
FU NCI NIH HHS [P01 CA134294]; NHGRI NIH HHS [R01 HG006292, R01 HG007508,
U54 HG007963]; NICHD NIH HHS [R21 HD060207]; NIEHS NIH HHS [P30
ES000002]; NIMH NIH HHS [R01 MH071537, R01 MH096764]
NR 33
TC 0
Z9 0
U1 8
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2016
VL 40
IS 8
BP 722
EP 731
DI 10.1002/gepi.21993
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA EE5GO
UT WOS:000389633800004
PM 27488097
ER
PT J
AU Loud, JT
Bremer, RC
Mai, PL
Peters, JA
Giri, N
Stewart, DR
Greene, MH
Alter, BP
Savage, SA
AF Loud, Jennifer T.
Bremer, Renee C.
Mai, Phuong L.
Peters, June A.
Giri, Neelam
Stewart, Douglas R.
Greene, Mark H.
Alter, Blanche P.
Savage, Sharon A.
TI Research participant interest in primary, secondary, and incidental
genomic findings
SO GENETICS IN MEDICINE
LA English
DT Article
DE familial cancer syndromes; genetic testing; incidental findings;
intentions to receive research genetic results; whole genome/exome
sequencing
ID GENETIC RESEARCH; RETURN; EXOME; ATTITUDES; PREFERENCES; CHILDREN;
DISEASE; VIEWS
AB Purpose: To define the frequency with which adult research participants consent to be offered clinically validated research genetic test results (RR) and incidental findings (IF).
Methods: Consents were obtained from 506 adults enrolled in one of three studies within the National Cancer Institute Clinical Genetics Branch's Familial Cancer Research Program. A cross-sectional analysis was performed involving the choices indicated on study consents regarding receipt of RR and IF.
Results: Ninety-seven percent opted to receive RR and IF. Participants who declined (n = 16) included two cancer survivors who were mutation-positive (1 = RR and 1 = both), eight who knew their primary mutation status (3 = RR; 4 = IF; 1 = both), three nonbloodline relatives (1 = RR; 2 = both), one untested but with the syndromic phenotype (1 = IF), and two parents of an affected child (2 = both). We speculate that these individuals either already had sufficient information, were not prepared to learn more, or felt that the information would not change their personal health-care decision making.
Conclusions: Adult research participants from families at high genetic risk for cancer overwhelmingly indicated their preference to receive both RR and IF. Future research will seek to identify the reasons for declining RR and IF and to study the impact of receipt of RR and IF on personal medical decision making.
C1 [Loud, Jennifer T.; Bremer, Renee C.; Mai, Phuong L.; Peters, June A.; Giri, Neelam; Stewart, Douglas R.; Greene, Mark H.; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
RP Loud, JT (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
EM LoudJ@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health. We are grateful to the study participants
for their valuable contributions to our research.
NR 23
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2016
VL 18
IS 12
BP 1218
EP 1225
DI 10.1038/gim.2016.36
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA EE4HU
UT WOS:000389563700009
PM 27101135
ER
PT J
AU Hunter, JE
Irving, SA
Biesecker, LG
Buchanan, A
Jensen, B
Lee, K
Martin, CL
Milko, L
Muessig, K
Niehaus, AD
O'Daniel, J
Piper, MA
Ramos, EM
Schully, SD
Scott, AF
Slavotinek, A
Sobreira, N
Strande, N
Weaver, M
Webber, EM
Williams, MS
Berg, JS
Evans, JP
Goddard, KAB
AF Hunter, Jessica Ezzell
Irving, Stephanie A.
Biesecker, Leslie G.
Buchanan, Adam
Jensen, Brian
Lee, Kristy
Martin, Christa Lese
Milko, Laura
Muessig, Kristin
Niehaus, Annie D.
O'Daniel, Julianne
Piper, Margaret A.
Ramos, Erin M.
Schully, Sheri D.
Scott, Alan F.
Slavotinek, Anne
Sobreira, Nara
Strande, Natasha
Weaver, Meredith
Webber, Elizabeth M.
Williams, Marc S.
Berg, Jonathan S.
Evans, James P.
Goddard, Katrina A. B.
CA ClinGen Resource
TI A standardized, evidence-based protocol to assess clinical actionability
of genetic disorders associated with genomic variation
SO GENETICS IN MEDICINE
LA English
DT Article
DE clinical actionability; exome sequencing; genome sequencing; incidental
findings; secondary findings
ID INCIDENTAL FINDINGS; MANAGEMENT; EXOME; GUIDELINES; MEDICINE
AB Purpose: Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research.
Methods: We developed a practical, standardized protocol to identify available evidence and generate qualitative summary reports of actionability for disorders and associated genes. We applied a semi-quantitative metric to score actionability.
Results: We generated summary reports and actionability scores for the 56 genes and associated disorders recommended by the American College of Medical Genetics and Genomics for return as secondary findings from clinical genome-scale sequencing. We also describe the challenges that arose during the development of the protocol that highlight important issues in characterizing actionability across a range of disorders.
Conclusion: The ClinGen framework for actionability assessment will assist research and clinical communities in making clear, efficient, and consistent determinations of actionability based on transparent criteria to guide analysis and reporting of findings from clinical genome-scale sequencing.
C1 [Hunter, Jessica Ezzell; Irving, Stephanie A.; Muessig, Kristin; Piper, Margaret A.; Webber, Elizabeth M.; Goddard, Katrina A. B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97232 USA.
[Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Buchanan, Adam; Williams, Marc S.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA.
[Jensen, Brian] Univ N Carolina, Sch Med, Div Cardiol, McAllister Heart Inst, Chapel Hill, NC USA.
[Lee, Kristy; Milko, Laura; O'Daniel, Julianne; Strande, Natasha; Berg, Jonathan S.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA USA.
[Niehaus, Annie D.; Ramos, Erin M.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Schully, Sheri D.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[Scott, Alan F.; Sobreira, Nara] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Slavotinek, Anne] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Weaver, Meredith] Amer Coll Med Genet & Genom, Bethesda, MD USA.
RP Hunter, JE (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97232 USA.
EM Jessica.E.Hunter@kpchr.org
OI Strande, Natasha/0000-0001-5148-9772; Hunter,
Jessica/0000-0002-1117-1097
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Human Genome Research Institute; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[1U41HG006834-01A1, 1U01HG007437-01, 1U01HG007436-01, 1UO1HG00648701];
Intramural Research Program of the National Human Genome Research
Institute
FX This project has been funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
no. HHSN261200800001E. The ClinGen consortium is also funded by the
National Human Genome Research Institute and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development through
contracts 1U41HG006834-01A1, 1U01HG007437-01, 1U01HG007436-01, and
1UO1HG00648701. The efforts of L.G.B. were supported by the Intramural
Research Program of the National Human Genome Research Institute.
NR 23
TC 2
Z9 2
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2016
VL 18
IS 12
BP 1258
EP 1268
DI 10.1038/gim.2016.40
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA EE4HU
UT WOS:000389563700014
PM 27124788
ER
PT J
AU Lee, EMJ
Xu, K
Mosbrook, E
Links, A
Guzman, J
Adams, DR
Flynn, E
Valkanas, E
Toro, C
Tifft, CJ
Boerkoel, CF
Gahl, WA
Sincan, M
AF Lee, Elizabeth M. J.
Xu, Karen
Mosbrook, Emma
Links, Amanda
Guzman, Jessica
Adams, David R.
Flynn, Elise
Valkanas, Elise
Toro, Camillo
Tifft, Cynthia J.
Boerkoel, Cornelius F.
Gahl, William A.
Sincan, Murat
TI Pharmacogenomic incidental findings in 308 families: The NIH Undiagnosed
Diseases Program experience
SO GENETICS IN MEDICINE
LA English
DT Article
DE next generation sequencing; NIH undiagnosed; diseases program;
pharmacogenomics; precision medicine; secondary findings
ID DNA-SEQUENCING DATA; PEDIATRIC PHARMACOGENOMICS; GENETIC-VARIANTS; DATA
SETS; FRAMEWORK; MORPHINE; OPRM1; POLYMORPHISMS; ASSOCIATION; GENOTYPE
AB PURPOSE: Using single-nucleotide polymorphism (SNP) chip and exome sequence data from individuals participating in the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP), we evaluated the number and therapeutic informativeness of incidental pharmacogenetic variants.
METHODS: Pharmacogenomics Knowledgebase (PharmGKB) annotated sequence variants were identified in 1,101 individuals. Medication records of participants were used to identify individuals prescribed medications with a genetic variant that might alter efficacy.
RESULTS: A total of 395 sequence variants, including 19 PharmGKB 1A and 1B variants, were identified in SNP chip sequence data, and 388 variants, including 21 PharmGKB 1A and 1B variants, were identified in the exome sequence data. Nine participants had incidental pharmacogenetic variants associated with altered efficacy of a prescribed medication.
CONCLUSIONS: Despite the small size of the NIH UDP patient cohort, we identified pharmacogenetic incidental findings potentially useful for guiding therapy. Consequently, groups conducting clinical genomic studies might consider reporting of pharmacogenetic incidental findings
C1 [Lee, Elizabeth M. J.; Xu, Karen; Mosbrook, Emma; Links, Amanda; Guzman, Jessica; Adams, David R.; Flynn, Elise; Valkanas, Elise; Toro, Camillo; Tifft, Cynthia J.; Boerkoel, Cornelius F.; Gahl, William A.; Sincan, Murat] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Elizabeth M. J.; Xu, Karen; Mosbrook, Emma; Links, Amanda; Guzman, Jessica; Adams, David R.; Flynn, Elise; Valkanas, Elise; Toro, Camillo; Tifft, Cynthia J.; Boerkoel, Cornelius F.; Gahl, William A.; Sincan, Murat] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Sincan, M (reprint author), NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.; Sincan, M (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM sincanm@mail.nih.gov
OI Lee, Elizabeth/0000-0003-3412-1591
FU Common Fund, Office of the Director; Intramural Research Program of the
National Human Genome Research Institute (NIH, Bethesda, MD, USA)
FX We thank NHGRI Intramural Sequencing Center and Appistry, Inc., for
their sequencing, alignment, genotyping, and annotation services. This
work was supported in part by the Common Fund, Office of the Director,
and the Intramural Research Program of the National Human Genome
Research Institute (NIH, Bethesda, MD, USA).
NR 20
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2016
VL 18
IS 12
BP 1303
EP 1307
DI 10.1038/gim.2016.47
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA EE4HU
UT WOS:000389563700020
PM 27253732
ER
PT J
AU Yu, W
Gwinn, M
Dotson, WD
Green, RF
Clyne, M
Wulf, A
Bowen, S
Kolor, K
Khoury, MJ
AF Yu, Wei
Gwinn, Marta
Dotson, W. David
Green, Ridgely Fisk
Clyne, Mindy
Wulf, Anja
Bowen, Scott
Kolor, Katherine
Khoury, Muin J.
TI A knowledge base for tracking the impact of genomics on population
health
SO GENETICS IN MEDICINE
LA English
DT Article
ID PREVENTION; MEDICINE; BEDSIDE
AB Purpose: We created an online knowledge base (the Public Health Genoinics Knowledge Base (PHGKB)) to provide system, atically curated and updated informatkin that bridges population-based research on genomics with clinical and public health applications
Methods: Weekly horizon scanning of a wide variety of online, resources is used to-retrieve relevant scientific publications, guide, lines, and commentaries. After curation by domain experts, links are deposited-inta Web-based databases.
Results: PHGKB currently consists of nine component databases. Users can search the entire knowledge base or search one or more component databases directly and choose options. for customizing the display of their search results.
Conclusion: PHGKB offers researchers, policy makers, practitioners, and the general public a way to fmd information they need to tinder- stand the complicated landscape of genomics and population health.
C1 [Yu, Wei; Gwinn, Marta; Dotson, W. David; Green, Ridgely Fisk; Wulf, Anja; Bowen, Scott; Kolor, Katherine; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Gwinn, Marta] McKing Consulting Corp, Atlanta, GA USA.
[Green, Ridgely Fisk] Carter Consulting Inc, Atlanta, GA USA.
[Clyne, Mindy] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Clyne, Mindy] Kelly Serv, Troy, NY USA.
[Wulf, Anja] Cadence Grp, Atlanta, GA USA.
RP Yu, W (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
EM wby0@cdc.gov
OI Dotson, William David/0000-0002-9606-6594
FU Intramural CDC HHS [CC999999]
NR 8
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2016
VL 18
IS 12
BP 1312
EP 1314
DI 10.1038/gim.2016.63
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA EE4HU
UT WOS:000389563700022
PM 27280867
ER
PT J
AU Mishkin, G
Minasian, LM
Kohn, EC
Noone, AM
Temkin, SM
AF Mishkin, Grace
Minasian, Lori M.
Kohn, Elise C.
Noone, Anne-Michelle
Temkin, Sarah M.
TI The generalizability of NCI-sponsored clinical trials accrual among
women with gynecologic malignancies
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Clinical trials; Disparities; SEER
ID CANCER-TREATMENT TRIALS; UNITED-STATES; RACIAL/ETHNIC DIFFERENCES;
MINORITY PARTICIPATION; AFRICAN-AMERICANS; CERVICAL-CANCER;
ONCOLOGY-GROUP; DISPARITIES; ENROLLMENT; AGE
AB Objectives. Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population.
Methods. Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data.
Results. There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time.
Conclusions. Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Mishkin, Grace; Kohn, Elise C.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Minasian, Lori M.; Temkin, Sarah M.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Noone, Anne-Michelle] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Temkin, SM (reprint author), NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
EM temkinsm@mail.nih.gov
NR 37
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Z9 0
U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD DEC
PY 2016
VL 143
IS 3
BP 611
EP 616
DI 10.1016/j.ygyno.2016.09.026
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA ED9EO
UT WOS:000389173200027
PM 27697287
ER
PT J
AU Sips, M
Liu, QQ
Draghi, M
Ghebremichael, M
Berger, CT
Suscovich, TJ
Sun, Y
Walker, BD
Carrington, M
Altfeld, M
Brouckaert, P
De Jager, PL
Alter, G
AF Sips, Magdalena
Liu, Qingquan
Draghi, Monia
Ghebremichael, Musie
Berger, Christoph T.
Suscovich, Todd J.
Sun, Yongtao
Walker, Bruce D.
Carrington, Mary
Altfeld, Marcus
Brouckaert, Peter
De Jager, Philip L.
Alter, Galit
TI HLA-C levels impact natural killer cell subset distribution and function
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE HLA-C; KIR; Natural killer cells; HIV-1
ID HUMAN CYTOMEGALOVIRUS-INFECTION; CLASS-I MOLECULES; MHC CLASS-I; NK
CELLS; INHIBITORY RECEPTORS; SURFACE EXPRESSION; SELF-TOLERANCE; B
HAPLOTYPES; HIV-1; EDUCATION
AB Differences in HLA-C expression are inversely correlated with HIV viral load set-point and slower progression to AIDS, linked to enhanced cytotoxic T cell immunity. Yet, beyond T cells, HLA-C serves as a dominant ligand for natural killer (NK) cell killer immunoglobulin-like receptors (KIR). Thus, we speculated that HLA-C expression levels may also impact NK activity, thereby modulating HIV antiviral control. Phenotypic and functional profiling was performed on freshly isolated PBMCs. HLA-C expression was linked to changes in NK subset distribution and licensing, particularly in HLA-C1/C1, KIR2DL3+2DL2-individuals. Moreover, high levels of HLA-C, were associated with reduced frequencies of anergic CD56(neg) NKs and lower frequencies of KIR2DL1/2/3+ NK cells, pointing to an HLA-C induced influence on the NK cell development in the absence of disease. In HIV infection, several spontaneous controllers, that expressed higher levels of HLA-C demonstrated robust NK-IFN-gamma secretion in response to target cells, highlighting a second disease induced licensing phenotype. Thus this population study points to a potential role for HLA-C levels both in NI(cell education and development. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Sips, Magdalena; Draghi, Monia; Ghebremichael, Musie; Berger, Christoph T.; Suscovich, Todd J.; Walker, Bruce D.; Carrington, Mary; Altfeld, Marcus; Alter, Galit] Ragan Inst MGH MIT & Harvard, Cambridge, MA USA.
[Sips, Magdalena; Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium.
[Liu, Qingquan] Fourth Mil Med Univ, Tangdu Hosp, Dept Endocrinol, Xian, Shaanxi, Peoples R China.
[Berger, Christoph T.] Univ Basel Hosp, Basel, Switzerland.
[Sun, Yongtao] Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian, Shaanxi, Peoples R China.
[Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA.
[Altfeld, Marcus] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany.
[De Jager, Philip L.] Brigham & Womens Hosp, Div Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA.
[De Jager, Philip L.] Harvard Med Sch, Cambridge, MA USA.
[De Jager, Philip L.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
RP Alter, G (reprint author), Ragan Inst MGH MIT & Harvard, Cambridge, MA USA.
EM galter@mgh.harvard.edu
FU PhenoGenetic Project at Brigham & Women's Hospital [RC2 GM093080]; Ragon
Institute; National Institute of Health [R01 AI080289]; NIH Harvard
Center for AIDS Research [P30 AI060354-02]; Frederick National
Laboratory for Cancer Research [HHSN261200800001E]; NIH, Frederick
National Lab, Center for Cancer Research
FX We thank the subjects of the PhenoGenetic Project at Brigham & Women's
Hospital for the samples that they have provided (RC2 GM093080). This
work was supported by the Ragon Institute, the National Institute of
Health (R01 AI080289) and NIH Harvard Center for AIDS Research (P30
AI060354-02). This project has been funded in whole or in part with
federal funds from the Frederick National Laboratory for Cancer
Research, under Contract No. HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This Research was supported in part by the Intramural
Research Program of the NIH, Frederick National Lab, Center for Cancer
Research.
NR 42
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PD DEC
PY 2016
VL 77
IS 12
BP 1147
EP 1153
DI 10.1016/j.humimm.2016.08.004
PG 7
WC Immunology
SC Immunology
GA EE9RY
UT WOS:000389965100008
PM 27521484
ER
PT J
AU Lippens, C
Duraes, FV
Dubrot, J
Brighouse, D
Lacroix, M
Irla, M
Aubry-Lachainaye, JP
Reith, W
Mandl, JN
Hugues, S
AF Lippens, Carla
Duraes, Fernanda V.
Dubrot, Juan
Brighouse, Dale
lacroix, MathilDe
Irla, Magali
Aubry-Lachainaye, Jean-Pierre
Reith, Walter
Mandl, Judith N.
Hugues, Stephanie
TI IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Review
DE Regulatory T cells; Plasmacytoid dendritic cells; Indoleamine
2,3-dyoxygenase; Antigen presentation; Tolerance; Experimental
autoimmune; encephalomyelitis
ID PLASMACYTOID DENDRITIC CELLS; REGULATORY T-CELLS; INDOLEAMINE
2,3-DIOXYGENASE EXPRESSION; RESTRICTED ANTIGEN PRESENTATION; TRYPTOPHAN
CATABOLISM; TRANSGENIC MICE; IN-VIVO; VIRAL-INFECTION; TOLERANCE;
INDUCTION
AB Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine-2,3dioxygenase (IDO) in steady-state lymph nodes (LNs). IDO expression by LN pDCs was closely dependent on MHCII-mediated, antigen-dependent, interactions with Treg. We further established that IDO production by pDCs was necessary to confer suppressive function to Tregs. During EAE development, IDO expression by pDCs was required for the generation of Tregs capable of dampening the priming of encephalitogenic T cell and disease severity. Thus, we describe a novel crosstalk between pDCs and Tregs: Tregs shape tolerogenic functions of pDCs prior to inflammation, such that pDCs in turn, promote Treg suppressive functions during autoimmunity. (C) 2016 The Authors. Published by Elsevier Ltd.
C1 [Lippens, Carla; Duraes, Fernanda V.; Dubrot, Juan; Brighouse, Dale; lacroix, MathilDe; Irla, Magali; Reith, Walter; Hugues, Stephanie] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
[Aubry-Lachainaye, Jean-Pierre] Univ Geneva, Flow Cytometry Core Facil, CH-1211 Geneva 4, Switzerland.
[Mandl, Judith N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Duraes, Fernanda V.] Novartis Inst BioMed Res, Basel, Switzerland.
[Irla, Magali] Aix Marseille Univ, Ctr Immunol Marseille Luminy, INSERM, CNRS UMR7280,U1104, Marseille, France.
[Mandl, Judith N.] McGill Univ, Dept Physiol, Life Sci Complex, Montreal, PQ, Canada.
[Mandl, Judith N.] McGill Univ, Complex Traits Grp, Life Sci Complex, Montreal, PQ, Canada.
RP Hugues, S (reprint author), Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
EM stephanie.hugues@unige.ch
OI Irla, Magali/0000-0001-8803-9708
FU Swiss National Science Foundation [PP00P3_152951]; European Research
Council [281365]; Swiss Multiple Sclerosis Society; Intramural Research
Program of NIAID, NIH
FX The authors thank C. Gameiro for excellent assistance in flow cytometry,
the E. Shevach lab for providing us with Scurfy mice and T. Sparwasser
for providing us with DEREG mice. We also thank R. Germain, Leslie Guery
and I. Dunand-Sauthier for valuable discussions, D. Merkler and M.
Gannage for reviewing the manuscript, and C. Orabona, M. Benkhoucha and
G. Schneiter for technical help. This work was supported by the Swiss
National Science Foundation (PP00P3_152951 to S.H.), the European
Research Council (281365 to S.H.) and the Swiss Multiple Sclerosis
Society (to S.H), and by the Intramural Research Program of NIAID, NIH
(to J.N.M.).
NR 61
TC 0
Z9 0
U1 3
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD DEC
PY 2016
VL 75
BP 39
EP 49
DI 10.1016/j.jaut.2016.07.004
PG 11
WC Immunology
SC Immunology
GA EE6OD
UT WOS:000389731200005
PM 27470005
ER
PT J
AU Yau, MS
Demissie, S
Zhou, YH
Anderson, DE
Lorbergs, AL
Kiel, DP
Allaire, BT
Yang, LJ
Cupples, LA
Travison, TG
Bouxsein, ML
Karasik, D
Samelson, EJ
AF Yau, Michelle S.
Demissie, Serkalem
Zhou, Yanhua
Anderson, Dennis E.
Lorbergs, Amanda L.
Kiel, Douglas P.
Allaire, Brett T.
Yang, Laiji
Cupples, L. Adrienne
Travison, Thomas G.
Bouxsein, Mary L.
Karasik, David
Samelson, Elizabeth J.
TI Heritability of Thoracic Spine Curvature and Genetic Correlations With
Other Spine Traits: The Framingham Study
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE AGING; QCT; DISEASES AND DISORDERS RELATED TO BONE; GENETIC RESEARCH;
EPIDEMIOLOGY
ID FACET JOINT OSTEOARTHRITIS; LOW-BACK-PAIN; ABDOMINAL AORTIC
CALCIFICATION; LOWER-EXTREMITY PERFORMANCE; COMMUNITY-BASED POPULATION;
MUSCLE FAT INFILTRATION; BONE-MINERAL DENSITY; OLDER MEN;
COMPUTED-TOMOGRAPHY; DISC DEGENERATION
AB Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co-occurring measures of spine health may provide insight into the etiology of hyperkyphosis. The purpose of our study was to estimate heritability of thoracic spine curvature using T-4-T-12 kyphosis (Cobb) angle and genetic correlations between thoracic spine curvature and vertebral fracture, intervertebral disc height narrowing, facet joint osteoarthritis (OA), lumbar spine volumetric bone mineral density (vBMD), and paraspinal muscle area and density, which were all assessed from computed tomography (CT) images. Participants included 2063 women and men in the second and third generation offspring of the original cohort of the Framingham Study. Heritability of kyphosis angle, adjusted for age, sex, and weight, was 54% (95% confidence interval [CI], 43% to 64%). We found moderate genetic correlations between kyphosis angle and paraspinal muscle area (G), 0.05; 95% CI, -0.15 to 0.24) were low. Thoracic spine curvature may be heritable and share genetic factors with other age-related spine traits including trunk muscle size, vertebral fracture, and bone mineral density. (c) 2016 American Society for Bone and Mineral Research.
C1 [Yau, Michelle S.; Lorbergs, Amanda L.; Kiel, Douglas P.; Yang, Laiji; Travison, Thomas G.; Karasik, David; Samelson, Elizabeth J.] Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
[Yau, Michelle S.; Lorbergs, Amanda L.; Kiel, Douglas P.; Travison, Thomas G.; Samelson, Elizabeth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Yau, Michelle S.; Lorbergs, Amanda L.; Kiel, Douglas P.; Travison, Thomas G.; Samelson, Elizabeth J.] Harvard Med Sch, Boston, MA USA.
[Demissie, Serkalem; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Anderson, Dennis E.; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA.
[Anderson, Dennis E.; Allaire, Brett T.; Bouxsein, Mary L.] Harvard Med Sch, Dept Orthoped Surg, Boston, MA USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Karasik, David] Bar Ilan Univ, Fac Med Galilee, Safed, Israel.
RP Yau, MS (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM michelleyau@hsl.harvard.edu
OI Karasik, David/0000-0002-8826-0530
FU NIH (National Institute on Aging [NIA]) [R01AG041658]; NIH (National
Heart Lung and Blood Institute [NHLBI] Framingham Heart Study)
[HHSN268201500001I]; NIH [NIA T32AG023480]; Friends of Hebrew
SeniorLife; ISF [1283/14]
FX This study was supported by the NIH (National Institute on Aging [NIA],
R01AG041658; National Heart Lung and Blood Institute [NHLBI] Framingham
Heart Study, Contract No. HHSN268201500001I); MSY is supported by NIH
(NIA T32AG023480) and Friends of Hebrew SeniorLife; DK is supported by
ISF Grant No. 1283/14.
NR 62
TC 1
Z9 1
U1 8
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD DEC
PY 2016
VL 31
IS 12
BP 2077
EP 2084
DI 10.1002/jbmr.2925
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EE2WF
UT WOS:000389445100004
PM 27455046
ER
PT J
AU Nielson, CM
Liu, CT
Smith, AV
Ackert-Bicknell, CL
Reppe, S
Jakobsdottir, J
Wassel, C
Register, TC
Oei, L
Alonso, N
Oei, EH
Parimi, N
Samelson, EJ
Nalls, MA
Zmuda, J
Lang, T
Bouxsein, M
Latourelle, J
Claussnitzer, M
Siggeirsdottir, K
Srikanth, P
Lorentzen, E
Vandenput, L
Langefeld, C
Raffield, L
Terry, G
Cox, AJ
Allison, MA
Criqui, MH
Bowden, D
Ikram, MA
Mellstrom, D
Karlsson, MK
Carr, J
Budoff, M
Phillips, C
Cupples, LA
Chou, WC
Myers, RH
Ralston, SH
Gautvik, KM
Cawthon, PM
Cummings, S
Karasik, D
Rivadeneira, F
Gudnason, V
Orwoll, ES
Harris, TB
Ohlsson, C
Kiel, DP
Hsu, YH
AF Nielson, Carrie M.
Liu, Ching-Ti
Smith, Albert V.
Ackert-Bicknell, Cheryl L.
Reppe, Sjur
Jakobsdottir, Johanna
Wassel, Christina
Register, Thomas C.
Oei, Ling
Alonso, Nerea
Oei, Edwin H.
Parimi, Neeta
Samelson, Elizabeth J.
Nalls, Mike A.
Zmuda, Joseph
Lang, Thomas
Bouxsein, Mary
Latourelle, Jeanne
Claussnitzer, Melina
Siggeirsdottir, Kristin
Srikanth, Priya
Lorentzen, Erik
Vandenput, Liesbeth
Langefeld, Carl
Raffield, Laura
Terry, Greg
Cox, Amanda J.
Allison, Matthew A.
Criqui, Michael H.
Bowden, Don
Ikram, M. Arfan
Mellstrom, Dan
Karlsson, Magnus K.
Carr, John
Budoff, Matthew
Phillips, Caroline
Cupples, L. Adrienne
Chou, Wen-Chi
Myers, Richard H.
Ralston, Stuart H.
Gautvik, Kaare M.
Cawthon, Peggy M.
Cummings, Steven
Karasik, David
Rivadeneira, Fernando
Gudnason, Vilmundur
Orwoll, Eric S.
Harris, Tamara B.
Ohlsson, Claes
Kiel, Douglas P.
Hsu, Yi-Hsiang
TI Novel Genetic Variants Associated With Increased Vertebral Volumetric
BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3
and EPHB2
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE BONE QCT; CT; ANALYSIS; QUANTITATION OF BONE; OSTEOPOROSIS; DISEASES AND
DISORDERS OF; RELATED TO BONE; GENERAL POPULATION STUDIES; EPIDEMIOLOGY;
HUMAN ASSOCIATION STUDIES; GENETIC RESEARCH; FRACTURE RISK ASSESSMENT
ID BONE-MINERAL DENSITY; GENOME-WIDE ASSOCIATION; OSTEOPOROTIC FRACTURES;
QUANTITATIVE CT; LUMBAR SPINE; OLDER MEN; HERITABILITY; LOCI;
DIFFERENTIATION; HOMEOSTASIS
AB Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (=0.22, p=1.9x10(-8)) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (=0.09, p=1.2x10(-10)) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4x10(-4)). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (=0.12, FDR p=1.7x10(-3), functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. (c) 2016 American Society for Bone and Mineral Research.
C1 [Nielson, Carrie M.; Srikanth, Priya] Oregon Hlth & Sci Univ, Sch Publ Hlth, 3181 SW Sam Jackson Pk Rd,CR113, Portland, OR 97239 USA.
[Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Smith, Albert V.; Jakobsdottir, Johanna; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Ackert-Bicknell, Cheryl L.] Univ Rochester, Dept Orthopaed & Rehabil, Rochester, NY USA.
[Reppe, Sjur] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway.
[Reppe, Sjur; Gautvik, Kaare M.] Lovisenberg Diakonale Hosp, Oslo, Norway.
[Reppe, Sjur; Gautvik, Kaare M.] Univ Oslo, Inst Basic Med Sci, Oslo, Norway.
[Wassel, Christina] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT USA.
[Register, Thomas C.] Wake Forest Sch Med, Dept Pathol, Winston Salem, NC USA.
[Oei, Ling] Erasmus MC, Internal Med, Rotterdam, Netherlands.
[Oei, Ling] NCHA, Leiden, Netherlands.
[Alonso, Nerea] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Oei, Edwin H.] Erasmus MC, Radiol & Nucl Med, Rotterdam, Netherlands.
[Parimi, Neeta; Cawthon, Peggy M.; Cummings, Steven] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Samelson, Elizabeth J.; Karasik, David; Kiel, Douglas P.; Hsu, Yi-Hsiang] Harvard Med Sch, Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
[Nalls, Mike A.; Phillips, Caroline; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Zmuda, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Lang, Thomas] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA.
[Bouxsein, Mary] Harvard Univ Med Sch, Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA USA.
[Latourelle, Jeanne; Myers, Richard H.] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Claussnitzer, Melina; Kiel, Douglas P.] Harvard Univ Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Claussnitzer, Melina; Chou, Wen-Chi; Hsu, Yi-Hsiang] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Claussnitzer, Melina] Tech Univ Munich, Munich, Germany.
[Siggeirsdottir, Kristin] Iceland Heart Assoc, Imaging, Kopavogur, Iceland.
[Lorentzen, Erik] Gothenburg Univ, Dept Bioinformat, Gothenburg, Sweden.
[Vandenput, Liesbeth; Mellstrom, Dan; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
[Langefeld, Carl] Wake Forest Sch Med, Publ Hlth Sci, Winston Salem, NC USA.
[Raffield, Laura] Wake Forest Sch Med, Ctr Human Genom, Winston Salem, NC USA.
[Raffield, Laura] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.
[Terry, Greg; Carr, John] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Cox, Amanda J.; Bowden, Don] Wake Forest Sch Med, Dept Biochem, Ctr Diabet Res, Winston Salem, NC USA.
[Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
[Bowden, Don] Wake Forest Sch Med, Internal Med Endocrinol, Winston Salem, NC USA.
[Bowden, Don] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.
[Ikram, M. Arfan; Rivadeneira, Fernando] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Karlsson, Magnus K.] Lund Univ, Malmo Univ Hosp, Dept Orthopaed & Clin Sci, Malmo, Sweden.
[Budoff, Matthew] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Ralston, Stuart H.] Univ Edinburgh, Rheumat Dis Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Cawthon, Peggy M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Karasik, David] Bar Ilan Univ, Fac Med Galilee, Safed, Israel.
[Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Orwoll, Eric S.] Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA.
[Hsu, Yi-Hsiang] Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci, Boston, MA USA.
RP Nielson, CM (reprint author), Oregon Hlth & Sci Univ, Sch Publ Hlth, 3181 SW Sam Jackson Pk Rd,CR113, Portland, OR 97239 USA.; Kiel, DP; Hsu, YH (reprint author), Harvard Med Sch, Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM nielsoca@ohsu.edu; kiel@hsl.harvard.edu; YiHsiangHsu@hsl.harvard.edu
OI Karasik, David/0000-0002-8826-0530; Vandenput,
Liesbeth/0000-0002-1712-6131; Allison, Matthew/0000-0003-0777-8272;
Carr, John/0000-0002-4398-8237
FU NIH [N01-AG-12100]; National Institutes of Health [R01 HL67348, R01
HL092301, R01 AR48797, F31 AG044879, HHSN268200782096C]; National Heart,
Lung, and Blood Institute [U01 HL067893, U01 HL067894, U01 HL067896, U01
HL067897, U01 HL056567, U01 HL056568, U01 HL067901]; US National
Institute for Arthritis, Musculoskeletal and Skin Diseases and National
Institute on Aging [R01 AR 41398, R01 AR061162, R01 AR 050066]; National
Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center; Intramural Research Program of the NIH, National Institute on
Aging; U.S. National Institute of Aging (NIA) [N01AG62101, N01AG62103,
N01AG62106]; NIA grant [1R01AG032098]; National Heart, Lung, and Blood
Institute (NHLBI); MESA [N01-HC-95159, N01-HC-95160, N01-HC-95161,
N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166,
N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040,
DK063491]; NHLBI [N02-HL-64278]; Bone Mineral Density [HL072403];
National Institutes of Health; National Institute on Aging (NIA) [R01
AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01
AG027574, R01 AG027576]; National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing
Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01
AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01
AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]; MrOS ancillary
study 'GWAS in MrOS and SOF' [RC2 AR058973]; NIAMS [K01 AR062655];
Swedish Research Council; Swedish Foundation for Strategic Research;
ALF/LUA research grant from the Sahlgrenska University Hospital;
Lundberg Foundation; Torsten and Ragnar Soderberg's Foundation; Novo
Nordisk Foundation; Erasmus Medical Centre and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and
Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission (DG XII); Municipality of
Rotterdam; Netherlands Organisation of Scientific Research NWO
Investments [175.010.2005.011, 911-03-012]; Genetic Laboratory of the
Department of Internal Medicine, Erasmus MC; Research Institute for
Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; NIH/NIAMS
[AR060234, AR060981]; EU [LSHM-CT-2003-502941]; South-Eastern Norway
Regional Health Authority; Oslo University Hospital, Ullevaal
FX Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik):
The Age, Gene/Environment Susceptibility Reykjavik Study was funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). The Fracture Registry is funded by the Icelandic
Heart Association. Diabetes Heart Study: The authors thank the other
investigators, the staff, and the participants of the DHS study for
their valuable contributions. This study was supported by the National
Institutes of Health through R01 HL67348 and R01 HL092301 (to DWB), R01
AR48797 (to JJC), and F31 AG044879 (to LMR). Family Heart Study: This
study was supported by grants from the National Heart, Lung, and Blood
Institute (U01 HL067893, U01 HL067894, U01 HL067896, U01 HL067897, U01
HL056567, U01 HL056568, and U01 HL067901). Framingham: The study was
funded by grants from the US National Institute for Arthritis,
Musculoskeletal and Skin Diseases and National Institute on Aging (R01
AR 41398 and R01 AR061162 to DPK; R01 AR 050066 to DK). The Framingham
Heart Study of the National Heart, Lung, and Blood Institute of the
National Institutes of Health and Boston University School of Medicine
were supported by the National Heart, Lung, and Blood Institute's
Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix,
Inc. for genotyping services (N02-HL-6-4278). Analyses reflect
intellectual input and resource development from the Framingham Heart
Study investigators participating in the SNP Health Association Resource
(SHARe) project. A portion of this research was conducted using the
Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center. Health, Aging,
and Body Composition (Health ABC): This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. This research was supported by the U.S. National Institute of
Aging (NIA) contracts N01AG62101, N01AG62103, and N01AG62106. The
genomewide association study was funded by NIA grant 1R01AG032098 to
Wake Forest University Health Sciences and genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
fully funded through a federal contract from the National Institutes of
Health to The Johns Hopkins University, contract number
HHSN268200782096C. We thank the participants of the Health, Aging, and
Body Composition Study. Multi-Ethnic Study of Atherosclerosis (MESA):
MESA and the MESA SHARe project are conducted and supported by the
National Heart, Lung, and Blood Institute (NHLBI) in collaboration with
MESA investigators. Support for MESA is provided by contracts
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168,
N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. Funding for
SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping
was performed at Affymetrix (Santa Clara, CA, USA) and the Broad
Institute of Harvard and MIT (Boston, MA, USA) using the Affymetrix
Genome-Wide Human SNP Array 6.0. Support for the Bone Mineral Density
dataset was provided by grant HL072403. Osteoporotic Fractures in Men
(MrOS)-USA: The Osteoporotic Fractures in The Osteoporotic Fractures in
Men (MrOS) Study is supported by National Institutes of Health funding.;
The following institutes provide support: the National Institute on
Aging (NIA), the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), the National Center for Advancing Translational
Sciences (NCATS), and NIH Roadmap for Medical Research under the
following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01
AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and
UL1 TR000128. The National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study
'GWAS in MrOS and SOF' under the grant number RC2 AR058973. CMN is
supported by NIAMS K01 AR062655. Osteoporotic Fractures in Men
(MrOS)-Sweden: The MrOS Sweden study is supported by the Swedish
Research Council, the Swedish Foundation for Strategic Research, the
ALF/LUA research grant from the Sahlgrenska University Hospital, the
Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation and
the Novo Nordisk Foundation. Rotterdam Studies: The Rotterdam Study is
funded by Erasmus Medical Centre and Erasmus University, Rotterdam,
Netherlands Organization for the Health Research and Development
(ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam. We are grateful to the study participants,
the staff from the Rotterdam Study and the participating general
practitioners and pharmacists. The generation and management of GWAS
genotype data for the Rotterdam Study (RS I, RS II, RS III) was executed
by the Human Genotyping Facility of the Genetic Laboratory of the
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
The GWAS datasets are supported by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012),
the Genetic Laboratory of the Department of Internal Medicine, Erasmus
MC, the Research Institute for Diseases in the Elderly (014-93-015;
RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands
Organisation for Scientific Research (NWO) Netherlands Consortium for
Healthy Aging (NCHA), project nr. 050-060-810. We thank Pascal Arp, Mila
Jhamai, Marijn Verkerk, Lizbeth Herrera, and Marjolein Peters, MSc, and
Carolina Medina-Gomez, MSc, for their help in creating the GWAS
database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina
Medina-Gomez, MSc, for the creation and analysis of imputed data. Study
of Osteoporotic Fractures: The Study of Osteoporotic Fractures (SOF) is
supported by National Institutes of Health funding. The National
Institute on Aging (NIA) provides support under the following grant
numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01
AG005394, R01 AG027574, and R01 AG027576. Expression studies (C. L.
Ackert-Bicknell): NIH/NIAMS AR060234 and AR060981. Expression studies
(S. Reppe and K. Gautvik): This work was supported by the 6th EU
framework program to "OSTEOGENE" [LSHM-CT-2003-502941]; the
South-Eastern Norway Regional Health Authority; and Oslo University
Hospital, Ullevaal.
NR 58
TC 2
Z9 2
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD DEC
PY 2016
VL 31
IS 12
BP 2085
EP 2097
DI 10.1002/jbmr.2913
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EE2WF
UT WOS:000389445100005
PM 27476799
ER
PT J
AU Blaine, KP
Press, C
Lau, K
Sliwa, J
Rao, VK
Hill, C
AF Blaine, Kevin P.
Press, Christopher
Lau, Ken
Sliwa, Jan
Rao, Vidya K.
Hill, Charles
TI Comparative effectiveness of epsilon-aminocaproic acid and tranexamic
acid on postoperative bleeding following cardiac surgery during a
national medication shortage
SO JOURNAL OF CLINICAL ANESTHESIA
LA English
DT Article
DE epsilon-aminocaproic acid; Tranexamic acid; Blood conservation;
Perioperative bleeding; Cardiac surgery
ID CARDIOPULMONARY BYPASS; APROTININ; TRANSFUSION; IMPACT
AB Study objective: The aim of this study was to compare the effectiveness of epsilon-aminocaproic acid (epsilon ACA) and tranexamic acid (TXA) in contemporary clinical practice during a national medication shortage.
Design: A retrospective cohort study.
Setting: The study was performed in all consecutive cardiac surgery patients (n = 128) admitted to the cardiac-surgical intensive care unit after surgery at a single academic center immediately before and during a national medication shortage.
Measurements: Demographic, clinical, and outcomes data were compared by descriptive statistics using X-2 and t test. Surgical drainage and transfusions were compared by multivariate linear regression for patients receiving epsilon ACA before the shortage and TXA during the shortage.
Main results: In multivariate analysis, no statistical difference was found for surgical drain output (OR 1.10, CI 0.97-1.26, P = .460) or red blood cell transfusion requirement (OR 1.79, CI 0.79-2.73, P = .176). Patients receiving epsilon ACA were more likely to receive rescue hemostatic medications (OR 1.62, CI 1.02-2.55, P = .041).
Conclusions: Substitution of sACA with TXA during a national medication shortage produced equivalent postoperative bleeding and red cell transfusions, although patients receiving sACA were more likely to require supplemental hemostatic agents. Published by Elsevier Inc.
C1 [Blaine, Kevin P.; Press, Christopher; Lau, Ken; Sliwa, Jan; Rao, Vidya K.; Hill, Charles] Stanford Univ, Med Ctr, Dept Anesthesia Pain & Perioperat Med, 300 Pasteur Dr,H3580, Stanford, CA 94305 USA.
[Lau, Ken] Anesthesia Serv Med Grp, 3626 Ruffin Rd, San Diego, CA 92123 USA.
[Sliwa, Jan] Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA.
RP Blaine, KP (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 9000 Rockville Pike 2C145, Bethesda, MD 20892 USA.
EM kevin.blaine@nih.gov
FU Stanford University School of Medicine Department of Anesthesiology,
Pain, and Perioperative Medicine
FX The authors would like to acknowledge the technical assistance of Fred
Hurt, DPharm, and the operating room pharmacy staff at Stanford
University Medical Center. This project was supported solely by
departmental funds from the Stanford University School of Medicine
Department of Anesthesiology, Pain, and Perioperative Medicine.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0952-8180
EI 1873-4529
J9 J CLIN ANESTH
JI J. Clin. Anesth.
PD DEC
PY 2016
VL 35
BP 516
EP 523
DI 10.1016/j.jclinane.2016.08.037
PG 8
WC Anesthesiology
SC Anesthesiology
GA EE7HD
UT WOS:000389785600092
PM 27871586
ER
PT J
AU Deandres-Galiana, EJ
Fernandez-Martinez, JL
Saligan, LN
Sonis, ST
AF Deandres-Galiana, Enrique J.
Luis Fernandez-Martinez, Juan
Saligan, Leorey N.
Sonis, Stephen T.
TI Impact of Microarray Preprocessing Techniques in Unraveling Biological
Pathways
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE cancer genomics; DNA arrays; gene expression; gene networks
ID TIKHONOVS REGULARIZATION; CLONING; NOISE
AB To better understand the impact of microarray preprocessing normalization techniques on the analysis of biological pathways in the prediction of chronic fatigue (CF) following radiation therapy, this study has compared the list of predictive genes found using the Robust Multiarray Averaging (RMA) and the Affymetrix MAS5 method, with the list that is obtained working with raw data (without any preprocessing). First, we modeled the spiked-in data set where differentially expressed genes were known and spiked-in at different known concentrations, showing that the precisions established by different gene ranking methods were higher than working with raw data. The results obtained from the spiked-in experiment were extrapolated to the CF data set to run learning and blind validation. RMA and MAS5 provided different sets of discriminatory genes that have a higher predictive accuracy in the learning phase, but lower predictive accuracy during the blind validation phase, suggesting that the genetic signatures generated using both preprocessing techniques cannot be generalizable. The pathways found using the raw data set better described what is a priori known for the CF disease. Besides, RMA produced more reliable pathways than MAS5. Understanding the strengths of these two preprocessing techniques in phenotype prediction is critical for precision medicine. Particularly, this article concludes that biological pathways might be better unraveled working with raw expression data. Moreover, the interpretation of the predictive gene profiles generated by RMA and MAS5 should be done with caution. This is an important conclusion with a high translational impact that should be confirmed in other disease data sets.
C1 [Deandres-Galiana, Enrique J.; Luis Fernandez-Martinez, Juan] Univ Oviedo, Dept Math, E-33006 Oviedo, Asturias, Spain.
[Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA.
[Sonis, Stephen T.] ST Sonis Biomodels LLC, Watertown, MA USA.
RP Fernandez-Martinez, JL (reprint author), Univ Oviedo, Dept Math, E-33006 Oviedo, Asturias, Spain.
EM jlfm@uniovi.es
OI deAndres-Galiana, Enrique J/0000-0001-8555-3832
FU Ministerio de Economia y Competitividad [TIN2011-23558]
FX Enrique J. de Andres was supported by the Ministerio de Economia y
Competitividad (grant TIN2011-23558).
NR 28
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
EI 1557-8666
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD DEC
PY 2016
VL 23
IS 12
BP 957
EP 968
DI 10.1089/cmb.2016.0042
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA EE2NE
UT WOS:000389420500004
PM 27494192
ER
PT J
AU Sheeler, RD
Mundell, T
Hurst, SA
Goold, SD
Thorsteinsdottir, B
Tilburt, JC
Danis, M
AF Sheeler, Robert D.
Mundell, Tim
Hurst, Samia A.
Goold, Susan Dorr
Thorsteinsdottir, Bjorg
Tilburt, Jon C.
Danis, Marion
TI Self-Reported Rationing Behavior Among US Physicians: A National Survey
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE cost; physician attitudes; physician behavior; rationing
ID RESPONSE RATES; CARE
AB Rationing is a controversial topic among US physicians. Understanding their attitudes and behaviors around rationing may be essential to a more open and sensible professional discourse on this important but controversial topic.
To describe rationing behavior and associated factors among US physicians.
Survey mailed to US physicians in 2012 to evaluate self-reported rationing behavior and variables related to this behavior.
US physicians across a full spectrum of practice settings.
A total of 2541 respondents, representing 65.6 % of the original mailing list of 3872 US addresses.
The study was a cross-sectional analysis of physician attitudes and self-reported behaviors, with neutral language representations of the behaviors as well as an embedded experiment to test the influence of the word "ration" on perceived responsibility.
Overall percentage of respondents reporting rationing behavior in various contexts and assessment of attitudes toward rationing.
In total, 1348 respondents (53.1 %) reported having personally refrained within the past 6 months from using specific clinical services that would have provided the best patient care, because of health system cost. Prescription drugs (n = 1073 [48.3 %]) and magnetic resonance imaging (n = 922 [44.5 %]) were most frequently rationed. Surgical and procedural specialists were less likely to report rationing behavior (adjusted odds ratio [OR] [95 % CI], 0.8 [0.9-0.9] and 0.5 [0.4-0.6], respectively) compared to primary care. Compared with small or solo practices, those in medical school settings reported less rationing (adjusted OR [95 % CI], 0.4 [0.2-0.7]). Physicians who self-identified as very or somewhat liberal were significantly less likely to report rationing (adjusted OR [95 % CI], 0.7 [0.6-0.9]) than those self-reporting being very or somewhat conservative. A more positive opinion about rationing tended to align with greater odds of rationing.
More than one-half of respondents engaged in behavior consistent with rationing. Practicing physicians in specific subgroups were more likely to report rationing behavior.
C1 [Sheeler, Robert D.] Mayo Clin, Dept Family Med, Rochester, MN 55905 USA.
[Mundell, Tim] Univ Iowa, Iowa City, IA USA.
[Hurst, Samia A.] Univ Geneva, Inst Eth Hist & Human, Geneva, Switzerland.
[Goold, Susan Dorr] Univ Michigan, Med Ctr, Ctr Bioeth & Social Sci Med, Div Gen Internal Med, Ann Arbor, MI 48109 USA.
[Thorsteinsdottir, Bjorg; Tilburt, Jon C.] Mayo Clin, Biomed Eth Program, Rochester, MN USA.
[Thorsteinsdottir, Bjorg] Mayo Clin, Div Primary Care Internal Med, Rochester, MN USA.
[Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA.
[Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN USA.
[Tilburt, Jon C.] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Hlth Care Deli, Rochester, MN USA.
[Danis, Marion] Natl Inst Hlth, Dept Bioeth, Bethesda, MD USA.
RP Sheeler, RD (reprint author), Mayo Clin, Dept Family Med, Rochester, MN 55905 USA.
EM sheeler.robert@mayo.edu
RI Hurst, Samia/A-9661-2008
OI Hurst, Samia/0000-0002-1980-5226
FU Greenwall Foundation; Mayo Clinic Program in Professionalism and Ethics;
Research Early Career Development Award from the Mayo Foundation
FX This research was funded by a grant from The Greenwall Foundation, the
Mayo Clinic Program in Professionalism and Ethics, and a Research Early
Career Development Award from the Mayo Foundation. The authors would
like to thank Katherine Humeniuk for her support in fielding of the
survey and for providing preliminary analysis of the data. Joel Pacyna
contributed importantly to the preparation and formatting of revised
manuscripts.
NR 11
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD DEC
PY 2016
VL 31
IS 12
BP 1444
EP 1451
DI 10.1007/s11606-016-3756-5
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA EE5DX
UT WOS:000389626600009
PM 27435251
ER
PT J
AU Takahashi, S
Fukami, T
Masuo, Y
Brocker, CN
Xie, C
Krausz, KW
Wolf, CR
Henderson, CJ
Gonzalez, FJ
AF Takahashi, Shogo
Fukami, Tatsuki
Masuo, Yusuke
Brocker, Chad N.
Xie, Cen
Krausz, Kristopher W.
Wolf, C. Roland
Henderson, Colin J.
Gonzalez, Frank J.
TI Cyp2c70 is responsible for the species difference in bile acid
metabolism between mice and humans
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE chenodeoxycholic acid; cytochrome P450; Cyp2c70; enzyme kinetics; liver;
muricholic acid; ursodeoxycholic acid
ID DRUG-DRUG INTERACTION; BETA-MURICHOLIC ACID; X RECEPTOR;
CHENODEOXYCHOLIC ACID; MOUSE LINES; ENTEROHEPATIC CIRCULATION;
URSODEOXYCHOLIC ACID; RAT-LIVER; CYTOCHROME-P450; OBESITY
AB Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYPs) and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6-position to form -muricholic acid (MCA) and ursodeoxycholic acid (UDCA) to form -MCA. However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known. Comparison of several Cyp-null mouse lines revealed that -MCA and -MCA were not detected in the liver samples from Cyp2c-cluster null (Cyp2c-null) mice. Global bile acid analysis further revealed the absence of MCAs and their conjugated derivatives, and high concentrations of CDCA and UDCA in Cyp2c-null mouse cecum and feces. Analysis of recombinant CYPs revealed that -MCA and -MCA were produced by oxidation of CDCA and UDCA by Cyp2c70, respectively. CYP2C9-humanized mice have similar bile acid metabolites as the Cyp2c-null mice, indicating that human CYP2C9 does not oxidize CDCA and UDCA, thus explaining the species differences in production of MCA. Because humans do not produce MCA, they lack tauro--MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis.
C1 [Takahashi, Shogo; Fukami, Tatsuki; Masuo, Yusuke; Brocker, Chad N.; Xie, Cen; Krausz, Kristopher W.; Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Wolf, C. Roland; Henderson, Colin J.] Univ Dundee, Ninewells Hosp, Jacqui Wood Canc Ctr, Sch Med,Div Canc, Dundee DD1 9SY, Scotland.
RP Gonzalez, FJ (reprint author), Natl Canc Inst, Lab Metab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
OI Wolf, Charles Roland/0000-0002-6969-0113
FU National Cancer Institute Intramural Research Program, Center for Cancer
Research; National Institutes of Health [U54 ES16015]; Cancer Research
UK [C4639/A10822]; Japanese Society for the Promotion of Science
Research Fellowship for Japanese Biomedical and Behavioral Researchers
at the National Institutes of Health (KAITOKU-NIH); program for
Advancing Strategic International Networks to Accelerate the Circulation
of Talented Researchers from the Japanese Society for the Promotion of
Sciences [S2601]
FX This work was supported by the National Cancer Institute Intramural
Research Program, Center for Cancer Research, and National Institutes of
Health Grant U54 ES16015 (F.J.G), and a Programme Grant support from
Cancer Research UK, C4639/A10822 to C.R.W. S.T. was supported by a
Japanese Society for the Promotion of Science Research Fellowship for
Japanese Biomedical and Behavioral Researchers at the National
Institutes of Health (KAITOKU-NIH). T.F. and Y.M. were supported by a
program for Advancing Strategic International Networks to Accelerate the
Circulation of Talented Researchers (S2601) from the Japanese Society
for the Promotion of Sciences. The content of this work is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 37
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PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD DEC
PY 2016
VL 57
IS 12
BP 2130
EP 2137
DI 10.1194/jlr.M071183
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA EE3FK
UT WOS:000389473000004
PM 27638959
ER
PT J
AU Muessgens, D
Thirugnanasambandam, N
Shitara, H
Popa, T
Hallett, M
AF Muessgens, Diana
Thirugnanasambandam, Nivethida
Shitara, Hitoshi
Popa, Traian
Hallett, Mark
TI Dissociable roles of preSMA in motor sequence chunking and hand
switching-a TMS study
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE presupplementary motor area; transcranial magnetic stimulation;
chunking; hand switching; motor sequence learning
ID MEDIAL FRONTAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; SIMPLE
REACTION-TIME; OCCIPITAL FACE AREA; CEREBRAL-BLOOD-FLOW; HUMAN BRAIN;
MOVEMENT; SUPPLEMENTARY; INHIBITION; ACTIVATION
AB Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within-chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously.
C1 [Muessgens, Diana; Thirugnanasambandam, Nivethida; Shitara, Hitoshi; Popa, Traian; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Muessgens, D (reprint author), Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden.
EM diana.muessgens@nih.gov
OI Popa, Traian/0000-0003-1160-4830
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program
FX Support for this study was provided by the National Institute of
Neurological Disorders and Stroke Intramural Research Program.
NR 43
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U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD DEC
PY 2016
VL 116
IS 6
BP 2637
EP 2646
DI 10.1152/jn.00565.2016
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA EE5LF
UT WOS:000389648300015
PM 27655967
ER
PT J
AU Canavier, CC
Evans, RC
Oster, AM
Pissadaki, EK
Drion, G
Kuznetsov, AS
Gutkin, BS
AF Canavier, Carmen C.
Evans, Rebekah C.
Oster, Andrew M.
Pissadaki, Eleftheria K.
Drion, Guillaume
Kuznetsov, Alexey S.
Gutkin, Boris S.
TI Implications of cellular models of dopamine neurons for disease
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Review
DE nonlinear dynamics; dopaminergic signaling
ID SUBSTANTIA-NIGRA NEURONS; COUPLED-OSCILLATOR MODEL; GENE POTASSIUM
CHANNELS; VENTRAL TEGMENTAL AREA; DEPOLARIZATION BLOCK;
PARKINSONS-DISEASE; FIRING PATTERN; PYRAMIDAL NEURONS;
ACTION-POTENTIALS; IN-VITRO
AB This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models.
C1 [Canavier, Carmen C.] Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, New Orleans, LA USA.
[Evans, Rebekah C.] NINDS, Cellular Neurophysiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Oster, Andrew M.] Eastern Washington Univ, Dept Math, Cheney, WA 99004 USA.
[Pissadaki, Eleftheria K.] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA.
[Drion, Guillaume] Univ Liege, Dept Elect Engn & Comp Sci, Liege, Belgium.
[Kuznetsov, Alexey S.] Indiana Univ Purdue Univ, Dept Math Sci, Indianapolis, IN 46202 USA.
[Kuznetsov, Alexey S.] Indiana Univ Purdue Univ, Ctr Math Biosci, Indianapolis, IN 46202 USA.
[Gutkin, Boris S.] Ecole Normale Super PSL Res Univ, Grp Neural Theory, LNC INSERM U960, Dept Etud Cognit, Paris, France.
[Gutkin, Boris S.] NRU Higher Sch Econ, Ctr Cognit & Decis Making, Moscow, Russia.
[Pissadaki, Eleftheria K.] Univ Sheffield, Dept Comp Sci, Sheffield, S Yorkshire, England.
RP Canavier, CC (reprint author), Louisiana State Univ Hlth, 1901 Perdido St, New Orleans, LA 70112 USA.
EM ccanav@lsuhsc.edu
FU National Institutes of Health (NIH) National Institute of Neurological
Disorders and Stroke (NINDS) [R01-NS-061097]; Russian Academic
Excellence Project [5-100]; L'Agence Nationale de la Recherche NEUCOMP
[ANR-10-LABX-0087 IEC, ANR-10-IDEX-0001-02 PSL]; NIH National Institute
on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA-022821]; Eastern
Washington University Faculty Grant for Research and Creative Works; NIH
NINDS Intramural Research Program [NS-003135]
FX This work was supported by National Institutes of Health (NIH) National
Institute of Neurological Disorders and Stroke (NINDS) Grant
R01-NS-061097 to C. C. Canavier, Russian Academic Excellence Project
"5-100" and L'Agence Nationale de la Recherche NEUCOMP, ANR-10-LABX-0087
IEC, and ANR-10-IDEX-0001-02 PSL to B. S. Gutkin, NIH National Institute
on Alcohol Abuse and Alcoholism (NIAAA) Grant R01-AA-022821 to A. S.
Kuznetsov, and Eastern Washington University Faculty Grant for Research
and Creative Works to A. M. Oster. R. C. Evans was supported by NIH
NINDS Intramural Research Program Grant NS-003135 to Zayd M. Khaliq.
NR 124
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U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD DEC
PY 2016
VL 116
IS 6
BP 2815
EP 2830
DI 10.1152/jn.00530.2016
PG 16
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA EE5LF
UT WOS:000389648300031
PM 27582295
ER
PT J
AU Di Giovanni, V
Bourdon, C
Wang, DX
Seshadri, S
Senga, E
Versloot, CJ
Voskuijl, W
Semba, RD
Trehan, I
Moaddel, R
Ordiz, MI
Zhang, L
Parkinson, J
Manary, MJ
Bandsma, RHJ
AF Di Giovanni, Valeria
Bourdon, Celine
Wang, Dominic X.
Seshadri, Swapna
Senga, Edward
Versloot, Christian J.
Voskuijl, Wieger
Semba, Richard D.
Trehan, Indi
Moaddel, Ruin
Ordiz, M. Isabel
Zhang, Ling
Parkinson, John
Manary, Mark J.
Bandsma, Robert H. J.
TI Metabolomic Changes in Serum of Children with Different Clinical
Diagnoses of Malnutrition
SO JOURNAL OF NUTRITION
LA English
DT Article
DE marasmus; kwashiorkor; children; severe acute malnutrition; targeted
metabolomics; metabolites; p180 kit
ID MIDDLE-INCOME COUNTRIES; KWASHIORKOR; CARNITINE; UNDERNUTRITION;
DYSFUNCTION; MORTALITY; MARASMUS
AB Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear.
Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls.
Methods: We studied children aged 9-59 mo frorh Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured.
Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynureninetryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not.
Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were Profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.
C1 [Di Giovanni, Valeria; Bourdon, Celine; Wang, Dominic X.; Versloot, Christian J.; Zhang, Ling; Bandsma, Robert H. J.] Hosp Sick Children, Dept Physiol & Expt Med, Toronto, ON, Canada.
[Seshadri, Swapna; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON, Canada.
[Bandsma, Robert H. J.] Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON, Canada.
[Bandsma, Robert H. J.] Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.
[Senga, Edward; Bandsma, Robert H. J.] Univ Malawi, Coll Med, Dept Biomed Sci, Blantyre, Malawi.
[Voskuijl, Wieger; Trehan, Indi] Univ Malawi, Coll Med, Dept Pediat & Child Hlth, Blantyre, Malawi.
[Manary, Mark J.] Univ Malawi, Coll Med, Sch Publ Hlth & Family Med, Blantyre, Malawi.
[Voskuijl, Wieger] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Global Child Hlth Grp, Amsterdam, Netherlands.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Trehan, Indi; Moaddel, Ruin] NIA, NIH, Baltimore, MD 21224 USA.
[Ordiz, M. Isabel; Manary, Mark J.] Washington Univ, Dept Pediat, St Louis, MO 63130 USA.
[Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
[Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
RP Bandsma, RHJ (reprint author), Hosp Sick Children, Dept Physiol & Expt Med, Toronto, ON, Canada.; Bandsma, RHJ (reprint author), Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON, Canada.; Bandsma, RHJ (reprint author), Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.; Bandsma, RHJ (reprint author), Univ Malawi, Coll Med, Dept Biomed Sci, Blantyre, Malawi.
FU Hospital for Sick Children, Toronto, Canada; Intramural Research Program
of the National Institute on Aging, NIH; Children's Discovery Institute
of Washington University; St. Louis Children's Hospital
FX This study was supported by an internal grant to RHJB from the Hospital
for Sick Children, Toronto, Canada. It was also supported in part by the
Intramural Research Program of the National Institute on Aging, NIH (RM)
and the Children's Discovery Institute of Washington University and St.
Louis Children's Hospital (IT, MJM). This is a free access article,
distributed under terms
(http.//www.nutrition.org/publications/guidelines-and-policies/license/)
that permit unrestricted noncommercial use, distribution, and
reproduction in any medium, provided the original work is properly
cited.
NR 41
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U1 6
U2 6
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2016
VL 146
IS 12
BP 2436
EP 2444
DI 10.3945/jn.116.239145
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE2CP
UT WOS:000389391600003
PM 27807038
ER
PT J
AU Nielsen, SJ
Trak-Fellermeier, MA
Joshipura, K
Dye, BA
AF Nielsen, Samara Joy
Trak-Fellermeier, Maria Angelica
Joshipura, Kaumudi
Dye, Bruce A.
TI Dietary Fiber Intake Is Inversely Associated with Periodontal Disease
among US Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
DE periodontal disease; dietary fiber; whole grains; NHANES; nutrition;
epidemiology
ID BLOOD-PRESSURE; VASCULAR-DISEASE; HYPERTENSION; PREVALENCE; NHANES;
OLDER
AB Background: Approximately 47% of adults in the United States have periodontal disease. Dietary guidelines recommend a diet providing adequate fiber. Healthier dietary habits, particularly an increased fiber intake, may contribute to periodontal disease prevention.
Objective: Our objective was to evaluate the relation of dietary fiber intake and its sources with periodontal disease in the US adult population (>= 30 y of age).
Methods: Data from 6052 adults participating in NHANES 2009-2012 were used. Periodontal disease was defined (according to the CDC/American Academy of Periodontology) as severe, moderate, mild, and none. Intake was assessed by 24-h dietary recalls. The relation between periodontal disease and dietary fiber, whole-grain, and fruit and vegetable intakes were evaluated by using multivariate models, adjusting for sociodemographic characteristics and dentition status.
Results: In the multivariate logistic model, the lowest quartile of dietary fiber was associated with moderate-severe periodontitis (compared with mild-none) compared with the highest dietary fiber intake quartile (OR: 1.30; 95% CI: 1.00, 1.69). In the multivariate multinomial logistic model, intake in the lowest quartile of dietary fiber was associated with higher severity of periodontitis than dietary fiber intake in the highest quartile (OR: 1.27; 95% CI: 1.00, 1.62). In the adjusted logistic model, whole-grain intake was not associated with moderate-severe periodontitis. However, in the adjusted multinomial logistic model, adults consuming whole grains in the lowest quartile were more likely to have more severe periodontal disease than were adults consuming whole grains in the highest quartile (OR: 1.32; 95% CI: 1.08, 1.62). In fully adjusted logistic and multinomial logistic models, fruit and vegetable intake was not significantly associated with periodontitis.
Conclusions: We found an inverse relation between dietary fiber intake and periodontal disease among US adults >= 30 y old. Periodontal disease was associated with low whole-grain intake but not with low fruit and vegetable intake.
C1 [Nielsen, Samara Joy] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Sports Med & Nutr, Pittsburgh, PA 15260 USA.
[Trak-Fellermeier, Maria Angelica; Joshipura, Kaumudi] Univ Puerto Rico, Sch Dent Med, Ctr Clin Res & Hlth Promot, Med Sci Campus, San Juan, PR 00936 USA.
[Dye, Bruce A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Nielsen, SJ (reprint author), Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Sports Med & Nutr, Pittsburgh, PA 15260 USA.
EM snielsen@pitt.edu
NR 26
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PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2016
VL 146
IS 12
BP 2530
EP 2536
DI 10.3945/jn.116.237065
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE2CP
UT WOS:000389391600013
PM 27798338
ER
PT J
AU Khan, RJ
Gebreab, SY
Riestra, P
Sims, M
Gaye, A
Xu, RH
Davis, SK
AF Khan, Rumana J.
Gebreab, Samson Y.
Riestra, Pia
Sims, Mario
Gaye, Amadou
Xu, Ruihua
Davis, Sharon K.
TI Associations between Vitamin D and Cardiovascular Disease Risk Factors
in African Americans Are Partly Explained by Circulating Adipokines and
C-Reactive Protein: The Jackson Heart Study
SO JOURNAL OF NUTRITION
LA English
DT Article
DE 25-hydroxyvitamin D; African Americans; cardiovascular disease risk
factors; path analysis; adipokine
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; RENIN-ANGIOTENSIN
SYSTEM; BODY-FAT DISTRIBUTION; 25-HYDROXYVITAMIN D; SERUM
25-HYDROXYVITAMIN-D; LEPTIN CONCENTRATIONS; INSULIN SENSITIVITY;
METABOLIC SYNDROME; D DEFICIENCY
AB Background: Although it is recognized that vitamin D deficiency is associated with cardiovascular disease (CVD) risk factors, and is more common in African Americans (AAs), the pathologic mechanisms by which vitamin D may influence these risk factors are poorly understood.
Objectives: We explored the association between vitamin D status, as reflected by serum 25-hydroxyvitamin D [25(OH)D] concentrations, and CVD risk factors including mean arterial pressure (MAP), fasting plasma glucose (FPG), plasma HDL cholesterol, and waist circumference (WC) in adult AAs. We also tested whether plasma C-reactive protein (CRP), adipokines (adiponectin and leptin), and aldosterone mediated the associations between 25(OH)D and these risk factors.
Methods: Data on 4010 (63.8% women; mean age: 54.0 y) individuals from the Jackson Heart Study were analyzed. Multivariable linear regression models were used to examine the associations of 25(OH)D with CVD risk factors. We used path analysis and bootstrapping methods to quantify and test the share of these associations that was statistically explained by each of the mediators by decomposing the associations into direct and indirect effects.
Results: Serum 25(OH)D concentrations were inversely associated with WC, FPG, and MAP and were positively associated with HDL cholesterol in multivariable analysis. A nearly 20% effect of 25(OH)D on MAP was masked by aldosterone (total indirect effect: beta = 0.01, P < 0.05). Approximately 23% of the effect of 25(OH)D on WC (beta = 0.03, P < 0.05) and similar to 9% of the effect of 25(OH)D on FPG (beta = -0.02, P < 0.05) were mediated through CRP, adiponectin, and leptin together. A 23% share of the association between 25(OH)D and HDL cholesterol was mediated by adiponectin alone (beta = 0.03, P < 0.05).
Conclusions: Our findings suggest that the associations between vitamin D status and CVD risk factors in AAs are partially mediated through circulating adipokines and CRP. More evidence, however, is required from longitudinal and randomized controlled studies to validate our findings.
C1 [Khan, Rumana J.; Gebreab, Samson Y.; Riestra, Pia; Gaye, Amadou; Xu, Ruihua; Davis, Sharon K.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, Cardiovasc Sect, Social Epidemiol Unit,NIH, Bethesda, MD 20892 USA.
[Sims, Mario] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA.
RP Khan, RJ (reprint author), NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, Cardiovasc Sect, Social Epidemiol Unit,NIH, Bethesda, MD 20892 USA.
OI Gaye, Amadou/0000-0002-1180-2792
FU Intramural Research Program of the NIH; National Heart, Lung, and Blood
Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]; National Institute on Minority
Health and Health Disparities
FX Supported by the Intramural Research Program of the NIH. The Jackson
Heart Study is supported by contracts HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and
HHSN268201300050C from the National Heart, Lung, and Blood Institute and
the National Institute on Minority Health and Health Disparities.
NR 39
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PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2016
VL 146
IS 12
BP 2537
EP 2543
DI 10.3945/jn.116.239509
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE2CP
UT WOS:000389391600014
PM 27798347
ER
PT J
AU Ma, JT
Jacques, PF
Meigs, JB
Fox, CS
Rogers, GT
Smith, CE
Hruby, A
Saltzman, E
McKeown, NM
AF Ma, Jiantao
Jacques, Paul F.
Meigs, James B.
Fox, Caroline S.
Rogers, Gail T.
Smith, Caren E.
Hruby, Adela
Saltzman, Edward
McKeown, Nicola M.
TI Sugar-Sweetened Beverage but Not Diet Soda Consumption Is Positively
Associated with Progression of Insulin Resistance and Prediabetes
SO JOURNAL OF NUTRITION
LA English
DT Article
DE sugar-sweetened beverages; diet soda; insulin resistance; HOMA-IR;
prediabetes
ID CARDIOMETABOLIC RISK-FACTORS; RANDOMIZED CONTROLLED-TRIAL; SOFT DRINK
CONSUMPTION; CORONARY-HEART-DISEASE; METABOLIC SYNDROME;
CARDIOVASCULAR-DISEASE; GLYCEMIC INDEX; AGED ADULTS; FRUIT JUICE; MEN
AB Background: Previous studies have shown an inconsistent relation between habitual beverage consumption and insulin resistance and prediabetes.
Objective: The objective of the present study was to test the hypothesis that the consumption of sugar-sweetened beverages (SSBs), rather than diet soda, is associated with long-term progression of insulin resistance and the development of prediabetes.
Methods: We analyzed the prospective association between cumulative mean consumption of SSBs or diet soda and incident prediabetes (n = 1685) identified across a median of 14 y of follow-up in participants [mean +/- SD age: 51.9 +/- 9.2 y; 59.6% women; mean +/- SD body mass index (BMI; kg/m(2)): 26.3 +/- 4.4] of the Framingham Offspring cohort. The prospective association between beverage consumption and change in homeostasis model assessment of insulin resistance (HOMA-IR; n = 2076) over 7 y was also analyzed. The cumulative mean consumption of SSBs and diet soda was estimated by using food-frequency questionnaires. Multivariable Cox proportional hazards models and linear regression models were implemented to estimate the HRs of incident prediabetes and change in HOMA-IR, respectively.
Results: After adjustment for multiple potential confounders, including baseline BMI, we observed that SSB intake was positively associated with incident prediabetes (P-trend < 0.001); the highest SSB consumers (>3 servings/wk; median: 6 servings/wk) had a 46% higher risk of developing prediabetes than did the SSB nonconsumers (HR: 1.46; 95% CI: 1.16, 1.83). Higher SSB intake was also associated with a greater increase in HOMA-IR (P-trend = 0.006). No prospective associations were observed between diet soda intake and risk of prediabetes (P-trend = 0.24) or changes in HOMA-IR (P-trend = 0.25). These associations were similar after additional adjustment for change in BMI.
Conclusion: Regular SSB intake, but not diet soda intake, is associated with a greater increase in insulin resistance and a higher risk of developing prediabetes in a group of middle-aged adults.
C1 [Ma, Jiantao; Jacques, Paul F.; Rogers, Gail T.; Hruby, Adela; McKeown, Nicola M.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr Epidemiol Lab, Boston, MA 02111 USA.
[Smith, Caren E.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA.
[Saltzman, Edward] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Energy Metab Lab, Boston, MA 02111 USA.
[Meigs, James B.] Harvard Med Sch, Dept Med, Div Gen Internal Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Populat Sci Branch, Framingham, MA USA.
RP McKeown, NM (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr Epidemiol Lab, Boston, MA 02111 USA.
EM nicola.mckeown@tufts.edu
FU NIH/National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Boston University School of Medicine; USDA (USDA)
[58-1950-0-014]
FX Supported by the NIH/National Heart, Lung, and Blood Institute's
Framingham Heart Study (contract N01-HC-25195), the Boston University
School of Medicine, and the USDA (USDA agreement 58-1950-0-014).
NR 38
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U1 6
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PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2016
VL 146
IS 12
BP 2544
EP 2550
DI 10.3945/jn.116.234047
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE2CP
UT WOS:000389391600015
PM 27934644
ER
PT J
AU Kirkpatrick, SI
Potischman, N
Dodd, KW
Douglass, D
Zimmerman, TP
Kahle, LL
Thompson, FE
George, SM
Subar, AF
AF Kirkpatrick, Sharon I.
Potischman, Nancy
Dodd, Kevin W.
Douglass, Deirdre
Zimmerman, Thea P.
Kahle, Lisa L.
Thompson, Frances E.
George, Stephanie M.
Subar, Amy F.
TI The Use of Digital Images in 24-Hour Recalls May Lead to Less
Misestimation of Portion Size Compared with Traditional Interviewer
Administered Recalls
SO JOURNAL OF NUTRITION
LA English
DT Article
DE 24-hour recall; dietary intake; portion size; Automated
Self-Administered 24-hour dietary assessment tool; Automated
Multiple-Pass Method
ID MULTIPLE-PASS METHOD; DIETARY ASSESSMENT; FOOD PHOTOGRAPHS; ACCURACY;
NUTRIENT; RESOURCE; VALIDITY; AIDS
AB Background: The Automated Self-Administered 24-hour (ASA24) dietary recall system enhances the feasibility of collecting high-quality intake data in population-based studies.
Objective: The aim of this study was to assess the accuracy of portion size reporting in the ASA24 compared with interviewer-administered recalls.
Methods: True intake for 3 meals was ascertained in 81 adults aged 20-70 y from the Washington, DC area. Participants were randomly assigned to complete an unannounced ASA24 or an interviewer-administered Automated Multiple-Pass Method (AM PM) recall the following day. An adapted Bland-Altman approach was used to assess agreement between true and reported portion sizes. Linear regression was used to assess log-scale differences between true and reported portion sizes by recall mode. The proportions of reported portion sizes within 10% and 25% of truth were estimated. Analyses were conducted for all foods and drinks and predetermined categories.
Results: Mean differences between true and reported portion sizes were 3.7 g for the ASA24 and 11.8 g for the AMPM. According to the Bland-Altman-type plots, between 92% and 100% (depending on food or drink category and recall mode) of observations fell within the limits of agreement. After adjustment for multiple testing, the mean ratio of reported to true portion sizes was significantly >1 for the categories of all foods and drinks, all foods excluding liquids, amorphous or soft foods, and small pieces among AM PM respondents. Misestimation in the AM PM was significantly different from that in the ASA24 for all foods and drinks and for all foods excluding liquids. Small proportions of reported portions fell within 10% (16.2% for the ASA24 and 14.9% for the AMPM) and 25% (37.5% for the ASA24 and 33.2% for the AMPM) of truth.
Conclusions: The results raise the possibility that digital images tailored to different types and formats of foods may facilitate improved estimation of amounts eaten but highlight the need for continued work in this aspect of dietary assessment. This trial was registered at clinicaltrials.gov as NCT00978406.
C1 [Kirkpatrick, Sharon I.] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON, Canada.
[Potischman, Nancy] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
[George, Stephanie M.] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA.
[Dodd, Kevin W.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Thompson, Frances E.; Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Douglass, Deirdre; Zimmerman, Thea P.] Westat Corp, Rockville, MD USA.
[Kahle, Lisa L.] Informat Management Serv Inc, Rockville, MD USA.
RP Kirkpatrick, SI (reprint author), Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON, Canada.
EM sharon.kirkpatrick@uwaterloo.ca
FU Canadian Cancer Society Research Institute Capacity Development Award
[702855]; US government via Westat [NO2-PC-64406, HHSN261200644006C]
FX At the time that data collection and the initial analyses were
conducted, Sharon I Kirkpatrick, Nancy Potischman, and Stephanie M
George were with the Division of Cancer Control and Population Sciences
(DCCPS) at the National Cancer Institute. Sharon I Kirkpatrick is
currently funded by a Canadian Cancer Society Research Institute
Capacity Development Award (grant no. 702855). The data for this study
were collected by the US government via a contract with Westat
(NO2-PC-64406, HHSN261200644006C).
NR 27
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2016
VL 146
IS 12
BP 2567
EP 2573
DI 10.3945/jn.116.237271
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE2CP
UT WOS:000389391600018
PM 27807039
ER
PT J
AU McCorvy, JD
Olsen, RHJ
Roth, BL
AF McCorvy, John D.
Olsen, Reid H. J.
Roth, Bryan L.
TI Psilocybin for depression and anxiety associated with life-threatening
illnesses
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID SEROTONIN 5-HT2A RECEPTORS; SUICIDE
C1 [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA.
RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.; Roth, BL (reprint author), Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA.
EM bryan_roth@med.unc.edu
NR 20
TC 0
Z9 0
U1 23
U2 23
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
EI 1461-7285
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD DEC
PY 2016
VL 30
IS 12
BP 1209
EP 1210
DI 10.1177/0269881116675771
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA EE9AC
UT WOS:000389917000009
PM 27909171
ER
PT J
AU Tempero, M
AF Tempero, Margaret
TI An Oncologist's Letter to Santa
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Tempero, Margaret] UCSF, Pancreas Ctr, Med, San Francisco, CA 94143 USA.
[Tempero, Margaret] UCSF, Pancreas Ctr, San Francisco, CA 94143 USA.
[Tempero, Margaret] ASCO Board, San Francisco, CA USA.
[Tempero, Margaret] ASCO, San Francisco, CA USA.
[Tempero, Margaret] ASCO, Conquer Canc Fdn Board, San Francisco, CA USA.
[Tempero, Margaret] ASCO Methods Clin Canc Res, AACR, San Francisco, CA USA.
[Tempero, Margaret] NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA.
[Tempero, Margaret] NCI, Board Sci Counselors Subcomm A, Bethesda, MD 20892 USA.
[Tempero, Margaret] Canc Prevent & Res Inst Texas, Sci Steering Comm, Austin, TX USA.
[Tempero, Margaret] Canc Prevent & Res Inst Texas, Clin & Translat Study Sect, Austin, TX USA.
[Tempero, Margaret] Lustgarten Fdn, Sci Advisory Boards, Bethpage, NY USA.
[Tempero, Margaret] V Fdn, Pancreat Canc Act Network, Bethpage, NY USA.
[Tempero, Margaret] Alberta Canada Canc Board, Edmonton, AB, Canada.
[Tempero, Margaret] EORTC, Copenhagen, Denmark.
[Tempero, Margaret] US FDA, Oncol Drug Advisory Comm, Rockville, MD 20857 USA.
[Tempero, Margaret] UNMC, Eppley Canc Ctr, Omaha, NE USA.
[Tempero, Margaret] UCSF, Div Med Oncol, San Francisco, CA 94143 USA.
[Tempero, Margaret] UCSF, Helen Diller Family Comprehens Canc Ctr, Res Programs, San Francisco, CA 94143 USA.
RP Tempero, M (reprint author), UCSF, Pancreas Ctr, Med, San Francisco, CA 94143 USA.; Tempero, M (reprint author), UCSF, Pancreas Ctr, San Francisco, CA 94143 USA.; Tempero, M (reprint author), ASCO, Conquer Canc Fdn Board, San Francisco, CA USA.; Tempero, M (reprint author), ASCO Methods Clin Canc Res, AACR, San Francisco, CA USA.; Tempero, M (reprint author), Canc Prevent & Res Inst Texas, Sci Steering Comm, Austin, TX USA.; Tempero, M (reprint author), Canc Prevent & Res Inst Texas, Clin & Translat Study Sect, Austin, TX USA.; Tempero, M (reprint author), Lustgarten Fdn, Sci Advisory Boards, Bethpage, NY USA.; Tempero, M (reprint author), V Fdn, Pancreat Canc Act Network, Bethpage, NY USA.; Tempero, M (reprint author), Alberta Canada Canc Board, Edmonton, AB, Canada.; Tempero, M (reprint author), EORTC, Copenhagen, Denmark.; Tempero, M (reprint author), UCSF, Div Med Oncol, San Francisco, CA 94143 USA.; Tempero, M (reprint author), UCSF, Helen Diller Family Comprehens Canc Ctr, Res Programs, San Francisco, CA 94143 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD DEC
PY 2016
VL 14
IS 12
BP 1491
EP 1491
PG 1
WC Oncology
SC Oncology
GA EE9QU
UT WOS:000389962100001
PM 27956532
ER
PT J
AU Redmond, SM
Yao, TJ
Russell, JS
Rice, ML
Hoffman, HJ
Siberry, GK
Frederick, T
Purswani, M
Williams, PL
AF Redmond, Sean M.
Yao, Tzy-Jyun
Russell, Jonathan S.
Rice, Mabel L.
Hoffman, Howard J.
Siberry, George K.
Frederick, Toni
Purswani, Murli
Williams, Paige L.
CA Pediat HIV AIDS Cohort Study
TI Longitudinal Evaluation of Language Impairment in Youth With Perinatally
Acquired Human Immunodeficiency Virus (HIV) and Youth With Perinatal HIV
Exposure
SO JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
LA English
DT Article
DE antiretroviral therapy; language development; language impairment;
perinatal HIV; youth
ID FOLLOW-UP; CHILDREN; INFECTION; OUTCOMES
AB Background. Language impairment (LI) risk is increased for perinatally acquired human immunodeficiency virus-infected (PHIV) and perinatally exposed to HIV but uninfected (PHEU) youth. This study evaluates the persistence of LI in these groups.
Methods. The Clinical Evaluation of Language Fundamentals was repeated on participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol 18 months postbaseline. Regression models identified factors associated with change in standardized score (SC) and the resolution or development of LI.
Results. Of 319 participants, 112 had LI at baseline. Upon re-evaluation, SCs were highly stable and changes were similar in PHIV (n = 212) and PHEU (n = 107) participants. Those with family history of language delays had a 2.39 point lower mean increase in SCs than those without, after controlling for demographic and socioeconomic factors and baseline LI status. Among PHIV participants, CD4 count,350 cells/mm(3) was associated with lower mean SC change (4.32 points), and exposure to combination antiretroviral therapy (cART) or protease inhibitors (PIs) was associated with a higher mean SC change (5.93 and 4.19 points, respectively). Initial LI was persistent in most cases (78%); 20 new cases occurred (10%). Female sex was associated with higher odds of LI resolution. Among PHIV, duration and baseline cART and history of PI use were associated with LI resolution; higher percentage of detectable viral loads before baseline was associated with lower odds of resolution.
Conclusions. The PHIV and PHEU youth are at risk for persistent LI, and family history of language delays was a risk factor for persistence of problems. Measures of successful HIV treatment predicted more favorable outcomes among PHIV youth.
C1 [Redmond, Sean M.] Univ Utah, Commun Sci & Disorders, Salt Lake City, UT 84112 USA.
[Yao, Tzy-Jyun; Russell, Jonathan S.; Williams, Paige L.] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
[Rice, Mabel L.] Univ Kansas, Child Language Program, Lawrence, KS 66045 USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Frederick, Toni] Univ Southern Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, Los Angeles, CA 90033 USA.
[Purswani, Murli] Bronx Lebanon Hosp Ctr, Div Pediat Infect Dis, Dept Pediat, New York, NY USA.
RP Redmond, SM (reprint author), 390 S 1530 E,BEHS 1201, Salt Lake City, UT 84112 USA.
EM sean.redmond@health.utah.edu
FU NICHD NIH HHS [U01 HD052102, U01 HD052104]
NR 9
TC 1
Z9 1
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2048-7193
EI 2048-7207
J9 J PEDIATR INFECT DIS
JI J. Pediatr. Infect. Dis. Soc.
PD DEC
PY 2016
VL 5
SU 1
BP S33
EP S40
DI 10.1093/jpids/piw045
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA EE8DQ
UT WOS:000389855700005
PM 27856674
ER
PT J
AU Pinzone, MR
Graf, E
Lynch, L
McLaughlin, B
Hecht, FM
Connors, M
Migueles, SA
Hwang, WT
Nunnari, G
O'Doherty, U
AF Pinzone, Marilia Rita
Graf, Erin
Lynch, Lindsay
McLaughlin, Brigit
Hecht, Frederick M.
Connors, Mark
Migueles, Stephen A.
Hwang, Wei-Ting
Nunnari, Giuseppe
O'Doherty, Una
TI Monitoring Integration over Time Supports a Role for Cytotoxic T
Lymphocytes and Ongoing Replication as Determinants of Reservoir Size
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PRIMARY HIV-1 INFECTION; ANTIRETROVIRAL THERAPY; ELITE CONTROLLERS;
LATENT RESERVOIR; CELL-ACTIVATION; IMMUNE CONTROL; PLASMA VIRUS;
IN-VIVO; DNA; QUANTIFICATION
AB The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio. Cytotoxic T lymphocyte (CTL) function as assessed by infected CD4 T-cell elimination (ICE) and granzyme B activity did not significantly change over time in ECs, suggesting that the gradual increase in integrated HIV DNA observed in ECs was not a result of progressive loss of immune-mediated control. Also, acutely infected (n = 7) but not chronically infected (n = 6) patients exhibited a significant drop in integrated HIV DNA 12 months after ART initiation. In conclusion, in the absence of ART, integrated HIV accumulates over time both in NCs and in ECs, at variable individual rates. Starting ART early in infection leads to a greater drop in integrated HIV DNA than does initiating treatment after years of infection. The increase in integrated HIV DNA over time suggests that early treatment may be of benefit in limiting HIV reservoirs.
IMPORTANCE
The establishment of a latent reservoir represents a barrier to cure among HIV-infected individuals. The dynamics of HIV reservoir accumulation over time in patients before antiviral therapy is underexplored, in large part because it is difficult to accurately and reproducibly measure the size of HIV reservoir in this setting. In our study, we compared the dynamics of integrated HIV DNA over time in ECs and NCs before and after ART was initiated. We found that integrated HIV DNA levels progressively increase over time in the absence of ART, but with a higher, albeit variable, rate in NCs compared to ECs. In addition, integrated HIV DNA declines more dramatically when ART is initiated in acute rather than chronic HIV infection, suggesting important differences between acute and chronic infection. Our study highlights the role of HIV replication and CTL control in reservoir accumulation in sanctuary sites and why ART appears to be more effective in acute infection.
C1 [Pinzone, Marilia Rita] Univ Catania, Dept Clin & Expt Med, Infect Dis Unit, Catania, Italy.
[Pinzone, Marilia Rita; Graf, Erin; Lynch, Lindsay; McLaughlin, Brigit; O'Doherty, Una] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Hecht, Frederick M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Hecht, Frederick M.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA.
[Connors, Mark; Migueles, Stephen A.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hwang, Wei-Ting] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Nunnari, Giuseppe] Univ Messina, Dept Clin & Expt Med, Infect Dis Unit, Messina, Italy.
RP O'Doherty, U (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM unao@mail.med.upenn.edu
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [R21AI096993, R21AI106557, R21AI116216, T32AI007632]; amfAR, The
Foundation for AIDS Research (amfAR)
FX This work, including the efforts of Una O'Doherty, was funded by HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) (R21AI096993, R21AI106557, R21AI116216, and
T32AI007632). This work, including the efforts of Una O'Doherty, was
funded by amfAR, The Foundation for AIDS Research (amfAR).
NR 54
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 23
BP 10436
EP 10445
DI 10.1128/JVI.00242-16
PG 10
WC Virology
SC Virology
GA EE8VL
UT WOS:000389904500001
PM 27630237
ER
PT J
AU Deng, J
Mitsuki, Y
Shen, GM
Ray, JC
Cicala, C
Arthos, J
Dustin, ML
Hioe, CE
AF Deng, Jing
Mitsuki, Yu-ya
Shen, Guomiao
Ray, Jocelyn C.
Cicala, Claudia
Arthos, James
Dustin, Michael L.
Hioe, Catarina E.
TI HIV Envelope gp120 Alters T Cell Receptor Mobilization in the
Immunological Synapse of Uninfected CD4 T Cells and Augments T Cell
Activation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIROLOGICAL SYNAPSES;
MONOCLONAL-ANTIBODIES; TYPE-1 INFECTION; DENDRITIC CELLS; STOP SIGNAL;
MICROCLUSTERS; BINDING; ENV; SUBSETS
AB HIV is transmitted most efficiently from cell to cell, and productive infection occurs mainly in activated CD4 T cells. It is postulated that HIV exploits immunological synapses formed between CD4 T cells and antigen-presenting cells to facilitate the targeting and infection of activated CD4 T cells. This study sought to evaluate how the presence of the HIV envelope (Env) in the CD4 T cell immunological synapse affects synapse formation and intracellular signaling to impact the downstream T cell activation events. CD4 T cells were applied to supported lipid bilayers that were reconstituted with HIV Env gp120, anti-T cell receptor (anti-TCR) monoclonal antibody, and ICAM-1 to represent the surface of HIV Env-bearing antigen-presenting cells. The results showed that the HIV Env did not disrupt immunological synapse formation. Instead, the HIV Env accumulated with TCR at the center of the synapse, altered the kinetics of TCR recruitment to the synapse and affected synapse morphology over time. The HIV Env also prolonged Lck phosphorylation at the synapse and enhanced TCR-induced CD69 upregulation, interleukin-2 secretion, and proliferation to promote virus infection. These results suggest that HIV uses the immunological synapse as a conduit not only for selective virus transmission to activated CD4 T cells but also for boosting the T cell activation state, thereby increasing its likelihood of undergoing productive replication in targeted CD4 T cells.
IMPORTANCE
There are about two million new HIV infections every year. A better understanding of how HIV is transmitted to susceptible cells is critical to devise effective strategies to prevent HIV infection. Activated CD4 T cells are preferentially infected by HIV, although how this is accomplished is not fully understood. This study examined whether HIV co-opts the normal T cell activation process through the so-called immunological synapse. We found that the HIV envelope is recruited to the center of the immunological synapse together with the T cell receptor and enhances the T cell receptor-induced activation of CD4 T cells. Heightened cellular activation promotes the capacity of CD4 T cells to support productive HIV replication. This study provides evidence of the exploitation of the normal immunological synapse and T cell activation process by HIV to boost the activation state of targeted CD4 T cells and promote the infection of these cells.
C1 [Deng, Jing; Dustin, Michael L.] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA.
[Deng, Jing; Shen, Guomiao; Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Mitsuki, Yu-ya; Hioe, Catarina E.] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA.
[Ray, Jocelyn C.; Cicala, Claudia; Arthos, James] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Dustin, Michael L.] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Kennedy Inst Rheumatol, Headington, England.
[Hioe, Catarina E.] James J Peters Vet Affairs Med Ctr, Res Serv, Bronx, NY 10468 USA.
RP Hioe, CE (reprint author), Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA.; Hioe, CE (reprint author), James J Peters Vet Affairs Med Ctr, Res Serv, Bronx, NY 10468 USA.
EM catarina.hioe@mssm.edu
FU U.S. Department of Veterans Affairs (VA); HHS \ NIH \ National Institute
of Allergy and Infectious Diseases (NIAID) [AI093210, AI100151,
AI102740, AI043542]
FX This work, including the efforts of Catarina E. Hioe, was funded by U.S.
Department of Veterans Affairs (VA) (Research Career Scientist Award).
This work, including the efforts of Catarina E. Hioe, was funded by U.S.
Department of Veterans Affairs (VA) (Merit Review Award). This work,
including the efforts of Catarina E. Hioe, was funded by HHS vertical
bar NIH vertical bar National Institute of Allergy and Infectious
Diseases (NIAID) (AI093210). This work, including the efforts of
Catarina E. Hioe, was funded by HHS vertical bar NIH vertical bar
National Institute of Allergy and Infectious Diseases (NIAID)
(AI100151). This work, including the efforts of Catarina E. Hioe, was
funded by HHS vertical bar NIH vertical bar National Institute of
Allergy and Infectious Diseases (NIAID) (AI102740). This work, including
the efforts of Michael L. Dustin, was funded by HHS vertical bar NIH
vertical bar National Institute of Allergy and Infectious Diseases
(NIAID) (AI043542).
NR 65
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 23
BP 10513
EP 10526
DI 10.1128/JVI.01532-16
PG 14
WC Virology
SC Virology
GA EE8VL
UT WOS:000389904500007
PM 27630246
ER
PT J
AU Longo, NS
Sutton, MS
Shiakolas, AR
Guenaga, J
Jarosinski, MC
Georgiev, IS
Mckee, K
Bailer, RT
Louder, MK
O'Dell, S
Connors, M
Wyatt, RT
Mascola, JR
Doria-Rose, NA
AF Longo, Nancy S.
Sutton, Matthew S.
Shiakolas, Andrea R.
Guenaga, Javier
Jarosinski, Marissa C.
Georgiev, Ivelin S.
Mckee, Krisha
Bailer, Robert T.
Louder, Mark K.
O'Dell, Sijy
Connors, Mark
Wyatt, Richard T.
Mascola, John R.
Doria-Rose, Nicole A.
TI Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite
of the HIV-1 Envelope Glycoprotein and Display a Preference for
Quaternary Binding
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; B-CELL
POPULATIONS; GP41-GP120 INTERFACE; PERIPHERAL-BLOOD; GENE USAGE; POTENT;
RECOGNITION; IG; MEMORY
AB One of the goals of HIV-1 vaccine development is the elicitation of neutralizing antibodies against vulnerable regions on the envelope glycoprotein (Env) viral spike. Broadly neutralizing antibodies targeting the Env glycan-V3 region (also called the N332 glycan supersite) have been described previously, with several single lineages each derived from different individual donors. We used a high-throughput B-cell culture method to isolate neutralizing antibodies from an HIV-1-infected donor with high serum neutralization breadth. Clonal relatives from three distinct antibody lineages were isolated. Each of these antibody lineages displayed modest breadth and potency but shared several characteristics with the well-characterized glycan-V3 antibodies, including dependence on glycans N332 and N301, VH4 family gene utilization, a heavy chain complementarity-determining region 2 (CDRH2) insertion, and a longer-than-average CDRH3. In contrast to previously described glycan-V3 antibodies, these antibodies preferentially recognized the native Env trimer compared to monomeric gp120. These data indicate the diversity of antibody specificities that target the glycan-V3 site. The quaternary binding preference of these antibodies suggests that that their elicitation likely requires the presentation of a native-like trimeric Env immunogen.
IMPORTANCE
Broadly neutralizing antibodies targeting the HIV-1 glycan-V3 region with single lineages from individual donors have been described previously. Here we describe three lineages from a single donor, each of which targets glycan-V3. Unlike previously described glycan-V3 antibodies, these mature antibodies bind preferentially to the native Env trimer and weakly to the gp120 monomer. These data extend our knowledge of the immune response recognition of the N332 supersite region and suggest that the mode of epitope recognition is more complex than previously anticipated.
C1 [Longo, Nancy S.; Sutton, Matthew S.; Shiakolas, Andrea R.; Jarosinski, Marissa C.; Georgiev, Ivelin S.; Mckee, Krisha; Bailer, Robert T.; Louder, Mark K.; O'Dell, Sijy; Mascola, John R.; Doria-Rose, Nicole A.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Guenaga, Javier; Wyatt, Richard T.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Georgiev, Ivelin S.] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN USA.
[Louder, Mark K.] NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Longo, Nancy S.] 9610 Barroll Lane, Kensington, MD USA.
[Sutton, Matthew S.] Univ Wisconsin, Madison, WI USA.
[Jarosinski, Marissa C.] Univ Med & Dent New Jersey, New Brunswick, NJ USA.
RP Doria-Rose, NA (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nicole.doriarose@nih.gov
FU Vaccine Research Center, Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA; International AIDS Vaccine Initiative (IAVI); Bill &
Melinda Gates Foundation; Ministry of Foreign Affairs of Denmark; Irish
Aid; Ministry of Finance of Japan; Ministry of Foreign Affairs of the
Netherlands; Norwegian Agency for Development Cooperation (NORAD);
United Kingdom Department for International Development (DFID); United
States Agency for International Development (USAID)
FX This work, including the efforts of Nancy S. Longo, Matthew S. Sutton,
Marissa C. Jarosinski, Andrea R. Shiakolas, Ivelin S. Georgiev, Krisha
McKee, Robert T. Bailer, Mark K. Louder, Sijy O'Dell, Mark Connors, John
R. Mascola, and Nicole A. Doria-Rose, was funded by intramural research
programs of the Vaccine Research Center, Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA. This work, including the efforts of
Javier Guenaga and Richard T. Wyatt, was funded by the International
AIDS Vaccine Initiative (IAVI), made possible by generous support from
many donors, including the Bill & Melinda Gates Foundation, the Ministry
of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of
Japan, the Ministry of Foreign Affairs of the Netherlands, the Norwegian
Agency for Development Cooperation (NORAD), the United Kingdom
Department for International Development (DFID), and the United States
Agency for International Development (USAID). The full list of IAVI
donors is available at http://www.iavi.org.
NR 53
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 23
BP 10574
EP 10586
DI 10.1128/JVI.01012-16
PG 13
WC Virology
SC Virology
GA EE8VL
UT WOS:000389904500012
PM 27654288
ER
PT J
AU Nelson, MI
Stucker, KM
Schobel, SA
Trovao, NS
Das, SR
Dugan, VG
Nelson, SW
Sreevatsan, S
Killian, ML
Nolting, JM
Wentworth, DE
Bowman, AS
AF Nelson, Martha I.
Stucker, Karla M.
Schobel, Seth A.
Trovao, Nidia S.
Das, Suman R.
Dugan, Vivien G.
Nelson, Sarah W.
Sreevatsan, Srinand
Killian, Mary L.
Nolting, Jacqueline M.
Wentworth, David E.
Bowman, Andrew S.
TI Introduction, Evolution, and Dissemination of Influenza A Viruses in
Exhibition Swine in the United States during 2009 to 2013
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DYNAMICS; HUMANS
AB The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio (n = 262) and Indiana (n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans.
IMPORTANCE
Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.
C1 [Nelson, Martha I.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Stucker, Karla M.; Schobel, Seth A.; Das, Suman R.; Dugan, Vivien G.; Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA.
[Trovao, Nidia S.] Katholieke Univ Leuven, Leuven, Belgium.
[Nelson, Sarah W.; Nolting, Jacqueline M.; Bowman, Andrew S.] Ohio State Univ, Columbus, OH 43210 USA.
[Sreevatsan, Srinand] Univ Minnesota, St Paul, MN 55108 USA.
[Killian, Mary L.] USDA, Natl Vet Serv Labs, Ames, IA 50010 USA.
[Stucker, Karla M.] George Sch, Newtown, PA USA.
[Schobel, Seth A.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA.
[Das, Suman R.] Vanderbilt Univ, Med Ctr, Dept Med, Ctr Translat Immunol & Infect Dis, Nashville, TN USA.
[Dugan, Vivien G.] NIAID, Off Genom & Adv Technol, NIH, Rockville, MD USA.
[Wentworth, David E.] Ctr Dis Control & Prevent, Virol Surveillance & Diag Branch, Influenza Div, Atlanta, GA USA.
RP Bowman, AS (reprint author), Ohio State Univ, Columbus, OH 43210 USA.
EM bowman.214@osu.edu
OI Sreevatsan, Srinand/0000-0002-5162-2403; Sequeira Trovao,
Nidia/0000-0002-2106-1166
FU HHS \ National Institutes of Health (NIH) [HHSN272201400006C,
HHSN272201400008C, HHSN266200700007C, HHSN272200900007C, U19-AI-110819]
FX This work, including the efforts of Sarah W. Nelson, Jacqueline M.
Nolting, and Andrew S. Bowman, was funded by HHS vertical bar National
Institutes of Health (NIH) (HHSN272201400006C). This work, including the
efforts of Martha I. Nelson, was funded by HHS vertical bar National
Institutes of Health (NIH) (HHSN272201400008C). This work, including the
efforts of Sarah W. Nelson, Srinand Sreevatsan, Jacqueline M. Nolting,
and Andrew S. Bowman, was funded by HHS vertical bar National Institutes
of Health (NIH) (HHSN266200700007C). This work, including the efforts of
Karla M. Stucker, Seth A. Schobel, Suman R. Das, Vivien G. Dugan, and
David E. Wentworth, was funded by HHS vertical bar National Institutes
of Health (NIH) (HHSN272200900007C). This work, including the efforts of
Suman R. Das and David E. Wentworth, was funded by HHS vertical bar
National Institutes of Health (NIH) (U19-AI-110819).
NR 17
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2016
VL 90
IS 23
BP 10963
EP 10971
DI 10.1128/JVI.01457-16
PG 9
WC Virology
SC Virology
GA EE8VL
UT WOS:000389904500044
PM 27681134
ER
PT J
AU Bansal, N
McCulloch, CE
Lin, F
Robinson-Cohen, C
Rahman, M
Kusek, JW
Andersons, AH
Xie, DW
Townsend, RR
Lora, CM
Wright, J
Go, AS
Ojo, A
Alper, A
Lustigova, E
Cuevas, M
Kallem, R
Hsu, CY
AF Bansal, Nisha
McCulloch, Charles E.
Lin, Feng
Robinson-Cohen, Cassianne
Rahman, Mahboob
Kusek, John W.
Andersons, Amanda H.
Xie, Dawei
Townsend, Raymond R.
Lora, Claudia M.
Wright, Jackson
Go, Alan S.
Ojo, Akinlolu
Alper, Arnold
Lustigova, Eva
Cuevas, Magda
Kallem, Radhakrishna
Hsu, Chi-yuan
CA CRIC Study Investigatorsis
TI Different components of blood pressure are associated with increased
risk of atherosclerotic cardiovascular disease versus heart failure in
advanced chronic kidney disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE blood pressure; cardiovascular disease; chronic kidney disease
ID RENAL-INSUFFICIENCY COHORT; BASE-LINE CHARACTERISTICS;
HEMODIALYSIS-PATIENTS; PULSE PRESSURE; MAINTENANCE HEMODIALYSIS;
MORTALITY RISK; OLDER-ADULTS; CKD; DEATH; DIALYSIS
AB Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate <30 ml/min per 1.73 m(2) and not on dialysis. The association of systolic (SBP), diastolic (DBP), and pulse pressure with the risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction, or peripheral arterial disease) and heart failure was tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46-2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54-4.11]) for DBP >90 mm Hg versus <80 mm Hg and higher pulse pressure (2.67 [1.82-3.92]) for pulse pressure >68 mm Hg versus <51 mm Hg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05-1.92]) for pulse pressure >68 mm Hg versus <51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP, and pulse pressure with the risk of atherosclerotic CVD, whereas only higher pulse pressure was independently associated with a greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure decreases the risk of CVD events in patients with stage 4 and 5 chronic kidney disease.
C1 [Bansal, Nisha; Robinson-Cohen, Cassianne] Univ Washington, Dept Med, Seattle, WA USA.
[McCulloch, Charles E.; Lin, Feng] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA.
[Rahman, Mahboob; Wright, Jackson] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Kusek, John W.] NIDDK, Bethesda, MD 20892 USA.
[Andersons, Amanda H.; Xie, Dawei] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Lora, Claudia M.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Ojo, Akinlolu] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Alper, Arnold] Tulane Univ, Dept Med, New Orleans, LA 70118 USA.
[Lustigova, Eva] Tulane Univ, Sch Publ Hlth, New Orleans, LA 70118 USA.
[Cuevas, Magda] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Hsu, Chi-yuan] Kaiser Permanente, Div Res, Dept Med, Oakland, CA USA.
RP Bansal, N (reprint author), Univ Washington, Kidney Res Inst, 908 Jefferson St,3rd Floor, Seattle, WA 98104 USA.
EM nbansal@nephrology.washington.edu
OI Robinson-Cohen, Cassianne/0000-0003-4783-7046
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028,
U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at
the University of Pennsylvania Clinical and Translational Science Award
NIH/National Center for Advancing Translational Sciences [UL1TR000003,
K01 DK092353]; Johns Hopkins University [UL1 TR-000424]; University of
Maryland [GCRC M01 RR-16500]; Clinical and Translational Science
Collaborative of Cleveland from the National Center for Advancing
Translational Sciences component of the NIH [UL1TR000439]; NIH road map
for Medical Research; Michigan Institute for Clinical and Health
Research (MICHR) [UL1TR000433]; University of Illinois at Chicago
National Center for Advancing Translational Sciences [UL1RR029879];
Tulane University Translational Research in Hypertension and Renal
Biology [P30GM103337]; Kaiser Permanente [NIH/NCRR UCSF-CTSI UL1
RR-024131]; [K23 DK088865]; [R01 DK70939]; [K24 DK92291]
FX This work was supported by the following grants: K23 DK088865 (NB), R01
DK70939 (Hsu and CH), K24 DK92291 (CH). Funding for the CRIC study was
obtained under a cooperative agreement from National Institute of
Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984,
U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and
U01DK060902). This work was supported in part by the Perelman School of
Medicine at the University of Pennsylvania Clinical and Translational
Science Award NIH/National Center for Advancing Translational Sciences
(UL1TR000003 and K01 DK092353) (A.H.A.), Johns Hopkins University (UL1
TR-000424), University of Maryland (GCRC M01 RR-16500), Clinical and
Translational Science Collaborative of Cleveland (UL1TR000439) from the
National Center for Advancing Translational Sciences component of the
NIH and NIH road map for Medical Research, Michigan Institute for
Clinical and Health Research (MICHR) (UL1TR000433), University of
Illinois at Chicago National Center for Advancing Translational Sciences
(UL1RR029879), Tulane University Translational Research in Hypertension
and Renal Biology (P30GM103337), and Kaiser Permanente (NIH/NCRR
UCSF-CTSI UL1 RR-024131).
NR 42
TC 0
Z9 0
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD DEC
PY 2016
VL 90
IS 6
BP 1348
EP 1356
DI 10.1016/j.kint.2016.08.009
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA EE4EZ
UT WOS:000389556400028
PM 27717485
ER
PT J
AU Schmid, D
Behrens, G
Matthews, CE
Leitzmann, MF
AF Schmid, Daniela
Behrens, Gundula
Matthews, Charles E.
Leitzmann, Michael F.
TI Physical Activity and Risk of Colon Cancer in Diabetic and Nondiabetic
US Adults
SO MAYO CLINIC PROCEEDINGS
LA English
DT Article
ID SERUM 25-HYDROXYVITAMIN D; NIH-AARP DIET; COLORECTAL-CANCER; INSULIN
SENSITIVITY; RECTAL-CANCER; LIFE-STYLE; INFLAMMATORY MARKERS; SEDENTARY
BEHAVIOR; GLUCOSE-TOLERANCE; NATIONAL-HEALTH
AB Objective: To determine whether moderate to vigorous physical activity is associated with a decreased risk of colon cancer in diabetic patients.
Patients and Methods: We evaluated the association between physical activity and colon cancer in 25,753 patients with a self-reported history of diabetes and in 274,965 nondiabetic individuals from the National Institutes of Health-AARP Diet and Health Study who were aged 50 to 71 years in 1995-1996. Moderate to vigorous physical activity was assessed at baseline using a self-administered questionnaire. Follow-up for colon cancer incidence extended to December 31, 2011.
Results: During 13.0 years of follow-up, 480 diabetic patients and 4151 nondiabetic individuals had development of colon cancer. Among diabetic patients, compared with never/rarely engaging in physical activity, more than 7 h/wk of physical activity exhibited a reduced risk of colon cancer in the age-and sex-adjusted model (hazard ratio [HR], 0.74; 95% CI, 0.56-0.996; P =.16 for trend). This association was attenuated and no longer statistically significant after additional control for other covariates (HR, 0.78; 95% CI, 0.58-1.05; P =.29 for trend). By comparison, physical activity was inversely related to colon cancer risk in nondiabetic individuals (multivariate-adjusted HR, 0.81; 95% CI, 0.73-0.89; P<. 001 for trend).
Conclusion: In this investigation of the relationship between physical activity and colon cancer in diabetic patients, we found a statistically significant inverse relationship in the age-and sex-adjusted model, which was no longer statistically significant in the multivariate-adjusted model. A reduced risk was noted among nondiabetic individuals, irrespective of other covariates. Future studies with a larger number of participants are required to explore whether physical activity beneficially affects colon cancer risk among diabetic patients. (C) 2016 Mayo Foundation for Medical Education and Research
C1 [Schmid, Daniela; Behrens, Gundula; Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
[Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Metab Epidemiol Branch, Bethesda, MD 20814 USA.
RP Schmid, D (reprint author), Univ Regensburg, Dept Epidemiol & Prevent Med, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
EM daniela.schmid@klinik.uni-regensburg.de
OI Behrens, Gundula/0000-0002-9355-6491
NR 84
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0025-6196
EI 1942-5546
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD DEC
PY 2016
VL 91
IS 12
BP 1693
EP 1705
DI 10.1016/j.mayocp.2016.08.017
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA EE3YW
UT WOS:000389539500008
PM 27916155
ER
PT J
AU Mueller, GA
Thompson, PM
DeRose, EF
O'Connell, TM
London, RE
AF Mueller, Geoffrey A.
Thompson, Peter M.
DeRose, Eugene F.
O'Connell, Thomas M.
London, Robert E.
TI A metabolomic, geographic, and seasonal analysis of the contribution of
pollen-derived adenosine to allergic sensitization
SO METABOLOMICS
LA English
DT Article
DE NMR; Metabolomics; Pollen; Adenosine; Allergy
ID EICOSANOID-LIKE SUBSTANCES; UNITED-STATES; AIRWAY EPITHELIA; EXPOSURE;
CHALLENGE; MEDIATORS; PROTEINS; DISEASE; GRAINS
AB Background Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated.
Objective This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine.
Methods An NMR metabolomics approach was used to measure metabolite concentrations in 26 pollen extracts. Pollen count data was analyzed from five cities to model exposure.
Results A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 mu M) followed by trees (23 mu M) and weeds (19 mu M). Pollen count data showed that tree pollen was typically 5-10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to be only 1.1, 0.11, and 0.12 mu g, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels.
Conclusion Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization.
C1 [Mueller, Geoffrey A.; Thompson, Peter M.; DeRose, Eugene F.; London, Robert E.] NIEHS, Lab Genome Integr & Struct Biol, 111 TW Alexander Dr MD-MR01, Res Triangle Pk, NC 27709 USA.
[O'Connell, Thomas M.] Indiana Univ Sch Med, Dept Otolaryngol Head & Neck Surg, Indianapolis, IN 46202 USA.
RP Mueller, GA (reprint author), NIEHS, Lab Genome Integr & Struct Biol, 111 TW Alexander Dr MD-MR01, Res Triangle Pk, NC 27709 USA.
EM mueller3@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01-ES102885-01]
FX This research was supported by Research Project Number Z01-ES102885-01
to REL in the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health.
NR 34
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1573-3882
EI 1573-3890
J9 METABOLOMICS
JI Metabolomics
PD DEC
PY 2016
VL 12
IS 12
AR 187
DI 10.1007/s11306-016-1130-6
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EE4VS
UT WOS:000389604300012
ER
PT J
AU VanBlargan, LA
Goo, L
Pierson, TC
AF VanBlargan, Laura A.
Goo, Leslie
Pierson, Theodore C.
TI Deconstructing the Antiviral Neutralizing-Antibody Response:
Implications for Vaccine Development and Immunity
SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
LA English
DT Review
ID WEST-NILE-VIRUS; BORNE ENCEPHALITIS-VIRUS; HUMAN MONOCLONAL-ANTIBODIES;
MEMORY B-CELLS; HIV-1 ENVELOPE TRIMER; PROTEIN DOMAIN-III; CRYO-EM
STRUCTURE; RECOMBINANT SUBVIRAL PARTICLES; FLAVIVIRUS MEMBRANE-FUSION;
CROSS-REACTIVE ANTIBODIES
AB The antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies.
C1 [VanBlargan, Laura A.; Goo, Leslie; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Goo, L; Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leslie.goo@nih.gov; piersontc@mail.nih.gov
FU Division of Intramural Research, National Institute for Allergy and
Infectious Diseases
FX This work was supported by the Division of Intramural Research, National
Institute for Allergy and Infectious Diseases.
NR 298
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1092-2172
EI 1098-5557
J9 MICROBIOL MOL BIOL R
JI Microbiol. Mol. Biol. Rev.
PD DEC
PY 2016
VL 80
IS 4
DI 10.1128/MMBR.00024-15
PG 22
WC Microbiology
SC Microbiology
GA ED2NK
UT WOS:000388683500005
PM 27784796
ER
PT J
AU Dersh, D
Iwamoto, Y
Argon, Y
AF Dersh, Devin
Iwamoto, Yuichiro
Argon, Yair
TI Tay-Sachs disease mutations in HEXA target the alpha chain of
hexosaminidase A to endoplasmic reticulum-associated degradation
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID HUMAN BETA-HEXOSAMINIDASE; LYSOSOMAL STORAGE DISORDERS; SITE-DIRECTED
MUTAGENESIS; PROTEIN-FOLDING DISEASES; GM2 GANGLIOSIDOSIS;
SANDHOFF-DISEASE; ADULT FORM; CRYSTAL-STRUCTURE; PRO-ALPHA; FIBROBLASTS
AB Loss of function of the enzyme beta-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay-Sachs disease (TSD). It has been proposed that mutations in the alpha chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA alpha mutants, seeking to identify relevant cellular quality control mechanisms. The alpha mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type alpha. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA beta chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant alpha degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant alpha folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD.
C1 [Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Dersh, Devin] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Argon, Y (reprint author), Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM yargon@mail.med.upenn.edu
FU NIH [GM-077480, AG-18001]; [F31-NS084666-01]
FX We thank Oscar Burrone (ICGEB, Trieste) for advice on the
retrotranslocation assay and Davide Eletto for advice with molecular
biology techniques. The following colleagues generously supplied
plasmids and antibodies: Oscar Burrone (ICGEB, Trieste), Richard Proia
(National Institutes of Health [NIH]), Elizabeth Neufeld (University of
California, Los Angels), Ron Kopito (Stanford), Marek Michalak
(University of Alberta, Canada), Linda Hendershot (St. Jude Children's
Hospital), and John Christianson (University of Oxford, United Kingdom).
This work was supported by training grant F31-NS084666-01 (to D.D.) and
NIH grants GM-077480 and AG-18001 (to Y.A.).
NR 56
TC 0
Z9 0
U1 15
U2 15
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD DEC 1
PY 2016
VL 27
IS 24
BP 3813
EP 3827
DI 10.1091/mbc.E16-01-0012
PG 15
WC Cell Biology
SC Cell Biology
GA EE4UX
UT WOS:000389602000003
PM 27682588
ER
PT J
AU Sher, A
AF Sher, Alan
TI Journal club A THIRD SIGNAL FROM CONDITIONED DCS DICTATES MICROBIAL
EFFECTOR CHOICE
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT News Item
C1 [Sher, Alan] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Sher, A (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM asher@niaid.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD DEC
PY 2016
VL 16
IS 12
BP 722
EP 722
DI 10.1038/nri.2016.126
PG 1
WC Immunology
SC Immunology
GA ED8PX
UT WOS:000389134500007
PM 27841281
ER
PT J
AU Chen, WJ
ten Dijke, P
AF Chen, WanJun
ten Dijke, Peter
TI Immunoregulation by members of the TGF beta superfamily
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; BONE MORPHOGENETIC PROTEIN-6;
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ALLERGIC AIRWAY INFLAMMATION;
EPIDERMAL LANGERHANS CELLS; HUMAN DENDRITIC CELLS; FC FUSION PROTEIN;
ACTIVIN-A; RHEUMATOID-ARTHRITIS
AB The transforming growth factor-beta (TGF beta) superfamily is encoded by 33 genes and includes TGF beta, bone morphogenetic proteins (BMPs) and activins. Although TGF beta is well recognized as a crucial regulator of immune responses, the immunoregulatory functions of other TGF beta family members are less clear. However, recent evidence suggests that BMPs and activins have important roles in regulating immune responses. In this Review, we briefly outline the signalling pathways of the TGF beta superfamily and discuss new insights into the immunoregulatory functions of BMPs and activins in the context of infection, inflammation and cancer.
C1 [Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
[ten Dijke, Peter] Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, Dept Mol Cell Biol, Leiden, Netherlands.
RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.; ten Dijke, P (reprint author), Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, Dept Mol Cell Biol, Leiden, Netherlands.
EM wchen@dir.nidcr.nih.gov; P.ten_Dijke@lumc.nl
FU Intramural Research Program of the US National Institutes of Health
FX The authors thank all of the members in the Mucosal Immunology Section,
National Institute for Dental and Craniofacial Research, for their help
preparing the tables and figures. We also thank Y. Wu and V. Chen for
critically reading the manuscript. This research was supported by The
Intramural Research Program of the US National Institutes of Health
(W.J.C.).
NR 205
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U1 9
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD DEC
PY 2016
VL 16
IS 12
BP 723
EP 740
DI 10.1038/nri.2016.112
PG 18
WC Immunology
SC Immunology
GA ED8PX
UT WOS:000389134500008
PM 27885276
ER
PT J
AU Sati, P
Oh, J
Constable, RT
Evangelou, N
Guttmann, CRG
Henry, RG
Klawiter, EC
Mainero, C
Massacesi, L
McFarland, H
Nelson, F
Ontaneda, D
Rauscher, A
Rooney, WD
Samaraweera, APR
Shinohara, RT
Sobel, RA
Solomon, AJ
Treaba, CA
Wuerfel, J
Zivadinov, R
Sicotte, NL
Pelletier, D
Reich, DS
AF Sati, Pascal
Oh, Jiwon
Constable, R. Todd
Evangelou, Nikos
Guttmann, Charles R. G.
Henry, Roland G.
Klawiter, Eric C.
Mainero, Caterina
Massacesi, Luca
McFarland, Henry
Nelson, Flavia
Ontaneda, Daniel
Rauscher, Alexander
Rooney, William D.
Samaraweera, Amal P. R.
Shinohara, Russell T.
Sobel, Raymond A.
Solomon, Andrew J.
Treaba, Constantina A.
Wuerfel, Jens
Zivadinov, Robert
Sicotte, Nancy L.
Pelletier, Daniel
Reich, Daniel S.
CA NIAMS Cooperative
TI The central vein sign and its clinical evaluation for the diagnosis of
multiple sclerosis: a consensus statement from the North American
Imaging in Multiple Sclerosis Cooperative
SO NATURE REVIEWS NEUROLOGY
LA English
DT Review
ID WHITE-MATTER LESIONS; CERVICAL-SPINAL CORD; MS LESIONS; 7 TESLA;
BRAIN-LESIONS; PREDICT CONVERSION; PARENCHYMAL VEINS; MCDONALD CRITERIA;
HIGH-RESOLUTION; FLAIR-ASTERISK
AB Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.
C1 [Sati, Pascal; McFarland, Henry; Reich, Daniel S.] NINDS, Translat Neuroradiol Sect, NIH, 10 Ctr Dr MSC 1400,Bldg 10 Room 5C103, Bethesda, MD 20892 USA.
[Oh, Jiwon] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada.
[Oh, Jiwon] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Constable, R. Todd] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Evangelou, Nikos; Samaraweera, Amal P. R.] Univ Nottingham, Dept Clin Neurosci, Nottingham, England.
[Guttmann, Charles R. G.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Ctr Neurol Imaging, Boston, MA USA.
[Henry, Roland G.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Klawiter, Eric C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Mainero, Caterina; Treaba, Constantina A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[Massacesi, Luca] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy.
[Nelson, Flavia] Univ Texas Hlth Sci Ctr Houston, Multiple Sclerosis Res Grp, Dept Neurol, Houston, TX 77030 USA.
[Ontaneda, Daniel] Cleveland Clin Fdn, Mellen Ctr MS Treatment & Res, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Rauscher, Alexander] Univ British Columbia, Dept Pediat, Div Neurol, UBC MRI Res Ctr, Vancouver, BC, Canada.
[Rooney, William D.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA.
[Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Sobel, Raymond A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Solomon, Andrew J.] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT USA.
[Wuerfel, Jens] Univ Basel Hosp, Med Image Anal Ctr, Basel, Switzerland.
[Zivadinov, Robert] SUNY Buffalo, Buffalo Neuroimaging Anal Ctr, Dept Neurol, Buffalo, NY USA.
[Sicotte, Nancy L.] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
[Pelletier, Daniel] Univ Southern Calif, Multiple Sclerosis Ctr, Dept Neurol, Keck Sch Med, Los Angeles, CA USA.
RP Sati, P (reprint author), NINDS, Translat Neuroradiol Sect, NIH, 10 Ctr Dr MSC 1400,Bldg 10 Room 5C103, Bethesda, MD 20892 USA.
EM satip@ninds.nih.gov
FU Race to Erase Multiple Sclerosis; Intramural Research Program of the
National Institute of Neurological Disorders and Stroke
FX The authors would like to thank Christina J. Azevedo, Michael G. Dwyer,
Leorah Freeman, Christoph Juchem, Shannon Kolind, Naila Makhani, Govind
Nair, Nico Papinutto, Haochang Shou, Daniel Schwartz, Ferdinand
Schweser, Elizabeth Sweeney, Ian Tagge, Shahamat Tauhid and Subhash
Tummala for their participation in, and contribution to, the group
workshop at the NAIMS meeting in Los Angeles. Matthew Schindler is
acknowledged for helpful suggestions. The authors also acknowledge Rohit
Bakshi, Peter Calabresi, Ciprian Crainiceanu and Jack Simon for their
contribution as NAIMS members. The authors, on behalf of the NAIMS
Cooperative, would also like to thank the Race to Erase Multiple
Sclerosis for financial support, and Joel Arnold, Aracely Delgadillo,
and Liz Seares for helping with organization of the NAIMS meeting. This
research was supported in part by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke.
NR 67
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
EI 1759-4766
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD DEC
PY 2016
VL 12
IS 12
BP 714
EP 722
DI 10.1038/nrneurol.2016.166
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA EE6PP
UT WOS:000389735000006
PM 27834394
ER
PT J
AU Sarkar, J
Liu, Y
AF Sarkar, Jaya
Liu, Yie
TI The origin of oxidized guanine resolves the puzzle of oxidation-induced
telomere-length alterations
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
ID DNA-SYNTHESIS; BASE DAMAGE; DELETION; REPAIR; YEAST; TRF2; OGG1
AB Although oxidative stress has long been considered to be a major factor contributing to telomere shortening, recent work has established that oxidative stress and DNA damage are linked to telomere lengthening. Now, Opresko and colleagues resolve this apparent discrepancy by showing that differential modulation of telomerase activity depends on the origin of a common oxidative guanine lesion.
C1 [Sarkar, Jaya] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Liu, Yie] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
RP Liu, Y (reprint author), Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
EM liuyie@mail.nih.gov
NR 20
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD DEC
PY 2016
VL 23
IS 12
BP 1070
EP 1071
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA EE4GC
UT WOS:000389559300007
PM 27922610
ER
PT J
AU Bates, MN
Reed, BR
Liu, S
Eisen, EA
Hammond, SK
AF Bates, Michael N.
Reed, Bruce R.
Liu, Sa
Eisen, Ellen A.
Hammond, S. Katharine
TI Solvent exposure and cognitive function in automotive technicians
SO NEUROTOXICOLOGY
LA English
DT Article
DE Automotive repair; Automotive technician; Cognitive function; Hexane;
Occupational exposure; Solvent
ID DIGIT SYMBOL; PERFORMANCE; MEMORY; SPEED; AGE
AB Automotive technicians are commonly exposed to organic and chlorinated solvents, particularly through use of cleaning products. Occupational solvent exposures have been associated with deficits in cognitive function but, to our knowledge, no previous studies have investigated automotive technicians. The purpose of the present study was to investigate whether previous exposures to n-hexane, in particular, or general solvents posed a persistent neurotoxic hazard to automotive workers.
Enrolled in the study were 830 San Francisco Bay Area automotive repair workers. Each participant underwent a battery of cognitive function tests to investigate central nervous system impairment, with a primary focus on the domains of psychomotor speed, fine motor function, memory and mood. Cognitive test results regressed against estimated hexane and total solvent exposures showed little evidence of associations. Exposures to both solvents and hexane were well below the occupational exposure limits.
Our results provide some reassurance about persistent neuropsychological effects in automotive workers who use solvent-based products and those who previously used hexane-containing automotive cleaning products, since this solvent is believed no longer to be used in automotive cleaning products. The lack of observed effect in this study may be attributable to low exposures, or it may reflect improved cognitive function since hexane use in automotive cleaning products was discontinued. However, impacts on results of exposure misclassification and/or the healthy worker survivor effect cannot be discounted. Irrespective of the outcome of this study, the main known neurologic effect of n-hexane is peripheral neuropathy, and such an association in automotive technicians is not excluded by these results. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Bates, Michael N.; Liu, Sa; Eisen, Ellen A.; Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Reed, Bruce R.] Univ Calif Davis, Dept Neurol, Davis, CA USA.
[Reed, Bruce R.] Natl Inst Hlth, Ctr Sci Review, Bethesda, MD 20892 USA.
RP Bates, MN (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
EM m_bates@berkeley.edu
OI Bates, Michael/0000-0003-4122-0715
FU National Institute of Environmental Health Sciences of the National
Institutes of Health [R01 ES014049]
FX This work was supported by the National Institute of Environmental
Health Sciences of the National Institutes of Health (grant number R01
ES014049).
NR 25
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD DEC
PY 2016
VL 57
BP 22
EP 30
DI 10.1016/j.neuro.2016.08.009
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA EE3NT
UT WOS:000389497000003
PM 27545874
ER
PT J
AU Golding, J
Gregory, S
Emond, A
Iles-Caven, Y
Hibbeln, J
Taylor, CM
AF Golding, Jean
Gregory, Steven
Emond, Alan
Iles-Caven, Yasmin
Hibbeln, Joseph
Taylor, Caroline M.
TI Prenatal mercury exposure and offspring behaviour in childhood and
adolescence
SO NEUROTOXICOLOGY
LA English
DT Article
DE ALSPAC; Prenatal mercury exposure; Dietary fish; Child behaviour;
Adolescent behaviour
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FISH CONSUMPTION;
METHYLMERCURY EXPOSURE; DIFFICULTIES QUESTIONNAIRE; PREGNANT-WOMEN;
COHORT; AGE; STRENGTHS; OUTCOMES; CHILDREN
AB Background: There is considerable discussion over the possible harm caused by fetal exposure to mercury, but evidence of such harm is contradictory at levels commonly found in populations with moderate intakes of fish. Further information is needed to inform debate and clarify policy recommendations.
Material: Data were collected prospectively for the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood taken in the first half of pregnancy was assayed for mercury. The outcomes were offspring behavioural assessments collected using the Strengths and Difficulties Questionnaire at seven time points between ages 4 and 16-17 years; five were completed by the mother and two by the teacher. Socioeconomic and biological confounders were first taken into account; further analyses added maternal blood selenium. Separate analyses compared the relationships between prenatal mercury levels and behaviour traits treated as continuous measures in women who ate fish with those who ate no fish in order to determine whether the relationships differed; the hypothesis was that fish consumption had benefits on the brain and masked any mercury effects. In order to prevent Type II errors, the P value for significance was set at 0.10.
Results: Prenatal mercury measurements and offspring behaviour results were available for between 2776 (at 47 months) to 1599 mother-child pairs (at 16-17 years). Even given a P value of 0.10, the number of significant results was no greater than expected apart from the relationships with peer problems at 4, 6 and 10-11 years where the relationships with prenatal mercury were negative (i.e. the greater the level of mercury the fewer the problems the child had with his/her peers). There were no significant differences between the associations with mercury found among the offspring of women who ate fish in pregnancy and those who did not, nor did adjustment for selenium make a difference.
Conclusions: There were no adverse effects of maternal prenatal mercury levels on the behaviour of the offspring. A similar lack of relationship was found when the analyses were confined to those offspring whose mothers had eaten fish in pregnancy, and no consistent differences were found between the fish and non-fish eaters. (C) 2016 The Author(s). Published by Elsevier B.V.
C1 [Golding, Jean; Gregory, Steven; Emond, Alan; Iles-Caven, Yasmin; Taylor, Caroline M.] Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, Avon, England.
[Hibbeln, Joseph] NIAAA, NIH, Rockville, MD 20852 USA.
RP Golding, J (reprint author), Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Barley House, Bristol BS8 2BN, Avon, England.
EM jean.golding@bristol.ac.uk
OI Golding, Jean/0000-0003-2826-3307
FU Wellcome Trust [102215/2/13/2, 104077/Z/14/Z]; NOAA; Intramural Research
Program of NIAAA, NIH
FX We are extremely grateful to all the families who took part in this
study, the midwives for their help in recruiting them, and the whole
ALSPAC team, which includes interviewers, computer and laboratory
technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses. The UK Medical Research Council and
the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of
Bristol currently provide core support for ALSPAC. CMT was supported by
a Wellcome Trust Career Re-Entry Fellowship (Grant ref: 104077/Z/14/Z).
This publication is the work of the authors; Jean Golding and Steven
Gregory will serve as guarantors for the contents of this paper.; The
assays of the maternal blood samples were carried out at the Centers for
Disease Control and Prevention with funding from NOAA, and the
statistical analyses were carried out in Bristol with funding from NOAA
and support from the Intramural Research Program of NIAAA, NIH. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the views of the CDC, NOAA or the NIH.
NR 29
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U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD DEC
PY 2016
VL 57
BP 87
EP 94
DI 10.1016/j.neuro.2016.09.003
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA EE3NT
UT WOS:000389497000011
PM 27633321
ER
PT J
AU Gage, JC
Hunt, WC
Schiffman, M
Katki, HA
Cheung, LA
Myers, O
Cuzick, J
Wentzensen, N
Kinney, W
Castle, PE
Wheeler, CM
AF Gage, Julia C.
Hunt, William C.
Schiffman, Mark
Katki, Hormuzd A.
Cheung, Li A.
Myers, Orrin
Cuzick, Jack
Wentzensen, Nicolas
Kinney, Walter
Castle, Philip E.
Wheeler, Cosette M.
CA New Mexico HPV Pap Registry
TI Similar Risk Patterns After Cervical Screening in Two Large US
Populations Implications for Clinical Guidelines
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS; UNITED-STATES; CANCER; WOMEN; CYTOLOGY;
MANAGEMENT; HPV; PRECANCER
AB OBJECTIVE: To compare the risks of histologic high-grade cervical intraepithelial neoplasia (CIN) or worse after different cervical cancer screening test results between two of the largest U.S. clinical practice research data sets.
METHODS: The New Mexico Human Papillomavirus (HPV) Pap Registry is a statewide registry representing a diverse population experiencing varied clinical practice delivery. Kaiser Permanente Northern California is a large integrated health care delivery system practicing routine HPV cotesting since 2003. In this retrospective cohort study, a logistic-Weibull survival model was used to estimate and compare the cumulative 3- and 5-year risks of histologic CIN 3 or worse among women aged 21-64 years screened in 2007-2011 in the New Mexico HPV Pap Registry and 2003-2013 in Kaiser Permanente Northern California. Results were stratified by age and baseline screening result: negative cytology, atypical squamous cells of undetermined significance (ASC-US) (with or without HPV triage), low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion.
RESULTS: There were 453,618 women in the New Mexico HPV Pap Registry and 1,307,528 women at Kaiser Permanente Northern California. The 5-year CIN 3 or worse risks were similar within screening results across populations: cytology negative (0.52% and 0.30%, respectively, P<001), HPV-negative and ASC-US (0.72% and 0.49%, respectively, P=.5), ASC-US (3.4% and 3.4%, respectively, P=.8), HPV-positive and ASC-US (7.7% and 7.1%, respectively, P=.3), low-grade squamous intraepithelial lesion (6.5% and 5.4%, respectively, P=.009), and high-grade squamous intraepithelial lesion (53.1% and 50.4%, respectively, P=.2). Cervical intraepithelial neoplasia grade 2 or worse risks and 3-year risks had similar trends across populations. Age-stratified analyses showed more variability, especially among women aged younger than 30 years, but patterns of risk stratification were comparable.
CONCLUSION: Current U.S. cervical screening and management recommendations are based on comparative risks of histologic high-grade CIN after screening test results. The similar results from these two large cohorts from different real-life clinical practice settings support risk-based management thresholds across U.S. clinical populations and practice settings.
C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA.
Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA.
[Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
Informat Management Serv Inc, Calverton, MD USA.
Queen Mary Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, London, England.
Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
Albert Einstein Coll Med, New York, NY USA.
RP Wheeler, CM (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Pathol, House Prevent Epidemiol HOPE,1816 Sigma Chi Rd NE, Albuquerque, NM 87131 USA.
EM cwheeler@salud.unm.edu
FU Qiagen; Roche; GenProbe/Hologic; Abbott; BD; Cepheid; Genera; Trovagene;
University of New Mexico from Merck and Co., Inc.
FX Dr. Schiffman and Dr. Gage have received HPV testing for research at no
cost from Roche and BD. Dr. Cuzick has received research funding and
reagents from Qiagen, Roche, GenProbe/Hologic, Abbott, BD, Cepheid,
Genera, and Trovagene and has been personally compensated for Advisory
Boards or Speakers Bureau activities from Trovagene, GenProbe/Hologic,
Abbott, BD, Merck, and Cepheid. Dr. Wentzensen has received cervical
cancer screening assays in-kind or at reduced cost from BD, Cepheid,
Hologic, and Roche. Dr. Castle has received HPV tests and testing for
research at a reduced or no cost from Qiagen and Roche, has been
compensated for serving as a member on a Data and Safety Monitoring
Board for Merck, and as a consultant for BD, Cepheid, Roche, GE
Healthcare, ClearPath, Guided Therapeutics, and Gen-Probe/Hologic. Dr.
Wheeler has received funding through the University of New Mexico from
Merck and Co., Inc. and Glaxo SmithKline for human papillomavirus (HPV)
vaccine studies and equipment and reagents from Roche Molecular Systems
for HPV genotyping. The remaining authors did not report any potential
conflicts of interest.
NR 25
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD DEC
PY 2016
VL 128
IS 6
BP 1248
EP 1257
DI 10.1097/AOG.0000000000001721
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE5KH
UT WOS:000389645200008
PM 27824767
ER
PT J
AU Blackwell, SC
Landon, MB
Mele, L
Reddy, UM
Casey, BM
Wapner, RJ
Varner, MW
Rouse, DJ
Thorp, JM
Sciscione, A
Catalano, P
Saade, G
Caritis, SN
Sorokin, Y
Grobman, WA
AF Blackwell, Sean C.
Landon, Mark B.
Mele, Lisa
Reddy, Uma M.
Casey, Brian M.
Wapner, Ronald J.
Varner, Michael W.
Rouse, Dwight J.
Thorp, John M., Jr.
Sciscione, Anthony
Catalano, Patrick
Saade, George
Caritis, Steve N.
Sorokin, Yoram
Grobman, William A.
CA Eunice Kennedy Shriver Natl Inst
TI Relationship Between Excessive Gestational Weight Gain and Neonatal
Adiposity in Women With Mild Gestational Diabetes Mellitus
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID BODY-MASS INDEX; PREGNANCY; OBESITY; OUTCOMES; INFANTS; MOTHERS
AB OBJECTIVE: To evaluate the relationships among excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus.
METHODS: This is a secondary analysis of a multicenter randomized clinical trial of women with mild gestational diabetes mellitus. Based on self-reported prepregnancy body weight, gestational weight gain was categorized as excessive if it was greater than 2009 Institute of Medicine guidelines. Maternal outcomes and neonatal anthropomorphic characteristics were compared between women with excessive weight gain and those without excessive weight gain. Multiple linear and logistic regression analyses were performed to adjust for confounding factors.
RESULTS: We studied 841 women who participated in the main trial and had prepregnancy body mass index (BMI) and delivery information available (n=431 treatment group, n=410 no treatment). After adjustment for factors including treatment and prepregnancy BMI, excessive weight gain remained associated with large for gestational age (adjusted odds ratio [OR] 2.94, 95% confidence interval [CI] 1.81-4.93), birth weight greater than 4,000 g (adjusted OR 2.56, 95% CI 1.54-4.40), preeclampsia (adjusted OR 2.96, 95% CI 1.35-7.03), and cesarean delivery for labor arrest (adjusted OR 2.37, 95% CI 1.30-4.44). In addition, excessive weight gain was independently associated with increased total neonatal fat (P<.001) and birth weight (P<. 001).
CONCLUSION: In women with both treated and untreated mild gestational diabetes mellitus, excessive gestational weight gain was independently associated with both greater birth weight and adiposity.
C1 Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Dept Obstet & Gynecol, Houston, TX 77030 USA.
Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
Univ Texas Southwestern Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX USA.
Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
George Washington Univ, Dept Obstet & Gynecol, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Obstet & Gynecol, Bethesda, MD USA.
RP Blackwell, SC (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Sci, 6431 Fannin,Suite 3-286, Houston, TX 77030 USA.
EM Sean.Blackwell@uth.tmc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869,
HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410,
HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers
Grant [M01-RR00034]; National Center for Research Resources
[UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136,
HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118,
HD36801), General Clinical Research Centers Grant (M01-RR00034), and the
National Center for Research Resources (UL1-RR024989, M01-RR00080,
UL1-RR025764, C06-RR11234). Comments and views of the authors do not
necessarily represent views of the NICHD.
NR 27
TC 0
Z9 0
U1 7
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD DEC
PY 2016
VL 128
IS 6
BP 1325
EP 1332
DI 10.1097/AOG.0000000000001773
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA EE5KH
UT WOS:000389645200013
PM 27824768
ER
PT J
AU Veerappan, M
El-Hage-Sleiman, AKM
Tai, V
Chiu, SJ
Winter, KP
Stinnett, SS
Hwang, TS
Hubbard, GB
Michelson, M
Gunther, R
Wong, WT
Chew, EY
Toth, CA
AF Veerappan, Malini
El-Hage-Sleiman, Abdul-Karim M.
Tai, Vincent
Chiu, Stephanie J.
Winter, Katrina P.
Stinnett, Sandra S.
Hwang, Thomas S.
Hubbard, G. Baker, III
Michelson, Michelle
Gunther, Randall
Wong, Wai T.
Chew, Emily Y.
Toth, Cynthia A.
CA Age Related Eye Dis Study Ancillar
TI Optical Coherence Tomography Reflective Drusen Substructures Predict
Progression to Geographic Atrophy in Age-related Macular Degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID EYE DISEASE; AUTOMATIC SEGMENTATION; COMPLEMENT ACTIVATION;
HYPERREFLECTIVE FOCI; IDENTIFICATION; MACULOPATHY; EPITHELIUM;
PATHOLOGY; IMAGES; SDOCT
AB Purpose: Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression.
Design: Retrospective analysis in a prospective study.
Participants: Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study.
Methods: Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye.
Main Outcome Measures: Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs.
Results: Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001-0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002-0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008-0.05).
Conclusions: Optical coherence tomography-reflective drusen substructures are optical coherence tomography-based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography-reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis. (C) 2016 by the American Academy of Ophthalmology
C1 [Veerappan, Malini; El-Hage-Sleiman, Abdul-Karim M.; Tai, Vincent; Chiu, Stephanie J.; Winter, Katrina P.; Stinnett, Sandra S.; Hubbard, G. Baker, III; Michelson, Michelle; Chew, Emily Y.] Duke Univ, Med Ctr, Duke Eye Ctr, 2351 Erwin Rd,Box 3802, Durham, NC 27710 USA.
[Hwang, Thomas S.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
[Hubbard, G. Baker, III] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA.
[Wong, Wai T.; Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
[Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
RP Veerappan, M (reprint author), Duke Univ, Med Ctr, Duke Eye Ctr, 2351 Erwin Rd,Box 3802, Durham, NC 27710 USA.
EM malini.veerappan@dm.duke.edu
RI Wong, Wai/B-6118-2017;
OI Wong, Wai/0000-0003-0681-4016; Sleiman, Karim/0000-0002-4017-4908
FU National Eye Institute; Genentech; Alcon; Bioptigen
FX The author(s) have made the following disclosure(s): A-K.M.E-H.S., V.T.,
K.P.W., S.S.S., T.S.H., G.B.H., M.M., R.G., W.T.W., and E.Y.C.: Grants -
National Eye Institute, Genentech, Alcon, and Bioptigen during the
conduct of the study.; S.J.C.: Grants - National Eye Institute,
Genentech, Alcon, and Bioptigen during the conduct of the study; Patent
- segmentation and identification of layered structures in images (US
20110182517 A1).; C.A.T.: Royalties - Alcon; Research grants for this
study - National Eye Institute, Alcon, Bioptigen, and Genentech.
NR 39
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2016
VL 123
IS 12
BP 2554
EP 2570
DI 10.1016/j.ophtha.2016.08.047
PG 17
WC Ophthalmology
SC Ophthalmology
GA EE3YZ
UT WOS:000389539900023
PM 27793356
ER
PT J
AU Shantha, JG
Crozier, I
Varkey, JB
Kraft, CS
Lyon, GM
Mehta, AK
Carlson, RD
Hill, CE
Kumar, G
Debiec, MR
Patel, PS
Olsen, TW
Nussenblatt, RB
Martin, DF
Stroher, U
Uyeki, TM
Ribner, BS
Franzco, JRS
Yeh, S
AF Shantha, Jessica G.
Crozier, Ian
Varkey, Jay B.
Kraft, Colleen S.
Lyon, G. Marshall, III
Mehta, Aneesh K.
Carlson, Renee Donahue
Hill, Charles E.
Kumar, Gokul
Debiec, Matthew R.
Patel, Purnima S.
Olsen, Timothy W.
Nussenblatt, Robert B.
Martin, Daniel F.
Stroeher, Ute
Uyeki, Timothy M.
Ribner, Bruce S.
Franzco, Justine R. Smith
Yeh, Steven
TI Long-term Management of Panuveitis and Iris Heterochromia in an Ebola
Survivor
SO OPHTHALMOLOGY
LA English
DT Editorial Material
ID VIRUS DISEASE
C1 [Shantha, Jessica G.; Kumar, Gokul; Debiec, Matthew R.; Patel, Purnima S.; Olsen, Timothy W.; Yeh, Steven] Emory Univ, Sch Med, Emory Eye Ctr, Dept Ophthalmol, Atlanta, GA USA.
[Crozier, Ian] Mulago Hosp Complex, Infect Dis Inst, Kampala, Uganda.
[Varkey, Jay B.; Kraft, Colleen S.; Lyon, G. Marshall, III; Mehta, Aneesh K.; Carlson, Renee Donahue; Ribner, Bruce S.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA.
[Kraft, Colleen S.; Hill, Charles E.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
[Stroeher, Ute; Uyeki, Timothy M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Franzco, Justine R. Smith] Flinders Univ S Australia, Adelaide, SA, Australia.
RP Yeh, S (reprint author), 1365B Clifton Rd NE, Atlanta, GA 30322 USA.
EM steven.yeh@emory.edu
FU NCATS NIH HHS [UL1 TR000454]; NEI NIH HHS [P30 EY006360]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2016
VL 123
IS 12
BP 2626
EP 2628
PG 3
WC Ophthalmology
SC Ophthalmology
GA EE3YZ
UT WOS:000389539900031
PM 27594198
ER
PT J
AU Harrandah, AM
Fitzpatrick, SG
Smith, MH
Wang, DR
Cohen, DM
Chan, EKL
AF Harrandah, Amani M.
Fitzpatrick, Sarah G.
Smith, Molly H.
Wang, Dunrui
Cohen, Donald M.
Chan, Edward K. L.
TI MicroRNA-375 as a biomarker for malignant transformation in oral lesions
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
LA English
DT Article
ID INHIBITS CELL-PROLIFERATION; PREMALIGNANT LESIONS; MIR-375 EXPRESSION;
GASTRIC-CANCER; LEUKOPLAKIA; CARCINOMA; SURVIVAL; MIR-21; SIGNATURE;
INVASION
AB Objective. Malignant transformation of oral premalignant lesions is the key process in the progression to oral squamous cell carcinoma (OSCC). Previously, we identified miR-7 and miR-21 as candidate oncogenes and miR-375 and miR-494 as candidate tumor suppressors in OSCC. We aim to evaluate these microRNAs as biomarkers of malignant transformation in oral premalignant lesions.
Study Design. Formalin-fixed, paraffin-embedded samples from progressive premalignant lesions and paired sequential OSCC tumors at the same site were obtained from same patients (n-31). Total RNA was extracted and analyzed for microRNA levels using real-time polymerase chain reaction.
Results. MiR-375 expression in progressive lesions was clearly lower than in nonprogressive control lesions (average eightfold difference, P = .0004). Furthermore, the expression of miR-375 decreased significantly after the progression from premalignant lesion to OSCC (P < .0001). Receiver operating characteristic curve analysis revealed that miR-375 was able to differentiate between progressive and nonprogressive premalignant lesions (P < .0001).
Conclusions. MiR-375 downregulation in oral premalignant lesions is associated with a higher risk of malignant transformation.
C1 [Harrandah, Amani M.; Chan, Edward K. L.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL USA.
[Fitzpatrick, Sarah G.; Smith, Molly H.; Cohen, Donald M.] Univ Florida, Coll Dent, Dept Oral & Maxillofacial Diagnost Sci, Gainesville, FL USA.
[Wang, Dunrui] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chan, EKL (reprint author), Univ Florida, Dept Oral Biol, 1600 SW Archer Rd, Gainesville, FL 32610 USA.
EM Echan@ufl.edu
FU University of Florida institutional funds, Andrew J. Semesco Foundation,
Ocala, Florida, USA; UMM ALQURA University, Saudi Arabia; Saudi Arabian
Cultural Mission
FX This study was funded by the University of Florida institutional funds,
Andrew J. Semesco Foundation, Ocala, Florida, USA; UMM ALQURA
University, Saudi Arabia; and Saudi Arabian Cultural Mission to the
United States.
NR 41
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-4403
EI 1528-395X
J9 OR SURG OR MED OR PA
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
PD DEC
PY 2016
VL 122
IS 6
BP 743
EP +
DI 10.1016/j.oooo.2016.07.022
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA EE3ZC
UT WOS:000389540200016
PM 27720656
ER
PT J
AU Branham, K
Matsui, H
Biswas, P
Guru, AA
Hicks, M
Suk, JJ
Li, H
Jakubosky, D
Long, T
Telenti, A
Nariai, N
Heckenlively, JR
Frazer, KA
Sieving, PA
Ayyagari, R
AF Branham, Kari
Matsui, Hiroko
Biswas, Pooja
Guru, Aditya A.
Hicks, Michael
Suk, John J.
Li, He
Jakubosky, David
Long, Tao
Telenti, Amalio
Nariai, Naoki
Heckenlively, John R.
Frazer, Kelly A.
Sieving, Paul A.
Ayyagari, Radha
TI Establishing the involvement of the novel gene AGBL5 in retinitis
pigmentosa by whole genome sequencing
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE ophthalmology; whole genome sequencing
ID MUTATIONS; DISCOVERY; FRAMEWORK; DEGENERATION; ALIGNMENT; VARIANTS;
ACCURATE; TUBULIN
AB While more than 250 genes are known to cause inherited retinal degenerations (IRD), nearly 40-50% of families have the genetic basis for their disease unknown. In this study we sought to identify the underlying cause of IRD in a family by whole genome sequence (WGS) analysis. Clinical characterization including standard ophthalmic examination, fundus photography, visual field testing, electroretinography, and review of medical and family history was performed. WGS was performed on affected and unaffected family members using Illumina HiSeq X10. Sequence reads were aligned to hg19 using BWA-MEM and variant calling was performed with Genome Analysis Toolkit. The called variants were annotated with SnpEff v4.11, PolyPhen v2.2.2, and CADD v1.3. Copy number variations were called using Genome STRiP (svtoolkit 2.00.1611) and SpeedSeq software. Variants were filtered to detect rare potentially deleterious variants segregating with disease. Candidate variants were validated by dideoxy sequencing. Clinical evaluation revealed typical adolescent-onset recessive retinitis pigmentosa (arRP) in affected members. WGS identified about 4 million variants in each individual. Two rare and potentially deleterious compound heterozygous variants p.Arg281Cys and p.Arg487* were identified in the gene ATP/GTP binding protein like 5 (AGBL5) as likely causal variants. No additional variants in IRD genes that segregated with disease were identified. Mutation analysis confirmed the segregation of these variants with the IRD in the pedigree. Homology models indicated destabilization of AGBL5 due to the p.Arg281Cys change. Our findings establish the involvement of mutations in AGBL5 in RP and validate the WGS variant filtering pipeline we designed.
C1 [Branham, Kari; Heckenlively, John R.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA.
[Matsui, Hiroko; Li, He; Jakubosky, David; Nariai, Naoki; Frazer, Kelly A.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Biswas, Pooja; Guru, Aditya A.; Suk, John J.; Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Inst, 9415 Campus Point Dr,JRC206, La Jolla, CA 92037 USA.
[Hicks, Michael; Long, Tao; Telenti, Amalio] Human Longev Inc, San Diego, CA USA.
[Frazer, Kelly A.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Frazer, Kelly A.] Univ Calif San Diego, Rady Childrens Hosp, Div Genome Informat Sci, La Jolla, CA 92093 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Ayyagari, R (reprint author), Univ Calif San Diego, Shiley Eye Inst, 9415 Campus Point Dr,JRC206, La Jolla, CA 92037 USA.
EM rayyagari@ucsd.edu
FU Foundation Fighting Blindness; Research to Prevent Blindness; National
Eye Institute [EY-21237, P30-EY-22589]
FX The Foundation Fighting Blindness, Research to Prevent Blindness (to
Department of Ophthalmology at University of California San Diego, La
Jolla, CA, and Kellogg Eye Center, University of Michigan, Ann Arbor,
MI); National Eye Institute Grants EY-21237, P30-EY-22589.
NR 33
TC 0
Z9 0
U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
EI 1531-2267
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD DEC
PY 2016
VL 48
IS 12
BP 922
EP 927
DI 10.1152/physiolgenomics.00101.2016
PG 6
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA EE5IL
UT WOS:000389639700005
PM 27764769
ER
PT J
AU Hotaling, NA
Jeon, J
Wade, MB
Luong, D
Palmer, XL
Bharti, K
Simon, CG
AF Hotaling, Nathan A.
Jeon, Jun
Wade, Mary Beth
Luong, Derek
Palmer, Xavier-Lewis
Bharti, Kapil
Simon, Carl G., Jr.
TI Training to Improve Precision and Accuracy in the Measurement of Fiber
Morphology
SO PLOS ONE
LA English
DT Article
ID NANOFIBER SCAFFOLD; IMAGE-ANALYSIS; DIFFERENTIATION; REPRODUCIBILITY;
STANDARDS; DIAMETER; CELLS
AB An estimated $7.1 billion dollars a year is spent due to irreproducibility in pre-clinical data from errors in data analysis and reporting. Therefore, developing tools to improve measurement comparability is paramount. Recently, an open source tool, DiameterJ, has been deployed for the automated analysis of scanning electron micrographs of fibrous scaffolds designed for tissue engineering applications. DiameterJ performs hundreds to thousands of scaffold fiber diameter measurements from a single micrograph within a few seconds, along with a variety of other scaffold morphological features, which enables a more rigorous and thorough assessment of scaffold properties. Herein, an online, publicly available training module is introduced for educating DiameterJ users on how to effectively analyze scanning electron micrographs of fibers and the large volume of data that a DiameterJ analysis yields. The end goal of this training was to improve user data analysis and reporting to enhance reproducibility of analysis of nanofiber scaffolds. User performance was assessed before and after training to evaluate the effectiveness of the training modules. Users were asked to use DiameterJ to analyze reference micrographs of fibers that had known diameters. The results showed that training improved the accuracy and precision of measurements of fiber diameter in scanning electron micrographs. Training also improved the precision of measurements of pore area, porosity, intersection density, and characteristic fiber length between fiber intersections. These results demonstrate that the DiameterJ training module improves precision and accuracy in fiber morphology measurements, which will lead to enhanced data comparability.
C1 [Hotaling, Nathan A.; Palmer, Xavier-Lewis; Simon, Carl G., Jr.] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA.
[Hotaling, Nathan A.; Jeon, Jun; Bharti, Kapil] NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA.
[Wade, Mary Beth; Luong, Derek] Univ Akron, Dept Polymer Sci, Akron, OH 44325 USA.
RP Hotaling, NA (reprint author), NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA.; Hotaling, NA (reprint author), NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA.
EM Nathan.Hotaling@nih.gov
OI Hotaling, Nathan/0000-0001-8423-6464
NR 33
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 1
PY 2016
VL 11
IS 12
AR e0167664
DI 10.1371/journal.pone.0167664
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3JC
UT WOS:000389482700221
PM 27907145
ER
PT J
AU Shevtsova, E
Shevtsov, A
Mukanov, K
Filipenko, M
Kamalova, D
Sytnik, I
Syzdykov, M
Kuznetsov, A
Akhmetova, A
Zharova, M
Karibaev, T
Tarlykov, P
Ramanculov, E
AF Shevtsova, Elena
Shevtsov, Alexandr
Mukanov, Kasim
Filipenko, Maxim
Kamalova, Dinara
Sytnik, Igor
Syzdykov, Marat
Kuznetsov, Andrey
Akhmetova, Assel
Zharova, Mira
Karibaev, Talgat
Tarlykov, Pavel
Ramanculov, Erlan
TI Epidemiology of Brucellosis and Genetic Diversity of Brucella abortus in
Kazakhstan
SO PLOS ONE
LA English
DT Article
ID TANDEM-REPEAT ANALYSIS; MELITENSIS; STRAIN; MLVA; REEMERGENCE;
COUNTRIES; DISEASE; VACCINE; HEALTH; CATTLE
AB Brucellosis is a major zoonotic infection in Kazakhstan. However, there is limited data on its incidence in humans and animals, and the genetic diversity of prevalent strains is virtually unstudied. Additionally, there is no detailed overview of Kazakhstan brucellosis control and eradication programs. Here, we analyzed brucellosis epidemiological data, and assessed the effectiveness of eradication strategies employed over the past 70 years to counteract this infection. We also conducted multiple loci variable-number tandem repeat analysis (MLVA) of Brucella abortus strains found in Kazakhstan. We analyzed official data on the incidence of animal brucellosis in Kazakhstan. The records span more than 70 years of anti-brucellosis campaigns, and contain a brief description of the applied control strategies, their effectiveness, and their impact on the incidence in humans. The MLVA-16 method was used to type 94 strains of B. abortus and serial passages of B. abortus 82, a strain used in vaccines. MLVA-8 and MLVA-11 analyses clustered strains into a total of four and seven genotypes, respectively; it is the first time that four of these genotypes have been described. MLVA-16 analysis divided strains into 28 distinct genotypes having genetic similarity coefficient that varies from 60 to100% and a Hunter & Gaston diversity index of 0.871. MST analysis reconstruction revealed clustering into "Kazakhstani-Chinese (Central Asian)", "European" and "American" lines. Detection of multiple genotypes in a single outbreak confirms that poorly controlled trade of livestock plays a crucial role in the spread of infection. Notably, the MLVA-16 profile of the B. abortus 82 strain was unique and did not change during 33 serial passages. MLVA genotyping may thus be useful for epidemiological monitoring of brucellosis, and for tracking the source(s) of infection. We suggest that countrywide application of MLVA genotyping would improve the control of brucellosis in Kazakhstan.
C1 [Shevtsova, Elena; Shevtsov, Alexandr; Mukanov, Kasim; Filipenko, Maxim; Kamalova, Dinara; Tarlykov, Pavel] Natl Biotechnol Ctr, Astana, Kazakhstan.
[Filipenko, Maxim] Inst Chem Biol & Fundamental Med, Novosibirsk, Russia.
[Filipenko, Maxim] Novosibirsk State Univ, Novosibirsk, Russia.
[Sytnik, Igor; Akhmetova, Assel; Zharova, Mira; Karibaev, Talgat] Natl Reference Ctr Vet, Astana, Kazakhstan.
[Syzdykov, Marat; Kuznetsov, Andrey] Kazakh Sci Ctr Quarantine & Zoonot Dis, Alma Ata, Kazakhstan.
[Ramanculov, Erlan] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan.
RP Shevtsov, A (reprint author), Natl Biotechnol Ctr, Astana, Kazakhstan.
EM ncbshevtsov@gmail.com
RI Kuznetsov, Andrey/K-8824-2014; Tarlykov, Pavel/C-2587-2012
OI Kuznetsov, Andrey/0000-0003-2354-533X; Tarlykov,
Pavel/0000-0003-2075-307X
FU Ministry of Education and Science of the Republic of Kazakhstan
[N0115RK01870]
FX This work was supported by funding received from the Ministry of
Education and Science of the Republic of Kazakhstan, grant no.
N0115RK01870. AS received the funding. (http://sc.edu.gov.kz/main/?L=2).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 0
Z9 0
U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 1
PY 2016
VL 11
IS 12
AR e0167496
DI 10.1371/journal.pone.0167496
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3JC
UT WOS:000389482700170
PM 27907105
ER
PT J
AU Winther, M
Holdfeldt, A
Gabl, M
Wang, JM
Forsman, H
Dahlgren, C
AF Winther, Malene
Holdfeldt, Andre
Gabl, Michael
Wang, Ji Ming
Forsman, Huamei
Dahlgren, Claes
TI Formylated MHC Class lb Binding Peptides Activate Both Human and Mouse
Neutrophils Primarily through Formyl Peptide Receptor 1
SO PLOS ONE
LA English
DT Article
ID CLASS-IB MOLECULE; STAPHYLOCOCCUS-AUREUS; RESPIRATORY BURST; LIGAND;
RESPONSES; H2-M3; FPR; TUBERCULOSIS; INFLAMMATION; RECOGNITION
AB Two different immune recognition systems have evolved in parallel to recognize peptides starting with an N-formylated methionine, and recognition similarities/differences between these two systems have been investigated. A number of peptides earlier characterized in relation to the H2-M3 complex that presents N-formylated peptides to cytotoxic T cells, have been characterized in relation to the formyl peptide receptors expressed by phagocytic neutrophils in both men (FPRs) and mice (Fprs). FPR1/Fpr1 was identified as the preferred receptor for all fMet-containing peptides examined, but there was no direct correlation between H2-M3 binding and the neutrophil activation potencies. Similarly, there was no direct correlation between the activities induced by the different peptides in human and mouse neutrophils, respectively. The formyl group was important in both H2-M3 binding and FPR activation, but FPR2 was the preferred receptor for the non-formylated peptide. The structural requirements differed between the H2-M3 and FPR/Fpr recognition systems and these data suggest that the two recognition systems have different evolutionary traits.
C1 [Winther, Malene; Holdfeldt, Andre; Gabl, Michael; Forsman, Huamei; Dahlgren, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
[Wang, Ji Ming] Frederick Natl Lab Canc Res, Ctr Canc Res, Frederick, MD USA.
RP Dahlgren, C (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
EM Claes.Dahlgren@microbio.gu.se
FU Swedish research council; King Gustaf the Vth 80-year foundation; Clas
Groschinsky foundation; Ake Wiberg foundation; IngaBritt and Arne
Lundbergs foundation; Sahlgrenska university hospital
FX The research was supported by grants from the Swedish research council,
The King Gustaf the Vth 80-year foundation, the Clas Groschinsky
foundation, the Ake Wiberg foundation, from IngaBritt and Arne Lundbergs
foundation, and the Sahlgrenska university hospital through the national
ALF-agreement. The funding agencies had no influence on the study
design, data collection and analysis, or writing and submission of the
report.; We thank the members of the Phagocyte Research Group at the
Sahlgrenska Academy for critically discussing the results and the
manuscript. The research was supported by grants from the Swedish
research council, The King Gustaf the Vth 80-year foundation, the Clas
Groschinsky foundation, the Ake Wiberg foundation, from IngaBritt and
Arne Lundbergs foundation and, the Sahlgrenska university hospital
through the national ALF-agreement. The funding agencies had no
influence on the study design, data collection and analysis, or writing
and submission of the report.
NR 34
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 1
PY 2016
VL 11
IS 12
AR e0167529
DI 10.1371/journal.pone.0167529
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE3JC
UT WOS:000389482700184
PM 27907124
ER
PT J
AU Hales, CM
Dammer, EB
Deng, QD
Duong, DM
Gearing, M
Troncoso, JC
Thambisetty, M
Lah, JJ
Shulman, JM
Levey, AI
Seyfried, NT
AF Hales, Chadwick M.
Dammer, Eric B.
Deng, Qiudong
Duong, Duc M.
Gearing, Marla
Troncoso, Juan C.
Thambisetty, Madhav
Lah, James J.
Shulman, Joshua M.
Levey, Allan I.
Seyfried, Nicholas T.
TI Changes in the detergent-insoluble brain proteome linked to amyloid and
tau in Alzheimer's Disease progression
SO PROTEOMICS
LA English
DT Article
DE Aggregation; Biomedicine; Mass spectrometry; Neurodegeneration;
Proteostasis; Spliceosome
ID A-BETA; NEURODEGENERATIVE DISEASE; NEUROFIBRILLARY TANGLES; PROTEINS;
DEMENTIA; TOXICITY; COMPLEX; THERAPEUTICS; AGGREGATION; ASSOCIATION
AB Despite a key role of amyloid-beta (A beta) in Alzheimer's disease (AD), mechanisms that link A beta plaques to tau neurofibrillary tangles and cognitive decline still remain poorly understood. The purpose of this study was to quantify proteins in the sarkosyl-insoluble brain proteome correlated with A beta and tau insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry-based proteomics, we quantified 2711 sarkosyl-insoluble proteins across the prefrontal cortex from 35 individual cases representing control, AsymAD, MCI and AD. Significant enrichment of A beta and tau in AD was observed, which correlated with neuropathological measurements of plaque and tau tangle density, respectively. Pairwise correlation coefficients were also determined for all quantified proteins to A beta and tau, across the 35 cases. Notably, six of the ten most correlated proteins to A beta were U1 small nuclear ribonucleoproteins (U1 snRNPs). Three of these U1 snRNPs (U1A, SmD and U1-70K) also correlated with tau consistent with their association with tangle pathology in AD. Thus, proteins that cross-correlate with both A beta and tau, including specific U1 snRNPs, may have potential mechanistic roles in linking A beta plaques to tau tangle pathology during AD progression.
C1 [Hales, Chadwick M.; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Hales, Chadwick M.; Dammer, Eric B.; Deng, Qiudong; Duong, Duc M.; Gearing, Marla; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA USA.
[Dammer, Eric B.; Deng, Qiudong; Duong, Duc M.; Seyfried, Nicholas T.] Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA.
[Gearing, Marla] Emory Univ, Sch Med, Dept Expt Pathol, Atlanta, GA USA.
[Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
[Thambisetty, Madhav] NIA, NIH, Baltimore, MD 21224 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Dept Neurol, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Dept Neurosci, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Shulman, Joshua M.] Texas Childrens Hosp, Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Program Dev Biol, Houston, TX 77030 USA.
RP Seyfried, NT (reprint author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM nseyfri@emory.edu
FU Accelerating Medicine Partnership AD [U01AG046161-02]; NINDS Emory
Neuroscience Core [P30NS055077]; Johns Hopkins Alzheimer's Disease
Research Center [P50AG05146]; Emory Alzheimer's Disease Research Center
[P50AG025688]; Intramural Research Program of the NIH, National
Institute on Aging; NINDS [K08NS087121]; American Brain Foundation;
Alzheimer's Association (ALZ); Alzheimer's Research UK (ARUK); Michael
J. Fox Foundation for Parkinson's Research (MJFF); Weston Brain
Institute Biomarkers Across Neurodegenerative Diseases Grant [11060];
BrightFocus Foundation [A2015332S]
FX We are grateful to participants in the Baltimore Longitudinal Study of
Aging (BLSA) and Emory brain bank donors for their invaluable
contribution. Funding: Support was provided by the Accelerating Medicine
Partnership AD grant U01AG046161-02, the NINDS Emory Neuroscience Core
(P30NS055077), the Johns Hopkins Alzheimer's Disease Research Center
(P50AG05146), and the Emory Alzheimer's Disease Research Center
(P50AG025688). This research was also supported in part by the
Intramural Research Program of the NIH, National Institute on Aging. CMH
is supported by NINDS K08NS087121 and by the American Brain Foundation.
NTS is supported in part by an Alzheimer's Association (ALZ),
Alzheimer's Research UK (ARUK), The Michael J. Fox Foundation for
Parkinson's Research (MJFF), and the Weston Brain Institute Biomarkers
Across Neurodegenerative Diseases Grant (11060). JCT was also supported
by a BrightFocus Foundation (A2015332S).
NR 64
TC 0
Z9 0
U1 10
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD DEC
PY 2016
VL 16
IS 23
BP 3042
EP 3053
DI 10.1002/pmic.201600057
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA ED9VA
UT WOS:000389220000013
PM 27718298
ER
PT J
AU Wood, CS
Weis, CP
Caro, CM
Roe, A
AF Wood, Carol S.
Weis, Christopher P.
Caro, Carla M.
Roe, Amy
TI A practice analysis of toxicology
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Toxicology; Practice analysis; Delineation; Examination specifications
AB In 2015, the American Board of Toxicology (ABT), with collaboration from the Society of Toxicology (SOT), in consultation with Professional Examination Service, performed a practice analysis study of the knowledge required for general toxicology. The purpose of this study is to help assure that the examination and requirements for attainment of Diplomate status are relevant to modern toxicology and based upon an empirical foundation of knowledge. A profile of the domains and tasks used in toxicology practice was developed by subject-matter experts representing a broad range of experiences and perspectives. An on-line survey of toxicologists, including Diplomates of the ABT and SOT members, confirmed the delineation. Results of the study can be used to improve understanding of toxicology practice, to better serve all toxicologists, and to present the role of toxicologists to those outside the profession. Survey results may also be used by the ABT Board of Directors to develop test specifications for the certifying examination and will be useful for evaluating and updating the content of professional preparation, development, and continuing education programs. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Wood, Carol S.] Oak Ridge Natl Lab, POB 2008,Bldg 1507,MS 6407, Oak Ridge, TN 38501 USA.
[Weis, Christopher P.] NIEHS, 31 Ctr Dr,Bldg 31,Room B1C02, Bethesda, MD 20892 USA.
[Caro, Carla M.] Profess Exam Serv, 475 Riverside Dr,6th Floor, New York, NY 10115 USA.
[Roe, Amy] Procter & Gamble Co, 8700 Mason Montgomery Rd, Cincinnati, OH 45040 USA.
RP Wood, CS (reprint author), Oak Ridge Natl Lab, POB 2008,Bldg 1507,MS 6407, Oak Ridge, TN 38501 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD DEC
PY 2016
VL 82
BP 140
EP 146
DI 10.1016/j.yrtph.2016.09.017
PG 7
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA EE6PU
UT WOS:000389735500013
PM 27647630
ER
PT J
AU Ferguson, KK
Cantonwine, DE
McElrath, TF
Mukherjee, B
Meeker, JD
AF Ferguson, Kelly K.
Cantonwine, David E.
McElrath, Thomas F.
Mukherjee, Bhramar
Meeker, John D.
TI Repeated measures analysis of associations between urinary bisphenol-A
concentrations and biomarkers of inflammation and oxidative stress in
pregnancy
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE BPA; Oxidative stress; Inflammation; IL-6; Pregnancy; Biomarkers;
Longitudinal
ID C-REACTIVE PROTEIN; PHTHALATE METABOLITE; PRETERM BIRTH; HUMAN EXPOSURE;
RISK; MARKERS; GROWTH; WOMEN; VARIABILITY; GENERATION
AB Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit. Inflammation markers, including C-reactive protein and four cytokines were measured in plasma from the same time points. In adjusted models, an interquartile range increase in BPA was associated with significant increases in both oxidative stress biomarkers (5-9% increase). Additionally, we observed significantly higher IL-6 concentrations in association with an interquartile range increase in BPA (8.95% increase). These systemic changes consequent to BPA exposure may mediate adverse birth outcomes and/or fetal development. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Ferguson, Kelly K.] Natl Inst Environm Hlth Sci, Epidemiol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC USA.
[Ferguson, Kelly K.; Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
[Cantonwine, David E.; McElrath, Thomas F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 75 Francis St, Boston, MA USA.
[Mukherjee, Bhramar] Univ Michigan, Sch Publ Hlth, Dept Biostat, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu
OI Ferguson, Kelly/0000-0001-8467-3250
FU National Institute of Environmental Health Sciences, National Institutes
of Health [R01ES018872, P42ES017198, P30ES017885]
FX Funding was provided by the National Institute of Environmental Health
Sciences, National Institutes of Health, grant numbers: R01ES018872,
P42ES017198, and P30ES017885.
NR 40
TC 0
Z9 0
U1 4
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD DEC
PY 2016
VL 66
BP 93
EP 98
DI 10.1016/j.reprotox.2016.10.002
PG 6
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA EE5XS
UT WOS:000389683500010
PM 27751756
ER
PT J
AU Makanjuola, V
Esan, Y
Oladeji, B
Kola, L
Appiah-Poku, J
Harris, B
Othieno, C
Price, L
Seedat, S
Gureje, O
AF Makanjuola, Victor
Esan, Yomi
Oladeji, Bibilola
Kola, Lola
Appiah-Poku, John
Harris, Benjamin
Othieno, Caleb
Price, Leshawndra
Seedat, Soraya
Gureje, Oye
TI Explanatory model of psychosis: impact on perception of self-stigma by
patients in three sub-saharan African cities
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Article
DE Explanatory model; Psychosis; Self-stigma; Sub-saharan Africa; Religious
theme
ID SCHIZOPHRENIA SPECTRUM DISORDERS; COMMON MENTAL-DISORDERS; INTERNALIZED
STIGMA; TRADITIONAL HEALERS; ILLNESS-SCALE; SOUTH-INDIA; PEOPLE;
COMMUNITY; EXPERIENCES; OUTPATIENTS
AB Most cultures in sub-Saharan Africa subscribe to the belief that the root cause of psychosis is supernatural. Individuals in the community who hold a religiomagical explanatory model of causation have been shown to exhibit more stigmatizing attitudes towards people with psychosis. Self-stigma among individuals with psychosis is less frequently studied.
We used a mixed-method approach, consisting of key informant's interviews to elicit information on explanatory models of causation of psychosis and questionnaire assessment of internalized stigma with an adapted version of the Scale for Internalized Stigma of Mental Illness. Twenty-four, 31, and 30 subjects with recent experience of utilizing the service of traditional or faith healers for severe mental disorders in Ibadan (Nigeria), Kumasi (Ghana), and Nairobi (Kenya), respectively, were interviewed.
About 44 % (42.1 %) of the Nigerian respondents had a high (severe) level of self-stigma with the respective proportions among Ghanaian and Kenyan respondents being 20.7 and 37.5 %. Compared with 4 out of a total of 12 respondents (33.3 %) who reported low self-stigma reported supernatural attribution, 14 out of 20 respondents (70 %) with the highest level of self-stigma reported supernatural attribution across the three sites. When low scorers ascribed supernatural causation, it was often with a religious focus.
There is a greater tendency for persons with high levels of self-stigma than those with low levels to ascribe supernatural attribution to their experience of a severe mental health condition.
C1 [Makanjuola, Victor; Esan, Yomi; Oladeji, Bibilola; Gureje, Oye] Univ Ibadan, Dept Psychiat, Ibadan, Nigeria.
[Kola, Lola] World Hlth Org Country Off, Abuja, Nigeria.
[Appiah-Poku, John] Kwame Nkuruma Univ Sci & Technol, Kumasi, Ghana.
[Harris, Benjamin] Univ Liberia, Monrovia, Liberia.
[Othieno, Caleb] Univ Nairobi, Nairobi, Kenya.
[Price, Leshawndra] NIMH, Bethesda, MD 20892 USA.
[Seedat, Soraya] Univ Stellenbosch, Stellenbosch, South Africa.
RP Makanjuola, V (reprint author), Univ Ibadan, Dept Psychiat, Ibadan, Nigeria.
EM vmakanjuola@yahoo.com
OI MAKANJUOLA, VICTOR/0000-0001-7449-0506
NR 48
TC 0
Z9 0
U1 8
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0933-7954
EI 1433-9285
J9 SOC PSYCH PSYCH EPID
JI Soc. Psychiatry Psychiatr. Epidemiol.
PD DEC
PY 2016
VL 51
IS 12
BP 1645
EP 1654
DI 10.1007/s00127-016-1274-8
PG 10
WC Psychiatry
SC Psychiatry
GA EE4XL
UT WOS:000389608800008
PM 27491966
ER
PT J
AU Lyden, P
Weymer, S
Coffey, C
Cudkowicz, M
Berg, S
O'Brien, S
Fisher, M
Haley, EC
Khatri, P
Saver, J
Levine, S
Levy, H
Rymer, M
Wechsler, L
Jadhav, A
McNeil, E
Waddy, S
Pryor, K
AF Lyden, Patrick
Weymer, Sara
Coffey, Chris
Cudkowicz, Merit
Berg, Samantha
O'Brien, Sarah
Fisher, Marc
Haley, E. Clarke
Khatri, Pooja
Saver, Jeff
Levine, Steven
Levy, Howard
Rymer, Marilyn
Wechsler, Lawrence
Jadhav, Ashutosh
McNeil, Elizabeth
Waddy, Salina
Pryor, Kent
TI Selecting Patients for Intra-Arterial Therapy in the Context of a
Clinical Trial for Neuroprotection
SO STROKE
LA English
DT Article
DE activated protein C; clinical trial; neuroprotective agents;
thrombectomy; thrombolysis
ID ACUTE ISCHEMIC-STROKE; ACTIVATED PROTEIN-C; TISSUE-PLASMINOGEN
ACTIVATOR; INTRAVENOUS THROMBOLYSIS; ANTICOAGULANT ACTIVITY;
ENDOVASCULAR TREATMENT; REPERFUSION INJURY; RANDOMIZED-TRIALS;
CEREBRAL-ISCHEMIA; ANIMAL-MODELS
AB Background and Purpose-The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial.
Methods-The study drug, 3K3A-APC, is a pleiotropic cytoprotectant and may reduce thrombolysis-associated hemorrhage. The NeuroNEXT trial NN104 (RHAPSODY) is designed to establish a maximally tolerated dose of 3K3A-APC. Each trial site provided their IAT selection criteria. An expert panel reviewed site criteria and published evidence. Finally, the trial leadership designed IAT selection criteria.
Results-Derived selection criteria reflected consistency among the sites and comparability to published IAT trials. A protocol amendment allowing IAT (and relaxed age, National Institutes of Health Stroke Scale, and time limits) in the RHAPSODY trial was implemented on June 15, 2015. Recruitment before and after the amendment improved from 8 enrolled patients (601 screened, 1.3%) to 51 patients (821 screened, 6.2%; odds ratio [95% confidence limit] of 4.9 [2.3-10.4]; P<0.001). Gross recruitment was 0.11 patients per site month versus 0.43 patients per site per month, respectively, before and after the amendment.
Conclusions-It is feasible to include IAT in a neuroprotectant trial for acute ischemic stroke. Criteria are presented for including such patients in a manner that is consistent with published evidence for IAT while still preserving the ability to test the role of the putative neuroprotectant.
C1 [Lyden, Patrick] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
[Weymer, Sara; Levy, Howard; Pryor, Kent] ZZ Biotech LLC, Houston, TX USA.
[Coffey, Chris; O'Brien, Sarah] Univ Iowa, Dept Biostat, Iowa City, IA USA.
[Cudkowicz, Merit; Berg, Samantha] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA.
[Fisher, Marc] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Haley, E. Clarke] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Khatri, Pooja] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH 45221 USA.
[Saver, Jeff] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Levine, Steven] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA.
[Rymer, Marilyn] Univ Kansas Hosp, Dept Neurol, Kansas City, MO USA.
[Wechsler, Lawrence; Jadhav, Ashutosh] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA.
[McNeil, Elizabeth; Waddy, Salina] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Weymer, Sara] Fate Therapeut, San Diego, CA USA.
[McNeil, Elizabeth] Biogen, Cambridge, MA USA.
RP Lyden, P (reprint author), Dept Neurol, 127 S San Vicente Blvd,AHSP A6417, Los Angeles, CA 90048 USA.
EM lydenp@cshs.org
FU National Institutes of Neurological Disorders and Stroke [U01NS088312];
National Institutes of Neurological Disorders and Stroke (Clinical
Coordinating Center) [U01NS077179]; National Institutes of Neurological
Disorders and Stroke (Data Coordinating Center) [U01NS077352]
FX This study was funded by the National Institutes of Neurological
Disorders and Stroke (U01NS088312). The NeuroNEXT Network is supported
by the National Institutes of Neurological Disorders and Stroke
(Clinical Coordinating Center: U01NS077179; Data Coordinating Center:
U01NS077352).
NR 39
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD DEC
PY 2016
VL 47
IS 12
BP 2979
EP 2985
DI 10.1161/STROKEAHA.116.013881
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA EE2ON
UT WOS:000389424200029
PM 27803392
ER
PT J
AU Tokar, EJ
AF Tokar, Erik J.
TI MicroRNAs: small molecules with big effects
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Editorial Material
C1 [Tokar, Erik J.] NIEHS, Stem Cell Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Tokar, EJ (reprint author), Div Natl Toxicol Program, Natl Toxicol Program Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM tokare@niehs.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD DEC 1
PY 2016
VL 312
SI SI
BP 1
EP 2
DI 10.1016/j.taap.2016.11.004
PG 2
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA EE8JA
UT WOS:000389870300001
PM 27927287
ER
PT J
AU Smith, RC
Barillas-Mury, C
AF Smith, Ryan C.
Barillas-Mury, Carolina
TI Plasmodium Oocysts: Overlooked Targets of Mosquito Immunity
SO TRENDS IN PARASITOLOGY
LA English
DT Review
ID MALARIA PARASITE DEVELOPMENT; IN-VIVO ANALYSIS; ANOPHELES-GAMBIAE;
AEDES-AEGYPTI; FUNCTIONAL-CHARACTERIZATION; ANTIPLASMODIAL IMMUNITY;
DROSOPHILA MODEL; MIDGUT INVASION; PROTEIN; INFECTION
AB Although the ability of mosquitoes to limit Plasmodium infection is well documented, many questions remain as to how malaria parasites are recognized and killed by the mosquito host. Recent evidence suggests that anti Plasmodium immunity is multimodal, with different immune mechanisms regulating ookinete and oocyst survival. However, most experiments determine the number of mature oocysts, without considering that different immune mechanisms may target different developmental stages of the parasite. Complement-like proteins have emerged as important determinants of early immunity targeting the ookinete stage, yet the mechanisms by which the mosquito late-phase immune response limits oocyst survival are less understood. Here, we describe the known components of the mosquito immune system that limit oocyst development, and provide insight into their possible mechanisms of action.
C1 [Smith, Ryan C.] Iowa State Univ, Dept Entomol, Ames, IA 50011 USA.
[Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Smith, RC (reprint author), Iowa State Univ, Dept Entomol, Ames, IA 50011 USA.
EM smithr@iastate.edu
FU Agricultural Experiment Station at Iowa State University; intramural
Research Program of the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by the Agricultural Experiment Station at Iowa
State University (to R.C.S.) and by the intramural Research Program of
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (to C.B.M.),
NR 99
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4922
EI 1471-5007
J9 TRENDS PARASITOL
JI Trends Parasitol.
PD DEC
PY 2016
VL 32
IS 12
BP 979
EP 990
DI 10.1016/j.pt.2016.08.012
PG 12
WC Parasitology
SC Parasitology
GA EE6OZ
UT WOS:000389733400010
PM 27639778
ER
PT J
AU Bartlett, DH
Silk, SB
AF Bartlett, Doreen H.
Silk, Susan B.
TI Office of Laboratory Animal Welfare Comments
SO ZEBRAFISH
LA English
DT Article
DE PHS Policy; OLAW; vertebrate animal; guide; performance standards;
Animal Welfare Assurance
AB In support of the new column in Zebrafish dedicated to initiating conversations about animal care policies and compliance for the zebrafish, the Office of Laboratory Animal Welfare (OLAW) has offered the following clarification and guidance.
C1 [Bartlett, Doreen H.; Silk, Susan B.] NIH, Off Lab Anim Welf, Bldg 10, Bethesda, MD 20892 USA.
RP Bartlett, DH (reprint author), NIH, Off Lab Anim Welf, Bldg 10, Bethesda, MD 20892 USA.
EM olawdoa@mail.nih.gov
NR 5
TC 0
Z9 0
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1545-8547
EI 1557-8542
J9 ZEBRAFISH
JI Zebrafish
PD DEC
PY 2016
VL 13
IS 6
BP 563
EP 564
DI 10.1089/zeb.2016.1344
PG 2
WC Developmental Biology; Zoology
SC Developmental Biology; Zoology
GA EE2MJ
UT WOS:000389418100015
PM 27779465
ER
PT J
AU Landovitz, RJ
Tran, TTT
Cohn, SE
Ofotokun, I
Godfrey, C
Kuritzkes, DR
Lennox, JL
Currier, JS
Ribaudo, HJ
AF Landovitz, Raphael J.
Tran, Thuy Tien T.
Cohn, Susan E.
Ofotokun, Ighovwhera
Godfrey, Catherine
Kuritzkes, Daniel R.
Lennox, Jeffrey L.
Currier, Judith S.
Ribaudo, Heather J.
TI HIV Transmission Risk Behavior in a Cohort of HIV-Infected Treatment-Na
< ve Men and Women in the United States
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Condom use; HIV transmission; ART-naive; Behavior
ID EARLY ANTIRETROVIRAL THERAPY; SEXUAL-BEHAVIOR; PREVENTION; PROPHYLAXIS;
INITIATION; IMPACT; ADULTS; KENYA
AB Antiretroviral therapy (ART) can minimize HIV transmission. Prevention benefits may be compromised by barriers to virologic suppression, and by increased condomless sex among those initiating ART. We evaluated condomless sex in a cohort of HIVinfected US individuals poised to initiate ART in a clinical trial. We assessed partner and sex act type, condom use, and perception of infectiousness. Six percent of participants reported as not infectious; men who have sex with men were more likely to perceive high infectivity. Prevalence of condomless sex was 44 %; 74 % of those also reported homosexual acquisition of HIV. Predictors of increased risk of condomless sex included greater numbers of lifetime partners, recent stimulant drug use and an HIV-positive or unknown serostatus partner. In the context of serodifferent partners, lower perception of infectiousness was also associated with a higher risk of condomless sex. Results highlight opportunities for prevention education for HIV infected individuals at ART initiation.
C1 [Landovitz, Raphael J.; Currier, Judith S.] Univ Calif Los Angeles, Div Infect Dis, UCLA Ctr Clin AIDS Res & Educ, 11075 Santa Monica Blvd,Suite 100, Los Angeles, CA 90025 USA.
[Tran, Thuy Tien T.; Ribaudo, Heather J.] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
[Cohn, Susan E.] Northwestern Univ, Sch Med, Div Infect Dis, Chicago, IL USA.
[Ofotokun, Ighovwhera; Lennox, Jeffrey L.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA.
[Godfrey, Catherine] NIH, Div Aids, Therapeut Res Branch, Bldg 10, Bethesda, MD 20892 USA.
[Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
RP Landovitz, RJ (reprint author), Univ Calif Los Angeles, Div Infect Dis, UCLA Ctr Clin AIDS Res & Educ, 11075 Santa Monica Blvd,Suite 100, Los Angeles, CA 90025 USA.
EM rlandovitz@mednet.ucla.edu
FU National Institute of Allergy and Infectious Diseases [U01AI068636];
National Institute of Mental Health (NIMH), National Institute of Dental
and Craniofacial Research (NIDCR); AIDS Clinical Trials Group; Site Data
Management Center Grant [UM1AI68634]; ACTG; CTSA [UL1 TR000445,
1UL1TR001111, UL1 TR001082, UL1TR000124, UL1 TR024160, UL1 TR000454, UL1
TR000170, UL1TR000439, UL1TR001079, UL1TR000058, 5UL1 RR024156,
UL1TR000457]; CFAR [P30 AI50410, 5-P30-AI-045008-15, P30 AI050409, P30
AI060354]; Cathi Basler-University of Colorado Hospital CRS
[2UM1AI069432]; UCLA CARE Center CRS [A1069424]; Univ. of Rochester ACTG
CRS/AIDS CARE CRS/Trillium Health [2UM1 AI069511-08]; Maria Laura
Martinez-Houston AIDS Research Team CRS [2 UM1 AI069503-08, 2 UM1
AI068636-08]; CPCRA CTU [UM1 AI069503]; RN- UCSF HIV/AIDS CRS [UM1
AI069496]; UCSF-CTSA [UL1 TR000004]; [AI069439]; [UM1AI069494];
[AI69432]; [2UM1AI069439-08]; [UM1 AI069423-08]; [UM1AI069439];
[2UM1AI069452-08]; [AI069432]; [AI069424]; [UM1-AI069534-08]; [U01
AI069471]; [2UM1AI069415-09]; [5U01 AI069471]; [A1069423-08];
[2UM1A1069412-08]; [2UM1 AI069418-08]; [UM 1 A1069503]; [AI069477];
[UM1AI069472]; [AI 69501]; [2UM1AI069503-08]; [UM1 AI069532]; [UM
AI069481]; [2UM1 AI069465]; [AI-069471]; [AI069501]; [1U01AI069494];
[5UM1 AI069484-07]; [2UM1-AI069470-08]; [AI069556]; [U01AI069447];
[UM1AI069419]; [2UM1AI069412-08]; [UM1 AI069494]
FX The project described was supported by Award Number U01AI068636 from the
National Institute of Allergy and Infectious Diseases and supported by
National Institute of Mental Health (NIMH), National Institute of Dental
and Craniofacial Research (NIDCR). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Allergy and Infectious
Diseases or the National Institutes of Health. The study team would like
to additionally thank the ACTG CRS's that conducted the A5257 protocol
and the A5257 study participants. The protocol received support from the
AIDS Clinical Trials Group, the Site Data Management Center Grant of
UM1AI68634, the ACTG specialty laboratories listed in the manuscript,
and the clinical research sites. From the sites we acknowledge the
following personnel and AIDS Clinical Trials Unit Grants: Michelle
Saemann, RN and Jennifer Baer, RN-Cincinnati CRS (Site 2401) Grant
AI069439; Dr. Susan Koletar, Mark Hite RN-Ohio State University CRS
(Site 2301) Grant UM1AI069494; Linda Meixner, RN and Edward Seefried,
RN-UCSD Antiviral Research Center CRS (Site 701) Grant AI69432; Vicki
Bailey, RN and Rebecca Basham, CCRP- Vanderbilt Therapeutics CRS (Site
3652) Grant 2UM1AI069439-08, CTSA Grant UL1 TR000445; David Currin RN
and Miriam Chicurel-Bayard RN-Chapel Hill CRS (Site 3201) Grant UM1
AI069423-08, CTSA Grant 1UL1TR001111, CFAR Grant P30 AI50410; Teresa
Spitz and Judy Frain-Washington University Therapeutics CRS (Site 2101)
Grant UM1AI069439; Elizabeth Lindsey, RN and Tamara James -Alabama
Therapeutics CRS (Site 5801) Grant 2UM1AI069452-08; Beverly Putnam and
Cathi Basler-University of Colorado Hospital CRS (Site 6101) Grant
2UM1AI069432, CTSA Grant UL1 TR001082; Michael P. Dube, MD and Bartolo
Santos, RN-University of Southern California CRS (Site 1201) Grant
AI069432; Eric Daar and Sadia Shaik Harbor UCLA CRS (Site 603) Grant
AI069424, CTSA Grant UL1TR000124; Pablo TebasMD and Aleshia Thomas RN,
BSN-Penn Therapeutics CRS (Site 6201) Grant UM1-AI069534-08, CFAR Grant
5-P30-AI-045008-15; Roger Bedimo, MD and Michelle Mba, MPHTrinity Health
and Wellness Center (Site 31443) Grant U01 AI069471; David Cohn MD and
Fran Moran RN-Denver Public Health CRS (Site 31470) Grant UM1 AI069503;
Jorge L. Santana Bagur, MD and Ileana Boneta Dueno, RN-Puerto Rico AIDS
Clinical Trials Unit CRS (Site 5401) Grant 2UM1AI069415-09; Babafemi
Taiwo, MBBS, Baiba Berzins, MPH-Northwestern University CRS (Site 2701)
Grant 5U01 AI069471; Dr. Emery Chang and Maria Palmer-UCLA CARE Center
CRS (Site 601) Grant A1069424; Mary Adams, RN and Christine Hurley, RN -
Univ. of Rochester ACTG CRS/AIDS CARE CRS/Trillium Health (Site
1101/Site 1108) Grant 2UM1 AI069511-08, CTSA Grant UL1 TR024160; Timothy
Lane and Cornelius Van Dam-Greensboro CRS (Site 3203) Grant A1069423-08;
Karen Tashima MD and Helen Patterson LPN - The Miriam Hospital (TMH) CRS
(Site 2951) Grant 2UM1A1069412-08; Carlos del Rio, MD & Ericka Patrick,
RN- The Ponce de Leon Ctr. CRS (Site 5802) Grant 2UM1 AI069418-08, CFAR
Grant P30 AI050409, CTSA Grant UL1 TR000454; Norman Markowitz and Indira
Brar-Henry Ford Hosp. CRS (Site 31472) Grant UM 1 A1069503; Roberto C.
Arduino, MD, and Maria Laura Martinez-Houston AIDS Research Team CRS
(Site 31473) Grant 2 UM1 AI069503-08, 2 UM1 AI068636-08; Rose Kim, MD
and Yolanda Smith, BA-Cooper Univ. Hosp. CRS (Site 31476) Grant UM1
AI069503; Hector Bolivar, MD, Margaret A. Fischl, MD Univ.; of Miami
AIDS Clinical Research Unit (ACRU) CRS (Site 901) Grant AI069477; Edward
Telzak, MD and Richard Cindrich, MD-Bronx-Lebanon Hosp. Ctr. CRS (Site
31469) Grant UM1 AI069503; Paul Sax MD and Cheryl Keenan RN BC- Brigham
and Women's Hospital Therapeutics CRS (Site 107) Grant UM1AI069472; CFAR
Grant P30 AI060354, CTSA UL1 TR000170; Kim Whitely, RN and Traci Davis,
RN- MetroHealth CRS (Site 2503) Grant AI 69501; CTSA Grant UL1TR000439;
Dr. Rodger D. MacArthur and Marti Farrough, RN, BSN - Wayne State Univ.
CRS (Site 31478) Grant 2UM1AI069503-08; Judith A. Aberg, MD and Michelle
S Cespedes, MPH, MD - NY Univ. HIV/AIDS CRS (Site 401) Grant UM1
AI069532; Shelia Dunaway, MD and Sheryl Storey, PA-C-University of
Washington AIDS CRS (Site 1401) Grant UM AI069481; Joel Gallant, MD, and
Ilene Wiggins, RN -Johns Hopkins University CRS (Site 201) Grant 2UM1
AI069465, CTSA Grant UL1TR001079; Beverly Sha, MD and Veronica Navarro,
RN - Rush University CRS (Site 2702) Grant AI-069471; Vicky Watson RN
and Daniel Nixon DO, PhD - Virginia Commonwealth Univ. Medical Ctr. CRS
(Site 31475) CPCRA CTU award UM1 AI069503, CTSA UL1TR000058; Annie
Luetkemeyer, MD and Jay Dwyer, RN- UCSF HIV/AIDS CRS (Site 801) Grant
UM1 AI069496, UCSF-CTSA Grant UL1 TR000004; Kristen Allen RN and
Patricia Walton RN-Case CRS (Site 2501) Grant AI069501; Dr. Princy Kumar
and Dr. Joseph Timpone-Georgetown University CRS (Site 1008) Grant
1U01AI069494; Mehri McKellar, MD and Jacquelin Granholm, RN-Duke Univ.
Med. Ctr. Adult CRS (Site 1601) Grant 5UM1 AI069484-07; Michael T Yin,
MD MS and Madeline Torres, RN-Columbia Physicians and Surgeons CRS (Site
30329) Grant 2UM1-AI069470-08, CTSA 5UL1 RR024156; Sandra Valle, PA-C
and Debbie Slamowitz, RN-Stanford CRS (Site 501) Grant AI069556; Charles
E. Davis Jr., M.D. and William A. Blattner, M.D. - IHV Baltimore
Treatment CRS (Site 4651) Grant U01AI069447; BMC ACTG CRS (Site 104)
Benjamin Linus, MD, UM1 AI069472; Beth Israel Deaconess Med. Ctr., ACTG
CRS (Site 103) Mary Albrecht, MD, UM1 AI069472; CFAR Grant P30 AI060354;
Christina Megill, PA-C and Valery Hughes, NP-Cornell Chelsea CRS (Site
7804) Grant UM1AI069419, CTSA Grant UL1TR000457; Teri Flynn, MSN, ANP
and Amy Sbrolla BSN, RN Massachusetts General Hospital CRS (Site 101)
Grant 2UM1AI069412-08; CFAR Grant P30 AI060354; Sharon Riddler, MD and
Lisa Klevens, BSN-University of Pittsburgh CRS (Site 1001) Grant UM1
AI069494.
NR 31
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD DEC
PY 2016
VL 20
IS 12
BP 2983
EP 2995
DI 10.1007/s10461-016-1365-2
PG 13
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA ED1AF
UT WOS:000388575100020
PM 26979419
ER
PT J
AU Pfeiffer, CM
Sternberg, MR
Hamner, HC
Crider, KS
Lacher, DA
Rogers, LM
Bailey, RL
Yetley, EA
AF Pfeiffer, Christine M.
Sternberg, Maya R.
Hamner, Heather C.
Crider, Krista S.
Lacher, David A.
Rogers, Lisa M.
Bailey, Regan L.
Yetley, Elizabeth A.
TI Applying inappropriate cutoffs leads to misinterpretation of folate
status in the US population
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE deficiency; insufficiency; microbiologic assay; NHANES;
radioprotein-binding assay
ID BIO-RAD RADIOASSAY; WHOLE-BLOOD FOLATE; MICROBIOLOGIC ASSAY;
UNITED-STATES; RBC FOLATE; NHANES 1988-2010; NATIONAL-HEALTH; SERUM
FOLATE; LC-MS/MS; NUTRITION
AB Background: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution. Objective: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs.
Design: In the cross-sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988-2006) and, afterwards, with the use of a microbiologic assay (2007-2010). We compared prevalence estimates for assay matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12-49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay).
Results: Pre folic acid fortification (1988-1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999-2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988-1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined post fortification (1999-2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007-2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively.
Conclusions: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge.
C1 [Pfeiffer, Christine M.; Sternberg, Maya R.] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Hamner, Heather C.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Crider, Krista S.] CDC, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA.
[Lacher, David A.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Rogers, Lisa M.] WHO Geneva, Geneva, Switzerland.
[Bailey, Regan L.] Purdue Univ, Nutr Sci, W Lafayette, IN 47907 USA.
[Bailey, Regan L.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
EM cfp8@cdc.gov
NR 30
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2016
VL 104
IS 6
BP 1607
EP 1615
DI 10.3945/ajcn.116.138529
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA EE0RV
UT WOS:000389287500014
PM 27680995
ER
PT J
AU Swanger, SA
Chen, WJ
Wells, G
Burger, PB
Tankovic, A
Bhattacharya, S
Strong, KL
Hu, C
Kusumoto, H
Zhang, J
Adams, DR
Millichap, JJ
Petrovski, S
Traynelis, SF
Yuan, H
AF Swanger, Sharon A.
Chen, Wenjuan
Wells, Gordon
Burger, Pieter B.
Tankovic, Anel
Bhattacharya, Subhrajit
Strong, Katie L.
Hu, Chun
Kusumoto, Hirofumi
Zhang, Jing
Adams, David R.
Millichap, John J.
Petrovski, Slave
Traynelis, Stephen F.
Yuan, Hongjie
TI Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in
the GluN2A and GluN2B Agonist Binding Domains
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID D-ASPARTATE RECEPTOR; MOLECULAR-DYNAMICS SIMULATIONS; ONSET EPILEPTIC
ENCEPHALOPATHY; AUTISM SPECTRUM DISORDERS; SITE-DIRECTED MUTAGENESIS;
SUBUNIT MESSENGER-RNAS; DE-NOVO MUTATIONS; LIGAND-BINDING; GLUTAMATE
BINDING; ENDOPLASMIC-RETICULUM
AB Epilepsy and intellectual disability are associated with rare variants in the GluN2A and GluN2B (encoded by GRIN2A and GRIN2B) subunits of the N-methyl-D-aspartate receptor (NMDAR), a ligand-gated ion channel with essential roles in brain development and function. By assessing genetic variation across GluN2 domains, we determined that the agonist binding domain, transmembrane domain, and the linker regions between these domains were particularly intolerant to functional variation. Notably, the agonist binding domain of GluN2B exhibited significantly more variation intolerance than that of GluN2A. To understand the ramifications of missense variation in the agonist binding domain, we investigated the mechanisms by which 25 rare variants in the GluN2A and GluN2B agonist binding domains dysregulated NMDAR activity. When introduced into recombinant human NMDARs, these rare variants identified in individuals with neurologic disease had complex, and sometimes opposing, consequences on agonist binding, channel gating, receptor biogenesis, and forward trafficking. Our approach combined quantitative assessments of these effects to estimate the overall impact on synaptic and non-synaptic NMDAR function. Interestingly, similar neurologic diseases were associated with both gain-and loss-of-function variants in the same gene. Most rare variants in GluN2A were associated with epilepsy, whereas GluN2B variants were associated with intellectual disability with or without seizures. Finally, discerning the mechanisms underlying NMDAR dysregulation by these rare variants allowed investigations of pharmacologic strategies to correct NMDAR function.
C1 [Swanger, Sharon A.; Chen, Wenjuan; Tankovic, Anel; Bhattacharya, Subhrajit; Strong, Katie L.; Hu, Chun; Kusumoto, Hirofumi; Zhang, Jing; Traynelis, Stephen F.; Yuan, Hongjie] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Wells, Gordon; Burger, Pieter B.; Strong, Katie L.] Emory Univ, Dept Chem, 1515 Pierce Dr, Atlanta, GA 30322 USA.
[Adams, David R.] NHGRI, Undiagnosed Dis Network, NIH, Bethesda, MD 20892 USA.
[Millichap, John J.] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Millichap, John J.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Millichap, John J.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Petrovski, Slave] Univ Melbourne, Austin Hlth, Dept Med, Melbourne, Vic 3050, Australia.
[Petrovski, Slave] Royal Melbourne Hosp, Melbourne, Vic 3050, Australia.
[Traynelis, Stephen F.; Yuan, Hongjie] Emory Univ, Sch Med, CFERV, Atlanta, GA 30322 USA.
[Chen, Wenjuan] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410013, Hunan, Peoples R China.
[Wells, Gordon] Univ Stellenbosch, Dept Biochem, ZA-7602 Stellenbosch, South Africa.
RP Traynelis, SF; Yuan, H (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.; Traynelis, SF; Yuan, H (reprint author), Emory Univ, Sch Med, CFERV, Atlanta, GA 30322 USA.
EM strayne@emory.edu; hyuan@emory.edu
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development [R01HD082373]; National Center for Advancing Translational
Sciences of the NIH [UL1TR000454]; National Institute of Neurological
Disorders and Stroke [F32NS086361, NS036654]; Xiangya-Emory Medical
Schools Visiting Student Program; Janssen
FX The authors would like to thank the Exome Aggregation Consortium and the
groups that provided exome variant data for comparison. A full list of
contributing groups can be found at the ExAC website. The authors also
thank Dr. Dennis Liotta for generous support of this study. Research
reported in this publication was supported by the Eunice Kennedy Shriver
National Institute of Child Health & Human Development (R01HD082373 to
H.Y.), the National Center for Advancing Translational Sciences of the
NIH (UL1TR000454 to H.Y.), the National Institute of Neurological
Disorders and Stroke (F32NS086361 to S.A.S. and NS036654 to S.F.T.), and
the Xiangya-Emory Medical Schools Visiting Student Program (to W.C.).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the funding agencies. S.F.T.
is co-founder of NeurOp Inc., a consultant of Janssen Pharmaceuticals,
Pfizer, and NeurOp Inc., and a PI on a research grant from Janssen to
Emory University. S.P. serves on the advisory board of Pairnomix.
NR 101
TC 2
Z9 2
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 1
PY 2016
VL 99
IS 6
BP 1261
EP 1280
DI 10.1016/j.ajhg.2016.10.002
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA ED8VI
UT WOS:000389148600003
PM 27839871
ER
PT J
AU Arno, G
Agrawal, SA
Eblimit, A
Bellingham, J
Xu, MC
Wang, F
Chakarova, C
Parfitt, DA
Lane, A
Burgoyne, T
Hull, S
Carss, KJ
Fiorentino, A
Hayes, MJ
Munro, PM
Nicols, R
Pontikos, N
Holder, GE
Asomugha, C
Raymond, FL
Moore, AT
Plagnol, V
Michaelides, M
Hardcastle, AJ
Li, YM
Cukras, C
Webster, AR
Cheetham, ME
Chen, R
AF Arno, Gavin
Agrawal, Smriti A.
Eblimit, Aiden
Bellingham, James
Xu, Mingchu
Wang, Feng
Chakarova, Christina
Parfitt, David A.
Lane, Amelia
Burgoyne, Thomas
Hull, Sarah
Carss, Keren J.
Fiorentino, Alessia
Hayes, Matthew J.
Munro, Peter M.
Nicols, Ralph
Pontikos, Nikolas
Holder, Graham E.
Asomugha, Chinwe
Raymond, F. Lucy
Moore, Anthony T.
Plagnol, Vincent
Michaelides, Michel
Hardcastle, Alison J.
Li, Yumei
Cukras, Catherine
Webster, Andrew R.
Cheetham, Michael E.
Chen, Rui
CA UKIRDC
TI Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID HEREDITARY SPASTIC PARAPLEGIA; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS;
OPTIC CUPS; DISEASE; IDENTIFICATION; MECHANISMS; GENES; EXPRESSION;
GENOMICS
AB Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy.
C1 [Arno, Gavin; Bellingham, James; Chakarova, Christina; Parfitt, David A.; Lane, Amelia; Burgoyne, Thomas; Hull, Sarah; Fiorentino, Alessia; Hayes, Matthew J.; Munro, Peter M.; Pontikos, Nikolas; Holder, Graham E.; Moore, Anthony T.; Michaelides, Michel; Hardcastle, Alison J.; Webster, Andrew R.; Cheetham, Michael E.] UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
[Arno, Gavin; Hull, Sarah; Holder, Graham E.; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.] Moorfields Eye Hosp, London EC1V 2PD, England.
[Agrawal, Smriti A.; Eblimit, Aiden; Xu, Mingchu; Wang, Feng; Li, Yumei; Chen, Rui] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Agrawal, Smriti A.; Eblimit, Aiden; Xu, Mingchu; Wang, Feng; Li, Yumei; Chen, Rui] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Carss, Keren J.; Raymond, F. Lucy] Cambridge Univ Hosp NHS Fdn Trust, NIHR BioResource Rare Dis, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
[Carss, Keren J.] Univ Cambridge, Dept Haematol, NHS Blood & Transplant Ctr, Cambridge CB2 0PT, England.
[Nicols, Ralph] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
[Asomugha, Chinwe] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA.
[Raymond, F. Lucy] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England.
[Moore, Anthony T.] UCSF, Sch Med, Dept Ophthalmol, Koret Vis Ctr, San Francisco, CA 94133 USA.
[Plagnol, Vincent] UCL, Genet Inst, London WC1E 6BT, England.
[Cukras, Catherine] NEI, NIH, Bethesda, MD 20892 USA.
RP Cheetham, ME (reprint author), UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.; Chen, R (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.; Chen, R (reprint author), Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
EM michael.cheetham@ucl.ac.uk; ruichen@bcm.edu
OI Burgoyne, Thomas/0000-0002-8428-720X; Lord, Emma/0000-0001-9216-7382;
Cheetham, Michael/0000-0001-6429-654X
FU Foundation Fighting Blindness [BR-GE-0613-0618-BCM]; National Eye
Institute [R01EY022356, R01EY020540]; NEI vision core grant
[P30EY002520]; RP Fighting Blindness and Fight for Sight; Wellcome Trust
[092621]; National Institute for Health Research (UK); Biomedical
Research Centre at Moorfields Eye Hospital; UCL Institute of
Ophthalmology; Fight for Sight UK; Moorfields Eye Hospital Special
Trustees; Foundation Fighting Blindness - USA
FX We thank all the individuals and their family members for participating
in this study. We also thank the Integrated Microscopy Core at Baylor
College of Medicine for OCT experiments. Additionally, we thank Dr.
Anand Swaroop for providing the Reep6 antibody and Dr. Peter MacLeish
for providing the 7G6 antibody. We would also like to thank the National
Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE) and Amy
Turiff, the NEI coordinator, the UK Inherited Retinal Disease Consortium
(UKIRDC), and the NIHR BioResource - RareDiseases project
(BRIDGE-SPEED). This project was funded by the Foundation Fighting
Blindness (BR-GE-0613-0618-BCM) and National Eye Institute (R01EY022356,
R01EY020540) to R.C. Sequencing effort is also supported by the NEI
vision core grant (P30EY002520). The UKIRDC is funded by RP Fighting
Blindness and Fight for Sight. This project was also supported by The
Wellcome Trust (092621 to M.E.C.), The National Institute for Health
Research (UK), Biomedical Research Centre at Moorfields Eye Hospital and
UCL Institute of Ophthalmology, Fight for Sight UK, Moorfields Eye
Hospital Special Trustees, and Foundation Fighting Blindness - USA.
NR 34
TC 0
Z9 0
U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 1
PY 2016
VL 99
IS 6
BP 1305
EP 1315
DI 10.1016/j.ajhg.2016.10.008
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA ED8VI
UT WOS:000389148600006
PM 27889058
ER
PT J
AU Vince, N
Li, HC
Ramsuran, V
Naranbhai, V
Duh, FM
Fairfax, BP
Saleh, B
Knight, JC
Anderson, SK
Carrington, M
AF Vince, Nicolas
Li, Hongchuan
Ramsuran, Veron
Naranbhai, Vivek
Duh, Fuh-Mei
Fairfax, Benjamin P.
Saleh, Bahara
Knight, Julian C.
Anderson, Stephen K.
Carrington, Mary
TI HLA-C Level Is Regulated by a Polymorphic Oct1 Binding Site in the HLA-C
Promoter Region
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID WHOLE-GENOME ASSOCIATION; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; HIV
CONTROL; TRANSCRIPTION FACTOR; WIDE ASSOCIATION; OCTAMER MOTIF;
PROTEINS; IMMUNOGLOBULIN; ACTIVATION
AB Differential HLA-C levels influence several human diseases, but the mechanisms responsible are incompletely characterized. Using a validated prediction algorithm, we imputed HLA-C cell surface levels in 228 individuals from the 1000 Genomes dataset. We tested 68,726 SNPs within the MHC for association with HLA-C level. The HLA-C promoter region variant, rs2395471, 800 bp upstream of the transcription start site, gave the most significant association with HLA-C levels (p = 4.2 x 10(-66)). This imputed expression quantitative trait locus, termed impeQTL, was also shown to associate with HLA-C expression in a genome-wide association study of 273 donors in which HLA-C mRNA expression levels were determined by quantitative PCR (qPCR) (p = 1.8 x 10(-20)) and in two cohorts where HLA-C cell surface levels were determined directly by flow cytometry (n = 369 combined, p < 10(-15)). rs2395471 is located in an Oct1 transcription factor consensus binding site motif where the A allele is predicted to have higher affinity for Oct1 than the G allele. Mobility shift electrophoresis demonstrated that Oct1 binds to both alleles in vitro, but decreased HLA-C promoter activity was observed in a luciferase reporter assay for rs2395471_G relative to rs2395471_A on a fixed promoter background. The rs2395471 variant accounts for up to 36% of the explained variation of HLA-C level. These data strengthen our understanding of HLA-C transcriptional regulation and provide a basis for understanding the potential consequences of manipulating HLA-C levels therapeutically.
C1 [Vince, Nicolas; Li, Hongchuan; Ramsuran, Veron; Duh, Fuh-Mei; Saleh, Bahara; Anderson, Stephen K.; Carrington, Mary] Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Vince, Nicolas; Ramsuran, Veron; Naranbhai, Vivek; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
[Naranbhai, Vivek; Fairfax, Benjamin P.; Knight, Julian C.] Univ Oxford, Wellcome Trust, Ctr Human Genet, Oxford OX3 7BN, England.
[Naranbhai, Vivek] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, ZA-4091 Durban, South Africa.
RP Carrington, M (reprint author), Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Carrington, M (reprint author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
EM carringm@mail.nih.gov
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
Intramural Research Program of the NIH; Frederick National Lab; Center
for Cancer Research; European Research Council [281824]; NIHR Oxford
Biomedical Research Centre; Wellcome Trust [090532/Z/09/Z, 074318,
088891]; European Research Council under the European Union [281824];
Medical Research Council [98082]; Rhodes Trust
FX This project has been funded in whole or in part with federal funds from
the Frederick National Laboratory for Cancer Research, under contract
no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported in part by the Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research. J.C.K.
is supported by European Research Council funding (grant agreement no.
281824) and the NIHR Oxford Biomedical Research Centre and Wellcome
Trust (core facilities grant 090532/Z/09/Z). The Oxford cohort was
supported by the Wellcome Trust (grants 074318 [J.C.K.], 088891
[B.P.F.], and 090532/Z/09/Z [core facilities Wellcome Trust Centre for
Human Genetics including High-Throughput Genomics Group]), the European
Research Council under the European Union's Seventh Framework Programme
(FP7/2007-2013)/ERC Grant agreement no. 281824 (J.C.K.), the Medical
Research Council (98082 [J.C.K]), and the NIHR Oxford Biomedical
Research Centre. V.N. was supported by the Rhodes Trust.
NR 40
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 1
PY 2016
VL 99
IS 6
BP 1353
EP 1358
DI 10.1016/j.ajhg.2016.09.023
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA ED8VI
UT WOS:000389148600010
PM 27817866
ER
PT J
AU George, A
Zand, DJ
Hufnagel, RB
Sharma, R
Sergeev, YV
Legare, JM
Rice, GM
Schwoerer, JAS
Rius, M
Tetri, L
Gamm, DM
Bharti, K
Brooks, BP
AF George, Aman
Zand, Dina J.
Hufnagel, Robert B.
Sharma, Ruchi
Sergeev, Yuri V.
Legare, Janet M.
Rice, Gregory M.
Schwoerer, Jessica A. Scott
Rius, Mariana
Tetri, Laura
Gamm, David M.
Bharti, Kapil
Brooks, Brian P.
TI Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis,
Microphthalmia, Macrocephaly, Albinism, and Deafness
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID WAARDENBURG SYNDROME; TFE FAMILY; MOUSE; GENE; MELANOCYTES; HOMOLOG;
NETWORK; PROTEIN
AB Human MITF is, by convention, called the "microphthalmia-associated transcription factor'' because of previously published seminal mouse genetic studies; however, mutations in MITF have never been associated with microphthalmia in humans. Here, we describe a syndrome that we term COMMAD, characterized by coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. COMMAD is associated with biallelic MITF mutant alleles and hence suggests a role for MITF in regulating processes such as optic-fissure closure and bone development or homeostasis, which go beyond what is usually seen in individuals carrying monoallelic MITF mutations.
C1 [George, Aman; Hufnagel, Robert B.; Sergeev, Yuri V.; Rius, Mariana; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Zand, Dina J.; Brooks, Brian P.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Sharma, Ruchi; Bharti, Kapil] NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA.
[Legare, Janet M.; Rice, Gregory M.; Tetri, Laura; Gamm, David M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53726 USA.
[Schwoerer, Jessica A. Scott; Gamm, David M.] Univ Wisconsin, Sch Med & Publ Hlth, McPherson Eye Res Inst, Madison, WI 53726 USA.
[Schwoerer, Jessica A. Scott; Gamm, David M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
[Zand, Dina J.] US FDA, Off New Drugs, Off Drug Evaluat 3, Div Gastroenterol & Inborn Errors Prod, Silver Spring, MD 20993 USA.
[Rius, Mariana] SUNY Stony Brook, Sch Marine & Atmospher Sci, Stony Brook, NY 11790 USA.
RP Brooks, BP (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.; Brooks, BP (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA.
EM brian.brooks1@nih.gov
FU NEI
FX We are grateful to the probands and their families. We thank Dr. Heinz
Arnheiter for critical comments on the manuscript, Dr. James Lister
(Virginia Commonwealth University, Richmond, VA) for the zebrafish mitfa
construct, Drs. Noriko Esumi (Wilmer Eye Institute, Johns Hopkins
University, Baltimore, MD) and Sridhar Mani (Albert Einstein College of
Medicine, Bronx, NY) for luciferase promoter constructs, Drs. Chun Gao
and Robert Farris (Biological Imaging Core, National Eye Institute
[NEI]) for expert assistance with confocal laser-scanning microscopy
experiments, Ramakrishna Alur for technical assistance, Delphine Blain
for genetic counseling, the NEI Clinical Photography Section for
outstanding technical assistance, and Anna Larson and Tyler Fayard for
zebrafish breeding and maintenance. This work was supported by the
intramural program of the NEI.
NR 23
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U1 4
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 1
PY 2016
VL 99
IS 6
BP 1388
EP 1394
DI 10.1016/j.ajhg.2016.11.004
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA ED8VI
UT WOS:000389148600014
PM 27889061
ER
PT J
AU Reynolds, JA
Rosenberg, AZ
Smith, CK
Sergeant, JC
Rice, GI
Briggs, TA
Bruce, IN
Kaplan, MJ
AF Reynolds, John A.
Rosenberg, Avi Z.
Smith, Carolyne K.
Sergeant, Jamie C.
Rice, Gillian I.
Briggs, Tracy A.
Bruce, Ian N.
Kaplan, Mariana J.
TI Vitamin D Deficiency Is Associated With Endothelial Dysfunction and
Increases Type I Interferon Gene Expression in a Murine Model of
Systemic Lupus Erythematosus
SO Arthritis & Rheumatology
LA English
DT Article
ID 25-HYDROXYVITAMIN D DEFICIENCY; DISEASE-ACTIVITY INDEX;
CARDIOVASCULAR-DISEASE; RISK-FACTOR; SIGNATURE; WOMEN
AB Objective. Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD) and impaired endothelial repair. Although vitamin D deficiency is associated with increased CVD risk in the general population, a causal relationship has not been demonstrated. We aimed to determine whether vitamin D deficiency directly modulates endothelial dysfunction and immune responses in a murine model of SLE.
Methods. Vitamin D deficiency was induced in lupus-prone MRL/lpr mice by dietary restriction for 6 weeks. Endothelium-dependent vasorelaxation was quantified using aortic ring myography, and endothelial repair mechanisms were assessed by evaluating the phenotype and function of bone marrow endothelial progenitor cells (EPCs) and with the use of an in vivo Matrigel plug model. Lupus disease activity was determined by evaluating expression of interferon-stimulated genes (ISGs) in splenic tissue, positivity for serum autoantibodies, and renal histology. To validate the findings, expression of ISGs was also measured in whole blood from vitamin D-deficient and vitamin D-sufficient patients with SLE.
Results. Vitamin D deficiency resulted in impaired endothelium-dependent vasorelaxation and decreases in neoangiogenesis without a change in the total number of EPCs. There were no differences in anti-double-stranded DNA titers, proteinuria, or glomerulonephritis (activity or chronicity) between vitamin D-deficient or sufficient mice. Vitamin D deficiency was associated with a trend toward increased ISG expression both in mice and in patients with SLE.
Conclusion. These findings indicate that vitamin D deficiency is associated with hampered vascular repair and reduced endothelial function, and may modulate type I interferon responses.
C1 [Reynolds, John A.; Rosenberg, Avi Z.; Smith, Carolyne K.; Kaplan, Mariana J.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Reynolds, John A.; Briggs, Tracy A.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England.
[Reynolds, John A.; Briggs, Tracy A.] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Rosenberg, Avi Z.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Sergeant, Jamie C.; Bruce, Ian N.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Sergeant, Jamie C.; Bruce, Ian N.] Univ Manchester, Manchester, Lancs, England.
[Rice, Gillian I.] Univ Manchester, Manchester, Lancs, England.
RP Kaplan, MJ (reprint author), NIH, System Autoimmun Branch, NIAMSD, 10 Ctr Dr,6D-47C, Bethesda, MD 20892 USA.
EM mariana.kaplan@nih.gov
FU NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases Intramural Research Program); North West England MRC Fellowship
Scheme in Clinical Pharmacology and Therapeutics - MRC [G1000417/94909];
ICON; GlaxoSmithKline; AstraZeneca; Medicines Evaluation Unit Ltd.;
Arthritis Research UK [20380]; NIHR Manchester Biomedical Research Unit;
NIHR Manchester Wellcome Trust Clinical Research Facility
FX Supported by the NIH (National Institute of Arthritis and
Musculoskeletal and Skin Diseases Intramural Research Program). Dr.
Reynolds is an MRC Clinical Training Fellow and his work was supported
by the North West England MRC Fellowship Scheme in Clinical Pharmacology
and Therapeutics, which is funded by the MRC (grant G1000417/94909),
ICON, GlaxoSmithKline, AstraZeneca, and the Medicines Evaluation Unit
Ltd. Dr. Bruce is an NIHR Senior Investigator and his work was funded by
Arthritis Research UK (grant 20380), the NIHR Manchester Biomedical
Research Unit, and the NIHR Manchester Wellcome Trust Clinical Research
Facility.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD DEC
PY 2016
VL 68
IS 12
BP 2929
EP 2935
DI 10.1002/art.39803
PG 7
WC Rheumatology
SC Rheumatology
GA ED8XE
UT WOS:000389153400013
PM 27390112
ER
PT J
AU Wolfe, F
Walitt, B
AF Wolfe, Frederick
Walitt, Brian
TI Fibromyalgia is overdiagnosed in the general population: comment on the
article by Hootman et al
SO Arthritis & Rheumatology
LA English
DT Letter
ID PREVALENCE; ARTHRITIS
C1 [Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA.
[Walitt, Brian] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Wolfe, F (reprint author), Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA.
NR 9
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD DEC
PY 2016
VL 68
IS 12
BP 3043
EP 3044
DI 10.1002/art.39839
PG 3
WC Rheumatology
SC Rheumatology
GA ED8XE
UT WOS:000389153400028
PM 27564249
ER
PT J
AU Takahashi, YK
Schoenbaum, G
AF Takahashi, Yuji K.
Schoenbaum, Geoffrey
TI Ventral Striatal Lesions Disrupt Dopamine Neuron Signaling of
Differences in Cue Value Caused by Changes in Reward Timing but Not
Number
SO BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE dopamine; ventral striatum; reward prediction error; single unit; rat
ID ORBITOFRONTAL CORTEX; PREDICTION ERRORS; NUCLEUS-ACCUMBENS; IMPULSIVE
CHOICE; DORSAL STRIATUM; TEGMENTAL AREA; SIZED REWARDS; AMYGDALA;
ENCODE; REPRESENTATION
AB We recently showed that ventral striatal (VS) lesions abolished reward prediction errors that reflect changes in reward timing while leaving relatively unaffected errors that reflect changes in reward number. Here we extended those results by examining whether normal learning-related changes in firing to the reward-predictive cues in the same dopamine neurons were also disrupted by VS lesions. This analysis revealed that dopamine neurons recorded in VS-lesioned rats failed to show value-related changes in firing to the cues in timing but showed normal changes in number blocks. This effect suggests that the loss of reward-evoked error signals in the timing blocks impaired encoding of the cue value in downstream areas, which then supply these predictions to dopamine neurons at the time of cue presentation.
C1 [Takahashi, Yuji K.; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Baltimore, MD USA.
[Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
RP Schoenbaum, G (reprint author), 251 Bayview Blvd,Suite 200,Bldg BRC, Baltimore, MD 21224 USA.
EM geoffrey.schoenbaum@nih.gov
FU National Institute on Drug Abuse
FX This work was supported by funding from the National Institute on Drug
Abuse. The opinions expressed in this article are those of the authors'
and do not reflect the view of the National Institutes of Health, the
Department of Health and Human Services, or the United States
government.
NR 57
TC 0
Z9 0
U1 1
U2 1
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7044
EI 1939-0084
J9 BEHAV NEUROSCI
JI Behav. Neurosci.
PD DEC
PY 2016
VL 130
IS 6
BP 593
EP 599
DI 10.1037/bne0000169
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA ED3ID
UT WOS:000388741900007
PM 27854448
ER
PT J
AU George, J
Renn, L
Verthelyi, D
Roederer, M
Rabin, RL
Mattapallil, JJ
AF George, Jeffy
Renn, Lynnsey
Verthelyi, Daniela
Roederer, Mario
Rabin, Ronald L.
Mattapallil, Joseph J.
TI Early treatment with reverse transcriptase inhibitors significantly
suppresses peak plasma IFN alpha in vivo during acute simian
immunodeficiency virus infection
SO CELLULAR IMMUNOLOGY
LA English
DT Article
DE HIV; SIV; IFN alpha; IFN beta; Subtypes; Dendritic cells; Mucosa
ID CD4(+) T-CELLS; PATHOGENIC SIV INFECTION; HEPATITIS-C VIRUS; DENDRITIC
CELLS; INTERFERON-ALPHA; RHESUS MACAQUES; GASTROINTESTINAL-TRACT; HIV-1
INFECTION; LYMPH-NODES; ANTIRETROVIRAL THERAPY
AB Innate interferons (IFN) are comprised of multiple Type I and III subtypes. The in vivo kinetics of subtype responses during human immunodeficiency virus (HIV) infection is not well defined. Using the acute simian immunodeficiency virus (SIV) infection model, we show that plasma IFN alpha levels peak at day 10 post-infection (pi) after which they rapidly declined. The mRNA expression of Type I and III IFN subtypes were significantly elevated in the lymph nodes (LN) at day 10 pi. Though the expression levels of all subtypes declined by day 14-31 pi, numerous subtypes remained elevated suggesting that ongoing viral replication in LN continues to drive induction of these subtypes. Interestingly, treatment with reverse transcriptase (RT) inhibitors at day 7 pi significantly suppressed plasma IFNa responses by day 10 pi that significantly correlated with cell-associated SIV DNA loads suggesting that RT byproducts such as viral DNA likely plays a role in driving IFN responses during acute SIV infection. Quantification of Type I and III subtype transcripts in sorted subsets of LN CD4+ and CD8+ T cells, CD14+/CD14- monocytes/-macrophages, and total CD11c/CD123+ dendritic cells (DC) at day 10 pi showed that DC expressed similar to 3-4 log more subtype transcripts as compared to the other subsets. Taken together, our results provide new insights into the kinetics of innate interferon responses during early stages of infection, and provide evidence that DC's are a major in vivo source of innate IFN during acute SIV infection. Published by Elsevier Inc.
C1 [George, Jeffy; Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Renn, Lynnsey; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Verthelyi, Daniela] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Roederer, Mario] NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
EM joseph.mattapallil@usuhs.edu
FU Uniformed Services University of the Health Sciences
FX The described project was supported by funds from the Uniformed Services
University of the Health Sciences to JJM. The opinions or assertions
contained herein are the private ones of the authors and are not to be
construed as official or reflecting the views of the Department of
Defense, the Uniformed Services University of the Health Sciences or any
other agency of the U.S. Government.
NR 84
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U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0008-8749
EI 1090-2163
J9 CELL IMMUNOL
JI Cell. Immunol.
PD DEC
PY 2016
VL 310
BP 156
EP 164
DI 10.1016/j.cellimm.2016.09.003
PG 9
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA ED4MS
UT WOS:000388823700017
PM 27622386
ER
PT J
AU Sertedaki, A
Markou, A
Vlachakis, D
Kossida, S
Campanac, E
Hoffman, DA
Sierra, MD
Xekouki, P
Stratakis, CA
Kaltsas, G
Piaditis, GP
Chrousos, GP
Charmandari, E
AF Sertedaki, Amalia
Markou, Athina
Vlachakis, Dimitrios
Kossida, Sophia
Campanac, Emilie
Hoffman, Dax A.
Sierra, Maria De La Luz
Xekouki, Paraskevi
Stratakis, Constantine A.
Kaltsas, Gregory
Piaditis, George P.
Chrousos, George P.
Charmandari, Evangelia
TI Functional characterization of two novel germline mutations of the KCNJ5
gene in hypertensive patients without primary aldosteronism but with
ACTH-dependent aldosterone hypersecretion
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID FAMILIAL HYPERALDOSTERONISM; REMEDIABLE ALDOSTERONISM; HEREDITARY
HYPERTENSION; SIGNALING PATHWAYS; POTASSIUM CHANNEL; SECRETION;
PREVALENCE; DIAGNOSIS; MODEL; FORM
AB BackgroundGermline mutations of the KCNJ5 gene encoding Kir34, a member of the inwardly rectifying K+ channel, have been identified in normal' adrenal glands, patients with familial hyperaldosteronism (FH) type III, aldosterone-producing adenomas (APAs) and sporadic cases of primary aldosteronism (PA).
ObjectiveTo present two novel KCNJ5 gene mutations in hypertensive patients without PA, but with Adrenocorticotropic hormone (ACTH)-dependent aldosterone hypersecretion.
Design and PatientsTwo hypertensive patients without PA, who exhibited enhanced ACTH-dependent response of aldosterone secretion, underwent genetic testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. Genomic DNA was isolated from peripheral white blood cells, and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Structural biology studies were also carried out.
ResultsTwo novel germline heterozygous KCNJ5 mutations, p.V259M and p.Y348N, were detected in the two subjects. Electrophysiological studies showed that the Y348N mutation resulted in significantly less negative reversal potentials, suggesting loss of ion selectivity, while the V259M mutation did not affect the Kir3.4 current. In the mutated structural biology model, the N348 mutant resulted in significant loss of the ability for hydrogen bonding, while the M259 mutant was capable of establishing weaker interactions. The CYP11B1/CYP11B2 chimeric gene was not detected.
ConclusionsThese findings expand on the clinical spectrum of phenotypes associated with KCNJ5 mutations and implicate these mutations in the pathogenesis of hypertension associated with increased aldosterone response to ACTH stimulation.
C1 [Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens, Greece.
[Markou, Athina; Piaditis, George P.] G Gennimatas Gen Hosp, Dept Endocrinol & Diabet Ctr, Athens, Greece.
[Vlachakis, Dimitrios; Kossida, Sophia] Acad Athens, Biomed Res Fdn, Bioinformat & Med Informat Team, Athens, Greece.
[Campanac, Emilie; Hoffman, Dax A.] Natl Inst Hlth, Program Dev Neurosci, Mol Neurophysiol & Biophys Sect, Bethesda, MD USA.
[Sierra, Maria De La Luz; Xekouki, Paraskevi; Stratakis, Constantine A.] Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Kaltsas, Gregory] Univ Athens, Sch Med, Laikon Hosp, Dept Pathophysiol, Athens, Greece.
RP Sertedaki, A (reprint author), Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens, Greece.
EM aserted@med.uoa.gr
RI Charmandari, Evangelia/B-6701-2011;
OI Hoffman, Dax/0000-0001-6999-2157; Vlachakis,
Dimitrios/0000-0003-1823-6102
FU National and Kapodistrian University of Athens Medical School, Athens,
Greece; Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, Bethesda, MD, USA
FX A positive control DNA sample for the presence of the CYP11B1/CYP11B2
hybrid gene was kindly provided by Dr Shengxin Xu from Prof RD Gordon.
This work was supported in part by the National and Kapodistrian
University of Athens Medical School, Athens, Greece, and the intramural
programme of the Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda,
MD, USA.
NR 30
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2016
VL 85
IS 6
BP 845
EP 851
DI 10.1111/cen.13132
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EC1DU
UT WOS:000387844500004
PM 27293068
ER
PT J
AU Lee, JJ
Pedley, A
Marqusee, E
Sutherland, P
Hoffmann, U
Massaro, JM
Fox, CS
AF Lee, Jane J.
Pedley, Alison
Marqusee, Ellen
Sutherland, Patrice
Hoffmann, Udo
Massaro, Joseph M.
Fox, Caroline S.
TI Thyroid function and cardiovascular disease risk factors in euthyroid
adults: a cross-sectional and longitudinal study
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID BODY-MASS INDEX; WEIGHT-LOSS; ADIPOSE-TISSUE; FREE-THYROXINE; SERUM TSH;
FREE T4; METABOLIC SYNDROME; HORMONE LEVELS; HEART-DISEASE; ASSOCIATION
AB Objective and designWe explored the cross-sectional and longitudinal associations of thyroid function within the normal range with cardiovascular disease (CVD) risk factors and adiposity measures.
Patients and measurementsA total of 3483 (504% women) participants for the cross-sectional CVD study and 1630 (412% women) participants for the cross-sectional body composition substudy were drawn from the Framingham Third Generation Exam 1; 2912 participants (501% women) for the longitudinal CVD study and 713 participants (359% women) for the longitudinal body composition substudy were drawn from the Framingham Third Generation Exams 1-2. Thyroid function was assessed by thyrotropin [thyroid-stimulating hormone (TSH)] and free thyroxine (fT4) concentrations within the reference range at Exam 1. The associations between thyroid function and CVD risk factors were modelled via multivariable-adjusted regression models. Multivariable adjustment included age, sex, current smoking, postmenopausal status and BMI.
ResultsCross-sectionally, higher TSH concentration was associated with increased odds of hypertriglyceridaemia [odds ratio (OR)=110], and higher BMI ( = 019 kg/m(2)), total cholesterol ( = 005 mmol/l), triglycerides ( = 00006 mmol/l) and subcutaneous adipose tissue (SAT) volume ( = 388 cm(3)) (all P < 005). Cross-sectionally, fT4 was inversely associated with metabolic and adiposity-related CVD risk factors, including obesity (OR = 117), hypertriglyceridaemia (OR = 109), BMI ( = 042 kg/m(2)), total cholesterol ( = 005 mmol/l), triglycerides ( = 00002 mmol/l), visceral adipose tissue (VAT) volume ( = -207 cm(3)) and attenuation (017 HU) and VAT/SAT ratio ( = -001) (all P < 005). However, during 61 years of follow-up, baseline TSH and fT4 levels were not longitudinally associated with CVD risk factors and adiposity measures.
ConclusionsThyroid function within the normal range is cross-sectionally, but not longitudinally, associated with CVD risk factors and adiposity measures.
C1 [Lee, Jane J.; Pedley, Alison; Sutherland, Patrice; Fox, Caroline S.] Populat Studies Branch, Framingham Heart Study, Div Intramural Res, Natl Heart Lung & Blood Inst, Framingham, MA USA.
[Marqusee, Ellen] Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA.
[Marqusee, Ellen] Harvard Med Sch, Boston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Med Sch, Boston, MA USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (contract N01-HC-25195).
NR 34
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2016
VL 85
IS 6
BP 932
EP 941
DI 10.1111/cen.13124
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EC1DU
UT WOS:000387844500015
PM 27256825
ER
PT J
AU Luiz, HV
Yu, R
Wolf, K
Miao, N
Mannes, A
Pacak, K
AF Luiz, Henrique V.
Yu, Run
Wolf, Katherine
Miao, Ning
Mannes, Andrew
Pacak, Karel
TI The Author's Reply: inappropriate adrenoreceptor blockade prior to
pheochromocytoma removal - "A timely reappraisal'
SO CLINICAL ENDOCRINOLOGY
LA English
DT Letter
ID CLINICAL-PRACTICE; PARAGANGLIOMA
C1 [Luiz, Henrique V.; Wolf, Katherine; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD USA.
[Luiz, Henrique V.] Hosp Garcia de Orta, Dept Endocrinol & Diabetol, Almada, Portugal.
[Yu, Run] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Los Angeles, CA 90095 USA.
[Miao, Ning; Mannes, Andrew] NIH, Dept Perioperat Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD USA.
EM karel@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008735-15]
NR 6
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2016
VL 85
IS 6
BP 990
EP 991
DI 10.1111/cen.13234
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EC1DU
UT WOS:000387844500024
PM 27623515
ER
PT J
AU Liangpunsakul, S
Puri, P
Shah, VH
Kamath, P
Sanyal, A
Urban, T
Ren, XW
Katz, B
Radaeva, S
Chalasani, N
Crabb, DW
AF Liangpunsakul, Suthat
Puri, Puneet
Shah, Vijay H.
Kamath, Patrick
Sanyal, Arun
Urban, Thomas
Ren, Xiaowei
Katz, Barry
Radaeva, Svetlana
Chalasani, Naga
Crabb, David W.
CA Translational Res & Evolving Alcoh
TI Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on
Occurrence and Severity of Alcoholic Hepatitis
SO Clinical Gastroenterology and Hepatology
LA English
DT Article
DE TREAT; Alcohol Intake; Gender; TLFB; Alcoholic Hepatitis; Body Weight
ID LIVER-CIRRHOSIS MORTALITY; FATTY LIVER; RISK; DISEASE; PNPLA3;
METAANALYSIS; POPULATION; DRINKING; PATHOGENESIS; PREDICTORS
AB BACKGROUND & AIMS: Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex.
METHODS: We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for All. We also explored the association between PNPLA3 variants and AH.
RESULTS: Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with All. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007).
CONCLUSIONS: Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for All may be associated with the PNPLA3 rs738409 polymorphism.
C1 [Liangpunsakul, Suthat; Chalasani, Naga; Crabb, David W.] Indiana Univ Sch Med, Dept Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA.
[Ren, Xiaowei; Katz, Barry] Indiana Univ Sch Med, Richard M Fairbanks Sch Publ Hlth, Dept Biostat, Indianapolis, IN 46202 USA.
[Liangpunsakul, Suthat] Richard L Roudebush Vet Adm Med Ctr, Dept Med, Indianapolis, IN USA.
[Puri, Puneet; Sanyal, Arun] Virginia Commonwealth Univ, Dept Med, Div Gastroenterol & Hepatol, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Shah, Vijay H.; Kamath, Patrick] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Urban, Thomas] Univ N Carolina, Eshelman Sch Pharm, Ctr Pharmacogen & Individualized Therapy, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Radaeva, Svetlana] NIAAA, NIH, Rockville, MD 20852 USA.
[Crabb, David W.] Eskenazi Hlth, Indianapolis, IN USA.
RP Liangpunsakul, S (reprint author), Indiana Univ, Div Gastroenterol & Hepatol, 550 North Univ Blvd,UH 4100, Indianapolis, IN 46202 USA.
EM sliangpu@iupui.edu
OI Puri, Pier Lorenzo/0000-0003-4964-0095
FU National Institute on Alcohol Abuse and Alcoholism [5U01AA021883-04,
5U01AA021891-04, 5U01AA021788-04, 5U01AA021840-04]
FX The Translational Research and Evolving Alcoholic Hepatitis Treatment
Consortium is supported by the National Institute on Alcohol Abuse and
Alcoholism (5U01AA021883-04, 5U01AA021891-04, 5U01AA021788-04, and
5U01AA021840-04).
NR 31
TC 0
Z9 0
U1 6
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD DEC
PY 2016
VL 14
IS 12
BP 1831
EP 1838
DI 10.1016/j.cgh.2016.05.041
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EE0QD
UT WOS:000389283100024
PM 27320325
ER
PT J
AU De Boer, YS
Kosinski, AS
Urban, TJ
Zhao, Z
Long, NY
Chalasani, N
Kleiner, DE
Hoofnagle, JH
AF De Boer, Ynto S.
Kosinski, Andrzej S.
Urban, Thomas J.
Zhao, Zhen
Long, Nanye
Chalasani, Naga
Kleiner, David E.
Hoofnagle, Jay H.
TI Characterizing Drug-Induced Liver Injury With Autoimmune Features Reply
SO Clinical Gastroenterology and Hepatology
LA English
DT Letter
C1 [De Boer, Ynto S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[De Boer, Ynto S.] Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands.
[Kosinski, Andrzej S.] Duke Clin Res Inst, Durham, NC USA.
[Urban, Thomas J.; Long, Nanye] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Zhao, Zhen] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
[Chalasani, Naga] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP De Boer, YS (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.; De Boer, YS (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands.
OI de Boer, Ynto/0000-0002-4066-7593
NR 3
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD DEC
PY 2016
VL 14
IS 12
BP 1845
EP 1846
DI 10.1016/j.cgh.2016.08.011
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EE0QD
UT WOS:000389283100031
PM 27546581
ER
PT J
AU McMahon, S
AF McMahon, Sheri
TI Minimizing Hazards Associated With Live-Virus Immunotherapeutic Cancer
Vaccines
SO Clinical Journal of Oncology Nursing
LA English
DT Article
DE vaccine; vaccinia; injection; risk; restrictions; safety
ID PROSTATE-CANCER
AB Therapeutic cancer vaccines that use attenuated vaccinia viruses as delivery vectors are undergoing clinical trials at dozens of sites internationally. Even in an attenuated form, these live viruses can cause severe illness if they are accidentally transmitted to immunocompromised people, pregnant women, or people with certain skin conditions. Oncology nurses should become familiar with how to manage patients' vaccine injection sites to minimize these risks to patients' close contacts and the community at large.
At a Glance
Immunotherapeutic vaccines in clinical trials show promise in oncology treatments.
Viral vector vaccines are generally safe for those working with them, and precautions needed are similar to those of other biohazardous materials, such as chemotherapy.
Staff and patient education are important and necessary to minimize potential risks and hazards associated with the administration of immunotherapeutic vaccines.
C1 [McMahon, Sheri] NCI, Off Res Nursing, NIH, Bethesda, MD 20892 USA.
RP McMahon, S (reprint author), NCI, Off Res Nursing, NIH, Bethesda, MD 20892 USA.
EM sheri.mcmahon@nih.gov
NR 12
TC 0
Z9 0
U1 2
U2 2
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
EI 1538-067X
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD DEC
PY 2016
VL 20
IS 6
BP 602
EP 604
DI 10.1188/16.CJON.602-604
PG 3
WC Oncology; Nursing
SC Oncology; Nursing
GA EE0AA
UT WOS:000389234100011
PM 27857270
ER
PT J
AU Pratt, B
Allen, KA
Hyder, AA
AF Pratt, Bridget
Allen, Katharine A.
Hyder, Adnan A.
TI Health Systems Research Consortia and the Promotion of Health Equity in
Low and Middle-Income Countries
SO DEVELOPING WORLD BIOETHICS
LA English
DT Article
DE Research ethics; global justice; health equity; health systems research;
research consortia; low and middle-income countries
ID INTERNATIONAL RESEARCH; RESEARCH ETHICS; GLOBAL JUSTICE; EXPLORATION
AB Health systems research is widely identified as an indispensable means to achieve the goal of health equity between and within countries. Numerous health systems research consortia comprised of institutions from high-income countries and low and middle-income countries (LMICs) are currently undertaking programs of research in LMICs. These partnerships differ from collaborations that carry out single projects in the multiplicity of their goals, scope of their activities, and nature of their management. Recent conceptual work has explored what features might be necessary for health systems research consortia and their research programs to promote health equity. Identified features include selecting research priorities that focus on improving access to high-quality health services and/or financial protection for disadvantaged populations in LMICs and conducting research capacity strengthening that promotes the independent conduct of health systems research in LMICs. Yet, there has been no attempt to investigate whether existing consortia have such characteristics. This paper describes the results of a survey undertaken with health systems research consortia leaders worldwide to assess how consistent current practice is with the proposed ethical guidance. The findings suggest that consortia may be fairly well organised to promote health equity, but have scope for improvement, particularly in terms of achieving inclusive priority-setting.
C1 [Pratt, Bridget] Univ Melbourne, Nossal Inst Global Hlth, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Allen, Katharine A.] Johns Hopkins Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Hyder, Adnan A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Hyder, Adnan A.] Hlth Syst Program, Baltimore, MD USA.
[Hyder, Adnan A.] Int Injury Res Unit, Baltimore, MD USA.
[Hyder, Adnan A.] Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA.
[Hyder, Adnan A.] NIH, Fogarty Int Res Eth Training Program, Bloomberg Sch Publ Health, Bldg 10, Bethesda, MD 20892 USA.
RP Pratt, B (reprint author), Univ Melbourne, Nossal Inst Global Hlth, 161 Barry St, Carlton, Vic 3053, Australia.
EM bpratt2@jhu.edu
FU Australian National Health and Medical Research Council (NHMRC) Early
Career Sidney Sax Public Health Overseas Fellowship [1052346]; Future
Health Systems Initiative; UK Department for International Development
FX Bridget Pratt is supported by an Australian National Health and Medical
Research Council (NHMRC) Early Career Sidney Sax Public Health Overseas
Fellowship (Award No. 1052346). The contents of this article are solely
the responsibility of the authors and do not reflect the views of the
NHMRC. Adnan A. Hyder and Bridget Pratt are also supported by the Future
Health Systems Initiative, which is funded by the UK Department for
International Development.
NR 27
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1471-8731
EI 1471-8847
J9 DEV WORLD BIOETH
JI Dev. World Bioeth.
PD DEC
PY 2016
VL 16
IS 3
BP 148
EP 157
DI 10.1111/dewb.12116
PG 10
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA EC0LF
UT WOS:000387791700005
PM 26990669
ER
PT J
AU Melnikov, S
Mailliot, J
Rigger, L
Neuner, S
Shin, BS
Yusupova, G
Dever, TE
Micura, R
Yusupov, M
AF Melnikov, Sergey
Mailliot, Justine
Rigger, Lukas
Neuner, Sandro
Shin, Byung-Sik
Yusupova, Gulnara
Dever, Thomas E.
Micura, Ronald
Yusupov, Marat
TI Molecular insights into protein synthesis with proline residues
SO EMBO REPORTS
LA English
DT Article
DE hydrolysis-resistant aminoacyl-tRNA analogs; peptide bond formation;
proline; protein synthesis; ribosome
ID PEPTIDE-BOND FORMATION; AMINOACYL-TRANSFER-RNA; EUKARYOTIC RIBOSOME;
STRUCTURAL INSIGHTS; CRYSTAL-STRUCTURE; EFFICIENT ACCESS; EF-P;
TRANSLATION; HYDROLYSIS; MIMICS
AB Proline is an amino acid with a unique cyclic structure that facilitates the folding of many proteins, but also impedes the rate of peptide bond formation by the ribosome. As a ribosome substrate, proline reacts markedly slower when compared with other amino acids both as a donor and as an acceptor of the nascent peptide. Furthermore, synthesis of peptides with consecutive proline residues triggers ribosome stalling. Here, we report crystal structures of the eukaryotic ribosome bound to analogs of mono- and diprolyl-tRNAs. These structures provide a high-resolution insight into unique properties of proline as a ribosome substrate. They show that the cyclic structure of proline residue prevents proline positioning in the amino acid binding pocket and affects the nascent peptide chain position in the ribosomal peptide exit tunnel. These observations extend current knowledge of the protein synthesis mechanism. They also revise an old dogma that amino acids bind the ribosomal active site in a uniform way by showing that proline has a binding mode distinct from other amino acids.
C1 [Melnikov, Sergey; Mailliot, Justine; Yusupova, Gulnara; Yusupov, Marat] CNRS UMR7104, Inst Genet & Mol & Cellular Biol, INSERM UMR964, Illkirch Graffenstaden, France.
[Melnikov, Sergey; Mailliot, Justine; Yusupova, Gulnara; Yusupov, Marat] Strasbourg Univ, Strasbourg, France.
[Rigger, Lukas; Neuner, Sandro; Micura, Ronald] Leopold Franzens Univ, Inst Organ Chem, Innsbruck, Austria.
[Shin, Byung-Sik; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Yusupov, M (reprint author), CNRS UMR7104, Inst Genet & Mol & Cellular Biol, INSERM UMR964, Illkirch Graffenstaden, France.; Yusupov, M (reprint author), Strasbourg Univ, Strasbourg, France.; Micura, R (reprint author), Leopold Franzens Univ, Inst Organ Chem, Innsbruck, Austria.; Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM thomas.dever@nih.gov; ronald.micura@uibk.ac.at; marat@igbmc.fr
OI Mailliot, Justine/0000-0002-1026-542X
FU Foundation pour la Recherche Medicale en France [SPF20111223404];
Austrian Science Fund FWF [P21641, I1040]; French National Research
Agency [ANR-15-CE11-0021-01]; European Research Council [294312]; Human
Frontier Science Progra [RGP0062/2012]
FX We are grateful to Petr Sergiev (Lomonosov Moscow State University) for
providing us with sparsomycin; to the staff of Proxima 1 beamline at the
synchrotron SOLEIL (France), and in particular to Andrew Thompson and
Pierre Legrand for providing rapid access to the beam and for assisting
with data collection, and to members of T.D., R.M., and M.Y. teams for
insightful and inspiring discussions! We also thank Corwin Miller and
members of Tom Steitz and Dieter Sll laboratories (Yale University) for
critically reading and commenting on the manuscript. We also thank
Catherine Dunlavey (University of St. Andrews, UK) for editorial support
during the manuscript preparation. This work was supported by Foundation
pour la Recherche Medicale en France SPF20111223404 (to S.M.), the
Austrian Science Fund FWF (P21641 and I1040 to R.M.), the French
National Research Agency ANR-15-CE11-0021-01 (to G.Y.), the European
Research Council advanced grant 294312 and the Human Frontier Science
Program grant RGP0062/2012 (both to M.Y.), the Russian Government
Program of Competitive Growth of Kazan Federal University (both to M.Y.
and G.Y.), and in part by the Intramural Research Program of the
National Institutes of Health, NICHD (T.D.). The structures were
deposited to the protein data bank with accession codes 5dtv, 5lyb,
5tga, and 5tgm.
NR 44
TC 0
Z9 0
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1469-221X
EI 1469-3178
J9 EMBO REP
JI EMBO Rep.
PD DEC
PY 2016
VL 17
IS 12
BP 1776
EP 1784
DI 10.15252/embr.201642943
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE1GQ
UT WOS:000389329400015
PM 27827794
ER
PT J
AU Darr, R
Nambuba, J
Del Rivero, J
Janssen, I
Merino, M
Todorovic, M
Balint, B
Jochmanova, I
Prchal, JT
Lechan, RM
Tischler, AS
Popovic, V
Miljic, D
Adams, KT
Prall, FR
Ling, A
Golomb, MR
Ferguson, M
Nilubol, N
Chen, CC
Chew, E
Taieb, D
Stratakis, CA
Fojo, T
Yang, CZ
Kebebew, E
Zhuang, ZP
Pacak, K
AF Darr, Roland
Nambuba, Joan
Del Rivero, Jaydira
Janssen, Ingo
Merino, Maria
Todorovic, Milena
Balint, Bela
Jochmanova, Ivana
Prchal, Josef T.
Lechan, Ronald M.
Tischler, Arthur S.
Popovic, Vera
Miljic, Dragana
Adams, Karen T.
Prall, F. Ryan
Ling, Alexander
Golomb, Meredith R.
Ferguson, Michael
Nilubol, Naris
Chen, Clara C.
Chew, Emily
Taieb, David
Stratakis, Constantine A.
Fojo, Tito
Yang, Chunzhang
Kebebew, Electron
Zhuang, Zhengping
Pacak, Karel
TI Novel insights into the polycythemia-paraganglioma-somatostatinoma
syndrome
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE pheochromocytoma; paraganglioma; somatostatinoma; polycythemia; HIF2A
mutation
ID HIPPEL-LINDAU-DISEASE; OF-FUNCTION MUTATIONS; HIF2A MUTATIONS; FAMILIAL
ERYTHROCYTOSIS; PHEOCHROMOCYTOMA; GENE; HYPOXIA; TUMORS; HYPERTENSION;
SUPERIORITY
AB Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and bringsinto perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [F-18]- fluorodihydroxyphenylalanine ([F-18]-FDOPA). Therefore, [F-18]-FDOPA PET/CT, not [Ga-68]-(DOTA)-[Tyr3]-octreotate ([Ga-68]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The longterm prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.
C1 [Darr, Roland; Nambuba, Joan; Del Rivero, Jaydira; Janssen, Ingo; Jochmanova, Ivana; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
[Merino, Maria] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Todorovic, Milena] Univ Belgrade, Clin Ctr Serbia, Inst Hematol, Belgrade, Serbia.
[Todorovic, Milena] Univ Belgrade, Fac Med, Belgrade, Serbia.
[Balint, Bela] Univ Belgrade, Mil Med Acad, Inst Transfusiol & Hemobiol, Belgrade, Serbia.
[Balint, Bela] Univ Belgrade, Inst Med Res, Belgrade, Serbia.
[Jochmanova, Ivana] Pavol Jozef Safarik Univ Kosice, Fac Med, Dept Internal Med 1, Kosice, Slovakia.
[Prchal, Josef T.] Univ Utah, Div Hematol, Salt Lake City, UT USA.
[Lechan, Ronald M.] Tufts Med Ctr, Tupper Res Inst, Boston, MA USA.
[Lechan, Ronald M.] Tufts Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA USA.
[Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA.
[Popovic, Vera; Miljic, Dragana] Univ Belgrade, Fac Med, Clin Ctr Serbia, Inst Endocrinol, Belgrade, Serbia.
[Prall, F. Ryan] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA.
[Prall, F. Ryan] Indiana Univ Sch Med, Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA.
[Ling, Alexander] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Golomb, Meredith R.] Indiana Univ Sch Med, Dept Neurol, Div Child Neurol, Indianapolis, IN 46202 USA.
[Ferguson, Michael] Indiana Univ Hlth, Riley Hosp Children, Indianapolis, IN USA.
[Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Clara C.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Chew, Emily] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, Marseille, France.
[Taieb, David] Aix Marseille Univ, Inst Paoli Calmettes, Marseille Cancerol Res Ctr, CERIMED, Marseille, France.
[Taieb, David] Aix Marseille Univ, Inst Paoli Calmettes, Marseille Cancerol Res Ctr, Inserm UMR1068, Marseille, France.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, NIH, Bethesda, MD USA.
[Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Chunzhang; Zhuang, Zhengping] NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Neurological Disorders and Stroke;
German Research Foundation (DFG) [DA 1630/1-1]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Neurological Disorders and Stroke; and the German Research Foundation
(DFG) (grant number DA 1630/1-1 to R D).
NR 47
TC 0
Z9 0
U1 3
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD DEC
PY 2016
VL 23
IS 12
BP 899
EP 908
DI 10.1530/ERC-16-0231
PG 10
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA ED6BU
UT WOS:000388940100014
PM 27679736
ER
PT J
AU Neelavalli, J
Krishnamurthy, U
Jella, PK
Mody, SS
Yadav, BK
Hendershot, K
Hernandez-Andrade, E
Yeo, L
Cabrera, MD
Haacke, EM
Hassan, SS
Romero, R
AF Neelavalli, Jaladhar
Krishnamurthy, Uday
Jella, Pavan K.
Mody, Swati S.
Yadav, Brijesh K.
Hendershot, Kelly
Hernandez-Andrade, Edgar
Yeo, Lami
Cabrera, Maria D.
Haacke, Ewart M.
Hassan, Sonia S.
Romero, Roberto
TI Magnetic resonance angiography of fetal vasculature at 3.0 T
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Non-contrast magnetic resonance angiography; Time of flight vascular
imaging; Placental vasculature; Fetal circulation; Pseudo-triggering
ID SPATIOTEMPORAL IMAGE CORRELATION; 4-DIMENSIONAL ULTRASONOGRAPHY;
RELAXATION RATES; NEONATAL BRAIN; MR-ANGIOGRAPHY; BLOOD; HEART; ARTERY;
SUSCEPTIBILITY; T-2-ASTERISK
AB Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy.
aEuro cent 3D-visualization of fetal vasculature is feasible using non-contrast MRA at 3.0 T.
aEuro cent Visualization of placental vasculature is also possible with this method.
aEuro cent Fetal MRA can serve as a vascular localizer for quantitative MRI studies.
aEuro cent This method can be extended to 1.5 T.
C1 [Neelavalli, Jaladhar; Krishnamurthy, Uday; Jella, Pavan K.; Mody, Swati S.; Yadav, Brijesh K.; Hendershot, Kelly; Cabrera, Maria D.; Haacke, Ewart M.] Wayne State Univ, Dept Radiol, Sch Med, 4201 St Antoine, Detroit, MI 48201 USA.
[Neelavalli, Jaladhar; Krishnamurthy, Uday; Yadav, Brijesh K.; Haacke, Ewart M.] Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA.
[Mody, Swati S.] Childrens Hosp Michigan, Dept Radiol, Detroit, MI 48201 USA.
[Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Neelavalli, J (reprint author), Wayne State Univ, Dept Radiol, Sch Med, 4201 St Antoine, Detroit, MI 48201 USA.; Neelavalli, J (reprint author), Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA.
EM jneelava@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; STTR from the NHLBI [1R42HL112580-01A1]; Wayne
State University by W.K. Kellogg Foundation [P3018205]
FX The scientific guarantor of this publication is Dr. Jaladhar Neelavalli.
The authors of this manuscript declare no relationships with any
companies whose products or services may be related to the subject
matter of the article. This research was supported, in part, by the
Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; by the STTR grant from the NHLBI -
1R42HL112580-01A1); and by Wayne State University's Perinatology Virtual
Discovery Grant to J.N. (made possible by W.K. Kellogg Foundation award
P3018205). No complex statistical methods were necessary for this paper.
Institutional Review Board approval was obtained. Written informed
consent was obtained from all subjects (patients) in this study. Parts
of the data reported in this paper were presented as an abstract at the
25th World Congress on Ultrasound in Obstetrics and Gynecology, 11-14
October 2015, Montreal, Quebec, Canada. Methodology: prospective,
experimental and performed at one institution.
NR 36
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
EI 1432-1084
J9 EUR RADIOL
JI Eur. Radiol.
PD DEC
PY 2016
VL 26
IS 12
BP 4570
EP 4576
DI 10.1007/s00330-016-4243-4
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EC0SJ
UT WOS:000387810700044
PM 27189488
ER
PT J
AU Ward, H
Tang, L
Poonia, B
Kottilil, S
AF Ward, Haley
Tang, Lydia
Poonia, Bhawna
Kottilil, Shyam
TI Treatment of hepatitis B virus: an update
SO FUTURE MICROBIOLOGY
LA English
DT Review
DE cccDNA; eradication; HBV; hepatitis B; Toll-like receptors; TLRs
ID CHRONIC VIRAL-INFECTION; ALPHA-GLUCOSIDASE INHIBITORS; CHRONIC HBV
INFECTION; CLOSED CIRCULAR DNA; PLASMACYTOID DENDRITIC CELLS; COMPLEX
THERAPEUTIC VACCINE; LARGE ENVELOPE PROTEIN; ZINC-FINGER NUCLEASES;
REPLICATION IN-VIVO; TERM-FOLLOW-UP
AB Chronic hepatitis B virus infection is a global health concern as it affects over 240 million people worldwide and an estimated 686,000 people die annually as a result of complications of the disease. With the development of newer antiviral drugs, viral suppression of HBV is achievable, however elimination of HBV from infected individuals (functional cure) remains an issue. Due to persistence of HBV DNA (cccDNA) in infected cells, chronically infected patients who discontinue therapy prior to HBsAg loss or seroconversion are likely to relapse. Several novel therapeutic strategies are being researched and studied in clinical trials. Here we review these novel strategies to achieve sustained cure or elimination of HBV. These strategies include the targeting of the host or viral factors required for viral persistence as well as therapeutic vaccines.
C1 [Ward, Haley] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Tang, Lydia; Poonia, Bhawna; Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA.
RP Kottilil, S (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA.
EM skottilil@ihv.umaryland.edu
NR 167
TC 0
Z9 0
U1 10
U2 10
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0913
EI 1746-0921
J9 FUTURE MICROBIOL
JI Future Microbiol.
PD DEC
PY 2016
VL 11
IS 12
BP 1581
EP 1597
DI 10.2217/fmb-2016-0128
PG 17
WC Microbiology
SC Microbiology
GA ED2LM
UT WOS:000388676400009
PM 27855500
ER
PT J
AU Dekker, JP
Frank, KM
AF Dekker, John P.
Frank, Karen M.
TI Next-Generation Epidemiology: Using Real-Time Core Genome Multilocus
Sequence Typing To Support Infection Control Policy
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Editorial Material
ID ESCHERICHIA-COLI; OUTBREAK; RESOLUTION; SURVEILLANCE; TRANSMISSION;
STRAIN; SCHEME; MLST
AB Multidrug-resistant bacteria are responsible for substantial morbidity and mortality worldwide. Tracking the nosocomial spread of resistant bacteria is critical to infection control. Mellmann et al. (J. Clin. Microbiol. 54: 2874-2881, 2016, http://dx.doi.org/10.1128/JCM.00790-16) have described prospective whole-genome sequencing with core genome multilocus sequencing typing (cgMLST) analysis for real-time surveillance and have addressed the practical aspects of implementing this type of operation in the hospital setting.
C1 [Dekker, John P.; Frank, Karen M.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Frank, KM (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM Karen.frank@nih.gov
NR 28
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD DEC
PY 2016
VL 54
IS 12
BP 2850
EP 2853
DI 10.1128/JCM.01714-16
PG 4
WC Microbiology
SC Microbiology
GA ED9RF
UT WOS:000389209600003
PM 27629902
ER
PT J
AU Dekker, JP
AF Dekker, John P.
TI Molecular Assay Validation Using Genomic Sequence Databases
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Editorial Material
ID CAMPYLOBACTER-JEJUNI; SPECIES CONCEPT; DIVERSITY; MLST; COLI; PCR
AB Whole-genome sequence databases offer new in silico approaches for designing and validating PCR assays in the clinical microbiology laboratory. An article in this issue of the Journal of Clinical Microbiology (M. J. Jansen van Rensburg, C. Swift, A. J. Cody, C. Jenkins, and M. C. J. Maiden, J Clin Microbiol, 54: 2882-2890, 2016, http://dx.doi.org/10.1128/JCM.01522-16) demonstrates the use of publicly available genomic sequence data to evaluate a PCR assay for distinguishing Campylobacter species.
C1 [Dekker, John P.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Dekker, JP (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM john.dekker@nih.gov
NR 25
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD DEC
PY 2016
VL 54
IS 12
BP 2854
EP 2856
DI 10.1128/JCM.01522-16
PG 3
WC Microbiology
SC Microbiology
GA ED9RF
UT WOS:000389209600004
PM 27733633
ER
PT J
AU Joo, EE
Lombaert, IMA
Yamada, KM
AF Joo, E. E.
Lombaert, I. M. A.
Yamada, K. M.
TI Hyperacetylation of Microtubules in Mesenchymal Cells Increases
Cytokeratin 14-Positive Epithelial Progenitors in Developing Salivary
Glands
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE salivary physiology; morphogenesis; cell differentiation; cell
signaling; epithelial-mesenchymal interaction; extracellular matrix
(ECM)
ID STEM-CELLS; BRANCHING MORPHOGENESIS; EXTRACELLULAR-MATRIX;
PARASYMPATHETIC INNERVATION; TISSUE ARCHITECTURE; FIBRONECTIN; CANCER;
ORGANOGENESIS; REGENERATION; ACETYLATION
AB Cells engage in bidirectional communication with their surroundings. This reciprocal dialogue between cells and their cellular microenvironments often governs the maintenance and differentiation of stem/progenitor cells. Here, the authors present evidence that in developing salivary gland explants, a single posttranslational change in microtubules in mesenchymal cells alters the mesenchymal microenvironment and promotes the maintenance and differentiation of a subset of epithelial progenitor cells that impairs branching morphogenesis. Specifically, the authors report that hyperacetylation of microtubules in mesenchymal cells increased cytokeratin 14-positive ( K14(+)) progenitors and their differentiated progeny, myoepithelial cells, in epithelial basal and suprabasal layers in the distal endbud region of developing salivary glands. Mechanistically, this process engages the transforming growth factor beta 1 protein and Notch signaling pathways. This report establishes that a simple posttranslational change in the cytoskeletal system of mesenchyme dictates the maintenance and differentiation of adjacent epithelial progenitor cells to alter branching morphogenesis of the epithelium.
C1 [Joo, E. E.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
[Lombaert, I. M. A.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Matrix & Morphogenesis Sect, NIH, Bethesda, MD 20892 USA.
RP Joo, EE; Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
EM jooeu@mail.nih.gov; kenneth.yamada@nih.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, National
Institutes of Health. EEJ and KMY designed studies and EEJ performed
experiments. IMAL designed and performed qPCR, recombination, and
fluorescence activated cell sorting assays. EEJ, IMAL, and KMY wrote the
manuscript. The authors declare no potential conflicts of interest with
respect to the authorship and/or publication of this article. IMAL is
currently affiliated with the Biologic and Material Sciences, School of
Dentistry and Biointerfaces Institute, University of Michigan, Ann
Arbor, MI, USA.
NR 31
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD DEC
PY 2016
VL 95
IS 13
BP 1518
EP 1527
DI 10.1177/0022034516662450
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA ED4WB
UT WOS:000388851500012
PM 27542391
ER
PT J
AU Doussau, A
Grady, C
AF Doussau, Adelaide
Grady, Christine
TI Deciphering assumptions about stepped wedge designs: the case of Ebola
vaccine research
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID CLUSTER-RANDOMIZED-TRIALS; EMERGENCY DRUG DISCOVERY; SAMPLE-SIZE
CALCULATION; PREVENTIVE THERAPY; CLINICAL SCIENCE; IMPLEMENTATION;
EFFICACY; EVALUATE; ETHICS; ISSUES
AB Ethical concerns about randomising persons to a no-treatment arm in the context of Ebola epidemic led to consideration of alternative designs. The stepped wedge (SW) design, in which participants or clusters are randomised to receive an intervention at different time points, gained popularity. Common arguments in favour of using this design are (1) when an intervention is likely to do more good than harm, (2) all participants should receive the experimental intervention at some time point during the study and (3) the design might be preferable for practical reasons. We examine these assumptions when considering Ebola vaccine research. First, based on the claim that a stepped wedge design is indicated when it is likely that the intervention will do more good than harm, we reviewed published and ongoing SW trials to explore previous use of this design to test experimental drugs or vaccines, and found that SW design has never been used for trials of experimental drugs or vaccines. Given that Ebola vaccines were all experimental with no prior efficacy data, the use of a stepped wedge design would have been unprecedented. Second, we show that it is rarely true that all participants receive the intervention in SW studies, but rather, depending on certain design features, all clusters receive the intervention. Third, we explore whether the SW design is appealing for feasibility reasons and point out that there is significant complexity. In the setting of the Ebola epidemic, spatiotemporal variation may have posed problematic challenges to a stepped wedge design for vaccine research. Finally, we propose a set of points to consider for scientific reviewers and ethics committees regarding proposals for SW designs.
C1 [Doussau, Adelaide; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Bldg 10-1C118, Bethesda, MD 20892 USA.
RP Doussau, A (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Bldg 10-1C118, Bethesda, MD 20892 USA.
EM doussau2.adelaide@gmail.com
NR 61
TC 0
Z9 0
U1 4
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
EI 1473-4257
J9 J MED ETHICS
JI J. Med. Ethics
PD DEC
PY 2016
VL 42
IS 12
BP 797
EP 804
DI 10.1136/medethics-2015-103292
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA ED6PG
UT WOS:000388977100009
PM 27754861
ER
PT J
AU Pan, E
Supko, JG
Kaley, TJ
Butowski, NA
Cloughesy, T
Jung, J
Desideri, S
Grossman, S
Ye, XB
Park, DM
AF Pan, Edward
Supko, Jeffrey G.
Kaley, Thomas J.
Butowski, Nicholas A.
Cloughesy, Timothy
Jung, Jinkyu
Desideri, Serena
Grossman, Stuart
Ye, Xiaobu
Park, Deric M.
TI Phase I study of RO4929097 with bevacizumab in patients with recurrent
malignant glioma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Glioma; Notch; Gamma secretase; Bevacizumab; Clinical trial
ID GAMMA-SECRETASE INHIBITOR; ADVANCED SOLID TUMORS; CANCER STEM-CELLS;
BREAST-CANCER; NOTCH; ACTIVATION; PATHWAY; HIF-1-ALPHA; LUNG;
ANGIOGENESIS
AB Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combination of bevacizumab and RO4929097, an inhibitor of the notch signaling cascade. A phase I clinical trial was conducted through the Adult Brain Tumor Consortium in subjects with recurrent malignant glioma. Primary objectives were to assess safety and to define the maximum tolerated dose of RO4929097 in combination with bevacizumab. Secondary objectives were to determine overall survival, progression free survival, radiographic response, pharmacokinetic evaluation, and tissue biomarker analysis. Thirteen subjects were enrolled. Of the three subjects treated with the highest dose of RO4929097, one grade 3 toxicity and one grade 2 toxicity were observed. Definitive maximum tolerated dose of RO4929097 in combination with bevacizumab was not identified due to manufacturer's decision to halt drug production. 2 of 12 evaluable subjects demonstrated radiographic response; one subject experienced CR and the second PR. The median overall survival was 10.9 months with a median progression-free survival of 3.7 months. Two subjects remained free of disease progression at 6 months from treatment initiation. PK evaluation did not identify clinically significant drug-drug interactions. All analyzed tissue specimens revealed activation of notch signaling. Combination of RO4929097 and bevacizumab was well-tolerated. Given the compelling scientific rationale, additional studies of antiangiogenic and notch signaling inhibitors should be considered.
C1 [Pan, Edward] UT Southwestern Med Ctr, Simmons Comprehens Canc Ctr, Dept Med, Dallas, TX 75390 USA.
[Supko, Jeffrey G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA.
[Butowski, Nicholas A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Cloughesy, Timothy] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Jung, Jinkyu; Park, Deric M.] NCI, Neurooncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Desideri, Serena; Grossman, Stuart; Ye, Xiaobu] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
RP Pan, E (reprint author), UT Southwestern Med Ctr, Simmons Comprehens Canc Ctr, Dept Med, Dallas, TX 75390 USA.; Park, DM (reprint author), NCI, Neurooncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
EM Edward.Pan@UTSouthwestern.edu; deric.park@nih.gov
FU [CA UM1 137443]
FX CA UM1 137443 awarded to ABTC.
NR 35
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD DEC
PY 2016
VL 130
IS 3
BP 571
EP 579
DI 10.1007/s11060-016-2263-1
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA ED6FE
UT WOS:000388950700020
PM 27826680
ER
PT J
AU Marosi, K
Kim, SW
Moehl, K
Scheibye-Knudsen, M
Cheng, AW
Cutler, R
Camandola, S
Mattson, MP
AF Marosi, Krisztina
Kim, Sang Woo
Moehl, Keelin
Scheibye-Knudsen, Morten
Cheng, Aiwu
Cutler, Roy
Camandola, Simonetta
Mattson, Mark P.
TI 3-Hydroxybutyrate regulates energy metabolism and induces BDNF
expression in cerebral cortical neurons
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE bdnf; ketone; mitochondria; nf-kb; p300
ID FACTOR-KAPPA-B; NEUROTROPHIC FACTOR; KETONE-BODIES; DIETARY RESTRICTION;
BETA-HYDROXYBUTYRATE; MOUSE MODEL; MOLECULAR-MECHANISMS;
ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; OXIDATIVE STRESS
AB During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD(+)/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain-derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons. The mechanism by which 3OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF-B, and activity of the histone acetyltransferase p300/EP300. Because BDNF plays important roles in synaptic plasticity and neuronal stress resistance, our findings suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets.
C1 [Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin; Cheng, Aiwu; Cutler, Roy; Camandola, Simonetta; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Scheibye-Knudsen, Morten] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, Copenhagen, Denmark.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mark.mattson@nih.gov
FU Intramural Research Program of the National Institute on Aging
FX We thank Erez Eitan for providing assistance with some of the
experiments. This research was supported, in its entirety, by the
Intramural Research Program of the National Institute on Aging. None of
the authors have any conflicts of interest to declare.
NR 78
TC 2
Z9 2
U1 10
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2016
VL 139
IS 5
BP 769
EP 781
DI 10.1111/jnc.13868
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA ED8QA
UT WOS:000389134800009
PM 27739595
ER
PT J
AU Chittiboina, P
Talagala, L
Merkle, H
Sarlls, JE
Montgomery, BK
Piazza, MG
Scott, G
Ray-Chaudhury, A
Lonser, RR
Oldfield, EH
Koretsky, AP
Butman, JA
AF Chittiboina, Prashant
Talagala, Lalith
Merkle, Hellmut
Sarlls, Joelle E.
Montgomery, Blake K.
Piazza, Martin G.
Scott, Gretchen
Ray-Chaudhury, Abhik
Lonser, Russell R.
Oldfield, Edward H.
Koretsky, Alan P.
Butman, John A.
TI Endosphenoidal coil for intraoperative magnetic resonance imaging of the
pituitary gland during transsphenoidal surgery
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE endosphenoidal coil; transsphenoidal surgery; intraoperative magnetic
resonance imaging; pituitary adenoma; pituitary surgery
ID CAVERNOUS SINUS INVASION; TO-NOISE RATIO; CUSHINGS-DISEASE; DURAL
INVASION; MRI; ADENOMAS; MICROADENOMAS; ULTRASONOGRAPHY; ACQUISITION;
BRAIN
AB OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [Esc]) during transsphenoidal surgery (TSS) was developed and assessed.
METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 x 0.25 x 0.50 mm(3) and 0.15 x 0.15 x 0.30 mm(3), respectively.
RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections.
CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus.
C1 [Chittiboina, Prashant; Montgomery, Blake K.; Piazza, Martin G.; Scott, Gretchen; Ray-Chaudhury, Abhik; Lonser, Russell R.; Oldfield, Edward H.] NINDS, Surg Neurol Branch, 10 Ctr Dr,Rm 3D20, Bethesda, MD 20892 USA.
[Talagala, Lalith; Sarlls, Joelle E.] NIH, MRI Res Facil, Bldg 10, Bethesda, MD 20892 USA.
[Merkle, Hellmut; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, 10 Ctr Dr,Rm 3D20, Bethesda, MD 20892 USA.
[Butman, John A.] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Lonser, Russell R.] Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA.
[Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
RP Chittiboina, P (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Rm 3D20, Bethesda, MD 20892 USA.
EM prashant.chittiboina@nih.gov
FU intramural research program of the National Institute of Neurological
Disorders and Stroke at the National Institutes of Health (NIH); NIH
FX This study was funded by the intramural research program of the National
Institute of Neurological Disorders and Stroke at the National
Institutes of Health (NIH). This research was also made possible through
the NIH Medical Research Scholars Program, a public-private partnership
supported jointly by the NIH and generous contributions to the
Foundation for the NIH.
NR 37
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD DEC
PY 2016
VL 125
IS 6
BP 1451
EP 1459
DI 10.3171/2015.11.JNS151465
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA ED3XY
UT WOS:000388783000015
PM 26991390
ER
PT J
AU Mehta, GU
Feldman, MJ
Wang, H
Ding, D
Chittiboina, P
AF Mehta, Gautam U.
Feldman, Michael J.
Wang, Herui
Ding, Dale
Chittiboina, Prashant
TI Unilateral vestibular schwannoma in a patient with schwannomatosis in
the absence of LZTR1 mutation
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE cranial nerve; LZTR1; schwannomatosis; vestibular schwannoma
ID DIAGNOSTIC-CRITERIA
AB The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.
C1 [Mehta, Gautam U.; Feldman, Michael J.; Wang, Herui; Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Rm 3D20, Bethesda, MD 20892 USA.
[Mehta, Gautam U.; Ding, Dale] Univ Virginia Hlth Syst, Dept Neurosurg, Charlottesville, VA USA.
RP Mehta, GU (reprint author), NINDS, Surg Neurol Branch, 10 Ctr Dr,Rm 3D20, Bethesda, MD 20892 USA.
EM gautam.mehta@nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke at the National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health (NIH).
NR 9
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD DEC
PY 2016
VL 125
IS 6
BP 1469
EP 1471
DI 10.3171/2015.11.JNS151766
PG 3
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA ED3XY
UT WOS:000388783000017
PM 26848914
ER
PT J
AU Jahns, L
Johnson, LK
Scheett, AJ
Stote, KS
Raatz, SK
Subar, AF
Tande, D
AF Jahns, Lisa
Johnson, LuAnn K.
Scheett, Angela J.
Stote, Kim S.
Raatz, Susan K.
Subar, Amy F.
Tande, Desiree
TI Measures of Diet Quality across Calendar and Winter Holiday Seasons
among Midlife Women: A 1-Year Longitudinal Study Using the Automated
Self-Administered 24-Hour Recall
SO Journal of the Academy of Nutrition and Dietetics
LA English
DT Article
DE Season; Holiday; Diet quality; Healthy Eating Index 2010 (HEI-2010);
Automated Self-Administered 24-Hour Recall (ASA24)
ID WEIGHT-GAIN; NUTRIENT INTAKE; ENERGY-INTAKE; BODY-WEIGHT; MEN;
CONSUMPTION; POPULATION; OVERWEIGHT; AMERICANS; RESOURCE
AB Background Systematic seasonal bias may confound efforts to estimate usual dietary intake and diet quality. Little is known about dietary quality over the winter holiday season.
Objectives The aims of this study were to test for differences in intakes of energy, percentage of energy from macronutrients, fruits and vegetables, and diet quality measured using the Healthy Eating Index 2010 (HEI-2010) by calendar and winter holiday seasons.
Design Longitudinal cohort design.
Participants/setting Data were derived from the Life in All Seasons study. Two cohorts of women aged 40 to 60 years (N=52) from the greater Grand Forks, ND, area were followed for 1 year each between July 2012 and July 2014. Each woman completed an online diet recall using the Automated Self-Administered 24-Hour Recall every 10 days during the year, with a 92% response rate.
Statistical analyses Effects of calendar and winter holiday seasons on intakes of energy, percent energy from macronutrients, HEI-2010 total and component scores, and grams per day of individual fruits and vegetables were tested using mixed linear models.
Results The mean total HEI-2010 score was 60.1 +/- 1.4. There were seasonal differences in some HEI-2010 component scores, but not in total scores. More lettuce or mixed lettuce salad was consumed during summer than during winter (P=0.034), and more fresh tomatoes were consumed during summer and fall compared with winter (P=0.001). More corn, berries, peaches and nectarines, and melons (P<0.001) were consumed during summer. There was no seasonal difference in reported intakes of energy (P=0.793). The total HEI-2010 score for dietary intake observed over the winter holiday season was lower than the rest of the year (P<0.001). Reported energy intake was not different (P=0.228).
Conclusions In this population, diet quality is significantly lower during the winter holiday period, but mostly consistent by season. Multiple recalls in any season can give a reasonable representation of usual overall diet quality throughout the year.
C1 [Jahns, Lisa; Johnson, LuAnn K.; Scheett, Angela J.; Raatz, Susan K.] ARS, USDA, Grand Forks Human Nutr Res Ctr, 2420 2nd Ave N, Grand Forks, ND 58203 USA.
[Stote, Kim S.] SUNY Empire State Coll, Hlth Sci, Saratoga Springs, NY 12866 USA.
[Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Tande, Desiree] Univ North Dakota, Dept Nutr & Dietet, Grand Forks, ND 58201 USA.
RP Jahns, L (reprint author), ARS, USDA, Grand Forks Human Nutr Res Ctr, 2420 2nd Ave N, Grand Forks, ND 58203 USA.
EM lisa.jahns@ars.usda.gov
FU US Department of Agriculture (USDA), Agricultural Research Service [USDA
5450-51000-48-00D, USDA 3062-51000-51-00D]
FX This study was funded by the US Department of Agriculture (USDA),
Agricultural Research Service (USDA 5450-51000-48-00D and USDA
3062-51000-51-00D). The contents of this publication do not necessarily
reflect the views or policies of the USDA or the Agricultural Research
Service, nor does mention of trade names, commercial products, or
organizations imply endorsement from the US government.
NR 31
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
EI 2212-2680
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD DEC
PY 2016
VL 116
IS 12
BP 1961
EP 1969
DI 10.1016/j.jand.2016.07.013
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA ED9QY
UT WOS:000389208800011
PM 27618574
ER
PT J
AU Goldstein, BI
Blanco, C
He, JP
Merikangas, K
AF Goldstein, Benjamin I.
Blanco, Carlos
He, Jian-Ping
Merikangas, Kathleen
TI Correlates of Overweight and Obesity Among Adolescents With Bipolar
Disorder in the National Comorbidity Survey-Adolescent Supplement
(NCS-A)
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE bipolar disorder; obesity; overweight; epidemiologic
ID MAJOR DEPRESSIVE DISORDER; BODY-MASS INDEX; NUTRITION EXAMINATION
SURVEY; CARDIOVASCULAR-DISEASE; WEIGHT-GAIN; I-DISORDER; SPECTRUM
DISORDERS; EATING-DISORDER; UNITED-STATES; MENTAL-HEALTH
AB Objective: Despite substantial evidence on the prevalence and correlates of overweight and obesity (OW/OB) in adults with bipolar disorder (BD), little is known about this topic in adolescents with BD.
Method: The method consisted of the National Comorbidity Survey Adolescent Supplement, a face-to-face survey of mental disorders from 2001 through 2004, using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview. Participants were adolescents 13 to 17 years of age, with bipolar disorder I or II (n = 295), major depressive disorder (n = 1,112), or controls with neither mood disorder (n = 8,716). Analyses examined for group differences in the prevalence of OW/OB and for correlates of OW/OB in the group with BD.
Results: There were no significant differences in weight categories across groups. OW and OB in adolescents with BD were associated with significantly higher lifetime rates of suicide attempt (odds ratio 3.02, 95% CI 1.11-8.24), physical or sexual abuse (2.82, 1.20-6.60), binge eating or bulimia (2.66, 1.13-6.26), and conduct disorder (2.60, 1.10-6.13) in covariate-adjusted analyses. OW and 0)3 also were significantly associated with seeing a professional for depression, being hospitalized overnight for depression, and receiving general medical treatment.
Conclusion: The similar prevalence of OW/OB in adolescents with and without BD suggests that this potent association in adults likely comprises a consequence of BD or its correlates. In contrast, the strong association of OW/OB with proxies for depression severity, including suicide attempts and hospitalization, is already evident even in this young, nonclinical sample. Studies are warranted to determine whether early intervention of OW/OB in BD might optimize physical and mental health.
C1 [Goldstein, Benjamin I.] Sunnybrook Hlth Sci Ctr, Ctr Youth Bipolar Disorder, Toronto, ON, Canada.
[Goldstein, Benjamin I.] Univ Toronto, Toronto, ON, Canada.
[Blanco, Carlos] NIMH, Natl Inst Drug Abuse & Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[He, Jian-Ping; Merikangas, Kathleen] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[He, Jian-Ping; Merikangas, Kathleen] NIMH, Dev Trajectories Mental Disorders Branch, Bethesda, MD 20892 USA.
RP Goldstein, BI (reprint author), Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave,Room FG-53, Toronto, ON M4N 3M5, Canada.
FU Intramural Research Program of the National Institute of Mental Health
[ZIAMH002808]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (ZIAMH002808). The views and
opinions expressed in this article are those of the authors and should
not be construed to represent the views of any of the sponsoring
organizations, agencies, or US Government.
NR 61
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD DEC
PY 2016
VL 55
IS 12
BP 1020
EP 1026
DI 10.1016/j.jaac.2016.08.010
PG 7
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA EE0UF
UT WOS:000389293700004
PM 27871636
ER
PT J
AU Gold, AL
Brotman, MA
Adleman, NE
Lever, SN
Steuber, ER
Fromm, SJ
Mueller, SC
Pine, DS
Leibenluft, E
AF Gold, Andrea L.
Brotman, Melissa A.
Adleman, Nancy E.
Lever, Sara N.
Steuber, Elizabeth R.
Fromm, Stephen J.
Mueller, Sven C.
Pine, Daniel S.
Leibenluft, Ellen
TI Comparing Brain Morphometry Across Multiple Childhood Psychiatric
Disorders
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE voxel-based morphometry; bipolar disorder; disruptive mood dysregulation
disorder; anxiety disorders; prefrontal cortex
ID SEVERE MOOD DYSREGULATION; VOXEL-BASED MORPHOMETRY; GRAY-MATTER VOLUME;
GENERALIZED ANXIETY DISORDER; PEDIATRIC BIPOLAR DISORDER; MAJOR
DEPRESSIVE DISORDER; CORTICAL THICKNESS; HEALTHY-CHILDREN; RATING-SCALE;
SEX-DIFFERENCES
AB Objective: In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs.
Method: 3-Tesla T1-weighted magnetic resonance imaging scans were acquired in 184 youths (39 anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses were conducted. One-way analysis of variance tested GMV differences with whole-brain familywise error (p < .05) correction; secondary, exploratory whole-brain analyses used a threshold of p < .001, >= 200 voxels. Given recent frameworks advocating dimensional approaches in psychopathology research, we also tested GMV associations with continuous anxiety, irritability, and inattention symptoms.
Results: Specificity emerged in the left dorsolateral PFC (d1PFC), which differed among youth with BD, anxiety, and HVs; GMV was increased in youth with anxiety, but decreased in BD, relative to HVs. Secondary analyses revealed BD-specific GMV decreases in the right lateral PFC, right d1PFC, and dorsomedial PFC, and also anxiety specific GMV increases in the left d1PFC, right ventrolateral PFC, frontal pole, and right parahippocampal gyrus/lingual gyrus. Both BD and DMDD showed decreased GMV relative to HVs in the right d1PFC/superior frontal gyrus. GMV was not associated with dimensional measures of anxiety, irritability, or ADHD symptoms.
Conclusion: Both disorder-specific and shared GMV differences manifest in pediatric psychopathology. Some differences were specific to anxiety disorders, others specific to BD, and others shared between BD and DMDD. Further developmental research might map commonalities and differences of structure and function in diverse pediatric psychopathologies.
C1 [Gold, Andrea L.; Brotman, Melissa A.; Adleman, Nancy E.; Lever, Sara N.; Steuber, Elizabeth R.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, Bethesda, MD 20892 USA.
[Adleman, Nancy E.] Catholic Univ Amer, Washington, DC 20064 USA.
[Fromm, Stephen J.] Vantiv Inc, Lowell, MA USA.
[Mueller, Sven C.] Univ Ghent, B-9000 Ghent, Belgium.
RP Gold, AL (reprint author), Bldg 1-5K,MSC-2670, Bethesda, MD 20892 USA.
RI Brotman, Melissa/H-7409-2013;
OI Gold, Andrea/0000-0003-4447-776X
FU Intramural Research Program of the National Institute of Mental
Health/National Institutes of Health (NIMH/NIH) [ZIAMH002781,
ZIAMH002778-15, ZIAMH002786-13, 01-M-0192, 00-M-0198, 02-M-0021]
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health/National Institutes of Health
(NIMH/NIH), ZIAMH002781 (Pine), ZIAMH002778-15 (Leibenluft),
ZIAMH002786-13 (Leibenluft), and based on Clinical Study Protocols
01-M-0192, 00-M-0198, and 02-M-0021.
NR 63
TC 0
Z9 0
U1 20
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD DEC
PY 2016
VL 55
IS 12
BP 1027
EP 1037
DI 10.1016/j.jaac.2016.08.008
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA EE0UF
UT WOS:000389293700005
PM 27871637
ER
PT J
AU Palumbo, P
Klenk, J
Cattelani, L
Bandinelli, S
Ferrucci, L
Rapp, K
Chiari, L
Rothenbacher, D
AF Palumbo, Pierpaolo
Klenk, Jochen
Cattelani, Luca
Bandinelli, Stefania
Ferrucci, Luigi
Rapp, Kilian
Chiari, Lorenzo
Rothenbacher, Dietrich
TI Predictive Performance of a Fall Risk Assessment Tool for
Community-Dwelling Older People (FRAT-up) in 4 European Cohorts
SO Journal of the American Medical Directors Association
LA English
DT Article
DE Older people; falls; FRAT-up; prediction model; validation
ID INDIVIDUAL PROGNOSIS; EXTERNAL VALIDATION; DIAGNOSIS TRIPOD;
META-ANALYSIS; GO TEST; MODELS; METAANALYSIS; ADULTS; POPULATION;
ACCURACY
AB Background and objective: The fall risk assessment tool (FRAT-up) is a tool for predicting falls in community-dwelling older people based on a meta-analysis of fall risk factors. Based on the fall risk factor profile, this tool calculates the individual risk of falling over the next year. The objective of this study is to evaluate the performance of FRAT-up in predicting future falls in multiple cohorts.
Methods: Information about fall risk factors in 4 European cohorts of older people [Activity and Function in the Elderly (ActiFE), Germany; English Longitudinal Study of Aging (ELSA), England; Invecchiare nel Chianti (InCHIANTI), Italy; Irish Longitudinal Study on Aging (TILDA), Ireland] was used to calculate the FRAT-up risk score in individual participants. Information about falls that occurred after the assessment of the risk factors was collected from subsequent longitudinal follow-ups. We compared the performance of FRAT-up against those of other prediction models specifically fitted in each cohort by calculation of the area under the receiver operating characteristic curve (AUC).
Results: The AUC attained by FRAT-up is 0.562 [95% confidence interval (CI) 0.530-0.594] for ActiFE, 0.699 (95% CI 0.680-0.718) for ELSA, 0.636 (95% CI 0.594-0.681) for InCHIANTI, and 0.685 (95% CI 0.660-0.709) for TILDA. Mean FRAT-up AUC as estimated from meta-analysis is 0.646 (95% CI 0.584-0.708), with substantial heterogeneity between studies. In each cohort, FRAT-up discriminant ability is surpassed, at most, by the cohort-specific risk model fitted on that same cohort.
Conclusions: We conclude that FRAT-up is a valid approach to estimate risk of falls in populations of community-dwelling older people. However, further studies should be performed to better understand the reasons for the observed heterogeneity across studies and to refine a tool that performs homogeneously with higher accuracy measures across different populations. (C) 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc.
C1 [Palumbo, Pierpaolo; Chiari, Lorenzo] Univ Bologna, Dept Elect Elect & Informat Engn Guglielmo Marcon, Bologna, Italy.
[Klenk, Jochen; Rapp, Kilian] Robert Bosch Krankenhaus, Dept Geriatr, Stuttgart, Germany.
[Klenk, Jochen; Rapp, Kilian] Robert Bosch Krankenhaus, Clin Geriatr Rehabil, Stuttgart, Germany.
[Klenk, Jochen; Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
[Cattelani, Luca] Univ Bologna, Dept Comp Sci & Engn DISI, Bologna, Italy.
[Bandinelli, Stefania] Tuscany Ctr, Local Hlth Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Chiari, Lorenzo] Univ Bologna, Hlth Sci & Technol Interdept Ctr Ind Res, Bologna, Italy.
RP Palumbo, P (reprint author), Univ Bologna, Biolab, Dept Elect Elect & Informat Engn Guglielmo Marcon, Viale Risorgimento 2, I-40136 Bologna, BO, Italy.
EM pierpaolo.palumbo@unibo.it
RI Klenk, Jochen/C-2164-2012;
OI Klenk, Jochen/0000-0002-5987-447X; Palumbo,
Pierpaolo/0000-0002-4438-1787
FU Ministry of Science, Research and Arts, state of Baden-Wuerttemberg,
Germany, as part of the Geriatric Competence Center, Ulm University;
National Institute of Aging in the United States; National Institute on
Aging (National Institutes of Health, National Institute on Aging,
Bethesda, MD); Italian Health Ministry; National Institutes of Health
contract; Government of Ireland through the Office of the Minister for
Health and Children; Atlantic Philanthropies; Irish Life
FX The ActiFE study was supported by grants from the Ministry of Science,
Research and Arts, state of Baden-Wuerttemberg, Germany, as part of the
Geriatric Competence Center, Ulm University.; The data relative to ELSA
were made available through the United Kingdom Data Archive. ELSA was
developed by a team of researchers based at the NatCen Social Research,
University College London and the Institute for Fiscal Studies. The data
were collected by NatCen Social Research. The funding is provided by the
National Institute of Aging in the United States, and a consortium of
United Kingdom government departments coordinated by the Office for
National Statistics. The developers and funders of ELSA and the Archive
do not bear any responsibility for the analyses or interpretations
presented here.; The InCHIANTI study is currently supported by a grant
from the National Institute on Aging (National Institutes of Health,
National Institute on Aging, Bethesda, MD) and is coordinated by the
Tuscany Regional Health Agency in a partnership with the Florence Health
Care Agency, the local Administrators, and the primary care physicians
of Greve in Chianti and Bagno a Ripoli. The study was initially managed
by the National Institute on Research and Care of the Elderly (Ancona,
Italy), and it was funded by Italian Health Ministry and by a National
Institutes of Health contract. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript. TILDA is an interinstitutional initiative led by Trinity
College Dublin.; TILDA data have been co-funded by the Government of
Ireland through the Office of the Minister for Health and Children, by
Atlantic Philanthropies, and by Irish Life; have been collected under
the Statistics Act, 1993, of the Central Statistics Office. The project
has been designed and implemented by the TILDA study team, Department of
Health and Children. Copyright and all other intellectual property
rights relating to the data are vested in TILDA. Ethical approval for
each wave of data collection is granted by the Trinity College Research
Ethics Committee. TILDA data is accessible for free from the following
sites: Irish Social Science Data Archive at University College Dublin
http://www.ucd.ie/issda/data/tilda/; Interuniversity Consortium for
Political and Social Research at the University of Michigan
(http://www.icpsr.umich.edu/icpsrweb/ICPSR/studies/34315).
NR 61
TC 0
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U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
EI 1538-9375
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD DEC 1
PY 2016
VL 17
IS 12
BP 1106
EP 1113
DI 10.1016/j.jamda.2016.07.015
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA ED9NM
UT WOS:000389198200007
PM 27594522
ER
PT J
AU Ritt, DA
Abreu-Blanco, MT
Bindu, L
Durrant, DE
Zhou, M
Specht, SI
Stephen, AG
Holderfield, M
Morrison, DK
AF Ritt, Daniel A.
Abreu-Blanco, Maria T.
Bindu, Lakshman
Durrant, David E.
Zhou, Ming
Specht, Suzanne I.
Stephen, Andrew G.
Holderfield, Matthew
Morrison, Deborah K.
TI Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced
Phospho-Regulatory Circuit
SO MOLECULAR CELL
LA English
DT Article
ID FEEDBACK PHOSPHORYLATION; MYELODYSPLASTIC SYNDROME; KINASE
PHOSPHORYLATION; PROTEIN-KINASES; CELL-DEATH; RIGOSERTIB; ERK;
TRANSDUCTION; ACTIVATION; MECHANISM
AB Ras pathway signaling plays a critical role in cell growth control and is often upregulated in human cancer. The Raf kinases selectively interact with GTP-bound Ras and are important effectors of Ras signaling, functioning as the initiating kinases in the ERK cascade. Here, we identify a route for the phospho-inhibition of Ras/Raf/MEK/ERK pathway signaling that is mediated by the stress-activated JNK cascade. We find that key Ras pathway components, the RasGEF Sos1 and the Rafs, are phosphorylated on multiple S/TP sites in response to JNK activation and that the hyperphosphorylation of these sites renders the Rafs and Sos1 unresponsive to upstream signals. This phospho-regulatory circuit is engaged by cancer therapeutics, such as rigosertib and paclitaxel/Taxol, that activate JNK through mitotic and oxidative stress as well as by physiological regulators of the JNK cascade and may function as a signaling checkpoint to suppress the Ras pathway during conditions of cellular stress.
C1 [Ritt, Daniel A.; Durrant, David E.; Specht, Suzanne I.; Morrison, Deborah K.] NCI Frederick, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Abreu-Blanco, Maria T.; Bindu, Lakshman; Zhou, Ming; Stephen, Andrew G.; Holderfield, Matthew] NCI Ras Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI Frederick, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [ZIA BC 010329,
HHSN261200800001E]
FX This project was supported by federal funds from the National Cancer
Institute, National Institutes of Health, under project number ZIA BC
010329 and contract number HHSN261200800001E.
NR 32
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U1 8
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD DEC 1
PY 2016
VL 64
IS 5
BP 875
EP 887
DI 10.1016/j.molcel.2016.10.029
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EE3RS
UT WOS:000389515500005
PM 27889448
ER
PT J
AU Choi, S
Hedman, AC
Sayedyahossein, S
Thapa, N
Sacks, DB
Anderson, RA
AF Choi, Suyong
Hedman, Andrew C.
Sayedyahossein, Samar
Thapa, Narendra
Sacks, David B.
Anderson, Richard A.
TI Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation
by scaffolded phosphoinositide kinases
SO NATURE CELL BIOLOGY
LA English
DT Article
ID FOCAL ADHESION KINASE; 3-KINASE PATHWAY; PHOSPHATE KINASE; EXOCYST
COMPLEX; CELL REGULATION; INSULIN ACTION; BREAST-CANCER; LEADING-EDGE;
IQGAP1; MEMBRANE
AB Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P-3) is crucial for development, cell growth and survival, and motility, and it becomes dysfunctional in many diseases including cancers. Here we reveal a mechanism for PtdIns(3,4,5)P-3 generation by scaffolded phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIII alpha and PIPKI alpha, which sequentially generate PtdIns(3,4,5) P3 from phosphatidylinositol. By scaffolding these kinases into functional proximity, the PtdIns(4,5)P-2 generated is selectively used by PI(3)K for PtdIns(3,4,5)P-3 generation, which then signals to PDK1 and Akt that are also in the complex. Moreover, multiple receptor types stimulate the assembly of this IQGAP1-PI(3) K signalling complex. Blockade of IQGAP1 interaction with PIPKI alpha or PI(3)K inhibited PtdIns(3,4,5)P-3 generation and signalling, and selectively diminished cancer cell survival, revealing a target for cancer chemotherapy.
C1 [Choi, Suyong; Thapa, Narendra; Anderson, Richard A.] Univ Wisconsin, Sch Med & Publ Hlth, 1300 Univ Ave, Madison, WI 53706 USA.
[Hedman, Andrew C.; Sayedyahossein, Samar; Sacks, David B.] NIH, Dept Lab Med, 10 Ctr Dr, Bethesda, MD 20892 USA.
RP Anderson, RA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, 1300 Univ Ave, Madison, WI 53706 USA.
EM raanders@wisc.edu
OI Anderson, Richard/0000-0001-6265-8359
FU National Institutes of Health (NIH); Intramural Research Program of the
NIH; American Heart Association fellowships
FX We would like to thank T. Balla for the PH domain constructs, and all
members of the R.A.A. and D.B.S. laboratories, A. Rapreager, P. Lambert,
M. Sussman and R. Kimple (University of Wisconsin-Madison) for helpful
discussions. This work was supported by National Institutes of Health
(NIH) grants to R.A.A., the Intramural Research Program of the NIH to
D.B.S. and American Heart Association fellowships to S.C.
NR 78
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U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD DEC
PY 2016
VL 18
IS 12
BP 1324
EP +
DI 10.1038/ncb3441
PG 59
WC Cell Biology
SC Cell Biology
GA ED8PY
UT WOS:000389134600010
PM 27870828
ER
PT J
AU de Cabo, R
Navas, P
AF de Cabo, Rafael
Navas, Pacido
TI Spermidine to the rescue for an aging heart
SO NATURE MEDICINE
LA English
DT Editorial Material
ID AUTOPHAGY; RESVERATROL; POLYAMINES; LONGEVITY
C1 [de Cabo, Rafael] NIA, US NIH, Baltimore, MD 21224 USA.
[Navas, Pacido] Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, Inst Carlos III, CABD,CSIC,CIBERER, Seville, Spain.
RP de Cabo, R (reprint author), NIA, US NIH, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
OI , rafael/0000-0003-2830-5693
NR 10
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U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2016
VL 22
IS 12
BP 1389
EP 1390
DI 10.1038/nm.4243
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA EE4CI
UT WOS:000389549000014
PM 27923032
ER
PT J
AU Khurana, S
Fuentes, S
Coyle, EM
Ravichandran, S
Davey, RT
Beigel, JH
AF Khurana, Surender
Fuentes, Sandra
Coyle, Elizabeth M.
Ravichandran, Supriya
Davey, Richard T., Jr.
Beigel, John H.
TI Human antibody repertoire after VSV-Ebola vaccination identifies novel
targets and virus-neutralizing IgM antibodies
SO NATURE MEDICINE
LA English
DT Article
ID PROTECTS NONHUMAN-PRIMATES; RANDOMIZED CLINICAL-TRIAL; INFLUENZA
VACCINE; MEDIATED PROTECTION; AFFINITY MATURATION; B-CELLS; INFECTION;
RESPONSES; GLYCOPROTEIN; CHALLENGE
AB Development of an effective vaccine against Ebola virus is of high priority. However, knowledge about potential correlates of protection and the durability of immune response after vaccination is limited. Here, we elucidate the human antibody repertoire after administration of vesicular stomatitis virus (VSV)-Ebola vaccine at 3 million, 20 million and 100 million plaque-forming units (PFU) and homologous VSV-Ebola vaccine boost in healthy adult volunteers. Whole genome-fragment phage display libraries, expressing linear and conformational epitopes of Ebola glycoprotein (GP), showed higher diversity of antibody epitopes in individuals vaccinated with 20 million PFU than in those vaccinated with 3 million or 100 million PFU. Surface plasmon resonance kinetics showed higher levels of GP-binding antibodies after a single vaccination with 20 million or 100 million PFU than with 3 million PFU, and these correlated strongly with neutralization titers. A second vaccination did not boost antibody or virus neutralization titers, which declined rapidly, and induced only minimal antibody affinity maturation. Isotype analysis revealed a predominant IgM response even after the second vaccination, which contributed substantially to virus neutralization in vitro. These findings may help identify new vaccine targets and aid development and evaluation of effective countermeasures against Ebola.
C1 [Khurana, Surender; Fuentes, Sandra; Coyle, Elizabeth M.; Ravichandran, Supriya] US FDA, Div Viral Prod, CBER, Silver Spring, MD 20993 USA.
[Davey, Richard T., Jr.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Beigel, John H.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD USA.
RP Khurana, S (reprint author), US FDA, Div Viral Prod, CBER, Silver Spring, MD 20993 USA.
EM surender.khurana@fda.hhs.gov
FU US National Institute of Allergy and Infectious Diseases; FDA-MCMi-Ebola
funds; US National Cancer Institute [HHSN261200800001E]; US Department
of Defense (DoD) Medical Countermeasures Systems' Joint Vaccine
Acquisition Program at Fort Detrick, Maryland
FX We thank S. Rubin and H. Golding for reviewing the manuscript and J.
Voell, P. Munoz, R. McConnell, H. Baus, C. Rehm and J. Metcalf for help
with clinical studies. We thank J. Crowe (Vanderbilt University) for the
gift of MAb 289 and MAb 324. The clinical trial from which the test sera
were derived was funded partly by the US National Institute of Allergy
and Infectious Diseases. The antibody characterization work described in
this manuscript was supported by FDA-MCMi-Ebola funds to S.K. The latter
funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript. This project was
funded in whole or in part with federal funds from the US National
Cancer Institute under contract HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the US
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
government. We thank the US Army Medical Research Institute of
Infectious Diseases team, including S. Kwilas, M. Wisniewski and J.
Hooper, for providing the pseudovirion neutralization assay data used in
this study. The pseudovirion work was funded by the US Department of
Defense (DoD) Medical Countermeasures Systems' Joint Vaccine Acquisition
Program at Fort Detrick, Maryland. The opinions, interpretations,
conclusions and recommendations contained herein are those of the
authors and are not necessarily endorsed by the US DoD.
NR 40
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2016
VL 22
IS 12
BP 1439
EP +
DI 10.1038/nm.4201
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA EE4CI
UT WOS:000389549000021
PM 27798615
ER
PT J
AU Osuna, CE
Lim, SY
Deleage, C
Griffin, BD
Stein, D
Schroeder, LT
Omange, RW
Best, K
Luo, M
Hraber, PT
Andersen-Elyard, H
Ojeda, EFC
Huang, S
Vanlandingham, DL
Higgs, S
Perelson, AS
Estes, JD
Safronetz, D
Lewis, MG
Whitney, JB
AF Osuna, Christa E.
Lim, So-Yon
Deleage, Claire
Griffin, Bryan D.
Stein, Derek
Schroeder, Lukas T.
Omange, Robert Were
Best, Katharine
Luo, Ma
Hraber, Peter T.
Andersen-Elyard, Hanne
Ojeda, Erwing Fabian Cardozo
Huang, Scott
Vanlandingham, Dana L.
Higgs, Stephen
Perelson, Alan S.
Estes, Jacob D.
Safronetz, David
Lewis, Mark G.
Whitney, James B.
TI Zika viral dynamics and shedding in rhesus and cynomolgus macaques
SO NATURE MEDICINE
LA English
DT Article
ID NATURAL-KILLER-CELLS; WEST NILE VIRUS; SEXUAL TRANSMISSION; DENGUE
VIRUS; INFECTION; BRAZIL; MOSQUITOS; OUTBREAK; SERUM; EXPRESSION
AB Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.
C1 [Osuna, Christa E.; Lim, So-Yon; Whitney, James B.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA.
[Deleage, Claire; Estes, Jacob D.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA.
[Griffin, Bryan D.; Stein, Derek; Schroeder, Lukas T.; Omange, Robert Were; Luo, Ma; Safronetz, David] Natl Microbiol Lab, Winnipeg, MB, Canada.
[Best, Katharine; Hraber, Peter T.; Ojeda, Erwing Fabian Cardozo; Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Andersen-Elyard, Hanne; Lewis, Mark G.] Bioqual, Rockville, MD USA.
[Huang, Scott; Vanlandingham, Dana L.; Higgs, Stephen] Kansas State Univ, Biosecur Res Inst, Manhattan, KS 66506 USA.
[Whitney, James B.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
RP Whitney, JB (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA.; Whitney, JB (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
EM jwhitne2@bidmc.harvard.edu
OI Osuna, Christa/0000-0003-2761-2456; Hraber, Peter/0000-0002-2920-4897
FU National Cancer Institute ( NIH Contract) [HHSN261200800001E]; NIH
[AI028433, OD0110995]; Public Health Agency of Canada
FX We thank B. Finneyfrock, Z. Pippin, A. Dodson and A. Cook for their
expert animal husbandry and care, and J. Guedj for suggestions about the
model simulations. CD38 antibodies were obtained from the NIH Nonhuman
Primate Reagent Resource supported by HHSN272200900037C and OD010976.
The data presented in this study are tabulated in the main paper and in
the supplementary materials. This work was supported in part by federal
funds from the National Cancer Institute ( NIH Contract
HHSN261200800001E). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the US Government. A.S.P.
acknowledges support from NIH grants AI028433 and OD0110995. D.S.
acknowledges support from the Public Health Agency of Canada.
NR 54
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2016
VL 22
IS 12
BP 1448
EP +
DI 10.1038/nm.4206
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA EE4CI
UT WOS:000389549000022
PM 27694931
ER
PT J
AU Lee, J
Boutz, DR
Chromikova, V
Joyce, MG
Vollmers, C
Leung, K
Horton, AP
DeKosky, BJ
Lee, CH
Lavinder, JJ
Murrin, EM
Chrysostomou, C
Hoi, KH
Tsybovsky, Y
Thomas, PV
Druz, A
Zhang, BS
Zhang, Y
Wang, LS
Kong, WP
Park, D
Popova, LI
Dekker, CL
Davis, MM
Carter, CE
Ross, TM
Ellington, AD
Wilson, PC
Marcotte, EM
Mascola, JR
Ippolito, GC
Krammer, F
Quake, SR
Kwong, PD
Georgiou, G
AF Lee, Jiwon
Boutz, Daniel R.
Chromikova, Veronika
Joyce, M. Gordon
Vollmers, Christopher
Leung, Kwanyee
Horton, Andrew P.
DeKosky, Brandon J.
Lee, Chang-Han
Lavinder, Jason J.
Murrin, Ellen M.
Chrysostomou, Constantine
Hoi, Kam Hon
Tsybovsky, Yaroslav
Thomas, Paul V.
Druz, Aliaksandr
Zhang, Baoshan
Zhang, Yi
Wang, Lingshu
Kong, Wing-Pui
Park, Daechan
Popova, Lyubov I.
Dekker, Cornelia L.
Davis, Mark M.
Carter, Chalise E.
Ross, Ted M.
Ellington, Andrew D.
Wilson, Patrick C.
Marcotte, Edward M.
Mascola, John R.
Ippolito, Gregory C.
Krammer, Florian
Quake, Stephen R.
Kwong, Peter D.
Georgiou, George
TI Molecular-level analysis of the serum antibody repertoire in young
adults before and after seasonal influenza vaccination
SO NATURE MEDICINE
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; IN-VIVO; NEUTRALIZING EPITOPE; VIRUS
HEMAGGLUTININ; ELECTRON-MICROSCOPY; H5N1 VACCINATION; GLOBULAR HEAD; B
VIRUSES; PROTECTION; VACCINES
AB Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for similar to 60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.
C1 [Lee, Jiwon; DeKosky, Brandon J.; Lee, Chang-Han; Lavinder, Jason J.; Murrin, Ellen M.; Chrysostomou, Constantine; Park, Daechan; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.
[Boutz, Daniel R.; Horton, Andrew P.; Ellington, Andrew D.; Marcotte, Edward M.; Georgiou, George] Univ Texas Austin, Ctr Syst & Synthet Biol, Austin, TX 78712 USA.
[Chromikova, Veronika; Krammer, Florian] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Joyce, M. Gordon; Leung, Kwanyee; Thomas, Paul V.; Druz, Aliaksandr; Zhang, Baoshan; Zhang, Yi; Wang, Lingshu; Kong, Wing-Pui; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Vollmers, Christopher; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Hoi, Kam Hon; Georgiou, George] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Tsybovsky, Yaroslav] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res Inc, Frederick, MD USA.
[Popova, Lyubov I.; Wilson, Patrick C.] Univ Chicago, Dept Med, Rheumatol Sect, Gwen Knapp Ctr Lupus & Immunol Res, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Dekker, Cornelia L.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Davis, Mark M.; Quake, Stephen R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Davis, Mark M.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
[Carter, Chalise E.; Ross, Ted M.] Univ Georgia, Dept Infect Dis, Ctr Vaccines & Immunol, Athens, GA 30602 USA.
[Ellington, Andrew D.; Marcotte, Edward M.; Ippolito, Gregory C.; Georgiou, George] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
[Quake, Stephen R.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
[DeKosky, Brandon J.] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hoi, Kam Hon] Genentech Inc, Antibody Engn Dept, San Francisco, CA 94080 USA.
[Popova, Lyubov I.] SRI Int, Div Infect Dis, Harrisonburg, VA USA.
RP Georgiou, G (reprint author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.; Georgiou, G (reprint author), Univ Texas Austin, Ctr Syst & Synthet Biol, Austin, TX 78712 USA.; Georgiou, G (reprint author), Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.; Georgiou, G (reprint author), Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
EM gg@che.utexas.edu
OI Park, Daechan/0000-0003-4991-5247
FU NIH [5U19AI057234-09, PO1 AI089618, U19 AI109946]; NIH-NCRR CTSA award
[UL1 RR025744]; Intramural Research Program of the Vaccine Research
Center, NIAID, NIH; Frederick National Laboratory for Cancer Research,
NIH [HHSN261200800001E]; Leidos Biomedical Research, Inc.; DTRA contract
[HDTRA1-12-C-0105]; CPRIT grant [673 RP100890]; Clayton Foundation;
Centers of Influenza Virus Research and Surveillance (CEIRS)
[HHSN272201400008C, HHSN272201400005C]; Welch Foundation [F1515, F1654]
FX We are grateful to C. Das for help with monoclonal antibody expression,
G. Wu, S. Schatzle and Y. Wine for preliminary experiments and advice,
and S. Harrison and A. Schmidt (Harvard Medical School) for providing
rHAs and critical comments on the manuscript. We are indebted to
Sanofi-Pasteur for their kind gift of IIV1s and to BEI Resources for
rHAs. We also thank our study volunteers and S. Mackey for clinical
project management, and regulatory and data management support, and S.
Swope for conducting the study visits. This work was supported by NIH
grants 5U19AI057234-09 (G. G.), PO1 AI089618 (G. G.) and U19 AI109946
(F.K. and P.C.W.), NIH-NCRR CTSA award number UL1 RR025744 (C.L.D.), the
Intramural Research Program of the Vaccine Research Center, NIAID, NIH
(M.G.J., K.L., P.V.T., A.D., B.Z., Y.Z., L.W., W.-P.K., J.R.M. and
P.D.K.), federal funds from the Frederick National Laboratory for Cancer
Research, NIH, under contract HHSN261200800001E and Leidos Biomedical
Research, Inc. (Y.T.), DTRA contract HDTRA1-12-C-0105 (G.G.), CPRIT
grant 673 RP100890 for LC-MS/MS instrumentation at University of Texas
at Austin (G. G.), the Clayton Foundation (G. G.), the Centers of
Influenza Virus Research and Surveillance (CEIRS) contracts
HHSN272201400008C (F.K.) and HHSN272201400005C (P.C.W.), and Welch
Foundation grants F1515 (E.M.Marcotte) and F1654 (A.D.E.).
NR 59
TC 0
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U1 7
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2016
VL 22
IS 12
BP 1456
EP +
DI 10.1038/nm.4224
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA EE4CI
UT WOS:000389549000023
ER
PT J
AU Jarret, A
McFarland, AP
Horner, SM
Kell, A
Schwerk, J
Hong, M
Badil, S
Joslyn, RC
Baker, DP
Carrington, M
Hagedorn, CH
Gale, M
Savan, R
AF Jarret, Abigail
McFarland, Adelle P.
Horner, Stacy M.
Kell, Alison
Schwerk, Johannes
Hong, MeeAe
Badil, Samantha
Joslyn, Rochelle C.
Baker, Darren P.
Carrington, Mary
Hagedorn, Curt H.
Gale, Michael, Jr.
Savan, Ram
TI Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral
signaling
SO NATURE MEDICINE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RECEPTOR MESSENGER-RNA; GENETIC-VARIATION; HCV
INFECTION; IFN THERAPY; III IFN; EXPRESSION; IL28B; LIVER; ALPHA
AB Hepatitis C virus (HCV) infects 200 million people globally, and 60-80% of cases persist as a chronic infection that will progress to cirrhosis and liver cancer in 2-10% of patients(1-3). We recently demonstrated that HCV induces aberrant expression of two host microRNAs (miRNAs), miR-208b and miR-499a-5p, encoded by myosin genes in infected hepatocytes(4). These miRNAs, along with AU-rich-element-mediated decay, suppress IFNL2 and IFNL3, members of the type III interferon (IFN) gene family, to support viral persistence. In this study, we show that miR-208b and miR-499a-5p also dampen type I IFN signaling in HCV-infected hepatocytes by directly down-regulating expression of the type I IFN receptor chain, IFNAR1. Inhibition of these miRNAs by using miRNA inhibitors during HCV infection increased expression of IFNAR1. Additionally, inhibition rescued the antiviral response to exogenous type I IFN, as measured by a marked increase in IFN-stimulated genes and a decrease in HCV load. Treatment of HCV-infected hepatocytes with type I IFN increased expression of myosins over HCV infection alone. Since these miRNAs can suppress type III IFN family members, these data collectively define a novel cross-regulation between type I and III IFNs during HCV infection.
C1 [Jarret, Abigail; McFarland, Adelle P.; Horner, Stacy M.; Kell, Alison; Schwerk, Johannes; Hong, MeeAe; Badil, Samantha; Joslyn, Rochelle C.; Gale, Michael, Jr.; Savan, Ram] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Baker, Darren P.] Biogen Idec Inc, Cambridge, MA USA.
[Carrington, Mary] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Leidos Biomed Res Frederick, Frederick, MD USA.
[Carrington, Mary] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
[Hagedorn, Curt H.] Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA.
[Hagedorn, Curt H.] Univ Arkansas Med Sci, Genet Program, Little Rock, AR 72205 USA.
[Hagedorn, Curt H.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[McFarland, Adelle P.] Univ Washington, Dept Microbiol, Mol & Cellular Biol Program, Seattle, WA 98195 USA.
[Horner, Stacy M.] Duke Univ, Med Ctr, Ctr Virol, Dept Mol Genet & Microbiol, Durham, NC USA.
[Baker, Darren P.] Sanofi Genzyme, Cambridge, MA USA.
RP Savan, R (reprint author), Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
EM savanram@uw.edu
FU NIAID NIH HHS [R01 AI108765]
NR 41
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2016
VL 22
IS 12
BP 1475
EP +
DI 10.1038/nm.4211
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA EE4CI
UT WOS:000389549000026
PM 27841874
ER
PT J
AU Parkman, HP
Hallinan, EK
Hasler, WL
Farrugia, G
Koch, KL
Calles, J
Snape, WJ
Abell, TL
Sarosiek, I
McCallum, RW
Nguyen, L
Pasricha, PJ
Clarke, J
Miriel, L
Lee, L
Tonascia, J
Hamilton, F
AF Parkman, H. P.
Hallinan, E. K.
Hasler, W. L.
Farrugia, G.
Koch, K. L.
Calles, J.
Snape, W. J.
Abell, T. L.
Sarosiek, I.
McCallum, R. W.
Nguyen, L.
Pasricha, P. J.
Clarke, J.
Miriel, L.
Lee, L.
Tonascia, J.
Hamilton, F.
CA NIDDK Gastroparesis Clinical Res C
TI Nausea and vomiting in gastroparesis: similarities and differences in
idiopathic and diabetic gastroparesis
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Article
DE diabetic gastroparesis; gastric emptying; gastroparesis; Nausea;
vomiting
ID UPPER GASTROINTESTINAL DISORDERS; SYMPTOM SEVERITY; GASTRIC RETENTION;
VALIDATION; INDEX; MEAL
AB BackgroundNausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG).
MethodsGastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting.
Key ResultsOf 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p=0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating.
Conclusions & InferencesNausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.
C1 [Parkman, H. P.] Temple Univ, Philadelphia, PA 19122 USA.
[Hallinan, E. K.; Pasricha, P. J.; Clarke, J.; Miriel, L.; Lee, L.; Tonascia, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Hasler, W. L.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Farrugia, G.] Mayo Clin, Rochester, MN USA.
[Koch, K. L.; Calles, J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Snape, W. J.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Abell, T. L.] Univ Louisville, Louisville, KY 40292 USA.
[Sarosiek, I.; McCallum, R. W.] Texas Tech Univ, El Paso, TX USA.
[Nguyen, L.] Stanford Univ, Palo Alto, CA 94304 USA.
[Hamilton, F.] NIDDK, Bethesda, MD 20892 USA.
RP Parkman, HP (reprint author), Temple Univ, Sch Med, Gastroenterol Sect, Parkinson Pavil,8th Floor,3401 North Broad St, Philadelphia, PA 19140 USA.
EM henry.parkman@temple.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]
FX The Gastroparesis Clinical Research Consortium (GpCRC) is supported by
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) (grants U01DK073983, U01DK073975, U01DK073985, U01DK074007,
U01DK073974, U01DK074008).
NR 25
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1350-1925
EI 1365-2982
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD DEC
PY 2016
VL 28
IS 12
BP 1902
EP 1914
DI 10.1111/nmo.12893
PG 13
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA ED8VD
UT WOS:000389148100014
PM 27350152
ER
PT J
AU Basuli, F
Zhang, X
Jagoda, EM
Choyke, PL
Swenson, RE
AF Basuli, Falguni
Zhang, Xiang
Jagoda, Elaine M.
Choyke, Peter L.
Swenson, Rolf E.
TI Facile room temperature synthesis of fluorine-18 labeled fluoronicotinic
acid-2,3,5,6-tetrafluorophenyl ester without azeotropic drying of
fluorine-18
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; LATE-STAGE FLUORINATION; IONIC LIQUID;
RADIOPHARMACEUTICALS; RADIOFLUORINATION; RADIOSYNTHESES; BIOMOLECULES;
SYSTEM; RANGE; PET
AB Fluorine-18 labeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester has been successfully synthesized in an unprecedented way by flowing an acetonitrile solution of its quaternary ammonium salt precursor (N,N,N-trimethy1-5-((2,3,5,6-tetrafluorophenoxy)carbonyl)pyridin-2-aminium trifluoromethanesulfonate, 1) through an anion exchange cartridge. The fluorination reaction proceeded at room temperature without azeotropic drying of the fluoride. Over 75% conversion was observed with 10 mg of precursor in 2:8, acetonitrile: t-butanol in 1 min. The total synthesis time was 5 min which is similar to 30 min shorter than the current literature method. Published by Elsevier Inc.
C1 [Basuli, Falguni; Zhang, Xiang; Swenson, Rolf E.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20852 USA.
[Jagoda, Elaine M.; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Basuli, F (reprint author), NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20852 USA.
EM bhattacharyyaf@mail.nih.gov
FU federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported [in part] by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 36
TC 1
Z9 1
U1 5
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD DEC
PY 2016
VL 43
IS 12
BP 770
EP 772
DI 10.1016/j.nucmedbio.2016.08.008
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EE0TB
UT WOS:000389290700004
PM 27693671
ER
PT J
AU Kim, H
Lee, SJ
Kim, JS
Davies-Venn, C
Cho, HJ
Won, SJ
Dejene, E
Yao, ZS
Kim, I
Paik, CH
Bluemke, DA
AF Kim, Heejung
Lee, Sung-Jin
Kim, Jin Su
Davies-Venn, Cynthia
Cho, Hong-Jun
Won, Samuel J.
Dejene, Eden
Yao, Zhengsheng
Kim, Insook
Paik, Chang H.
Bluemke, David A.
TI Pharmacokinetics and microbiodistribution of Cu-64-labeled
collagen-binding peptides in chronic myocardial infarction
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE collagen-specific peptides; extracellular space fraction; fibrosis;
myocardial infarction; PET imaging
ID ENERGY COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; GLYCOPROTEIN-VI;
CONTRAST AGENT; GD-DOTA; FIBROSIS; PET; IDENTIFICATION; RAT
AB ObjectivesThe aim of the study is to evaluate the pharmacokinetics and microbiodistribution of Cu-64-labeled collagen-binding peptides.MethodsThe affinity constant (K-D), association (k(a)), and dissociation rate constant (k(d)) for the peptide collagelin or its analog (named CRPA) binding to collagen were measured by biolayer interferometric analysis. Rats (n=4-5) with myocardial infarction or normal were injected intravenously with the Cu-64-labeled peptides or Cu-64-DOTA as a control. Dynamic PET imaging was performed for 60min at 7-8 weeks after infarct. Fluorine-18 fluorodeoxyglucose PET imaging was performed to identify the viable myocardium. To validate the PET images, slices of heart samples from the base to the apex were analyzed using autoradiography and histology.ResultThe peptides bound to collagen with a K-D of approximate to 0.9 mu mol/l. The Cu-64-peptides and Cu-64-DOTA accumulated in the infarct area (confirmed by autoradiography and histology images) within 1min of injection and were excreted rapidly through the renal system. The blood clearance curves were biphasic with elimination half-lives of 21.92.4, 26.2 +/- 4.6, and 21.2 +/- 2.1min for Cu-64-CRPA, Cu-64-collagelin, and the control Cu-64-DOTA, respectively. The clearance half-lives from the focal fibrotic tissue (24.1 +/- 1.5, 25.6 +/- 8.0, and 21.4 +/- 1.3min, respectively) and remote myocardium (20.8 +/- 0.7, 21.0 +/- 5.5, and 19.1 +/- 2.4min, respectively) were not significantly different. The uptake ratios of infarct-to-remote myocardium (1.93 +/- 0.18, 2.15 +/- 0.38, and 1.88 +/- 0.08, respectively) for Cu-64-CRPA, Cu-64-collagelin, and Cu-64-DOTA remained stable for the time period between 10 and 60min.ConclusionThe distribution of the Cu-64-collagelin probes corresponds to the heterogeneous distribution of expanded extracellular space in the setting of myocardial infarction. The overall washout rate from the fibrous tissue was determined by the slow washout rate (t(1/2)20min) of the peptides from the extracellular space to the vasculature, not by the dissociation rate (t(1/2)<2min) of the Cu-64-peptides from collagen.
C1 [Kim, Heejung; Lee, Sung-Jin; Kim, Jin Su; Davies-Venn, Cynthia; Cho, Hong-Jun; Won, Samuel J.; Dejene, Eden; Yao, Zhengsheng; Paik, Chang H.; Bluemke, David A.] NIH, Radiopharmaceut Lab, Dept Radiol & Imaging Sci, Ctr Clin,Nucl Med Div, Bldg 10, Bethesda, MD 20892 USA.
[Kim, Insook] Frederick Natl Lab, Leidos Biomed Res Inc, Appl & Dev Res Directorate, Frederick, MD USA.
[Kim, Jin Su] Korea Inst Radiol & Med Sci, Mol Imaging Res Ctr, Seoul, South Korea.
RP Paik, CH (reprint author), NIH, Radiopharmaceut Lab, Dept Radiol & Imaging Sci, Ctr Clin,Nucl Med Div, Bldg 10, Bethesda, MD 20892 USA.
EM cpaik@mail.nih.gov
FU Intramural Research Program of Clinical Center, NIH; NCI
[HHSN261200800001E]
FX This research was supported by the Intramural Research Program of
Clinical Center, NIH and NCI contract no. HHSN261200800001E.
NR 26
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U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD DEC
PY 2016
VL 37
IS 12
BP 1306
EP 1317
DI 10.1097/MNM.0000000000000590
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EC0RS
UT WOS:000387809000014
PM 27623511
ER
PT J
AU Li, WY
Dorans, KS
Wilker, EH
Rice, MB
Schwartz, J
Coull, BA
Koutrakis, P
Gold, DR
Fox, CS
Mittleman, MA
AF Li, Wenyuan
Dorans, Kirsten S.
Wilker, Elissa H.
Rice, Mary B.
Schwartz, Joel
Coull, Brent A.
Koutrakis, Petros
Gold, Diane R.
Fox, Caroline S.
Mittleman, Murray A.
TI Residential Proximity to Major Roadways, Fine Particulate Matter, and
Adiposity: The Framingham Heart Study
SO Obesity
LA English
DT Article
ID AEROSOL OPTICAL DEPTH; LONG-TERM EXPOSURE; BODY-MASS INDEX;
AIR-POLLUTION; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; PM2.5
CONCENTRATIONS; LONGITUDINAL COHORT; TISSUE COMPARTMENTS; OXIDATIVE
STRESS
AB Objective: Higher traffic-related air pollution has been associated with higher body mass index (BMI) among children. However, few studies have assessed the associations among adults.
Methods: Participants (N = 2,372) from the Framingham Offspring and Third Generation cohorts who underwent multidetector-computed tomography scans (2002-2005) were included. Residential-based proximity to the nearest major roadway and 1-year average levels of fine particulate matter (PM2.5) air pollution were estimated. BMI was measured at Offspring examination 7 (1998-2001) and Third Generation examination 1 (2002-2005); subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using multidetector-computed tomography. Linear regression models were used for continuous BMI, SAT, and VAT and logistic models for the binary indicator of obesity (BMI >= 30 kg/m(2)), adjusting for demographic variables, individual- and area-level measures of socioeconomic position, and clinical and lifestyle factors.
Results: Participants who lived 60 m from a major roadway had 0.37 kg/m(2) higher BMI (95% CI: 0.10 to 0.65 kg/m(2)), 78.4 cm(3) higher SAT (95% CI: 4.5 to 152.3 cm(3)), and 41.8 cm(3) higher VAT (95% CI: -4.7 to 88.2 cm(3)) than those who lived 440 m away.
Conclusions: Living closer to a major roadway was associated with higher overall and abdominal adiposity.
C1 [Li, Wenyuan; Dorans, Kirsten S.; Wilker, Elissa H.; Schwartz, Joel; Mittleman, Murray A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Li, Wenyuan; Dorans, Kirsten S.; Wilker, Elissa H.; Rice, Mary B.; Mittleman, Murray A.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Cardiol, Cardiovasc Epidemiol Res Unit, Boston, MA 02115 USA.
[Rice, Mary B.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA USA.
[Schwartz, Joel; Koutrakis, Petros; Gold, Diane R.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Gold, Diane R.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Gold, Diane R.] Harvard Med Sch, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
RP Mittleman, MA (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.; Mittleman, MA (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Cardiol, Cardiovasc Epidemiol Res Unit, Boston, MA 02115 USA.
EM mmittlem@hsph.harvard.edu
OI Li, Wenyuan/0000-0001-6196-9964
FU USEPA [RD-83479801]; National Heart, Lung, and Blood Institute of the
National Institutes of Health [HHSN268201500001I, N01-HC-25195,
T32HL007575]; National Institutes of Environmental Health Sciences [P01
ES09825, K23ES026204, P30ES000002]
FX This publication was made possible by USEPA grant RD-83479801. Further,
USEPA does not endorse the purchase of any commercial products or
services mentioned in the publication. The views expressed in this
manuscript are those of the authors and do not necessarily represent the
views of the National Heart, Lung, and Blood Institute; the National
Institutes of Health; or the U.S. Department of Health and Human
Services. This work was further supported by the National Heart, Lung,
and Blood Institute of the National Institutes of Health contracts and
grants HHSN268201500001I, N01-HC-25195, and T32HL007575 and National
Institutes of Environmental Health Sciences grants P01 ES09825,
K23ES026204, and P30ES000002.
NR 37
TC 2
Z9 2
U1 7
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD DEC
PY 2016
VL 24
IS 12
BP 2593
EP 2599
DI 10.1002/oby.21630
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA ED8VH
UT WOS:000389148500023
PM 27804220
ER
PT J
AU Mendoza-Villanueva, D
Balamurugan, K
Ali, HR
Kim, SR
Sharan, S
Johnson, RC
Merchant, AS
Caldas, C
Landberg, G
Sterneck, E
AF Mendoza-Villanueva, D.
Balamurugan, K.
Ali, H. R.
Kim, S-R
Sharan, S.
Johnson, R. C.
Merchant, A. S.
Caldas, C.
Landberg, G.
Sterneck, E.
TI The C/EBP delta protein is stabilized by estrogen receptor alpha
activity, inhibits SNAI2 expression and associates with good prognosis
in breast cancer
SO ONCOGENE
LA English
DT Article
ID CCAAT/ENHANCER-BINDING PROTEINS; MAMMARY-GLAND INVOLUTION;
GENE-EXPRESSION; TUMOR PROGRESSION; CELL-STATE; CYCLIN D1; SLUG;
PATHWAY; BETA; IDENTIFICATION
AB Hypoxia and inflammatory cytokines like interleukin-6 (IL-6, IL6) are strongly linked to cancer progression, and signal in part through the transcription factor Ccaat/enhancer-binding protein d (C/EBPd, CEBPD), which has been shown to promote mesenchymal features and malignant progression of glioblastoma. Here we report a different role for C/EBPd in breast cancer. We found that the C/EBPd protein is expressed in normal breast epithelial cells and in low-grade cancers. C/EBPd protein (but not mRNA) expression correlates with estrogen receptor (ER+) and progesterone receptor (PGR) expression and longer progression-free survival of breast cancer patients. Specifically in ER+ breast cancers, CEBPD-but not the related CEBPB-mRNA in combination with IL6 correlated with lower risk of progression. Functional studies in cell lines showed that ERa promotes C/EBPd expression at the level of protein stability by inhibition of the FBXW7 pathway. Furthermore, we found that C/EBPd attenuates cell growth, motility and invasiveness by inhibiting expression of the SNAI2 (Slug) transcriptional repressor, which leads to expression of the cyclin-dependent kinase inhibitor CDKN1A (p21(CIP1/WAF1)). These findings identify a molecular mechanism by which ERa signaling reduces the aggressiveness of cancer cells, and demonstrate that C/EBPd can have different functions in different types of cancer. Furthermore, our results support a potentially beneficial role for the IL-6 pathway specifically in ER+ breast cancer and call for further evaluation of the role of intra-tumoral IL-6 expression and of which cancers might benefit from current attempts to target the IL-6 pathway as a therapeutic strategy.
C1 [Mendoza-Villanueva, D.; Balamurugan, K.; Kim, S-R; Sharan, S.; Sterneck, E.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
[Ali, H. R.; Caldas, C.] Univ Cambridge, Cambridge Inst, Dept Oncol, Canc Res UK,Li Ka Shing Ctr, Cambridge, England.
[Johnson, R. C.; Merchant, A. S.] Frederick Natl Lab, CCR Collaborat Bioinformat Resource, Adv Biomed Comp Ctr, Leidos Biomed, Frederick, MD USA.
[Landberg, G.] Univ Manchester, Breakthrough Breast Canc Unit, Inst Canc Sci, Paterson Inst Canc Res, Manchester, Lancs, England.
[Kim, S-R] US FDA, Div Biotechnol Review & Res 4, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Landberg, G.] Gothenburg Univ, Dept Pathol, Sahlgrenska Canc Ctr, Medicinaregatan 1F, S-40530 Gothenburg, Sweden.
RP Sterneck, E (reprint author), NCI, Lab Cell & Dev Signaling, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
EM sternecg@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute;
Frederick National Laboratory (NIH) [HHSN261200800001E]; National
Council on Science and Technology (CONACYT), Mexico
FX We are thankful to the Laboratory Animal Sciences Program (Leidos
Biomedical Research, Inc., Frederick National Laboratory for Cancer
Research) for excellent support, especially Donna Butcher and Glenn
Summers for superb services, and Bao Tran and Jyoti Shetty (Leidos
Biomedical Research, Inc.) for mRNA-Seq data. We also thank Elise
Nilsson for excellent technical assistance. We thank student interns
Katherine L Zhou and Yasmin Y Lachir for their valuable contributions,
Linda Miller for preparation of plasmids, and Allen Kane and Joseph
Meyer (Leidos Biomedical Research, Inc.) for preparing the figures for
publication. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute and in part with Federal
Funds from the Frederick National Laboratory (NIH) under contract no.
HHSN261200800001E. DM-V was supported in part by a scholarship from the
National Council on Science and Technology (CONACYT), Mexico. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products or organizations imply
endorsement by the US Government.
NR 58
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD DEC 1
PY 2016
VL 35
IS 48
BP 6166
EP 6176
DI 10.1038/onc.2016.156
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA ED4YH
UT WOS:000388857700002
PM 27181204
ER
PT J
AU Venturutti, L
Russo, RIC
Rivas, MA
Mercogliano, MF
Izzo, F
Oakley, RH
Pereyra, MG
De Martino, M
Proietti, CJ
Yankilevich, P
Roa, JC
Guzman, P
Cortese, E
Allemand, DH
Huang, TH
Charreau, EH
Cidlowski, JA
Schillaci, R
Elizalde, PV
AF Venturutti, L.
Russo, R. I. Cordo
Rivas, M. A.
Mercogliano, M. F.
Izzo, F.
Oakley, R. H.
Pereyra, M. G.
De Martino, M.
Proietti, C. J.
Yankilevich, P.
Roa, J. C.
Guzman, P.
Cortese, E.
Allemand, D. H.
Huang, T. H.
Charreau, E. H.
Cidlowski, J. A.
Schillaci, R.
Elizalde, P. V.
TI MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive
breast and gastric cancer via its novel targets CCNJ and FUBP1
SO ONCOGENE
LA English
DT Article
ID ELEMENT-BINDING PROTEIN-1; GROWTH-HORMONE RECEPTOR; NF-KAPPA-B;
CELL-PROLIFERATION; TYROSINE KINASE; UP-REGULATION; EXPRESSION;
RESISTANCE; MYC; MICRORNA
AB ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ-and lapatinib-resistant ErbB-2-positive BC and GC.
C1 [Venturutti, L.; Russo, R. I. Cordo; Mercogliano, M. F.; Izzo, F.; Pereyra, M. G.; De Martino, M.; Proietti, C. J.; Charreau, E. H.; Schillaci, R.; Elizalde, P. V.] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Lab Mol Mech Carcinogenesis, Buenos Aires, DF, Argentina.
[Rivas, M. A.] Weill Cornell Med, Dept Med, New York, NY USA.
[Oakley, R. H.; Cidlowski, J. A.] NIEHS, US Dept HHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Pereyra, M. G.] Hosp Gen Agudos Juan A Fernandez, Serv Anat Patol, Buenos Aires, DF, Argentina.
[Yankilevich, P.] Max Planck Gesell, Inst Invest Biomed Buenos Aires, CONICET, Partner Inst, Buenos Aires, DF, Argentina.
[Roa, J. C.; Guzman, P.] Univ La Frontera, Dept Anat Patol BIOREN, Temuco, Chile.
[Roa, J. C.] Pontificia Univ Catolica Chile, Escuela Med, Dept Anat Patol, Santiago, Chile.
[Roa, J. C.] Pontificia Univ Catolica Chile, Adv Ctr Chron Dis ACCDIS, Santiago, Chile.
[Cortese, E.] Hosp Aeronaut Cent, Serv Ginecol, Buenos Aires, DF, Argentina.
[Allemand, D. H.] Hosp Gen Agudos Juan A Fernandez, Unidad Patol Mamaria, Buenos Aires, DF, Argentina.
[Huang, T. H.] Univ Texas San Antonio, Dept Mol Med, Inst Biotechnol Canc Therapy & Res Expt IBYME, San Antonio, TX USA.
RP Elizalde, PV (reprint author), Consejo Nacl Invest Cient & Tecn, Lab Mol Mech Carcinogenesis, Inst Biol & Med Expt IBYME, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina.
EM patriciaelizalde@ibyme.conicet.gov.ar
FU Susan G Komen for the Cure [KG090250]; National Institute of Cancer
(INC, Argentina); National Agency of Scientific Promotion of Argentina
(ANPCyT) [IDB/PICT 2012-668, PID 2012-066]; ANPCyT [IDB/PICT 2012-382,
IDB/PICT 2008-189, 2012-1017]; Henry Moore Institute of Argentina
[Oncomed-Reno CONICET 1819/03]; CONICET [PIP 59]
FX We thank AA Molinolo (UCSD, San Diego, CA, USA) for his constant help.
This work was supported by KG090250 investigator-initiated research
grant from Susan G Komen for the Cure, Financial Assistance for National
Research Projects from the National Institute of Cancer (INC,
Argentina), IDB/PICT 2012-668 and PID 2012-066 from National Agency of
Scientific Promotion of Argentina (ANPCyT), awarded to PVE; IDB/PICT
2012-382 from ANPCyT, awarded to RS; Oncomed-Reno CONICET 1819/03, from
Henry Moore Institute of Argentina, awarded to PVE and RS; IDB/PICT
2008-189 and 2012-1017 from ANPCyT, PIP 59 from CONICET, awarded to CJP.
NR 76
TC 2
Z9 2
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD DEC 1
PY 2016
VL 35
IS 48
BP 6189
EP 6202
DI 10.1038/onc.2016.151
PG 14
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA ED4YH
UT WOS:000388857700004
PM 27157613
ER
PT J
AU Tang, W
Wang, H
Ha, HL
Tassi, I
Bhardwaj, R
Claudio, E
Siebenlist, U
AF Tang, W.
Wang, H.
Ha, H. L.
Tassi, I.
Bhardwaj, R.
Claudio, E.
Siebenlist, U.
TI The B-cell tumor promoter Bcl-3 suppresses inflammation associated colon
tumorigenesis in epithelial cells
SO ONCOGENE
LA English
DT Article
ID NF-KAPPA-B; COLITIS-ASSOCIATED TUMORIGENESIS; GERMINAL CENTER REACTIONS;
NECROSIS-FACTOR-ALPHA; SPLENIC MICROARCHITECTURE; COLORECTAL-CANCER;
MICE DEFICIENT; CARCINOGENESIS; ONCOPROTEIN; ACTIVATION
AB Bcl-3 is an atypical member of the inhibitor of kappa light polypeptide gene enhancer in B-cells (I.B) family. It associates with p50/nuclear factor-kappa B1 (NF-kappa B1) and p52/NF-kappa B2 homodimers in nuclei where it modulates transcription in a context-dependent manner. A subset of B-cell tumors exhibits recurrent translocations of Bcl-3, resulting in overexpression. Elevated expression without translocations is also observed in various B-cell lymphomas and even some solid tumors. Here we investigated the role of Bcl-3 in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors, a mouse model for colitis-associated colorectal cancers in humans. Contrary to expectations, Bcl-3 suppressed colorectal tumor formation: Bcl-3-deficient mice were relatively protected from DSS-induced epithelial damage and developed more polyps after AOM/DSS treatment, although polyp size was unaffected. DSSchallenged mutant mice exhibited increased recruitment of myeloid-derived suppressor cells, consistent with protection of the epithelium. Loss of Bcl-3 in intestinal epithelial cells was sufficient to increase tumorigenesis. The added tumor burden in mutant mice was dependent on tumor necrosis factor-a (TNF alpha), a tumorigenic, NF-kappa B-mediated signaling pathway that was dampened by Bcl-3. These findings reveal a tumor-suppressive role for Bcl-3 in this inflammation-associated cancer model. Bcl-3 thus functions as a tumor promoter or suppressor, depending on the cellular and environmental context.
C1 [Tang, W.; Wang, H.; Ha, H. L.; Tassi, I.; Bhardwaj, R.; Claudio, E.; Siebenlist, U.] NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Siebenlist, U (reprint author), NIH, Bldg 10,Room 11N210, Bethesda, MD 20892 USA.
EM usiebenlist@niaid.nih.gov
FU Intramural Research Program of NIAID, NIH
FX We greatly appreciate the constructive inputs provided by all members of
the Siebenlist laboratory. This research was supported by the Intramural
Research Program of NIAID, NIH.
NR 34
TC 0
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U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD DEC 1
PY 2016
VL 35
IS 48
BP 6203
EP 6211
DI 10.1038/onc.2016.152
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA ED4YH
UT WOS:000388857700005
PM 27132515
ER
PT J
AU Li, Y
Bouchlaka, MN
Wolff, J
Grindle, KM
Lu, L
Qian, S
Zhong, X
Pflum, N
Jobin, P
Kahl, BS
Eickhoff, JC
Wuerzberger-Davis, SM
Miyamoto, S
Thomas, CJ
Yang, DT
Capitini, CM
Rui, L
AF Li, Y.
Bouchlaka, M. N.
Wolff, J.
Grindle, K. M.
Lu, L.
Qian, S.
Zhong, X.
Pflum, N.
Jobin, P.
Kahl, B. S.
Eickhoff, J. C.
Wuerzberger-Davis, S. M.
Miyamoto, S.
Thomas, C. J.
Yang, D. T.
Capitini, C. M.
Rui, L.
TI FBXO10 deficiency and BTK activation upregulate BCL2 expression in
mantle cell lymphoma
SO ONCOGENE
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BRUTONS TYROSINE KINASE; FACTOR-KAPPA-B;
FOLLICULAR LYMPHOMA; RECEPTOR; IBRUTINIB; THERAPY; APOPTOSIS; SURVIVAL;
MALIGNANCIES
AB Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathways is critical to enhance the efficacy of ibrutinib. Here, we focus on the BCL2 anti-apoptotic pathway. In a tissue microarray of 62 MCL samples, BCL2 expression positively correlated with BTK expression. Increased levels of BCL2 were shown to be due to a defect in protein degradation because of no or little expression of the E3 ubiquitin ligase FBXO10, as well as transcriptional upregulation through BTK-mediated canonical nuclear factor-kappa B activation. RNA-seq analysis confirmed that a set of anti-apoptotic genes (for example, BCL2, BCL-XL and DAD1) was downregulated by BTK short hairpin RNA. The downregulated genes also included those that are critical for B-cell growth and proliferation, such as BCL6, MYC, PIK3CA and BAFF-R. Targeting BCL2 by the specific inhibitor ABT-199 synergized with ibrutinib in inhibiting growth of both ibrutinib-sensitive and -resistant cancer cells in vitro and in vivo. These results suggest co-targeting of BTK and BCL2 as a new therapeutic strategy in MCL, especially for patients with primary resistance to ibrutinib.
C1 [Li, Y.; Wolff, J.; Grindle, K. M.; Pflum, N.; Jobin, P.; Kahl, B. S.; Rui, L.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Li, Y.; Bouchlaka, M. N.; Grindle, K. M.; Kahl, B. S.; Wuerzberger-Davis, S. M.; Miyamoto, S.; Yang, D. T.; Capitini, C. M.; Rui, L.] Univ Wisconsin, Carbone Canc Ctr, Sch Med & Publ Hlth, Madison, WI USA.
[Bouchlaka, M. N.; Capitini, C. M.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA.
[Lu, L.; Qian, S.; Zhong, X.] Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI USA.
[Lu, L.; Qian, S.; Zhong, X.] Univ Wisconsin, Genet Lab, Madison, WI USA.
[Eickhoff, J. C.] Univ Wisconsin, Dept Biostat & Med Informat, Sch Med & Publ Hlth, Madison, WI USA.
[Wuerzberger-Davis, S. M.; Miyamoto, S.] Univ Wisconsin, Dept Oncol, Sch Med & Publ Hlth, Madison, WI USA.
[Thomas, C. J.] NIH, Div Preclin Innovat, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Yang, D. T.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA.
[Kahl, B. S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
RP Yang, DT; Capitini, CM; Rui, L (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Div Hematol Oncol, Dept Med, 1111 Highland Ave, Madison, WI 53705 USA.
EM dtyang@wisc.edu; ccapitini@pediatrics.wisc.edu; lrui@medicine.wisc.edu
FU UW-Madison Start-up funds; KL2 Scholar Award [UL1TR0000427,
KL2TR000428]; NIH [R01 CA187299]; MACC fund; National Institutes of
Health/National Cancer Institute [K08 CA174750]; USDA National Institute
of Food and Agriculture [Hatch 1002874]; UW Forward Lymphoma Fund;
University of Wisconsin Carbone Cancer Center (UWCCC); NIH/NCI UW
Comprehensive Cancer Center Support [P30 CA014520]
FX We thank Dr Louis Staudt for providing the reagents, Dr Sameer Mathur
for providing peripheral blood mononuclear cells, Dr Wei Huang for
helping with analysis of immunohistochemical data, Drs Debra Bloom and
Peiman Hematti for providing CD40, BAFF and BAFF receptor antibody, and
Kirsti Walker for monitoring xenografted mice. This work was supported
by the UW-Madison Start-up funds, KL2 Scholar Award (UL1TR0000427 and
KL2TR000428), and NIH R01 CA187299 to LR, the MACC fund and the National
Institutes of Health/National Cancer Institute (K08 CA174750) to CMC,
the UW-Madison Start-up funds and USDA National Institute of Food and
Agriculture (Hatch 1002874) to XZ, and the UW Forward Lymphoma Fund. We
thank the University of Wisconsin Carbone Cancer Center (UWCCC) for the
funds to complete this project. This work was also supported in part by
NIH/NCI P30 CA014520- UW Comprehensive Cancer Center Support.
NR 55
TC 0
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U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD DEC 1
PY 2016
VL 35
IS 48
BP 6223
EP 6234
DI 10.1038/onc.2016.155
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA ED4YH
UT WOS:000388857700007
PM 27157620
ER
PT J
AU Marques, EA
Gudnason, V
Lang, T
Sigurdsson, G
Sigurdsson, S
Aspelund, T
Siggeirsdottir, K
Launer, L
Eiriksdottir, G
Harris, TB
AF Marques, E. A.
Gudnason, V.
Lang, T.
Sigurdsson, G.
Sigurdsson, S.
Aspelund, T.
Siggeirsdottir, K.
Launer, L.
Eiriksdottir, G.
Harris, T. B.
TI Association of bone turnover markers with volumetric bone loss,
periosteal apposition, and fracture risk in older men and women: the
AGES-Reykjavik longitudinal study
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Aging; Bone turnover; Endosteal bone loss; Fracture risk; Periosteal
apposition; QCT
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; BIOCHEMICAL MARKERS;
FEMORAL-NECK; TRABECULAR BONE; ELDERLY-WOMEN; OSTEOPOROSIS; PREDICTION;
RESORPTION; SURFACE; METABOLISM
AB Association between serum bone formation and resorption markers and cortical and trabecular bone loss and the concurrent periosteal apposition in a population-based cohort of 1069 older adults was assessed. BTM levels moderately reflect the cellular events at the endosteal and periosteal surfaces but are not associated with fracture risk.
We assessed whether circulating bone formation and resorption markers (BTM) were individual predictors for trabecular and cortical bone loss, periosteal expansion, and fracture risk in older adults aged 66 to 93 years from the AGES-Reykjavik study.
The sample for the quantitative computed tomography (QCT)-derived cortical and trabecular BMD and periosteal expansion analysis consisted of 1069 participants (474 men and 595 women) who had complete baseline (2002 to 2006) and follow-up (2007 to 2011) hip QCT scans and serum baseline BTM. During the median follow-up of 11.7 years (range 5.4-12.5), 54 (11.4 %) men and 182 (30.6 %) women sustained at least one fracture of any type.
Increase in BTM levels was associated with faster cortical and trabecular bone loss at the femoral neck and proximal femur in men and women. Higher BTM levels were positively related with periosteal expansion rate at the femoral neck in men. Markers were not associated with fracture risk.
This data corroborates the notion from few previous studies that both envelopes are metabolically active and that BTM levels may moderately reflect the cellular events at the endosteal and periosteal surfaces. However, our results do not support the routine use of BTM to assess fracture risk in older men and women. In light of these findings, further studies are justified to examine whether systemic markers of bone turnover might prove useful in monitoring skeletal remodeling events and the effects of current osteoporosis drugs at the periosteum.
C1 [Marques, E. A.; Launer, L.; Harris, T. B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Gudnason, V.; Sigurdsson, G.; Sigurdsson, S.; Aspelund, T.; Siggeirsdottir, K.; Eiriksdottir, G.] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Gudnason, V.; Sigurdsson, G.] Univ Iceland, Reykjavik, Iceland.
[Lang, T.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Sigurdsson, G.] Landspitalinn Univ Hosp, Reykjavik, Iceland.
[Aspelund, T.] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland.
RP Marques, EA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM elisa.marques@nih.gov
FU National Institutes of Health [N01-AG-012100]; National Institute on
Aging Intramural Research Program, Hjartavernd (Icelandic Heart
Association); Althingi (Icelandic Parliament)
FX This study was funded by the National Institutes of Health contract
N01-AG-012100, the National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). EAM and TBH were supported in part by and
the Intramural Research Program of the National Institutes of Health,
National Institute on Aging.
NR 38
TC 0
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U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD DEC
PY 2016
VL 27
IS 12
BP 3485
EP 3494
DI 10.1007/s00198-016-3675-7
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA ED6GI
UT WOS:000388953700009
PM 27341810
ER
PT J
AU Ovejero, D
Lim, YH
Boyce, AM
Gafni, RI
McCarthy, E
Nguyen, TA
Eichenfield, LF
DeKlotz, CMC
Guthrie, LC
Tosi, LL
Thornton, PS
Choate, KA
Collins, MT
AF Ovejero, D.
Lim, Y. H.
Boyce, A. M.
Gafni, R. I.
McCarthy, E.
Nguyen, T. A.
Eichenfield, L. F.
DeKlotz, C. M. C.
Guthrie, L. C.
Tosi, L. L.
Thornton, P. S.
Choate, K. A.
Collins, M. T.
TI Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural
history, and treatment
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Epidermal nevus syndrome; FGF23; Hypophosphatemic rickets; RASopathies;
Skeletal dysplasia
ID EPIDERMAL NEVUS-SYNDROME; D-RESISTANT RICKETS; CONGENITAL MELANOCYTIC
NEVI; POLYOSTOTIC FIBROUS DYSPLASIA; FIBROBLAST GROWTH FACTOR-23;
TUMOR-INDUCED OSTEOMALACIA; CENTRAL PRECOCIOUS PUBERTY; POSTZYGOTIC HRAS
MUTATION; FEUERSTEIN-MIMS-SYNDROME; PHAKOMATOSIS PIGMENTOKERATOTICA
AB Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found.
CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic RAS mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia.
Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed.
Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported.
An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.
C1 [Ovejero, D.; Boyce, A. M.; Gafni, R. I.; Guthrie, L. C.; Collins, M. T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr,Room 228,MSC 4320, Bethesda, MD 20892 USA.
[Ovejero, D.] Univ Autonoma Barcelona, Dept Med, Barcelona, Spain.
[Lim, Y. H.; Choate, K. A.] Yale Univ, Dept Dermatol, Sch Med, New Haven, CT USA.
[McCarthy, E.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Nguyen, T. A.] Albert Einstein Coll Med, Bronx, NY USA.
[Nguyen, T. A.; Eichenfield, L. F.] Univ Calif San Diego, Dept Dermatol & Pediat, San Diego & Rady Childrens Hosp, San Diego, CA USA.
[DeKlotz, C. M. C.] Georgetown Univ, Div Dermatol, Dept Med, Med Ctr, Washington, DC USA.
[DeKlotz, C. M. C.] Georgetown Univ, Dept Pediat, Med Ctr, Washington, DC USA.
[Tosi, L. L.] Childrens Natl Hlth Syst, Bone Hlth Program, Div Orthopaed & Sports Med, Washington, DC USA.
[Thornton, P. S.] Cook Children Med Ctr, Dept Endocrinol & Diabet, Ft Worth, TX USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr,Room 228,MSC 4320, Bethesda, MD 20892 USA.
EM mc247k@nih.gov
OI DeKlotz, Cynthia/0000-0002-6410-8710
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, National Institutes of Health; Department of
Health and Human Services, Bethesda, MD; Doris Duke Charitable
Foundation Clinical Scientist Development Award; Doris Duke Charitable
Foundation; Yale Center for Mendelian Genomics (NIH) [U54 HG006504];
Medical Scientist Training Program at Yale University
FX This study was supported in part by the Division of Intramural Research,
National Institute of Dental and Craniofacial Research, National
Institutes of Health, and Department of Health and Human Services,
Bethesda, MD (D.O., A.M.B., R.I.G., L.G.C., and M.T.C.). K.A.C. was
supported by a Doris Duke Charitable Foundation Clinical Scientist
Development Award, and Y.H.L. by a Doris Duke Charitable Foundation
Medical Student Research Fellowship and the Yale Center for Mendelian
Genomics (NIH U54 HG006504). YHL is also supported by the Medical
Scientist Training Program at Yale University.
NR 65
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD DEC
PY 2016
VL 27
IS 12
BP 3615
EP 3626
DI 10.1007/s00198-016-3702-8
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA ED6GI
UT WOS:000388953700023
PM 27497815
ER
PT J
AU Kaplan, SL
Edgar, JC
Ford, EG
Adgent, MA
Schall, JI
Kelly, A
Umbach, DM
Rogan, WJ
Stallings, VA
Darge, K
AF Kaplan, Summer L.
Edgar, J. Christopher
Ford, Eileen G.
Adgent, Margaret A.
Schall, Joan I.
Kelly, Andrea
Umbach, David M.
Rogan, Walter J.
Stallings, Virginia A.
Darge, Kassa
TI Size of testes, ovaries, uterus and breast buds by ultrasound in healthy
full-term neonates ages 0-3 days
SO PEDIATRIC RADIOLOGY
LA English
DT Article
DE Breast; Measurements; Neonate; Ovary; Testis; Uterus; Ultrasound
ID TESTICULAR VOLUME; GIRLS; UTERINE; NEWBORN; BIRTH; BOYS; INFANTS;
PUBERTY
AB Hormonally sensitive organs in the neonate can change size within days of birth as circulating maternal estrogen wanes. Although several reports document the size of these organs through infancy, few focus attention on the near-birth period. Clinical and research evaluation of hormonal and genitourinary disorders would benefit from reference size standards.
We describe the size of the uterus, ovaries, testes and breast buds in healthy term neonates.
As part of the Infant Feeding and Early Development (IFED) study, we sonographically measured the largest diameter of these organs in sagittal, transverse and anterior-posterior planes for 194 female and 204 male newborns up to 3 days old. We calculated mean, median and percentiles for longest axis length and for volume calculated from measured diameters. We evaluated size differences by laterality, gender and race and compared our observations against published values.
Mean length and mean volume were as follows: uterus, 4.2 cm and 10.0 cm(3); ovary, 1.0 cm and 0.2 cm(3); testis, 1.1 cm and 0.3 cm(3) (0.4 cm(3) Lambert volume); female breast bud, 1.2 cm and 0.7 cm(3); male breast bud, 1.1 cm and 0.6 cm(3). Breast buds were larger in females than males. Laterality differences were typically below the precision of clinical measurement. No significant race differences were detected.
Using data from our large cohort together with published values, we provide guidelines for evaluating the size of reproductive organs within the first 3 days of age. Discrepancies between our results and published values are likely attributable to technique.
C1 [Kaplan, Summer L.; Edgar, J. Christopher; Darge, Kassa] Childrens Hosp Philadelphia, Dept Radiol, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
[Edgar, J. Christopher; Kelly, Andrea; Stallings, Virginia A.; Darge, Kassa] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ford, Eileen G.; Schall, Joan I.; Stallings, Virginia A.] Childrens Hosp Philadelphia, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA.
[Adgent, Margaret A.; Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Kelly, Andrea] Childrens Hosp Philadelphia, Dept Pediat, Div Endocrinol, Philadelphia, PA 19104 USA.
[Umbach, David M.] NIEHS, Biostat & Computat Biol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kaplan, SL (reprint author), Childrens Hosp Philadelphia, Dept Radiol, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM kaplans2@email.chop.edu
RI Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
NR 24
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
EI 1432-1998
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD DEC
PY 2016
VL 46
IS 13
BP 1837
EP 1847
DI 10.1007/s00247-016-3681-0
PG 11
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA ED3IO
UT WOS:000388743000010
PM 27580909
ER
PT J
AU Sesma, JI
Weitzer, CD
Livraghi-Butrico, A
Dang, H
Donaldson, S
Alexis, NE
Jacobson, KA
Harden, TK
Lazarowski, ER
AF Sesma, Juliana I.
Weitzer, Clarissa D.
Livraghi-Butrico, Alessandra
Dang, Hong
Donaldson, Scott
Alexis, Neil E.
Jacobson, Kenneth A.
Harden, T. Kendall
Lazarowski, Eduardo R.
TI UDP-glucose promotes neutrophil recruitment in the lung
SO Purinergic Signalling
LA English
DT Article
DE UDP-glucose; P2Y(14) receptor; Purinergic receptors; Neutrophils; Lung
inflammation
ID PROTEIN-COUPLED RECEPTOR; CHANNEL-OVEREXPRESSING MICE; HUMAN AIRWAY
EPITHELIA; P2Y(14) RECEPTOR; CYSTIC-FIBROSIS; NUCLEOSIDE
DIPHOSPHOKINASE; SIGNALING MOLECULES; INTERNATIONAL UNION; SURFACE
DEHYDRATION; ADENOSINE RECEPTORS
AB In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y(14) receptors (P2Y(14)R). However, the physiological/pathophysiological consequences of UDP-sugar release are incompletely defined. Here, we report that UDP-glucose levels are abnormally elevated in lung secretions from patients with cystic fibrosis (CF) as well as in a mouse model of CF-like disease, the beta ENaC transgenic (Tg) mouse. Instillation of UDP-glucose into wild-type mouse tracheas resulted in enhanced neutrophil lung recruitment, and this effect was nearly abolished when UDP-glucose was co-instilled with the P2Y(14)R antagonist PPTN [4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl-2-naphthoic acid]. Importantly, administration of PPTN to beta ENaC-Tg mice reduced neutrophil lung inflammation. These results suggest that UDP-glucose released into the airways acts as a local mediator of neutrophil inflammation.
C1 [Sesma, Juliana I.; Livraghi-Butrico, Alessandra; Dang, Hong; Donaldson, Scott; Lazarowski, Eduardo R.] Univ N Carolina, Sch Med, Marsico Lung Inst, Cyst Fibrosis Res Ctr, 6007 Thurston Bowles Bldg,CB 7248, Chapel Hill, NC 27599 USA.
[Weitzer, Clarissa D.; Harden, T. Kendall] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC USA.
[Alexis, Neil E.] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Sch Med, Chapel Hill, NC USA.
[Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Lazarowski, ER (reprint author), Univ N Carolina, Sch Med, Marsico Lung Inst, Cyst Fibrosis Res Ctr, 6007 Thurston Bowles Bldg,CB 7248, Chapel Hill, NC 27599 USA.
EM eduardo_lazarowski@med.unc.edu
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health (NIH) National Institute of General
Medical Sciences [R01-GM38213]; NIH National Heart, Lung, and Blood
Institute [P01-HL110873]; National Institute of Diabetes and Digestive
and Kidney Diseases Intramural Research Program; NIH Specialized Centers
of Clinically Orientated Research [P50-HL084934]; US EPA cooperative
agreement [CR 833463015-35475, NHLBI-RO1 HL080337]; American Cystic
Fibrosis Foundation [SESMA1510]; North Carolina Translational & Clinical
Science [NCTraCS 550KR101513]; NIH [P30-DK065988]
FX This work was supported by the National Institutes of Health (NIH)
National Institute of General Medical Sciences [R01-GM38213] (TKH), the
NIH National Heart, Lung, and Blood Institute [P01-HL110873] (ERL), the
National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Research Program (KAJ), the NIH Specialized Centers of
Clinically Orientated Research [P50-HL084934] (SD), the US EPA
cooperative agreement CR 833463015-35475 and NHLBI-RO1 HL080337 (NEA),
and the American Cystic Fibrosis Foundation [SESMA1510] and North
Carolina Translational & Clinical Science [NCTraCS 550KR101513] (JIS).
The Histology/Microscopy and Mouse Cores were supported by NIH
P30-DK065988.
NR 54
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD DEC
PY 2016
VL 12
IS 4
BP 627
EP 635
DI 10.1007/s11302-016-9524-5
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA EE1IX
UT WOS:000389335800004
PM 27421735
ER
PT J
AU Schmitz-Valckenberg, S
Sadda, S
Staurenghi, G
Chew, EY
Fleckenstein, M
Holz, FG
AF Schmitz-Valckenberg, Steffen
Sadda, Srinivas
Staurenghi, Giovanni
Chew, Emily Y.
Fleckenstein, Monika
Holz, Frank G.
CA CAM Grp
TI GEOGRAPHIC ATROPHY Semantic Considerations and Literature Review
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Review
DE age-related macular degeneration; geographic atrophy; retinal imaging;
fundus grading; color fundus photography; spectral domain optical
coherence tomography; confocal scanning laser ophthalmoscopy
ID RETINAL-PIGMENT EPITHELIUM; SENILE MACULAR DEGENERATION; AREOLAR
CHOROIDAL DYSTROPHY; FUNDUS AUTOFLUORESCENCE; EYE DISEASE; PROGRESSION;
SECONDARY; MACULOPATHY; PATTERNS; OUTCOMES
AB Purpose: There is a lack of agreement regarding the types of lesions and clinical conditions that should be included in the term "geographic atrophy." Varied and conflicting views prevail throughout the literature and are currently used by retinal experts and other health care professionals.
Methods: We reviewed the nominal definition of the term "geographic atrophy" and conducted a search of the ophthalmologic literature focusing on preceding terminologies and the first citations of the term "geographic atrophy" secondary to age-related macular degeneration.
Results: According to the nominal definition, the term "geography" stands for a detailed description of the surface features of a specific region, indicating its relative position. However, it does not necessarily imply that the borders of the region must be sharply demarcated or related to any anatomical structures. The term "geographical areas of atrophy" was initially cited in the 1960s in the ophthalmologic literature in the context of uveitic eye disease and shortly thereafter also for the description of variants of "senile macular degeneration." However, no direct explanation could be found in the literature as to why the terms "geographical" and "geographic" were chosen. Presumably the terms were used as the atrophic regions resembled the map of a continent or well-defined country borders on thematic geographical maps. With the evolution of the terminology, the commonly used adjunct "of the retinal pigment epithelium" was frequently omitted and solely the term "geographic atrophy" prevailed for the nonexudative late-stage of age-related macular degeneration itself. Along with the quantification of atrophic areas, based on different imaging modalities and the use of both manual and semiautomated approaches, various and inconsistent definitions for the minimal lesion diameter or size of atrophic lesions have also emerged.
Conclusion: Reconsideration of the application of the term "geographic atrophy" in the context of age-related macular degeneration seems to be prudent given ongoing advances in multimodal retinal imaging technology with identification of various phenotypic characteristics, and the observation of atrophy development in eyes under antiangiogenic therapy.
C1 [Schmitz-Valckenberg, Steffen; Fleckenstein, Monika; Holz, Frank G.] Univ Bonn, GRADE Reading Ctr, Dept Ophthalmol, Bonn, Germany.
[Sadda, Srinivas] Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA.
[Staurenghi, Giovanni] Univ Milan, Luigi Sacco Hosp, Eye Clin, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Holz, FG (reprint author), Univ Bonn, Dept Ophthalmol, Ernst Abbe Str 2, D-53127 Bonn, Germany.
EM frank.holz@ukb.uni-bonn.de
FU Intramural NIH HHS [Z99 EY999999]
NR 92
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD DEC
PY 2016
VL 36
IS 12
BP 2250
EP 2264
DI 10.1097/IAE.0000000000001258
PG 15
WC Ophthalmology
SC Ophthalmology
GA ED6DB
UT WOS:000388944100002
PM 27552292
ER
PT J
AU Cukras, C
Flamendorf, J
Wong, WT
Ayyagari, R
Cunningham, D
Sieving, PA
AF Cukras, Catherine
Flamendorf, Jason
Wong, Wai T.
Ayyagari, Radha
Cunningham, Denise
Sieving, Paul A.
TI LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE late-onset retinal degeneration; fundus autofluorescence; optical
coherence tomography; retinal atrophy; reticular pseudodrusen
ID OPTICAL COHERENCE TOMOGRAPHY; RETICULAR MACULAR DISEASE; SUBRETINAL
DRUSENOID DEPOSITS; ANTERIOR LENS ZONULES; AUTOFLUORESCENCE
CHARACTERISTICS; PSEUDOXANTHOMA ELASTICUM; GEOGRAPHIC ATROPHY; S163R
MUTATION; L-ORD; PSEUDODRUSEN
AB Purpose: To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms.
Methods: Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up.
Results: Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy.
Conclusion: Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.
C1 [Cukras, Catherine; Flamendorf, Jason; Wong, Wai T.; Cunningham, Denise; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
[Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA.
RP Cukras, C (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM cukrasc@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute Intramural Research Program; NIH; Pfizer Inc;
Doris Duke Charitable Foundation; Alexandria Real Estate Equities, Inc;
Howard Hughes Medical Institute
FX Supported by the National Eye Institute Intramural Research Program.
Portions of this research were made possible through the National
Institutes of Health (NIH) Medical Research Scholars Program, a
public-private partnership supported jointly by the NIH, and generous
contributions to the Foundation for the NIH from Pfizer Inc, The Doris
Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc and
Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as
well as other private donors.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD DEC
PY 2016
VL 36
IS 12
BP 2348
EP 2356
DI 10.1097/IAE.0000000000001113
PG 9
WC Ophthalmology
SC Ophthalmology
GA ED6DB
UT WOS:000388944100013
PM 27388725
ER
PT J
AU Soucy, K
Fairhurst, RM
Lynn, GM
Fomalont, K
Wynn, TA
Siegel, RM
AF Soucy, Katie
Fairhurst, Rick M.
Lynn, Geoffrey M.
Fomalont, Kevin
Wynn, Thomas A.
Siegel, Richard M.
TI Breaking the Mold: Partnering with the National Institutes of Health
Intramural Research Program to Accelerate PhD Training
SO TRENDS IN IMMUNOLOGY
LA English
DT Letter
ID PLURIPOTENT STEM-CELLS; FIBROSIS
AB Immunology is an increasingly interdisciplinary field. Here we describe a new model for interinstitutional graduate training as partnerships between complementary laboratories. This collaborative model reduces time to graduation without compromising productivity or alumni outcomes. We offer our experience with one such program and thoughts on the ingredients for their success.
Despite tremendous recent advances in technology, communications, and the translation of basic scientific discoveries into new diagnostics and therapies for human diseases, graduate training in immunology and other areas of biomedical research in the_ United States has remained remarkably unchanged since the early 20th century, with coursework and laboratory rotations taking up much of the first 2 years, and a single mentor shepherding the student through a research project over 3 or more subsequent years. The time to graduation still averages more than 6 years in the biomedical sciences field (http://www.nsf.govistatistics/2016/nsf16300/), with uncertain benefit of this extended time to research productivity and career advancement.
C1 [Soucy, Katie; Fairhurst, Rick M.; Lynn, Geoffrey M.; Fomalont, Kevin; Wynn, Thomas A.] Natl Inst Allergy & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Siegel, Richard M.] Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bethesda, MD 20892 USA.
RP Siegel, RM (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bethesda, MD 20892 USA.
EM SiegelR@mail.nih.gov
NR 12
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
EI 1471-4981
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD DEC
PY 2016
VL 37
IS 12
BP 813
EP 815
DI 10.1016/j.it.2016.10.005
PG 3
WC Immunology
SC Immunology
GA EE2ET
UT WOS:000389397200001
PM 27838188
ER
PT J
AU Fessler, MB
AF Fessler, Michael B.
TI The Intracellular Cholesterol Landscape: Dynamic Integrator of the
Immune Response
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID LIPID-METABOLISM; NLRP3 INFLAMMASOME; STEROL-METABOLISM; ADAPTIVE
IMMUNITY; CELL-MIGRATION; LXR-ALPHA; KEY ROLE; T-CELLS;
25-HYDROXYCHOLESTEROL; INTERFERON
AB Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon (IFN) response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, 'professional' role for sterols and oxysterols in macrophage and T-cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease.
C1 [Fessler, Michael B.] Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, MD 27709 USA.
RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, MD 27709 USA.
EM fesslerm@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental Heath
Sciences [Z01 ES102005]
FX The author thanks Paul Windsor for assistance with figure production.
This work was supported by the National Institutes of Health, National
Institute of Environmental Heath Sciences (Z01 ES102005).
NR 76
TC 1
Z9 1
U1 9
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
EI 1471-4981
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD DEC
PY 2016
VL 37
IS 12
BP 819
EP 830
DI 10.1016/j.it.2016.09.001
PG 12
WC Immunology
SC Immunology
GA EE2ET
UT WOS:000389397200003
PM 27692616
ER
PT J
AU Basavalingappa, RH
Massilamany, C
Krishnan, B
Gangaplara, A
Kang, GB
Khanzad-Sharghi, V
Han, ZJ
Othman, S
Li, QS
Riethoven, JJ
Sobel, RA
Steffen, D
Reddy, J
AF Basavalingappa, Rakesh H.
Massilamany, Chandirasegaran
Krishnan, Bharathi
Gangaplara, Arunakumar
Kang, Guobin
Khanzad-Sharghi, Vahid
Han, Zhongji
Othman, Shadi
Li, Qingsheng
Riethoven, Jean-Jack
Sobel, Raymond A.
Steffen, David
Reddy, Jay
TI Identification of an Epitope from Adenine Nucleotide Translocator 1 That
Induces Inflammation in Heart in A/J Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID PRIMARY BILIARY-CIRRHOSIS; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS;
IDIOPATHIC DILATED CARDIOMYOPATHY; CENTRAL-NERVOUS-SYSTEM; T-CELLS;
TRANSGENIC OVEREXPRESSION; EPITHELIAL-CELLS; ADP/ATP CARRIER; DISEASE;
PEPTIDES
AB Heart failure, a leading cause of death in humans, can emanate from myocarditis. Although most individuals with myocarditis recover spontaneously, some develop chronic dilated cardiomyopathy. Myocarditis may result from both infectious and noninfectious causes, including autoimmune responses to cardiac antigens. In support of this notion, intracellular cardiac antigens, like cardiac myosin heavy chain-alpha, cardiac troponin-I, and adenine nucleotide translocator 1 (ANT(1).), have been identified as autoantigens in cardiac autoimmunity. Herein, we demonstrate that ANT(1) can induce autoimmune myocarditis in A/J mice by generating autoreactive T cells. We show that ANTI encompasses multiple immunodominant epitopes (namely, ANT(1) 21-40, ANT(1). 31-50, ANT(1) 171-190, and ANT(1) 181-200). Although all four peptides induce comparable T-cell responses, only ANT(1). 21-40 was found to be a major myocarditogenic epitope in immunized animals. The myocarditis-inducing ability of ANT(1) 21-40 was associated with the generation of T cells producing predominantly IL-17A, and the antigen-sensitized T cells could transfer the disease to naive recipients. These data indicate that cardiac mitochondrial proteins can be target autoantigens in myocarditis, supporting the notion that the antigens released as a result of primary damage may contribute to the persistence of chronic inflammation through auto-immunity.
C1 [Basavalingappa, Rakesh H.; Massilamany, Chandirasegaran; Krishnan, Bharathi; Gangaplara, Arunakumar; Steffen, David; Reddy, Jay] Univ Nebraska, Sch Vet Med & Biomed Sci, Bldg VBS,Room 202, Lincoln, NE 68583 USA.
[Kang, Guobin; Li, Qingsheng] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
[Kang, Guobin; Li, Qingsheng] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
[Khanzad-Sharghi, Vahid; Han, Zhongji; Othman, Shadi] Univ Nebraska, Dept Biol Syst Engn, Lincoln, NE USA.
[Riethoven, Jean-Jack] Univ Nebraska, Ctr Biotechnol, Lincoln, NE USA.
[Sobel, Raymond A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Gangaplara, Arunakumar] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Reddy, J (reprint author), Univ Nebraska, Sch Vet Med & Biomed Sci, Bldg VBS,Room 202, Lincoln, NE 68583 USA.
EM nreddy2@unl.edu
OI Gangaplara, Arunakumar/0000-0001-6307-9391
FU NIH [HL114669]; National Institute of General Medical Science, Nebraska
Center for the Prevention of Obesity Diseases, University of
Nebraska-Lincoln [P20GM104320]
FX Supported by NIH grant HL114669 (J.R.), and the National Institute of
General Medical Science grant P20GM104320, Nebraska Center for the
Prevention of Obesity Diseases, University of Nebraska-Lincoln.
NR 65
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD DEC
PY 2016
VL 186
IS 12
BP 3160
EP 3175
DI 10.1016/j.ajpath.2016.08.005
PG 16
WC Pathology
SC Pathology
GA ED8EC
UT WOS:000389103800009
PM 27876151
ER
PT J
AU Blanco, C
Wall, MM
Okuda, M
Wang, S
Iza, M
Olfson, M
AF Blanco, Carlos
Wall, Melanie M.
Okuda, Mayumi
Wang, Shuai
Iza, Miren
Olfson, Mark
TI Pain as a Predictor of Opioid Use Disorder in a Nationally
Representative Sample
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ALCOHOL-USE DISORDER; INTERVIEW SCHEDULE AUDADIS; DRUG-USE DISORDERS;
GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; QUALITY-OF-LIFE;
UNITED-STATES; EPIDEMIOLOGIC-SURVEY; INDUCED HYPERALGESIA; NONMEDICAL
USE
AB Objective: The authors sought to ascertain the relationship between moderate and more severe pain and prescription opioid use disorders in the noninstitutionalized U.S. population.
Method: A structural equation model was used to assess prospectively the interdependency of pain and prescription opioid use disorder at waves 1(2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Pain was measured with a 5-point scale of pain-related interference in daily activities and dichotomized as "no pain" (no or little interference) or "pain" (moderate to extreme interference). Prescription opioid use disorder was assessed with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version). Other covariates included age, sex, anxiety or mood disorders, and family history of drug, alcohol, and behavioral problems.
Results: In the structural equation model, pain and prescription opioid use disorders were significantly associated with one another at baseline and at 3-year follow-up. However, whereas pain at baseline was also significantly associated with prescription opioid use disorder at follow-up, prescription opioid use disorder at baseline was not associated with pain at follow-up. These associations were independent of several background demographic and clinical characteristics. The path for pain interference was associated with a 41% relative increase in the risk of developing a prescription opioid use disorder.
Conclusions: Painful conditions contribute to the risk of prescription opioid use disorders. To help reduce the incidence of prescription opioid abuse and dependence among adults with moderate to severe pain, careful monitoring and consideration of nonopioid alternative treatments is warranted.
C1 [Olfson, Mark] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA.
Columbia Univ, New York, NY USA.
Fdn Jimenez Diaz, Dept Psychiat, Madrid, Spain.
RP Olfson, M (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
EM mo49@cumc.columbia.edu
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural
Program, NIAAA; NIH [MH076051, MH082773, CA133050]; New York State
Psychiatric Institute
FX The National Epidemiologic Survey on Alcohol and Related Conditions was
sponsored by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and funded in part by the Intramural Program, NIAAA. Work on
this manuscript was supported by NIH grants MH076051, MH082773, and
CA133050 and the New York State Psychiatric Institute (Drs. Blanco,
Olfson, and Wall).
NR 45
TC 3
Z9 3
U1 1
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD DEC
PY 2016
VL 173
IS 12
BP 1189
EP 1195
DI 10.1176/appi.ajp.2016.15091179
PG 7
WC Psychiatry
SC Psychiatry
GA ED7CB
UT WOS:000389012200008
PM 27444794
ER
PT J
AU Kabakus, IM
Borofsky, S
Mertan, FV
Greer, M
Daar, D
Wood, BJ
Pinto, PA
Choyke, PL
Turkbey, B
AF Kabakus, Ismail M.
Borofsky, Samuel
Mertan, Francesca V.
Greer, Matthew
Daar, Dagane
Wood, Bradford J.
Pinto, Peter A.
Choyke, Peter L.
Turkbey, Baris
TI Does Abstinence From Ejaculation Before Prostate MRI Improve Evaluation
of the Seminal Vesicles?
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE ejaculation; MRI; prostate; seminal vesicles
AB OBJECTIVE. The purpose of the present study is to determine whether abstinence from ejaculation before undergoing multiparametric prostate MRI increases seminal vesicle (SV) volume and therefore improves diagnostic interpretation of the SVs.
MATERIALS AND METHODS. This retrospective study included 238 patients who underwent 3-T MRI of the prostate over a 4-month period. Patients were requested to complete a questionnaire that asked how long it had been since their last ejaculation (i.e., < 3 days vs >= 3 days). Forty-two patients (mean patient age, 62.0 years) indicated that it had been less than 3 days since their last ejaculation and were designated as group 1, whereas the remainder indicated an interval of 3 days or more since their last ejaculation. A group of 42 age-matched subjects (mean patient age, 62.1 years) were randomly selected from the remaining 196 patients and were designated as group 2. SV volumes were measured manually. Two radiologists who were blinded to group assignment and patient characteristics scored the right and left SVs separately to determine diagnostic interpretability, which was scored on a 3-point scale as follows: a score of 1 denoted that the SVs were not dilated and the score was nondiagnostic, a score of 2 indicated that the SVs were not dilated but the score was diagnostic, and a score of 3 denoted that the SVs were dilated and the score was diagnostic. Volume differences and interpretability scores were analyzed using a t test. Interobserver agreement was analyzed using the Cohen kappa statistic. A separate analysis was performed to evaluate differences in diagnostic interpretability for patients 60 years and younger versus patients older than 60 years, by use of the chi-square test and relative risk ratio analysis.
RESULTS. The right, left, and total SV volumes for group 1 were 3.1 mL, 2.9 mL, and 6.0 mL, respectively, whereas those for group 2 were 4.7 mL, 4.1 mL, and 8.8 mL, respectively (p = 0.011). The mean interpretability scores for group 1 and group 2 were 2.0 and 2.5, respectively. For group 1, reader 1 and reader 2 assigned a nondiagnostic score for 10 and 13 patients, respectively, whereas for group 2, they assigned a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.03, for reader 2). For men in group 1 who were older than 60 years, reader 1 and reader 2 gave a nondiagnostic score for nine and 11 patients, respectively; whereas for men in group 2 who were older than 60 years, the readers gave a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.05, for reader 2).
CONCLUSION. For men older than 60 years, abstinence from ejaculation for 3 or more days before undergoing MRI examination resulted in larger SV volumes and lower rates of nondiagnostic evaluation and therefore might improve evaluation of SV invasion on multiparametric MRI. The difference is less striking in men 60 years and younger.
C1 [Kabakus, Ismail M.] Hacettepe Univ, Dept Radiol, Ankara, Turkey.
[Borofsky, Samuel] George Washington Univ, Dept Radiol, Washington, DC USA.
[Mertan, Francesca V.; Greer, Matthew; Daar, Dagane; Choyke, Peter L.; Turkbey, Baris] NIH, Mol Imaging Program, 10 Ctr Dr,Bldg 10,Rm B3B85, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NIH, Dept Intervent Radiol, Bldg 10, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NIH, Dept Urol, Bldg 10, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NIH, Mol Imaging Program, 10 Ctr Dr,Bldg 10,Rm B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
OI Greer, Matthew/0000-0003-4409-4398
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD DEC
PY 2016
VL 207
IS 6
BP 1205
EP 1209
DI 10.2214/AJR.16.16278
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED2MS
UT WOS:000388681400016
PM 27657193
ER
PT J
AU Lim, H
Linet, MS
Van Dyke, ME
Miller, DL
Simon, SL
Sigurdson, AJ
Kitahara, CM
AF Lim, Hyeyeun
Linet, Martha S.
Van Dyke, Miriam E.
Miller, Donald L.
Simon, Steven L.
Sigurdson, Alice J.
Kitahara, Cari M.
TI Changing Patterns in the Performance of Fluoroscopically Guided
Interventional Procedures and Adherence to Radiation Safety Practices in
a US Cohort of Radiologic Technologists
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE cardiovascular catheterizations; fluoroscopically guided procedures;
radiation safety practices; radiologic technologists
ID AMERICAN-HEART-ASSOCIATION; IONIZING-RADIATION; CANCER-RISKS;
CARDIOLOGISTS; DISEASE; HEALTH; PROTECTION; HAZARDS; WORKING; UPDATE
AB OBJECTIVE. Information is limited on changes over time in the types of fluoroscopically guided interventional procedures performed and associated radiation safety practices used by radiologic technologists. MATERIALS AND
METHODS. Our study included 12,571 U.S. radiologic technologists who were certified for at least 2 years in 1926-1982 and who reported in a 2012-2013 survey that they ever performed or assisted with fluoroscopically guided interventional procedures. They completed a mailed questionnaire in 2013-2014 describing their detailed work practices for 21 fluoroscopically guided interventional procedures and associated radiation safety practices from the 1950s through 2009.
RESULTS. Overall, the proportion of technologists who reported working with therapeutic fluoroscopically guided interventional procedures, including percutaneous coronary interventions, increased over time, whereas the proportion of technologists who worked with diagnostic fluoroscopically guided interventional procedures, including diagnostic cardiovascular catheterization and neuroangiographic procedures, decreased. We also observed substantial increases in the median number of times per month that technologists worked with diagnostic cardiovascular catheterizations and percutaneous coronary interventions. In each time period, most technologists reported consistently (>= 75% of work time) wearing radiation monitoring badges and lead aprons during fluoroscopically guided interventional procedures. However, fewer than 50% of the technologists reported consistent use of thyroid shields, lead glasses, and room shields during fluoroscopically guided interventional procedures, even in more recent time periods.
CONCLUSION. This study provides a detailed historical assessment of fluoroscopically guided interventional procedures performed and radiation safety practices used by radiologic technologists from the 1950s through 2009. Results can be used in conjunction with badge dose data to estimate organ radiation dose for studies of radiation-related health risks in radiologic technologists who have worked with fluoroscopically guided interventional procedures.
C1 [Lim, Hyeyeun; Linet, Martha S.; Simon, Steven L.; Sigurdson, Alice J.; Kitahara, Cari M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 9069 Med Ctr Dr, Rockville, MD 20850 USA.
[Van Dyke, Miriam E.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Lim, H (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 9069 Med Ctr Dr, Rockville, MD 20850 USA.
EM Hyeyeun.lim@nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health, U.S.
Department of Health and Human Services
FX Supported by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, U.S. Department of Health and Human Services.
NR 35
TC 0
Z9 0
U1 7
U2 7
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD DEC
PY 2016
VL 207
IS 6
BP 1350
EP 1359
DI 10.2214/AJR.15.15979
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED2MS
UT WOS:000388681400037
PM 27575031
ER
PT J
AU Amano, M
Salcedo-Gomez, PM
Zhao, R
Yedidi, RS
Das, D
Bulut, H
Delino, NS
Sheri, VR
Ghosh, AK
Mitsuya, H
AF Amano, Masayuki
Salcedo-Gomez, Pedro Miguel
Zhao, Rui
Yedidi, Ravikiran S.
Das, Debananda
Bulut, Haydar
Delino, Nicole S.
Sheri, Venkata Reddy
Ghosh, Arun K.
Mitsuya, Hiroaki
TI A Modified P1 Moiety Enhances In Vitro Antiviral Activity against
Various Multidrug-Resistant HIV-1 Variants and In Vitro Central Nervous
System Penetration Properties of a Novel Nonpeptidic Protease Inhibitor,
GRL-10413
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG DISCOVERY; ANTIRETROVIRAL THERAPY;
BIS-TETRAHYDROFURAN; CRYSTAL-STRUCTURES; X-RAY; LIGAND; POTENT; PI;
REPLICATION
AB We report here that GRL-10413, a novel nonpeptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a hydroxyethylamine sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50] of 0.00035 to 0.0018 mu M), with minimal cytotoxicity (50% cytotoxic concentration [CC50] =35.7 mu M). GRL-10413 blocked the infectivity and replication of HIV-1NL4-3 variants selected by use of atazanavir, lopinavir, or amprenavir (APV) at concentrations of up to 5 mu M(EC50 =0.0021 to 0.0023 mu M). GRL-10413 also maintained its strong antiviral activity against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to various antiviral regimens after long-term antiretroviral therapy. The development of resistance against GRL-10413 was significantly delayed compared to that against APV. In addition, GRL-10413 showed favorable central nervous system (CNS) penetration properties as assessed with an in vitro blood-brain barrier (BBB) reconstruction system. Analysis of the crystal structure of HIV-1 protease in complex with GRL-10413 demonstrated that the modified P1 moiety of GRL-10413 has a greater hydrophobic surface area and makes greater van der Waals contacts with active site amino acids of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants, with favorable CNS penetration capability, and that the newly modified P1 moiety may confer desirable features in designing novel anti-HIV-1 PIs.
C1 [Amano, Masayuki; Salcedo-Gomez, Pedro Miguel; Zhao, Rui; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto, Japan.
[Amano, Masayuki; Salcedo-Gomez, Pedro Miguel; Zhao, Rui; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto, Japan.
[Yedidi, Ravikiran S.; Das, Debananda; Bulut, Haydar; Delino, Nicole S.; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Yedidi, Ravikiran S.] GSL Med Coll & Gen Hosp, Dept Pharmacol, Rajahmundry, Andhra Pradesh, India.
[Sheri, Venkata Reddy; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Sheri, Venkata Reddy; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Mitsuya, Hiroaki] Natl Ctr Global Hlth, Tokyo, Japan.
[Mitsuya, Hiroaki] Med Res Inst, Tokyo, Japan.
RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto, Japan.
EM hm21q@nih.gov
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU HHS \ National Institutes of Health (NIH) [GM53386]; Ministry of Health,
Labor and Welfare (MHLW)
FX This work, including the efforts of Arun K. Ghosh, was funded by HHS
vertical bar National Institutes of Health (NIH) (GM53386). This work,
including the efforts of Hiroaki Mitsuya, was funded by Ministry of
Health, Labor and Welfare (MHLW).
NR 54
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Z9 0
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD DEC
PY 2016
VL 60
IS 12
BP 7046
EP 7059
DI 10.1128/AAC.01428-16
PG 14
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA ED7QO
UT WOS:000389064300005
PM 27620483
ER
PT J
AU Lestner, JM
Groll, AH
Aljayyoussi, G
Seibel, NL
Shad, A
Gonzalez, C
Wood, LV
Jarosinski, PF
Walsh, TJ
Hope, WW
AF Lestner, Jodi M.
Groll, Andreas H.
Aljayyoussi, Ghaith
Seibel, Nita L.
Shad, Aziza
Gonzalez, Corina
Wood, Lauren V.
Jarosinski, Paul F.
Walsh, Thomas J.
Hope, William W.
TI Population Pharmacokinetics of Liposomal Amphotericin B in
Immunocompromised Children
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID LIPOPROTEINS; DISEASES; SERUM; TRIAL; ASPERGILLOSIS; AMBISOME; THERAPY;
SAFETY
AB Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (C-max) and areas under the concentration-time curve from 0 to 24 h (AUC(0-24)) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC(0-24) and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors.
C1 [Lestner, Jodi M.; Hope, William W.] Univ Liverpool, Antimicrobial Pharmacodynam & Therapeut, Liverpool, Merseyside, England.
[Groll, Andreas H.] Univ Childrens Hosp Munster, Ctr Bone Marrow Transplantat, Dept Pediat Hematology Oncol, Munster, Germany.
[Aljayyoussi, Ghaith] Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England.
[Seibel, Nita L.; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD USA.
[Seibel, Nita L.] Childrens Natl Med Ctr & George Washington Univ S, Washington, DC USA.
[Shad, Aziza] NCI, Clin Investigat Branch, Canc Treatment Evaluat Program, Bethesda, MD USA.
[Gonzalez, Corina] Univ Med Ctr, Dept Pediat, Div Pediat Hematology Oncol, Washington, DC USA.
[Wood, Lauren V.] NCI, Ctr Canc Res, Bethesda, MD USA.
[Jarosinski, Paul F.] Natl Inst Hlth Clin Ctr, Dept Pharm, Bethesda, MD USA.
[Walsh, Thomas J.] Weill Cornell Med Ctr, Transplantat Oncol Infect Dis Program, New York, NY USA.
[Walsh, Thomas J.] Weill Cornell Med Ctr, Dept Pediat, New York, NY USA.
[Walsh, Thomas J.] Weill Cornell Med Ctr, Dept Microbiol, New York, NY USA.
RP Lestner, JM (reprint author), Univ Liverpool, Antimicrobial Pharmacodynam & Therapeut, Liverpool, Merseyside, England.
EM jlestner@liverpool.ac.uk
OI Hope, William/0000-0001-6187-878X
FU Astellas Pharma (Astellas)
FX This work, including the efforts of Thomas J. Walsh, was funded by
Astellas Pharma (Astellas).
NR 18
TC 1
Z9 1
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD DEC
PY 2016
VL 60
IS 12
BP 7340
EP 7346
DI 10.1128/AAC.01427-16
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA ED7QO
UT WOS:000389064300037
PM 27697762
ER
PT J
AU Kharfan-Dabaja, MA
Kumar, A
Hamadani, M
Stilgenbauer, S
Ghia, P
Anasetti, C
Dreger, P
Montserrat, E
Perales, MA
Alyea, EP
Awan, FT
Ayala, E
Barrientos, JC
Brown, JR
Castro, JE
Furman, RR
Gribben, J
Hill, BT
Mohty, M
Moreno, C
O'Brien, S
Pavletic, SZ
Pinilla-Ibarz, J
Reddy, NM
Sorror, M
Bredeson, C
Carpenter, P
Savani, BN
AF Kharfan-Dabaja, Mohamed A.
Kumar, Ambuj
Hamadani, Mehdi
Stilgenbauer, Stephan
Ghia, Paolo
Anasetti, Claudio
Dreger, Peter
Montserrat, Emili
Perales, Miguel-Angel
Alyea, Edwin P.
Awan, Farrukh T.
Ayala, Ernesto
Barrientos, Jacqueline C.
Brown, Jennifer R.
Castro, Januario E.
Furman, Richard R.
Gribben, John
Hill, Brian T.
Mohty, Mohamad
Moreno, Carol
O'Brien, Susan
Pavletic, Steven Z.
Pinilla-Ibarz, Javier
Reddy, Nishitha M.
Sorror, Mohamed
Bredeson, Christopher
Carpenter, Paul
Savani, Bipin N.
TI Clinical Practice Recommendations for Use of Allogeneic Hematopoietic
Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the
Guidelines Committee of the American Society for Blood and Marrow
Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Chronic lymphocytic leukemia; Allogeneic hematopoietic cell
transplantation; BCR inhibitors; BCL-2 inhibitors
ID RICHTER-SYNDROME; REDUCED-INTENSITY; FLOW-CYTOMETRY; 17P DELETION;
FOLLOW-UP; MUTATIONAL STATUS; PERIPHERAL-BLOOD; BONE-MARROW; SINGLE-ARM;
CLL
AB We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations high-light the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL. (C) 2016 American Society for Blood and Marrow Transplantation.
C1 [Kharfan-Dabaja, Mohamed A.; Anasetti, Claudio; Ayala, Ernesto] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA.
[Kharfan-Dabaja, Mohamed A.; Anasetti, Claudio; Ayala, Ernesto; Pinilla-Ibarz, Javier] Univ S Florida, Morsani Coll Med, Dept Oncol Sci, Tampa, FL USA.
[Kumar, Ambuj] Univ S Florida, Coll Med, Program Comparat Effectiveness Res, Tampa, FL USA.
[Hamadani, Mehdi] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Stilgenbauer, Stephan] Univ Ulm, Internal Med 3, Ulm, Germany.
[Ghia, Paolo] IRCCS San Raffaele Hosp, Dept Oncohaematol, Milan, Italy.
[Ghia, Paolo] IRCCS San Raffaele Hosp, Div Expt Oncol, Milan, Italy.
[Ghia, Paolo] Univ Vita Salute San Raffaele, Milan, Italy.
[Dreger, Peter] Heidelberg Univ, Dept Med 5, Heidelberg, Germany.
[Montserrat, Emili] Univ Barcelona, Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
[Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA.
[Alyea, Edwin P.; Brown, Jennifer R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA.
[Awan, Farrukh T.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Barrientos, Jacqueline C.] Hofstra Northwell Sch Med, CLL Res & Treatment Program, New Hyde Pk, NY USA.
[Castro, Januario E.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Furman, Richard R.] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA.
[Gribben, John] Queen Mary Univ London, John Vane Canc Ctr, Barts Canc Inst, Charterhouse Sq, London, England.
[Hill, Brian T.] Cleveland Clin, Dept Hematol & Med Oncol, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Mohty, Mohamad] Univ Paris 06, St Antoine Hosp, Dept Haematol, Paris, France.
[Mohty, Mohamad] INSERM, UMRs938, Paris, France.
[Moreno, Carol] Hosp Santa Creu St Pau, Barcelona, Spain.
[O'Brien, Susan] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA.
[Pavletic, Steven Z.] NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Pinilla-Ibarz, Javier] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA.
[Reddy, Nishitha M.; Savani, Bipin N.] Vanderbilt Univ, Sch Med, Dept Med, Div Hematol Oncol, Nashville, TN 37212 USA.
[Sorror, Mohamed; Carpenter, Paul] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Sorror, Mohamed; Carpenter, Paul] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Bredeson, Christopher] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada.
[Bredeson, Christopher] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
RP Kharfan-Dabaja, MA (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, 12902 Magnolia Dr,FOB 3, Tampa, FL 33612 USA.
EM Mohamed.Kharfan-Dabaja@Moffitt.org
FU Takeda Oncology; Sanofi; Otsuka; AbbVie; Amgen; Boehringer-Ingelheim;
Celgene; Genentech; Genzyme; Gilead; GlaxoSmithKline; Janssen;
Mundipharma; Novartis; Pharmacyclics; Hoffmann La-Roche; GSK; Roche;
Acerta; TG Therapeutics; Regeneron; ProNAi
FX The authors have nothing to disclose. Conflict of interest statement:
M.H.: Research funding by Takeda Oncology, Sanofi, and Otsuka; Honoraria
from Celgene; Consultancy by Medimmune, Pharmacyclics and Cellerant.
S.S.: Honoraria for consultancy, research support, and travel support
from AbbVie, Amgen, Boehringer-Ingelheim, Celgene, Genentech, Genzyme,
Gilead, GlaxoSmithKline, Janssen, Mundipharma, Novartis, Pharmacyclics,
Hoffmann La-Roche, and Sanofi. P.G.: Advisory board for AbbVie, Adaptive
Biotechnologies, Gilead, Janssen, Pharmacyclics, and Roche; Research
funding from Gilead, GSK, and Roche. P.D.: Research support from Janssen
and and Gilead; Honoraria for speaker and advisory board services from
Janssen, Gilead, Novartis, and Roche. F.T.A.: Advisory boards for Gilead
and Novartis Oncology. J.G.: Honoraria from Janssen, Roche/Genentech,
Abbie, Pharmacyclics, Gilead, and Celgene. B.T.H.: Advisory boards for
Pharmacyclics and Gilead; Research funding from Abbvie. M.M.: Honoraria
for speaking engagements and research support from Janssen. S.O.:
Consultant for Amgen, Celgene, and GSK; Advisory board for CLL Global
Research Foundation; Research support from Acerta, TG Therapeutics,
Regeneron, Gilead, Pharmacyclics, and ProNAi. J.P.-I.: Consultant for
Janssen, Gilead, Pharmacyclics, Abbvie, and Celgene; Speaker Bureau for
TEVA, Pharmacyclics, and Gilead. N.M.R.: Advisory boards of AbbVie and
Gilead. All other authors report no conflicts of interest.
NR 76
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD DEC
PY 2016
VL 22
IS 12
BP 2117
EP 2125
DI 10.1016/j.bbmt.2016.09.013
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA ED8CM
UT WOS:000389099600003
PM 27660167
ER
PT J
AU Shah, NN
Loeb, DM
Khuu, H
Stroncek, D
Ariyo, T
Raffeld, M
Delbrook, C
Mackall, CL
Wayne, AS
Fry, TJ
AF Shah, Nirali N.
Loeb, David M.
Khuu, Hahn
Stroncek, David
Ariyo, Tolu
Raffeld, Mark
Delbrook, Cindy
Mackall, Crystal L.
Wayne, Alan S.
Fry, Terry J.
TI Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic
Cell Vaccination and Donor Lymphocyte Infusion in Patients with
Hematologic Malignancies and Post-Transplantation Relapse
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Wilms' tumor 1 (WT1); Dendritic cell vaccine; Post-transplantation
relapse; Leukemia
ID ACUTE MYELOID-LEUKEMIA; WT1 PEPTIDE VACCINATION; ACUTE
LYMPHOBLASTIC-LEUKEMIA; 2ND INTERNATIONAL WORKSHOP; GENE WT1;
CANCER-IMMUNOTHERAPY; LEUKOCYTE INFUSIONS; ANTITUMOR IMMUNITY;
HIGH-RISK; TRANSPLANTATION
AB Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft versus-host disease (GVHD). The Wilms' tumor 1 (WTI) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues. In this pilot trial, we assessed safety and feasibility of a WTI peptide-loaded donor-derived dendritic cell (DC) vaccine given with DLI designed to enhance and direct the graft-versus-leukemia effect. Secondary objectives were to evaluate immunologic and clinical responses. A total of 5 subjects, median age 17 years (range, 9 to 19 years), with post-HCT relapse were enrolled. Disease subtypes included acute lymphoblastic leukemia (n =3), acute myelogenous leukemia (n = 1), and Hodgkin lymphoma (n=1). Successful vaccine production was feasible from all donors. DC vaccination and DLI were well tolerated. One recipient developed grade 1 skin GVHD not requiring systemic therapy. The most common adverse events included grade 1 reversible pain and pruritus at the vaccine injection and delayed-type hypersensitivity (DTH) skin testing sites. There were no grade 3 or higher adverse events related to the research. Immune responses consisted of ELISpot response in 3 recipients and positive DTH tests to WTI peptide cocktail in 2 subjects. Our study provides 1 of the first attempts to apply tumor-specific vaccine therapy to the allogeneic setting. Preliminary results show the DC-based vaccination is safe and feasible after allogeneic HCT, with a suggestion that this approach can be used to sensitize the repopulated allogeneic-donor immune system to WT1. Future directions may include testing of vaccination strategies in the early post-transplantation setting for relapse prevention. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation.
C1 [Shah, Nirali N.; Ariyo, Tolu; Delbrook, Cindy; Mackall, Crystal L.; Wayne, Alan S.; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Loeb, David M.] Johns Hopkins Univ, Pediat Oncol, Baltimore, MD USA.
[Khuu, Hahn; Stroncek, David] NCI, Dept Transfus Med, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Raffeld, Mark] Univ Southern Calif, Heck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Wayne, Alan S.] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90027 USA.
RP Shah, NN (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Room 1W-3750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Nirali.Shah@nih.gov
FU Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute
FX We gratefully acknowledge the study participants and their families,
referring medical care teams, and the faculty and staff of the National
Institutes of Health. This research was supported by the Intramural
Research Program of the NIH, Center for Cancer Research, National Cancer
Institute.
NR 30
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD DEC
PY 2016
VL 22
IS 12
BP 2149
EP 2154
DI 10.1016/j.bbmt.2016.08.028
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA ED8CM
UT WOS:000389099600007
PM 27634018
ER
PT J
AU Gadalla, SM
Wang, T
Dagnall, C
Haagenson, M
Spellman, SR
Hicks, B
Jones, K
Katki, HA
Lee, SJ
Savage, SA
AF Gadalla, Shahinaz M.
Wang, Tao
Dagnall, Casey
Haagenson, Michael
Spellman, Stephen R.
Hicks, Belynda
Jones, Kristine
Katki, Hormuzd A.
Lee, Stephanie J.
Savage, Sharon A.
TI Effect of Recipient Age and Stem Cell Source on the Association between
Donor Telomere Length and Survival after Allogeneic Unrelated
Hematopoietic Cell Transplantation for Severe Aplastic Anemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Aplastic anemia; Telomere length; Survival; Hematopoietic cell
transplantation; Donor selection
ID BONE-MARROW; PERIPHERAL-BLOOD; CHILDREN; STABILITY; JAPAN; TIME; PCR;
SCT
AB We previously showed an association between donor leukocyte relative telomere length (RTL) and posthematopoietic cell transplantation (HCT) survival in patients with severe aplastic anemia (SAA) who received bone marrow grafts at ages <40 years. Here, we tested the generalizability of the prior findings in an independent validation cohort and by recipient age and stem cell source in the combined discovery and validation cohorts. We used monoplex quantitative real-time PCR to measure RTL in: (1) a new SAA validation cohort of 428 patients (age range,2 to 77 years) with available pretransplantation donor blood samples in the Center for International Blood and Marrow Transplant Research repository, and (2) 278 patients from the original cohort who had sufficient DNA to repeat RTL testing. We used Cox proportional hazard models to calculate hazard ratios (HRs), and 95% confidence intervals (CIs) across categories of donor RTL. Data from the validation cohort showed no association between donor RTL and patient survival, but further analysis identified differences by recipient age and stem cell source as the likely explanation. In patients <40 years, the HR comparing longest with shortest and middle RTL tertiles = .75; 95% CI,.44 to 1.30 versus HR = 1.05; 95% CI, .59 to 1.89 for patients >= 40 years, P interaction = .37. In bone marrow recipients, the HR = .68; 95% CI, .72 to 1.10 versus HR = 1.29; 95% CI, .64 to 2.62 for peripheral blood stem cell grafts; P interaction = .88. Analyses using data from the 2 cohorts showed a statistically significant survival benefit only in <40-year-old patients receiving bone marrow graft (HR comparing longest and middle RTL tertiles with shortest = .69; 95% CI, .50 to .95, P = .02). The study suggested that the association between donor RTL and post-HCT outcomes in recipients with SAA may vary by recipient age and stem cell source. A larger study is needed to account for multiple comparisons and to further test the generalizability of our findings. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation.
C1 [Gadalla, Shahinaz M.; Katki, Hormuzd A.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wang, Tao; Lee, Stephanie J.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Wang, Tao] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Dagnall, Casey; Hicks, Belynda; Jones, Kristine] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Dagnall, Casey; Hicks, Belynda; Jones, Kristine] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Haagenson, Michael; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
RP Gadalla, SM (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E-534, Rockville, MD 20850 USA.
EM gadallas@mail.nih.gov
OI Dagnall, Casey/0000-0001-7334-4718
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute; U.S. Public Health Service from the
National Cancer Institute [U24-CA76518]; National Heart Lung and Blood
Institute; National Institute of Allergy and Infectious Diseases, Heath
Resources, and Services Administration [HHSH234200637015C]; Office of
Naval Research [N00014-13-1-0039, N00014-14-1-0028]
FX The study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute;
by a U.S. Public Health Service grant (U24-CA76518) from the National
Cancer Institute, the National Heart Lung and Blood Institute and the
National Institute of Allergy and Infectious Diseases, Heath Resources,
and Services Administration (HHSH234200637015C); and by 2 grants
N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research.
NR 28
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD DEC
PY 2016
VL 22
IS 12
BP 2276
EP 2282
DI 10.1016/j.bbmt.2016.09.012
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA ED8CM
UT WOS:000389099600026
PM 27641680
ER
PT J
AU Wilcox, A
Silverman, D
Friesen, M
Locke, S
Russ, D
Hyun, N
Colt, J
Figueroa, J
Rothman, N
Moore, L
Koutros, S
AF Wilcox, Amber N.
Silverman, Debra T.
Friesen, Melissa C.
Locke, Sarah J.
Russ, Daniel E.
Hyun, Noorie
Colt, Joanne S.
Figueroa, Jonine D.
Rothman, Nathaniel
Moore, Lee E.
Koutros, Stella
TI Smoking status, usual adult occupation, and risk of recurrent urothelial
bladder carcinoma: data from The Cancer Genome Atlas (TCGA) Project
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Bladder cancer; Recurrence; Occupation; Smoking status; Diesel exhaust
ID RADICAL CYSTECTOMY; OUTCOMES; EXPOSURE; EXHAUST; MEN; P53
AB Tobacco smoking and occupational exposures are the leading risk factors for developing urothelial bladder carcinoma (UBC), yet little is known about the contribution of these two factors to risk of UBC recurrence. We evaluated whether smoking status and usual adult occupation are associated with time to UBC recurrence for 406 patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project.
Kaplan-Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification group and time to UBC recurrence.
Data on time to recurrence were available for 358 patients over a median follow-up time of 15 months. Of these, 133 (37.2%) experienced a recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank p = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR 1.8, 95% CI 1.1, 3.0) and for those employed in production occupations (HR 2.0, 95% CI 1.1, 3.6).
These findings suggest smoking status impacts risk of UBC recurrence, although several previous studies provided equivocal evidence regarding this association. In addition to the known causal relationship between occupational exposure and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence.
C1 [Wilcox, Amber N.; Silverman, Debra T.; Friesen, Melissa C.; Locke, Sarah J.; Hyun, Noorie; Colt, Joanne S.; Rothman, Nathaniel; Moore, Lee E.; Koutros, Stella] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 9609 Med Ctr Dr, Rockville, MD USA.
[Russ, Daniel E.] NIH, Div Computat Biosci, Dept Hlth & Human Serv, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
RP Koutros, S (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 9609 Med Ctr Dr, Rockville, MD USA.
EM koutross@mail.nih.gov
RI Friesen, Melissa/A-5362-2009
FU National Institutes of Health, NCI, Division of Cancer Epidemiology and
Genetics [Z01CP010119]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NCI, Division of Cancer Epidemiology and
Genetics (Z01CP010119).
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2016
VL 27
IS 12
BP 1429
EP 1435
DI 10.1007/s10552-016-0821-7
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA ED1EM
UT WOS:000388587400003
PM 27804056
ER
PT J
AU Chen, XY
Chen, RM
Chen, ZY
Chen, JP
Shung, KK
Zhou, QF
AF Chen, Xiaoyang
Chen, Ruimin
Chen, Zeyu
Chen, Jiping
Shung, K. Kirk
Zhou, Qifa
TI Transparent lead lanthanum zirconate titanate (PLZT) ceramic fibers for
high-frequency ultrasonic transducer applications
SO CERAMICS INTERNATIONAL
LA English
DT Article
DE PLZT fiber; Composites; Extrusion; Biomedical applications
ID INTRAVASCULAR ULTRASOUND; THICKNESS-MODE; COMPOSITES; ELEMENT
AB This paper presents fabrication of transparent lanthanum zirconate titanate (PLZT) fibers using extrusion technique. The diameter of the sintered PLZT fiber is about 400-mu m, and the fibers exhibit very good transparency. Measured dielectric constant, remnant polarization and coercive field of PLZT fiber were found to be 2340, 22.5-mu C/cm(2), and 9.8-kV/cm, respectively. The transparent piezoelectric materials may exhibit great potential for Photoacoustic (PA) imaging and hybrid intravascular imaging combining OCT and ultrasound imaging by using the transparent fiber as the path of light propagation and ultrasonic transducer material. In our study, these transparent PLZT fibers were designed to fabricate two types of high-frequency ultrasonic transducers: small aperture single PLZT fiber/epoxy composite and large aperture 1-3 PLZT fiber/epoxy composite ultrasonic transducers. Besides, a 20-mu m tungsten wire phantom and the cornea of the porcine eye were also imaged with the 1-3 PLZT fiber/epoxy composite ultrasonic transducer to demonstrate its imaging capability. (C) 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
C1 [Chen, Xiaoyang] Sichuan Univ, Coll Mat Sci & Engn, Chengdu 610064, Peoples R China.
[Chen, Ruimin; Chen, Zeyu; Shung, K. Kirk; Zhou, Qifa] Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Chen, Ruimin; Chen, Zeyu; Shung, K. Kirk; Zhou, Qifa] Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Chen, Jiping] Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA.
RP Zhou, QF (reprint author), Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.; Zhou, QF (reprint author), Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM qifazhou@usc.edu
FU National Institutes of Health [P41-EB002182]; China Scholarship Council
of China (CSC)
FX This work was supported by the National Institutes of Health (Grant No.
P41-EB002182) and the China Scholarship Council of China (CSC).
NR 29
TC 0
Z9 0
U1 10
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0272-8842
EI 1873-3956
J9 CERAM INT
JI Ceram. Int.
PD DEC
PY 2016
VL 42
IS 16
BP 18554
EP 18559
DI 10.1016/j.ceramint.2016.08.195
PG 6
WC Materials Science, Ceramics
SC Materials Science
GA ED0OV
UT WOS:000388542700079
ER
PT J
AU Newmeyer, MN
Swortwood, MJ
Barnes, AJ
Abulseoud, OA
Scheidweiler, KB
Huestis, MA
AF Newmeyer, Matthew N.
Swortwood, Madeleine J.
Barnes, Allan J.
Abulseoud, Osama A.
Scheidweiler, Karl B.
Huestis, Marilyn A.
TI Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after
Controlled Smoked, Vaporized, and Oral Cannabis Administration in
Frequent and Occasional Cannabis Users: Identification of Recent
Cannabis Intake
SO CLINICAL CHEMISTRY
LA English
DT Article
ID PLASMA; INGESTION; DELTA(9)-TETRAHYDROCANNABINOL; METABOLITE; MARIJUANA;
TETRAHYDROCANNABINOL; DISPOSITION; EXCRETION; MARKER; THC
AB BACKGROUND: There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Delta(9)-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for <= 2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Delta(9)-tetrahydrocannabivarin (THCV), and 11-nor-9carboxy- THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used.
METHODS: We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration.
RESULTS: Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC >= 5 mu g/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively.
CONCLUSIONS: Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. (C) 2016 American Association for Clinical Chemistry
C1 [Newmeyer, Matthew N.; Swortwood, Madeleine J.; Barnes, Allan J.; Abulseoud, Osama A.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD USA.
[Newmeyer, Matthew N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Huestis, Marilyn A.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Scheidweiler, KB (reprint author), NIDA, Chem & Drug Metab, Clin Pharmacol & Therapeut Res Branch, IRP,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM kscheidweiler@intra.nida.nih.gov
OI Newmeyer, Matthew/0000-0002-0653-1553
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX M.N. Newmeyer, The Intramural Research Program, National Institute on
Drug Abuse, NIH, to institution; M.Huestis, The Intramural Research
Program, National Institute on Drug Abuse, NIH, to institution.
NR 28
TC 3
Z9 3
U1 13
U2 13
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD DEC
PY 2016
VL 62
IS 12
BP 1579
EP 1592
DI 10.1373/clinchem.2016.263475
PG 14
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA ED5XN
UT WOS:000388926800008
PM 27899456
ER
PT J
AU Mennigen, JA
Zhang, DP
AF Mennigen, Jan A.
Zhang, Dapeng
TI MicroTrout: A comprehensive, genome-wide miRNA target prediction
framework for rainbow trout, Oncorhynchus mykiss
SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS
LA English
DT Article
ID MEDIATED REPRESSION; MICRORNAS; EXPRESSION; IDENTIFICATION; ZEBRAFISH;
EVOLUTION; DIFFERENTIATION; PROLIFERATION; CONSEQUENCES; TRANSLATION
AB Rainbow trout represent an important teleost research model and aquaculture species. As such, rainbow trout are employed in diverse areas of biological research, including basic biological disciplines such as comparative physiology, toxicology, and, since rainbow trout have undergone both teleost- and salmonid-specific rounds of genome duplication, molecular evolution. In recent years, microRNAs (miRNAs, small non-protein coding RNAs) have emerged as important posttranscriptional regulators of gene expression in animals. Given the increasingly recognized importance of miRNAs as an additional layer in the regulation of gene expression and hence biological function, recent efforts using RNA- and genome sequencing approaches have resulted in the creation of several resources for the construction of a comprehensive repertoire of rainbow trout miRNAs and isomiRs (variant miRNA sequences that all appear to derive from the same gene but vary in sequence due to post-transcriptional processing). Importantly, through the recent publication of the rainbow trout genome (Berthelot et al., 2014), mRNA 3'UTR information has become available, allowing for the first time the genome-wide prediction of miRNA-target RNA relationships in this species. We here report the creation of the microtrout database, a comprehensive resource for rainbow trout miRNA and annotated 3'UTRs. The comprehensive database was used to implement an algorithm to predict genome-wide rainbow trout-specific miRNA-mRNA target relationships, generating an improved predictive framework over previously published approaches. This work will serve as a useful framework and sequence resource to experimentally address the role of miRNAs in several research areas using the rainbow trout model, examples of which are discussed. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Mennigen, Jan A.] Univ Ottawa, Dept Biol, 20 Marie Curie, Ottawa, ON K1N 6N5, Canada.
[Zhang, Dapeng] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Mennigen, JA (reprint author), Univ Ottawa, Dept Biol, 20 Marie Curie, Ottawa, ON K1N 6N5, Canada.
EM jan.mennigen@uottawa.ca
NR 47
TC 2
Z9 2
U1 6
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1744-117X
EI 1878-0407
J9 COMP BIOCHEM PHYS D
JI Comp. Biochem. Physiol. D-Genomics Proteomics
PD DEC
PY 2016
VL 20
BP 19
EP 26
DI 10.1016/j.cbd.2016.07.002
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA ED8BS
UT WOS:000389097500003
PM 27494513
ER
PT J
AU Calkins, MJ
Vartanian, V
Owen, N
Kirkali, G
Jaruga, P
Dizdaroglu, M
McCullough, AK
Lloyd, RS
AF Calkins, Marcus J.
Vartanian, Vladimir
Owen, Nichole
Kirkali, Guldal
Jaruga, Pawel
Dizdaroglu, Miral
McCullough, Amanda K.
Lloyd, R. Stephen
TI Enhanced sensitivity of Neill-/- mice to chronic UVB exposure
SO DNA REPAIR
LA English
DT Article
DE DNA base excision repair; DNA glycosylases; UV-induced inflammation;
Oxidatively-induced DNA base damage
ID CYCLOBUTANE PYRIMIDINE DIMER; INDUCED OXIDATIVE DAMAGE;
LEMLI-OPITZ-SYNDROME; CIS-THYMINE GLYCOL; HIGH-FAT DIET;
ULTRAVIOLET-RADIATION; HUMAN SKIN; MURINE EPIDERMIS; IN-VIVO;
MASS-SPECTROMETRY
AB Oxidative stress and reactive oxygen species (ROS)-induced DNA base damage are thought to be central mediators of UV -induced carcinogenesis and skin aging. However, increased steady-state levels of ROS-induced DNA base damage have not been reported after chronic UV exposure. Accumulation of ROS-induced DNA base damage is governed by rates of lesion formation and repair. Repair is generally performed by Base Excision Repair(BER), which is initiated by DNA glycosylases, such as 8-oxoguanine glycosylase and Nei-Endonuclease VIII-Like 1 (NEIL1). In the current study, UV light (UVB) was used to elicit protracted low-level ROS challenge in wild-type (WT) and Neill -/- mouse skin. Relative to WT controls, Neill -/-mice showed an increased sensitivity to tissue destruction from the chronic UVB exposure, and corresponding enhanced chronic inflammatory responses as measured by cytokine message levels and profiling, as well as neutrophil infiltration. Additionally, levels of several ROS-induced DNA lesions were measured including 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5formamidopyrimidine (FapyGua), 8-hydroxyguanine (8-OH-Gua), 5,6-dihydroxyuracil (5,6-diOH-Ura) and thymine glycol (ThyGly). In WT mice, chronic UVB exposure led to increased steady-state levels of FapyGua, FapyAde, and ThyGly with no significant increases in 8-OH-Gua or 5,6-di0H-Ura. Interestingly, the lesions that accumulated were all substrates of NEIL1 Collectively, these data suggest that NEIL1-initiated repair of a subset of ROS-induced DNA base lesions may be insufficient to prevent the initiation of inflammatory pathways during chronic UV exposure in mouse skin. (c) 2016 Elsevier B.V. All rights reserved.
C1 [Calkins, Marcus J.; Vartanian, Vladimir; Owen, Nichole; McCullough, Amanda K.; Lloyd, R. Stephen] Oregon Hlth & Sci Univ, Oregon Inst Occupat Hlth Sci, Portland, OR 97239 USA.
[Kirkali, Guldal; Jaruga, Pawel; Dizdaroglu, Miral] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
[McCullough, Amanda K.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
[Lloyd, R. Stephen] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA.
[Calkins, Marcus J.] Natl Cheng Kung Univ, Inst Clin Med, Tainan, Taiwan.
[Kirkali, Guldal] NCI, NIH, Bethesda, MD 20841 USA.
RP Lloyd, RS (reprint author), 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM lloydst@ohsu.edu
FU NIH [R01 DK075974]; Training Program in the Molecular Basis of
Skin/Mucosa Pathobiology [T32-CA106195]
FX This work was partially supported by NIH R01 DK075974 (RSL) and the
Training Program in the Molecular Basis of Skin/Mucosa Pathobiology
(T32-CA106195) supported MJC. Certain commercial equipment or materials
are identified in this paper in order to specify adequately the
experimental procedure. Such identification does not imply
recommendation or endorsement by the National Institute of Standards and
Technology, nor does it imply that the materials or equipment identified
are necessarily the best available for the purpose.
NR 46
TC 1
Z9 1
U1 7
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD DEC
PY 2016
VL 48
BP 43
EP 50
DI 10.1016/j.dnarep.2016.10.010
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA ED7ZN
UT WOS:000389091400005
PM 27818081
ER
PT J
AU Vitiello, B
Ordonez, AE
AF Vitiello, Benedetto
Ordonez, Anna E.
TI Pharmacological treatment of children and adolescents with depression
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE Antidepressants; children and adolescents; depressive disorder;
efficacy; safety
ID SEROTONIN REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED
CONTROLLED-TRIALS; DOUBLE-BLIND EFFICACY; QUALITY-OF-LIFE;
ANTIDEPRESSANT TREATMENT; CLINICAL-TRIALS; PEDIATRIC DEPRESSION; MAJOR
DEPRESSION; MENTAL-DISORDERS
AB Introduction: Despite an increasing number of studies, there is debate whether antidepressants have a favorable benefit/risk balance in depressed youth.Areas covered: A systematic search identified 23 systematic reviews and meta-analyses published between 2010-2016. More than 30 controlled clinical trials were conducted in adolescents, but only a few in pre-pubertal patients. About one-third of the trials were severely statistically underpowered. Most studies failed to detect differences from placebo, but a few found fluoxetine effective. Although no suicide occurred in these studies, antidepressants increased suicidality risk (including suicidal ideation and behavior) versus placebo (OR=2.39). Only two placebo-controlled trials with acceptable statistical power were publicly funded: both showed efficacy of fluoxetine, and one found a higher incidence of suicidality (OR=3.7, 95% C.I. 1.00-13.7).Expert opinion: In youth, antidepressants have, on average, a small therapeutic effect. The high placebo response is exacerbated by the large number of sites in many industry-funded studies. There is evidence that fluoxetine leads to greater and faster improvement than placebo or psychotherapy in adolescents. Considering both the high response to non-specific interventions and safety concerns, antidepressants should be used cautiously in youth, and limited to patients with moderate-to-severe depression for whom psychosocial interventions are either ineffective or not feasible.
C1 [Vitiello, Benedetto] NIMH, Treatment & Prevent Intervent Res Branch, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Ordonez, Anna E.] NIMH, Off Clin Res, Bethesda, MD 20892 USA.
RP Vitiello, B (reprint author), NIMH, MSC 9633,6001 Execut Blvd Rm 7147, Bethesda, MD 20892 USA.
EM bvitiell@mail.nih.gov
NR 47
TC 0
Z9 0
U1 13
U2 13
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD DEC
PY 2016
VL 17
IS 17
BP 2273
EP 2279
DI 10.1080/14656566.2016.1244530
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA ED3LP
UT WOS:000388750900004
PM 27690663
ER
PT J
AU Mayorova, TD
Tian, S
Cai, W
Semmens, DC
Odekunle, EA
Zandawala, M
Badi, Y
Rowe, ML
Egertova, M
Elphick, MR
AF Mayorova, Tatiana D.
Tian, Shi
Cai, Weigang
Semmens, Dean C.
Odekunle, Esther A.
Zandawala, Meet
Badi, Yusef
Rowe, Matthew L.
Egertova, Michaela
Elphick, Maurice R.
TI Localization of Neuropeptide Gene Expression in Larvae of an Echinoderm,
the Starfish Asterias rubens
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE neuropeptide precursor; mRNA in situ hybridization; larval nervous
system; bipinnaria; brachiolaria; attachment complex; Echinodermata
ID URCHIN STRONGYLOCENTROTUS-PURPURATUS; NERVOUS-SYSTEM; SEA-STAR;
BRACHIOLARIA LARVAE; HYDRACTINIA-ECHINATA; SALMFAMIDE NEUROPEPTIDE;
DENDRASTER-EXCENTRICUS; RFAMIDE NEUROPEPTIDES; NEURAL ARCHITECTURE;
ILYANASSA-OBSOLETA
AB Neuropeptides are an ancient class of neuronal signaling molecules that regulate a variety of physiological and behavioral processes in animals. The life cycle of many animals includes a larval stage(s) that precedes metamorphic transition to a reproductively active adult stage but, with the exception of Drosophila melanogaster and other insects, research on neuropeptide signaling has hitherto largely focused on adult animals. However, recent advances in genome/transcriptome sequencing have facilitated investigation of neuropeptide expression/function in the larvae of protostomian (e.g., the annelid Platynereis durnerilii) and deuterostomian (e.g., the urochordate Ciona intestinalis) invertebrates. Accordingly, here we report the first multi-gene investigation of larval neuropeptide precursor expression in a species belonging to the phylum Echinodermata the starfish Asterias rubens. Whole-mount mRNA in situ hybridization was used to visualize in bipinnaria and brachiolaria stage larvae the expression of eight neuropeptide precursors: L-type SALMFamide (Si), F-type SALMFamide (S2), vasopressin/oxytocin-type, NGFFYamide, thyrotropin-releasing hormone-type, gonadotropin-releasing hormone-type, calcitonin-type and corticotropin-releasing hormone-type. Expression of only three of the precursors (Si, S2, NGFFYamide) was observed in bipinnaria larvae but by the brachiolaria stage expression of all eight precursors was detected. An evolutionarily conserved feature of larval nervous systems is the apical organ and in starfish larvae this comprises the bilaterally symmetrical lateral ganglia, but only the Si and S2 precursors were found to be expressed in these ganglia. A prominent feature of brachiolaria larvae is the attachment complex, comprising the brachia and adhesive disk, which mediates larval attachment to a substratum prior to metamorphosis. Interestingly, all of the neuropeptide precursors examined here are expressed in the attachment complex, with distinctive patterns of expression suggesting potential roles for neuropeptides in the attachment process. Lastly, expression of several neuropeptide precursors is associated with ciliary bands, suggesting potential roles for the neuropeptides derived from these precursors in control of larval locomotion and/or feeding. In conclusion, our findings provide novel perspectives on the evolution and development of neuropeptide signaling systems and neuroanatomical insights into neuropeptide function in echinoderm larvae.
C1 [Mayorova, Tatiana D.; Tian, Shi; Cai, Weigang; Semmens, Dean C.; Odekunle, Esther A.; Zandawala, Meet; Badi, Yusef; Rowe, Matthew L.; Egertova, Michaela; Elphick, Maurice R.] Queen Mary Univ London, Sch Biol & Chem Sci, Dept Oranismal Biol, London, England.
[Mayorova, Tatiana D.] Russian Acad Sci, Koltzov Inst Dev Biol, Dev Neurobiol Lab, Moscow, Russia.
[Mayorova, Tatiana D.] NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Elphick, MR (reprint author), Queen Mary Univ London, Sch Biol & Chem Sci, Dept Oranismal Biol, London, England.
EM m.relphick@qmul.ac.uk
OI Zandawala, Meet/0000-0001-6498-2208
FU European Molecular Biology Organization fellowship [ASTF 168-2014];
Russian Foundation for Basic Research [15-04-04298]; BBSRC
[BB/M001644/1]; Leverhulme Trust [RGP-2013-351]; China Scholarship
Council; Society for Experimental Biology
FX This study was supported by a European Molecular Biology Organization
fellowship awarded to TM (ASTF 168-2014), Russian Foundation for Basic
Research (grant 15-04-04298 awarded to TM), BBSRC (grant BB/M001644/1),
the Leverhulme Trust (grant RGP-2013-351), the China Scholarship Council
and the Society for Experimental Biology.
NR 80
TC 0
Z9 0
U1 9
U2 9
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD DEC 1
PY 2016
VL 10
AR 553
DI 10.3389/fnins.2016.00553
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA ED7TT
UT WOS:000389075000001
PM 27990106
ER
PT J
AU Polizzotto, MN
Uldrick, TS
Wyvill, KM
Aleman, K
Peer, CJ
Bevans, M
Sereti, I
Maldarelli, F
Whitby, D
Marshall, V
Goncalves, PH
Khetani, V
Figg, WD
Steinberg, SM
Zeldis, JB
Yarchoan, R
AF Polizzotto, Mark N.
Uldrick, Thomas S.
Wyvill, Kathleen M.
Aleman, Karen
Peer, Cody J.
Bevans, Margaret
Sereti, Irini
Maldarelli, Frank
Whitby, Denise
Marshall, Vickie
Goncalves, Priscila H.
Khetani, Vikram
Figg, William D.
Steinberg, Seth M.
Zeldis, Jerome B.
Yarchoan, Robert
TI Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without
HIV Infection: A Phase I/II Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; MULTIPLE-MYELOMA; LENALIDOMIDE; TRIAL;
HUMAN-HERPESVIRUS-8; CHEMOTHERAPY; PACLITAXEL; RESPONSES; CEREBLON;
DISEASE
AB Purpose
Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS.
Methods
The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL).
Results
Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% Cl, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% Cl, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% Cl, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy (P = .03). Significant increases in CD4(+) and CD8(+) cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 (P = .05).
Conclusion
Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity. (C) 2016 by American Society of Clinical Oncology
C1 [Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen; Peer, Cody J.; Maldarelli, Frank; Goncalves, Priscila H.; Figg, William D.; Steinberg, Seth M.; Yarchoan, Robert] NCI, Bethesda, MD 20892 USA.
[Bevans, Margaret] NIH, Bethesda, MD USA.
[Sereti, Irini] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Whitby, Denise; Marshall, Vickie] Frederick Natl Canc Lab Canc Res, Frederick, MD USA.
[Khetani, Vikram; Zeldis, Jerome B.] Celgene Corp, Summit, NJ USA.
RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM robert.yarchoan@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; National Cancer Institute; Celgene
Corporation; National Cancer Institute [HHSN261200800001E]; Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, and by a Cooperative Research and
Development Agreement (CRADA) between the National Cancer Institute and
Celgene Corporation. It was further supported by the National Cancer
Institute, under Contract No. HHSN261200800001E (V.M. and D.W.) and by
the Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (I.S.).
NR 30
TC 1
Z9 1
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 1
PY 2016
VL 34
IS 34
BP 4125
EP +
DI 10.1200/JCO.2016.69.3812
PG 9
WC Oncology
SC Oncology
GA ED5YM
UT WOS:000388929900012
PM 27863194
ER
PT J
AU Hassan, R
Thomas, A
Alewine, C
Le, DT
Jaffee, EM
Pastan, I
AF Hassan, Raffit
Thomas, Anish
Alewine, Christine
Le, Dung T.
Jaffee, Elizabeth M.
Pastan, Ira
TI Mesothelin Immunotherapy for Cancer: Ready for Prime Time?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PANCREATIC DUCTAL ADENOCARCINOMA; PROLONGED PATIENT SURVIVAL;
TRIPLE-NEGATIVE BREAST; MONOCLONAL-ANTIBODY K1; EXTRAHEPATIC BILE-DUCT;
PHASE-I TRIAL; OVARIAN-CANCER; RECOMBINANT IMMUNOTOXIN; EXPRESSING
MESOTHELIN; PLEURAL MESOTHELIOMA
AB Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer. (C) 2016 by American Society of Clinical Oncology
C1 [Hassan, Raffit; Thomas, Anish; Alewine, Christine; Pastan, Ira] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Le, Dung T.; Jaffee, Elizabeth M.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
RP Hassan, R (reprint author), NCI, Thorac & GI Oncol Branch, Bldg 10CRC,Rm 4-5330, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute (NCI), Center for Cancer Research; NCI
[1K23CA163672]
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute (NCI), Center for Cancer
Research, and in part by Grant No. 1K23CA163672 from NCI (D.T.L.).
NR 87
TC 2
Z9 2
U1 8
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 1
PY 2016
VL 34
IS 34
BP 4171
EP +
DI 10.1200/JCO.2016.68.3672
PG 10
WC Oncology
SC Oncology
GA ED5YM
UT WOS:000388929900017
PM 27863199
ER
PT J
AU Bjorklund, P
Pacak, K
Crona, J
AF Bjorklund, P.
Pacak, K.
Crona, J.
TI Precision medicine in pheochromocytoma and paraganglioma: current and
future concepts
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT Symposium on New Genetics with Impact on Treatment of Endocrine Tumour
Disease
CY JUN 04-05, 2015
CL Uppsala, SWEDEN
DE cancer metabolism; neuroendocrine tumours; paraganglioma; personalized
medicine; pheochromocytoma; precision medicine
ID ENDOCRINE NEOPLASIA TYPE-2; VONHIPPEL-LINDAU-DISEASE; PANCREATIC
NEUROENDOCRINE TUMORS; AUTOSOMAL-DOMINANT PARAGANGLIOMA;
POSITRON-EMISSION-TOMOGRAPHY; OF-FUNCTION MUTATIONS; GERM-LINE
MUTATIONS; SUCCINATE-DEHYDROGENASE; GENE-MUTATIONS; MALIGNANT
PHEOCHROMOCYTOMAS
AB Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.
C1 [Bjorklund, P.; Crona, J.] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
[Pacak, K.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol Program Reprod & Adult E, Bethesda, MD USA.
RP Crona, J (reprint author), Uppsala Univ, Expt Surg Grp, Akademiska Sjukhuset,Ing 70,FOA2, S-75185 Uppsala, Sweden.
EM Joakim.crona@surgsci.uu.se
NR 148
TC 2
Z9 2
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
EI 1365-2796
J9 J INTERN MED
JI J. Intern. Med.
PD DEC
PY 2016
VL 286
IS 6
BP 559
EP 573
DI 10.1111/joim.12507
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA ED0ZN
UT WOS:000388573300004
ER
PT J
AU Valantine, H
AF Valantine, Hannah
TI NIH's Essential 21st-Century Research Challenge: Enhancing Scientific
Workforce Diversity
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID SCIENCE
C1 [Valantine, Hannah] NIH, Sci Workforce Divers, Bldg 10, Bethesda, MD 20892 USA.
RP Valantine, H (reprint author), NIH, Off Director, Sci Workforce Divers, 1 Ctr Dr,Rm 316, Bethesda, MD 20892 USA.
EM hannah.valantine@nih.gov
NR 18
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2016
VL 136
IS 12
BP 2327
EP 2329
DI 10.1016/j.jid.2016.07.042
PG 3
WC Dermatology
SC Dermatology
GA ED2KP
UT WOS:000388673500007
PM 27884286
ER
PT J
AU Jo, JH
Deming, C
Kennedy, EA
Conlan, S
Polley, EC
Ng, WL
Segre, JA
Kong, HH
AF Jo, Jay-Hyun
Deming, Clay
Kennedy, Elizabeth A.
Conlan, Sean
Polley, Eric C.
Ng, Weng-Lan
Segre, Julia A.
Kong, Heidi H.
CA NISC Comparative Sequencing Progra
TI Diverse Human Skin Fungal Communities in Children Converge in Adulthood
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; HEALTHY-SUBJECTS; MICROBIOTA; AGE;
PREVALENCE; DISEASES; GENDER; GENE
AB Understanding the skin mycobiome (fungal communities) is important because both commensal and pathogenic fungi can drive cutaneous disease depending on host status and body sites, including the scalp, feet, and groin. Interestingly, age may also affect skin fungal infections as certain dermatophytoses (i.e., tinea capitis) are more frequent in children than adults. We previously described the skin mycobiomes in healthy adults, showing lipophilic fungi Malassezia predominate in most skin sites. Because children have less sebaceous skin before puberty, we compared the fungal communities of primary clinical samples from healthy children and adults, based on sequencing of a fungal phylogenetic marker. Although Malassezia predominated on the trunk, head, and arm skin of adults (age 18-39), children (age <14) had more diverse fungal communities, for example, Eurotiomycetes, which includes common dermatophytes. Species-level classification showed that Malassezia globosa predominated in children. Collectively, our findings indicate that prepubertal skin is colonized by diverse fungi, whereas adult skin is predominantly obligatory lipophilic Malassezia, suggesting that fungal communities on skin profoundly shift during puberty. Mycobiome shifts during puberty are likely due to alterations in sebaceous gland activation and sebum composition. This study provides a foundational framework for studies investigating interactions between fungi, skin, and pediatric dermatophytosis.
C1 [Jo, Jay-Hyun; Kennedy, Elizabeth A.; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Deming, Clay; Conlan, Sean; Ng, Weng-Lan; Segre, Julia A.] NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Polley, Eric C.] NCI, Biometr Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Polley, Eric C.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN 55905 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.; Segre, JA (reprint author), NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
EM jsegre@nhgri.nih.gov; konghe@mail.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU NIH NCI/CCR; NHGRI; Korean Health Technology R&D Project, Ministry of
Health and Welfare, Republic of Korea [HI15C1095]; National Institutes
of Health [1UH2AR057504-01, 4UH3AR057504-02]
FX We thank Mark C. Udey, Keisuke Nagao, and Carmen Contreras-Sesvold for
their helpful discussions; and Sheila Phang and Amynah Pradhan for their
underlying efforts. This work was supported by NIH NCI/CCR and NHGRI
Intramural Research Program and a grant of the Korean Health Technology
R&D Project, Ministry of Health and Welfare, Republic of Korea
(HI15C1095; J-HJ). Sequencing was funded by grants from the National
Institutes of Health (1UH2AR057504-01 and 4UH3AR057504-02). This work
utilized the computational resources of the NIH HPC Biowulf cluster
(http://hpc.nih.gov).
NR 40
TC 1
Z9 1
U1 6
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2016
VL 136
IS 12
BP 2356
EP 2363
DI 10.1016/j.jid.2016.05.130
PG 8
WC Dermatology
SC Dermatology
GA ED2KP
UT WOS:000388673500014
PM 27476723
ER
PT J
AU Shi, JX
Zhou, WY
Zhu, B
Hyland, PL
Bennett, H
Xiao, YZ
Zhang, XJ
Burke, LS
Song, L
Hsu, CH
Yan, CH
Chen, QR
Meerzaman, D
Dagnall, CL
Burdette, L
Hicks, B
Freedman, ND
Chanock, SJ
Yeager, M
Tucker, MA
Goldstein, AM
Yang, XR
AF Shi, Jianxin
Zhou, Weiyin
Zhu, Bin
Hyland, Paula L.
Bennett, Hunter
Xiao, Yanzi
Zhang, Xijun
Burke, Laura S.
Song, Lei
Hsu, Chih Hao
Yan, Chunhua
Chen, Qingrong
Meerzaman, Daoud
Dagnall, Casey L.
Burdette, Laurie
Hicks, Belynda
Freedman, Neal D.
Chanock, Stephen J.
Yeager, Meredith
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
TI Rare Germline Copy Number Variations and Disease Susceptibility in
Familial Melanoma
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID PANCREATIC-CANCER; CDKN2A MUTATIONS; PRONE FAMILIES; MC1R VARIANTS;
RISK; ASSOCIATION; GENES; DUPLICATION; EXPRESSION; GENOMEL
AB Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and single nucleotide polymorphism arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanomaprone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g., PARP1, CDKN2A) or cosegregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare cosegregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.
C1 [Shi, Jianxin; Zhu, Bin; Hyland, Paula L.; Bennett, Hunter; Xiao, Yanzi; Burke, Laura S.; Song, Lei; Freedman, Neal D.; Chanock, Stephen J.; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Zhou, Weiyin; Zhang, Xijun; Dagnall, Casey L.; Burdette, Laurie; Hicks, Belynda; Yeager, Meredith] Frederick Natl Lab Canc Res, Canc Genom Res Lab, Leidos Biomed Res, Frederick, MD USA.
[Burke, Laura S.] Stat Collaborat Inc, Washington, DC USA.
[Hsu, Chih Hao; Yan, Chunhua; Chen, Qingrong; Meerzaman, Daoud] NCI, Computat Genom Res Grp, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
RP Yang, XR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM royang@mail.nih.gov
OI Dagnall, Casey/0000-0001-7334-4718
FU NIH, NCI, DCEG
FX We are indebted to the participating families, whose generosity and
cooperation have made this study possible. We thank Roche Nimblegen,
Oxford Gene Technology, and Biodiscovery for their molecular and
informatics services. We thank investigators from the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study (ATBC), Cancer Prevention Study-II
(CPS-II, American Cancer Society), Linxian Nutrition Intervention Trial
(NITC), The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer
Screening Trial, and Shanxi Upper Gastrointestinal Cancer Genetics Study
(SHNX), for allowing us to use control GWAS data. We also acknowledge
the contributions to this work that were made by Virginia Pichler,
Deborah Zametkin, Mary Fraser, and Barbara Rogers. This research was
supported by the Intramural Research Program of the NIH, NCI, DCEG.
NR 27
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2016
VL 136
IS 12
BP 2436
EP 2443
DI 10.1016/j.jid.2016.07.023
PG 8
WC Dermatology
SC Dermatology
GA ED2KP
UT WOS:000388673500023
PM 27476724
ER
PT J
AU Vanbellingen, T
Wapp, M
Stegmayer, K
Bertschi, M
Abela, E
Kubel, S
Nyffeler, T
Muri, R
Walther, S
Nef, T
Hallett, M
Bohlhalter, S
AF Vanbellingen, Tim
Wapp, Manuela
Stegmayer, Katharina
Bertschi, Manuel
Abela, Eugenio
Kubel, Stefanie
Nyffeler, Thomas
Muri, Rene
Walther, Sebastian
Nef, Tobias
Hallett, Mark
Bohlhalter, Stephan
TI Theta burst stimulation over premotor cortex in Parkinson's disease: an
explorative study on manual dexterity
SO JOURNAL OF NEURAL TRANSMISSION
LA English
DT Article
DE Manual dexterity; Premotor cortex; Limb kinetic apraxia; Parkinson's
disease; Coin rotation
ID TRANSCRANIAL MAGNETIC STIMULATION; LIMB-KINETIC APRAXIA; HUMAN MOTOR
CORTEX; FINGER DEXTERITY; EXCITABILITY
AB Dorsal pre-motor cortex (PMd) is thought to play a role in fine motor control. The aim of the present study was to investigate whether inhibitory or excitatory stimulation of PMd would have an impact on manual dexterity in Parkinson's disease (PD). Fifteen patients with PD participated in this study. High resolution structural MRI was used for neuro-navigated TBS. Participants were targeted with one train of TBS in three experimental sessions: sham stimulation over vertex, continuous TBS (cTBS) over PMd and intermittent TBS (iTBS) over PMd, respectively. Dexterity was measured by a coin rotation task (CRT), which is a valid measure to detect limb kinetic apraxia (LKA). Neither cTBS or iTBS significantly interfered with CRT. Post hoc sub-analysis in a group of PD patients (n = 5) with stronger baseline impairment, indicating LKA, revealed further deterioration of dexterous performance for the cTBS condition (p = 0.04). This sham controlled pilot study demonstrates that TBS over PMd does not significantly interfere with dexterity in PD. However, patients with dexterous impairment qualifying for LKA may be more susceptible to TBS.
C1 [Vanbellingen, Tim; Kubel, Stefanie; Nyffeler, Thomas; Bohlhalter, Stephan] Luzerner Kantonsspital, Neurol & Neurorehabil Ctr, Luzern, Switzerland.
[Vanbellingen, Tim; Bertschi, Manuel; Nyffeler, Thomas; Muri, Rene; Bohlhalter, Stephan] Univ Hosp Bern, Inselspital, Percept & Eye Movement Lab, Dept Neurol, Bern, Switzerland.
[Vanbellingen, Tim; Bertschi, Manuel; Nyffeler, Thomas; Muri, Rene; Bohlhalter, Stephan] Univ Hosp Bern, Inselspital, Percept & Eye Movement Lab, Dept Clin Res, Bern, Switzerland.
[Vanbellingen, Tim; Nyffeler, Thomas; Muri, Rene; Nef, Tobias] Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland.
[Wapp, Manuela; Abela, Eugenio] Univ Hosp Bern, Inselspital, Inst Diagnost & Intervent Neuroradiol, SCAN, Bern, Switzerland.
[Stegmayer, Katharina; Walther, Sebastian] Univ Hosp Psychiat, Bern, Switzerland.
[Nef, Tobias] Univ Bern, Gerontechnol & Rehabil Grp, Bern, Switzerland.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Bohlhalter, S (reprint author), Luzerner Kantonsspital, Neurol & Neurorehabil Ctr, Luzern, Switzerland.; Bohlhalter, S (reprint author), Univ Hosp Bern, Inselspital, Percept & Eye Movement Lab, Dept Neurol, Bern, Switzerland.; Bohlhalter, S (reprint author), Univ Hosp Bern, Inselspital, Percept & Eye Movement Lab, Dept Clin Res, Bern, Switzerland.
EM stephan.bohlhalter@luks.ch
RI Stegmayer, Katharina/A-6117-2017; Walther, Sebastian /E-3486-2010
OI Walther, Sebastian /0000-0003-4026-3561
FU Swiss National Science Foundation [320030_129668/1]
FX We are grateful for the skilled editing by Prof. Dr. Einar Wilder-Smith.
This study was supported by the Swiss National Science Foundation, Grant
No. 320030_129668/1.
NR 37
TC 0
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U1 1
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0300-9564
EI 1435-1463
J9 J NEURAL TRANSM
JI J. Neural Transm.
PD DEC
PY 2016
VL 123
IS 12
BP 1387
EP 1393
DI 10.1007/s00702-016-1614-6
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA ED1SX
UT WOS:000388626300004
PM 27619658
ER
PT J
AU Stein, MB
Ursano, RJ
Campbell-Sills, L
Colpe, LJ
Fullerton, CS
Heeringa, SG
Nock, MK
Sampson, NA
Schoenbaum, M
Sun, XY
Jain, S
Kessler, RC
AF Stein, Murray B.
Ursano, Robert J.
Campbell-Sills, Laura
Colpe, Lisa J.
Fullerton, Carol S.
Heeringa, Steven G.
Nock, Matthew K.
Sampson, Nancy A.
Schoenbaum, Michael
Sun, Xiaoying
Jain, Sonia
Kessler, Ronald C.
CA Army STARRS Collaborators
TI Prognostic Indicators of Persistent Post-Concussive Symptoms after
Deployment-Related Mild Traumatic Brain Injury: A Prospective
Longitudinal Study in US Army Soldiers
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE concussion; deployment; mental health; military; stress; traumatic brain
injury
ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY PERSONNEL; FORCES PERSONNEL;
ASSESS RISK; TRACK-TBI; POSTCONCUSSION; PREDICTORS; RESILIENCE;
POLYTRAUMA; MANAGEMENT
AB Mild traumatic brain injury (mTBI), or concussion, is prevalent in the military. The course of recovery can be highly variable. This study investigates whether deployment-acquired mTBI is associated with subsequent presence and severity of post-concussive symptoms (PCS) and identifies predictors of persistent PCS among US Army personnel who sustained mTBI while deployed to Afghanistan. We used data from a prospective longitudinal survey of soldiers assessed 1-2 months before a 10-month deployment to Afghanistan (T0), on redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were PCS at T2 and T3. Predictors considered were: sociodemographic factors, number of previous deployments, pre-deployment mental health and TBI history, and mTBI and other military-related stress during the index deployment. The study sample comprised 4518 soldiers, 822 (18.2%) of whom experienced mTBI during the index deployment. After adjusting for demographic, clinical, and deployment-related factors, deployment-acquired mTBI was associated with nearly triple the risk of reporting any PCS and with increased severity of PCS when symptoms were present. Among those who sustained mTBI, severity of PCS at follow-up was associated with history of pre-deployment TBI(s), pre-deployment psychological distress, more severe deployment stress, and loss of consciousness or lapse of memory (versus being "dazed'' only) as a result of deployment-acquired mTBI. In summary, we found that sustaining mTBI increases risk for persistent PCS. Previous TBI(s), pre-deployment psychological distress, severe deployment stress, and loss of consciousness or lapse of memory resulting from mTBI(s) are prognostic indicators of persistent PCS after an index mTBI. These observations may have actionable implications for prevention of chronic sequelae of mTBI in the military and other settings.
C1 [Stein, Murray B.; Campbell-Sills, Laura] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.; Sun, Xiaoying; Jain, Sonia] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
[Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Ursano, Robert J.; Fullerton, Carol S.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Rockville, MD 20857 USA.
[Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Nock, Matthew K.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
[Sampson, Nancy A.; Kessler, Ronald C.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA.
RP Stein, MB (reprint author), Univ Calif San Diego, 9500 Gilman Dr,Mailcode 0855, La Jolla, CA 92093 USA.
EM mstein@ucsd.edu
FU Department of the Army; U.S. Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
(NIH/NIMH) [U01MH087981]
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement number U01MH087981 with the U.S. Department of
Health and Human Services, National Institutes of Health, National
Institute of Mental Health (NIH/NIMH). The contents are solely the
responsibility of the authors and do not necessarily represent the views
of the Department of Health and Human Services, NIMH, the Veterans
Administration, Department of the Army, or the Department of Defense.
NR 33
TC 0
Z9 0
U1 6
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD DEC 1
PY 2016
VL 33
IS 23
BP 2125
EP 2132
DI 10.1089/neu.2015.4320
PG 8
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA ED2JG
UT WOS:000388669800008
PM 26905672
ER
PT J
AU Lin, C
Bradshaw, T
Perk, T
Harmon, S
Eickhoff, J
Jallow, N
Choyke, PL
Dahut, WL
Larson, S
Humm, JL
Perlman, S
Apolo, AB
Morris, MJ
Liu, G
Jeraj, R
AF Lin, Christie
Bradshaw, Tyler
Perk, Timothy
Harmon, Stephanie
Eickhoff, Jens
Jallow, Ngoneh
Choyke, Peter L.
Dahut, William L.
Larson, Steven
Humm, John Laurence
Perlman, Scott
Apolo, Andrea B.
Morris, Michael J.
Liu, Glenn
Jeraj, Robert
TI Repeatability of Quantitative F-18-NaF PET: A Multicenter Study
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE sodium fluoride; PET; repeatability; metastatic prostate cancer;
multicenter clinical trial
ID F-18-FLUORIDE PET/CT; BONE METASTASES; PROSTATE-CANCER; F-18-SODIUM
FLUORIDE; STATISTICAL-METHODS; MALIGNANT-TUMORS; LUNG-CANCER;
REPRODUCIBILITY; AGREEMENT; SPECT
AB F-18-NaF, a PET radiotracer of bone turnover, has shown potential as an imaging biomarker for assessing the response of bone metastases to therapy. This study aimed to evaluate the repeatability of F-18-NaF PET-derived SUV imaging metrics in individual bone lesions from patients in a multicenter study. Methods: Thirty-five castration-resistant prostate cancer patients with multiple metastases underwent 2 whole-body (test-retest) F-18-NaF PET/CT scans 3 +/- 2 d apart from 1 of 3 imaging sites. A total of 411 bone lesions larger than 1.5 cm(3) were automatically segmented using an SUV threshold of 15 g/mL. Two levels of analysis were performed: lesion-level, in which measures were extracted from individual-lesion regions of interest (ROI), and patient-level, in which all lesions within a patient were grouped into a patient ROI for analysis. Uptake was quantified with SUVmax, SUVmean, and SUVtotal. Test-retest repeatability was assessed using Bland Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation, critical percentage difference, and repeatability coefficient. The 95% limit of agreement (LOA) of the ratio between test and retest measurements was calculated. Results: At the lesion level, the coefficient of variation for SUVmax, SUVmean, and SUVtotal was 14.1%, 6.6%, and 25.5%, respectively. At the patient level, it was slightly smaller: 12.0%, 5.3%, and 18.5%, respectively. ICC was excellent (>0.95) for all SUV metrics. Lesion-level 95% LOA for SUVmax SUVmean, and SUVtotal was (0.76, 1.32), (0.88, 1.14), and (0.63, 1.71), respectively. Patient-level 95% LOA was slightly narrower, at (0.79, 1.26), (0.89, 1.10), and (0.70, 1.44), respectively. We observed significant differences in the variance and sample mean of lesion-level and patient-level measurements between imaging sites. Conclusion: The repeatability of SUVmax, SUVmean, and SUVtotal for F-18-NaF PET/CT was similar between lesion-arid patient-level ROIs. We found significant differences in lesion-level and patient-level distributions between sites. These results can be used to establish F-18-NaF PET-based criteria for assessing treatment response at the lesion and patient levels. F-18-NaF PET demonstrates repeatability levels useful for clinically quantifying the response of bone lesions to therapy.
C1 [Lin, Christie; Perk, Timothy; Harmon, Stephanie; Liu, Glenn; Jeraj, Robert] Univ Wisconsin, Dept Med Phys, 1530 Med Sci Ctr, Madison, WI 53706 USA.
[Bradshaw, Tyler; Perlman, Scott] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Eickhoff, Jens] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Jallow, Ngoneh] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA.
[Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dahut, William L.; Apolo, Andrea B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Larson, Steven; Humm, John Laurence] Mem Sloan Kettering Canc Ctr, Dept Radiol, Mol Imaging & Therapy Serv, 1275 York Ave, New York, NY 10021 USA.
[Perlman, Scott; Liu, Glenn; Jeraj, Robert] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Morris, Michael J.] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA.
RP Jeraj, R (reprint author), Wisconsin Inst Med Res, Dept Med Phys, 1111 Highland Ave,Room 7003, Madison, WI 53705 USA.
EM rjeraj@wisc.edu
FU Prostate Cancer Foundation (PCF) through the PCF Creativity Award; PCF
Mazzone Challenge Award
FX The costs of publication of this article were defrayed in part by the
payment of page charges. Therefore, and solely to indicate this fact,
this article is hereby marked "advertisement" in accordance with 18 USC
section 1734. This study was supported by the Prostate Cancer Foundation
(PCF) through the PCF Creativity Award and the PCF Mazzone Challenge
Award to Drs. Liu and Jeraj and was conducted within the Prostate Cancer
Clinical Trials Consortium (PCCTC). No other potential conflict of
interest relevant to this article was reported.
NR 31
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Z9 1
U1 1
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD DEC
PY 2016
VL 57
IS 12
BP 1872
EP 1879
DI 10.2967/jnumed.116.177295
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED8FG
UT WOS:000389106800012
PM 27445292
ER
PT J
AU Shrestha, SS
Liow, JS
Jenko, K
Ikawa, M
Zoghbi, SS
Innis, RB
AF Shrestha, Stal S.
Liow, Jeih-San
Jenko, Kimberly
Ikawa, Masamichi
Zoghbi, Sami S.
Innis, Robert B.
TI The 5-HT1A Receptor PET Radioligand C-11-CUMI-101 Has Significant
Binding to alpha(1)-Adrenoceptors in Human Cerebellum, Limiting Its Use
as a Reference Region
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE autoradiography; 5-HT1A receptor; CUMI-101; cerebellum;
alpha(1)-adrenoceptor; cross-reactivity
ID BRAIN; DISEASE; LIGAND
AB Prazosin, a potent and selective ai-adrenoceptor antagonist, displaces 25% of C-11-CUMI-101 ([O-methyl-C-11]2-(4-(4-(2-methoxy-phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione) binding in monkey cerebellum. We sought to estimate the percentage contamination of C-11-CUMI-101 binding to al-adrenoceptors in human cerebellum under in vivo conditions. In vitro receptor-binding techniques were used to measure alpha(1)-adrenoceptor density and the affinity of CUMI-101 for these receptors in human, monkey, and rat cerebellum. Methods: Binding potential (maximum number of binding sites x affinity [(1/dissociation constant]) was determined using in vitro homogenate binding assays in human, monkey, and rat cerebellum. H-3-prazosin was used to determine the maximum number of binding sites, as well as the dissociation constant of H-3-prazosin and the inhibition constant of CUMI-101. Results: alpha(1)-adrenoceptor density and the affinity of CUMI-101 for these receptors were similar across species. Cerebellar binding potentials were 3.7 for humans, 2.3 for monkeys, and 3.4 for rats. Conclusion: Reasoning by analogy, 25% of C-11-CUMI-101 uptake in human cerebellum reflects binding to alpha(1)-adrenoceptors, suggesting that the cerebellum is of limited usefulness as a reference tissue for quantification in human studies.
C1 [Shrestha, Stal S.; Liow, Jeih-San; Jenko, Kimberly; Ikawa, Masamichi; Zoghbi, Sami S.; Innis, Robert B.] NIMH, Mol Imaging Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Shrestha, SS (reprint author), NIH, 10 Ctr Dr,B1D43, Bethesda, MD 20892 USA.
EM stal.shrestha@nih.gov
FU Intramural Research Program of the National Institute of Mental Health
(NIH) [ZIAMH002795]
FX The costs of publication of this article were defrayed in part by the
payment of page charges. Therefore, and solely to indicate this fact,
this article is hereby marked "advertisement" in accordance with 18 USC
section 1734. This study was funded by the Intramural Research Program
of the National Institute of Mental Health (NIH project ZIAMH002795). No
other potential conflict of interest relevant to this article was
reported.
NR 11
TC 0
Z9 0
U1 1
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD DEC
PY 2016
VL 57
IS 12
BP 1945
EP 1948
DI 10.2967/jnumed.116.174151
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED8FG
UT WOS:000389106800023
PM 27587705
ER
PT J
AU Deroose, CM
Hindie, E
Kebebew, E
Goichot, B
Pacak, K
Taieb, D
Imperiale, A
AF Deroose, Christophe M.
Hindie, Elif
Kebebew, Electron
Goichot, Bernard
Pacak, Karel
Taieb, David
Imperiale, Alessio
TI Molecular Imaging of Gastroenteropancreatic Neuroendocrine Tumors:
Current Status and Future Directions
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE gastroenteropancreatic neuroendocrine tumors (GEP NETs); PET/CT;
Ga-68-somatostatin analogues; F-18-FDOPA; F-18-FDG
ID CONSENSUS GUIDELINES UPDATE; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY;
MEDIATED RADIONUCLIDE THERAPY; GA-68-DOTATATE PET/CT;
GASTROINTESTINAL-TRACT; RADIATION-DOSIMETRY; ENDOCRINE TUMORS; RECEPTOR
PET/CT; UNKNOWN ORIGIN; F-18-DOPA PET
AB Through diagnostic imaging and peptide receptor radionuclide therapy, nuclear medicine has eamed a major role in gastroenteropancreatic neuroendocrine tumors (GEP NETs). GEP NETs are diagnosed fortuitously or on the basis of symptoms or hormonal syndrome. The functional tumor characteristics shown by radionuclide imaging allow for more accurate staging and treatment selection. Tumor grade helps determine which tracer should be selected. In the past, (111)ln-pentetreotide has been successful in well-differentiated (G1 and G2) tumors. However, PET/CT imaging with novel somatostatin analogs (e.g., Ga-68-DOTATOC, Ga-68-DOTATATE, Ga-68-DOTANOC, and Cu-64-DOTATATE) now offers improved sensitivity. F-18-fluorodihydroxyphenylalanine (F-18-FDOPA) is another interesting radiopharmaceutical. F-18-FDOPA sensitivity is influenced by a tumor's capacity to take up, decarboxylate, and store amine precursors. F-18-FDOPA sensitivities are highest in ileal NETs and may also be helpful in insulinomas. A high uptake of F-18-FDG with a low uptake of somatostatin analog usually indicates poorly differentiated tumors (G3). Starting from these principles, this article discusses theranostic approaches to GEP NETs, taking into account both primary and metastatic lesions.
C1 [Deroose, Christophe M.] Univ Hosp Leuven, Nucl Med, Leuven, Belgium.
[Hindie, Elif] Univ Bordeaux, Haut Leveque Hosp, Nucl Med, Bordeaux, France.
[Hindie, Elif] Univ Bordeaux, LabEx TRAIL, Bordeaux, France.
[Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Goichot, Bernard] Strasbourg Univ Hosp, Internal Med, Strasbourg, France.
[Pacak, Karel] Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, NIH, Bethesda, MD USA.
[Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, Nucl Med, Marseille, France.
[Taieb, David] European Ctr Res Med Imaging, Marseille, France.
[Taieb, David] INSERM, UMR1068, Marseille, France.
[Imperiale, Alessio] Strasbourg Univ Hosp, Biophys & Nucl Med, Strasbourg, France.
[Imperiale, Alessio] Univ Strasbourg, CNRS, ICube, Strasbourg, France.
[Imperiale, Alessio] Univ Strasbourg, Fac Med, FMTS, Strasbourg, France.
RP Imperiale, A (reprint author), Hautepierre Univ Hosp, Biophys & Nucl Med, 1 Ave Moliere, F-67098 Strasbourg 09, France.
EM alessio.imperiale@chru-strasbourg.fr
NR 59
TC 3
Z9 3
U1 1
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD DEC
PY 2016
VL 57
IS 12
BP 1949
EP 1956
DI 10.2967/jnumed.116.179234
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED8FG
UT WOS:000389106800024
PM 27811124
ER
PT J
AU Rieves, D
Jacobs, P
AF Rieves, Dwaine
Jacobs, Paula
TI The Use of Published Clinical Study Reports to Support US Food and Drug
Administration Approval of Imaging Agents
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE FDA; clinical trial reports; drug approval; imaging agents
ID TRIALS
AB Pharmaceutical companies typically perform prospective, multicenter phase 3 clinical studies to support approval of a new imaging agent by the U.S. Food and Drug Administration (FDA). In uncommon situations, the FDA has approved imaging agents based solely, or in large part, on the clinical study experience described in published reports, including reports of exploratory (i.e., phase 1 or 2) studies performed at a single clinical site. We performed a survey of published reports to assess the potential of the reported information to support FDA approval of a commonly cited investigational imaging agent. Our survey revealed critical data limitations in most publications, all of which reported exploratory clinical studies. Here we summarize the precedent for FDA approval of imaging agents using effectiveness data from publications, FDA guidance, and our experience in reviewing publications. We also present a key-data checklist for investigators to consider in the design, conduct, and reporting of exploratory clinical studies for publication. We encourage editors and peer reviewers to consider requiring these key data when reviewing these reports for publication.
C1 [Rieves, Dwaine; Jacobs, Paula] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Rieves, D (reprint author), 1907 New Hampshire Ave NW, Washington, DC 20009 USA.
EM dcrieves@msn.com
NR 16
TC 0
Z9 0
U1 0
U2 0
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD DEC
PY 2016
VL 57
IS 12
BP 2022
EP 2026
DI 10.2967/jnumed.116.178814
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA ED8FG
UT WOS:000389106800035
PM 27445294
ER
PT J
AU Sarangapani, PS
Weaver, J
Parupudi, A
Besong, TMD
Adams, GG
Harding, SE
Manikwar, P
Castellanos, MM
Bishop, SM
Pathak, JA
AF Sarangapani, Prasad S.
Weaver, Justin
Parupudi, Arun
Besong, Tabot M. D.
Adams, Gary G.
Harding, Stephen E.
Manikwar, Prakash
Castellanos, Maria M.
Bishop, Steven M.
Pathak, Jai A.
TI Both Reversible Self-Association and Structural Changes Underpin
Molecular Viscoelasticity of mAb Solutions
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE viscosity; protein structure; mAb; light scattering (dynamic);
calorimetry (DSC); rheology; analytical ultra-centrifugation; diffusion;
protein formulation; protein aggregation
ID MONOCLONAL-ANTIBODY SOLUTIONS; PROTEIN AGGREGATION KINETICS; 2ND
VIRIAL-COEFFICIENT; CONCENTRATION-DEPENDENCE; ANALYTICAL
ULTRACENTRIFUGATION; INTERACTION PARAMETER; THERAPEUTIC PROTEINS;
VISCOSITY BEHAVIOR; GLOBULAR-PROTEINS; LIGHT-SCATTERING
AB The role of antibody structure (conformation) in solution rheology is probed. It is demonstrated here that pH-dependent changes in the tertiary structure of 2 mAb solutions lead to viscoelasticity and not merely a shear viscosity (eta) increase. Steady shear flow curves on mAb solutions are reported over broad pH (3.0 <= pH <= 8.7) and concentration (2 mg/mL <= c <= 120 mg/mL) ranges to comprehensively characterize their rheology. Results are interpreted using size exclusion chromatography, differential scanning calorimetry, analytical ultracentrifugation, near-UV circular dichroism, and dynamic light scattering. Changes in tertiary structure with concentration lead to elastic yield stress and increased solution viscosity in solution of "mAb1." These findings are supported by dynamic light scattering and differential scanning calorimetry, which show increased hydrodynamic radius of mAb1 at low pH and a reduced melting temperature T-m, respectively. Conversely, another molecule at 120 mg/mL solution concentration is a strong viscoelastic gel due to perturbed tertiary structure (seen in circular dichroism) at pH 3.0, but the same molecule responds as a viscous liquid due to reversible self-association at pH 7.4 (verified by analytical ultracentrifugation). Both protein-protein interactions and structural perturbations govern pH-dependent viscoelasticity of mAb solutions. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
C1 [Sarangapani, Prasad S.; Manikwar, Prakash; Bishop, Steven M.; Pathak, Jai A.] Medimmune Inc, Formulat Sci Dept, One MedImmune Way, Gaithersburg, MD 20878 USA.
[Weaver, Justin] Medimmune Inc, Proc & Purificat Sci Dept, One MedImmune Way, Gaithersburg, MD 20878 USA.
[Parupudi, Arun] Medimmune Inc, Analyt Biotechnol Dept, One MedImmune Way, Gaithersburg, MD 20878 USA.
[Besong, Tabot M. D.; Adams, Gary G.; Harding, Stephen E.] Univ Nottingham, Sch Biosci, Natl Ctr Macromol Hydrodynam, Coll Rd,Sutton Bonnington Campus, Loughborough LE12 5RD, Leics, England.
[Castellanos, Maria M.] Penn State Univ, Mat Sci & Engn Dept, University Pk, PA 16802 USA.
[Sarangapani, Prasad S.] Regeneron Pharmaceut, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
[Weaver, Justin] Alexion Pharmaceut, 100 Coll St, New Haven, CT 06510 USA.
[Castellanos, Maria M.] Univ Maryland NIST, Inst Biotechnol & Biosci Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
[Besong, Tabot M. D.] 4700 King Abdullah Univ Sci & Technol, Funct Nanomat Lab, Thuwal 239556900, Saudi Arabia.
[Besong, Tabot M. D.] NIAID, Vaccine Prod Program, Vaccine Res Ctr, NIH, 9 West Watkins Mill Rd, Gaithersburg, MD 20878 USA.
RP Pathak, JA (reprint author), Medimmune Inc, Formulat Sci Dept, One MedImmune Way, Gaithersburg, MD 20878 USA.
EM jai.pathak@nih.gov
NR 69
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD DEC
PY 2016
VL 105
IS 12
BP 3496
EP 3506
DI 10.1016/j.xphs.2016.08.020
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA ED7FO
UT WOS:000389027800005
PM 27793346
ER
PT J
AU Perszyk, RE
DiRaddo, JO
Strong, KL
Low, CM
Ogden, KK
Khatri, A
Vargish, GA
Pelkey, KA
Tricoire, L
Liotta, DC
Smith, Y
McBain, CJ
Traynelis, SF
AF Perszyk, Riley E.
DiRaddo, John O.
Strong, Katie L.
Low, Chian-Ming
Ogden, Kevin K.
Khatri, Alpa
Vargish, Geoffrey A.
Pelkey, Kenneth A.
Tricoire, Ludovic
Liotta, Dennis C.
Smith, Yoland
McBain, Chris J.
Traynelis, Stephen F.
TI GluN2D-Containing N-methyl-D-Aspartate Receptors Mediate Synaptic
Transmission in Hippocampal Interneurons and Regulate Interneuron
Activity
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID GLUN1/GLUN2D NMDA RECEPTORS; MAJOR DEPRESSIVE DISORDER; SUBUNIT
MESSENGER-RNA; PROOF-OF-CONCEPT; POSTNATAL-DEVELOPMENT; DEPENDENT
PLASTICITY; PYRAMIDAL NEURONS; RAT; EXPRESSION; CELLS
AB N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamatergic receptors that have been implicated in learning, development, and neuropathological conditions. They are typically composed of GluN1 and GluN2A-D subunits. Whereas a great deal is known about the role of GluN2A- and GluN2B-containing NMDARs, much less is known about GluN2D-containing NMDARs. Here we explore the subunit composition of synaptic NMDARs on hippocampal interneurons. GluN2D mRNA was detected by single-cell PCR and in situ hybridization in diverse interneuron subtypes in the CA1 region of the hippocampus. The GluN2D subunit was detectable by immunoblotting and immunohistochemistry in all subfields of the hippocampus in young and adult mice. In whole-cell patch-clamp recordings from acute hippocampal slices, (+)-CIQ, the active enantiomer of the positive allosteric modulator CIQ, significantly enhanced the amplitude of the NMDAR component of miniature excitatory postsynaptic currents (mEPSCs) in CA1 interneurons but not in pyramidal cells. (+)-CIQ had no effect in slices from Grin2d-/- mice, suggesting that GluN2D-containing NMDARs participate in excitatory synaptic transmission onto hippocampal interneurons. The time course of the NMDAR component of the mEPSC was unaffected by (1)-CIQ potentiation and was not accelerated in slices from Grin2d-/- mice compared with wild-type, suggesting that GluN2D does not detectably slow the NMDAR EPSC time course at this age. (+)-CIQ increased the activity of CA1 interneurons as detected by the rate and net charge transfer of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from CA1 pyramidal cells. These data provide evidence that interneurons contain synaptic NMDARs possessing a GluN2D subunit, which can influence interneuron function and signal processing.
C1 [Perszyk, Riley E.; DiRaddo, John O.; Ogden, Kevin K.; Khatri, Alpa; Traynelis, Stephen F.] Emory Univ, Dept Pharmacol, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
[DiRaddo, John O.; Strong, Katie L.; Liotta, Dennis C.] Emory Univ, Dept Chem, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
[Smith, Yoland] Emory Univ, Dept Neurol, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
[Smith, Yoland] Emory Univ, Yerkes Natl Primate Res Ctr, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
[Smith, Yoland] Emory Univ, Morris K Udall Ctr Excellence Parkinsons Dis Res, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
[Low, Chian-Ming] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore.
[Low, Chian-Ming] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anaesthesiol, Singapore, Singapore.
[Vargish, Geoffrey A.; Pelkey, Kenneth A.; Tricoire, Ludovic; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
RP Traynelis, SF (reprint author), Emory Univ, Sch Med, Dept Pharma, Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA.
EM strayne@emory.edu
FU National Institute of Mental Health's Psychoactive Drug Screening
Program [HHSN-271-2013-00017-C]; Pfizer; Janssen Research and
Development; NeurOp Inc.
FX The authors thank Phoung Le and Jing Zhang for outstanding technical
assistance; Susan Jenkins and Jean-Francois Pare for help with
immunostaining; and the National Institute of Mental Health's
Psychoactive Drug Screening Program, contract no. HHSN-271-2013-00017-C
(NIMH PDSP), for Ki determinations and receptor binding
profiles. The NIMH PDSP is directed by Bryan L. Roth at the University
of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at
NIMH, Bethesda, MD. Dennis Liotta, Katie Strong, and Stephen Traynelis
are inventors on Emory-owned IP. Dennis Liotta is a member of the Board
of Directors, and Stephen Traynelis is a paid consultant for NeurOp
Inc., a company developing NMDA receptor modulators. Stephen Traynelis
is a paid consultant for Pfizer and Janssen Research and Development.
The authors also thank Sharon Swanger for critical comments on the
manuscript.
NR 57
TC 0
Z9 0
U1 9
U2 9
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD DEC 1
PY 2016
VL 90
IS 6
BP 689
EP 702
DI 10.1124/mol.116.105130
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA ED3CQ
UT WOS:000388727300001
PM 27625038
ER
PT J
AU Sato, S
Huang, XP
Kroeze, WK
Roth, BL
AF Sato, Seiji
Huang, Xi-Ping
Kroeze, Wesley K.
Roth, Bryan L.
TI Discovery and Characterization of Novel GPR39 Agonists Allosterically
Modulated by Zinc
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MOLECULAR-MECHANISM; GLUCOSE-HOMEOSTASIS;
PANCREATIC-ISLETS; SENSING RECEPTOR; DRUG TARGETS; MOUSE;
IDENTIFICATION; PROSTATE; GHRELIN
AB In this study, we identified two previously described kinase inhibitors-3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl) imidazo[1,2-b] pyridazin-6-amine (LY2784544) and 1H-benzimidazole-4-carboxylic acid, 2-methyl-1-[[2-methyl-3-(trifluoromethyl) phenyl] methyl]-6-(4-morpholinyl)(GSK2636771)-as novel GPR39 agonists by unbiased small-molecule-based screening using a beta-arrestin recruitment screening approach (PRESTO-Tango). We characterized the signaling of LY2784544 and GSK2636771 and compared their signaling patterns with a previously described "GPR39-selective" agonist N-[3-chloro-4-[[[2-(methylamino)-6-(2-pyridinyl)-4-pyrimidinyl] amino] methyl] phenyl] methanesulfonamide (GPR39-C3) at both canonical and noncanonical signaling pathways. Unexpectedly, all three compounds displayed probe-dependent and pathway-dependent allosteric modulation by concentrations of zinc reported to be physiologic. LY2784544 and GS2636771 at GPR39 in the presence of zinc were generally as potent or more potent than their reported activities against kinases in whole-cell assays. These findings reveal an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR39 and expand the list of potential kinase off-targets to include understudied G protein-coupled receptors.
C1 [Sato, Seiji; Huang, Xi-Ping; Kroeze, Wesley K.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC USA.
RP Roth, BL (reprint author), Genet Med Bldg,Room 4072,120 Mason Farm Rd, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
FU National Institutes of Health [U01-MH104974]
FX This work was supported by the National Institutes of Health [Grant
U01-MH104974].
NR 60
TC 0
Z9 0
U1 5
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD DEC 1
PY 2016
VL 90
IS 6
BP 726
EP 737
DI 10.1124/mol.116.106112
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA ED3CQ
UT WOS:000388727300004
PM 27754899
ER
PT J
AU Sayers, BC
Germolec, DR
Walker, NJ
Shipkowski, KA
Stout, MD
Cesta, MF
Roycroft, JH
White, KL
Baker, GL
Dill, JA
Smith, MJ
AF Sayers, Brian C.
Germolec, Dori R.
Walker, Nigel J.
Shipkowski, Kelly A.
Stout, Matthew D.
Cesta, Mark F.
Roycroft, Joseph H.
White, Kimber L.
Baker, Gregory L.
Dill, Jeffrey A.
Smith, Matthew J.
TI Respiratory toxicity and immunotoxicity evaluations of microparticle and
nanoparticle C60 fullerene aggregates in mice and rats following
nose-only inhalation for 13 weeks
SO NANOTOXICOLOGY
LA English
DT Article
DE Buckminsterfullerene; immunotoxicity; inhalation; nanoparticles;
pulmonary inflammation
ID FEMALE B6C3F1 MICE; INCREASED PULMONARY TOXICITY; SCAVENGER RECEPTOR
CD163; HUMAN MONOCYTES; MACROPHAGE SUBPOPULATIONS; MONONUCLEAR
PHAGOCYTES; ULTRAFINE PARTICLES; LUNG INFLAMMATION; CARBON NANOTUBES;
ALPHA-SUBUNIT
AB C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50nm [nano-C60] and 1m [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2mg/m(3) (0.033 and 0.112 m(2)/m(3)), while micro-C60 exposures were 2, 15 and 30mg/m(3) (0.011, 0.084 and 0.167 m(2)/m(3)). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1 (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2mg/m(3) and micro-C60 exposure at 30mg/m(3). Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles.
C1 [Sayers, Brian C.; Germolec, Dori R.; Walker, Nigel J.; Shipkowski, Kelly A.; Stout, Matthew D.; Cesta, Mark F.; Roycroft, Joseph H.] NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
[White, Kimber L.; Smith, Matthew J.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA.
[Baker, Gregory L.; Dill, Jeffrey A.] Battelle Toxicol Northwest, Richland, WA USA.
[Smith, Matthew J.] Richard Bland Coll William & Mary, Petersburg, VA USA.
RP Sayers, BC (reprint author), DuPont Haskell Global Centers, 1090 Elkton Rd, Newark, DE 19711 USA.
EM Brian.C.Sayers@dupont.com
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Environmental Health Sciences (NIEHS); NTP
[N01-ES-55538, N01-ES-5553]
FX This work was supported [in part] by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS) and by NTP Contracts N01-ES-55538
and N01-ES-5553.
NR 56
TC 0
Z9 0
U1 9
U2 9
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1743-5390
EI 1743-5404
J9 NANOTOXICOLOGY
JI Nanotoxicology
PD DEC
PY 2016
VL 10
IS 10
BP 1458
EP 1468
DI 10.1080/17435390.2016.1235737
PG 11
WC Nanoscience & Nanotechnology; Toxicology
SC Science & Technology - Other Topics; Toxicology
GA ED3RU
UT WOS:000388767000008
PM 27618498
ER
PT J
AU Bielekova, B
AF Bielekova, Bibi
TI PERSPECTIVE Who dares, wins
SO NATURE
LA English
DT Editorial Material
ID MULTIPLE-SCLEROSIS
C1 [Bielekova, Bibi] US Natl Inst Neurol Disorders & Stroke, Neuroimmunol Dis Unit, Intramural Res Program, Bethesda, MD 20824 USA.
RP Bielekova, B (reprint author), US Natl Inst Neurol Disorders & Stroke, Neuroimmunol Dis Unit, Intramural Res Program, Bethesda, MD 20824 USA.
EM bibi.bielekova@nih.gov
FU US National Institute of Neurological Disorders and Stroke
NR 5
TC 0
Z9 0
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP S10
EP S10
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600005
PM 27902681
ER
PT J
AU Wilfert, AB
Chao, KR
Kaushal, M
Jain, S
Zollner, S
Adams, DR
Conrad, DF
AF Wilfert, Amy B.
Chao, Katherine R.
Kaushal, Madhurima
Jain, Sanjay
Zollner, Sebastian
Adams, David R.
Conrad, Donald F.
TI Genome-wide significance testing of variation from single case exomes
SO NATURE GENETICS
LA English
DT Article
ID SEQUENCE VARIANTS; GENETIC-VARIATION; HUMAN-DISEASE; MUTATION;
ASSOCIATION; GUIDELINES; FRAMEWORK
AB Standard techniques from genetic epidemiology are ill-suited to formally assess the significance of variants identified from a single case. We developed a statistical inference framework for identifying unusual functional variation from a single exome or genome, what we refer to as the 'n-of-one' problem. Using this approach we assessed our ability to identify the causal genotypes in over 5 million simulated cases of Mendelian disease, identifying 39% of disease genotypes as the most damaging unit in a typical exome background. We applied our approach to 129 n-of-one families from the Undiagnosed Diseases Program, nominating 60% of 30 disease genes determined to be diagnostic by a standard clinical workup. Our method can currently produce well-calibrated P values when applied to single genomes, can facilitate integration of multiple data types for n-of-one analyses, and, with further work, could become a widely used epidemiological method like linkage analysis or genome-wide association analysis.
C1 [Wilfert, Amy B.; Conrad, Donald F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Chao, Katherine R.; Adams, David R.] NIH, Undiagnosed Dis Program, Bldg 10, Bethesda, MD 20892 USA.
[Kaushal, Madhurima; Jain, Sanjay] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Jain, Sanjay; Conrad, Donald F.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63130 USA.
[Zollner, Sebastian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
RP Conrad, DF (reprint author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.; Conrad, DF (reprint author), Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63130 USA.
EM dconrad@genetics.wustl.edu
OI Conrad, Donald/0000-0003-3828-8970
FU US National Institutes of Health [R01MH101810]; March of Dimes
Foundation [6-FY14-430]
FX We thank D. Wilson and M. Stephens for helpful comments, N. Huang for
useful discussions and for providing updated versions of some
annotations used in this work, K. Vigh-Conrad for assistance in
preparing the figures, D. MacArthur, M. Lek and the members of the ExAC
Consortium for generous prepublication sharing of their data, and M.
Hoffmann and WU Kidney Translational Research Core (KTRC) for patient
enrolment and Genome Technology Access Center (GTAC) for exome
sequencing of CAKUT patients. Our work was supported by US National
Institutes of Health grant R01MH101810 (to D.F.C.), March of Dimes
Foundation grant #6-FY14-430 (to S.J.).
NR 21
TC 0
Z9 0
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD DEC
PY 2016
VL 48
IS 12
BP 1455
EP 1461
DI 10.1038/ng.3697
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA ED7BQ
UT WOS:000389011100005
PM 27776118
ER
PT J
AU Barban, N
Jansen, R
de Vlaming, R
Vaez, A
Mandemakers, JJ
Tropf, FC
Shen, X
Wilson, JF
Chasman, DI
Nolte, IM
Tragante, V
van der Laan, SW
Perry, JRB
Kong, A
Ahluwalia, TS
Albrecht, E
Yerges-Armstrong, L
Atzmon, G
Auro, K
Ayers, K
Bakshi, A
Ben-Avraham, D
Berger, K
Bergman, A
Bertram, L
Bielak, LF
Bjornsdottir, G
Bonder, MJ
Broer, L
Bui, M
Barbieri, C
Cavadino, A
Chavarro, JE
Turman, C
Concas, MP
Cordell, HJ
Davies, G
Eibich, P
Eriksson, N
Esko, T
Eriksson, J
Falahi, F
Felix, JF
Fontana, MA
Franke, L
Gandin, I
Gaskins, AJ
Gieger, C
Gunderson, EP
Guo, XQ
Hayward, C
He, CY
Hofer, E
Huang, HY
Joshi, PK
Kanoni, S
Karlsson, R
Kiechl, S
Kifley, A
Kluttig, A
Kraft, P
Lagou, V
Lecoeur, C
Lahti, J
Li-Gao, RF
Lind, PA
Liu, T
Makalic, E
Mamasoula, C
Matteson, L
Mbarek, H
McArdle, PF
McMahon, G
Meddens, SFW
Mihailov, E
Miller, M
Missmer, SA
Monnereau, C
van der Most, PJ
Myhre, R
Nalls, MA
Nutile, T
Kalafati, IP
Porcu, E
Prokopenko, I
Rajan, KB
Rich-Edwards, J
Rietveld, CA
Robino, A
Rose, LM
Rueedi, R
Ryan, KA
Saba, Y
Schmidt, D
Smith, JA
Stolk, L
Streeten, E
Tonjes, A
Thorleifsson, G
Ulivi, S
Wedenoja, J
Wellmann, J
Willeit, P
Yao, J
Yengo, L
Zhao, JH
Zhao, W
Zhernakova, DV
Amin, N
Andrews, H
Balkau, B
Barzilai, N
Bergmann, S
Biino, G
Bisgaard, H
Bonnelykke, K
Boomsma, DI
Buring, JE
Campbell, H
Cappellani, S
Ciullo, M
Cox, SR
Cucca, F
Toniolo, D
Davey-Smith, G
Deary, IJ
Dedoussis, G
Deloukas, P
van Duijn, CM
de Geus, EJC
Eriksson, JG
Evans, DA
Faul, JD
Sala, CF
Froguel, P
Gasparini, P
Girotto, G
Grabe, HJ
Greiser, KH
Groenen, PJF
de Haan, HG
Haerting, J
Harris, TB
Heath, AC
Heikkila, K
Hofman, A
Homuth, G
Holliday, EG
Hopper, J
Hypponen, E
Jacobsson, B
Jaddoe', VWV
Johannesson, M
Kahonen, M
Kajantie, E
Kardia, SLR
Keavney, B
Kolcic, I
Koponen, P
Kovacs, P
Kronenberg, F
Kutalik, Z
La Bianca, M
Lachance, G
Iacono, WG
Lai, S
Lehtimaki, T
Liewald, DC
Lindgren, CM
Liu, YM
Luben, R
Lucht, M
Luoto, R
Magnus, P
Magnusson, PKE
Martin, NG
McGue, M
McQuillan, R
Medland, SE
Meisinger, C
Mellstrom, D
Metspalu, A
Traglia, M
Milani, L
Mitchell, P
Montgomery, GW
Mook-Kanamori, D
de Mutsert, R
Nohr, EA
Ohlsson, C
Olsen, P
Ong, KK
Paternoster, L
Pattie, A
Penninx, BWJH
Perola, M
Peyser, PA
Pirastu, M
Polasek, O
Power, C
Kaprio, J
Raffel, LJ
Raikkonen, K
Raitakari, O
Ridker, PM
Ring, SM
Roll, K
Rudan, I
Ruggiero, D
Rujescu, D
Salomaa, V
Schlessinger, D
Schmidt, H
Schmidt, R
Schupf, N
Smit, J
Sorice, R
Spector, TD
Starr, JM
Stockl, D
Strauch, K
Stumvoll, M
Swertz, MA
Thorsteinsdottir, U
Thurik, AR
Timpson, NJ
Tung, JY
Uitterlinden, AG
Vaccargiu, S
Viikari, J
Vitart, V
Volzke, H
Vollenweider, P
Vuckovic, D
Waage, J
Wagner, GG
Wang, JJ
Wareham, NJ
Weir, DR
Willemsen, G
Willeit, J
Wright, AF
Zondervan, KT
Stefansson, K
Krueger, RF
Lee, JJ
Benjamin, DJ
Cesarini, D
Koellinger, PD
den Hoed, M
Snieder, H
Mills, MC
AF Barban, Nicola
Jansen, Rick
de Vlaming, Ronald
Vaez, Ahmad
Mandemakers, Jornt J.
Tropf, Felix C.
Shen, Xia
Wilson, James F.
Chasman, Daniel I.
Nolte, Illa M.
Tragante, Vinicius
van der Laan, Sander W.
Perry, John R. B.
Kong, Augustine
Ahluwalia, Tarunveer S.
Albrecht, Eva
Yerges-Armstrong, Laura
Atzmon, Gil
Auro, Kirsi
Ayers, Kristin
Bakshi, Andrew
Ben-Avraham, Danny
Berger, Klaus
Bergman, Aviv
Bertram, Lars
Bielak, Lawrence F.
Bjornsdottir, Gyda
Bonder, Marc Jan
Broer, Linda
Bui, Minh
Barbieri, Caterina
Cavadino, Alana
Chavarro, Jorge E.
Turman, Constance
Concas, Maria Pina
Cordell, Heather J.
Davies, Gail
Eibich, Peter
Eriksson, Nicholas
Esko, Tonu
Eriksson, Joel
Falahi, Fahimeh
Felix, Janine F.
Fontana, Mark Alan
Franke, Lude
Gandin, Ilaria
Gaskins, Audrey J.
Gieger, Christian
Gunderson, Erica P.
Guo, Xiuqing
Hayward, Caroline
He, Chunyan
Hofer, Edith
Huang, Hongyan
Joshi, Peter K.
Kanoni, Stavroula
Karlsson, Robert
Kiechl, Stefan
Kifley, Annette
Kluttig, Alexander
Kraft, Peter
Lagou, Vasiliki
Lecoeur, Cecile
Lahti, Jari
Li-Gao, Ruifang
Lind, Penelope A.
Liu, Tian
Makalic, Enes
Mamasoula, Crysovalanto
Matteson, Lindsay
Mbarek, Hamdi
McArdle, Patrick F.
McMahon, George
Meddens, S. Fleur W.
Mihailov, Evelin
Miller, Mike
Missmer, Stacey A.
Monnereau, Claire
van der Most, Peter J.
Myhre, Ronny
Nalls, Mike A.
Nutile, Teresa
Kalafati, Ioanna Panagiota
Porcu, Eleonora
Prokopenko, Inga
Rajan, Kumar B.
Rich-Edwards, Janet
Rietveld, Cornelius A.
Robino, Antonietta
Rose, Lynda M.
Rueedi, Rico
Ryan, Kathleen-A
Saba, Yasaman
Schmidt, Daniel
Smith, Jennifer A.
Stolk, Lisette
Streeten, Elizabeth
Toenjes, Anke
Thorleifsson, Gudmar
Ulivi, Sheila
Wedenoja, Juho
Wellmann, Juergen
Willeit, Peter
Yao, Jie
Yengo, Loic
Zhao, Jing Hua
Zhao, Wei
Zhernakova, Dania V.
Amin, Najaf
Andrews, Howard
Balkau, Beverley
Barzilai, Nir
Bergmann, Sven
Biino, Ginevra
Bisgaard, Hans
Bonnelykke, Klaus
Boomsma, Dorret I.
Buring, Julie E.
Campbell, Harry
Cappellani, Stefania
Ciullo, Marina
Cox, Simon R.
Cucca, Francesco
Toniolo, Daniela
Davey-Smith, George
Deary, Ian J.
Dedoussis, George
Deloukas, Panos
van Duijn, Cornelia M.
de Geus, Eco J. C.
Eriksson, Johan G.
Evans, Denis A.
Faul, Jessica D.
Sala, Cinzia Felicita
Froguel, Philippe
Gasparini, Paolo
Girotto, Giorgia
Grabe, Hans-Joergen
Greiser, Karin Halina
Groenen, Patrick J. F.
de Haan, Hugoline G.
Haerting, Johannes
Harris, Tamara B.
Heath, Andrew C.
Heikkila, Kauko
Hofman, Albert
Homuth, Georg
Holliday, Elizabeth G.
Hopper, John
Hypponen, Elina
Jacobsson, Bo
Jaddoe', Vincent W. V.
Johannesson, Magnus
Kahonen, Mika
Kajantie, Eero
Kardia, Sharon L. R.
Keavney, Bernard
Kolcic, Ivana
Koponen, Paivikki
Kovacs, Peter
Kronenberg, Florian
Kutalik, Zoltan
La Bianca, Martina
Lachance, Genevieve
Iacono, William G.
Lai, Sandra
Lehtimaki, Terho
Liewald, David C.
Lindgren, Cecilia M.
Liu, Yongmei
Luben, Robert
Lucht, Michael
Luoto, Riitta
Magnus, Per
Magnusson, Patrik K. E.
Martin, Nicholas G.
McGue, Matt
McQuillan, Ruth
Medland, Sarah E.
Meisinger, Christa
Mellstrom, Dan
Metspalu, Andres
Traglia, Michela
Milani, Lili
Mitchell, Paul
Montgomery, Grant W.
Mook-Kanamori, Dennis
de Mutsert, Renee
Nohr, Ellen A.
Ohlsson, Claes
Olsen, Porn
Ong, Ken K.
Paternoster, Lavinia
Pattie, Alison
Penninx, Brenda W. J. H.
Perola, Markus
Peyser, Patricia A.
Pirastu, Mario
Polasek, Ozren
Power, Chris
Kaprio, Jaakko
Raffel, Leslie J.
Raikkonen, Katri
Raitakari, Olli
Ridker, Paul M.
Ring, Susan M.
Roll, Kathryn
Rudan, Igor
Ruggiero, Daniela
Rujescu, Dan
Salomaa, Veikko
Schlessinger, David
Schmidt, Helena
Schmidt, Reinhold
Schupf, Nicole
Smit, Johannes
Sorice, Rossella
Spector, Tim D.
Starr, John M.
Stockl, Doris
Strauch, Konstantin
Stumvoll, Michael
Swertz, Morris A.
Thorsteinsdottir, Unnur
Thurik, A. Roy
Timpson, Nicholas J.
Tung, Joyce Y.
Uitterlinden, Andre G.
Vaccargiu, Simona
Viikari, Jorma
Vitart, Veronique
Voelzke, Henry
Vollenweider, Peter
Vuckovic, Dragana
Waage, Johannes
Wagner, Gert G.
Wang, Jie Jin
Wareham, Nicholas J.
Weir, David R.
Willemsen, Gonneke
Willeit, Johann
Wright, Alan F.
Zondervan, Krina T.
Stefansson, Kari
Krueger, Robert F.
Lee, James J.
Benjamin, Daniel J.
Cesarini, David
Koellinger, Philipp D.
den Hoed, Marcel
Snieder, Harold
Mills, Melinda C.
CA Bios Consortium
LifeLines Cohort Study
TI Genome-wide analysis identifies 12 loci influencing human reproductive
behavior
SO NATURE GENETICS
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; GENE PRIORITIZATION; QUALITY-CONTROL;
HUMAN-DISEASES; G1 PHASE; ASSOCIATION; FERTILITY; MOUSE; PROTEIN; AGE
AB The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.
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[de Vlaming, Ronald; Rietveld, Cornelius A.; Thurik, A. Roy; Uitterlinden, Andre G.; Koellinger, Philipp D.] Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.
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[Vaez, Ahmad; Nolte, Illa M.; Falahi, Fahimeh; van der Most, Peter J.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Vaez, Ahmad] Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Esfahan, Iran.
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[McMahon, George] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
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[Miller, Mike; Iacono, William G.; McGue, Matt; Krueger, Robert F.; Lee, James J.] Univ Minnesota, Dept Psychol, Minneapolis, MN USA.
[Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA.
[Missmer, Stacey A.] Harvard Med Sch, Boston, MA USA.
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[Porcu, Eleonora; Cucca, Francesco; Lai, Sandra] Cittadella Univ Monserrato, Ist Ric Genet & Biomed, CMR, Cagliari, Italy.
[Porcu, Eleonora; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy.
[Prokopenko, Inga] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Prokopenko, Inga; Lindgren, Cecilia M.] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
[Prokopenko, Inga; Lindgren, Cecilia M.] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Rajan, Kumar B.; Evans, Denis A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
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[Rich-Edwards, Janet] Harvard Med Sch, Boston, MA USA.
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[Rueedi, Rico; Bergmann, Sven] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.
[Rueedi, Rico; Bergmann, Sven; Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Saba, Yasaman; Schmidt, Helena] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria.
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[Willeit, Peter] Kings British Heart Fdn Ctr, Kings Coll London, London, England.
[Willeit, Peter] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
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[Andrews, Howard] New York State Psychiat Inst & Hosp, Data Coordinating Ctr, New York, NY 10032 USA.
[Biino, Ginevra] Natl Res Council Italy, Inst Mol Genet, Pavia, Italy.
[Ciullo, Marina; Sorice, Rossella] IRCCS Neuromed, Pozzilli, Isernia, Italy.
[Davey-Smith, George; Paternoster, Lavinia; Ring, Susan M.; Timpson, Nicholas J.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
[Eriksson, Johan G.; Lucht, Michael] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
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[Gasparini, Paolo; Girotto, Giorgia; Vuckovic, Dragana] Sidra, Div Expt Genet, Doha, Qatar.
[Grabe, Hans-Joergen] Univ Med Greifswald, Dept Psychiat, Greifswald, Germany.
[Greiser, Karin Halina] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Groenen, Patrick J. F.] Erasmus Univ, Erasmus Sch Econ, Econometric Inst, Rotterdam, Netherlands.
[Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Heath, Andrew C.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia.
[Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia.
[Holliday, Elizabeth G.] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Hypponen, Elina] Univ South Australia, Sansom Inst Hlth Res, Ctr Populat Hlth Res, Adelaide, SA, Australia.
[Hypponen, Elina] Univ South Australia, Sch Hlth Sci, Adelaide, SA, Australia.
[Hypponen, Elina] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
[Jacobsson, Bo] Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden.
[Johannesson, Magnus] Stockholm Sch Econ, Dept Econ, Stockholm, Sweden.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Tampere, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland.
[Kahonen, Mika] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Kajantie, Eero] Helsinki Univ Cent Hosp, Childrens Hosp, Helsinki, Finland.
[Kajantie, Eero] Univ Helsinki, Helsinki, Finland.
[Kajantie, Eero] Oulu Univ Hosp, MRC Oulu, Dept Obstet & Gynecol, Oulu, Finland.
[Kajantie, Eero] Univ Oulu, Oulu, Finland.
[Keavney, Bernard] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England.
[Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia.
[Koponen, Paivikki] Natl Inst Hlth & Welf, Hlth Monitoring Unit, Helsinki, Finland.
[Kovacs, Peter; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.
[Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol, Innsbruck, Austria.
[Kutalik, Zoltan] Lausanne Univ Hosp CHUV, Inst Social & Prevent Med, Lausanne, Switzerland.
[Lachance, Genevieve; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere, Finland.
[Lindgren, Cecilia M.] NIHR Oxford Biomed Res Ctr, Oxford, England.
[Lindgren, Cecilia M.] Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Luben, Robert] Univ Cambridge, Strangeways Res Lab, Cambridge, England.
[Luoto, Riitta] UKK Inst Hlth Promot, Tampere, Finland.
[McGue, Matt] Univ Southern Denmark, Inst Publ Hlth, Danish Aging Res Ctr, Odense, Denmark.
[McGue, Matt] Univ Southern Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark.
[Meisinger, Christa] Cent Hosp Augsburg, MONICA KORA Myocardial Infarct Registry, Augsburg, Germany.
[Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia.
[Montgomery, Grant W.] Univ Queensland, Mol Biosci, Brisbane, Qld, Australia.
[Mook-Kanamori, Dennis] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
[Mook-Kanamori, Dennis] King Faisal Specialist Hosp & Res Ctr, Epidemiol Sect, Dept BESC, Riyadh, Saudi Arabia.
[Nohr, Ellen A.] Univ Southern Denmark, Dept Clin Res, Res Unit Gynecol & Obstet, Odense, Denmark.
[Olsen, Porn] Aarhus Univ, Dept Clin Epidemiol, Aarhus, Denmark.
[Raffel, Leslie J.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
[Rujescu, Dan] Martin Luther Univ Halle Wittenberg, Dept Psychiat, Halle, Saale, Germany.
[Schlessinger, David] NIA, Lab Genet, Baltimore, MD 21224 USA.
[Schupf, Nicole; Stockl, Doris] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA.
[Schupf, Nicole; Stockl, Doris] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[Strauch, Konstantin] Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Thurik, A. Roy] Montpellier Business Sch, Montpellier, France.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Viikari, Jorma] Turku Univ Hosp, Div Med, Turku, Finland.
[Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Vollenweider, Peter] Lausanne Univ Hosp CHUV, Dept Internal Med, Lausanne, Switzerland.
[Wagner, Gert G.] Max Planck Inst Human Dev, German Socioecon Panel Study SOEP, Berlin, Germany.
[Wagner, Gert G.] Berlin Univ Technol TUB, Berlin, Germany.
[Zondervan, Krina T.] Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England.
[Zondervan, Krina T.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England.
[Benjamin, Daniel J.] Natl Bur Econ Res, Cambridge, MA 02138 USA.
[Cesarini, David] NYU, Dept Econ, New York, NY 10003 USA.
[Cesarini, David] Res Inst Ind Econ, Stockholm, Sweden.
[den Hoed, Marcel] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
RP Barban, N; Mills, MC (reprint author), Univ Oxford, Dept Sociol, Oxford, England.; Snieder, H (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.; den Hoed, M (reprint author), Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
EM nicola.barban@sociology.ox.ac.uk; marcel.den_hoed@medsci.uu.se;
h.snieder@umcg.nl; melinda.mills@nuffield.ox.ac.uk
RI Bertram, Lars/K-3889-2015; Wang, Jie Jin/P-1499-2014; Mitchell,
Paul/P-1498-2014; Bisgaard, Hans/N-4761-2016; Davey Smith,
George/A-7407-2013; Kronenberg, Florian/B-1736-2008; Johannesson,
Magnus/E-9680-2011; Colaus, PsyColaus/K-6607-2013; Magnusson,
Patrik/C-4458-2017; Yengo, Loic/D-2692-2017; Polasek, Ozren/B-6002-2011;
Kolcic, Ivana/E-2713-2017;
OI Lahti, Jari/0000-0002-4310-5297; Raikkonen, Katri/0000-0003-3124-3470;
de Geus, Eco/0000-0001-6022-2666; Hypponen, Elina/0000-0003-3670-9399;
van der Laan, Sander W./0000-0001-6888-1404; Bertram,
Lars/0000-0002-0108-124X; Wang, Jie Jin/0000-0001-9491-4898; Bisgaard,
Hans/0000-0003-4131-7592; Davey Smith, George/0000-0002-1407-8314;
Kronenberg, Florian/0000-0003-2229-1120; Johannesson,
Magnus/0000-0001-8759-6393; Yengo, Loic/0000-0002-4272-9305; Polasek,
Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Jansen,
Rick/0000-0002-3333-6737; Wedenoja, Juho/0000-0002-6155-0378; Bakshi,
Andrew/0000-0001-5650-7036; Girotto, Giorgia/0000-0003-4507-6589; Bui,
Minh/0000-0002-9099-6870; Barban, Nicola/0000-0002-4362-4652; Kaprio,
Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189;
Smith, Jennifer/0000-0002-3575-5468; Bonder, Marc
Jan/0000-0002-8431-3180
FU ERC Consolidator Grant SOCIOGENOME [615603]; Dutch Science Foundation
(NWO) grant (VIDI grant) [452-10-012]; UK ESRC/NCRM SOCGEN grant
[ES/N011856/1]; European Union [320116]; Wellcome Trust ISSF; John Fell
Fund; Swedish Research Council [2015-03657, 421-2013-1061,
537-2014-371]; Swedish Heart-Lung Foundation [20140543]; US National
Science Foundation (EAGER: 'Workshop for the Formation of a Social
Science Genetic Association Consortium'); National Institutes of Health
Office of Behavioral and Social Science Research; Ragnar Soderberg
Foundation [E9/11]; Jan Wallander and Tom Hedelius Foundation; ERC
[647648 EdGe]; Pershing Square Fund of the Foundations of Human
Behavior; NIA/NIH [P01-AG005842, P01-AG005842-20S2, P30-AG012810,
T32-AG000186-23, R01-AG042568-02]
FX For full acknowledgments, see the Supplementary Note. Funding to lead
this consortium was provided by grants awarded to M.C.M.: ERC
Consolidator Grant SOCIOGENOME (615603), a Dutch Science Foundation
(NWO) grant (VIDI grant 452-10-012), a UK ESRC/NCRM SOCGEN grant
(ES/N011856/1), the European Union's FP7 Families And Societies project
(320116), and the Wellcome Trust ISSF and John Fell Fund. M.d.H. was
supported by grants from the Swedish Research Council (2015-03657) and
the Swedish Heart-Lung Foundation (20140543). Research was carried out
in collaboration with the Social Science Genetic Association Consortium
(SSGAC), with funding from the US National Science Foundation (EAGER:
'Workshop for the Formation of a Social Science Genetic Association
Consortium'), a Supplementary grant from the National Institutes of
Health Office of Behavioral and Social Science Research, the Ragnar
Soderberg Foundation (E9/11), the Swedish Research Council
(421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC
Consolidator Grant (647648 EdGe), the Pershing Square Fund of the
Foundations of Human Behavior and the NIA/NIH through grants
P01-AG005842, P01-AG005842-20S2, P30-AG012810 and T32-AG000186-23 to
NBER and R01-AG042568-02 to the University of Southern California. X.S.
was supported by a grant from the Swedish Research Council
(537-2014-371). We thank X. Ding for research assistance, N. Pirastu, K.
Coward and L. Layman for valuable comments, and the University of Oxford
Advanced Research Computing (ARC) facility
(http://dx.doi.org/10.5281/zenodo.22558). This research has been
conducted using the UK Biobank Resource.
NR 79
TC 1
Z9 1
U1 21
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD DEC
PY 2016
VL 48
IS 12
BP 1462
EP 1472
DI 10.1038/ng.3698
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA ED7BQ
UT WOS:000389011100006
PM 27798627
ER
PT J
AU Lyons, JJ
Yu, XM
Hughes, JD
Le, QT
Jamil, A
Bai, Y
Ho, N
Zhao, M
Liu, YH
O'Connell, MP
Trivedi, NN
Nelson, C
DiMaggio, T
Jones, N
Matthews, H
Lewis, KL
Oler, AJ
Carlson, RJ
Arkwright, PD
Hong, C
Agama, S
Wilson, TM
Tucker, S
Zhang, Y
McElwee, JJ
Pao, M
Glover, SC
Rothenberg, ME
Hohman, RJ
Stone, KD
Caughey, GH
Heller, T
Metcalfe, DD
Biesecker, LG
Schwartz, LB
Milner, JD
AF Lyons, Jonathan J.
Yu, Xiaomin
Hughes, Jason D.
Le, Quang T.
Jamil, Ali
Bai, Yun
Ho, Nancy
Zhao, Ming
Liu, Yihui
O'Connell, Michael P.
Trivedi, Neil N.
Nelson, Celeste
DiMaggio, Thomas
Jones, Nina
Matthews, Helen
Lewis, Katie L.
Oler, Andrew J.
Carlson, Ryan J.
Arkwright, Peter D.
Hong, Celine
Agama, Sherene
Wilson, Todd M.
Tucker, Sofie
Zhang, Yu
McElwee, Joshua J.
Pao, Maryland
Glover, Sarah C.
Rothenberg, Marc E.
Hohman, Robert J.
Stone, Kelly D.
Caughey, George H.
Heller, Theo
Metcalfe, Dean D.
Biesecker, Leslie G.
Schwartz, Lawrence B.
Milner, Joshua D.
TI Elevated basal serum tryptase identifies a multisystem disorder
associated with increased TPSAB1 copy number
SO NATURE GENETICS
LA English
DT Article
ID JOINT HYPERMOBILITY SYNDROME; EPIDEMIOLOGY
AB Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown(1,2). Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding alpha-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of alpha-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of alpha-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.
C1 [Lyons, Jonathan J.; Yu, Xiaomin; Jamil, Ali; Bai, Yun; Liu, Yihui; O'Connell, Michael P.; Nelson, Celeste; DiMaggio, Thomas; Carlson, Ryan J.; Agama, Sherene; Wilson, Todd M.; Tucker, Sofie; Stone, Kelly D.; Metcalfe, Dean D.; Milner, Joshua D.] NIAID, Lab Allerg Dis, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hughes, Jason D.; McElwee, Joshua J.] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Le, Quang T.; Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
[Ho, Nancy; Heller, Theo] NIDDK, Liver Dis Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Zhao, Ming; Hohman, Robert J.] NIAID, Res Technol Branch, US Natl Inst Hlth, Rockville, MD USA.
[Trivedi, Neil N.; Caughey, George H.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA USA.
[Trivedi, Neil N.; Caughey, George H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Trivedi, Neil N.; Caughey, George H.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Jones, Nina] SAIC Frederick Inc, Frederick Natl Lab Clin Res, Clin Res Directorate CMRP, Frederick, MD USA.
[Matthews, Helen] NIAID, Immunol Lab, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
[Lewis, Katie L.; Hong, Celine; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Oler, Andrew J.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Arkwright, Peter D.] Univ Manchester, Royal Manchester Childrens Hosp, Inst Infect Immun & Resp Med, Manchester, Lancs, England.
[Zhang, Yu] NIAID, Host Def Lab, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Pao, Maryland] NIMH, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Glover, Sarah C.] Univ Florida, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA.
[Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45229 USA.
RP Milner, JD (reprint author), NIAID, Lab Allerg Dis, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jdmilner@niaid.nih.gov
OI Lyons, Jonathan/0000-0002-2346-8189
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, NIH; NCI [HHSN261200800001E]; ARTrust/The
Mastocytosis Society Research Award in Mastocytosis; Mast Cell
Activation Syndrome; NIH [HL024136]; Intramural Research Program of the
NHGRI
FX We thank the patients, their families, and the numerous healthy
volunteers who contributed to this research, as well as the clinical
staff of the LAD, NIMH, NIDDK, and NHGRI for their efforts, in
particular the Gastrointestinal and Psychiatry Consultation Liaison
Services physicians, especially T. Alqassem, who participated in the
care of these patients. We thank all the referring care providers, in
particular A. Maitland and M. Carter for each referring several families
for evaluation. We also acknowledge the collaborative spirit and efforts
of the NIAMS and NIAID clinical genomics programs, specifically the
investigators (M.J. Lenardo, H.S. Su, and R.T. Goldbach-Mansky) who
shared clinical genomics data and study samples. We also thank M.J.
Lenardo, W. Gahl, C. Akin, and J.-L. Casanova for their review of the
manuscript. Lastly, we thank D. Abdulazeez of VCU for performing the
tryptase immunoassays. This study was supported in part by the Division
of Intramural Research of the National Institute of Allergy and
Infectious Diseases, NIH. The involvement of N.J. was funded by NCI
contract HHSN261200800001E. Funding was also provided in part by
ARTrust/The Mastocytosis Society Research Award in Mastocytosis and/or
Mast Cell Activation Syndrome (J.J.L.) and by NIH HL024136 (G.H.C.).
L.G.B., C.H., and K.L.L. were supported by the Intramural Research
Program of the NHGRI.
NR 20
TC 2
Z9 2
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD DEC
PY 2016
VL 48
IS 12
BP 1564
EP 1569
DI 10.1038/ng.3696
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA ED7BQ
UT WOS:000389011100018
PM 27749843
ER
PT J
AU Adams, HHH
Hibar, DP
Chouraki, V
Stein, JL
Nyquist, PA
Renteria, ME
Trompet, S
Arias-Vasquez, A
Seshadri, S
Desrivieres, S
Beecham, AH
Jahanshad, N
Wittfeld, K
Van der Lee, SJ
Abramovic, L
Alhusaini, S
Amin, N
Andersson, M
Arfanakis, K
Aribisala, BS
Armstrong, NJ
Athanasiu, L
Axelsson, T
Beiser, A
Bernard, M
Bis, JC
Blanken, LME
Blanton, SH
Bohlken, MM
Boks, MP
Bralten, J
Brickman, AM
Carmichael, O
Chakravarty, MM
Chauhan, G
Chen, Q
Ching, CRK
Cuellar-Partida, G
Den Braber, A
Doan, NT
Ehrlich, S
Filippi, I
Ge, T
Giddaluru, S
Goldman, AL
Gottesman, RF
Greven, CU
Grimm, O
Griswold, ME
Guadalupe, T
Hass, J
Haukvik, UK
Hilal, S
Hofer, E
Hoehn, D
Holmes, AJ
Hoogman, M
Janowitz, D
Jia, T
Kasperaviciute, D
Kim, S
Klein, M
Kraemer, B
Lee, PH
Liao, J
Liewald, DCM
Lopez, LM
Luciano, M
Macare, C
Marquand, A
Matarin, M
Mather, KA
Mattheisen, M
Mazoyer, B
Mckay, DR
McWhirter, R
Milaneschi, Y
Mirza-Schreiber, N
Muetzel, RL
Maniega, SM
Nho, K
Nugent, AC
Loohuis, LMO
Oosterlaan, J
Papmeyer, M
Pappa, I
Pirpamer, L
Pudas, S
Puetz, B
Rajan, KB
Ramasamy, A
Richards, JS
Risacher, SL
Roiz-Santianez, R
Rommelse, N
Rose, EJ
Royle, NA
Rundek, T
Samann, PG
Satizabal, CL
Schmaal, L
Schork, AJ
Shen, L
Shin, J
Shumskaya, E
Smith, AV
Sprooten, E
Strike, LT
Teumer, A
Thomson, R
Tordesillas-Gutierrez, D
Toro, R
Trabzuni, D
Vaidya, D
Van der Grond, J
Van der Meer, D
Van Donkelaar, MMJ
Van Eijk, KR
Van Erp, TGM
Van Rooij, D
Walton, E
Westlye, LT
Whelan, CD
Windham, BG
Winkler, AM
Woldehawariat, G
Wolf, C
Wolfers, T
Xu, B
Yanek, LR
Yang, JY
Zijdenbos, A
Zwiers, MP
Agartz, I
Aggarwal, NT
Almasy, L
Ames, D
Amouyel, P
Andreassen, OA
Arepalli, S
Assareh, AA
Barral, S
Bastin, ME
Becker, DM
Becker, JT
Bennett, DA
Blangero, J
van Bokhoven, H
Boomsma, DI
Brodaty, H
Brouwer, RM
Brunner, HG
Buckner, RL
Buitelaar, JK
Bulayeva, KB
Cahn, W
Calhoun, VD
Cannon, DM
Cavalleri, GL
Chen, C
Cheng, CY
Cichon, S
Cookson, MR
Corvin, A
Crespo-Facorro, B
Curran, JE
Czisch, M
Dale, AM
Davies, GE
De Geus, EJC
De Jager, PL
de Zubicaray, GI
Delanty, N
Depondt, C
DeStefano, AL
Dillman, A
Djurovic, S
Donohoe, G
Drevets, WC
Duggirala, R
Dyer, TD
Erk, S
Espeseth, T
Evans, DA
Fedko, I
Fernandez, G
Ferrucci, L
Fisher, SE
Fleischman, DA
Ford, I
Foroud, TM
Fox, PT
Francks, C
Fukunaga, M
Gibbs, JR
Glahn, DC
Gollub, RL
Goring, HHH
Grabe, HJ
Green, RC
Gruber, O
Gudnason, V
Guelfi, S
Hansell, NK
Hardy, J
Hartman, CA
Hashimoto, R
Hegenscheid, K
Heinz, A
Le Hellard, S
Hernandez, DG
Heslenfeld, DJ
Ho, BC
Hoekstra, PJ
Hoffmann, W
Hofman, A
Holsboer, F
Homuth, G
Hosten, N
Hottenga, JJ
Pol, HEH
Ikeda, M
Ikram, MK
Jack, CR
Jenldnson, M
Johnson, R
Jonsson, EG
Jukema, JW
Kahn, RS
Kanai, R
Kloszewska, I
Knopman, DS
Kochunov, P
Kwok, JB
Lawrie, SM
Lemaitre, H
Liu, XM
Longo, DL
Longstreth, WT
Lopez, OL
Lovestone, S
Martinez, O
Martinot, JL
Mattay, VS
McDonald, C
McIntosh, AM
McMahon, KL
McMahon, FJ
Mecocci, P
Melle, I
Meyer-Lindenberg, A
Mohnke, S
Montgomery, GW
Morris, DW
Mosley, TH
Muhleisen, TW
Muller-Myhsok, B
Nalls, MA
Nauck, M
Nichols, TE
Niessen, WJ
Nothen, MM
Nyberg, L
Ohi, K
Olvera, RL
Ophoff, RA
Pandolfo, M
Paus, T
Pausova, Z
Penninx, BWJH
Pike, GB
Potkin, SG
Psaty, BM
Reppermund, S
Rietschel, M
Roffman, JL
Romanczuk-Seiferth, N
Rotter, JI
Ryten, M
Sacco, RL
Sachdev, PS
Saykin, AJ
Schmidt, R
Schofield, PR
Sigurdsson, S
Simmons, A
Singleton, A
Sisodiya, SM
Smith, C
Smoller, JW
Soininen, H
Srikanth, V
Steen, VM
Stott, DJ
Sussmann, JE
Thalamuthu, A
Tiemeier, H
Toga, AW
Traynor, BJ
Troncoso, J
Turner, JA
Tzourio, C
Uitterlinden, AG
Hernandez, MCV
Van der Brug, M
Van der Lugt, A
Van der Wee, NJA
Van Duijn, CM
Van Haren, NEM
Van't Ent, D
Van Tol, MJ
Vardarajan, BN
Veltman, DJ
Vernooij, MW
Volzke, H
Walter, H
Wardlaw, JM
Wassink, TH
Weale, ME
Weinberger, DR
Weiner, MW
Wen, W
Westman, E
White, T
Wong, TY
Wright, CB
Zielke, HR
Zonderman, AB
Deary, IJ
DeCarli, C
Schmidt, H
Martin, NG
De Craen, AJM
Wright, MJ
Launer, LJ
Schumann, G
Fornage, M
Franke, B
Debette, S
Medland, SE
Ikram, MA
Thompson, PM
AF Adams, Hieab H. H.
Hibar, Derrek P.
Chouraki, Vincent
Stein, Jason L.
Nyquist, Paul A.
Renteria, Miguel E.
Trompet, Stella
Arias-Vasquez, Alejandro
Seshadri, Sudha
Desrivieres, Sylvane
Beecham, Ashley H.
Jahanshad, Neda
Wittfeld, Katharine
Van der Lee, Sven J.
Abramovic, Lucija
Alhusaini, Saud
Amin, Najaf
Andersson, Micael
Arfanakis, Konstantinos
Aribisala, Benjamin S.
Armstrong, Nicola J.
Athanasiu, Lavinia
Axelsson, Tomas
Beiser, Alexa
Bernard, Manon
Bis, Joshua C.
Blanken, Laura M. E.
Blanton, Susan H.
Bohlken, Marc M.
Boks, Marco P.
Bralten, Janita
Brickman, Adam M.
Carmichael, Owen
Chakravarty, M. Mallar
Chauhan, Ganesh
Chen, Qiang
Ching, Christopher R. K.
Cuellar-Partida, Gabriel
Den Braber, Anouk
Doan, Nhat Trung
Ehrlich, Stefan
Filippi, Irina
Ge, Tian
Giddaluru, Sudheer
Goldman, Aaron L.
Gottesman, Rebecca F.
Greven, Corina U.
Grimm, Oliver
Griswold, Michael E.
Guadalupe, Tulio
Hass, Johanna
Haukvik, Unn K.
Hilal, Saima
Hofer, Edith
Hoehn, David
Holmes, Avram J.
Hoogman, Martine
Janowitz, Deborah
Jia, Tianye
Kasperaviciute, Dalia
Kim, Sungeun
Klein, Marieke
Kraemer, Bernd
Lee, Phil H.
Liao, Jiemin
Liewald, David C. M.
Lopez, Lorna M.
Luciano, Michelle
Macare, Christine
Marquand, Andre
Matarin, Mar
Mather, Karen A.
Mattheisen, Manuel
Mazoyer, Bernard
Mckay, David R.
McWhirter, Rebekah
Milaneschi, Yuri
Mirza-Schreiber, Nazanin
Muetzel, Ryan L.
Maniega, Susana Munoz
Nho, Kwangsik
Nugent, Allison C.
Loohuis, Loes M. Olde
Oosterlaan, Jaap
Papmeyer, Martina
Pappa, Irene
Pirpamer, Lukas
Pudas, Sara
Puetz, Benno
Rajan, Kumar B.
Ramasamy, Adaikalavan
Richards, Jennifer S.
Risacher, Shannon L.
Roiz-Santianez, Roberto
Rommelse, Nanda
Rose, Emma J.
Royle, Natalie A.
Rundek, Tatjana
Saemann, Philipp G.
Satizabal, Claudia L.
Schmaal, Lianne
Schork, Andrew J.
Shen, Li
Shin, Jean
Shumskaya, Elena
Smith, Albert V.
Sprooten, Emma
Strike, Lachlan T.
Teumer, Alexander
Thomson, Russell
Tordesillas-Gutierrez, Diana
Toro, Roberto
Trabzuni, Daniah
Vaidya, Dhananjay
Van der Grond, Jeroen
Van der Meer, Dennis
Van Donkelaar, Marjolein M. J.
Van Eijk, Kristel R.
Van Erp, Theo G. M.
Van Rooij, Daan
Walton, Esther
Westlye, Lars T.
Whelan, Christopher D.
Windham, Beverly G.
Winkler, Anderson M.
Woldehawariat, Girma
Wolf, Christiane
Wolfers, Thomas
Xu, Bing
Yanek, Lisa R.
Yang, Jingyun
Zijdenbos, Alex
Zwiers, Marcel P.
Agartz, Ingrid
Aggarwal, Neelum T.
Almasy, Laura
Ames, David
Amouyel, Philippe
Andreassen, Ole A.
Arepalli, Sampath
Assareh, Amelia A.
Barral, Sandra
Bastin, Mark E.
Becker, Diane M.
Becker, James T.
Bennett, David A.
Blangero, John
van Bokhoven, Hans
Boomsma, Dorret I.
Brodaty, Henry
Brouwer, Rachel M.
Brunner, Han G.
Buckner, Randy L.
Buitelaar, Jan K.
Bulayeva, Kazima B.
Cahn, Wiepke
Calhoun, Vince D.
Cannon, Dara M.
Cavalleri, Gianpiero L.
Chen, Christopher
Cheng, Ching -Yu
Cichon, Sven
Cookson, Mark R.
Corvin, Aiden
Crespo-Facorro, Benedicto
Curran, Joanne E.
Czisch, Michael
Dale, Anders M.
Davies, Gareth E.
De Geus, Eco J. C.
De Jager, Philip L.
de Zubicaray, Greig I.
Delanty, Norman
Depondt, Chantal
DeStefano, Anita L.
Dillman, Allissa
Djurovic, Srdjan
Donohoe, Gary
Drevets, Wayne C.
Duggirala, Ravi
Dyer, Thomas D.
Erk, Susanne
Espeseth, Thomas
Evans, Denis A.
Fedko, Iryna
Fernandez, Guillen
Ferrucci, Luigi
Fisher, Simon E.
Fleischman, Debra A.
Ford, Ian
Foroud, Tatiana M.
Fox, Peter T.
Francks, Clyde
Fukunaga, Masaki
Gibbs, J. Raphael
Glahn, David C.
Gollub, Randy L.
Goring, Harald H. H.
Grabe, Hans J.
Green, Robert C.
Gruber, Oliver
Gudnason, Vilmundur
Guelfi, Sebastian
Hansell, Narelle K.
Hardy, John
Hartman, Catharina A.
Hashimoto, Ryota
Hegenscheid, Katrin
Heinz, Andreas
Le Hellard, Stephanie
Hernandez, Dena G.
Heslenfeld, Dirk J.
Ho, Beng-Choon
Hoekstra, Pieter J.
Hoffmann, Wolfgang
Hofman, Albert
Holsboer, Florian
Homuth, Georg
Hosten, Norbert
Hottenga, Jouke-Jan
Pol, Hilleke E. Hulshoff
Ikeda, Masashi
Ikram, M. Kamran
Jack, Clifford R., Jr.
Jenldnson, Mark
Johnson, Robert
Jonsson, Erik G.
Jukema, J. Wouter
Kahn, Rene S.
Kanai, Ryota
Kloszewska, Iwona
Knopman, David S.
Kochunov, Peter
Kwok, John B.
Lawrie, Stephen M.
Lemaitre, Herve
Liu, Xinmin
Longo, Dan L.
Longstreth, W. T., Jr.
Lopez, Oscar L.
Lovestone, Simon
Martinez, Oliver
Martinot, Jean-Luc
Mattay, Venkata S.
McDonald, Colm
McIntosh, Andrew M.
McMahon, Katie L.
McMahon, Francis J.
Mecocci, Patrizia
Melle, Ingrid
Meyer-Lindenberg, Andreas
Mohnke, Sebastian
Montgomery, Grant W.
Morris, Derek W.
Mosley, Thomas H.
Muhleisen, Thomas W.
Mueller-Myhsok, Bertram
Nalls, Michael A.
Nauck, Matthias
Nichols, Thomas E.
Niessen, Wiro J.
Noethen, Markus M.
Nyberg, Lars
Ohi, Kazutaka
Olvera, Rene L.
Ophoff, Roel A.
Pandolfo, Massimo
Paus, Tomas
Pausova, Zdenka
Penninx, Brenda W. J. H.
Pike, G. Bruce
Potkin, Steven G.
Psaty, Bruce M.
Reppermund, Simone
Rietschel, Marcella
Roffman, Joshua L.
Romanczuk-Seiferth, Nina
Rotter, Jerome I.
Ryten, Mina
Sacco, Ralph L.
Sachdev, Perminder S.
Saykin, Andrew J.
Schmidt, Reinhold
Schofield, Peter R.
Sigurdsson, Sigurdur
Simmons, Andy
Singleton, Andrew
Sisodiya, Sanjay M.
Smith, Colin
Smoller, Jordan W.
Soininen, Hindu.
Srikanth, Velandai
Steen, Vidar M.
Stott, David J.
Sussmann, Jessika E.
Thalamuthu, Anbupalam
Tiemeier, Henning
Toga, Arthur W.
Traynor, Bryan J.
Troncoso, Juan
Turner, Jessica A.
Tzourio, Christophe
Uitterlinden, Andre G.
Hernandez, Maria C. Valdes
Van der Brug, Marcel
Van der Lugt, Aad
Van der Wee, Nic J. A.
Van Duijn, Cornelia M.
Van Haren, Neeltje E. M.
Van't Ent, Dennis
Van Tol, Marie Jose
Vardarajan, Badri N.
Veltman, Dick J.
Vernooij, Meike W.
Voelzke, Henry
Walter, Henrik
Wardlaw, Joanna M.
Wassink, Thomas H.
Weale, Michael E.
Weinberger, Daniel R.
Weiner, Michael W.
Wen, Wei
Westman, Eric
White, Tonya
Wong, Tien Y.
Wright, Clinton B.
Zielke, H. Ronald
Zonderman, Alan B.
Deary, Ian J.
DeCarli, Charles
Schmidt, Helena
Martin, Nicholas G.
De Craen, Anton J. M.
Wright, Margaret J.
Launer, Lenore J.
Schumann, Gunter
Fornage, Myriam
Franke, Barbara
Debette, Stephanie
Medland, Sarah E.
Ikram, M. Arfan
Thompson, Paul M.
CA Alzheimer's Dis Neuroimaging Initi
EPIGEN
IMAGEN
SYS
TI Novel genetic loci underlying human intracranial volume identified
through genome-wide association
SO NATURE NEUROSCIENCE
LA English
DT Article
ID COMMON VARIANTS; 17Q21.31 MICRODELETION; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE; HEAD CIRCUMFERENCE; BRAIN SIZE; IGF-I; METAANALYSIS;
CONSORTIUM; GROWTH
AB Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
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[Adams, Hieab H. H.; Niessen, Wiro J.; Van der Lugt, Aad; Vernooij, Meike W.; White, Tonya; Ikram, M. Arfan] Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
[Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Ching, Christopher R. K.; Whelan, Christopher D.; Thompson, Paul M.] Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.
[Chouraki, Vincent; Seshadri, Sudha; Beiser, Alexa; Satizabal, Claudia L.; Debette, Stephanie] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Chouraki, Vincent; Amouyel, Philippe] Univ Lille, RID AGE Risk Factors & Mol Determinants Aging Rel, CHU Lille, Inserm,Inst Pasteur Lille, Lille, France.
[Chouraki, Vincent; Seshadri, Sudha; Beiser, Alexa; Satizabal, Claudia L.; DeStefano, Anita L.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Stein, Jason L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Stein, Jason L.] Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC USA.
[Nyquist, Paul A.] Johns Hopkins Univ, Dept Neurol, Dept Anesthesia Crit Care Med, Dept Neurosurg, Baltimore, MD 21218 USA.
[Renteria, Miguel E.; Cuellar-Partida, Gabriel; Strike, Lachlan T.; Hansell, Narelle K.; Montgomery, Grant W.; Martin, Nicholas G.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Arias-Vasquez, Alejandro; Bralten, Janita; Hoogman, Martine; Klein, Marieke; Shumskaya, Elena; Van Donkelaar, Marjolein M. J.; Wolfers, Thomas; van Bokhoven, Hans; Brunner, Han G.; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
[Arias-Vasquez, Alejandro; Rommelse, Nanda; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.
[Arias-Vasquez, Alejandro; Greven, Corina U.; Richards, Jennifer S.; Van Rooij, Daan; Buitelaar, Jan K.; Fernandez, Guillen] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.
[Arias-Vasquez, Alejandro; Bralten, Janita; Hoogman, Martine; Klein, Marieke; Marquand, Andre; Richards, Jennifer S.; Rommelse, Nanda; Shumskaya, Elena; Van Donkelaar, Marjolein M. J.; Van Rooij, Daan; Wolfers, Thomas; Zwiers, Marcel P.; van Bokhoven, Hans; Brunner, Han G.; Buitelaar, Jan K.; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.
[Desrivieres, Sylvane; Jia, Tianye; Macare, Christine; Xu, Bing; Schumann, Gunter] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England.
[Beecham, Ashley H.; Blanton, Susan H.] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.
[Beecham, Ashley H.; Blanton, Susan H.; Sacco, Ralph L.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA.
[Wittfeld, Katharine; Hoffmann, Wolfgang] German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Greifswald, Germany.
[Wittfeld, Katharine; Janowitz, Deborah; Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat, Greifswald, Germany.
[Abramovic, Lucija; Bohlken, Marc M.; Boks, Marco P.; Brouwer, Rachel M.; Cahn, Wiepke; Pol, Hilleke E. Hulshoff; Kahn, Rene S.; Ophoff, Roel A.; Van Haren, Neeltje E. M.] UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
[Alhusaini, Saud] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Alhusaini, Saud; Whelan, Christopher D.; Cavalleri, Gianpiero L.; Delanty, Norman] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Andersson, Micael; Pudas, Sara; Nyberg, Lars] Umea Univ, Dept Integrat Med Biol, Umea, Sweden.
[Arfanakis, Konstantinos] IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
[Arfanakis, Konstantinos; Yang, Jingyun; Aggarwal, Neelum T.; Bennett, David A.; Fleischman, Debra A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Arfanakis, Konstantinos] Rush Univ, Med Ctr, Dept Diagnost Radiol & Nucl Med, Chicago, IL 60612 USA.
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[Aribisala, Benjamin S.] Lagos State Univ, Dept Comp Sci, Lagos, Nigeria.
[Aribisala, Benjamin S.; Maniega, Susana Munoz; Royle, Natalie A.; Bastin, Mark E.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.
[Armstrong, Nicola J.; Mather, Karen A.; Assareh, Amelia A.; Brodaty, Henry; Reppermund, Simone; Sachdev, Perminder S.; Thalamuthu, Anbupalam; Wen, Wei] Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.
[Armstrong, Nicola J.] Murdoch Univ, Math & Stat, Perth, WA, Australia.
[Athanasiu, Lavinia; Doan, Nhat Trung; Haukvik, Unn K.; Agartz, Ingrid; Andreassen, Ole A.; Jonsson, Erik G.; Melle, Ingrid] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.
[Athanasiu, Lavinia; Westlye, Lars T.; Andreassen, Ole A.; Espeseth, Thomas; Melle, Ingrid] Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway.
[Axelsson, Tomas] Uppsala Univ, Dept Med Sci Mol Med, Uppsala, Sweden.
[Axelsson, Tomas] Uppsala Univ, Sci Life Lab, Uppsala, Sweden.
[Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Bernard, Manon; Shin, Jean; Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.
[Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Blanken, Laura M. E.; Muetzel, Ryan L.; Pappa, Irene] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.
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[Brickman, Adam M.; Barral, Sandra; Vardarajan, Badri N.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
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[Carmichael, Owen] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
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[Chauhan, Ganesh] Univ Bordeaux, INSERM Unit U1219, Bordeaux, France.
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[Ching, Christopher R. K.] Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA USA.
[Den Braber, Anouk; Boomsma, Dorret I.; De Geus, Eco J. C.; Fedko, Iryna; Hottenga, Jouke-Jan; Van't Ent, Dennis] Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Den Braber, Anouk; Boomsma, Dorret I.; De Geus, Eco J. C.; Fedko, Iryna; Hottenga, Jouke-Jan; Van't Ent, Dennis] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Ehrlich, Stefan] Tech Univ Dresden, Fac Med, Div Psychol & Social Med & Dev Neurosci, Dresden, Germany.
[Ehrlich, Stefan; Holmes, Avram J.; Lee, Phil H.; Buckner, Randy L.; Gollub, Randy L.; Roffman, Joshua L.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
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[Filippi, Irina; Lemaitre, Herve; Martinot, Jean-Luc] Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.
[Filippi, Irina; Lemaitre, Herve; Martinot, Jean-Luc] Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France.
[Ge, Tian; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Ge, Tian; Lee, Phil H.; De Jager, Philip L.; Gollub, Randy L.; Green, Robert C.; Smoller, Jordan W.] Harvard Med Sch, Boston, MA USA.
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[Giddaluru, Sudheer; Djurovic, Srdjan; Le Hellard, Stephanie; Steen, Vidar M.] Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.
[Giddaluru, Sudheer; DeStefano, Anita L.; Le Hellard, Stephanie; Steen, Vidar M.] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway.
[Gottesman, Rebecca F.; Mattay, Venkata S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
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[Grimm, Oliver; Meyer-Lindenberg, Andreas; Rietschel, Marcella] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany.
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[Hass, Johanna; Walton, Esther] Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, Dresden, Germany.
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[Hilal, Saima; Chen, Christopher; Ikram, M. Kamran] Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.
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[Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT USA.
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[Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Saykin, Andrew J.] Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.
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[Lee, Phil H.] Harvard Med Sch, Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA USA.
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[Mazoyer, Bernard] UMR5296 Univ Bordeaux, CNRS, CEA, Bordeaux, France.
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[McWhirter, Rebekah] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia.
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[Papmeyer, Martina] Univ Bern, Univ Hosp Psychiat, Translat Res Ctr, Div Syst Neurosci Psychopathol, CH-3012 Bern, Switzerland.
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[Ramasamy, Adaikalavan] Univ Oxford, Jenner Inst Labs, Oxford, England.
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[Schmaal, Lianne] Orygen, Melbourne, Vic, Australia.
[Schmaal, Lianne] Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia.
[Schmaal, Lianne; Penninx, Brenda W. J. H.; Veltman, Dick J.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
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[Smith, Albert V.; Gudnason, Vilmundur; Sigurdsson, Sigurdur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
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[Strike, Lachlan T.; Hansell, Narelle K.; Wright, Margaret J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
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[Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry, W Midlands, England.
[Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry, W Midlands, England.
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[Niessen, Wiro J.] Delft Univ Technol, Fac Sci Appl, Delft, Netherlands.
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[Paus, Tomas] Child Mind Inst, New York, NY USA.
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[Sachdev, Perminder S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia.
[Simmons, Andy] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London, England.
[Simmons, Andy] Kings Coll London, Biomed Res Ctr Mental Hlth, London, England.
[Simmons, Andy] Kings Coll London, Biomed Res Unit Dementia, London, England.
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[Soininen, Hindu.] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
[Soininen, Hindu.] Kuopio Univ Hosp, Neuroctr Neurol, Kuopio, Finland.
[Srikanth, Velandai] Peninsula Hlth & Monash Univ, Dept Med, Melbourne, Vic, Australia.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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[Turner, Jessica A.] Georgia State Univ, Atlanta, GA 30303 USA.
[Tzourio, Christophe] Univ Bordeaux, Institute Neurodegenerat Disorders, CEA, CNRS,UMR 5293, Bordeaux, France.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Van der Brug, Marcel] Genentech Inc, San Francisco, CA 94080 USA.
[Van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
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[Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
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[Westman, Eric] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
[Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
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[Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
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RP Ikram, MA (reprint author), Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.; Ikram, MA (reprint author), Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.; Thompson, PM (reprint author), Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.; Ikram, MA (reprint author), Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
EM m.a.ikram@erasmusmc.nl; pthomp@usc.edu
RI Tzourio, christophe/B-4015-2009; Simmons, Andrew/B-8848-2008; Hardy,
John/C-2451-2009; Hansell, Narelle/A-4553-2016; Zwiers,
Marcel/D-2968-2009; Franke, Barbara/D-4836-2009; Meyer-Lindenberg,
Andreas/H-1076-2011; McMahon, Katie/C-6440-2009; Thomson,
Russell/H-5653-2012; Fernandez, Guillen/B-3771-2009; Cuellar Partida,
Gabriel/C-6686-2017;
OI Tzourio, christophe/0000-0002-6517-2984; Simmons,
Andrew/0000-0003-2306-5811; Hansell, Narelle/0000-0002-8229-9741;
Zwiers, Marcel/0000-0001-5483-2935; Franke, Barbara/0000-0003-4375-6572;
Meyer-Lindenberg, Andreas/0000-0001-5619-1123; McMahon,
Katie/0000-0002-6357-615X; Thomson, Russell/0000-0003-4949-4120;
Fernandez, Guillen/0000-0002-5522-0604; Adams,
Hieab/0000-0003-3687-2508; Rose, Emma/0000-0001-5365-4794; Zonderman,
Alan B/0000-0002-6523-4778; Vaidya, Dhananjay/0000-0002-7164-1601;
Beiser, Alexa/0000-0001-8551-7778; Westlye, Lars T./0000-0001-8644-956X;
de Geus, Eco/0000-0001-6022-2666; Kanai, Ryota/0000-0002-0186-2687;
McIntosh, Andrew/0000-0002-0198-4588; Cuellar Partida,
Gabriel/0000-0001-7648-4097; Desrivieres, Sylvane/0000-0002-9120-7060;
Cavalleri, Gianpiero/0000-0002-9802-0506; Pudas,
Sara/0000-0001-9512-3289; Westman, Eric/0000-0002-3115-2977; Arfanakis,
Konstantinos/0000-0001-9705-597X; Jonsson, Erik/0000-0001-8368-6332
FU National Heart, Lung and Blood Institute [HL105756]; National Institute
on Aging [AG033193]; NIH Institute, NIBIB [U54 EB020403]; NIH Institute,
NCI [U54 EB020403]; NIH [N01-AG-1-2100, 271201200022C, R01MH62873,
K99MH102357, R01 HD050735, P30AG10161, RF1AG15819, R01AG17917,
R01AG30146, R01AG40039, 5R01AG037212]; NIA Intramural Research Program;
Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic
Parliament); ADNI (National Institutes of Health Grant) [U01 AG024904];
DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute
on Aging; National Institute of Biomedical Imaging and Bioengineering;
lzheimer's Association; Alzheimer's Drug Discovery Foundation;
BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai
Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La
Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare;
Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research
& Development, LLC.; Johnson & Johnson Pharmaceutical Research &
Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale
Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals
Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda
Pharmaceutical Company; Canadian Institutes of Health Research; EU;
Kuopio University Hospital; National Heart, Lung, and Blood Institute
(NHLBI) [HHSN268201100005C, HSN268201100006C, HSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL70825, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C,
R01D0042157-01A, MH081802, 1RC2 MH089951, 1RC2 MH089995]; component of
the NIH and NIH Roadmap for Medical Research [UL1RR025005]; NIH R01
grant [NS087541]; Austrian Science Fund (FWF) [1904]; Medical University
of Graz; Steiermarkische Krankenanstalten Gesellschaft; Knut and Alice
Wallenberg (KAW) foundation; Torsten and Ragnar Soderbergs Foundation;
HelseVest RHF [911554]; Brain Research Imaging Centre Edinburgh, a
center in the Scottish Funding Council Scottish Imaging Network-A
Platform for Scientific Excellence (SINAPSE) Collaboration; National
Alliance for Research on Schizophrenia and Depression (NARSAD)
Independent Investigator Award; Health Foundation Clinician Scientist
Fellowship; European Community [602450, 278948, 602805, 643051];
Biobanking and Biomolecular Resources Research Infrastructure
(Netherlands) (BBMRI-NL); Hersenstichting Nederland; Netherlands
Organization for Scientific Research (NWO); NWO Gravitation grant
'Language in Interaction'; ERC [268800-NEUROSCHEMA]; ENIGMA Consortium
from the BD2K Initiative of a cross-NIH partnership [U54 EB020403];
Center for Brain Science Neuroinformatics Research Group; Athinoula A.
Martinos Center for Biomedical Imaging; Center for Human Genetic
Research; NIMH [K99 MH101367, R01-MH079799, K24MH094614, K01MH099232];
National Institute of Health [AG033193, AG011101, AG030146, AG008122,
AG054076, AG049607, AG010129, NS017950, U01AG49505]; International
Alzheimer's Association [NIRP-14-302587]; National Medical Research
Council, Singapore [0796/2003, IRG07nov013, IRG09nov014, STaR/0003/2008,
CG/SERI/2010]; Biomedical Research Council, Singapore [09/1/35/19/616];
National Medical Research Council, Singapore (NMRC/CG/NUHS)
[R-184-006-184-511]; Singapore Ministry of Health's National Medical
Research Council [NMRC/CSA/038/2013]; Wellcome Trust [084730,
082604/2/07/Z]; University College London (UCL)/University College
London Hospitals (UCLH) NIHR Biomedical Research Centre/Specialist
Biomedical Research Centres (CBRC/SBRC) [114]; European Union Marie
Curie Reintegration; UK NIHR [08-08-SCC]; Comprehensive Local Research
Network (CLRN) Flexibility and Sustainability Funding (FSF) [CEL1300];
Big Lottery Fund; Wolfson Trust; Epilepsy Society; UK Department of
Health's NIHR Biomedical Research Centres funding scheme; Science
Foundation Ireland [08/RFP/GEN1538]; Netherlands Organization for
Scientific Research NWO [MW904-61-193, 400-07-080, MagW 480-04-004,
51.02.060, 668.772]; European Research Council [ERC-230374]; High
Potential Grant Utrecht University; NWO Brain and Cognition
[433-09-220]; Neuroscience Campus Amsterdam; NHLBI [HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652,
R01HL105756, R01HL103612, R01HL120393, R01HL130114, R01 HL105756];
National Institute on Aging (NIA) [R01AG023629, R01AG15928, R01AG20098,
R01AG027002, R01AG05133, R01AG027058]; National Center for Advancing
Translational Sciences, CTSI grant [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
[DK063491]; Brainwave-the Irish Epilepsy Association; Epilepsy Research
UK [F1206]; European Commission [018947 (LSHG-CT-2006-01947), 223004];
European Community's Seventh Framework Programme (FP7) by the European
Commission under the programme "Quality of Life and Management of the
Living Resources" of 5th Framework Programme [HEALTH-F4-2007-201413,
QLG2-CT-2002-01254]; Netherlands Organization for Scientific Research;
Russian Foundation for Basic Research [NWO-RFBR 047.017.043];
Netherlands Brain Foundation [F2013(1)-28, 15F07[2]27]; National Heart,
Lung and Blood Institute's Framingham Heart Study [HHSN2682015000011];
ZonMw [TOP 40-00812-98-11021, 916.13.054]; National Institute of
Neurological Disorders and Stroke [R01NS062059]; National Heart, Lung,
and Blood Institute [U01 HL72518, HL097698]; National Institutes of
Health/National Center for Research Resources [M01-RR000052]; National
Institute of Mental Health [MH0708143, MH078111, MH083824]; Research
Facilities Improvement Program from the National Center for Research
Resources, NIH [C06 RR13556, C06 RR017515]; Swedish Research Council
[K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2,
K2012-61X-15078-09-3]; Stockholm County Council; Karolinska Institutet;
Knut and Alice Wallenberg Foundation; HUBIN project; Swedish Research
Council; European Union [602450, LSHM-CT-2007-037286, 603016];
Innovative Medicine Initiative Project EU-AIMS [115300-2]; Medical
Research Council Programme Grant "Developmental pathways into adolescent
substance abuse" [93558]; NIHR-biomedical Research Center "Mental
Health": Swedish Research Council FORMAS; German Federal Ministry for
Education and Research BMBF (Forschungsnetz AERIAL) [eMED SysAlc
01ZX1311A, 1EV0711]; US National Institutes of Health (Axon); US
National Institutes of Health (Testosterone); US National Institutes of
Health (Mental Health during Adolescence); US National Institutes of
Health [MH085772-01A1]; French MILDECA; Fondation pour la Recherche
Medicale; Brain & Cognition Excellence Program of the Netherlands
Organization for Scientific Research (NWO) [433-09-229]; Netherlands
Organization for Scientific Research (NWO) [016.130.669]; Research into
Ageing programme grant; Age UK-Disconnected Mind project; UK Medical
Research Council (MRC); Scottish Funding Council through the SINAPSE
Collaboration; Row Fogo Charitable Trust; UK Biotechnology and
Biological Sciences Research Council (BBSRC) [MRC MR/K026992/1]; UK MRC;
BBSRC [BB/F019394/1]; Innovation-Oriented Research Program on Genomics
(SenterNovem) [IGE05007]; Netherlands Consortium for Healthy Ageing
[050-060-810]; Department of Energy [DE-FG02-08ER64581]; German Federal
Ministry of Education and Research (BMBF) through the Integrated Genome
Research Network (IG) MooDS (Systematic Investigation of the Molecular
Causes of Major Mood Disorders and Schizophrenia) unde (NGFNplus)
[01GS08144, 01GS08147, 01GS08148]; German Federal Ministry of Education
and Research (BMBF) through the Integrated Network IntegraMent
(Integrated Understanding of Causes and Mechanisms in Mental Disorders)
under e:Med Programme [01ZX1314A, 01ZX1314C, 01ZX1314G];
Exzellenz-Stiftung of the Max Planck Society; Federal Ministry of
Education and Research (BMBF) [FKZ 01GS0481]; Bergen Research
Foundation; University of Bergen; Dr. Einar Martens Fund; K.G. Jebsen
Foundation; Research Council of Norway; Netherlands Organization for
Scientific Research [10-000-1002]; Center for Medical Systems Biology
(CSMB, NWO Genomics); Biobanking and Biomolecular Resources Research
Infrastructure (BBMRI-NL); VU University's Institutes for Health and
Care Research (EMGO+); University Medical Center Groningen; Leiden
University Medical Center; Genetic Association Information Network
(GAIN) of the Foundation for the National Institutes of Health; BiG
Grid; Dutch e-Science Grid - NWO; NWO Large Investment Grant
[1750102007010]; Radboud University Nijmegen Medical Center; University
Medical Center Groningen and Accare; VU University Amsterdam; NIMH
Intramural Research Program [ZIAMH002810, Z01MH002792, Z01MH002790];
Intramural Research Program of the NIH, National Institute on Aging;
NHMRC/Australian Research Council Strategic Award [401162]; NHMRC [R01
HD050735, 1045325, 310667, 401184, 525453, 568940, 389875, 486682,
1009064, 1061457]; Commonwealth Scientific and Industrial Research
Organisation Flagship Collaboration Fund Grant; Australian Government -
Dementia Collaborative Research Centre (DCRC), UNSW; Alzheimer's
Australia Dementia Research Foundation; Japanese Ministry of Health,
Labor and Welfare; Japanese Ministry of Education, Culture, Sports,
Science and Technology (MEXT) KAKENHI; Scientific Research on Innovative
Areas (Comprehensive Brain Science Network); Brain Sciences Project of
the Center for Novel Science Initiatives (CNSI); National Institutes of
Natural Sciences (NINS); Brain Mapping by Integrated Neurotechnologies
for Disease Studies (Brain/MINDS) from Japan Agency for Medical Research
and development, AMED; Instituto de Salud Carlos III [FIS00/3095,
01/3129, PI020499, PI060507, PI10/00183, PI14/00639]; SENY Fundacio
Research Grant [CI 2005-0308007]; Fundacion Marques de Valdecilla
[API07/011]; Carlos III Health Institute [CA12/00312]; Bristol-Myers
Squibb; Netherlands Heart Foundation [2001 D 032]; Netherlands Genomics
Initiative (Netherlands Consortium for Healthy Aging) [050-060-810];
Autism Speaks; Australian Research Council [FT0991634]; National Health
and Medical Research Council (NHMRC), Australia [1103623, 619667];
Translational Genomics Research Institute; Netherlands Organisation of
Scientific Research NWO [175.010.2005.011, 911-03-012]; Research
Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands
Genomics Initiative (NGI)/Netherlands Organisation for Scientific
Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission (DG XII); Municipality of
Rotterdam; Dutch Technology Foundation STW, NWO; Ministry of Economic
Affairs; European Research Council (ERC) under the European Union's
Horizon research and innovation programme [678543]; Joint Programme -
Neurodegenerative Disease Research working group on High-Dimensional
Research in Alzheimer's Disease (ZonMW) [733051031]; Van Leersum Grant
of the Royal Netherlands Academy of Arts and Sciences; Heart and Stroke
Foundation of Quebec; Canadian Foundation for Innovation; Tanenbaum
Chair in Population Neuroscience at the Rotman Research Institute,
University of Toronto; German Federal Ministry of Education and
Research; German Ministry of Cultural Affairs; Social Ministry of the
Federal State of Mecklenburg-West Pomerania [01ZZ9603, 01ZZ0103,
01ZZ0403]; network 'Greifswald Approach to Individualized Medicine
(GANI_MED)' - Federal Ministry of Education and Research [03IS2061A];
Federal Ministry of Education and Research [03ZIK012]; Siemens
Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West
Pomerania; Australian National Health and Medical Research Council
(NHMRC) Program [350833, 568969]; National Health and Medical Research
Council of Australia (NHMRC) [403000, 491109, 606543]; Wicking Dementia
Education and Research Centre; Heart Foundation Future Leader Fellowship
[100089]; Caisse Nationale Maladie des Travailleurs Salaries; Direction
Generale de la Sante; Mutuelle Generale de l'Education Nationale (MGEN);
Institut de la Longevite; Conseil Regionaux of Aquitaine; Conseil
Regionaux of Bourgogne; Fondation de France; Ministry of Research INSEAM
Programme "Cohortes et collections de donnees biologiques"; Fondation
Leducq; Research Council of Norway [213837, 223273, 229129]; South-East
Norway Health Authority [2013-123]; KG Jebsen Foundation; Netherlands
Organization for Health Research and Development ZonMW [917.46.370,
908-02-123]; French National Foundation on Alzheimer's disease and
related disorders; LABEX (laboratory of excellence program investment
for the future) DISTALZ grant; Inserm; Institut Pasteur de Lille;
University de Lille 2; Lille University Hospital; Medical Research
Council [503480]; Alzheimer's Research UK [503176]; German Federal
Ministry of Education and Research (BMBF): Competence Network Dementia
(CND) [01G10102, 01G10711, 01G10420]; NIH/NIA grant [R01 AG033193, U01
AG032984, U24 AG021886, U01 AG016976]; NIA [AG081220]; AGES
[N01-AG-12100]; Icelandic Heart Association; Erasmus University;
Alzheimer's Association [ADGC-10-196728]; [NWO/SPI 56-464-14192];
[MH59490]
FX CHARGE: Infrastructure for the CHARGE Consortium is supported in part by
the National Heart, Lung and Blood Institute grant HL105756 and for the
neuroCHARGE phenotype working group through the National Institute on
Aging grant AG033193.; ENIGMA: ENIGMA was supported in part by a
Consortium grant (U54 EB020403 to PMT) from the NIH Institutes
contributing to the Big Data to Knowledge (BD2K) Initiative, including
the NIBIB and NCI.; Age, Gene/Environment Susceptibility-Reykjavik Study
(AGES-Reykjavik): This study has been funded by NIH contracts
N01-AG-1-2100 and 271201200022C, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). The study was approved by the Icelandic National
Bioethics Committee, VSN: 00-063. The researchers are indebted to the
participants for their willingness to participate in the study.;
Alzheimer's Disease Neuroimaging Initiative (ADNI): Data collection and
sharing for this project was funded by the ADNI (National Institutes of
Health Grant U01 AG024904) and DOD ADNI (Department of Defense award
number W81XWH-12-2-0012). ADNI is funded by the National Institute on
Aging, the National Institute of Biomedical Imaging and Bioengineering,
and through generous contributions from the Alzheimer's Association;
Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec
Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals,
Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated
company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.;
Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson &
Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck
& Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier;
Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes
of Health Research provides funds to support ADNI clinical sites in
Canada. Private sector contributions are facilitated by the Foundation
for the National Institutes of Health (http://www.fnih.org). The grantee
organization is the Northern California Institute for Research and
Education, and the study is coordinated by the Alzheimer's Disease
Cooperative Study at the University of California, San Diego. ADNI data
are disseminated by the Laboratory of Neuro Imaging at the University of
Southern California.; ANM: AddNeuroMed was funded through the EU FP6
programme. HS: Academy of Finland, Research Council for Health, 258081,
UEFBrain, University of Eastern Finland, VTR funding Kuopio University
Hospital.; Atherosclerosis Risk In Communities Study (ARIC): The
Atherosclerosis Risk in Communities study was performed as a
collaborative study supported by National Heart, Lung, and Blood
Institute (NHLBI) contracts (HHSN268201100005C, HSN268201100006C,
HSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
R01HL70825, R01HL087641, R01HL59367, and R01HL086694; National Human
Genome Research Institute contract U01HG004402; and National Institutes
of Health (NIH) contract HHSN268200625226C. Infrastructure was partly
supported by grant no. UL1RR025005, a component of the NIH and NIH
Roadmap for Medical Research. This project was also supported by NIH R01
grant NS087541 to M.F.; Austrian Stroke Prevention Study Family
(ASPS-Fam): The ASPS-Fam is funded by the Austrian Science Fund (FWF)
project 1904, the Medical University of Graz and the Steiermarkische
Krankenanstalten Gesellschaft.; BETULA: This sample collection was
supported by a Wallenberg Scholar grant from the Knut and Alice
Wallenberg (KAW) foundation and a grant from Torsten and Ragnar
Soderbergs Foundation to Lars Nyberg. S.l.H. was supported by a grant
from HelseVest RHF (grant 911554).; Bipolar Family Study (BFS): The
Bipolar Family Study wishes to thank the Scottish Mental Health Research
Network for research assistant support, the Brain Research Imaging
Centre Edinburgh, a center in the Scottish Funding Council Scottish
Imaging Network-A Platform for Scientific Excellence (SINAPSE)
Collaboration, for image acquisition and the Wellcome Trust Clinical
Research Facility for genotyping. Genotyping was supported by the
National Alliance for Research on Schizophrenia and Depression (NARSAD)
Independent Investigator Award (to A.M.M.), and data collection was
supported by the Health Foundation Clinician Scientist Fellowship. The
research leading to these results also receives funding from the
European Community's Seventh Framework Programme (FP7/2007-2013) under
grant agreements #602450 (IMAGEMEND) and ongoing support from the
Wellcome Trust (Ref 104036/Z/14/Z).; Brain Imaging Genetics (BIG): This
work makes use of the BIG database, first established in Nijmegen, The
Netherlands, in 2007. This resource is now part of Cognomics
(http://www.cognomics.nl), a joint initiative by researchers of the
Donders Centre for Cognitive Neuroimaging, the Human Genetics and
Cognitive Neuroscience Departments of the Radboud University Medical
Center and the Max Planck Institute for Psycholinguistics in Nijmegen.
The Board of the Cognomics Initiative consists of B. Franke, S. Fisher,
G. Fernandez, P. Hagoort, H. Brunner, J. Buitelaar, H. van Bokhoven and
D. Norris. The Cognomics Initiative has received supported from the
participating departments and centers and from external grants, that is,
the Biobanking and Biomolecular Resources Research Infrastructure
(Netherlands) (BBMRI-NL), the Hersenstichting Nederland, and the
Netherlands Organization for Scientific Research (NWO). The research
leading to these results also receives funding from the NWO Gravitation
grant 'Language in Interaction', the European Community's Seventh
Framework Programme (FP7/2007-.2013) under grant agreements no 602450
(IMAGEMEND), no 278948 (TACTICS), and no 602805 (Aggressotype), as well
as from the European Community's Horizon 2020 programme under grant
agreement no 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In
addition, the work was supported by a grant for the ENIGMA Consortium
(grant number U54 EB020403) from the BD2K Initiative of a cross-NIH
partnership. We wish to thank all persons who kindly participated in the
BIG research.; Brain Genomics Superstruct Project (GSP): Data were
provided in part by the Brain Genomics Superstruct Project of Harvard
University and the Massachusetts General Hospital, with support from the
Center for Brain Science Neuroinformatics Research Group, the Athinoula
A. Martinos Center for Biomedical Imaging, and the Center for Human
Genetic Research. 20 individual investigators at Harvard and MGH
generously contributed data to GSP. This work is supported by NIMH
grants K99 MH101367 (P.H.L.), R01-MH079799 (J.W.S.), K24MH094614
(J.W.S.) and K01MH099232 (A.J.H.).; Brainscale and NTR-Adults: We would
like to thank all twin participants from the Netherlands Twin Register.
The NTR-adult and Brainscale studies were supported by the Netherlands
Organization for Scientific Research NWO [MW904-61-193 (E.d.G. and
D.B.), MaGW-nr: 400-07-080 (D. V't E.), MagW 480-04-004 (D.B.),
(51.02.060 (H.H.), 668.772 (D.B. and H.H.); NWO/SPI 56-464-14192 (D.B.),
the European Research Council (ERC-230374) (D.B.), High Potential Grant
Utrecht University (H.H.), NWO Brain and Cognition 433-09-220 (H.H.) and
the Neuroscience Campus Amsterdam.; Cardiovascular Health Study (CHS):
This research was supported by NHLBI contracts HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295,
R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL130114 with
additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided through
R01AG023629, R01AG15928, R01AG20098, R01AG027002, R01AG05133, and
R01AG027058 from the National Institute on Aging (NIA). A full list of
principal CHS investigators and institutions can be found at
http://CHS-NHLBI.org. The provision of genotyping data was supported in
part by the National Center for Advancing Translational Sciences, CTSI
grant UL1TR000124, and the National Institute of Diabetes and Digestive
and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.;
CHAP: This research was funded by grants from the National Institute of
Health (AG011101 and AG030146) and the International Alzheimer's
Association (NIRP-14-302587). DNA samples were collected during clinical
evaluations and population interviews, and analyzed at the Broad
Institute.; Epidemiology of Dementia in Singapore (EDIS): The Singapore
Malay Eye Study (SiMES) and the Singapore Chinese Eye. Study (SCES) are
funded by National Medical Research Council (grants 0796/2003,
IRG07nov013, IRG09nov014, STaR/0003/2008 and CG/SERI/2010) and
Biomedical Research Council (grants 09/1/35/19/616), Singapore. The
Genome Institute of Singapore, Agency for Science, Technology and
Research, Singapore provided services for genotyping. The Epidemiology
of Dementia in Singapore study is supported by the National Medical
Research Council, Singapore (NMRC/CG/NUHS/2010, grant no.
R-184-006-184-511). M.K.I. received additional funding from the
Singapore Ministry of Health's National Medical Research Council
(NMRC/CSA/038/2013).; EPIGEN: Work from the London Cohort was supported
by research grants from the Wellcome Trust (grant 084730 to S.M.S.),
University College London (UCL)/University College London Hospitals
(UCLH) NIHR Biomedical Research Centre/Specialist Biomedical Research
Centres (CBRC/SBRC) (grant 114 to S.M.S.), the European Union Marie
Curie Reintegration (to M. Matarin and S.M.S.), the UK NIHR (08-08-SCC),
the Comprehensive Local Research Network (CLRN) Flexibility and
Sustainability Funding (FSF) (grant CEL1300 to S.M.S.), The Big Lottery
Fund, the Wolfson Trust and the Epilepsy Society. This work was
undertaken at UCLH/UCL, which received a proportion of funding from the
UK Department of Health's NIHR Biomedical Research Centres funding
scheme. Work from the Royal College of Surgeons in Ireland was supported
by research grants from the Science Foundation Ireland (Research
Frontiers Programme award 08/RFP/GEN1538) and Brainwave-the Irish
Epilepsy Association. M. Matarin is funded by Epilepsy Research UK
(grant F1206).; Erasmus Rucphen Family study (ERF) The ERF study as a
part of EUROSPAN (European Special Populations Research Network) was
supported by European Commission FP6 STRP grant number 018947
(LSHG-CT-2006-01947) and also received funding from the European
Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement
HEALTH-F4-2007-201413 by the European Commission under the programme
"Quality of Life and Management of the Living Resources" of 5th
Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis
of the ERF data was supported by joint grant from Netherlands
Organization for Scientific Research and the Russian Foundation for
Basic Research (NWO-RFBR 047.017.043). We are grateful to all study
participants and their relatives, general practitioners and neurologists
for their contributions and to P. Veraart for her help in genealogy, J.
Vergeer for the supervision of the laboratory work and P. Snijders for
his help in data collection. N. Amin is supported by the Netherlands
Brain Foundation (project number F2013(1)-28). The ERF study genome-wide
array data and phenotype data (age and gender) is archived in European
Genome-Phenome Database (EGA). The study is archived in the DAC named
Erasmus Rucphen Family Study with the accession code: EGAS00001001134.
Researchers who wish to use other phenotypic data of the Erasmus Rucphen
Family Study must seek approval from the management team of the Erasmus
Rucphen Family study. They are advised to contact Cornelia van Duijn
(c.vanduijn@erasmusmc.nl).; Framingham Heart Study (FHS): This work was
supported by the dedication of the Framingham Study participants, the
National Heart, Lung and Blood Institute's Framingham Heart Study
(Contract No. HHSN2682015000011), and by grants from the National
Institute of Health (AG008122, AG054076, AG049607, AG033193, AG010129,
NS017950, and U01AG49505).; Generation R: The Generation R Study is
conducted by the Erasmus Medical Centre in close collaboration with the
Municipal Health Service Rotterdam area, and the Stichting
Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. We
gratefully acknowledge the contribution of general practitioners,
hospitals, midwives and pharmacies in Rotterdam. Additional support for
neuroimaging came from ZonMw TOP 40-00812-98-11021.; GeneSTAR: GeneSTAR
was supported by grants from the National Institute of Neurological
Disorders and Stroke (R01NS062059), the National Heart, Lung, and Blood
Institute (U01 HL72518, HL097698) and the National Institutes of
Health/National Center for Research Resources (M01-RR000052) to the
Johns Hopkins General Clinical Research Center. We would like to thank
the participants and families of GeneSTAR and our dedicated staff for
all their sacrifices.; GOBS: We acknowledge the ultimate source of our
data, the Mexican American community of San Antonio and surrounding
areas. Financial support for this study was provided by grants from the
National Institute of Mental Health MH0708143 (D.C. Glahn), MH078111 (J.
Blangero) and MH083824 (D.C. Glahn and J. Blangero). Theoretical
development of SOLAR is supported by MH59490 (J. Blangero). This
investigation was conducted, in part, in facilities constructed with
support from Research Facilities Improvement Program grant numbers C06
RR13556 and C06 RR017515 from the National Center for Research
Resources, NIH. Some of this work was performed at Texas Biomedical
Research Institute, where J. Blangero began this investigator-initiated
competitively publicly funded work.; HUBIN: This study was financed by
the Swedish Research Council (K2007-62X-15077-04-1,
K2008-62P-20597-01-3. K2010-62X-15078-07-2, K2012-61X-15078-09-3), the
regional agreement on medical training and clinical research between
Stockholm County Council and the Karolinska Institutet, the Knut and
Alice Wallenberg Foundation, and the HUBIN project. Genotyping was
performed by the SNP&SEQ Technology Platform in Uppsala. The platform is
part of Science for Life Laboratory at Uppsala University and supported
as a national infrastructure by the Swedish Research Council.; IMAGEN:
IMAGEN was supported by the European Union-funded FP6 Integrated Project
IMAGEN (Reinforcement-related behavior in normal brain function and
psychopathology) (LSHM-CT-2007-037286), the FP7 projects IMAGEMEND
(602450) and MATRICS (603016), and the Innovative Medicine Initiative
Project EU-AIMS (115300-2), the Medical Research Council Programme Grant
"Developmental pathways into adolescent substance abuse" (93558), as
well as the NIHR-biomedical Research Center "Mental Health": Further
support was provided by the Swedish Research Council FORMAS, and the
German Federal Ministry for Education and Research BMBF (eMED SysAlc
01ZX1311A; Forschungsnetz AERIAL; 1EV0711) and the US National
Institutes of Health (Axon, Testosterone and Mental Health during
Adolescence; MH085772-01A1), and grants from the French MILDECA and from
the Fondation pour la Recherche Medicale.; IMpACT: This study was funded
by a grant from the Brain & Cognition Excellence Program of the
Netherlands Organization for Scientific Research (NWO, grant 433-09-229)
and in part by the Netherlands Brain Foundation (grant number,
15F07[2]27). B. Franke is supported by a Vici grant from the Netherlands
Organization for Scientific Research (NWO; grant no 016.130.669). The
research leading to these results also receives funding from the
European Community's Seventh Framework Programme (FP7/2007-2013) under
grant agreements no 602450 (IMAGEMEND), no 278948 (TACTICS), and no
602805 (Aggressotype) as well as from the European Community's Horizon
2020 programme under grant agreement no 643051 (MiND). In addition, the
work was supported by a grant for the ENIGMA Consortium (grant number
U54 EB020403) from the BD2K Initiative of a cross-NIH partnership.;
LBC1936: We thank the LBC1936 participants and the members of the
LBC1936 research team who collected and collated the phenotypic and
genotypic data. This work was undertaken as part of the Cross Council
and University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology (CCACE; http://www.ccace.ed.ac.uk). This work was supported
by a Research into Ageing programme grant (to I.J.D.) and the Age
UK-funded Disconnected Mind project
(http://www.disconnectedmind.ed.ac.uk; to I.J.D. and J.M.W.), with
additional funding from the UK Medical Research Council (MRC; to I.J.D.,
J.M.W. and M.E.B.). J.M.W. is supported by the Scottish Funding Council
through the SINAPSE Collaboration (http://www.sinapse.ac.uk). M.V.M. is
supported by the Row Fogo Charitable Trust. CCACE (MRC MR/K026992/1) is
funded by the UK Biotechnology and Biological Sciences Research Council
(BBSRC) and the UK MRC. Genotyping was supported by a grant from the
BBSRC (BB/F019394/1).The image acquisition and analysis was performed at
the Brain Research Imaging Centre, University of Edinburgh
(http://www.bric.ed.ac.uk).; Leiden Longevity Study (LLS): The Leiden
Longevity Study was supported by a grant from the Innovation-Oriented
Research Program on Genomics (SenterNovem IGE05007) and the Netherlands
Consortium for Healthy Ageing (grant number 050-060-810).; Mind Clinical
Imaging Consortium (MCIC): Data used in the preparation of this work
were obtained from the Mind Clinical Imaging Consortium database through
the Mind Research Network (http://www.mrn.org). The MCIC project was
supported by the Department of Energy under Award Number
DE-FG02-08ER64581. MCIC is the result of efforts of co-investigators
from University of Iowa, University of Minnesota, University of New
Mexico, and Massachusetts General Hospital.; MooDS: The establishment of
the MooDS sample was funded by the German Federal Ministry of Education
and Research (BMBF) through the Integrated Genome Research Network (IG)
MooDS (Systematic Investigation of the Molecular Causes of Major Mood
Disorders and Schizophrenia; grant 01GS08144 to M.M. Nothen and S.
Cichon, grant 01GS08147 to J. Rietschel and A. Meyer-Lindenberg and
grant 01GS08148 to A. Heinz), under the auspices of the National Genome
Research Network plus (NGFNplus), and through the Integrated Network
IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental
Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A
to M.M. Nothen, grant 01ZX1314C to H. Walter, grant 01ZX1314G to M.
Rietschel).; MPIP: The MPIP Munich Morphometry Sample comprises images
acquired as part of the Munich Antidepressant Response Signature Study
and the Recurrent Unipolar Depression (RUD) Case-Control study performed
at the MPIP, and control subjects acquired at the
Ludwig-Maximilians-University, Munich, Department of Psychiatry. We
thank E. Meisenzahl and D. Rujescu for providing MRI and genetic data
for inclusion into the MPIP Munich Morphometry sample. We wish to
acknowledge A. Olynyik and radiographers R. Schirmer, E. Schreiter, R.
Borschke and I. Eidner for image acquisition and data preparation. We
thank D.P. Auer for local study management in the initial phase of the
RUD study. We are grateful to GlaxoSmithKline for providing the
genotypes of the Recurrent Unipolar Depression Case-Control Sample. We
thank the staff of the Center of Applied Genotyping (CAGT) for
generating the genotypes of the MARS cohort. The study is supported by a
grant of the Exzellenz-Stiftung of the Max Planck Society. This work has
also been funded by the Federal Ministry of Education and Research
(BMBF) in the framework of the National Genome Research Network (NGFN),
FKZ 01GS0481.; NCNG: this sample collection was supported by grants from
the Bergen Research Foundation and the University of Bergen, the Dr.
Einar Martens Fund, the K.G. Jebsen Foundation, the Research Council of
Norway, to S.L.H., V.M.S. and T.E.; NESDA: Funding was obtained from the
Netherlands Organization for Scientific Research (Geestkracht program
grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO
Genomics), Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI-NL), VU University's Institutes for Health and Care Research
(EMGO+) and Neuroscience Campus Amsterdam, University Medical Center
Groningen, Leiden University Medical Center, National Institutes of
Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2
MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were
funded by the Genetic Association Information Network (GAIN) of the
Foundation for the National Institutes of Health. Computing was
supported by BiG Grid, the Dutch e-Science Grid, which is financially
supported by NWO.; NeuroIMAGE: The NeuroIMAGE project was supported by
NIH Grant R01MH62873 (to S.V. Faraone), NWO Large Investment Grant
1750102007010 (to J. Buitelaar), and by grants from Radboud University
Nijmegen Medical Center, University Medical Center Groningen and Accare,
and VU University Amsterdam. The work contributing to this result also
receives support from the European Community's Seventh Framework
Programme (FP7/2007-2013) under grant agreements no 602450 (IMAGEMEND),
no 278948 (TACTICS) and no 602805 (Aggressotype) as well as from the
European Community's Horizon 2020 programme under grant agreement no
643051 (MiND). In addition, the work was supported by a grant for the
ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative
of a cross-NIH partnership.; NIMH-IRP: Supported in part by the NIMH
Intramural Research Program (ZIAMH002810; Z01MH002792; Z01MH002790).;
North American Brain Expression Consortium (NABEC): This research was
supported by the Intramural Research Program of the NIH, National
Institute on Aging.; Older Australian Twins Study (OATS): We would like
to acknowledge and thank the OATS participants, their supporters and
respective Research Teams. This work was supported by a number of
sources. OATS is supported by the NHMRC/Australian Research Council
Strategic Award 401162 and NHMRC Project Grant 1045325 to P. Sachdev and
colleagues. OATS was facilitated through access to the Australian Twin
Registry, a national research resource supported by the NHMRC Enabling
Grant 310667, administered by the University of Melbourne. DNA was
extracted by Genetic Repositories Australia, an Enabling Facility
supported by the NHMRC Grant 401184. OATS genotyping was partly funded
by a Commonwealth Scientific and Industrial Research Organisation
Flagship Collaboration Fund Grant. Henry Brodaty is supported by the
Australian Government funded Dementia Collaborative Research Centre
(DCRC), UNSW. Nicola Armstrong was supported by the NHMRC Project Grant
525453 and Karen Mather is supported by an Alzheimer's Australia
Dementia Research Foundation Postdoctoral Fellowship and the NHMRC
Capacity Building Grant 568940.; Osaka: This study was supported, in
part, by research grants from the Japanese Ministry of Health, Labor and
Welfare; the Japanese Ministry of Education, Culture, Sports, Science
and Technology (MEXT) KAKENHI and Scientific Research on Innovative
Areas (Comprehensive Brain Science Network); and the Brain Sciences
Project of the Center for Novel Science Initiatives (CNSI), the National
Institutes of Natural Sciences (NINS), and the Brain Mapping by
Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from
Japan Agency for Medical Research and development, AMED.; PAFIP: The
PAFIP study was supported by Instituto de Salud Carlos III, FIS00/3095,
01/3129, PI020499, PI060507, PI10/00183, PI14/00639, the SENY Fundacio
Research Grant CI 2005-0308007, and the Fundacion Marques de Valdecilla
API07/011. PAFIP wish to acknowledge WTCCC2 (Wellcome Trust Case Control
Consortium 2) for DNA Genotyping, Valdecilla Biobank for providing the
biological samples and associated data included in this study and Idival
Neuroimaging Unit for its help in the technical execution of this work.
D. Tordesillas-Gutierrez is funded by a contract from the Carlos III
Health Institute (CA12/00312).; PROSPER: The PROSPER study was supported
by an investigator-initiated grant obtained from Bristol-Myers Squibb.
J.W. Jukema is an Established Clinical Investigator of the Netherlands
Heart Foundation (grant 2001 D 032). Support for genotyping was provided
by the seventh framework program of the European commission (grant
223004) and by the Netherlands Genomics Initiative (Netherlands
Consortium for Healthy Aging grant 050-060-810).; QTIM: D.P.H., N.J.,
C.R.K.C. and P.M.T. are supported, in part, by NIH grants R01 NS080655,
R01AG040060, R01 EB008432, R01 MH097268, U01 AG024904, R01 MH085667, R01
MH089722, P41 EB015922, and R01 MH094343. R.K.W. is supported by
National Science Foundation (BCS-1229450). J.L.S. was supported by the
NIMH (K99MH102357) and Autism Speaks. G.Z. is supported by a Future
Fellowship (FT0991634) from the Australian Research Council. S.E.M. and
G.W.M. are supported by a National Health and Medical Research Council
(NHMRC), Australia, Fellowships (1103623, 619667). The QTIM study is
supported by grants from NIH (R01 HD050735) and the NHMRC (389875,
486682, 1009064). We thank the twins and siblings for their
participation, M. Grace and A. Eldridge for twin recruitment, A. Al
Najjar and other radiographers for scanning, K. McAloney and D. Park for
research support, and A. Henders and staff for DNA sample processing and
preparation.; ROS and MAP: The clinical, genomic, and neuroimaging data
for the Religious Orders Study and the Rush Memory and Aging Project was
funded by NIH grants P30AG10161, RF1AG15819, R01AG17917, R01AG30146,
R01AG40039, and the Translational Genomics Research Institute.;
Rotterdam Study: The generation and management of GWAS genotype data for
the Rotterdam Study are supported by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012).
This study is funded by the Research Institute for Diseases in the
Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO) project nr.
050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and
Erasmus University, Rotterdam, Netherlands Organization for the Health
Research and Development (ZonMw), the Research Institute for Diseases in
the Elderly (RIDE), the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII), and the Municipality of Rotterdam. This research is supported by
the Dutch Technology Foundation STW, which is part of the NWO, and which
is partly funded by the Ministry of Economic Affairs. This project has
received funding from the European Research Council (ERC) under the
European Union's Horizon 2020 research and innovation programme (grant
agreement No 678543). Further support was obtained through the Joint
Programme - Neurodegenerative Disease Research working group on
High-Dimensional Research in Alzheimer's Disease (ZonMW grant number
733051031). MAI is supported by ZonMW grant number 916.13.054. H.H.H.A.
is supported by the Van Leersum Grant of the Royal Netherlands Academy
of Arts and Sciences.; Saguenay Youth Study (SYS): The Saguenay Youth
Study project is funded by the Canadian Institutes of Health Research
(T.P., Z.P.), Heart and Stroke Foundation of Quebec (Z.P.), and the
Canadian Foundation for Innovation (Z.P.). T.P. is supported by the
Tanenbaum Chair in Population Neuroscience at the Rotman Research
Institute, University of Toronto.; SHIP and TREND: The SHIP data sets
are part of the Community Medicine Research net (CMR) of the University
of Greifswald, which is funded by the German Federal Ministry of
Education and Research and the German Ministry of Cultural Affairs, as
well as by the Social Ministry of the Federal State of Mecklenburg-West
Pomerania (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), and the network
'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by
the Federal Ministry of Education and Research (grant 03IS2061A).
Genome-wide data and MRI scans were supported by the Federal Ministry of
Education and Research (grant no. 03ZIK012) and a joint grant from
Siemens Healthcare, Erlangen, Germany, and the Federal State of
Mecklenburg-West Pomerania. The University of Greifswald is a member oft
the Cache Campus Program of the InterSystems GmbH.; Sydney Memory and
Ageing Study (Sydney MAS): We would like to thank the Sydney MAS
participants, their supporters and respective research teams. Sydney MAS
was supported by the Australian National Health and Medical Research
Council (NHMRC) Program Grants 350833 and 568969 to P. Sachdev, H.
Brodaty and G. Andrews. DNA was extracted by Genetic Repositories
Australia, an Enabling Facility supported by the NHMRC Grant 401184. H.
Brodaty is supported by the Australian Government funded Dementia
Collaborative Research Centre (DCRC), UNSW. N. Armstrong was supported
by the NHMRC Project Grant 525453 and K. Mather is supported by an
Alzheimer's Australia Dementia Research Foundation Postdoctoral
Fellowship. Both S. Reppermund and K. Mather are supported by the NHMRC
Capacity Building Grant 568940.; Tasmanian Study of Gait and Cognition
(TASCOG): The Tasmanian Study of Gait and Cognition is supported by
project grants from the National Health and Medical Research Council of
Australia (NHMRC; 403000, 491109, and 606543) and a grant from the
Wicking Dementia Education and Research Centre, Hobart. V.S. is
supported by a cofunded NHMRC Career Development Fellowship (1061457)
and a Heart Foundation Future Leader Fellowship (ID 100089).; Three-City
Dijon Study: The Three-City Study is conducted under a partnership
agreement among the Institut National de la Sante et de la Recherche
Medicale (INSEAM), the Victor Segalen-Bordeaux II University, and
Sanofi-Aventis. The Fondation pour la Recherche Medicale funded the
preparation and initiation of the study. The Three-City Study is also
supported by the Caisse Nationale Maladie des Travailleurs Salaries,
Direction Generale de la Sante, Mutuelle Generale de l'Education
Nationale (MGEN), Institut de la Longevite, Conseils Regionaux of
Aquitaine and Bourgogne, Fondation de France, and Ministry of Research
INSEAM Programme "Cohortes et collections de donnees biologiques."
Christophe Tzourio and Stephanie Debette are supported by a grant from
the Fondation Leducq.; TOP: The study was supported by the Research
Council of Norway (#213837, #223273, #229129), South-East Norway Health
Authority (#2013-123) and KG Jebsen Foundation. The research leading to
these results has received funding from the European Community's Seventh
Framework Programme (FP7/2007-2013) under grant agreement no 602450
(IMAGEMEND).; UMCU: UMCU acknowledgment data: This work was supported by
917.46.370 (H.H.) and 908-02-123 (H.H.) from the Netherlands
Organization for Health Research and Development ZonMW.; WHICAP: This
study was supported by a grant from the NIH (5R01AG037212). CHARGE
consortium: See ref. 40 for the general cognitive function GWAS, and
ref. 29 for the white matter lesion GWAS.; IGAP: We thank the
International Genomics of Alzheimer's Project (IGAP) for providing
summary results data for these analyses. The investigators within IGAP
contributed to the design and implementation of IGAP and/or provided
data but did not participate in analysis or writing of this report. IGAP
was made possible by the generous participation of the control subjects,
the patients, and their families. The i-Select chips was funded by the
French National Foundation on Alzheimer's disease and related disorders.
EADI was supported by the LABEX (laboratory of excellence program
investment for the future) DISTALZ grant, Inserm, Institut Pasteur de
Lille, University de Lille 2 and the Lille University Hospital. GERAD
was supported by the Medical Research Council (Grant no 503480),
Alzheimer's Research UK (Grant no 503176), the Wellcome Trust (Grant no
082604/2/07/Z) and German Federal Ministry of Education and Research
(BMBF): Competence Network Dementia (CND) grant no 01G10102, 01G10711,
01G10420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193
and the NIA AG081220 and AGES contract N01-AG-12100, the NHLBI grant R01
HL105756, the Icelandic Heart Association, and the Erasmus Medical
Center and Erasmus University. ADGC was supported by the NIH/NIA grants:
U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's
Association grant ADGC-10-196728.
NR 46
TC 0
Z9 0
U1 29
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD DEC
PY 2016
VL 19
IS 12
BP 1569
EP 1582
DI 10.1038/nn.4398
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA ED7BY
UT WOS:000389011900016
PM 27694991
ER
PT J
AU Garfield, AS
Shah, BP
Burgess, CR
Li, MM
Li, C
Steger, JS
Madara, JC
Campbell, JN
Kroeger, D
Scammell, TE
Tannous, BA
Myers, MG
Andermann, ML
Krashes, MJ
Lowell, BB
AF Garfield, Alastair S.
Shah, Bhavik P.
Burgess, Christian R.
Li, Monica M.
Li, Chia
Steger, Jennifer S.
Madara, Joseph C.
Campbell, John N.
Kroeger, Daniel
Scammell, Thomas E.
Tannous, Bakhos A.
Myers, Martin G., Jr.
Andermann, Mark L.
Krashes, Michael J.
Lowell, Bradford B.
TI Dynamic GABAergic afferent modulation of AgRP neurons
SO NATURE NEUROSCIENCE
LA English
DT Article
ID BROWN ADIPOSE-TISSUE; DORSOMEDIAL HYPOTHALAMUS; FEEDING CIRCUITS; LEPTIN
ACTION; NUCLEUS; HUNGER; PRESSURE; BEHAVIOR; OBESITY; POMC
AB Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues before ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the preconsummatory modulation of ARC(AgRP) neurons. In a manner reciprocal to ARC(AgRP) neurons, ARC-projecting leptin receptor expressing GABAergic vDMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, leptin receptor-expressing GABAergic vDMH neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARC(AgRP) neuron activity and feeding behavior.
C1 [Garfield, Alastair S.; Shah, Bhavik P.; Burgess, Christian R.; Li, Monica M.; Steger, Jennifer S.; Madara, Joseph C.; Campbell, John N.; Andermann, Mark L.; Lowell, Bradford B.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Garfield, Alastair S.] Univ Edinburgh, Ctr Integrat Physiol, Hugh Robson Bldg, Edinburgh, Midlothian, Scotland.
[Li, Chia; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Li, Chia; Krashes, Michael J.] NIDA, NIH, Baltimore, MD USA.
[Kroeger, Daniel; Scammell, Thomas E.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA.
[Tannous, Bakhos A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Myers, Martin G., Jr.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Myers, Martin G., Jr.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Andermann, Mark L.; Lowell, Bradford B.] Harvard Med Sch, Program Neurosci, Boston, MA USA.
[Garfield, Alastair S.; Shah, Bhavik P.] Pfizer, Cardiovasc & Metab Dis, Cambridge, MA 02139 USA.
RP Garfield, AS (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.; Garfield, AS (reprint author), Univ Edinburgh, Ctr Integrat Physiol, Hugh Robson Bldg, Edinburgh, Midlothian, Scotland.; Garfield, AS (reprint author), Pfizer, Cardiovasc & Metab Dis, Cambridge, MA 02139 USA.
EM alastair.garfield@pfizer.com; manderma@bidmc.harvard.edu;
michael.krashes@nih.gov; blowell@bidmc.harvard.edu
FU University of Edinburgh Chancellor's Fellowship; National Institutes of
Health [R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37
DK053477, P30 DK046200, R01 DK056731, P30 DK057521, F32 DK089710, DP2
DK105570-01, R01 DK109930]; McKnight Foundation; Klarman Family
Foundation; Richard and Susan Smith Family Foundation; Pew Scholars
Program in Biomedical Sciences; ADA Mentor-Based Fellowship; Davis
Family Foundation; AHA postdoctoral fellowship [14POST20100011];
Intramural Research Program of the NIH, The National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) [DK075087, DK075088];
NIH/NINDS [P30NS045776]
FX We thank B. Sabatini and K.W. Huang for assistance with in vivo fiber
photometry. We thank Drs. V. Jayaraman, R.A. Kerr, D.S. Kim, L.L. Looger
and K. Svoboda and the GENIE Project at Janelia Farm Research Campus,
Howard Hughes Medical Institute, for distribution of GCaMP6. This work
was supported by the University of Edinburgh Chancellor's Fellowship
(A.S.G.); National Institutes of Health grants R01 DK096010 (B.B.L.),
R01 DK089044 (B.B.L.), R01 DK071051 (B.B.L.), R01 DK075632 (B.B.L.), R37
DK053477 (B.B.L.), BNORC Transgenic Core P30 DK046200 (B.B.L.), R01
DK056731 (M.J.G.), BADERC Transgenic Core P30 DK057521 (B.B.L.), F32
DK089710 (M.J.K.), DP2 DK105570-01 (M.L.A.) and R01 DK109930 (M.L.A.);
the McKnight Foundation (M.L.A.); the Klarman Family Foundation
(M.L.A.); the Richard and Susan Smith Family Foundation (M.L.A.); the
Pew Scholars Program in Biomedical Sciences (M.L.A.); ADA Mentor-Based
Fellowship (B.P.S. and B.B.L.); Davis Family Foundation postdoctoral
fellowship award (C.R.B.); and AHA postdoctoral fellowship
14POST20100011 (J.N.C.). This research was supported, in part, by the
Intramural Research Program of the NIH, The National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK; DK075087, DK075088).
The GH Viral vector core facility was funded by NIH/NINDS grant
P30NS045776 (B.A.T.) for the preparation of the rabies virus.
NR 29
TC 2
Z9 2
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD DEC
PY 2016
VL 19
IS 12
BP 1628
EP 1635
DI 10.1038/nn.4392
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA ED7BY
UT WOS:000389011900022
PM 27643429
ER
PT J
AU Adiseshaiah, PP
Crist, RM
Hook, SS
McNeil, SE
AF Adiseshaiah, Pavan P.
Crist, Rachael M.
Hook, Sara S.
McNeil, Scott E.
TI Nanomedicine strategies to overcome the pathophysiological barriers of
pancreatic cancer
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID ADVANCED SOLID TUMORS; PHASE-III TRIAL; HEDGEHOG SIGNALING PATHWAY;
GEMCITABINE PLUS PLACEBO; DUCTAL ADENOCARCINOMA; NAB-PACLITAXEL;
COLORECTAL-CANCER; CLINICAL-TRIALS; DRUG-DELIVERY; BLOOD-VESSELS
AB Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancerrelated deaths. PDAC remains one of the most difficult-to-treat cancers, owing to its unique pathobiological features: a nearly impenetrable desmoplastic stroma, and hypovascular and hypoperfused tumour vessels render most treatment options largely ineffective. Progress in understanding the pathobiology and signalling pathways involved in disease progression is helping researchers to develop novel ways to fight PDAC, including improved nanotechnology-based drug-delivery platforms that have the potential to overcome the biological barriers of the disease that underlie persistent drug resistance. So-called 'nanomedicine' strategies have the potential to enable targeting of the Hedgehog-signalling pathway, the autophagy pathway, and specific RAS-mutant phenotypes, among other pathological processes of the disease. These novel therapies, alone or in combination with agents designed to disrupt the pathobiological barriers of the disease, could result in superior treatments, with increased efficacy and reduced off-target toxicities compared with the current standard-of-care regimens. By overcoming drug-delivery challenges, advances can be made in the treatment of PDAC, a disease for which limited improvement in overall survival has been achieved over the past several decades. We discuss the approaches to nanomedicine that have been pursued to date and those that are the focus of ongoing research, and outline their potential, as well as the key challenges that must be overcome.
C1 [Adiseshaiah, Pavan P.; Crist, Rachael M.; McNeil, Scott E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD 21702 USA.
[Hook, Sara S.] NCI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Adiseshaiah, PP (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD 21702 USA.
EM pavan.adiseshaiah@fnlcr.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012; Crist,
Rachael/K-7603-2012
FU Frederick National Laboratory for Cancer Research, US NIH
[HHSN261200800001E]
FX The authors thank Dr Stephan T. Stern and Dr Jennifer H. Grossman for
their critical review of the manuscript, and Allen Kane of Leidos
Biomedical Research for assistance with graphic illustrations. The work
of P.P.A., R.M.C., and S.E.M. has been funded, in whole or in part, by
Federal funds from the Frederick National Laboratory for Cancer
Research, US NIH, under contract HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 175
TC 1
Z9 1
U1 34
U2 34
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD DEC
PY 2016
VL 13
IS 12
BP 750
EP 765
DI 10.1038/nrclinonc.2016.119
PG 16
WC Oncology
SC Oncology
GA ED5YG
UT WOS:000388929200008
PM 27531700
ER
PT J
AU Hesse, BW
Greenberg, AJ
Rutten, LJF
AF Hesse, Bradford W.
Greenberg, Alexandra J.
Rutten, Lila J. Finney
TI The role of Internet resources in clinical oncology: promises and
challenges
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION-SEEKING; CONNECTED HEALTH;
CANCER; CARE; COMMUNICATION; SCIENCE; ACCESS; TELEDERMATOLOGY; ATTITUDES
AB The Internet is a valuable tool that continues to revolutionize many aspects of our lives; however, the ability to disseminate diverse data across populations and nations presents both opportunities and challenges. Online resources are increasingly used in health care, providing wider access to information for patients, researchers, and clinicians. At the turn of the millennium, the National Cancer Institute (NCI) predicted that Internet-based technologies would create a revolution in communication for oncology professionals and patients with cancer. Herein, findings from the NCI's Health Information National Trends Survey are reviewed to give insight into how Internet trends related to oncology patients are evolving. Future trends are discussed, including examples of 'connected health' in oncology; the spread of mobile and ubiquitous access points to Internet-hosted information; the diffusion of devices, sensors, and apps; the spread of personal data sharing; and an evolution in how networks can support person-centred and family-centred care.
C1 [Hesse, Bradford W.; Greenberg, Alexandra J.] NCI, HCIRB, BRP, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Rutten, Lila J. Finney] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Hlth Care Deli, Rochester, MN 55905 USA.
RP Hesse, BW (reprint author), NCI, HCIRB, BRP, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov
FU NIH National Cancer Institute; Cancer Prevention Fellowship at the
National Cancer Institute
FX The work of B.W.H., A.J.G., and L.J.F.R. is supported by the NIH
National Cancer Institute. A.J.G. was supported by the Cancer Prevention
Fellowship at the National Cancer Institute.
NR 103
TC 1
Z9 1
U1 9
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD DEC
PY 2016
VL 13
IS 12
BP 767
EP 776
DI 10.1038/nrclinonc.2016.78
PG 10
WC Oncology
SC Oncology
GA ED5YG
UT WOS:000388929200009
PM 27273045
ER
PT J
AU Lenardo, MJ
AF Lenardo, Michael J.
TI Focus on Research Clinical Genomics - Molecular Pathogenesis Revealed
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lenardo, Michael J.] NIAID, Clin Genom Program, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Lenardo, MJ (reprint author), NIAID, Clin Genom Program, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 2
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 1
PY 2016
VL 375
IS 22
BP 2117
EP 2119
DI 10.1056/NEJMp1611419
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA ED7GN
UT WOS:000389030400003
PM 27959769
ER
PT J
AU Baeten, JM
Palanee-Phillips, T
Brown, ER
Schwartz, K
Soto-Torres, LE
Govender, V
Mgodi, NM
Kiweewa, FM
Nair, G
Mhlanga, F
Siva, S
Bekker, LG
Jeenarain, N
Gaffoor, Z
Martinson, F
Makanani, B
Pather, A
Naidoo, L
Husnik, M
Richardson, BA
Parikh, UM
Mellors, JW
Marzinke, MA
Hendrix, CW
van der Straten, A
Ramjee, G
Chirenje, ZM
Nakabiito, C
Taha, TE
Jones, J
Mayo, A
Scheckter, R
Berthiaume, J
Livant, E
Jacobson, C
Ndase, P
White, R
Patterson, K
Germuga, D
Galaska, B
Bunge, K
Singh, D
Szydlo, DW
Montgomery, ET
Mensch, BS
Torjesen, K
Grossman, CI
Chakhtoura, N
Nel, A
Rosenberg, Z
McGowan, I
Hillier, S
AF Baeten, J. M.
Palanee-Phillips, T.
Brown, E. R.
Schwartz, K.
Soto-Torres, L. E.
Govender, V.
Mgodi, N. M.
Kiweewa, F. Matovu
Nair, G.
Mhlanga, F.
Siva, S.
Bekker, L. -G.
Jeenarain, N.
Gaffoor, Z.
Martinson, F.
Makanani, B.
Pather, A.
Naidoo, L.
Husnik, M.
Richardson, B. A.
Parikh, U. M.
Mellors, J. W.
Marzinke, M. A.
Hendrix, C. W.
van der Straten, A.
Ramjee, G.
Chirenje, Z. M.
Nakabiito, C.
Taha, T. E.
Jones, J.
Mayo, A.
Scheckter, R.
Berthiaume, J.
Livant, E.
Jacobson, C.
Ndase, P.
White, R.
Patterson, K.
Germuga, D.
Galaska, B.
Bunge, K.
Singh, D.
Szydlo, D. W.
Montgomery, E. T.
Mensch, B. S.
Torjesen, K.
Grossman, C. I.
Chakhtoura, N.
Nel, A.
Rosenberg, Z.
McGowan, I.
Hillier, S.
CA MTN-020-ASPIRE Study Team
TI Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in
Women
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PREEXPOSURE PROPHYLAXIS; ANTIRETROVIRAL PROPHYLAXIS; CLINICAL-TRIALS;
AFRICAN WOMEN; DOUBLE-BLIND; INFECTION; TENOFOVIR; THAILAND; SAFETY; MEN
AB BACKGROUND
Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.
METHODS
We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe.
RESULTS
Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 personyears, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [ CI], 1 to 46; P = 0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P = 0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P < 0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P = 0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups.
CONCLUSIONS
A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096.)
C1 [Baeten, J. M.; Richardson, B. A.; Ndase, P.] Univ Washington, Dept Global Hlth, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.
[Baeten, J. M.] Univ Washington, Dept Med, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.
[Baeten, J. M.; Husnik, M.] Univ Washington, Dept Epidemiol, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.
[Brown, E. R.; Richardson, B. A.] Univ Washington, Dept Biostat, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.
[Brown, E. R.; Husnik, M.; Richardson, B. A.; Berthiaume, J.; Patterson, K.; Szydlo, D. W.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, 1124 Columbia St, Seattle, WA 98104 USA.
[Palanee-Phillips, T.] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
[Govender, V.; Siva, S.; Jeenarain, N.; Gaffoor, Z.; Pather, A.; Naidoo, L.; Ramjee, G.] South African Med Res Council, HIV Prevent Res Unit, Durban, South Africa.
[Nair, G.] Ctr AIDS Programme Res South Africa, Durban, South Africa.
[Bekker, L. -G.] Univ Cape Town, Desmond Tutu HIV Ctr, Cape Town, South Africa.
[Schwartz, K.; Mayo, A.; Scheckter, R.; White, R.; Torjesen, K.] FHI 360, Durham, NC USA.
[Soto-Torres, L. E.; Germuga, D.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Grossman, C. I.] NIMH, NIH, Bethesda, MD 20892 USA.
[Chakhtoura, N.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, NIH, Bethesda, MD USA.
[Marzinke, M. A.; Hendrix, C. W.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Taha, T. E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Nel, A.; Rosenberg, Z.] Int Partnership Microbicides, Silver Spring, MD USA.
[Mgodi, N. M.; Mhlanga, F.; Chirenje, Z. M.] Univ Zimbabwe Univ Calif San Francisco Collaborat, Harare, Zimbabwe.
[Kiweewa, F. Matovu; Nakabiito, C.] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda.
[Martinson, F.] Univ North Carolina Project, Lilongwe, Malawi.
[Makanani, B.; Taha, T. E.] Queen Elizabeth Cent Hosp, Malawi Coll Med Johns Hopkins Univ Res Project, Blantyre, Malawi.
[Parikh, U. M.; Mellors, J. W.; McGowan, I.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Bunge, K.; Hillier, S.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Jones, J.; Livant, E.; Jacobson, C.; Galaska, B.; Singh, D.] Magee Womens Res Inst, Pittsburgh, PA USA.
[van der Straten, A.; Montgomery, E. T.] RTI Int, Womens Global Hlth Imperat, San Francisco, CA USA.
[van der Straten, A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Mensch, B. S.] Populat Council, 1230 York Ave, New York, NY 10021 USA.
RP Baeten, JM (reprint author), Univ Washington, Dept Global Hlth, Int Clin Res Ctr, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.
EM jbaeten@uw.edu
FU National Institute of Allergy and Infectious Diseases [UM1AI068633,
UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Mental Health
FX Supported by grants (UM1AI068633, UM1AI068615, and UM1AI106707) from the
National Institute of Allergy and Infectious Diseases, the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, and the National Institute of Mental Health.
NR 33
TC 17
Z9 17
U1 2
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 1
PY 2016
VL 375
IS 22
BP 2121
EP 2132
DI 10.1056/NEJMoa1506110
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA ED7GN
UT WOS:000389030400004
PM 26900902
ER
PT J
AU Hourigan, CS
Haferlach, T
Hokland, P
AF Hourigan, Christopher S.
Haferlach, Torsten
Hokland, Peter
TI Cord-Blood Transplantation in Patients with Minimal Residual Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID HEMATOPOIETIC-CELL TRANSPLANTATION; COMPLETE REMISSION
C1 [Hourigan, Christopher S.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Haferlach, Torsten] Munich Leukemia Lab, Munich, Germany.
[Hokland, Peter] Aarhus Univ Hosp, Aarhus, Denmark.
RP Hourigan, CS (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM hourigan@nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 1
PY 2016
VL 375
IS 22
BP 2204
EP 2204
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA ED7GN
UT WOS:000389030400024
PM 27959750
ER
PT J
AU Walkley, SU
Davidson, CD
Jacoby, J
Marella, PD
Ottinger, EA
Austin, CP
Porter, FD
Vite, CH
Ory, DS
AF Walkley, Steven U.
Davidson, Cristin D.
Jacoby, Jonathan
Marella, Philip D.
Ottinger, Elizabeth A.
Austin, Christopher P.
Porter, Forbes D.
Vite, Charles H.
Ory, Daniel S.
TI Fostering collaborative research for rare genetic disease: the example
of niemann-pick type C disease
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Article
DE Cyclodextrin; Collaborative science; Drug pipeline; Lysosomal disease;
Miglustat; Niemann-Pick C; Patient advocacy; Rare disease; Therapy
development; Translational medicine
ID CHOLESTEROL HOMEOSTASIS; NEURONAL CHOLESTEROL; MURINE MODEL; MOUSE;
2-HYDROXYPROPYL-BETA-CYCLODEXTRIN; PROGRESSION; STORAGE; NPC1;
ESTERIFICATION; GANGLIOSIDES
AB Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the "SOAR" mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders.
C1 [Walkley, Steven U.; Davidson, Cristin D.] Albert Einstein Coll Med, Rose F Kennedy Intellectual & Dev Disabil Res Ctr, Dominick P Purpura Dept Neurosci, 1410 Pelham Pkwy South, Bronx, NY 10461 USA.
[Jacoby, Jonathan] Hide & Seek Fdn Lysosomal Dis Res, 6475 East Pacific Coast Highway,Suite 466, Long Beach, CA 90803 USA.
[Marella, Philip D.] Danas Angels Res Trust, 15 East Putnam Ave,117, Greenwich, CT 06830 USA.
[Ottinger, Elizabeth A.] NIH, Div PreClin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20817 USA.
[Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Translat Med, NIH, DHHS, Rm 5-2571,10CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
[Vite, Charles H.] Univ Penn, Sch Vet Med, Dept Clin Sci, 3800 Spruce St, Philadelphia, PA 19104 USA.
[Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, Box 8086,660 S Euclid Ave, St Louis, MO 63110 USA.
RP Walkley, SU (reprint author), Albert Einstein Coll Med, Rose F Kennedy Intellectual & Dev Disabil Res Ctr, Dominick P Purpura Dept Neurosci, 1410 Pelham Pkwy South, Bronx, NY 10461 USA.
EM Steve.Walkley@einstein.yu.edu
RI Davidson, Cristin/F-4889-2017
OI Davidson, Cristin/0000-0002-5508-8113
FU Dana's Angel's Research Trust; Hide & Seek Foundation for Lysosomal
Disease Research; Hadley Hope; Race for Adam; Fight NPC; Andrews Firefly
Fund
FX We are grateful to the families who sponsor SOAR-NPC and collaborate
with the scientific research team in this endeavor: Dana's Angel's
Research Trust (Marella family), the Hide & Seek Foundation for
Lysosomal Disease Research, Hadley Hope (Hadley family), Race for Adam
(Recke family), Fight NPC (Chan family), and Andrews Firefly Fund
(Andrews family). The important roles that these funding groups play in
the operation of the SOAR-NPC Collaborative are outlined in the article.
Two individuals (JJ, PDM) associated with these groups also participated
in writing this article.
NR 36
TC 0
Z9 0
U1 9
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD DEC 1
PY 2016
VL 11
AR 161
DI 10.1186/s13023-016-0540-x
PG 11
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA ED7AW
UT WOS:000389009100001
PM 27903269
ER
PT J
AU Moss, JL
Reiter, PL
Truong, YK
Rimer, BK
Brewer, NT
AF Moss, Jennifer L.
Reiter, Paul L.
Truong, Young K.
Rimer, Barbara K.
Brewer, Noel T.
TI School Entry Requirements and Coverage of Nontargeted Adolescent
Vaccines
SO PEDIATRICS
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS; HPV VACCINATION; UNITED-STATES; IMMUNIZATION
REQUIREMENTS; NONMEDICAL EXEMPTIONS; IMPACT; RATES; RECOMMENDATIONS;
SCHOOLCHILDREN; MANDATES
AB BACKGROUND: Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states' school entry requirements and adolescent vaccination.
METHODS: We gathered data on states' school entry requirements for adolescent vaccination (tetanus, diphtheria, and pertussis [Tdap] booster; meningococcal; and HPV) from 2007 to 2012 from Immunization Action Coalition. The National Immunization Survey-Teen provided medical record-verified vaccination data for 99 921 adolescents. We calculated coverage (among 13- to 17-year-olds) for individual vaccinations and concomitant vaccination. HPV vaccination outcomes were among female adolescents. Analyses used weighted longitudinal multivariable models.
RESULTS: States with requirements for Tdap booster and meningococcal vaccination had 22 and 24 percentage point increases in coverage for these vaccines, respectively, compared with other states (both P < .05). States with HPV vaccination requirements had < 1 percentage point increase in coverage for this vaccine (P < .05). Tdap booster and meningococcal vaccination requirements, respectively, were associated with 8 and 4 percentage point spillover increases for HPV vaccination coverage (both P < .05) and with increases for concomitant vaccination (all P < .05).
CONCLUSIONS: Ensuring all states have meningococcal vaccination requirements could improve the nation's HPV vaccination coverage, given that many states already require Tdap booster but not meningococcal vaccination for school entry. Vaccination programs and clinicians should capitalize on changes in adolescent vaccination, including concomitant vaccination, that may arise after states adopt vaccination requirements. Additional studies are needed on the effects of HPV vaccination requirements and opt-out provisions.
C1 [Moss, Jennifer L.; Rimer, Barbara K.; Brewer, Noel T.] Univ N Carolina, Dept Hlth Behav, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Truong, Young K.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Rimer, Barbara K.; Brewer, Noel T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Reiter, Paul L.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
RP Moss, JL (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E514,MSC 9765, Bethesda, MD 20892 USA.
EM jennifer.moss@nih.gov
FU National Institutes of Health [F31 CA189411]; National Institutes of
Health (NIH); [NSF-DMS-1106962]
FX Supported by National Institutes of Health grant F31 CA189411 (principal
investigator: Jennifer L. Moss). Dr Truong was supported by
NSF-DMS-1106962. Funded by the National Institutes of Health (NIH).
NR 38
TC 1
Z9 1
U1 3
U2 3
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD DEC
PY 2016
VL 138
IS 6
AR e20161414
DI 10.1542/peds.2016-1414
PG 10
WC Pediatrics
SC Pediatrics
GA ED5WX
UT WOS:000388924800027
ER
PT J
AU McCafferty, CL
Sergeev, YV
AF McCafferty, Caitlyn L.
Sergeev, Yuri V.
TI In silico Mapping of Protein Unfolding Mutations for Inherited Disease
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; AMINO-ACID VARIANTS; RHODOPSIN GENE;
OCULAR FINDINGS; PERSONALIZED MEDICINE; DISULFIDE-ISOMERASE; MISSENSE
MUTATIONS; POLYPEPTIDE-CHAIN; STABILITY CHANGES; MECHANISMS
AB The effect of disease-causing missense mutations on protein folding is difficult to evaluate. To understand this relationship, we developed the unfolding mutation screen (UMS) for in silico evaluation of the severity of genetic perturbations at the atomic level of protein structure. The program takes into account the protein-unfolding curve and generates propensities using calculated free energy changes for every possible missense mutation at once. These results are presented in a series of unfolding heat maps and a colored protein 3D structure to show the residues critical to the protein folding and are available for quick reference. UMS was tested with 16 crystal structures to evaluate the unfolding for 1391 mutations from the ProTherm database. Our results showed that the computational accuracy of the unfolding calculations was similar to the accuracy of previously published free energy changes but provided a better scale. Our residue identity control helps to improve protein homology models. The unfolding predictions for proteins involved in age-related macular degeneration, retinitis pigmentosa, and Leber's congenital amaurosis matched well with data from previous studies. These results suggest that UMS could be a useful tool in the analysis of genotype-to-phenotype associations and next-generation sequencing data for inherited diseases.
C1 [McCafferty, Caitlyn L.; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Sergeev, YV (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM sergeevy@nei.nih.gov
NR 64
TC 1
Z9 1
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 1
PY 2016
VL 6
AR 37298
DI 10.1038/srep37298
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED6UR
UT WOS:000388992600001
PM 27905547
ER
PT J
AU Schuemie, MJ
Trifiro, G
Coloma, PM
Ryan, PB
Madigan, D
AF Schuemie, Martijn J.
Trifiro, Gianluca
Coloma, Preciosa M.
Ryan, Patrick B.
Madigan, David
TI Detecting adverse drug reactions following long-term exposure in
longitudinal observational data: The exposure-adjusted self-controlled
case series
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE adverse drug reactions; methods analysis; self-controlled case series;
claims databases; receiver operator characteristics curve
ID LEVODOPA-INDUCED DYSKINESIA; ORAL-CONTRACEPTIVES; PARKINSONS-DISEASE;
RISK; CANCER; COHORT; EPIDEMIOLOGY; MODEL; INHIBITORS; DEPENDENCE
AB Most approaches used in postmarketing drug safety monitoring, including spontaneous reporting and statistical risk identification using electronic health care records, are primarily suited to pick up only acute adverse drug effects. With the availability of increasingly larger electronic health record and administrative claims databases comes the opportunity to monitor for potential adverse effects that occur only after prolonged exposure to a drug, but analysis methods are lacking. We propose an adaptation of the self-controlled case series design that uses the notion of accumulated exposure to capture long-term effects of drugs and evaluate extensions to correct for age and recurrent events. Several variations of the approach are tested on simulated data and two large insurance claims databases. To evaluate performance a set of positive and negative control drug-event pairs was created by medical experts based on drug product labels and review of the literature. Performance on the real data was measured using the area under the receiver operator characteristics curve. The best performing method achieved an area under the receiver operator characteristics curve of 0.86 in the largest database using a spline model, adjustment for age, and ignoring recurrent events, but it appears this performance can only be achieved with very large data sets.
C1 [Schuemie, Martijn J.; Trifiro, Gianluca; Coloma, Preciosa M.] Erasmus Univ, Med Ctr Rotterdam, Dept Med Informat, POB 2040, NL-3000 CA Rotterdam, Netherlands.
[Schuemie, Martijn J.; Ryan, Patrick B.; Madigan, David] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD USA.
[Trifiro, Gianluca] Univ Messina, Dept Clin & Expt Med, Messina, Italy.
[Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, FL USA.
[Madigan, David] Columbia Univ, Dept Stat, New York, NY USA.
RP Schuemie, MJ (reprint author), Erasmus Univ, Med Ctr Rotterdam, Dept Med Informat, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM m.schuemie@erasmusmc.nl
FU Observational Medical Outcomes Partnership, Foundation for the National
Institutes of Health
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research has been funded by a grant from the Observational Medical
Outcomes Partnership, Foundation for the National Institutes of Health.
NR 39
TC 2
Z9 2
U1 1
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD DEC
PY 2016
VL 25
IS 6
BP 2577
EP 2592
DI 10.1177/0962280214527531
PG 16
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA ED1SR
UT WOS:000388625700012
PM 24685766
ER
PT J
AU van den Heuvel, MI
Thomason, ME
AF van den Heuvel, Marion I.
Thomason, Moriah E.
TI Functional Connectivity of the Human Brain in Utero
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID PRENATAL ALCOHOL EXPOSURE; RESTING-STATE NETWORKS; MAGNETIC-RESONANCE;
HUMAN FETAL; WHITE-MATTER; HEMODYNAMIC-RESPONSES; SPATIOTEMPORAL ATLAS;
PRETERM INFANTS; DEFAULT-MODE; FOLLOW-UP
AB The brain is subject to dramatic developmental processes during the prenatal period. Nevertheless, information about the development of functional brain networks during gestation is scarce. Until recently it has not been possible to probe function in the living human fetal brain. Advances in functional MRI have changed the paradigm, making it possible to measure spontaneous activity in the fetal brain and to cross-correlate functional signals to attain information about neural connectional architecture across human gestation. We summarize the earliest MRI studies of fetal neural functional connectivity and highlight unique challenges and limitations inherent in the technique. In addition, we discuss future directions to unlock the potential of fetal brain functional MRI research.
C1 [van den Heuvel, Marion I.; Thomason, Moriah E.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
[van den Heuvel, Marion I.; Thomason, Moriah E.] NICHHD, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA.
[Thomason, Moriah E.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
RP Thomason, ME (reprint author), Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.; Thomason, ME (reprint author), NICHHD, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA.; Thomason, ME (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
EM moriah@wayne.edu
FU National Institutes of Health [MH110793, ES026022]; NARSAD Young
Investigator Award; NIH [HHSN 275201300006C]
FX This project was supported by awards to M.E.T. from the National
Institutes of Health, MH110793 and ES026022, and by a NARSAD Young
Investigator Award. This project was also supported in part by NIH
contract HHSN 275201300006C. The authors also thank participant families
who generously shared their time.
NR 71
TC 1
Z9 1
U1 9
U2 9
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD DEC
PY 2016
VL 20
IS 12
BP 931
EP 939
DI 10.1016/j.tics.2016.10.001
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA ED8FE
UT WOS:000389106600007
PM 27825537
ER
PT J
AU Hand, TW
Vujkovic-Cvijin, I
Ridaura, VK
Belkaid, Y
AF Hand, Timothy W.
Vujkovic-Cvijin, Ivan
Ridaura, Vanessa K.
Belkaid, Yasmine
TI Linking the Microoiota, Chronic Disease, anc the Immune System
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; NEGLECTED TROPICAL DISEASES; RANDOMIZED
CONTROLLED-TRIAL; CHRONIC HIV-INFECTION; T-CELL RESPONSES; GUT
MICROBIOTA; INTESTINAL MICROBIOTA; COMMENSAL BACTERIA; ADIPOSE-TISSUE;
BEIGE FAT
AB Chronic inflammatory diseases (CIDs) are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many CIDs are associated with significant shifts in the microbiota toward inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system.
C1 [Hand, Timothy W.] Univ Pittsburgh, Richard King Mellon Inst Pediat Res, Childrens Hosp Pittsburgh, UPMC, Pittsburgh, PA 15224 USA.
[Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Belkaid, Yasmine] NIAID, Microbiome Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Hand, TW (reprint author), Univ Pittsburgh, Richard King Mellon Inst Pediat Res, Childrens Hosp Pittsburgh, UPMC, Pittsburgh, PA 15224 USA.
EM timothy.hand@chp.edu
FU NIAID [K22 AI108719]; NIH intramural program
FX The authors would like to apologize that due to length requirements not
all work in this burgeoning field could be discussed and properly cited.
This work was supported by NIAID K22 AI108719 (T.W.H.) and the NIH
intramural program (V.K.R, I.V-C., and Y.B,). The authors would like to
thank K. Gopalakrishna and J. Tometich for critical reading of the
manuscript.
NR 131
TC 1
Z9 1
U1 7
U2 7
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD DEC
PY 2016
VL 27
IS 12
BP 831
EP 843
DI 10.1016/jtem.2016.08.003
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA ED8DO
UT WOS:000389102400001
PM 27623245
ER
PT J
AU Kumar, NP
Moideen, K
Sivakumar, S
Menon, PA
Viswanathan, V
Kornfeld, H
Babu, S
AF Kumar, Nathella Pavan
Moideen, Kadar
Sivakumar, Shanmugam
Menon, Pradeep A.
Viswanathan, Vijay
Kornfeld, Hardy
Babu, Subash
TI Modulation of dendritic cell and monocyte subsets in tuberculosis
diabetes co-morbidity upon standard tuberculosis treatment
SO TUBERCULOSIS
LA English
DT Article
ID MELLITUS
AB Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting. blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Kumar, Nathella Pavan; Moideen, Kadar; Babu, Subash] Natl Inst Hlth, Int Ctr Excellence Res, NIRT, Madras, Tamil Nadu, India.
[Viswanathan, Vijay] Prof M Viswanathan Diabet Res Ctr, Madras, Tamil Nadu, India.
[Sivakumar, Shanmugam; Menon, Pradeep A.] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Kornfeld, Hardy] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Babu, Subash] NIAID, LPD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Kumar, NP (reprint author), NIH NIRT ICER, Natl Inst Res TB, Madras, Tamil Nadu, India.
EM pavankumarn@nirt.res.in
FU Indian Department of Biotechnology; Indian Council of Medical Research;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Division of Intramural Research, NIAID, NIH; CRDF
Global [USB1-31149-XX-13]
FX We thank the staff of Department of Clinical Research and the Department
of Bacteriology, NIRT for valuable assistance in bacterial cultures and
radiology and the Staff of MVDRC for valuable assistance in recruiting
the patients for this study, R. Anuradha, Prabha Chandran, Yukthi Bothra
and Gokul Raj of the NIH-ICER for technical assistance. This work was
jointly sponsored by the Indian Department of Biotechnology; the Indian
Council of Medical Research; and the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, and administered by
CRDF Global [grant USB1-31149-XX-13]. This work was also funded by the
Division of Intramural Research, NIAID, NIH.
NR 22
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD DEC
PY 2016
VL 101
BP 191
EP 200
DI 10.1016/j.tube.2016.10.004
PG 10
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA ED8DT
UT WOS:000389102900028
PM 27865391
ER
PT J
AU Varble, AJ
Ried, CD
Hammond, WJ
Marquis, KA
Woodruff, MC
Ferran, MC
AF Varble, Andrew J.
Ried, Christopher D.
Hammond, Warren J.
Marquis, Kaitlin A.
Woodruff, Matthew C.
Ferran, Maureen C.
TI The vesicular stomatitis virus matrix protein inhibits NF-kappa B
activation in mouse L929 cells
SO VIROLOGY
LA English
DT Article
DE Vesicular stomatitis virus; VSV; L929 cells; Matrix protein; M51
mutation; NF-kappa B (NF-kappa B); Interferon; IKK inhibitor; Canonical
pathway
ID HOST GENE-EXPRESSION; TRANSCRIPTION FACTOR; IN-VIVO; INDUCTION; RNA;
APOPTOSIS; ABILITY; AUTOPHAGY; TRANSPORT; MUTANTS
AB A previous study found that NF-kappa B activation is delayed in L929 cells infected with wild-type (wt) strains of VSV, while activation occurred earlier in cells infected with mutant strain T1026R1 (RI) that encodes a mutation in the cytotoxic matrix (M) protein. The integrity of the other R1 proteins is unknown; therefore our goal was to identify the viral component responsible for preventing NF-kappa B activation in L929 cells. We found that the M protein inhibits viral-mediated activation of NF-kappa B in the context of viral infection and when expressed alone via transfection, and that the M51R mutation in M abrogates this function. Addition of an l kappa B kinase (IKK) inhibitor blocked NF-kappa B activation and interferon-beta mRNA expression in cells infected with viruses encoding the M51R mutation in M. These results indicate that the VSV M protein inhibits activation of NF-kappa B by targeting an event upstream of IKK in the canonical pathway. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Varble, Andrew J.; Ried, Christopher D.; Hammond, Warren J.; Marquis, Kaitlin A.; Woodruff, Matthew C.; Ferran, Maureen C.] Rochester Inst Technol, Thomas Gosnell Sch Life Sci, 153 Lomb Mem Dr, Rochester, NY 14623 USA.
[Varble, Andrew J.] Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA.
[Ried, Christopher D.] Essex Technol Grp, La Vergne, TN USA.
[Hammond, Warren J.] Warren Hammond Entertainment, Boulder, CO USA.
[Marquis, Kaitlin A.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Woodruff, Matthew C.] Emory Univ, Atlanta, GA 30322 USA.
RP Ferran, MC (reprint author), Rochester Inst Technol, Thomas Gosnell Sch Life Sci, 153 Lomb Mem Dr, Rochester, NY 14623 USA.
EM mcfsbi@rit.edu
FU NIH/NIAID grant [R15 AIO58969]
FX We thank Douglas Lyles for generously providing the recombinant virus
strains. We thank Sanjay Maggirwar for his invaluable scientific input
and generous use of reagents and equipment. We also thank Jonelle
Mattiacio, Joanna Shisler, Hyla Sweet, and Brian Ward for their support
and insightful comments on the manuscript. We thank the Rochester
Institute of Technology (RIT) College of Science (COS) for helping to
support this work and the COS Summer Undergraduate Research Program and
the RIT Honors Program for supporting many of the undergraduates who
contributed to this work. This research was supported by the NIH/NIAID
grant R15 AIO58969 (M. F.). The funders had no role in study design,
data collection and interpretation, or the decision to submit the work
for publication.
NR 35
TC 0
Z9 0
U1 5
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD DEC
PY 2016
VL 499
BP 99
EP 104
DI 10.1016/j.virol.2016.09.009
PG 6
WC Virology
SC Virology
GA EC3YI
UT WOS:000388062600011
PM 27643886
ER
PT J
AU Boi, S
Rosenke, K
Hansen, E
Hendrick, D
Malik, F
Evans, LH
AF Boi, Stefano
Rosenke, Kyle
Hansen, Ethan
Hendrick, Duncan
Malik, Frank
Evans, Leonard H.
TI Endogenous retroviruses mobilized during friend murine leukemia virus
infection
SO VIROLOGY
LA English
DT Article
DE Retroviruses; Mouse; Pseudotyping; Endogenous; Proviruses
ID LONG TERMINAL REPEAT; FOCUS-FORMING VIRUSES; LUPUS-PRONE MICE;
OLIGONUCLEOTIDE PROBES; POLYTROPIC RETROVIRUS; HETERODUPLEX ANALYSIS;
THYMIC LYMPHOMAS; UP-REGULATION; MOLONEY-MULV; PROVIRAL DNA
AB We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.
C1 [Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Evans, LH (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
EM levans@niaid.nih.gov
FU Intramural Research Program of the NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH. The authors wish to thank K. Hasenkrug, S. Priola, and K.
Peterson for helpful discussions.
NR 64
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD DEC
PY 2016
VL 499
BP 136
EP 143
DI 10.1016/j.virol.2016.07.009
PG 8
WC Virology
SC Virology
GA EC3YI
UT WOS:000388062600015
PM 27657834
ER
PT J
AU Saligan, LN
Lukkahatai, N
Holder, G
Walitt, B
Machado-Vieira, R
AF Saligan, L. N.
Lukkahatai, N.
Holder, G.
Walitt, B.
Machado-Vieira, R.
TI Lower brain-derived neurotrophic factor levels associated with worsening
fatigue in prostate cancer patients during repeated stress from
radiation therapy
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE fatigue; depression; brain-derived neurotrophic factor; radiation;
prostate neoplasm
ID SYNAPTIC-TRANSMISSION; FUNCTIONAL ASSESSMENT; UP-REGULATION; BDNF;
PERFORMANCE; DEPRESSION; DISORDERS; SYSTEM; SCALE; RELEVANCE
AB Objectives. Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Methods. Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. Results. FACT-F scores of 47 subjects decreased from baseline (43.95 +/- 1.3) to mid-EBRT (38.36 +/- 1.5, P < 0.001), indicating worsening fatigue. SNAPIN levels were associated with fatigue scores (r(s) = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Conclusions. Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.
C1 [Saligan, L. N.; Lukkahatai, N.; Holder, G.; Walitt, B.] NINR, NIH, Bethesda, MD 20892 USA.
[Lukkahatai, N.] Univ Nevada, Sch Nursing, Las Vegas, NV USA.
[Machado-Vieira, R.] NIMH, NIH, Bethesda, MD USA.
RP Saligan, LN (reprint author), NINR, NIH, Bethesda, MD 20892 USA.; Saligan, LN (reprint author), 3 Ctr Dr,B3-5E14, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
FU Division of Intramural Research of the National Institute of Nursing
Research of the National Institutes of Health, Bethesda, Maryland
FX This study was supported by the Division of Intramural Research of the
National Institute of Nursing Research of the National Institutes of
Health, Bethesda, Maryland.
NR 48
TC 0
Z9 0
U1 2
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1562-2975
EI 1814-1412
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD DEC
PY 2016
VL 17
IS 8
BP 608
EP 614
DI 10.3109/15622975.2015.1012227
PG 7
WC Psychiatry
SC Psychiatry
GA ED1YR
UT WOS:000388641300005
PM 25815565
ER
PT J
AU Das, D
Velez, JI
Acosta, MT
Muenke, M
Arcos-Burgos, M
Easteal, S
AF Das, Debjani
Velez, Jorge I.
Acosta, Maria T.
Muenke, Maximilian
Arcos-Burgos, Mauricio
Easteal, Simon
TI Retrospective assessment of childhood ADHD symptoms for diagnosis in
adults: validity of a short 8-item version of the Wender-Utah Rating
Scale
SO ADHD-ATTENTION DEFICIT AND HYPERACTIVITY DISORDERS
LA English
DT Article
DE Adult ADHD; WURS; CAARS; ROC; Sensitivity; Specificity
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; LATE-ONSET; SUBTHRESHOLD DIAGNOSES; ROC ANALYSIS; RELIABILITY;
PREVALENCE; CURVES; WURS
AB The Wender-Utah Rating Scale (WURS) is a widely used self-report instrument for retrospective assessment of childhood ADHD. However, many WURS items are not specific to ADHD. Here, we investigated the effect of excluding these items on the performance of the WURS in predicting adult ADHD based on previous diagnosis and current clinically significant symptoms. The study was conducted on a sample of adults (n = 1014; 48 % male) participating in a family-based investigation of ADHD. Participants completed the 61-item WURS questionnaire and the 66-item Conners Adult ADHD Rating Scale. Receiver operating characteristic (ROC) curves were used to compare the performance of the eight-item WURS (WURS-8) and the longer WURS-25 in predicting previous ADHD diagnosis and current clinically significant ADHD symptoms. WURS-8 and WURS-25 have approximately the same power to predict adult ADHD, based on either previous diagnosis or current symptoms (area under the ROC curves > 0.8). WURS-8 performs at least as well as the longer WURS-25 in predicting adult ADHD. This 8-item questionnaire is thus a valid instrument and is especially useful for screening for ADHD in large epidemiological samples.
C1 [Das, Debjani; Velez, Jorge I.; Arcos-Burgos, Mauricio; Easteal, Simon] Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
[Velez, Jorge I.; Arcos-Burgos, Mauricio] Univ Antioquia, Neuroscience Res Grp, Medellin, Colombia.
[Velez, Jorge I.] Univ Norte, Dept Ind Engn, Barranquilla, Colombia.
[Acosta, Maria T.] Jennifer & Daniel Gilbert Neurofibromatosis Inst, Washington, DC USA.
[Acosta, Maria T.] Childrens Natl Med Ctr, Ctr Neurosci & Behav Med, Washington, DC USA.
[Acosta, Maria T.; Muenke, Maximilian; Arcos-Burgos, Mauricio] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA.
RP Das, D (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Bldg 131,Garran Rd, Canberra, ACT 2601, Australia.
EM debjani.das@anu.edu.au
NR 45
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 1866-6116
EI 1866-6647
J9 ADHD-ATTEND DEFICIT
JI ADHD-Attend. Deficit Hyperact. Disord.
PD DEC
PY 2016
VL 8
IS 4
BP 215
EP 223
DI 10.1007/s12402-016-0202-9
PG 9
WC Psychiatry
SC Psychiatry
GA EC1ER
UT WOS:000387847200006
PM 27510231
ER
PT J
AU Valkanas, E
Schaffer, K
Dunham, C
Maduro, V
du Souich, C
Rupps, R
Adams, DR
Baradaran-Heravi, A
Flynn, E
Malicdan, MC
Gahl, WA
Toro, C
Boerkoel, CF
AF Valkanas, Elise
Schaffer, Katherine
Dunham, Christopher
Maduro, Valerie
du Souich, Christele
Rupps, Rosemarie
Adams, David R.
Baradaran-Heravi, Alireza
Flynn, Elise
Malicdan, May C.
Gahl, William A.
Toro, Camilo
Boerkoel, Cornelius F.
TI Phenotypic Evolution of UNC80 Loss of Function
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE intellectual disability; growth restriction; failure to thrive;
seizures; emaciation
ID FEEDING DISORDERS; CHANNEL COMPLEX; CATION CHANNEL; SODIUM LEAK; NALCN
CAUSE; MUTATIONS; HYPOTONIA; ENCEPHALOPATHY; PRIORITIZATION; INTERACTOME
AB Failure to thrive arises as a complication of a heterogeneous group of disorders. We describe two female siblings with spastic paraplegia and global developmental delay but also, atypically for the HSPs, poor weight gain classified as failure to thrive. After extensive clinical and biochemical investigations failed to identify the etiology, we used exome sequencing to identify biallelic UNC80 mutations (NM_032504.1: c.[3983-3_3994delinsA];[2431C>T]. The paternally inherited NM_032504.1: c.3983-3_3994delinsA is predicted to encode p.Ser1328Argfs*19 and the maternally inherited NM_032504.1: c. 2431C>T is predicted to encode p.Arg811*. No UNC80 mRNA was detectable in patient cultured skin fibroblasts, suggesting UNC80 loss of function by nonsense mediated mRNA decay. Further supporting the UNC80 mutations as causative of these siblings' disorder, biallelic mutations in UNC80 have recently been described among individuals with an overlapping phenotype. This report expands the disease spectrum associated with UNC80 mutations. (C) 2016 Wiley Periodicals, Inc.
C1 [Valkanas, Elise; Schaffer, Katherine; Maduro, Valerie; Adams, David R.; Flynn, Elise; Malicdan, May C.; Gahl, William A.; Toro, Camilo; Boerkoel, Cornelius F.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Dunham, Christopher] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada.
[du Souich, Christele; Rupps, Rosemarie; Baradaran-Heravi, Alireza; Boerkoel, Cornelius F.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[du Souich, Christele; Rupps, Rosemarie; Baradaran-Heravi, Alireza; Boerkoel, Cornelius F.] Univ British Columbia, Child & Family Res Inst, Vancouver, BC, Canada.
[Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Boerkoel, CF (reprint author), Univ British Columbia, Childrens & Womens Hlth Ctr BC, Dept Med Genet, 4500 Oak St,Rm C234, Vancouver, BC V6H 3N1, Canada.
EM cboerkoel@gmail.com
FU National Human Genome Research Institute; Common Fund, Office of the
Director; Scottish Rite Foundation; Child and Family Research Institute
Establishment Award
FX Grant sponsor: National Human Genome Research Institute; Grant sponsor:
Common Fund, Office of the Director; Grant sponsor: Scottish Rite
Foundation (C.D.S.); Grant sponsor: Child and Family Research Institute
Establishment Award (C.F.B.).
NR 29
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD DEC
PY 2016
VL 170
IS 12
BP 3106
EP 3114
DI 10.1002/ajmg.a.37929
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA EC5TL
UT WOS:000388199100008
PM 27513830
ER
PT J
AU Prakash, SK
Bondy, CA
Maslen, CL
Silberbach, M
Lin, AE
Perrone, L
Limongelli, G
Michelena, HI
Bossone, E
Citro, R
Lemaire, SA
Body, SC
Milewicz, DM
AF Prakash, Siddharth K.
Bondy, Carolyn A.
Maslen, Cheryl L.
Silberbach, Michael
Lin, Angela E.
Perrone, Laura
Limongelli, Giuseppe
Michelena, Hector I.
Bossone, Eduardo
Citro, Rodolfo
Lemaire, Scott A.
Body, Simon C.
Milewicz, Dianna M.
CA BAVCon Investigators
GenTAC Registry Investigators
TI Autosomal and X Chromosome Structural Variants Are Associated with
Congenital Heart Defects in Turner Syndrome: The NHLBI GenTAC Registry
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE genomics; Turner syndrome; valvular heart disease; congenital heart
defects; X chromosome
ID BICUSPID AORTIC-VALVE; COPY-NUMBER VARIATION; TRANSPORTER GENE SLC2A3;
DISSECTION; EXPRESSION; ANEURYSMS; DELETION; GROWTH; CANCER; WOMEN
AB Turner Syndrome(TS) is adevelopmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 timesmore frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. (C) 2016 Wiley Periodicals, Inc.
C1 [Prakash, Siddharth K.; Milewicz, Dianna M.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Med Genet, Houston, TX 77030 USA.
[Bondy, Carolyn A.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Maslen, Cheryl L.; Silberbach, Michael] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA.
[Maslen, Cheryl L.; Silberbach, Michael] Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA.
[Lin, Angela E.] MassGeneral Hosp Children, Dept Med Genet, Boston, MA USA.
[Perrone, Laura; Limongelli, Giuseppe] Univ Naples 2, Dept Pediat F Fede, Naples, Italy.
[Michelena, Hector I.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Bossone, Eduardo; Citro, Rodolfo] Univ Hosp Scuola Med Salernitana, Dept Cardiol & Cardiac Surg, Salerno, Italy.
[Lemaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA.
[Body, Simon C.] Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA.
RP Prakash, SK (reprint author), Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Internal Med, 6431 Fannin St,MSB 6-106, Houston, TX 77030 USA.
EM siddharth.k.prakash@uth.tmc.edu
FU Baylor College of Medicine [1U54HD083092, 5R01HD039056, 5R01HL090506,
5R01HL091771]; Ohio State University and Nationwide Children's Hospital
[5R01HL109758]; US Federal Government [HHSN268200648199C,
HHSN268201000048C]; National Institute on Aging [U01AG009740,
RC2AG036495, RC4AG039029]; National Eye Institute; Johns Hopkins
University [HHSN268200782096C]; Collaborative Genetic Study of Nicotine
Dependence ( COGEND) [P01 CA089392]; University of Wisconsin
Transdisciplinary Tobacco Use Research Center [P50 DA019706, P50
CA084724]
FX Grant sponsor: Baylor College of Medicine; Grant numbers: 1U54HD083092,
5R01HD039056, 5R01HL090506, 5R01HL091771; Grant sponsor: Ohio State
University and Nationwide Children's Hospital; Grant number:
5R01HL109758; Grant sponsor: US Federal Government; Grant numbers :
HHSN268200648199C, HHSN268201000048C; Grant sponsor: National Institute
on Aging; Grant numbers: U01AG009740, RC2AG036495, RC4AG039029; Grant
sponsor: National Eye Institute; Grant sponsor: The Johns Hopkins
University; Grant number: HHSN268200782096C; Grant sponsor:
Collaborative Genetic Study of Nicotine Dependence ( COGEND); Grant
number: P01 CA089392; Grant sponsor: University of Wisconsin
Transdisciplinary Tobacco Use Research Center; Grant numbers: P50
DA019706, P50 CA084724.
NR 31
TC 2
Z9 2
U1 7
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD DEC
PY 2016
VL 170
IS 12
BP 3157
EP 3164
DI 10.1002/ajmg.a.37953
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA EC5TL
UT WOS:000388199100015
PM 27604636
ER
PT J
AU Grobman, WA
Parker, C
Wadhwa, PD
Willinger, M
Simhan, H
Silver, B
Wapner, RJ
Parry, S
Mercer, B
Haas, D
Peaceman, AM
Hunter, S
Wing, D
Caritis, S
Esplin, S
Hoffman, M
Ludmir, J
Iams, J
Long, E
Saade, G
Reddy, UM
AF Grobman, William A.
Parker, Corette
Wadhwa, Pathik D.
Willinger, Marian
Simhan, Hyagriv
Silver, Bob
Wapner, Ron J.
Parry, Samuel
Mercer, Brian
Haas, David
Peaceman, Alan M.
Hunter, Shannon
Wing, Deborah
Caritis, Steve
Esplin, Sean
Hoffman, Matt
Ludmir, Jack
Iams, Jay
Long, Emily
Saade, George
Reddy, Uma M.
CA Eunice Kennedy Shriver Natl Inst C
TI Racial/Ethnic Disparities in Measures of Self-reported Psychosocial
States and Traits during Pregnancy
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE psychosocial; stress; disparities; pregnancy
ID DEPRESSIVE SYMPTOMS; RACIAL DISPARITIES; STRESS; SCALE; POSTPARTUM;
OUTCOMES
AB Background The aim of this study was to determine whether racial/ethnic differences in psychosocial measures, independent of economic status, exist among a large population of pregnant nulliparas.
Methods Between October 2010 and September 2013, nulliparous women at eight U.S. medical centers were followed longitudinally during pregnancy and completed validated instruments to quantify several psychosocial domains: Cohen Perceived Stress Scale, trait subscale of the Spielberger Anxiety Inventory, Connor-Davidson Resilience Scale, Multidimensional Scale of Perceived Social Support, Krieger Racism Scale, Edinburgh Postnatal Depression Scale, and the Pregnancy Experience Scale. Scores were stratified and compared by self-reported race, ethnicity, and income.
Results Complete data were available for 8,128 of the 10,038 women enrolled in the study. For all measures, race and ethnicity were significantly associated (p < 0.001) with survey scores. Non-Hispanic black (NHB) women were most likely to score in the most unfavorable category for all measures, with the exception of the Pregnancy Experience Scale. The magnitude of these differences did not differ by income status (interaction, p > 0.05) except on the Krieger racism survey and the Edinburgh depression survey, which were exacerbated among NHB women with higher income (interaction, p < 0.001).
Conclusion Significant racial/ethnic disparities, independent of income status, exist in psychosocial measures during pregnancy.
C1 [Grobman, William A.; Peaceman, Alan M.] Northwestern Univ, Dept Obstet & Gynecol, 250 East Super St,Suite 05-2175, Chicago, IL 60611 USA.
[Parker, Corette; Hunter, Shannon] RTI Int, Div Biostat & Epidemiol, Res Triangle Pk, NC USA.
[Wadhwa, Pathik D.; Wing, Deborah] Univ Calif Irvine, Dept Obstet & Gynecol, Irvine, CA 92717 USA.
[Willinger, Marian; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Simhan, Hyagriv; Caritis, Steve] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Silver, Bob; Esplin, Sean] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Wapner, Ron J.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Parry, Samuel; Ludmir, Jack] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Mercer, Brian] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA.
[Haas, David; Long, Emily] Indiana Univ, Dept Obstet & Gynecol, Indianapolis, IN 46204 USA.
[Hoffman, Matt] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA.
[Iams, Jay] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Saade, George] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
RP Grobman, WA (reprint author), Northwestern Univ, Dept Obstet & Gynecol, 250 East Super St,Suite 05-2175, Chicago, IL 60611 USA.
EM w-grobman@northwestern.edu
OI Ludmir, Jack/0000-0002-9728-7444
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [U10 HD063036, U10 HD063072, U10 HD063047, U10
HD063037, U10 HD063041, U10 HD063020, U10 HD063046, U10 HD063048, U10
HD063053]
FX This study was supported by the following grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD): U10 HD063036, RTI International; U10 HD063072, Case Western
Reserve University; U10 HD063047, Columbia University; U10 HD063037,
Indiana University; U10 HD063041, University of Pittsburgh; U10
HD063020, Northwestern University; U10 HD063046, University of
California Irvine; U10 HD063048, University of Pennsylvania; and U10
HD063053, University of Utah.
NR 27
TC 0
Z9 0
U1 4
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD DEC
PY 2016
VL 33
IS 14
BP 1426
EP 1432
DI 10.1055/s-0036-1586510
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA ED0RH
UT WOS:000388549100014
PM 27500932
ER
PT J
AU Barber, S
Hickson, DA
Wang, X
Sims, M
Nelson, C
Diez-Roux, AV
AF Barber, Sharrelle
Hickson, DeMarc A.
Wang, Xu
Sims, Mario
Nelson, Cheryl
Diez-Roux, Ana V.
TI Neighborhood Disadvantage, Poor Social Conditions, and Cardiovascular
Disease Incidence Among African American Adults in the Jackson Heart
Study
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID GEOGRAPHIC LIFE ENVIRONMENTS; RESEARCH AGENDA; RISK-FACTORS; HEALTH;
MULTILEVEL; ATHEROSCLEROSIS; COHESION; DISORDER; OBESITY; STROKE
AB Objectives. To examine the impact of neighborhood conditions resulting from racial residential segregation on cardiovascular disease (CVD) risk in a socioeconomically diverse African American sample.
Methods. The study included 4096 African American women (n = 2652) and men (n = 1444) aged 21 to 93 years from the Jackson Heart Study (Jackson, Mississippi; 20002011). We assessed neighborhood disadvantage with a composite measure of 8 indicators from the 2000 US Census. We assessed neighborhood-level social conditions, including social cohesion, violence, and disorder, with self-reported, validated scales.
Results. Among African American women, each standard deviation increase in neighborhood disadvantage was associated with a 25% increased risk of CVD after covariate adjustment (hazard ratio = 1.25; 95% confidence interval = 1.05, 1.49). Risk also increased as levels of neighborhood violence and physical disorder increased after covariate adjustment. We observed no statistically significant associations among African American men in adjusted models.
Conclusions. Worse neighborhood economic and social conditions may contribute to increased risk of CVD among African American women. Policies directly addressing these issues may alleviate the burden of CVD in this group.
C1 [Barber, Sharrelle; Wang, Xu; Diez-Roux, Ana V.] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nesbit Hall,5th Floor,3215 Market St, Philadelphia, PA 19104 USA.
[Barber, Sharrelle; Wang, Xu; Diez-Roux, Ana V.] Ctr Integrat Approaches Hlth Dispar, Philadelphia, PA USA.
[Hickson, DeMarc A.; Sims, Mario] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Nelson, Cheryl] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Barber, S (reprint author), Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nesbit Hall,5th Floor,3215 Market St, Philadelphia, PA 19104 USA.
EM smb483@drexel.edu
FU Center for Integrative Approaches to Health Disparities - National
Institute of Minority Health and Health Disparities [NIMHD P60
MD002249]; National Heart, Lung, and Blood Institute [HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268201300050C]; NIMHD; National Institutes of Health, National
Heart, Lung, and Blood Institute [R01 HL071759]
FX This research was supported by the Center for Integrative Approaches to
Health Disparities funded by National Institute of Minority Health and
Health Disparities (NIMHD P60 MD002249; A. V. Diez-Roux). The Jackson
Heart Study is supported by contracts HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and
HHSN268201300050C from the National Heart, Lung, and Blood Institute and
the NIMHD. The creation of Jackson Heart Study neighborhood environment
variables was supported by the Michigan Center for Integrative
Approaches to Health Disparities funded by the NIMHD, by US
Environmental Protection Agency and NIMHD: Environment Supplement P60
MD002249 05S1 (PI: A. V. Diez-Roux), and by the Multi-ethnic Study of
Atherosclerosis Neighborhood Study R01 HL071759 (PI: A. V. Diez-Roux)
funded by the National Institutes of Health, National Heart, Lung, and
Blood Institute.
NR 36
TC 1
Z9 1
U1 8
U2 8
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD DEC
PY 2016
VL 106
IS 12
BP 2219
EP 2226
DI 10.2105/AJPH.2016.303471
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EC4IQ
UT WOS:000388091700051
PM 27736207
ER
PT J
AU Miettinen, M
Felisiak-Golabek, A
Wasag, B
Chmara, M
Wang, ZF
Butzow, R
Lasota, J
AF Miettinen, Markku
Felisiak-Golabek, Anna
Wasag, Bartosz
Chmara, Magdalena
Wang, Zengfeng
Butzow, Ralf
Lasota, Jerzy
TI Fumarase-deficient Uterine Leiomyomas An Immunohistochemical, Molecular
Genetic, and Clinicopathologic Study of 86 Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE leiomyoma; leiomyosarcoma; renal cell cancer; FH; immunohistochemistry
ID RENAL-CELL CANCER; HEREDITARY LEIOMYOMATOSIS; CARCINOMA SYNDROME; HLRCC
SYNDROME; FH MUTATIONS; HYDRATASE; FEATURES; LEIOMYOSARCOMAS;
INACTIVATION; TUMORS
AB Loss-of-function germline mutations in the fumarase (FH) gene of the Krebs cycle characterize hereditary leiomyomatosis and renal cell cancer syndrome. Fumarase (FH) deficiency can be diagnosed by the loss of immunohistochemical expression. In this study, we investigated the occurrence and clinicopathologic features of FH-deficient uterine smooth muscle tumors (SMTs). A total of 1583 uterine and 157 nonuterine SMTs were examined using a polyclonal FH antibody and automated immunohistochemistry, and 86 uterine leiomyomas with an FH loss were identified. The frequencies of FH deficiency for subcohorts of uterine SMTs were 1.6% for unselected nonatypical leiomyomas, 1.8% for cellular leiomyomas, 37.3% for atypical leiomyomas, and 0% for leiomyosarcomas. One extrauterine, retroperitoneal estrogen receptor-positive leiomyoma was also FH deficient. The patient age of FH-deficient uterine leiomyomas was 20 to 52 years (median, 38 y). Grossly, these tumors were often soft and amorphous resembling a fibrothecoma. Histologically, the FH-deficient nonatypical leiomyomas lacked cellular packeting and distinct collagenous zones and showed chain-like or palisading nuclear arrangements, prominent staghorn-shaped blood vessels, oval nuclei with no or at most mild atypia, small eosinophilic nucleoli, and a low mitotic rate (0 to 1/10HPF). The FH-deficient atypical leiomyomas had nuclear atypia often manifesting as multinucleation, prominent eosinophilic nucleoli, and mitotic activity up to 7/10HPF, with atypical mitoses seen in 32% of cases. However, similar histologic changes were seen in some non-FH-deficient atypical leiomyomas. Loss-of-function FH-gene mutations including 5 whole-gene deletions and 3 frameshift mutations were identified in 8 of 16 FH-deficient nonatypical leiomyomas using multiplex ligation-dependent probe amplification and Sanger sequencing, respectively. Follow-up data on patients with FH-deficient atypical uterine leiomyomas revealed 19 patients alive (median follow-up 27 y) and 5 patients dead. Deaths occurred 9 to 30 years after surgery at a median age of 72 years; causes of death could not be determined. These results indicate that FH-deficient uterine leiomyomas occur with a high frequency among atypical leiomyomas and infrequently in nonatypical leiomyomas and are often histologically distinctive. They seem to have a low biological potential and lack any significant association with leiomyosarcoma.
C1 [Miettinen, Markku; Felisiak-Golabek, Anna; Wang, Zengfeng; Lasota, Jerzy] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Wasag, Bartosz; Chmara, Magdalena] Med Univ Gdansk, Dept Biol & Genet, Gdansk, Poland.
[Butzow, Ralf] HusLab, Helsinki, Finland.
[Butzow, Ralf] Univ Helsinki, Helsinki, Finland.
RP Miettinen, M (reprint author), NCI, Pathol Lab, Surg Pathol Sect, 9000 Rockville Pike,Bldg 10,Rm 2S235C, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI's intramural research program
FX This work was supported as a part of NCI's intramural research program.
NR 23
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD DEC
PY 2016
VL 40
IS 12
BP 1661
EP 1669
DI 10.1097/PAS.0000000000000703
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA EC6CI
UT WOS:000388223500011
PM 27454940
ER
PT J
AU Duggan, MA
Anderson, WF
Altekruse, S
Penberthy, L
Sherman, ME
AF Duggan, Maire A.
Anderson, William F.
Altekruse, Sean
Penberthy, Lynne
Sherman, Mark E.
TI The Surveillance, Epidemiology, and End Results (SEER) Program and
Pathology Toward Strengthening the Critical Relationship
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE SEER; Surveillance, Epidemiology, and End Results program, pathology
ID POPULATION-BASED ANALYSIS; BREAST-CANCER; UNITED-STATES;
CERVICAL-CANCER; SURVIVAL; REGISTRY; CLASSIFICATION; MORTALITY;
CARCINOMA; DISEASE
AB The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute collects data on cancer diagnoses, treatment, and survival for approximately 30% of the United States (US) population. To reflect advances in research and oncology practice, approaches to cancer control are evolving from simply enumerating the development of cancers by organ site in populations to including monitoring of cancer occurrence by histopathologic and molecular subtype, as defined by driver mutations and other alterations. SEER is an important population-based resource for understanding the implications of pathology diagnoses across demographic groups, geographic regions, and time and provides unique insights into the practice of oncology in the US that are not attainable from other sources. It provides incidence, survival, and mortality data for histopathologic cancer subtypes, and data by molecular subtyping are expanding. The program is developing systems to capture additional biomarker data, results from special populations, and expand biospecimen banking to enable cutting-edge cancer research and oncology practice. Pathology has always been central and critical to the effectiveness of SEER, and strengthening this relationship in this modern era of cancer diagnosis could be mutually beneficial. Achieving this goal requires close interactions between pathologists and the SEER program. This review provides a brief overview of SEER, focuses on facets relevant to pathology practice and research, and highlights the opportunities and challenges for pathologists to benefit from and enhance the value of SEER data.
C1 [Duggan, Maire A.] Univ Calgary, Cumming Sch Med, Dept Pathol & Lab Med, Calgary, AB, Canada.
[Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Altekruse, Sean; Penberthy, Lynne] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Sherman, ME (reprint author), NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, 9609 Med Ctr Dr,Room 5E334, Bethesda, MD 20892 USA.
EM shermanm@exchange.nih.gov
FU Intramural Research Program of the National Cancer Institute
FX Funded in part by the Intramural Research Program of the National Cancer
Institute. The authors have disclosed that they have no significant
relationships with, or financial interest in, any commercial companies
pertaining to this article.
NR 40
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD DEC
PY 2016
VL 40
IS 12
BP E94
EP E102
DI 10.1097/PAS.0000000000000749
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA EC6CI
UT WOS:000388223500001
PM 27740970
ER
PT J
AU Karami, S
Yanik, EL
Moore, LE
Pfeiffer, RM
Copeland, G
Gonsalves, L
Hernandez, BY
Lynch, CF
Pawlish, K
Engels, EA
AF Karami, S.
Yanik, E. L.
Moore, L. E.
Pfeiffer, R. M.
Copeland, G.
Gonsalves, L.
Hernandez, B. Y.
Lynch, C. F.
Pawlish, K.
Engels, E. A.
TI Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the
United States
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
ID CANCER INCIDENCE; NATIVE KIDNEYS; DISEASE; DIALYSIS; SPECTRUM; ORGAN;
EXPERIENCE; SURVIVAL; PEOPLE; ESRD
AB Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987-2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27-6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p-trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.
C1 [Karami, S.; Yanik, E. L.; Moore, L. E.; Pfeiffer, R. M.; Engels, E. A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Copeland, G.] Michigan Dept Community Hlth, Michigan Canc Surveillance Program, Lansing, MI USA.
[Gonsalves, L.] Connecticut Dept Publ Hlth, Hartford, CT USA.
[Hernandez, B. Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lynch, C. F.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
[Pawlish, K.] New Jersey Dept Hlth, New Jersey State Canc Registry, Canc Epidemiol Serv, Trenton, NJ USA.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM karamis@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute;
Minneapolis Medical Research Foundation, Minneapolis, MN
[HHSH250201000018C]; SEER Program of the National Cancer Institute:
California [HHSN261201000036C, HHSN261201000035C, HHSN261 201000034C];
SEER Program of the National Cancer Institute: Connecticut
[HHSN261201000024C]; SEER Program of the National Cancer Institute:
Hawaii [HHSN2612 01000037C, N01-PC-35137, N01-PC-35139]; SEER Program of
the National Cancer Institute: Iowa [HSN261201 000032C, N01-PC-35143];
SEER Program of the National Cancer Institute: New Jersey
[HHSN261201300021I, N01-PC-2013-00021]; SEER Program of the National
Cancer Institute: Seattle-Puget Sound [N01-PC-35142]; SEER Program of
the National Cancer Institute: Utah [HHSN2612013000171]; National
Program of Cancer Registries of the Centers for Disease Control and
Prevention: California [1U58 DP000807-01]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: Colorado
[U58 DP000848-04]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention: Georgia [5U58DP003875-01]; National
Program of Cancer Registries of the Centers for Disease Control and
Prevention: Illinois [5U58DP003883-03]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: Maryland
[U58DP12-1205 3919-03]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention: Michigan [5U58DP003921-03];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: New Jersey [5U58/DP003931-02]; National Program of
Cancer Registries of the Centers for Disease Control and Prevention: New
York [U58DP003879]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention: North Carolina [U58DP000832];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: Texas [5U58DP000824-04]; state of California; state of
Colorado; state of Connecticut; state of Illinois; state of Iowa; state
of Massachusetts (Massachusetts Cancer Prevention and Control
Cooperative Agreement) [5458DP003920]; state of New Jersey; state of New
York (including the Cancer Surveillance Initiative); state of Texas;
state of Utah; state of Washington; University of Utah; Fred Hutchinson
Cancer Research Center in Seattle, WA; [HHSH234200537009C]
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute. The authors gratefully acknowledge the
support and assistance provided by individuals at the Health Resources
and Services Administration (Monica Lin), the SRTR (Ajay Israni, Bertram
Kasiske, Paul Newkirk, Jon Snyder), and the following cancer registries:
the states of California (Tina Clarke), Colorado (Jack Finch),
Connecticut, Georgia (Rana Bayakly), Hawaii (Michael Green), Iowa,
Illinois (Lori Koch), Michigan, New Jersey (Xiaoling Niu), New York (Amy
Kahn), North Carolina (Chandrika Rao), Texas (Melanie Williams), and
Utah (Janna Harrell), and the Seattle-Puget Sound area of Washington
(Margaret Madeleine). We also thank analysts at Information Management
Services for programming support (David Castenson, Matthew Chaloux,
Michael Curry, and Ruth Parsons). The authors also thank David Check
(National Cancer Institute) for assistance in producing the figures. The
SRTR is currently operated under contract number HHSH250201000018C
(Health Resources and Services Administration) by the Minneapolis
Medical Research Foundation, Minneapolis, MN. During the initial period
when registry linkages were performed, the SRTR was managed by Arbor
Research Collaborative for Health in Ann Arbor, MI (contract
HHSH234200537009C). The following cancer registries were supported by
the SEER Program of the National Cancer Institute: California (contracts
HHSN261201000036C, HHSN261201000035C, and HHSN261 201000034C),
Connecticut (HHSN261201000024C), Hawaii (HHSN2612 01000037C,
N01-PC-35137, and N01-PC-35139), Iowa (HSN261201 000032C and
N01-PC-35143), New Jersey (HHSN261201300021I, N01-PC-2013-00021),
Seattle-Puget Sound (N01-PC-35142), and Utah (HHSN2612013000171). The
following cancer registries were supported by the National Program of
Cancer Registries of the Centers for Disease Control and Prevention:
California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04),
Georgia (5U58DP003875-01), Illinois (5U58DP003883-03), Maryland
(U58DP12-1205 3919-03), Michigan (5U58DP003921-03), New Jersey
(5U58/DP003931-02), New York (U58DP003879), North Carolina
(U58DP000832), and Texas (5U58DP000824-04). Additional support was
provided by the states of California, Colorado, Connecticut, Illinois,
Iowa, Massachusetts (Massachusetts Cancer Prevention and Control
Cooperative Agreement 5458DP003920), New Jersey, New York (including the
Cancer Surveillance Initiative), Texas, Utah, and Washington, as well as
the University of Utah and Fred Hutchinson Cancer Research Center in
Seattle, WA.
NR 45
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U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD DEC
PY 2016
VL 16
IS 12
BP 3479
EP 3489
DI 10.1111/ajt.13862
PG 11
WC Surgery; Transplantation
SC Surgery; Transplantation
GA EC5WS
UT WOS:000388208600019
ER
PT J
AU Sotzny, F
Schormann, E
Kuhlewindt, I
Koch, A
Brehm, A
Goldbach-Mansky, R
Gilling, KE
Kruger, E
AF Sotzny, Franziska
Schormann, Eileen
Kuehlewindt, Ina
Koch, Annett
Brehm, Anja
Goldbach-Mansky, Raphaela
Gilling, Kate E.
Krueger, Elke
TI TCF11/Nrf1-Mediated Induction of Proteasome Expression Prevents
Cytotoxicity by Rotenone
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
DE neurodegeneration; oxidative stress; proteasome; rotenone; transcription
factor TCF11/Nrf1; ubiquitin
ID MITOCHONDRIAL COMPLEX-I; FACTOR E2-RELATED FACTOR-1; BZIP TRANSCRIPTION
FACTOR; OXIDATIVE-STRESS; PARKINSONS-DISEASE; ANTIOXIDANT RESPONSE;
SUBSTANTIA-NIGRA; ALPHA-SYNUCLEIN; 20S PROTEASOME; ENDOPLASMIC-RETICULUM
AB Aims: Precise regulation of cellular protein degradation is essential for maintaining protein and redox homeostasis. The ubiquitin proteasome system (UPS) represents one of the major degradation machineries, and UPS disturbances are strongly associated with neurodegeneration. We have previously shown that the transcription factor TCF11/Nrf1 induces antioxidant response element-mediated upregulation of UPS components in response to proteotoxic stress. Knockout of TCF11/Nrf1 is embryonically lethal, and therefore, the present investigation describes the role of oxidative stress in regulating TCF11/Nrf1-dependent proteasome expression in a model system relevant to Parkinson's disease.
Results: Using the human dopaminergic neuroblastoma cell line SH-SY5Y and mouse nigrostriatal organotypic slice cultures, gene and protein expression analysis and functional assays revealed oxidative stress is induced by the proteasome inhibitor epoxomicin or the mitochondrial complex I inhibitor rotenone and promotes the upregulation of proteasome expression and function mediated by TCF11/Nrf1 activation. In addition, we show that these stress conditions induce the unfolded protein response. TCF11/Nrf1, thus, has a cytoprotective function in response to oxidative and proteotoxic stress. Innovation and
Conclusion: We here demonstrate that adaption of the proteasome system in response to oxidative stress is dependent on TCF11/Nrf1 in this model system. We conclude that TCF11/Nrf1, therefore, plays a vital role in maintaining redox and protein homeostasis. This work provides a vital insight into the molecular mechanisms of neurodegeneration due to oxidative stress by rotenone, and further studies investigating the role of TCF11/Nrf1 in the human condition would be of considerable interest.
C1 [Sotzny, Franziska; Schormann, Eileen; Kuehlewindt, Ina; Koch, Annett; Brehm, Anja; Gilling, Kate E.; Krueger, Elke] Charite Univ Med Berlin, Inst Biochem, Charitepl 1, D-10117 Berlin, Germany.
[Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
RP Kruger, E (reprint author), Charite Univ Med Berlin, Inst Biochem, Charitepl 1, D-10117 Berlin, Germany.
EM elke.krueger@charite.de
FU Deutsche Forschungsgemeinschaft [KO 4144/1-1, KR 1915/5-1, SFB740 B3,
SFBTRR 43 B7]
FX This work was supported by the Deutsche Forschungsgemeinschaft (KO
4144/1-1; KR 1915/5-1; SFB740 B3; SFBTRR 43 B7). Elke Burger (Charite)
is acknowledged for her excellent technical assistance and Yin Liu (NIH,
Bethesda) for his support with cells from PRAAS patients.
NR 69
TC 0
Z9 0
U1 3
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD DEC 1
PY 2016
VL 25
IS 16
BP 870
EP 885
DI 10.1089/ars.2015.6539
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA EC6RA
UT WOS:000388262600002
PM 27345029
ER
PT J
AU Kannan, M
Sivaprakasam, C
Prinz, WA
Nachiappan, V
AF Kannan, Muthukumar
Sivaprakasam, Chinnarasu
Prinz, William A.
Nachiappan, Vasanthi
TI Endoplasmic reticulum stress affects the transport of
phosphatidylethanolamine from mitochondria to the endoplasmic reticulum
in S. cerevisiae
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE ER stress; Mitochondria; Phosphatidylcholine; ERMES; Lipid transport
ID YEAST SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLCHOLINE BIOSYNTHESIS;
PHOSPHATIDYLSERINE DECARBOXYLASE2; LIPID-METABOLISM; ER STRESS; GENE;
PHOSPHOLIPIDS; TRAFFICKING; METHYLATION; PROTEINS
AB Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two of the most abundant phospholipids in cells. Although both lipids can be synthesized in the endoplasmic reticulum (ER), in S. cerevisiae PE can also be produced in mitochondria and endosomes; this PE can be transported back to the ER where it is converted to PC. In this study we found that dithiothreitol (DTT), which induces ER stress, decreases PE export from mitochondria to the ER. This results in decreased levels of total cellular PC and mitochondrial PC. These decreases were not caused by changes in levels of PC synthesizing or degrading enzymes. PE export from mitochondria to the ER during ER stress was further reduced in cells lacking Mdm10p, a component of an ER-mitochondrial tethering complex that may facilitated lipid exchange between these compartments. We also found that reducing mitochondrial PC levels induces mitophagy. In conclusion, we show that ER stress affected PE export from mitochondria to ER and the Mdm10p is important for this process. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Kannan, Muthukumar; Prinz, William A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Sivaprakasam, Chinnarasu; Nachiappan, Vasanthi] Bharathidasan Univ, Sch Life Sci, Dept Biochem, Biomembrane Lab, Tiruchchirappalli 620024, Tamil Nadu, India.
RP Nachiappan, V (reprint author), Bharathidasan Univ, Sch Life Sci, Dept Biochem, Biomembrane Lab, Tiruchchirappalli 620024, Tamil Nadu, India.
EM vasanthibch@gmail.com
FU Bharathidasan University, Tiruchirappalli; Council of Scientific &
Industrial Research-CSIR, India
FX The financial support from Bharathidasan University, Tiruchirappalli,
Council of Scientific & Industrial Research-CSIR, India, and the
instrumentation facility provided by the Department of Science &
Technology (DST) under the DST-PURSE and DST-FIST programsare gratefully
acknowledged. The authors sincerely thank Prof. Ram Rajasekharan, Dept
of Biochemistry, Indian Institute of Science (Bangalore - India), for
his critical comments about this manuscript and also for generously
providing the reagents used in this study. We thank Prof. Ewald H.
Hettema, (University of Sheffield, Sheffield, UK) for providing the
OM45-GFP yeast strains, as well as Prof. Yoshinori Ohsumi, Prof.
Kuninori Suzuki (University of Tokyo, Japan), Prof. Jeffrey Brodsky
(University of Pittsburgh, PA, USA), and Prof. Marco Foiani, (University
of Milan, Italy) for providing Ape1, Atg8, Kart and Pgk1 antiserum,
respectively.
NR 39
TC 0
Z9 0
U1 9
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD DEC
PY 2016
VL 1861
IS 12
BP 1959
EP 1967
DI 10.1016/j.bbalip.2016.09.015
PN A
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA ED0QC
UT WOS:000388546000009
PM 27678054
ER
PT J
AU Shuch, B
Syed, J
Nguyen, K
Hoffman, J
Devesa, S
Suarez, A
AF Shuch, Brian
Syed, Jamil
Nguyen, Kevin
Hoffman, Jonathan
Devesa, Susan
Suarez, Alfie
TI Predictive factors of metachronous bilateral renal cell carcinoma: a
surveillance, epidemiology, and end results analysis
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 15th International Kidney Cancer Symposium
CY NOV 04-05, 2016
CL Miami, FL
C1 [Shuch, Brian; Syed, Jamil] Yale Sch Med, Dept Urol, New Haven, CT USA.
[Nguyen, Kevin; Suarez, Alfie] Yale Dept Urol, New Haven, CT USA.
[Hoffman, Jonathan; Devesa, Susan] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD DEC
PY 2016
VL 118
SU S5
BP 8
EP 8
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA EC9QC
UT WOS:000388478200010
ER
PT J
AU Simpkin, AJ
Donovan, JL
Tilling, K
Lane, JA
Martin, RM
Albertsen, PC
Bill-Axelson, A
Carter, HB
Bosch, JLHR
Ferrucci, L
Hamdy, FC
Holmberg, L
Metter, EJ
Neal, DE
Parker, CC
Metcalfe, C
AF Simpkin, Andrew J.
Donovan, Jenny L.
Tilling, Kate
Lane, J. Athene
Martin, Richard M.
Albertsen, Peter C.
Bill-Axelson, Anna
Carter, H. Ballentine
Bosch, J. L. H. Ruud
Ferrucci, Luigi
Hamdy, Freddie C.
Holmberg, Lars
Metter, E. Jeffrey
Neal, David E.
Parker, Christopher C.
Metcalfe, Chris
TI Prostate-specific antigen patterns in US and European populations:
comparison of six diverse cohorts
SO BJU INTERNATIONAL
LA English
DT Article
DE active surveillance; prostate specific antigen; prostate cancer
ID DOUBLING TIME CALCULATION; ACTIVE SURVEILLANCE; FOLLOW-UP; RADICAL
TREATMENT; JOHNS-HOPKINS; CANCER; VELOCITY; INTERVENTION; KINETICS;
OUTCOMES
AB Objective
To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa).
Subjects and Methods
We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations.
Results
The annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA-detected PCa, but there was no evidence of a different rate of PSA change between these populations.
Conclusion
We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies.
C1 [Simpkin, Andrew J.; Donovan, Jenny L.; Tilling, Kate; Lane, J. Athene; Martin, Richard M.; Metcalfe, Chris] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Martin, Richard M.] Univ Bristol, NIHR Bristol Nutr Biomed Res Unit, Bristol, Avon, England.
[Albertsen, Peter C.] Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA.
[Bill-Axelson, Anna] Uppsala Univ, Inst Surg Sci, Dept Urol, Uppsala, Sweden.
[Carter, H. Ballentine] Johns Hopkins Sch Med, Dept Urol, Baltimore, MA USA.
[Bosch, J. L. H. Ruud] Univ Med Ctr Utrecht, Dept Urol, Utrecht, Netherlands.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MA USA.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Holmberg, Lars] Kings Coll London, Fac Life Sci & Med, London, England.
[Holmberg, Lars] Reg Canc Ctr, Uppsala, Uppsala Orebro, Sweden.
[Metter, E. Jeffrey] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN USA.
[Neal, David E.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Parker, Christopher C.] Royal Marsden Hosp, Acad Urol Unit, Inst Canc Res, London, England.
RP Simpkin, AJ (reprint author), Oakfield House,Oakfield Rd, Bristol BS8 2BN, Avon, England.
EM andrew.simpkin@bristol.ac.uk
OI Tilling, Kate/0000-0002-1010-8926
FU National Institute for Health Research (NIHR) Health Services and
Delivery Research Programme [09/2000/63]; Medical Research Council
[MR/L011824/1]; NIHR Health Services and Delivery Research programme
[09/2000/63]; UK National Institute for Health Research, Health
Technology Assessment Programme [HTA 96/20/99]; Cancer Research UK/UK
Department of Health [C11043/A4286, C18281/A8145, C18281/A11326,
C18281/A15064]; World Cancer Research Fund; University of Bristol Cancer
Research Fund; National Cancer Research Institute; NIHR; University
Hospitals Bristol NHS Foundation Trust; University of Bristol; Prostate
Cancer Foundation; National Institute on Aging, National Institutes of
Health, USA
FX This project was funded by the National Institute for Health Research
(NIHR) Health Services and Delivery Research Programme (project number
09/2000/63), published in full in the NIHR Journals Library [42].
Further information is available at
http://www.journalslibrary.nihr.ac.uk/hsdr. This report presents
independent research commissioned by the NIHR. The views and opinions
expressed by authors in this publication are those of the authors and do
not necessarily reflect those of the Health Services and Delivery
Research programme, NIHR, NHS or the Department of Health (UK).; Dr.
Simpkin is funded by the Medical Research Council (MR/L011824/1) and
previously by the NIHR Health Services and Delivery Research programme
(project number 09/2000/63).; Professors Donovan, Hamdy and Neal are the
Principal Investigators and Dr. Lane is the Trial Coordinator of the
Prostate Testing for Cancer and Treatment (ProtecT) trial. Professors
Martin, Donovan, Hamdy and Neal are the Principal Investigators of the
Comparison Arm to ProtecT (CAP) trial. The ProtecT trial is funded by
the UK National Institute for Health Research, Health Technology
Assessment Programme (HTA 96/20/99) and the CAP trial by Cancer Research
UK/UK Department of Health (C11043/A4286, C18281/A8145, C18281/A11326
and C18281/A15064). Funding for additional research has been received
from the World Cancer Research Fund, the University of Bristol Cancer
Research Fund and the National Cancer Research Institute (formed by the
Department of Health, Medical Research Council and Cancer Research UK).;
The NIHR Bristol Nutrition Biomedical Research Unit (RMM) is funded by
the NIHR and is a partnership between the University Hospitals Bristol
NHS Foundation Trust and the University of Bristol. Funding for the
Johns Hopkins Hospital cohort was provided by the Prostate Cancer
Foundation. The BLSA is funded by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, USA.
NR 41
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD DEC
PY 2016
VL 118
IS 6
BP 911
EP 918
DI 10.1111/bju.13422
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA EC9QL
UT WOS:000388479100016
PM 26799945
ER
PT J
AU Mai, PL
Best, AF
Peters, JA
DeCastro, RM
Khincha, PP
Loud, JT
Bremer, RC
Rosenberg, PS
Savage, SA
AF Mai, Phuong L.
Best, Ana F.
Peters, June A.
DeCastro, Rosamma M.
Khincha, Payal P.
Loud, Jennifer T.
Bremer, Renee C.
Rosenberg, Philip S.
Savage, Sharon A.
TI Risks of First and Subsequent Cancers Among TP53 Mutation Carriers in
the National Cancer Institute Li-Fraumeni Syndrome Cohort
SO CANCER
LA English
DT Article
DE cumulative cancer risk; Li-Fraumeni syndrome; second cancer; second
cancer risk; TP53
ID BREAST-CANCER; P53 MUTATIONS; GERMLINE MUTATIONS; FAMILIAL SYNDROME;
GENE; SARCOMA; NEOPLASMS; CRITERIA; PANEL; SEX
AB BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome characterized by a very high lifetime cancer risk and an early age at diagnosis of a wide cancer spectrum. Precise estimates for the risk of first and subsequent cancers are lacking. METHODS: The National Cancer Institute's Li-Fraumeni Syndrome Study includes families meeting the diagnostic criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or >= 3 cancers. Herein, we estimated the cumulative risk and annual hazards for first and second cancers among TP53 mutation carriers (TP53 positive [TP53+]) using MATLAB statistical software. RESULTS: This study evaluated 286 TP53+ individuals from 107 families. The cumulative cancer incidence was 50% by age 31 years among TP53+ females and 46 years among males, and nearly 100% by age 70 years for both sexes. Cancer risk was highest after age 20 years for females, mostly due to breast cancer, whereas among males the risk was higher in childhood and later adulthood. Among females, the cumulative incidence rates by age 70 years for breast cancer, soft tissue sarcoma, brain cancer, and osteosarcoma were 54%, 15%, 6%, and 5%, respectively. Among males, the incidence rates were 22%, 19%, and 11%, respectively, for soft tissue sarcoma, brain cancer, and osteosarcoma. Approximately 49% of those with 1 cancer developed at least another cancer after a median of 10 years. The average age-specific risk of developing a second cancer was comparable to that of developing a first cancer. CONCLUSIONS: The cumulative cancer risk in TP53+ individuals was very high and varied by sex, age, and cancer type. Additional work, including prospective risk estimates, is needed to better inform personalized risk management. (C) 2016 American Cancer Society.
C1 [Mai, Phuong L.; Peters, June A.; DeCastro, Rosamma M.; Khincha, Payal P.; Loud, Jennifer T.; Bremer, Renee C.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 6E-456 MSC 9772, Rockville, MD 20850 USA.
[Best, Ana F.; Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 6E-456 MSC 9772, Rockville, MD 20850 USA.
EM savagesh@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
FX Supported by funding from the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health.
NR 34
TC 1
Z9 1
U1 9
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2016
VL 122
IS 23
BP 3673
EP 3681
DI 10.1002/cncr.30248
PG 9
WC Oncology
SC Oncology
GA EC8CH
UT WOS:000388367300015
PM 27496084
ER
PT J
AU Silver, MI
Schiffman, M
Fetterman, B
Poitras, NE
Gage, JC
Wentzensen, N
Lorey, T
Kinney, WK
Castle, PE
AF Silver, Michelle I.
Schiffman, Mark
Fetterman, Barbara
Poitras, Nancy E.
Gage, Julia C.
Wentzensen, Nicolas
Lorey, Thomas
Kinney, Walter K.
Castle, Philip E.
TI The Population Impact of Human Papillomavirus/Cytology Cervical
Cotesting at 3-Year Intervals: Reduced Cervical Cancer Risk and
Decreased Yield of Precancer per Screen
SO CANCER
LA English
DT Article
DE biopsy; cervical cancer; cervical intraepithelial neoplasia; colposcopy;
cotest; human papillomavirus; screening
ID FOLLOW-UP; HPV; PREVENTION; GUIDELINES; CYTOLOGY; DNA
AB BACKGROUND: The objective of cervical screening is to detect and treat precancer to prevent cervical cancer mortality and morbidity while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals currently is a recommended screening strategy in the United States, but the interval extension is controversial. In the current study, the authors examined the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. The effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer, also was considered. METHODS: Two cohorts were defined. The "open cohort" included all women screened at least once during the study period; >1 million cotests were performed. In a fixed "long-term screening cohort," the authors considered the cumulative impact of repeated screening at 3-year intervals by restricting the cohort to women first cotested in 2003 through 2004 (ie, no women entering screening later were added to this group). RESULTS: Detection of cervical intraepithelial neoplasia 3/adenocarcinoma in situ (CIN3/AIS) increased in the open cohort (2004-2006: 82.0/100,000 women screened; 2007-2009: 140.6/100,000 women screened; and 2010-2012: 126.0/100,000 women screened); cancer diagnoses were unchanged. In the long-term screening cohort, the detection of CIN3/AIS increased and then decreased to the original level (20042006: 80.5/100,000 women screened; 2007-2009: 118.6/100,000 women screened; and 2010-2012: 84.9./100,000 women screened). The number of cancer diagnoses was found to decrease. When viewed in terms of screening efficiency, the number of colposcopies performed to detect a single case of CIN3/AIS increased in the cohort with repeat screening. CONCLUSIONS: Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer. However, a greater number of colposcopies are required to detect a single precancer. (C) 2016 American Cancer Society.
C1 [Silver, Michelle I.; Schiffman, Mark; Gage, Julia C.; Wentzensen, Nicolas] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas] Kaiser Permanente Northern Calif, Reg Lab, Berkeley, CA USA.
[Kinney, Walter K.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Castle, Philip E.] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
RP Silver, MI (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E584, Bethesda, MD 20892 USA.
EM michelle.silver@nih.gov
FU Intramural Research Program at the National Cancer Institute; Kaiser
Permanente Northern California
FX Funding provided by a collaboration between the Intramural Research
Program at the National Cancer Institute and Kaiser Permanente Northern
California.
NR 13
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2016
VL 122
IS 23
BP 3682
EP 3686
DI 10.1002/cncr.30277
PG 5
WC Oncology
SC Oncology
GA EC8CH
UT WOS:000388367300016
PM 27657992
ER
PT J
AU Kumar, P
Thudium, E
Laliberte, K
Zaccardelli, D
Nelsen, A
AF Kumar, Parag
Thudium, Emily
Laliberte, Kevin
Zaccardelli, David
Nelsen, Andrew
TI A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes
of Administration
SO CLINICAL PHARMACOKINETICS
LA English
DT Review
ID PULMONARY-ARTERIAL-HYPERTENSION; CONTINUOUS SUBCUTANEOUS INFUSION;
HEALTHY ADULT VOLUNTEERS; INHALED TREPROSTINIL; ORAL TREPROSTINIL;
CONTROLLED-TRIAL; DIOLAMINE; THERAPY; BOSENTAN; EFFICACY
AB Treprostinil is available in three different formulations and four different routes of administration: Remodulin(A (R)) (treprostinil sodium, intravenous and subcutaneous administration), Tyvaso(A (R)) (treprostinil sodium, inhaled administration), and Orenitram(A (R)) (treprostinil diolamine, oral administration) for the treatment of pulmonary arterial hypertension (PAH). Pharmacokinetic studies have been performed in healthy volunteers and patients with PAH. The intent of this review is to outline pharmacokinetic considerations of the three treprostinil formulations and provide clinicians with a resource that may support clinical decisions in treating patients with PAH.
C1 [Kumar, Parag; Thudium, Emily; Laliberte, Kevin; Zaccardelli, David; Nelsen, Andrew] United Therapeutics Corp, 55 TW Alexander Dr,POB 14186, Res Triangle Pk, NC 27709 USA.
[Kumar, Parag] NIH, Clin Pharmacokinet Res Lab, Bldg 10, Bethesda, MD 20892 USA.
RP Nelsen, A (reprint author), United Therapeutics Corp, 55 TW Alexander Dr,POB 14186, Res Triangle Pk, NC 27709 USA.
EM ANelsen@unither.com
NR 39
TC 0
Z9 0
U1 1
U2 1
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 0312-5963
EI 1179-1926
J9 CLIN PHARMACOKINET
JI Clin. Pharmacokinet.
PD DEC
PY 2016
VL 55
IS 12
BP 1495
EP 1505
DI 10.1007/s40262-016-0409-0
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA EC5IV
UT WOS:000388169000002
PM 27286723
ER
PT J
AU Stoff, DM
Colosi, D
Rubtsova, A
Wingood, G
AF Stoff, David M.
Colosi, Deborah
Rubtsova, Anna
Wingood, Gina
TI HIV and Aging Research in Women: An Overview
SO CURRENT HIV/AIDS REPORTS
LA English
DT Article
DE HIV; Aging; Women; Women's Interagency HIV Study (WIHS); Aging/HIV
definitions; Aging/HIV models
ID OLDER-ADULTS; UNITED-STATES; COGNITIVE RESERVE; SOCIAL NETWORKS;
INFECTION; HEALTH; POPULATION; HIV/AIDS; TIME; CARE
AB This paper reviews some background issues as a foundation to place the ensuing supplement papers of this special issue section in context. The articles in this special supplement issue deepen and expand our understanding of biomedical, neurocognitive, and psychosocial aspects involved in human immunodeficiency virus (HIV) of older women, primarily through the use of the Women's Interagency HIV Study (WIHS) prospective cohort study. As it relates to research on the intersection between HIV and aging in women, we discuss (i) epidemiology as introduction, (ii) the cohort study design featuring the WIHS, (iii) definitions, (iv) models, and (v) section articles.
C1 [Stoff, David M.; Colosi, Deborah] NIMH, Bethesda, MD 20892 USA.
[Rubtsova, Anna] Emory Univ, Atlanta, GA 30322 USA.
[Wingood, Gina] Columbia Univ, New York, NY USA.
RP Stoff, DM (reprint author), NIMH, Bethesda, MD 20892 USA.
EM dstoff@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases (NIAID); Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD); National Cancer Institute (NCI); National Institute on Drug
Abuse (NIDA); National Institute on Mental Health (NIMH); National
Institute of Dental and Craniofacial Research (NIDCR); National
Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on
Deafness and other Communication Disorders (NIDCD); NIH Office of
Research on Women's Health
FX Data in this manuscript were collected by the Women's Interagency HIV
Study (WIHS). The contents of this publication are solely the
responsibility of the authors and do not represent the official views of
the National Institutes of Health (NIH). WIHS principal investigators
are the following: UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and
Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun
and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos),
U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson),
U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French),
U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye),
U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch),
U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy
Women's HIV Study, Northern California (Ruth Greenblatt, Bradley
Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and
Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; and
Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I-WIHS IV).
The WIHS is funded primarily by the National Institute of Allergy and
Infectious Diseases (NIAID), with additional co-funding from the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), the National Cancer Institute (NCI), the National Institute on
Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH).
Targeted supplemental funding for specific projects is also provided by
the National Institute of Dental and Craniofacial Research (NIDCR), the
National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National
Institute on Deafness and other Communication Disorders (NIDCD), and the
NIH Office of Research on Women's Health. WIHS data collection is also
supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA).
NR 59
TC 1
Z9 1
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD DEC
PY 2016
VL 13
IS 6
BP 383
EP 391
DI 10.1007/s11904-016-0338-4
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA EC4TO
UT WOS:000388127000009
PM 27771876
ER
PT J
AU Fraser, JL
Venditti, CP
AF Fraser, Jamie L.
Venditti, Charles P.
TI Methylmalonic and propionic acidemias: clinical management update
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE brain injury; liver transplantation; medical foods; methylmalonic
acidemia; propionic acidemia
ID DONOR LIVER-TRANSPLANTATION; TANDEM MASS-SPECTROMETRY; PERFORMANCE
LIQUID-CHROMATOGRAPHY; CLASSICAL ORGANIC ACIDURIAS; COA CARBOXYLASE
DEFICIENCY; COBALAMIN C DEFICIENCY; LONG-TERM MANAGEMENT; 10-YEAR
FOLLOW-UP; COENZYME-A MUTASE; INBORN-ERRORS
AB Purpose of review
Recent clinical studies and management guidelines for the treatment of the organic acidopathies methylmalonic acidemia (MMA) and propionic acidemia address the scope of interventions to maximize health and quality of life. Unfortunately, these disorders continue to cause significant morbidity and mortality due to acute and chronic systemic and end-organ injury.
Recent findings
Dietary management with medical foods has been a mainstay of therapy for decades, yet well controlled patients can manifest growth, development, cardiac, ophthalmological, renal, and neurological complications. Patients with organic acidopathies suffer metabolic brain injury that targets specific regions of the basal ganglia in a distinctive pattern, and these injuries may occur even with optimal management during metabolic stress. Liver transplantation has improved quality of life and metabolic stability, yet transplantation in this population does not entirely prevent brain injury or the development of optic neuropathy and cardiac disease.
Summary
Management guidelines should identify necessary screening for patients with methylmalonic acidemia and propionic acidemia, and improve anticipatory management of progressive end-organ disease. Liver transplantation improves overall metabolic control, but injury to nonregenerative tissues may not be mitigated. Continued use of medical foods in these patients requires prospective studies to demonstrate evidence of benefit in a controlled manner.
C1 [Fraser, Jamie L.] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC 20010 USA.
[Venditti, Charles P.] NHGRI, Med Genom & Metab Genet Branch, NIH, BG 10 RM 7N248A,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Venditti, CP (reprint author), NHGRI, Med Genom & Metab Genet Branch, NIH, BG 10 RM 7N248A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
FU National Human Genome Research Institute; Child Health Research Career
Development Award via Children's National Medical Center
FX The work was supported by the Intramural Research Program of the
National Human Genome Research Institute (CPV) and the Child Health
Research Career Development Award (K12) via Children's National Medical
Center (JLF).
NR 239
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U1 6
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8703
EI 1531-698X
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD DEC
PY 2016
VL 28
IS 6
BP 682
EP 693
DI 10.1097/MOP.0000000000000422
PG 12
WC Pediatrics
SC Pediatrics
GA EC0JF
UT WOS:000387785900002
PM 27653704
ER
PT J
AU Alawad, AS
Levy, C
AF Alawad, Ahmad Samer
Levy, Cynthia
TI FXR Agonists: From Bench to Bedside, a Guide for Clinicians
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Review
ID FARNESOID-X-RECEPTOR; PRIMARY BILIARY-CIRRHOSIS; PLACEBO-CONTROLLED
TRIAL; BILE-ACID; OBETICHOLIC ACID; NONALCOHOLIC STEATOHEPATITIS;
NUCLEAR RECEPTOR; METABOLIC SYNDROME; SPONTANEOUS HEPATOCARCINOGENESIS;
HEPATOCELLULAR-CARCINOMA
C1 [Alawad, Ahmad Samer] Natl Inst Hlth, NIDDK Liver Dis Branch, 10 Ctr Dr,CRC Bldg 10,RM 4-5722, Bethesda, MD 20892 USA.
[Levy, Cynthia] Univ Miami, Miller Sch Med, Div Hepatol, 1500 NW 12th Ave,Suite 1101, Miami, FL 33136 USA.
RP Levy, C (reprint author), Univ Miami, Miller Sch Med, Div Hepatol, 1500 NW 12th Ave,Suite 1101, Miami, FL 33136 USA.
EM clevy@med.miami.edu
NR 49
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U1 3
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD DEC
PY 2016
VL 61
IS 12
BP 3395
EP 3404
DI 10.1007/s10620-016-4334-8
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EC6DT
UT WOS:000388227400007
PM 27734248
ER
PT J
AU Heidemann, LA
Navarro, VJ
Ahmad, J
Hayashi, PH
Stolz, A
Kleiner, DE
Fontana, RJ
AF Heidemann, Lauren A.
Navarro, Victor J.
Ahmad, Jawad
Hayashi, Paul H.
Stolz, Andrew
Kleiner, David E.
Fontana, Robert J.
TI Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case
Series (vol 61, pg 2741, 2016)
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Correction
ID HEPATOTOXICITY; SUPPLEMENTS
C1 [Heidemann, Lauren A.; Fontana, Robert J.] Univ Michigan, Med Ctr, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA.
[Navarro, Victor J.] Einstein Healthcare Network, Dept Med, Philadelphia, PA USA.
[Ahmad, Jawad] Icahn Sch Med Mt Sinai Med Ctr, Dept Med, New York, NY USA.
[Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA.
[Stolz, Andrew] Univ So Calif, Los Angeles, CA USA.
[Kleiner, David E.] Natl Canc Inst, Natl Inst Hlth, Pathol Lab, Bethesda, MD USA.
RP Fontana, RJ (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA.
EM rfontana@med.umich.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD DEC
PY 2016
VL 61
IS 12
BP 3638
EP 3638
DI 10.1007/s10620-016-4290-3
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EC6DT
UT WOS:000388227400039
PM 27714508
ER
PT J
AU Papadakis, GZ
Holland, SM
Quezado, M
Patronas, NJ
AF Papadakis, Georgios Z.
Holland, Steven M.
Quezado, Martha
Patronas, Nicholas J.
TI Adrenal cryptococcosis in an immunosuppressed patient showing intensely
increased metabolic activity on F-18-FDG PET/CT
SO ENDOCRINE
LA English
DT Article
DE F-18-FDG PET/CT; Adrenal cryptococcosis; Primary adrenal insufficiency
AB Disseminated cryptococcosis most commonly occurs in immunosuppressed patients and can rarely affect the adrenal glands. We report on a patient with biopsy proven bilateral adrenal cryptococcosis resulting in primary adrenal insufficiency, which was evaluated with whole-body positron emission tomography/computed tomography scan using F-18-FDG. Both enlarged adrenal glands presented intensely increased F-18-FDG activity in the periphery, while central necrotic regions were photopenic. Although diagnosis was established by adrenal gland biopsy, F-18-FDG positron emission tomography/computed tomography scan can significantly contribute to the assessment of disease activity and monitoring of treatment response. Furthermore, fungal infections should always be considered when encountering hypermetabolic adrenal masses, especially in the setting of immunodeficient patients.
C1 [Papadakis, Georgios Z.; Patronas, Nicholas J.] NIH, Radiol & Imaging Sci Warren Grant Magnuson Clin C, Bldg 10, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA.
RP Patronas, NJ (reprint author), NIH, Radiol & Imaging Sci Warren Grant Magnuson Clin C, Bldg 10, Bethesda, MD 20892 USA.
EM NPatronas@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 3
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD DEC
PY 2016
VL 54
IS 3
BP 834
EP 836
DI 10.1007/s12020-016-1040-4
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EC5TA
UT WOS:000388197900031
PM 27473097
ER
PT J
AU Murray, AJ
Knight, NS
Cole, MA
Cochlin, LE
Carter, E
Tchabanenko, K
Pichulik, T
Gulston, MK
Atherton, HJ
Schroeder, MA
Deacon, RMJ
Kashiwaya, Y
King, MT
Pawlosky, R
Rawlins, JNP
Tyler, DJ
Griffin, JL
Robertson, J
Veech, RL
Clarke, K
AF Murray, Andrew J.
Knight, Nicholas S.
Cole, Mark A.
Cochlin, Lowri E.
Carter, Emma
Tchabanenko, Kirill
Pichulik, Tica
Gulston, Melanie K.
Atherton, Helen J.
Schroeder, Marie A.
Deacon, Robert M. J.
Kashiwaya, Yoshihiro
King, M. Todd
Pawlosky, Robert
Rawlins, J. Nicholas P.
Tyler, Damian J.
Griffin, Julian L.
Robertson, Jeremy
Veech, Richard L.
Clarke, Kieran
TI Novel ketone diet enhances physical and cognitive performance
SO FASEB JOURNAL
LA English
DT Article
DE metabolism; muscle; energetics; exercise; heart
ID BETA-HYDROXYBUTYRATE; UNCOUPLING PROTEINS; KETOGENIC DIET;
HEART-FAILURE; ESTER DIET; RAT-HEART; (R)-3-HYDROXYBUTYL
(R)-3-HYDROXYBUTYRATE; MITOCHONDRIAL BIOGENESIS; EXERCISE PERFORMANCE;
MAGNETIC-RESONANCE
AB Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [P-31]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.-Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M. K., Atherton, H. J., Schroeder, M. A., Deacon, R. M. J., Kashiwaya, Y., King, M. T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance.
C1 [Murray, Andrew J.; Knight, Nicholas S.; Cochlin, Lowri E.; Carter, Emma; Pichulik, Tica; Atherton, Helen J.; Schroeder, Marie A.; Tyler, Damian J.; Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
[Cole, Mark A.; Tchabanenko, Kirill; Robertson, Jeremy] Univ Oxford, Dept Chem, Oxford, England.
[Deacon, Robert M. J.; Rawlins, J. Nicholas P.] Univ Oxford, Dept Expt Psychol, Oxford, England.
[Murray, Andrew J.] Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England.
[Gulston, Melanie K.; Griffin, Julian L.] Univ Cambridge, Dept Biochem, Cambridge, England.
[Gulston, Melanie K.; Griffin, Julian L.] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge, England.
[Kashiwaya, Yoshihiro; King, M. Todd; Pawlosky, Robert; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA.
[Cole, Mark A.] Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England.
[Tchabanenko, Kirill] Queens Univ Belfast, Sch Chem & Chem Engn, Belfast, Antrim, North Ireland.
RP Murray, AJ (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England.
EM ajm267@cam.ac.uk
FU Defense Advanced Research Projects Agency; Research Councils UK
FX The authors thank Dr. Joseph Bielitsky, the late Dr. Catherine Golden,
Dr. Brett Giroir, and Dr. Kerrie DeMarco (Defense Advanced Research
Projects Agency, Arlington, VA, USA), whose constant support and advice
made this study possible. A.J.M. thanks the Research Councils UK for
supporting his Academic Fellowship. This work was supported by the
Defense Advanced Research Projects Agency. The intellectual property
covering the uses of ketone bodies and esters are owned by BTG, Ltd.,
the University of Oxford, and the U.S. National Institutes of Health.
Should royalties ever accrue from these patents, A.J.M., R.L.V., M.T.K.,
and K.C., as named inventors, may receive a share of royalties as
determined by the terms of the respective institutions. K.C. is director
of T Delta S, Ltd., a company spun out of the University of Oxford to
develop products on the basis of ketone ester nutrition.
NR 67
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U1 30
U2 30
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD DEC
PY 2016
VL 30
IS 12
BP 4021
EP 4032
DI 10.1096/fj.201600773R
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA EC5UG
UT WOS:000388201500010
PM 27528626
ER
PT J
AU Goetzl, EJ
Kapogiannis, D
Schwartz, JB
Lobach, IV
Goetzl, L
Abner, EL
Jicha, GA
Karydas, AM
Boxer, A
Miller, BL
AF Goetzl, Edward J.
Kapogiannis, Dimitrios
Schwartz, Janice B.
Lobach, Iryna V.
Goetzl, Laura
Abner, Erin L.
Jicha, Gregory A.
Karydas, Anna M.
Boxer, Adam
Miller, Bruce L.
TI Decreased synaptic proteins in neuronal exosomes of frontotemporal
dementia and Alzheimer's disease
SO FASEB JOURNAL
LA English
DT Article
DE cognition; proteinopathy; neurotransmission; biomarkers
ID CEREBROSPINAL-FLUID BIOMARKER; CLINICAL-TRIALS; BLOOD EXOSOMES;
ADAS-COG; SYNAPTOPHYSIN; NEUROGRANIN; IDENTIFICATION; PLASTICITY;
CRITERIA; DECLINE
AB Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD). Plasma neuronal-derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross-sectional study, and from 9 patients with AD, 10 with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts. NDE levels of synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin were significantly lower in patients with FTD and AD than in controls, but those of growth-associated protein 43 and synapsin 1 were reduced only in patients with AD. Functionally relevant phosphorylation of synapsin 1 serine 9 was reduced in patients with FTD and AD, although total synapsin 1 protein was higher in FTD than in controls. NDE levels of synaptotagmin, synaptophysin, and neurogranin were decreased years before dementia inpatients with FTD and AD. NDE levels of synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid beta-peptide 42 or P-T181-tau, were correlated significantly with cognition assessed by mini-mental state examination or AD assessment scale-cognitive subscale. NDE synaptic proteins may be useful preclinical indices and progression measures in senile dementias.
C1 [Goetzl, Edward J.; Schwartz, Janice B.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Schwartz, Janice B.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
[Lobach, Iryna V.] Univ Calif San Francisco, Clin Translat Sci Inst, San Francisco, CA 94143 USA.
[Karydas, Anna M.; Boxer, Adam; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Goetzl, Edward J.; Schwartz, Janice B.] Jewish Home San Francisco, San Francisco, CA USA.
[Kapogiannis, Dimitrios] NIA, Lab Neurosci, Baltimore, MD 21224 USA.
[Goetzl, Laura] Temple Univ, Dept Obstet Gynecol & Reprod Sci, Philadelphia, PA 19122 USA.
[Abner, Erin L.; Jicha, Gregory A.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
RP Goetzl, EJ (reprint author), Univ Calif San Francisco, Geriatr Res Ctr, 1719 Broderick St, San Francisco, CA 94115 USA.
EM edward.goetzl@ucsf.edu
FU BAND2 Program of the Michael J. Fox Foundation for Parkinson's Research;
Alzheimer's Association; Weston Brain Institute (Toronto, ON, Canada);
Nanosomix; Intramural Program of the U.S. National Institutes of Health,
National Institute on Aging (NIA); NIA [P30 AG028383]; Acetylon;
iPierian; Archer Biosciences; Alzheimer's Research UK
FX The authors thank Sonya Anderson (University of Kentucky Alzheimer's
Disease Center) for organizing and distributing biospecimens and Judith
H. Goetzl (Jewish Home of San Francisco) for expert production of
graphic illustrations. This work was supported by a grant from the BAND2
Program of the Michael J. Fox Foundation for Parkinson's Research, the
Alzheimer's Association, Alzheimer's Research UK, and the Weston Brain
Institute (Toronto, ON, Canada), by a grant for methodological
development from Nanosomix (to E.J.G.), the Intramural Program of the
U.S. National Institutes of Health, National Institute on Aging (NIA; to
D.K.), and NIA Grant P30 AG028383 (to E.L.A.). E.J.G. has filed an
application with the U.S. Patent Office for the platform and
methodologies described in this report; he is a founder of Nanosomix,
but now receives no salary or consulting fees, but only support for
laboratory supplies. E.L.A. received travel support from Nanosomix for
the 2015 annual meeting of the American Association for the Advancement
of Science. A.B. declares that outside the submitted studies, he has
grants from the NIA, Tau Research Consortium, Allon Therapeutics,
Genentech, Bristol-Myers Squibb, TauRx, Alzheimer's Association,
Bluefield Project to Cure FTD, the Association for Frontotemporal
Degeneration, Alzheimer's Drug Discovery Foundation, EnVivo, C2N
Diagnostics, Pfizer, Eli Lilly, and Corticobasal Degeneration Solutions;
grants, personal fees, and nonfinancial support from Archer Biosciences;
personal fees from Acetylon; and personal fees from iPierian. The
remaining authors declare no conflicts of interest.
NR 36
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PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD DEC
PY 2016
VL 30
IS 12
BP 4141
EP 4148
DI 10.1096/fj.201600816R
PG 8
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA EC5UG
UT WOS:000388201500020
PM 27601437
ER
PT J
AU Rauzi, F
Kirkby, NS
Edin, ML
Whiteford, J
Zeldin, DC
Mitchell, JA
Warner, TD
AF Rauzi, Francesca
Kirkby, Nicholas S.
Edin, Matthew L.
Whiteford, James
Zeldin, Darryl C.
Mitchell, Jane A.
Warner, Timothy D.
TI Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet
cyclooxygenase-1
SO FASEB JOURNAL
LA English
DT Article
DE angiogenesis; eicosanoids; endothelium; prostaglandins
ID ANGIOGENESIS; ACID; AGGREGOMETRY; METABOLITES; EXPRESSION; MECHANISM;
VEGF; A(2)
AB Regular consumption of low-dose aspirin reduces the occurrence of colorectal, esophageal, stomach, and gastrointestinal cancers. The underlying mechanism is unknown but may be linked to inhibition of angiogenesis. Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid chromatography with tandem mass spectrometry analyses and immunoassays of human platelet releasates coupled with angiogenesis assays to search for the mediators of these effects. Blood or platelet-rich plasma from healthy volunteers stimulated with platelet activators produced a broad range of eicosanoids. Notably, preincubation of platelets with aspirin, but not with a P2Y12 receptor antagonist, caused a marked reduction in the production of 11-hydroxyeicosatetraenoic acid (HETE) and 15(S)-HETE, in addition to prostanoids such as thromboxane A(2). Releasates from activated platelets caused cell migration and tube formation in cultured human endothelial cells and stimulated the sprouting of rat aortic rings in culture. These proangiogenic effects were absent when platelets were treated with aspirin but returned by coincubation with exogenous 15(S)-HETE. These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. Thus, 15(S)-HETE represents a potential target for the development of novel antiangiogenic therapeutics, and blockade of its production may provide a mechanism for the anticancer effects of aspirin.
C1 [Rauzi, Francesca; Kirkby, Nicholas S.; Whiteford, James; Warner, Timothy D.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Kirkby, Nicholas S.; Mitchell, Jane A.] Imperial Coll London, Natl Heart & Lung Inst, London, England.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Warner, TD (reprint author), Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England.
EM t.d.warner@qmul.ac.uk
FU Wellcome Trust [085255/Z/08/Z]; British Heart Foundation
[FS/10/033/28271]; William Harvey Research Foundation; Intramural
Research Program of the U.S. National Institutes of Health (NIH)
National Institute of Environmental Health Sciences [Z01-025034]
FX This research was supported by the Wellcome Trust (Grant 085255/Z/08/Z),
the British Heart Foundation (Grant FS/10/033/28271), the William Harvey
Research Foundation, and the Intramural Research Program of the U.S.
National Institutes of Health (NIH) National Institute of Environmental
Health Sciences (Grant Z01-025034).
NR 26
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U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD DEC
PY 2016
VL 30
IS 12
BP 4256
EP 4266
DI 10.1096/fj.201600530R
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA EC5UG
UT WOS:000388201500030
PM 27633788
ER
PT J
AU Yang, F
Ma, HW
Belcher, J
Butler, MR
Redmond, TM
Boye, SL
Hauswirth, WW
Ding, XQ
AF Yang, Fan
Ma, Hongwei
Belcher, Joshua
Butler, Michael R.
Redmond, T. Michael
Boye, Sanford L.
Hauswirth, William W.
Ding, Xi-Qin
TI Targeting iodothyronine deiodinases locally in the retina is a
therapeutic strategy for retinal degeneration
SO FASEB JOURNAL
LA English
DT Article
DE thyroid hormone; photoreceptor; cone degeneration; iopanoic acid
ID THYROID-HORMONE RECEPTOR; ENDOPLASMIC-RETICULUM STRESS; CONE CELL-DEATH;
TYPE-3 DEIODINASE; GENE DELIVERY; MOUSE MODEL; PHOTORECEPTOR
DEGENERATION; CHANNEL DEFICIENCY; KNOCKOUT MOUSE; IN-VITRO
AB Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65(-/-) mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.
C1 [Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R.; Ding, Xi-Qin] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, 940 Stanton L Young Blvd,BMSB 553, Oklahoma City, OK 73104 USA.
[Butler, Michael R.] NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
[Boye, Sanford L.; Hauswirth, William W.] Univ Florida, Dept Ophthalmol, Gainesville, FL USA.
[Hauswirth, William W.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
RP Ding, XQ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, 940 Stanton L Young Blvd,BMSB 553, Oklahoma City, OK 73104 USA.
EM xi-qin-ding@ouhsc.edu
FU NIH NEI [P30EY021725, P30EY021721, T32EY023202, R01EY019490,
R21EY024583]; Research to Prevent Blindness; Foundation Fighting
Blindness; Knights Templar Eye Foundation
FX The authors thank Dr. Anand Swaroop [U.S. National Institutes of Health
(NIH) National Eye Institute (NEI)] for the Nrl-/- mouse
line; Dr. P. Reed Larsen (Brigham and Women's Hospital Boston, MA, USA)
for human DIO3 cDNA; Bruce Baretz (Lipoid LLC, Newark, NJ, USA) for
phospholipon 90G; Dr. Cheryl Craft (The University of Southern
California, Los Angeles, CA, USA) for anti-M-opsin and anti-cone
arrestin antibodies; Dr. Muna Naash (University of Houston, Houston, TX,
USA) for anti-S-opsin antibody; Dr. Robert Molday (University of British
Columbia, Vancouver, BC, Canada) for mouse anti-rhodopsin antibody 1D4;
and Imaging Core Facility of the Department of Cell Biology at the
University of Oklahoma Health Sciences Center for technical assistance.
This work was supported by NIH NEI Grants P30EY021725, P30EY021721,
T32EY023202, R01EY019490, and R21EY024583; an unrestricted grant to the
Department of Ophthalmology, University of Florida, from Research to
Prevent Blindness; the Foundation Fighting Blindness; and the Knights
Templar Eye Foundation. The authors declare no conflicts of interest.
NR 67
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U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD DEC
PY 2016
VL 30
IS 12
BP 4313
EP 4325
DI 10.1096/fj.201600715R
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA EC5UG
UT WOS:000388201500035
PM 27623928
ER
PT J
AU Prentoe, J
Verhoye, L
Moctezuma, RV
Buysschaert, C
Farhoudi, A
Wang, R
Alter, H
Meuleman, P
Bukh, J
AF Prentoe, Jannick
Verhoye, Lieven
Moctezuma, Rodrigo Velazquez
Buysschaert, Caroline
Farhoudi, Ali
Wang, Richard
Alter, Harvey
Meuleman, Philip
Bukh, Jens
TI HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV
in humanised mice
SO GUT
LA English
DT Article
ID HEPATITIS-C VIRUS; BROADLY NEUTRALIZING ANTIBODIES; CROSS-GENOTYPE
NEUTRALIZATION; HUMORAL IMMUNE-RESPONSE; CELL-CULTURE-SYSTEMS; B TYPE-I;
HUMAN LIVER; VACCINE; CHALLENGE; MUTATIONS
AB Objective HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility.
Design Analysis of HCV from human liver chimeric mice infected with cell-culture-derived prototype genotype 2a recombinant J6/JFH1 or HVR1-deleted variant J6/JFH1(Delta HVR1) identified adaptive mutations, which were analysed by reverse genetics in Huh7.5 and CD81-deficient S29 cells. The increased in vivo genomic stability of the adapted viruses facilitated ex vivo density analysis by ultracentrifugation and in vivo neutralisation experiments addressing the role of HVR1.
Results In vivo, J6/JFH1 and J6/JFH1(Delta HVR1) depended on single substitutions within amino acids 867-876 in non-structural protein, NS2. The identified A876P-substitution resulted in a 4.7-fold increase in genomic stability. In vitro, NS2 substitutions enhanced infectivity 5-10-fold by increasing virus assembly. Mouse-derived mJ6/JFH1(A876P) and mJ6/JFH1(Delta HVR1/A876P) viruses displayed similar heterogeneous densities of 1.02-1.1 g/mL. Human liver chimeric mice loaded with heterologous patient H (genotype 1a) immunoglobulin had partial protection against mJ6/JFH1(A876P) and complete protection against mJ6/JFH1(Delta HVR1/A876P). Interestingly, we identified a putative escape mutation, D476G, in mJ6/JFH1(A876P). This mutation in hypervariable region 2 conferred 6.6-fold resistance against H06 IgG in vitro.
Conclusions The A876P-substitution bridges in vitro and in vivo studies using J6/JFH1-based recombinants. We provide the first in vivo evidence that HVR1 protects cross-genotype conserved HCV neutralisation epitopes, which advocates the possibility of using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses.
C1 [Prentoe, Jannick; Moctezuma, Rodrigo Velazquez; Bukh, Jens] Hvidovre Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, Copenhagen, Denmark.
[Prentoe, Jannick; Moctezuma, Rodrigo Velazquez; Bukh, Jens] Hvidovre Univ Hosp, Clin Res Ctr, Copenhagen, Denmark.
[Prentoe, Jannick; Moctezuma, Rodrigo Velazquez; Bukh, Jens] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark.
[Verhoye, Lieven; Buysschaert, Caroline; Farhoudi, Ali; Meuleman, Philip] Univ Ghent, Ctr Vaccinol, Ghent, Belgium.
[Wang, Richard; Alter, Harvey] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Bukh, J (reprint author), Hvidovre Univ Hosp, Dept Infect Dis, 144,Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@sund.ku.dk
FU Faculty of Health and Medical Sciences, University of Copenhagen; Danish
Council for Independent Research, Medical Sciences; Lundbeck Foundation;
Novo Nordisk Foundation; Danish Council for Independent Research; Ghent
University [01G01712]; Research Foundation-Flanders [G.0521.12N];
Belgian state [IUAP P7/47-HEPRO-2]
FX This study was supported by Ph.D. stipends from Faculty of Health and
Medical Sciences, University of Copenhagen (JP, RVM), an individual
DFF-postdoctoral grant from the Danish Council for Independent Research,
Medical Sciences (JP), and research grants from the Lundbeck Foundation
(JP, JB), the Novo Nordisk Foundation (JB), the Danish Council for
Independent Research, Medical Sciences (JB), and an advanced top
researcher grant from the Danish Council for Independent Research (JB).
Additional support was provided to PM by the Ghent University (Concerted
Action Grant 01G01712), The Research Foundation-Flanders (Project
G.0521.12N) and the Belgian state (IUAP P7/47-HEPRO-2).
NR 48
TC 3
Z9 3
U1 2
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD DEC
PY 2016
VL 65
IS 12
BP 1988
EP 1997
DI 10.1136/gutjnl-2015-310300
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EC4MV
UT WOS:000388106600010
PM 26589670
ER
PT J
AU Geiger, JL
Bauman, JE
Gibson, MK
Gooding, WE
Varadarajan, P
Kotsakis, A
Martin, D
Gutkind, JS
Hedberg, ML
Grandis, JR
Argiris, A
AF Geiger, Jessica L.
Bauman, Julie E.
Gibson, Michael K.
Gooding, William E.
Varadarajan, Prakash
Kotsakis, Athanasios
Martin, Daniel
Gutkind, Jorge Silvio
Hedberg, Matthew L.
Grandis, Jennifer R.
Argiris, Athanassios
TI Phase II trial of everolimus in patients with previously treated
recurrent or metastatic head and neck squamous cell carcinoma
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE head and neck squamous cell carcinoma (HNSCC); everolimus; mammalian
target of rapamycin (mTOR) inhibitors; PIK3CA mutations; clinical trial
ID MAMMALIAN TARGET; CANCER STATISTICS; RANDOMIZED-TRIAL; RAPAMYCIN KINASE;
CETUXIMAB; PREVALENCE; INHIBITOR; MORTALITY; ERLOTINIB
AB Background. Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC.
Methods. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway.
Results. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue.
Conclusion. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. (C) 2016 Wiley Periodicals, Inc.
C1 [Geiger, Jessica L.; Bauman, Julie E.] Univ Pittsburgh, Div Hematol Oncol, Dept Internal Med, Pittsburgh, PA USA.
[Gibson, Michael K.] Case Western Univ, Div Hematol Oncol, Dept Internal Med, Cleveland, OH USA.
[Gooding, William E.] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA.
[Varadarajan, Prakash; Argiris, Athanassios] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, San Antonio, TX 78229 USA.
[Kotsakis, Athanasios] Univ Crete, Sch Med, Iraklion, Greece.
[Martin, Daniel; Gutkind, Jorge Silvio] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
[Hedberg, Matthew L.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA.
[Grandis, Jennifer R.] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA.
[Argiris, Athanassios] Hygeia Hosp, Dept Med Oncol, Athens, Greece.
RP Argiris, A (reprint author), Hygeia Hosp, Erythrou Stavrou 5, Athens 15123, Greece.
EM athanassios.argiris@gmail.com
FU University of Pittsburgh Cancer Institute [P30CA47904]; [F30CA180235];
[R01DE023685]
FX Contract grant sponsor: Hedberg; contract grant number: F30CA180235;
Grandis; contract grant number: R01DE023685; University of Pittsburgh
Cancer Institute; contract grant number: P30CA47904.
NR 27
TC 2
Z9 2
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
EI 1097-0347
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD DEC
PY 2016
VL 38
IS 12
BP 1759
EP 1764
DI 10.1002/hed.24501
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA EC8CI
UT WOS:000388367400005
PM 27232378
ER
PT J
AU Kaess, BM
Preis, SR
Beiser, A
Sawyer, DB
Chen, TC
Seshadri, S
Vasan, RS
AF Kaess, Bernhard M.
Preis, Sarah R.
Beiser, Alexa
Sawyer, Douglas B.
Chen, Tai C.
Seshadri, Sudha
Vasan, Ramachandran S.
TI Circulating vascular endothelial growth factor and the risk of
cardiovascular events
SO HEART
LA English
DT Article
ID CORONARY-HEART-DISEASE; ANGIOGENESIS; FRAMINGHAM; ATHEROSCLEROSIS;
METAANALYSIS; RECEPTOR; THERAPY; BIOLOGY; PLASMA; MICE
AB Objective To investigate the relation of circulating concentrations of vascular endothelial growth factor (VEGF) for the risk of developing cardiovascular disease (CVD) in a large community-based sample.
Methods We prospectively assessed the relation of circulating VEGF concentrations with the incidence of CVD among 3041 Framingham Heart Study participants (mean age 63.4 +/- 11.1 years, 59% women). Multivariable Cox proportional hazards models were estimated adjusting for standard risk factors to VEGF quartiles to incident CVD. Restricted cubic splines were used to examine the linearity of the association.
Results After a mean follow-up of 8.8 (+/- 2.8) years, 527 individuals experienced a first CVD event. Compared with participants in the first VEGF quartile, individuals in the second VEGF quartile had a 34% increased risk for future CVD (HR 1.34, 95% CI 1.03 to 1.74; p value=0.03) and individuals in third quartile had a 59% higher risk (HR 1.59; 95% CI 1.23 to 2.05, p value=0.0003). Individuals in the highest VEGF quartile had a similar cardiovascular risk as compared with those in the lowest VEGF quartile (HR 1.18, 95% CI 0.91 to 1.53, p value=0.21). Evaluation of restricted cubic splines confirmed the nonlinear, inverted U-shaped relation of serum VEGF and CVD events (p< 0.0001 for model fit, p=0.006 for non-linearity).
Conclusions Circulating VEGF concentrations exhibit a complex non-linear (inverted U-shaped) relation with the risk of developing CVD events, with the lowest risk experienced at the lower and upper end of the distribution. The underlying pathophysiological mechanisms remain to be elucidated.
C1 [Kaess, Bernhard M.; Preis, Sarah R.; Beiser, Alexa; Seshadri, Sudha; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Kaess, Bernhard M.] Tech Univ, German Heart Ctr, Lazarettstr 36, D-80838 Munich, Germany.
[Preis, Sarah R.; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Beiser, Alexa; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA USA.
[Sawyer, Douglas B.] Maine Med Ctr, Cardiol Div, Portland, ME 04102 USA.
[Chen, Tai C.] Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA.
[Chen, Tai C.] Boston Univ, Sch Med, Sect Diabet, Boston, MA 02118 USA.
[Chen, Tai C.] Boston Univ, Sch Med, Sect Nutr, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
RP Kaess, BM (reprint author), Tech Univ, German Heart Ctr, Lazarettstr 36, D-80838 Munich, Germany.
EM bernhard_kaess@gmx.de
OI Beiser, Alexa/0000-0001-8551-7778
FU Framingham Heart Study [N01-HC-25195, HHSN268201500001I]; National
Heart, Lung, and Blood Institute [HL-077477, HL093029, HL-K24-04334];
National Institute of Neurological Disorders and Stroke [NS17950];
National Institute of Aging [AG031287]; [AG008122]; [AG033040]
FX This work was supported by the Framingham Heart Study (contract nos
N01-HC-25195 and HHSN268201500001I) and by grants from the National
Heart, Lung, and Blood Institute (HL-077477, HL093029 and HL-K24-04334),
the National Institute of Neurological Disorders and Stroke (NS17950)
and the National Institute of Aging (AG031287). SS, AB and SRP were also
supported by AG008122 and AG033040.
NR 23
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U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD DEC 1
PY 2016
VL 102
IS 23
BP 1898
EP 1901
DI 10.1136/heartjnl-2015-309155
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EC9VF
UT WOS:000388491700012
PM 27354275
ER
PT J
AU Bornstein, MH
Hahn, CS
Putnick, DL
AF Bornstein, Marc H.
Hahn, Chun-Shin
Putnick, Diane L.
TI Stability of core language skill across the first decade of life in
children at biological and social risk
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Language development; health risk; social risk
ID COMMUNICATIVE DEVELOPMENT INVENTORIES; BEHAVIOR PROBLEMS; GRAMMATICAL
DEVELOPMENT; EARLY-CHILDHOOD; VOCABULARY; SPEECH; AGE; INTELLIGENCE;
ADOLESCENCE; ABILITY
AB BackgroundCommand of language is a fundamental skill, a cornerstone of multiple cognitive and socioemotional aspects of development, and a necessary ingredient of successful adjustment and functioning in society. Little is known about the developmental stability of language in at-risk youth or which biological and social risk factors moderate stability.
MethodsThis four-wave 10-year prospective longitudinal study evaluated stability of core language skill in 1,780 children in varying categories of biological and social risk in a multiage, multidomain, multimeasure, and multireporter framework.
ResultsStructural equationmodeling supported loadings of diverse age-appropriate measures of child language on single latent variables of core language skill at 15 and 25months and 5 and 11years, respectively. Core language skill was stable over the first decade of life; significant and comparable stability coefficients were obtained for children with diverse biological and social risks, including poor health, welfare status, teen motherhood, ethnicity, gender, birth order, and families that changed in income and maternal education over the study period; stability in language was strong even accounting for child nonverbal intelligence and social competence, maternal education and language, and the family home environment.
ConclusionsCore language skill varies in stability with age but is robustly stable in children regardless of multiple biological and social risk factors.
C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, Publ Hlth Serv, Bethesda, MD USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural Research Program of the NIH, NICHD
FX This research was supported by the Intramural Research Program of the
NIH, NICHD. The authors have declared that they have no competing or
potential conflicts of interest.
NR 84
TC 1
Z9 1
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD DEC
PY 2016
VL 57
IS 12
BP 1434
EP 1443
DI 10.1111/jcpp.12632
PG 10
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA EC9YN
UT WOS:000388500300011
PM 27605246
ER
PT J
AU Shaw, P
AF Shaw, Philip
TI Commentary: Mapping the young, resilient brain - reflections on Burt
etal. (2016)
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Editorial Material
DE Resilience; neuroanatomy; executive functions
AB The resilience of many children in the face of adversity has long been a research focus. The study by Burt etal. delineates the neuroanatomy of resilience, using invivo magnetic resonance images acquired on 1,800 youth. They find that resilient youth had a larger right lateral prefrontal cortex compared to youth who either lacked resilience or did not experience adversity. The size of the right lateral prefrontal cortex was further associated with a likelihood of a maladaptive problem of alcohol use. These findings implicate high-order regulatory processes supported by the right lateral prefrontal cortex as pivotal in resilience. The study also sets the stage for exploring how neuroimaging data, combined with behavioral and genomic information might be used to assess treatment efficacy and identify children who need therapeutic interventions to boost their resilience.
Read the full article at doi:
C1 [Shaw, Philip] NHGRI, Neurobehav Clin Res Sect, Social & Behav Res Branch, Blgd 31,B1 B37, Bethesda, MD 20892 USA.
[Shaw, Philip] NIH, Blgd 31,B1 B37, Bethesda, MD 20892 USA.
RP Shaw, P (reprint author), NHGRI, Neurobehav Clin Res Sect, Social & Behav Res Branch, Blgd 31,B1 B37, Bethesda, MD 20892 USA.; Shaw, P (reprint author), NIH, Blgd 31,B1 B37, Bethesda, MD 20892 USA.
EM shawp@mail.nih.gov
NR 9
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD DEC
PY 2016
VL 57
IS 12
BP 1465
EP 1466
DI 10.1111/jcpp.12613
PG 2
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA EC9YN
UT WOS:000388500300016
PM 27859344
ER
PT J
AU Similuk, M
Rao, VK
Churpek, J
Lenardo, M
AF Similuk, Morgan
Rao, V. Koneti
Churpek, Jane
Lenardo, Michael
TI Predispositions to Lymphoma: A Practical Review for Genetic Counselors
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Review
DE Lymphoma; Heredity; Predisposition; Cancer; Mechanism; Genetic
counseling; Risk assessment; Immunology
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; PRIMARY IMMUNODEFICIENCY
DISEASES; EPSTEIN-BARR-VIRUS; HODGKIN-LYMPHOMA; CANCER-RISK; HEMATOLOGIC
MALIGNANCIES; ATAXIA-TELANGIECTASIA; GERMLINE MUTATIONS; DOCK8
DEFICIENCY; PERSONAL CONTROL
AB This review provides a synopsis for genetic counselors of the major concepts of lymphoma predisposition: genomic instability, immune deficiency, inappropriate lymphoproliferation, and chronic antigen stimulation. We discuss syndromes typifying each of these mechanisms. Importantly, our review of the genetic counseling literature reveals sparse discussion of genetically-based immune-mediated lymphoma predisposition, which we address in depth here. We aim to increase awareness among genetic counselors and colleagues in oncology about familial susceptibility and facilitate critical thinking about lymphoma risk assessment. Clinical application of this knowledge is aided by recommendations for collection of personal and family history to guide risk assessment and testing. Lastly, we include a special discussion of genetic counseling issues including perceptions of the context, nature, and magnitude of lymphoma risk, as well as coping with awareness of susceptibility to lymphoma.
C1 [Similuk, Morgan; Rao, V. Koneti; Lenardo, Michael] NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
[Churpek, Jane] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
RP Similuk, M (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
EM morgan.similuk@nih.gov
FU NIH, National Institute of Allergy and Infectious Disease
FX This research was supported [in part] by the Intramural Research Program
of the NIH, National Institute of Allergy and Infectious Disease. Thank
you to June Peters for her thoughtful review and input.
NR 82
TC 1
Z9 1
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1059-7700
EI 1573-3599
J9 J GENET COUNS
JI J. Genet. Couns.
PD DEC
PY 2016
VL 25
IS 6
BP 1157
EP 1170
DI 10.1007/s10897-016-9979-0
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA EC5LP
UT WOS:000388177100003
PM 27265405
ER
PT J
AU Mitchell, GF
Hwang, SJ
Larson, MG
Hamburg, NM
Benjamin, EJ
Vasan, RS
Levy, D
Vita, JA
AF Mitchell, Gary F.
Hwang, Shih-Jen
Larson, Martin G.
Hamburg, Naomi M.
Benjamin, Emelia J.
Vasan, Ramachandran S.
Levy, Daniel
Vita, Joseph A.
TI Transfer function-derived central pressure and cardiovascular disease
events: the Framingham Heart Study Reply
SO JOURNAL OF HYPERTENSION
LA English
DT Letter
ID ARTERIAL STIFFNESS
C1 [Mitchell, Gary F.] Cardiovasc Engn Inc, 1 Edge Water Dr,Suite 201, Norwood, MA 02062 USA.
[Hwang, Shih-Jen; Larson, Martin G.; Vasan, Ramachandran S.; Levy, Daniel] NHLBIs Framingham Study, Framingham, MA USA.
[Hwang, Shih-Jen; Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hamburg, Naomi M.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA.
[Hamburg, Naomi M.; Benjamin, Emelia J.; Vasan, Ramachandran S.; Vita, Joseph A.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 1 Edge Water Dr,Suite 201, Norwood, MA 02062 USA.
EM GaryFMitchell@mindspring.com
NR 6
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0263-6352
EI 1473-5598
J9 J HYPERTENS
JI J. Hypertens.
PD DEC
PY 2016
VL 34
IS 12
BP 2489
EP 2490
DI 10.1097/HJH.0000000000001136
PG 3
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA EC0HM
UT WOS:000387780100027
PM 27805916
ER
PT J
AU Choi, Y
Abdelmegeed, MA
Song, BJ
AF Choi, Youngshim
Abdelmegeed, Mohamed A.
Song, Byoung-Joon
TI Preventive effects of dietary walnuts on high-fat-induced hepatic fat
accumulation, oxidative stress and apoptosis in mice
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Walnut; High-fat diet; Liver; CYP2E1; Oxidative stress; JNK; Apoptosis
ID NITRIC-OXIDE SYNTHASE; INDUCED NONALCOHOLIC STEATOHEPATITIS;
MITOCHONDRIAL RESPIRATORY-CHAIN; LIVER-DISEASE; HEPATOCYTE APOPTOSIS;
CYTOCHROME-P450 2E1; LIPID-PEROXIDATION; INSULIN-RESISTANCE; MURINE
STEATOHEPATITIS; ENDOTHELIAL FUNCTION
AB We hypothesized that dietary walnut would prevent high-fat-diet (HFD)-induced hepatic apoptosis based on its antioxidant properties. Male C57BL/6J mice were fed a rodent chow or HFD (45% energy-derived)+/- walnuts (21.5% energy-derived) for 6 weeks. Liver histological and biochemical analyses revealed significantly elevated fat accumulation in mice fed HFD compared to mice fed the chow or HFD +/- walnuts. Walnut supplementation prevented HFD-mediated alteration of the levels of key proteins in lipid homeostasis such as Sirt1, AMPK and FAS, leading to decreased fat accumulation. In addition, walnut supplementation to HFD significantly decreased the hepatic levels of cytochrome P450-2E1, nitrated proteins and lipid peroxidation. Furthermore, walnut supplementation decreased the activated cell-death-associated p-JNK and p-p38K accompanied with increased hepatocyte apoptosis in HFD group. The beneficial effects of dietary walnut likely result, at least partially, from its antioxidant ingredients and attenuating HFD-induced hepatic steatosis, nitroxidative stress and apoptosis. Published by Elsevier Inc.
C1 [Choi, Youngshim; Abdelmegeed, Mohamed A.; Song, Byoung-Joon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bj.song@nih.gov
FU Intramural Research Program of the National Institute on Alcohol Abuse
and Alcoholism; KRIBB Research Initiative Program (Korean Biomedical
Scientist Fellowship Program); Korea Research Institute of Bioscience
and Biotechnology, Republic of Korea
FX This work was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism and a grant to
Youngshim Choi from the KRIBB Research Initiative Program (Korean
Biomedical Scientist Fellowship Program), Korea Research Institute of
Bioscience and Biotechnology, Republic of Korea. We are thankful to Dr.
Klaus Gawrisch for supporting this study. We also appreciate Dr. Carol
Sloan at California Walnut Commission for providing fresh walnuts used
for our experiments.
NR 92
TC 0
Z9 0
U1 9
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD DEC
PY 2016
VL 38
BP 70
EP 80
DI 10.1016/j.jnutbio.2016.08.013
PG 11
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA EC8ZG
UT WOS:000388431000008
PM 27732911
ER
EF