FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Bhuiyan, MS
Abu Sayeed, M
Khanam, F
Leung, DT
Bhuiyan, TR
Sheikh, A
Salma, U
LaRocque, RC
Harris, JB
Pacek, M
Calderwood, SB
LaBaer, J
Ryan, ET
Qadri, F
Charles, RC
AF Bhuiyan, Md Saruar
Abu Sayeed, Md
Khanam, Farhana
Leung, Daniel T.
Bhuiyan, Taufiqur Rahman
Sheikh, Alaullah
Salma, Umme
LaRocque, Regina C.
Harris, Jason B.
Pacek, Marcin
Calderwood, Stephen B.
LaBaer, Joshua
Ryan, Edward T.
Qadri, Firdausi
Charles, Richelle C.
TI Cellular and Cytokine Responses to Salmonella enterica Serotype Typhi
Proteins in Patients with Typhoid Fever in Bangladesh
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID VIBRIO-CHOLERAE O1; SEROVAR TYPHI; IFN-GAMMA; TRANSCUTANEOUS
IMMUNIZATION; PROTECTIVE IMMUNITY; BACTERIAL CLEARANCE;
PERIPHERAL-BLOOD; TYPHIMURIUM; MICE; INFECTION
AB We assessed interferon-gamma (IFN-gamma) responses via enzyme-linked immunosorbent spot (ELISPOT) to a number of S. Typhi antigens in samples from humans with S. Typhi bacteremia and typhoid fever in Bangladesh. Compared with responses in healthy endemic zone controls, there were significantly increased IFN-gamma responses at the time of clinical presentation (acute phase) and at convalescence 14-28 days later. The majority (80-90%) of IFN-gamma expressing T cells were CD4+. We observed a significant increase in interleukin-17 (IL-17) positive CD4 + T cells at convalescent versus acute stage of infection using an intracellular cytokine staining assay. We also found that stimulated peripheral blood mononuclear cells (PBMCs) produced significantly increased levels of a number Of cytokines at the convalescent versus acute phase of infection, including IFN-gamma, MIP-1 beta, sCD40L, TNF-beta, IL-13, and IL-9. These results suggest that S. Typhi antigens induce a predominantly Th1 response, but that elevations in other cytokines may be modulatory.
C1 Int Ctr Diarrhoeal Dis Res, Div Vaccine Sci, Dhaka, Bangladesh.
[LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.; Charles, Richelle C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Pacek, Marcin; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA.
Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA.
EM saruar-bhuiyan@monash.edu; sabuj_11@yahoo.com; farhanak@icddrb.org;
dleung@partners.org; taufiqur@icddrb.org; alaullahsheikh@yahoo.com;
nayan_bmb2008@yahoo.com; rclarocque@partners.org; jbharris@partners.org;
marcin.pacek@ikerlan.es; scalderwood@partners.org;
joshua.labaer@asu.edu; etryan@partners.org; fqadri@icddrb.org;
recharles@partners.org
OI leung, daniel/0000-0001-8401-0801
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases [AI100023, AI077883, AI058935]; Fogarty
International Center [TW005572, R24 TW007988]; Howard Hughes Medical
Institute; Massachusetts General Hospital Physician Scientist
Development Award; Burroughs Welcome Fund/American Society of Tropical
Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious
Diseases; [HHSN266200400053C/N01-A1-40053]; [K01 TW07409]; [K01
TW07144]; [K08 AI089721]; [K08 AI100923]
FX This work was supported by the icddr,b and grants and contracts from the
National Institutes of Health, including the National Institute of
Allergy and Infectious Diseases (AI100023 and AI077883 [E.T.R., F.Q.];
AI058935 [S.B.C, E.T.R., and F.Q.]; contract
HHSN266200400053C/N01-A1-40053 [M.P. and LLD, Training Grant in Vaccine
Development and Public Health (TW005572 [M.S.B., F.K., A.S., and F.Q.]),
Career Development Awards (K01 TW07409 [J.B.H.], K01 TW07144 [R.C.L.].
K08 AI089721 [R.C.C.], K08 AI100923 [D.T.L.]), an American Recovery and
Reinvestment Act (ARRA) Post-doctoral Fellowship in Global Infectious
Diseases (TW005572 [D.T.L., R.C.C.]), a Clinical Research Scholars Award
(R24 TW007988 [S.B.C.]) from the Fogarty International Center, a
Physician Scientist Early Career Award from the Howard Hughes Medical
Institute (R.C.L.), a Massachusetts General Hospital Physician Scientist
Development Award (R.C.C.), and a Burroughs Welcome Fund/American
Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in
Tropical Infectious Diseases (D.T.L.).
NR 34
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2014
VL 90
IS 6
BP 1024
EP 1030
DI 10.4269/ajtmh.13-0261
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AI4FD
UT WOS:000336820200009
ER
PT J
AU Heathcote, GM
Bromage, TG
Sava, VJ
Hanson, DB
Anderson, BE
AF Heathcote, Gary M.
Bromage, Timothy G.
Sava, Vincent J.
Hanson, Douglas B.
Anderson, Bruce E.
TI Enigmatic Cranial Superstructures Among Chamorro Ancestors From the
Mariana Islands: Gross Anatomy and Microanatomy
SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY
BIOLOGY
LA English
DT Article
DE Chamorros; occipital torus tubercle; retromastoid process; posterior
supramastoid tubercle; entheses; functional anatomy; SEM survey
ID MUSCULOSKELETAL STRESS MARKERS; STANDARDIZED SCORING METHOD; TENDON
ENTHESES; BONE; OSTEOBIOGRAPHY; ATTACHMENT; HISTOLOGY; PROPOSAL;
ORIGINS; MUSCLES
AB This study focuses on the gross anatomy, anatomic relations, micro-anatomy, and the meaning of three enigmatic, geographically patterned, and quasi-continuous superstructures of the posterior cranium. Collectively known as occipital superstructures (OSSs), these traits are the occipital torus tubercle (TOT), retromastoid process (PR), and posterior supramastoid tubercle (TSP). When present, TOT, PR, and TSP develop at posterior cranial attachment sites of the upper trapezius, superior oblique, and sternocleidomastoid muscles, respectively. Marked expression and co-occurrence of these OSSs are virtually circumscribed within Oceania and reach highest recorded frequencies in protohistoric Chamorros (CHamoru) of the Mariana Islands. Prior to undertaking scanning electron microscopy (SEM) work, our working multifactorial model for OSS development was that early-onset, long-term, and chronic activity-related microtrauma at enthesis sites led to exuberant reactive or reparative responses in a substantial minority of genetically predisposed (and mostly male) individuals. SEM imaging, however, reveals topographic patterning that questions, but does not negate, activity induction of these superstructures. Although OSSs appear macroscopically as relatively large and discrete phenomena, SEM findings reveal a unique, widespread, and seemingly systemic distribution of structures over the occipital surface that have the appearance of OSS microforms. Nevertheless, apparent genetic underpinnings, anatomic relationships with muscle entheses, and positive correlation of OSS development with humeral robusticity continue to suggest that these superstructures have potential to at once bear witness to Chamorro population history and inform osteobiographical constructions of chronic activity patterns in individuals bearing them. Further work is outlined that would illuminate the proximate and ultimate meanings of OSS. (C) 2014 Wiley Periodicals, Inc.
C1 [Heathcote, Gary M.] St Thomas Univ, Dept Anthropol, Fredericton, NB E3B 5G3, Canada.
[Bromage, Timothy G.] NYU, Coll Dent, Hard Tissue Res Unit, Dept Biomat & Biomimet, New York, NY USA.
[Bromage, Timothy G.] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY USA.
[Sava, Vincent J.] Joint Base Pearl Harbor Hickam, JPAC Cent Identificat Lab, Honolulu, HI USA.
[Hanson, Douglas B.] Forsyth Inst, Cambridge, MA USA.
[Anderson, Bruce E.] Univ Arizona, Sch Anthropol, Tucson, AZ USA.
RP Heathcote, GM (reprint author), St Thomas Univ, Dept Anthropol, Fredericton, NB E3B 5G3, Canada.
EM zinjman@gmail.com
OI Heathcote, Gary/0000-0002-4384-0670
FU NSF; Max Planck; NIEHS; College of Liberal Arts and Social Sciences,
University of Guam
FX Grant sponsors: NSF and Max Planck (T.G.B.); NIEHS (D.B.H.); College of
Liberal Arts and Social Sciences, University of Guam (G.M.H.).
NR 101
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-8486
EI 1932-8494
J9 ANAT REC
JI Anat. Rec.
PD JUN
PY 2014
VL 297
IS 6
BP 1009
EP 1021
DI 10.1002/ar.22920
PG 13
WC Anatomy & Morphology
SC Anatomy & Morphology
GA AI7DJ
UT WOS:000337042100003
PM 24753475
ER
PT J
AU Genkinger, JM
Wang, M
Li, R
Albanes, D
Anderson, KE
Bernstein, L
van den Brandt, PA
English, DR
Freudenheim, JL
Fuchs, CS
Gapstur, SM
Giles, GG
Goldbohm, RA
Hakansson, N
Horn-Ross, PL
Koushik, A
Marshall, JR
McCullough, ML
Miller, AB
Robien, K
Rohan, TE
Schairer, C
Silverman, DT
Stolzenberg-Solomon, RZ
Virtamo, J
Willett, WC
Wolk, A
Ziegler, RG
Smith-Warner, SA
AF Genkinger, J. M.
Wang, M.
Li, R.
Albanes, D.
Anderson, K. E.
Bernstein, L.
van den Brandt, P. A.
English, D. R.
Freudenheim, J. L.
Fuchs, C. S.
Gapstur, S. M.
Giles, G. G.
Goldbohm, R. A.
Hakansson, N.
Horn-Ross, P. L.
Koushik, A.
Marshall, J. R.
McCullough, M. L.
Miller, A. B.
Robien, K.
Rohan, T. E.
Schairer, C.
Silverman, D. T.
Stolzenberg-Solomon, R. Z.
Virtamo, J.
Willett, W. C.
Wolk, A.
Ziegler, R. G.
Smith-Warner, S. A.
TI Dairy products and pancreatic cancer risk: a pooled analysis of 14
cohort studies
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE pancreatic cancer; dairy products; calcium intake; pooled analysis
ID FOOD-FREQUENCY QUESTIONNAIRE; VITAMIN-D STATUS; DIETARY ASSESSMENT;
UNITED-STATES; REGRESSION-MODELS; MALE SMOKERS; CALIFORNIA TEACHERS;
25-HYDROXYVITAMIN D; NUTRITIONAL FACTORS; EXOCRINE PANCREAS
AB .Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing a parts per thousand yen500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes a parts per thousand yen1300 with < 500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.
C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Wang, M.; Li, R.; Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wang, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Albanes, D.; Schairer, C.; Silverman, D. T.; Stolzenberg-Solomon, R. Z.; Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Mason Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Bernstein, L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Bernstein, L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[van den Brandt, P. A.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands.
[English, D. R.; Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Canc Epidemiol Ctr,Canc Council Victoria, Melbourne, Vic, Australia.
[Freudenheim, J. L.; Marshall, J. R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Fuchs, C. S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Fuchs, C. S.; Willett, W. C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Fuchs, C. S.; Willett, W. C.] Harvard Univ, Sch Med, Boston, MA USA.
[Gapstur, S. M.; McCullough, M. L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Goldbohm, R. A.] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands.
[Hakansson, N.; Wolk, A.] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Horn-Ross, P. L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Koushik, A.] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ, Canada.
[Miller, A. B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Robien, K.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA.
[Rohan, T. E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Genkinger, JM (reprint author), Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10019 USA.
EM jg3081@columbia.edu
RI Albanes, Demetrius/B-9749-2015;
OI Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099;
English, Dallas/0000-0001-7828-8188
FU National Institutes of Health [CA55075, CA139578]
FX This work was supported by National Institutes of Health grants #CA55075
and #CA139578.
NR 87
TC 10
Z9 10
U1 3
U2 17
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 JUN
PY 2014
VL 25
IS 6
BP 1106
EP 1115
DI 10.1093/annonc/mdu019
PG 10
WC Oncology
SC Oncology
GA AI6ZO
UT WOS:000337028100005
PM 24631943
ER
PT J
AU Boyer-Guittaut, M
Poillet, L
Liang, QL
Bole-Richard, E
Ouyang, XS
Benavides, GA
Chakrama, FZ
Fraichard, A
Darley-Usmar, VM
Despouy, G
Jouvenot, M
Delage-Mourroux, R
Zhang, JH
AF Boyer-Guittaut, Michael
Poillet, Laura
Liang, Qiuli
Bole-Richard, Elodie
Ouyang, Xiaosen
Benavides, Gloria A.
Chakrama, Fatima-Zahra
Fraichard, Annick
Darley-Usmar, Victor M.
Despouy, Gilles
Jouvenot, Michele
Delage-Mourroux, Regis
Zhang, Jianhua
TI The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality
control in MDA-MB-436 breast cancer cells
SO AUTOPHAGY
LA English
DT Article
DE autophagy; breast cancer; GABARAP; GABARAPL1; GEC1; LAMP1; LC3;
lysosome; MDA-MB-436; mitochondria; mitophagy
ID CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; PARKINSONS-DISEASE;
MESSENGER-RNAS; GLYCOGEN-METABOLISM; GABA(A) RECEPTOR; GENE-EXPRESSION;
SMOKE EXPOSURE; PROTEIN; GEC1
AB GABARAPL1/GEC1 is an early estrogen-induced gene which encodes a protein highly conserved from C. elegans to humans. Overexpressed GABARAPL1 interacts with GABA A or kappa opioid receptors, associates with autophagic vesicles, and inhibits breast cancer cell proliferation. However, the function of endogenous GABARAPL1 has not been extensively studied. We hypothesized that GABARAPL1 is required for maintaining normal autophagic flux, and plays an important role in regulating cellular bioenergetics and metabolism. To test this hypothesis, we knocked down GABARAPL1 expression in the breast cancer MDA-MB-436 cell line by shRNA. Decreased expression of GABARAPL1 activated procancer responses of the MDA-MB-436 cells including increased proliferation, colony formation, and invasion. In addition, cells with decreased expression of GABARAPL1 exhibited attenuated autophagic flux and a decreased number of lysosomes. Moreover, decreased GABARAPL1 expression led to cellular bioenergetic changes including increased basal oxygen consumption rate, increased intracellular ATP, increased total glutathione, and an accumulation of damaged mitochondria. Taken together, our results demonstrate that GABARAPL1 plays an important role in cell proliferation, invasion, and autophagic flux, as well as in mitochondrial homeostasis and cellular metabolic programs.
C1 [Boyer-Guittaut, Michael; Poillet, Laura; Bole-Richard, Elodie; Chakrama, Fatima-Zahra; Fraichard, Annick; Despouy, Gilles; Jouvenot, Michele; Delage-Mourroux, Regis] Univ Franche Comte, Lab Biochim, Estrogenes Express Genique & Pathol Syst Nerveux, F-25030 Besancon, France.
[Boyer-Guittaut, Michael; Liang, Qiuli; Ouyang, Xiaosen; Benavides, Gloria A.; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Boyer-Guittaut, Michael; Liang, Qiuli; Ouyang, Xiaosen; Benavides, Gloria A.; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL USA.
[Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA.
RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
EM michael.boyer-guittaut@univ-fcomte.fr; zhanja@uab.edu
OI Zhang, Jianhua/0000-0002-2128-9574
FU Universite of Franche-Comte; Region de Franche-Comte; VA merit award;
RDCC-APCC core (NIH P30 grant) [P30 AR48311]; [NIHR01-NS064090]
FX Michael Boyer-Guittaut would like to thank his colleagues from the
EA3922 team, Jacques Bahi, president of the Universite of Franche-Comte,
Abderrazzak Kadmiri, director of UFR-ST of the Universite of
Franche-Comte and the Universite of Franche-Comte for their support
during this research project performed at the University of Alabama in
Birmingham, AL, USA. Laura Poillet is supported by a fellowship of the
Region de Franche-Comte. The authors acknowledge funding from the
following sources: Dr Jianhua Zhang was supported by NIHR01-NS064090 and
a VA merit award. Flow cytometry was supported by RDCC-APCC core (NIH
P30 grant #P30 AR48311). The authors would like to thank Enid F Keyser
(UAB Flow cytometry core, Birmingham, AL) for her technical help using
the LSR-II Becton Dickinson flow cytometer. Authors are grateful to
Jianhua Zhang's and Victor M Darley-Usmar's laboratory members for their
technical help, advice, and critical reviewing of this manuscript.
NR 64
TC 14
Z9 14
U1 2
U2 16
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD JUN
PY 2014
VL 10
IS 6
BP 986
EP 1003
DI 10.4161/auto.28390
PG 18
WC Cell Biology
SC Cell Biology
GA AI6GT
UT WOS:000336970800004
PM 24879149
ER
PT J
AU Marshansky, V
Rubinstein, JL
Gruber, G
AF Marshansky, Vladimir
Rubinstein, John L.
Grueber, Gerhard
TI Eukaryotic V-ATPase: Novel structural findings and functional insights
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Review
DE Eukaryotic V-ATPase; Rotary proton-pumping nano-motor; Trafficking via
endocytotic and exocytotic pathways; Regulation of cellular receptors
function; Cytohesin-2/Arfs signaling; pH sensor
ID VACUOLAR H+-ATPASE; PROTON-TRANSLOCATING ATPASE; CLATHRIN-INDEPENDENT
ENDOCYTOSIS; IN-VIVO DISSOCIATION; BREAST-CANCER CELLS; NUCLEOTIDE
EXCHANGE FACTORS; CLC CHLORIDE TRANSPORTERS; RENAL TUBULAR-ACIDOSIS;
SUBUNIT-C VMA5P; ELECTRON-MICROSCOPY
AB The eukaryotic V-type adenosine triphosphatase (V-ATPase) is a multi-subunit membrane protein complex that is evolutionarily related to F-type adenosine triphosphate (ATP) synthases and A-ATP synthases. These ATPases/ATP synthases are functionally conserved and operate as rotary proton-pumping nano-motors, invented by Nature billions of years ago. In the first part of this review we will focus on recent structural findings of eukaryotic V-ATPases and discuss the role of different subunits in the function of the V-ATPase holocomplex. Despite structural and functional similarities between rotary ATPases, the eukaryotic V-ATPases are the most complex enzymes that have acquired some unconventional cellular functions during evolution. In particular, the novel roles of V-ATPases in the regulation of cellular receptors and their trafficking via endocytodc and exocytotic pathways were recently uncovered. In the second part of this review we will discuss these unique roles of V-ATPases in modulation of function of cellular receptors, involved in the development and progression of diseases such as cancer and diabetes as well as neurodegeneradve and kidney disorders. Moreover, it was recently revealed that the V-ATPase itself functions as an evolutionarily conserved pH sensor and receptor for cytohesin-2/Arf-family GTP-binding proteins. Thus, in the third part of the review we will evaluate the structural basis for and functional insights into this novel concept, followed by the analysis of the potentially essential role of V-ATPase in the regulation of this signaling pathway in health and disease. Finally, future prospects for structural and functional studies of the eukaryotic V-ATPase will be discussed. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Marshansky, Vladimir] Harvard Univ, Massachusetts Gen Hosp, Ctr Syst Biol,Sch Med, Program Membrane Biol,Div Nephrol,Simches Res Ctr, Boston, MA 02114 USA.
[Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Marshansky, Vladimir] Kadmon Pharmaceut Corp, Alexandria Ctr Life Sci, New York, NY 10016 USA.
[Rubinstein, John L.] Univ Toronto, Hosp Sick Children Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 1X8, Canada.
[Rubinstein, John L.] Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada.
[Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada.
[Grueber, Gerhard] Nanyang Technol Univ, Div Struct Biol & Biochem, Sch Biol Sci, Singapore 637551, Singapore.
[Grueber, Gerhard] ASTAR, Bioinformat Inst, Singapore 637551, Singapore.
RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Ctr Syst Biol,Program Membrane Biol, Boston, MA 02114 USA.
EM Vladimir_Marshansky@hms.harvard.edu
OI Rubinstein, John/0000-0003-0566-2209
FU NIH [DK038452]; BADERC [DK057521-08]; A*STAR BMRC [09/1/22/19/609];
Ministry of Education Tier 2, Singapore [MOE2011-T22-156, ARC 18/12];
CIHR [MOP81294]
FX Original work in the authors' laboratories is supported by NIH DK038452,
BADERC DK057521-08 (Marshansky) as well as by A*STAR BMRC,
09/1/22/19/609, Ministry of Education Tier 2 (MOE2011-T22-156; ARC
18/12), Singapore (Gruber) and by CIHR MOP81294 (Rubinstein). We thank
Dr. S. S. M. Malathy (School of Biological Sciences, NTU) for the art
work of the Figs. 2-4.
NR 266
TC 49
Z9 54
U1 7
U2 36
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
EI 0006-3002
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUN
PY 2014
VL 1837
IS 6
BP 857
EP 879
DI 10.1016/j.bbabio.2014.01.018
PG 23
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AI6UW
UT WOS:000337013500016
PM 24508215
ER
PT J
AU Halper-Stromberg, E
Steranka, J
Burns, KH
Sabunciyan, S
Irizarry, RA
AF Halper-Stromberg, Eitan
Steranka, Jared
Burns, Kathleen H.
Sabunciyan, Sarven
Irizarry, Rafael A.
TI Visualization and probability-based scoring of structural variants
within repetitive sequences
SO BIOINFORMATICS
LA English
DT Article
ID COPY-NUMBER; READ ALIGNMENT; HUMAN GENOME; DNA; QUALITY; MODEL
AB Motivation: Repetitive sequences account for approximately half of the human genome. Accurately ascertaining sequences in these regions with next generation sequencers is challenging, and requires a different set of analytical techniques than for reads originating from unique sequences. Complicating the matter are repetitive regions subject to programmed rearrangements, as is the case with the antigen-binding domains in the Immunoglobulin (Ig) and T-cell receptor (TCR) loci.
Results: We developed a probability-based score and visualization method to aid in distinguishing true structural variants from alignment artifacts. We demonstrate the usefulness of this method in its ability to separate real structural variants from false positives generated with existing upstream analysis tools. We validated our approach using both target-capture and whole-genome experiments. Capture sequencing reads were generated from primary lymphoid tumors, cancer cell lines and an EBV-transformed lymphoblast cell line over the Ig and TCR loci. Whole-genome sequencing reads were from a lymphoblastoid cell-line.
C1 [Halper-Stromberg, Eitan; Irizarry, Rafael A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA.
[Halper-Stromberg, Eitan] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD 21218 USA.
[Halper-Stromberg, Eitan] Univ Colorado, Computat Biosci Program, Denver, CO 80202 USA.
[Steranka, Jared] Johns Hopkins Univ Hosp, Dept Mol Biol & Genet, Baltimore, MD 21287 USA.
[Burns, Kathleen H.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA.
[Burns, Kathleen H.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Burns, Kathleen H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD USA.
[Sabunciyan, Sarven] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA.
[Sabunciyan, Sarven] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Halper-Stromberg, E (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA.
EM ehalper2@jhmi.edu
FU National Institutes of Health [R01HG005220]
FX The National Institutes of Health (R01HG005220).
NR 31
TC 2
Z9 2
U1 0
U2 10
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 JUN 1
PY 2014
VL 30
IS 11
BP 1514
EP 1521
DI 10.1093/bioinformatics/btu054
PG 8
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 AI7CU
UT WOS:000337040200004
PM 24501098
ER
PT J
AU Maeda, Y
Kettner, N
Holden, J
Lee, J
Kim, J
Cina, S
Malatesta, C
Gerber, J
McManus, C
Im, J
Libby, A
Mezzacappa, P
Morse, LR
Park, K
Audette, J
Tommerdahl, M
Napadow, V
AF Maeda, Yumi
Kettner, Norman
Holden, Jameson
Lee, Jeungchan
Kim, Jieun
Cina, Stephen
Malatesta, Cristina
Gerber, Jessica
McManus, Claire
Im, Jaehyun
Libby, Alexandra
Mezzacappa, Pia
Morse, Leslie R.
Park, Kyungmo
Audette, Joseph
Tommerdahl, Mark
Napadow, Vitaly
TI Functional deficits in carpal tunnel syndrome reflect reorganization of
primary somatosensory cortex
SO BRAIN
LA English
DT Article
DE functional magnetic resonance imaging (fMRI); median nerve neuropathy;
tactile stimulation; psychomotor performance; finger agnosia
ID TACTILE STIMULATION; SENSORY INFORMATION; ADULT MONKEYS; CORTICAL MAP;
HAND; PAIN; CAPACITY; BACK; MISLOCALIZATION; DEAFFERENTATION
AB The functional significance of brain plasticity seen in carpal tunnel syndrome is unclear. Using functional MRI and bio-behavioural testing, Maeda et al. link blurred primary somatosensory cortical representations of median nerve innervated fingers with symptomatology and impaired psychomotor performance and discrimination accuracy. Neuroplasticity in these patients is thus indeed maladaptive.Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20-60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit's contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release cycles (r = -0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients.
C1 [Maeda, Yumi; Kim, Jieun; Cina, Stephen; Gerber, Jessica; Im, Jaehyun; Libby, Alexandra; Mezzacappa, Pia; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Maeda, Yumi; Kettner, Norman; Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO 63017 USA.
[Holden, Jameson; Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA.
[Lee, Jeungchan; Park, Kyungmo; Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin 446701, South Korea.
[Malatesta, Cristina; McManus, Claire] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Medford, MA 02155 USA.
[Morse, Leslie R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA.
[Audette, Joseph] Atrium Hlth, Harvard Vanguard Med Associates, Dept Pain Med, Boston, MA 02215 USA.
RP Maeda, Y (reprint author), 2301 149 Thirteenth St, Charlestown, MA 02129 USA.
EM ymaeda@nmr.mgh.harvard.edu
RI Morse, Leslie/C-9442-2015
OI Morse, Leslie/0000-0002-7426-6341
FU National Center for Complementary and Alternative Medicine (NCCAM),
National Institutes of Health [R01-AT004714, R01-AT004714-02S1,
P01-AT002048]; National Centre for Research Resources (NCRR)
[P41RR14075, S10RR021110]
FX This work was supported by National Center for Complementary and
Alternative Medicine (NCCAM), National Institutes of Health
[R01-AT004714, R01-AT004714-02S1, P01-AT002048], as well as the National
Centre for Research Resources (NCRR) [P41RR14075, S10RR021110].
NR 53
TC 10
Z9 10
U1 0
U2 11
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 JUN
PY 2014
VL 137
BP 1741
EP 1752
DI 10.1093/brain/awu096
PN 6
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI6ZU
UT WOS:000337028900021
PM 24740988
ER
PT J
AU DeGutis, J
Cohan, S
Nakayama, K
AF DeGutis, Joseph
Cohan, Sarah
Nakayama, Ken
TI Holistic face training enhances face processing in developmental
prosopagnosia
SO BRAIN
LA English
DT Article
DE developmental prosopagnosia; computer-based cognitive remediation;
configural/holistic processing
ID CONGENITAL PROSOPAGNOSIA; ACQUIRED PROSOPAGNOSIA; RECOGNITION ABILITY;
INDIVIDUAL FACES; TEMPORAL CORTEX; MEMORY TEST; PERCEPTION; REVEALS;
AUTISM; DIFFICULTIES
AB Recent case studies suggest that face recognition can be improved in individual developmental prosopagnosics. Using a 3-week online program targeting holistic face processing, DeGutis et al. reveal perceptual improvements in 24 subjects. Those who reached more difficult levels of training showed the greatest improvements in holistic processing.Prosopagnosia has largely been regarded as an untreatable disorder. However, recent case studies using cognitive training have shown that it is possible to enhance face recognition abilities in individuals with developmental prosopagnosia. Our goal was to determine if this approach could be effective in a larger population of developmental prosopagnosics. We trained 24 developmental prosopagnosics using a 3-week online face-training program targeting holistic face processing. Twelve subjects with developmental prosopagnosia were assessed before and after training, and the other 12 were assessed before and after a waiting period, they then performed the training, and were then assessed again. The assessments included measures of front-view face discrimination, face discrimination with view-point changes, measures of holistic face processing, and a 5-day diary to quantify potential real-world improvements. Compared with the waiting period, developmental prosopagnosics showed moderate but significant overall training-related improvements on measures of front-view face discrimination. Those who reached the more difficult levels of training ('better' trainees) showed the strongest improvements in front-view face discrimination and showed significantly increased holistic face processing to the point of being similar to that of unimpaired control subjects. Despite challenges in characterizing developmental prosopagnosics' everyday face recognition and potential biases in self-report, results also showed modest but consistent self-reported diary improvements. In summary, we demonstrate that by using cognitive training that targets holistic processing, it is possible to enhance face perception across a group of developmental prosopagnosics and further suggest that those who improved the most on the training task received the greatest benefits.
C1 [DeGutis, Joseph] Boston Div VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Jamaica Plain, MA USA.
[DeGutis, Joseph; Cohan, Sarah; Nakayama, Ken] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA.
RP DeGutis, J (reprint author), Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA 02130 USA.
EM degutis@wjh.harvard.edu
FU National Institutes of Health [5R01EY013602-07]
FX We would like to acknowledge funding support from the National
Institutes of Health 5R01EY013602-07 awarded to KN and JD's Veterans
Affairs Career Development Award.
NR 59
TC 18
Z9 18
U1 3
U2 33
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 JUN
PY 2014
VL 137
BP 1781
EP 1798
DI 10.1093/brain/awu062
PN 6
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI6ZU
UT WOS:000337028900025
PM 24691394
ER
PT J
AU Ali, A
Ku, JH
Suhler, EB
Choi, D
Rosenbaum, JT
AF Ali, Amro
Ku, Jennifer H.
Suhler, Eric B.
Choi, Dongseok
Rosenbaum, James T.
TI The course of retinal vasculitis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SYSTEMIC ASSOCIATIONS; MULTIPLE-SCLEROSIS; DISEASE; CORTICOSTEROIDS;
PERIPHLEBITIS; EFFICACY
AB Aims To determine if characteristics of retinal vasculitis correlate with ocular complications, or the response to different lines of treatment.
Materials and methods We performed a computerised database analysis of 56 patients evaluated for uveitis at the Casey Eye Institute from September 1985 until May 2010. All patients had non-infectious retinal vasculitis and at least 1 year of follow-up.
Results Although occlusive vasculitis was rare, retinal neovascularisation occurred much more commonly in the occlusive vasculitis subgroup than among the nonocclusive vasculitis subgroup (p<0.01). Epiretinal membrane (ERM) was found more commonly in the retinal vasculitis patients who presented with cotton wool spots and intraretinal haemorrhage compared to retinal vasculitis patients who presented with sheathing noted on clinical examination (p<0.01). Smoking was significantly related to vision loss. Age at presentation below 40 years correlated with therapy beyond oral corticosteroids
Conclusions The heterogeneity of retinal vasculitis should be considered in providing prognostic information. Neovascularisation occurs more commonly in occlusive retinal vasculitis, and ERM is diagnosed more frequently in conjunction with cotton wool spots and intraretinal haemorrhage rather than just vascular sheathing. Cigarette use predicts visual loss and patients who are relatively young often receive treatment beyond oral corticosteroids.
C1 [Ali, Amro; Ku, Jennifer H.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA.
[Ku, Jennifer H.; Suhler, Eric B.; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA.
[Rosenbaum, James T.] Legacy Hlth Syst, Devers Eye Inst, Portland, OR USA.
RP Ku, JH (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Mailcode CEI,3375 Terwilliger blvd, Portland, OR 97239 USA.
EM kuj@ohsu.edu
FU Research to Prevent Blindness, through National Eye Institute; Stan and
Madelle Rosenfeld Family Trust the William and Mary Bauman Foundation
FX This work was supported by Research to Prevent Blindness, through a core
grant from the National Eye Institute, and by funds from the Stan and
Madelle Rosenfeld Family Trust the William and Mary Bauman Foundation.
NR 26
TC 3
Z9 3
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUN
PY 2014
VL 98
IS 6
BP 785
EP 789
DI 10.1136/bjophthalmol-2013-303443
PG 5
WC Ophthalmology
SC Ophthalmology
GA AI6JI
UT WOS:000336979100017
PM 24511084
ER
PT J
AU Haber, DA
Velculescu, VE
AF Haber, Daniel A.
Velculescu, Victor E.
TI Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating
Tumor DNA
SO CANCER DISCOVERY
LA English
DT Review
ID RESISTANT PROSTATE-CANCER; METASTATIC BREAST-CANCER;
ACQUIRED-RESISTANCE; COLORECTAL-CANCER; LUNG-CANCER; COPY NUMBER;
PERIPHERAL-BLOOD; EPITHELIAL-CELLS; DIGITAL PCR; RARE CELLS
AB The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell-derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments.
Significance: Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis.
C1 [Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Velculescu, Victor E.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
RP Velculescu, VE (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1550 Orleans St,Room 144, Baltimore, MD 21287 USA.
EM haber@helix.mgh.harvard.edu; velculescu@jhmi.edu
FU Howard Hughes Medical Institute; NIH [CA-129933, NIBIB-EB008047,
CA-121113]; Entertainment Industry Foundation [SU2C-AACR-DT0309,
SU2C-AACR-DT0509]; Breast Cancer Research Foundation; National
Foundation for Cancer Research; Johnson & Johnson Center for Excellence
in CTCs at Massachusetts General Hospital; European Community's Seventh
Framework Programme; Dr. Miriam and Sheldon G. Adelson Medical Research
Foundation; John G. Ballenger Trust; Commonwealth Foundation; Stand Up
To Cancer Dream Team Translational Cancer Research Grant
FX D.A. Haber is supported by the Howard Hughes Medical Institute, NIH
(CA-129933, NIBIB-EB008047), a Stand Up To Cancer Dream Team
Translational Cancer Research Grant, a Program of the Entertainment
Industry Foundation (SU2C-AACR-DT0309), the Breast Cancer Research
Foundation, the National Foundation for Cancer Research, and the Johnson
& Johnson Center for Excellence in CTCs at Massachusetts General
Hospital. V.E. Velculescu is supported by NIH (CA-121113), The European
Community's Seventh Framework Programme, the Dr. Miriam and Sheldon G.
Adelson Medical Research Foundation, the John G. Ballenger Trust, a
Stand Up To Cancer Dream Team Translational Cancer Research Grant, a
Program of the Entertainment Industry Foundation (SU2C-AACR-DT0509), and
the Commonwealth Foundation.
NR 115
TC 91
Z9 100
U1 7
U2 103
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2014
VL 4
IS 6
BP 650
EP 661
DI 10.1158/2159-8290.CD-13-1014
PG 12
WC Oncology
SC Oncology
GA AI8QG
UT WOS:000337185500022
PM 24801577
ER
PT J
AU Friboulet, L
Li, NX
Katayama, R
Lee, CC
Gainor, JF
Crystal, AS
Michellys, PY
Awad, MM
Yanagitani, N
Kim, S
Pferdekamper, AC
Li, J
Kasibhatla, S
Sun, F
Sun, XY
Hua, S
McNamara, P
Mahmood, S
Lockerman, EL
Fujita, N
Nishio, M
Harris, JL
Shaw, AT
Engelman, JA
AF Friboulet, Luc
Li, Nanxin
Katayama, Ryohei
Lee, Christian C.
Gainor, Justin F.
Crystal, Adam S.
Michellys, Pierre-Yves
Awad, Mark M.
Yanagitani, Noriko
Kim, Sungjoon
Pferdekamper, AnneMarie C.
Li, Jie
Kasibhatla, Shailaja
Sun, Frank
Sun, Xiuying
Hua, Su
McNamara, Peter
Mahmood, Sidra
Lockerman, Elizabeth L.
Fujita, Naoya
Nishio, Makoto
Harris, Jennifer L.
Shaw, Alice T.
Engelman, Jeffrey A.
TI The ALK Inhibitor Ceritinib Overcomes Crizotinib Resistance in Non-Small
Cell Lung Cancer
SO CANCER DISCOVERY
LA English
DT Article
ID EML4-ALK FUSION GENE; KINASE INHIBITOR; MUTATIONS; NEUROBLASTOMA; EGFR
AB Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib resistance. An interrogation of in vitro and in vivo models of acquired resistance to crizotinib, including cell lines established from biopsies of patients with crizotinib-resistant NSCLC, revealed that ceritinib potently overcomes crizotinib-resistant mutations. In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a cocrystal structure of ceritinib bound to ALK provides structural bases for this increased potency. However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.
C1 [Friboulet, Luc; Katayama, Ryohei; Gainor, Justin F.; Crystal, Adam S.; Awad, Mark M.; Mahmood, Sidra; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Friboulet, Luc; Katayama, Ryohei; Gainor, Justin F.; Crystal, Adam S.; Awad, Mark M.; Mahmood, Sidra; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lee, Christian C.; Michellys, Pierre-Yves; Kim, Sungjoon; Pferdekamper, AnneMarie C.; Li, Jie; Kasibhatla, Shailaja; Sun, Frank; Sun, Xiuying; Hua, Su; McNamara, Peter; Harris, Jennifer L.] Novartis Res Fdn, Genom Inst, San Diego, CA USA.
[Katayama, Ryohei; Fujita, Naoya] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo 170, Japan.
[Yanagitani, Noriko; Nishio, Makoto] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan.
RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY 149,13th St, Charlestown, MA 02129 USA.
EM jharris@gnf.org; ashaw1@mgh.harvard.edu; jengelman@partners.org
RI friboulet, luc/N-7276-2015
OI friboulet, luc/0000-0002-1129-4978
FU NIH [5R01CA16427302]; V Foundation Translational Research Grant;
NIH/National Cancer Institute [R01CA137008]; JSPS KAKENHI [25710015]
FX This work was supported by a grant from the NIH (5R01CA16427302 to A.T.
Shaw and J.A. Engelman), by a V Foundation Translational Research Grant
(to A.T. Shaw and J.A. Engelman) and by the NIH/National Cancer
Institute (R01CA137008 to J. A. Engelman). The study was also supported
by a grant from JSPS KAKENHI (25710015 to R. Katayama).
NR 18
TC 210
Z9 222
U1 8
U2 55
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2014
VL 4
IS 6
BP 662
EP 673
DI 10.1158/2159-8290.CD-13-0846
PG 12
WC Oncology
SC Oncology
GA AI8QG
UT WOS:000337185500023
PM 24675041
ER
PT J
AU Konijeti, GG
Sauk, J
Shrime, MG
Gupta, M
Ananthakrishnan, AN
AF Konijeti, Gauree G.
Sauk, Jenny
Shrime, Mark G.
Gupta, Meera
Ananthakrishnan, Ashwin N.
TI Cost-effectiveness of Competing Strategies for Management of Recurrent
Clostridium difficile Infection: A Decision Analysis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Clostridium difficile infection; vancomycin; fidaxomicin; metronidazole;
fecal microbiota transplant
ID FECAL MICROBIOTA TRANSPLANTATION; QUALITY-OF-LIFE; ULCERATIVE-COLITIS;
UNITED-STATES; DISEASE; HEALTH; VANCOMYCIN; FIDAXOMICIN; COLECTOMY;
THERAPY
AB Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI.
Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $ 50 000 per quality-adjusted life-year.
Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $ 17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates > 88.4% and CDI recurrence rates < 14.9%. Fidaxomicin required a cost <$ 1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin.
Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.
C1 [Konijeti, Gauree G.; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Konijeti, Gauree G.; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA.
[Shrime, Mark G.] Harvard Univ, Sch Med, Harvard Interfac Initiat Hlth Policy, Boston, MA USA.
[Gupta, Meera] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@partners.org
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
NIH [T32DK007191]; NIH [K23 DK091742]
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases of the NIH (award number T32DK007191). A.
N. A. is supported by the NIH (K23 DK091742).
NR 44
TC 41
Z9 42
U1 3
U2 15
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 JUN 1
PY 2014
VL 58
IS 11
BP 1507
EP 1514
DI 10.1093/cid/ciu128
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200004
PM 24692533
ER
PT J
AU Youngster, I
Sauk, J
Pindar, C
Wilson, RG
Kaplan, JL
Smith, MB
Alm, EJ
Gevers, D
Russell, GH
Hohmann, EL
AF Youngster, Ilan
Sauk, Jenny
Pindar, Christina
Wilson, Robin G.
Kaplan, Jess L.
Smith, Mark B.
Alm, Eric J.
Gevers, Dirk
Russell, George H.
Hohmann, Elizabeth L.
TI Fecal Microbiota Transplant for Relapsing Clostridium difficile
Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized,
Open-Label, Controlled Pilot Study
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE fecal microbiota transplant; Clostridium difficile; microbiome; frozen
inoculum
ID VANCOMYCIN; RECURRENCE; DISEASE; METRONIDAZOLE; EPIDEMIOLOGY; OUTCOMES;
CHILDREN
AB Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration.
Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires.
Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2-16) relapses prior to study enrollment, with 5 (range, 3-15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5-10) the day prior to FMT to 2 (IQR, 1-2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2-6) before transplant to 8 (IQR, 5-9) after transplant. No serious or unexpected adverse events occurred.
Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration.
C1 [Youngster, Ilan; Pindar, Christina; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Youngster, Ilan; Sauk, Jenny; Kaplan, Jess L.; Russell, George H.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA.
[Youngster, Ilan] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02445 USA.
[Sauk, Jenny; Wilson, Robin G.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Kaplan, Jess L.; Russell, George H.] Massachusetts Gen Hosp Children, Dept Pediat Gastroenterol & Nutr, Boston, MA USA.
[Smith, Mark B.; Alm, Eric J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Gevers, Dirk] MIT, Broad Inst, Cambridge, MA 02139 USA.
RP Youngster, I (reprint author), Boston Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02445 USA.
EM ilan.youngster@childrens.harvard.edu
RI Youngster, Ilan/J-5047-2014
OI Youngster, Ilan/0000-0001-5233-1213
FU National Institute of Allergy and Infectious Diseases, NIH, Department
of Health and Human Services [HHSN272200900018C]; National Center for
Advancing Translational Sciences, NIH [8UL1TR000170-05]; Harvard
University; National Center for Research Resources
FX The microbiome analysis was funded in part with federal funds from the
National Institute of Allergy and Infectious Diseases, NIH, Department
of Health and Human Services (contract number HHSN272200900018C). I. Y.
has received career support from Harvard Catalyst, The Harvard Clinical
and Translational Science Center, funded by the National Center for
Research Resources and the National Center for Advancing Translational
Sciences, NIH (award 8UL1TR000170-05), and financial contributions from
Harvard University and its affiliated academic healthcare centers.
NR 30
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U2 66
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 JUN 1
PY 2014
VL 58
IS 11
BP 1515
EP 1522
DI 10.1093/cid/ciu135
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200005
PM 24762631
ER
PT J
AU Siedner, MJ
Galar, A
Guzman-Suarez, BB
Kubiak, DW
Baghdady, N
Ferraro, MJ
Hooper, DC
O'Brien, TF
Marty, FM
AF Siedner, Mark J.
Galar, Alicia
Guzman-Suarez, Belisa B.
Kubiak, David W.
Baghdady, Nour
Ferraro, Mary Jane
Hooper, David C.
O'Brien, Thomas F.
Marty, Francisco M.
TI Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter
Species Bacteremia
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Enterobacter; ampC; bacteremia; cefepime; comparative effectiveness
ID LACTAMASE-PRODUCING ENTEROBACTERIACEAE; AMPC BETA-LACTAMASE;
KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE;
ANTIBIOTIC-RESISTANCE; SCORING SYSTEMS; INFECTIONS; THERAPY;
CEPHALOSPORINS
AB Background. Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy.
Methods. We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia >= 1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems.
Results. Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for >= 1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P <.01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI,.58-3.98; P =.39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI,.19-1.40; P =.19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses.
Conclusions. Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario.
C1 [Siedner, Mark J.; Ferraro, Mary Jane; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Siedner, Mark J.; Galar, Alicia; Guzman-Suarez, Belisa B.; Kubiak, David W.; O'Brien, Thomas F.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Kubiak, David W.; Baghdady, Nour] Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA.
RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ5, Boston, MA 02114 USA.
EM msiedner@partners.org
OI Galar, Alicia/0000-0002-9310-8752
FU National Institute of Mental Health [NIH K23 MH099916]; National
Institute of General Medical Sciences [NIH R01 GM103525]
FX M. J. S. receives support from the National Institute of Mental Health
(NIH K23 MH099916) and T. F. O. receives support from the National
Institute of General Medical Sciences (NIH R01 GM103525).
NR 35
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U1 0
U2 3
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 JUN 1
PY 2014
VL 58
IS 11
BP 1554
EP 1563
DI 10.1093/cid/ciu182
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200011
PM 24647022
ER
PT J
AU Bogoch, II
Scully, EP
Zachary, KC
Yawetz, S
Mayer, KH
Bell, CM
Andrews, JR
AF Bogoch, Isaac I.
Scully, Eileen P.
Zachary, Kimon C.
Yawetz, Sigal
Mayer, Kenneth H.
Bell, Chaim M.
Andrews, Jason R.
TI Patient Attrition Between the Emergency Department and Clinic Among
Individuals Presenting for HIV Nonoccupational Postexposure Prophylaxis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV; postexposure prophylaxis; prevention; care linkage; retention
ID SEXUAL ASSAULT; PREEXPOSURE PROPHYLAXIS; TENOFOVIR DF; ADHERENCE;
EXPOSURE; MEN; SEROCONVERSION; EMTRICITABINE; TOLERABILITY; METAANALYSIS
AB Background. Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP.
Methods. From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART.
Results. Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI],.93-.99) and self-payment (aOR, 0.32; 95% CI,.11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI,.15-.79).
Conclusions. Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections.
C1 [Bogoch, Isaac I.] Univ Hlth Network, Div Internal Med, London, ON, Canada.
[Bogoch, Isaac I.] Univ Hlth Network, Div Infect Dis, London, ON, Canada.
[Bell, Chaim M.] Mt Sinai Hosp, Div Internal Med, Toronto, ON, Canada.
[Bogoch, Isaac I.; Bell, Chaim M.] Univ Toronto, Fac Med, Toronto, ON M5S 1A1, Canada.
[Scully, Eileen P.; Yawetz, Sigal] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Scully, Eileen P.; Zachary, Kimon C.; Yawetz, Sigal; Mayer, Kenneth H.; Andrews, Jason R.] Harvard Univ, Sch Med, Boston, MA USA.
[Zachary, Kimon C.; Andrews, Jason R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA.
RP Bogoch, II (reprint author), Toronto Gen Hosp, 14EN 209,200 Elizabeth S, Toronto, ON M5G 2C4, Canada.
EM isaac.bogoch@uhn.ca
RI Bell, Chaim/C-4611-2015
OI Bell, Chaim/0000-0002-3778-9469
FU Canadian Institute of Health Research (CIHR); Canadian Patient Safety
Institute Chair in Patient Safety and Continuity of Care; Merck; Gilead;
Bristol-Meyers-Squibb
FX I. I. B. is supported by a Canadian Institute of Health Research (CIHR)
fellowship award; C. M. B. is supported by a CIHR and Canadian Patient
Safety Institute Chair in Patient Safety and Continuity of Care; and K.
H. M. has unrestricted research grants from Merck, Gilead and
Bristol-Meyers-Squibb.
NR 23
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U1 1
U2 6
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 JUN 1
PY 2014
VL 58
IS 11
BP 1618
EP 1624
DI 10.1093/cid/ciu118
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200020
PM 24723288
ER
PT J
AU Weir, CR
Butler, J
Thraen, I
Woods, PA
Hermos, J
Ferguson, R
Gleason, T
Barrus, R
Fiore, L
AF Weir, Charlene R.
Butler, Jorie
Thraen, Iona
Woods, Patricia A.
Hermos, John
Ferguson, Ryan
Gleason, Theresa
Barrus, Robyn
Fiore, Louis
TI Veterans Healthcare Administration providers' attitudes and perceptions
regarding pragmatic trials embedded at the point of care
SO CLINICAL TRIALS
LA English
DT Article
ID CLINICAL-RESEARCH; EQUIPOISE; RECRUITMENT; UNCERTAINTY; BARRIERS;
ETHICS; TIME
AB Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation. The purpose of this study is to evaluate provider's perceptions and beliefs regarding the POC-R program.
Methods Provider focus groups and interviews were conducted at seven VA medical facilities involving 62 providers. A semi-structured script was used that included descriptions of four use cases and targeted questions regarding perceptions, concerns, and attitudes about the POC-R program. Sessions were audio-taped, de-identified, transcribed, and analyzed using systematic qualitative techniques to create response categories and overarching themes.
Results The emergent themes were as follows: (1) POC-R is a valuable component of evidence-based practice, providing an opportunity to base clinical practice on more generalizable evidence as well as providing tools to improve local practice; (2) POC-R highlights the tension between the need for autonomy of practice and compliance with protocols; (3) POC-R may create increased time and burden resulting from added research responsibilities; (4) concern about the scientific validity and reliability of results; (5) potential for a negative impact on the provider-patient relationship; and (6) uncertainty regarding what constitutes equipoise, given differences in provider knowledge and preferences. Despite substantive concerns, barriers were generally felt to be solvable. Implementation should include provider education, careful attention to workflow for all arms of the study, inclusion of the entire team, and adequate oversight.
Limitations The study design is qualitative with limited implications for causal inference. Participants are from the VA and may not be representative of other clinicians.
Conclusion VA providers are supportive of the importance and value of pragmatic trials in general and of POC-R in particular. However, providers have significant concerns regarding the burden, ethics, and evidence regarding equipoise. Results are discussed in terms of implementation recommendations.
C1 [Weir, Charlene R.; Butler, Jorie; Thraen, Iona; Barrus, Robyn] VA Ctr Informat Decis Enhancement & Surveillance, Salt Lake City, UT 84105 USA.
[Weir, Charlene R.; Butler, Jorie; Thraen, Iona; Barrus, Robyn] VA Salt Lake City SLC Hlth Care Syst, GRECC, Salt Lake City, UT 84105 USA.
[Weir, Charlene R.] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA.
[Woods, Patricia A.; Hermos, John; Ferguson, Ryan; Fiore, Louis] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, VA Cooperat Studies Program, US Dept Vet Affairs, Boston, MA USA.
[Hermos, John; Fiore, Louis] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Ferguson, Ryan; Fiore, Louis] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Gleason, Theresa] US Dept Vet Affairs, Dept Vet Affairs, Off Res & Dev, Washington, DC USA.
RP Weir, CR (reprint author), VA Ctr Informat Decis Enhancement & Surveillance, 500 Foothill Blvd 182, Salt Lake City, UT 84105 USA.
EM Charlene.weir@utah.edu
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Clinical Science Research & Development Service [VA ID: SPLF-001-11S]
FX This study was supported by the Department of Veterans Affairs, Veterans
Health Administration, Office of Clinical Science Research & Development
Service (VA ID: SPLF-001-11S). Dr Weir is the Associate Director of the
Informatics Decision Enhancement and Surveillance (IDEAS) Center of
Innovation at the VA Salt Lake City, Utah.
NR 24
TC 1
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U1 0
U2 6
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 JUN
PY 2014
VL 11
IS 3
BP 292
EP 299
DI 10.1177/1740774514523848
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI3UX
UT WOS:000336791500003
PM 24651565
ER
PT J
AU Saini, J
Bansal, V
Chandra, A
Madan, J
Jain, UK
Chandra, R
Jain, SM
AF Saini, Jyoti
Bansal, Vikas
Chandra, Ankush
Madan, Jitender
Jain, Upendra Kumar
Chandra, Ramesh
Jain, Sarvesh Malviya
TI Bleomycin sulphate loaded nanostructured lipid particles augment oral
bioavailability, cytotoxicity and apoptosis in cervical cancer cells
SO COLLOIDS AND SURFACES B-BIOINTERFACES
LA English
DT Article
DE Bleomycin sulphate; Nanostructured lipid particles; Cytotoxicity;
Apoptosis; Cellular uptake; Bioavailability
ID INTRACELLULAR DELIVERY; SURFACE-CHEMISTRY; CELLULAR UPTAKE;
NANOPARTICLES; PHARMACOKINETICS; SYSTEMS; MICROENVIRONMENT;
CHEMOTHERAPY; PERSPECTIVE; LIPOSOMES
AB In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4 +/- 5.4 nm and 45.3 +/- 3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH similar to 6.8 +/- 0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (similar to 5.6 fold lower IC50), improved intracellular concentration (similar to 4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P < 0.0001) smaller elimination rate constant (K-E), volume of distribution (V-d) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P < 0.0001) similar to 3.4 fold (66.20 +/- 2.57%) higher bioavailability than BLM solution (19.56 +/- 0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Saini, Jyoti; Bansal, Vikas; Madan, Jitender; Jain, Upendra Kumar] Chandigarh Coll Pharm, Dept Pharmaceut, Mohali 140307, Punjab, India.
[Chandra, Ankush] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Chandra, Ramesh] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Delhi 110007, India.
[Jain, Sarvesh Malviya] Oniosome Hlth Care Private Ltd, Mohali 160071, Punjab, India.
RP Madan, J (reprint author), Chandigarh Coll Pharm, Dept Pharmaceut, Mohali 140307, Punjab, India.
EM jitenderpharmacy@gmail.com
OI Chandra, Ankush/0000-0003-1843-3894
NR 50
TC 7
Z9 7
U1 2
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0927-7765
EI 1873-4367
J9 COLLOID SURFACE B
JI Colloid Surf. B-Biointerfaces
PD JUN 1
PY 2014
VL 118
BP 101
EP 110
DI 10.1016/j.colsurfb.2014.03.036
PG 10
WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials
SC Biophysics; Chemistry; Materials Science
GA AI6VA
UT WOS:000337013900014
PM 24732397
ER
PT J
AU Fathi, AT
Chen, YB
AF Fathi, Amir T.
Chen, Yi-Bin
TI Treatment of Relapse of Acute Myeloid Leukemia After Allogeneic
Hematopoietic Stem Cell Transplantation
SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS
LA English
DT Article
DE Acute myeloid leukemia; Allogeneic hematopoietic stem cell
transplantation; Relapse; Graft-vs.-host disease (GVHD); Emerging
therapies
ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSIONS; ACUTE
MYELOGENOUS LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; INTERNAL TANDEM
DUPLICATION; UMBILICAL-CORD BLOOD; G-CSF CLAG; OLDER PATIENTS;
MYELODYSPLASTIC SYNDROMES; HEMATOLOGIC MALIGNANCIES
AB Disease relapse remains a major cause of mortality for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Historically, patients who experience disease relapse after HSCT have a dismal prognosis with very few long-term survivors. There is no standard treatment for patients in this situation given the variability in patient characteristics, disease biology, complications such as graft-vs.-host disease (GVHD) and infections, donor availability, and patient choice. Here, we discuss the current options for treatment of relapsed AML after HSCT including conventional chemotherapy, novel agents, donor leukocyte infusion, second allogeneic HSCT, and emerging therapies.
C1 [Fathi, Amir T.] Massachusetts Gen Hosp, Ctr Leukemia, Boston, MA 02114 USA.
[Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA.
RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Cox 108,55 Fruit St, Boston, MA 02114 USA.
EM afathi@partners.org; ychen6@partners.org
FU Otsuka; Seattle Genetics; Bayer/Onyx; Novartis, Inc.
FX Dr. Yi-Bin Chen served as a consultant for Otsuka Pharmaceuticals and
Seattle Genetics. Dr. Chen received grants from Otsuka, Seattle
Genetics, Bayer/Onyx, and Novartis, Inc.
NR 71
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Z9 4
U1 2
U2 3
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1558-8211
EI 1558-822X
J9 CURR HEMATOL MALIG R
JI Curr. Hematol. Malig. Rep.
PD JUN
PY 2014
VL 9
IS 2
BP 186
EP 192
DI 10.1007/s11899-014-0209-2
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA AI6IE
UT WOS:000336975400013
PM 24643311
ER
PT J
AU Hamdy, O
Marchetti, A
Hegazi, RA
Mechanick, JI
AF Hamdy, Osama
Marchetti, Albert
Hegazi, Refaat A.
Mechanick, Jeffrey I.
TI The Transcultural Diabetes Nutrition Algorithm Toolkit: Survey and
Content Validation in the United States, Mexico, and Taiwan
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Article
ID CLINICAL ALGORITHM; GUIDELINES; MANAGEMENT; ADULTS
AB Background: Evidence demonstrates that medical nutrition therapy (MNT) in prediabetes and type 2 diabetes (T2D) improves glycemic control and reduces diabetes risks and complications. Consequently, MNT is included in current clinical practice guidelines. Guideline recommendations, however, are frequently limited by their complexity, contradictions, personal and cultural rigidity, and compromised portability. The transcultural Diabetes Nutrition Algorithm (tDNA) was developed to overcome these limitations. To facilitate tDNA uptake and usage, an instructional Patient Algorithm Therapy (PATh) toolkit was created. Content validation of tDNA-PATh is needed before widespread implementation.
Subjects and Methods: Healthcare providers (n = 837) in Mexico (n = 261), Taiwan (n = 250), and the United States (n = 326) were questioned about challenges implementing MNT in clinical practice and the projected utilization and impact of tDNA-PATh. To assess the international portability and applicability of tDNA-PATh, the survey was conducted in countries with distinct ethnic and cultural attributes. Potential respondents were screened for professional and practice demographics related to diabetes. The questionnaire was administered electronically after respondents were exposed to core tDNA-PATh components.
Results: Overall, 61% of respondents thought that tDNA-PATh could help overcome MNT implementation challenges, 91% indicated positive impressions, 83% believed they would adopt tDNA-PATh, and 80% thought tDNA-PATh would be fairly easy to implement.
Conclusions: tDNA-PATh appears to be an effective culturally sensitive tool to foster MNT in clinical practice. By providing simple culturally specific instructions, tDNA-PATh may help to overcome current impediments to implementing recommended lifestyle modifications. Specific guidance provided by tDNA-PATh, together with included patient education materials, may increase healthcare provider efficiency.
C1 [Hamdy, Osama] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Marchetti, Albert] Med Educ & Res Alliance Inc, New York, NY USA.
[Marchetti, Albert] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Hegazi, Refaat A.] Abbott Nutr, Columbus, OH USA.
[Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY USA.
RP Marchetti, A (reprint author), Med Educ & Res Alliance Inc, 12 Haines Ave, Linwood, NJ 08221 USA.
EM albertmarchetti@yahoo.com
FU Abbott Nutrition International
FX The development of this article was funded by Abbott Nutrition
International.
NR 15
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Z9 6
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1520-9156
EI 1557-8593
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD JUN
PY 2014
VL 16
IS 6
BP 378
EP 384
DI 10.1089/dia.2013.0276
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI5GS
UT WOS:000336894200007
PM 24471559
ER
PT J
AU Edrey, YH
Salmon, AB
AF Edrey, Yael H.
Salmon, Adam B.
TI Revisiting an age-old question regarding oxidative stress
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Aging; Life span; Longevity; Age-related disease; Mouse models; Free
radicals
ID METHIONINE-SULFOXIDE-REDUCTASE; MANGANESE SUPEROXIDE-DISMUTASE;
REPLICATIVE LIFE-SPAN; TRANSGENIC MICE; MUSCLE ATROPHY;
INSULIN-RESISTANCE; MITOCHONDRIAL-FUNCTION; ALZHEIMERS-DISEASE; KNOCKOUT
MOUSE; IN-VIVO
AB Significant advances in maintaining health;throughout life can be made through a clear understanding of the fundamental mechanisms that regulate aging. The Oxidative Stress Theory of Aging (OSTA) is probably the most well studied mechanistic theory of aging and suggests that the rate of aging is controlled by accumulation of oxidative damage. To directly test the OSTA, aging has been measured in several lines of mice with genetic alterations in the expression of enzymatic antioxidants. Under its strictest interpretation, these studies do not support the OSTA, as modulation of antioxidant expression does not generally affect mouse life span. However, the incidence of many age-related diseases and pathologies is altered in these models, suggesting that oxidative stress does significantly influence some aspects of the aging process. Further, oxidative stress may affect aging in disparate patterns among tissues or under various environmental conditions. In this review, we summarize the current literature regarding aging in antioxidant mutant mice and offer several interpretations of their support of the OSTA. Published by Elsevier Inc.
C1 [Edrey, Yael H.; Salmon, Adam B.] Sam & Ann Barshop Inst Longev & Aging Studies & S, San Antonio, TX 78229 USA.
[Salmon, Adam B.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA.
RP Salmon, AB (reprint author), South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM salmona@uthscsa.edu
FU Geriatric Research, Education and Clinical Center of the South Texas
Veterans Health Care Systems; San Antonio Nathan Shock Center [NIA 5P30
AG013319-19]; San Antonio Area Foundation
FX The authors thank Arlan Richardson, Holly Van Remmen, and Yuji Ikeno for
discussions that led to the compilation of this review and their
yeoman's work over the past 15+ years in regard to testing the OSTA
under the criteria above. This work was supported by the Geriatric
Research, Education and Clinical Center of the South Texas Veterans
Health Care Systems, a pilot grant from the San Antonio Nathan Shock
Center (NIA 5P30 AG013319-19), and a Biomedical Research Grant from the
San Antonio Area Foundation.
NR 128
TC 24
Z9 24
U1 1
U2 30
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 JUN
PY 2014
VL 71
BP 368
EP 378
DI 10.1016/j.freeradbiomed.2014.03.038
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AI5FP
UT WOS:000336891100033
PM 24704971
ER
PT J
AU Morris, DL
Fernando, MMA
Taylor, KE
Chung, SA
Nititham, J
Alarcon-Riquelme, ME
Barcelloss, LF
Behrens, TW
Cotsapas, C
Gaffney, PM
Graham, RR
Pons-Estel, BA
Gregersen, PK
Harley, JB
Hauser, SL
Hom, G
Langefeld, CD
Noble, JA
Rioux, JD
Seldin, MF
Vyse, TJ
Criswell, LA
AF Morris, D. L.
Fernando, M. M. A.
Taylor, K. E.
Chung, S. A.
Nititham, J.
Alarcon-Riquelme, M. E.
Barcelloss, L. F.
Behrens, T. W.
Cotsapas, C.
Gaffney, P. M.
Graham, R. R.
Pons-Estel, B. A.
Gregersen, P. K.
Harley, J. B.
Hauser, S. L.
Hom, G.
Langefeld, C. D.
Noble, J. A.
Rioux, J. D.
Seldin, M. F.
Vyse, T. J.
Criswell, L. A.
CA Syst Lupus Erythematosus Genet Con
TI MHC associations with clinical and autoantibody manifestations in
European SLE
SO GENES AND IMMUNITY
LA English
DT Article
DE Sub-phenotype analysis; MHC; meta-analysis; genetics; systemic lupus
erythematosus; Europeans
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; RO SS-A;
SUSCEPTIBILITY VARIANTS; RHEUMATOID-ARTHRITIS; LOCI; MODEL; DISEASES;
REGION
AB Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis- of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.
C1 [Morris, D. L.; Fernando, M. M. A.; Vyse, T. J.] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England.
[Taylor, K. E.; Chung, S. A.; Nititham, J.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA.
[Alarcon-Riquelme, M. E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Invest Oncol, GENYO, Dept Human DNA Variabil, Granada, Spain.
[Alarcon-Riquelme, M. E.; Gaffney, P. M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA.
[Barcelloss, L. F.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Genet Epidemiol & Genom Lab, Berkeley, CA 94720 USA.
[Behrens, T. W.; Graham, R. R.; Hom, G.] Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA USA.
[Cotsapas, C.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA.
[Pons-Estel, B. A.] Hosp Prov Rosario, Rheumatol Serv, Rosario, Argentina.
[Gregersen, P. K.] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA.
[Harley, J. B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Hauser, S. L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Langefeld, C. D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Wake Forest, NC USA.
[Noble, J. A.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
[Rioux, J. D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Rioux, J. D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
[Seldin, M. F.] Univ Calif Davis, Davis, CA 95616 USA.
RP Morris, DL (reprint author), Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England.
EM david.l.morris@kcl.ac.uk
RI Rioux, John/A-9599-2015;
OI Rioux, John/0000-0001-7560-8326; Alarcon Riquelme, Marta
Eugenia/0000-0002-7632-4154; Cotsapas, Chris/0000-0002-7772-5910
FU Swedish Research Council, lnstituto de Salud Carlos III [PI12/02558];
FEDER; EU; BIOLUPUS RNP; European Science Foundation; American College
of Rheumatology Rheumatology Research Foundation Physician Scientist
Development Award; National Institutes of Health; National Center for
Advancing Translational Sciences through UCSF-CTSI [KL2TR000143];
Clinician Scientist Fellowship [18239]; DLM [17761/PI TJV]; Swedish
Research Council and Instituto de Salud Carlos III [PS09/00129]; FEDER
funds of the European Union; Consejeria de Salud de Andalucia [PI0012];
National Institutes of Allergy and Infectious Diseases [AI067152];
Wellcome Trust Case-Control Consortium [076113, 085475]; NIH [AR052300,
AR02175, AR22804, AR42460, AI024717, AI083194, AR62277, AI082714,
AI53747, AI31584, DE15223, RR20143, PR094002, AI62629, AR48940, AR19084,
AR043274, AI063274, AI40076, AR052125, HG006828, AR048929, AR049084]
FX We thank the original study participants and their families for their
contributions to this research, along with clinical colleagues who
facilitated data collection. We thank Alexander Dilthey for his advice
during the HLA imputation. We also thank the investigators of IMAGEN
(John D Rioux, Philippe Goyette, Timothy J Vyse, Lennart Hammarstrom,
Michelle MA Fernando, Todd Green, Philip L De Jager, Sylvain Foisy,
Joanne Wang, Paul IW de Bakker, Stephen Leslie, Gilean McVean, Leonid
Padyukov, Lars Alfredsson, Vito Annese, David A Hafler, Qiang
Pan-Hammarstrom, Ritva Matell, Stephen J Sawcer, Alastair D Compston,
Bruce AC Cree, Daniel B Mirel, Mark J Daly, Tim W Behrens, Lars
Klareskog, Peter K Gregersen, Jorge R Oksenberg and Stephen L Hauser).;
A full list of the investigators who contributed to the generation of
the Wellcome Trust Case-Control Consortium data is available from the
WTCCC website (see Web Resources).; This study was founded by Swedish
Research Council, lnstituto de Salud Carlos III (PI12/02558) partly
financed by FEDER funds of the EU, and the BIOLUPUS RNP funded by the
European Science Foundation to MEA-R; American College of Rheumatology
Rheumatology Research Foundation Physician Scientist Development Award
and National Institutes of Health, National Center for Advancing
Translational Sciences through UCSF-CTSI Grant KL2TR000143 to SAC.;
Arthritis Research UK funded a Clinician Scientist Fellowship for MMAF
(ref 18239) and the Arthritis Research UK funded DLM under (ref 17761/PI
TJV). MEA-R was funded by the Swedish Research Council and Instituto de
Salud Carlos III grant number PS09/00129 cofinanced through FEDER funds
of the European Union and the Consejeria de Salud de Andalucia PI0012.;
The IMAGEN consortium was supported by Grant AI067152 from the National
Institutes of Allergy and Infectious Diseases.; Funding for the Wellcome
Trust Case-Control Consortium project was provided by the Wellcome Trust
under award 076113 and 085475.; Cord blood samples were collected by V L
Nimgaonkar's group at the University of Pittsburgh, as part of a
multi-institutional collaborative research project with J Smoller, MD
DSc and P Sklar, MD PhD. (Massachusetts General Hospital; grant MH
63420).; Support for the Illumina MHC Panel study was provided by the
NIH (AR052300, AR02175, AR22804, AR62277, AR42460, AI024717, AI083194,
AR62277, AI082714, AI53747, AI31584, DE15223, RR20143, PR094002,
AI62629, AR48940, AR19084, AR043274, AI063274, AI40076, AR052125,
HG006828, AR048929, and AR049084), research grants from the US
Department of Veterans Affairs, US Department of Defense (PR094002),
American College of Rheumatology, Alliance for Lupus Research,
Rheuminations, the Lupus Foundation of Minnesota and the Mary Kirkland
Center for Lupus Research. This study was performed in part in the
General Clinical Research Center, Moffitt Hospital, University of
California San Francisco, with funds provided by the National Center for
Research Resources, 5 M01 RR-00079, US Public Health Service.
NR 26
TC 17
Z9 18
U1 1
U2 6
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 JUN
PY 2014
VL 15
IS 4
BP 210
EP 217
DI 10.1038/gene.2014.6
PG 8
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA AI5CT
UT WOS:000336883700002
PM 24598797
ER
PT J
AU Wojcik, GL
Thio, CL
Kao, WHL
Latanich, R
Goedert, JJ
Mehta, SH
Kirk, GD
Peter, MG
Cox, AL
Kims, AY
Chungs, RT
Thomas, DL
Duggal, P
AF Wojcik, G. L.
Thio, C. L.
Kao, W. H. L.
Latanich, R.
Goedert, J. J.
Mehta, S. H.
Kirk, G. D.
Peter, M. G.
Cox, A. L.
Kims, A. Y.
Chungs, R. T.
Thomas, D. L.
Duggal, P.
TI Admixture analysis of spontaneous hepatitis C virus clearance in
individuals of African descent
SO GENES AND IMMUNITY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; INFECTION; IL28B; INFERENCE;
ANCESTRY; HOST; MAP
AB Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792 721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 x 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations.
C1 [Wojcik, G. L.; Kao, W. H. L.; Mehta, S. H.; Kirk, G. D.; Thomas, D. L.; Duggal, P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Thio, C. L.; Kao, W. H. L.; Latanich, R.; Cox, A. L.; Thomas, D. L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Peter, M. G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kims, A. Y.; Chungs, R. T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
RP Duggal, P (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6539, Baltimore, MD 21205 USA.
EM pduggal@jhsph.edu
FU Office of AIDS Research through the Center for Inherited Diseases at
Johns Hopkins University; National Institute on Drug Abuse [R01DA013324,
DA033541, DA012568, DA04334]; National Institute of Allergy and
Infectious Diseases [U19AI088791, AI082630, UO1-AI-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Frederick
National Laboratory for Cancer Research [HHSN261200800001E]; Intramural
Research Programs of the National Institutes of Health; Frederick
National Laboratory for Cancer Research; Eunice Kennedy Shriver National
Institute of Child Health and Human Development [UO1-HD-32632]; National
Cancer Institute; National Institute on Drug Abuse; National Institute
on Deafness Other Communication Disorders; National Center for Research
Resources (UCSF-CTSI Grant) [UL1 RR024131]; Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research
FX Primary data are available through the central NIH GWAS data repository
at the National Center for Biotechnology Information (NCBI), National
Library of Medicine
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).
This project was funded in whole or in part by the Office of AIDS
Research through the Center for Inherited Diseases at Johns Hopkins
University, the National Institute on Drug Abuse (R01DA013324, DA033541,
DA012568 and DA04334), the National Institute of Allergy and Infectious
Diseases (U19AI088791 and AI082630), and the Frederick National
Laboratory for Cancer Research (contract HHSN261200800001E). This
research was supported in part by the Intramural Research Programs of
the National Institutes of Health and the Frederick National Laboratory
for Cancer Research. The WINS is funded by the National Institute of
Allergy and Infectious Diseases (U01-AI-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (UO1-HD-32632). The study is co-funded by the National
Cancer Institute, the National Institute on Drug Abuse, and the National
Institute on Deafness and Other Communication Disorders. Funding is also
provided by the National Center for Research Resources (UCSF-CTSI Grant
Number UL1 RR024131). 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. This
Research was supported in part by the Intramural Research Program of the
NIH, Frederick National Lab, Center for Cancer Research.
NR 29
TC 0
Z9 0
U1 1
U2 2
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 JUN
PY 2014
VL 15
IS 4
BP 241
EP 246
DI 10.1038/gene.2014.11
PG 6
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA AI5CT
UT WOS:000336883700006
PM 24622687
ER
PT J
AU Stewart, DR
Brems, H
Gomes, AG
Ruppert, SL
Callens, T
Williams, J
Claes, K
Bober, MB
Hachen, R
Kaban, LB
Li, H
Lin, A
McDonald, M
Melancon, S
Ortenberg, J
Radtke, HB
Samson, I
Saul, RA
Shen, J
Siqveland, E
Toler, TL
van Maarle, M
Wallace, M
Williams, M
Legius, E
Messiaen, L
AF Stewart, Douglas R.
Brems, Hilde
Gomes, Alicia G.
Ruppert, Sarah L.
Callens, Tom
Williams, Jennifer
Claes, Kathleen
Bober, Michael B.
Hachen, Rachel
Kaban, Leonard B.
Li, Hua
Lin, Angela
McDonald, Marie
Melancon, Serge
Ortenberg, June
Radtke, Heather B.
Samson, Ignace
Saul, Robert A.
Shen, Joseph
Siqveland, Elizabeth
Toler, Tomi L.
van Maarle, Merel
Wallace, Margaret
Williams, Misti
Legius, Eric
Messiaen, Ludwine
TI Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular
analyses determine whether patients have neurofibromatosis type 1,
coincidental manifestations, or a distinct disorder
SO GENETICS IN MEDICINE
LA English
DT Article
DE cafe-au-lait macule; giant cell lesion; Jaffe-Campanacci syndrome;
neurofibromatosis type 1; nonossifying-fibroma
ID GIANT-CELL GRANULOMA; OF-THE-LITERATURE; NF1 GENE;
ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; MUTATIONAL SPECTRUM; PHENOTYPE;
CHERUBISM; DELETIONS; TUMORS; IDENTIFICATION
AB Purpose: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and cafe-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1.
Methods: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Cainpanacci syndrome of Jaffe-Campanacci syndrome-related features, We also performed somatic NF1 mutation testing on nonossifying fibromas and giant, cell lesions.
Results: Pathogenic germline NF1 mutations Were identified 13 of 14 patients with multiple cafe-au-lait macules and niultiple non-ossifying fibromas or giant cell lesions ("classicar Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institues of Health diagnostic criteria for neurofibromatosis type 1. Somatic NFI mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1-negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions.
Conclusion: In this study, the majority of patients with cafe-au-lait macules and nonossifying fibromas Or giant cell lesions harbored a pathogenic gerinline NF1 mutation,suggesting that many Jaffe-Campanacci syndrome cases may-actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NFI in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1-associated tumors.
C1 [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA.
[Brems, Hilde; Legius, Eric] Univ Louvain, Dept Human Genet, Louvain, Belgium.
[Brems, Hilde; Legius, Eric] Leuven Univ Hosp, Ctr Human Genet, Louvain, Belgium.
[Gomes, Alicia G.; Callens, Tom; Williams, Jennifer; Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Med Genom Lab, Birmingham, AL USA.
[Ruppert, Sarah L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium.
[Bober, Michael B.] Alfred I DuPont Hosp Children, Dept Pediat, Div Med Genet, Wilmington, DE USA.
[Hachen, Rachel] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Li, Hua; Wallace, Margaret] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA.
[McDonald, Marie] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[McDonald, Marie] Duke Univ, Med Ctr, Dept Med Genet, Durham, NC USA.
[Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Med Genet, Montreal, PQ H3H 1P3, Canada.
[Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat, Montreal, PQ H3H 1P3, Canada.
[Radtke, Heather B.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Samson, Ignace] Univ Hosp Leuven, Dept Orthoped Surg, Louvain, Belgium.
[Saul, Robert A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA.
[Shen, Joseph] Childrens Hosp Cent Calif, Madera, CA USA.
[Siqveland, Elizabeth] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA.
[Toler, Tomi L.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA.
[van Maarle, Merel] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Williams, Misti] LewisGale Reg Hlth Syst, Dept Clin Genet, Salem, VA USA.
RP Stewart, DR (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA.
EM drstewart@mail.nih.gov; lmessiaen@uabmc.edu
OI Bober, Michael/0000-0002-6178-1264; Toler, Tomi/0000-0002-1637-8310
FU Medical Genomics Laboratory at the University of Alabama Birmingham;
Hayward Foundation (MRW laboratory); Division of Intramural Research of
the National Human Genome Research Institute (NHGRI); Division of Cancer
Epidemiology and Genetics of the National Cancer Institute's Intramural
Research Program; National Cancer Institute, National Institutes of
Health; Research Foundation Flanders (FWO) at the KULeuven; Clinical
Research Foundation of the University Hospitals Leuven; FWO-Vlaanderen
[G057806N]
FX This work was supported by internal funds from the Medical Genomics
Laboratory at the University of Alabama Birmingham, the Hayward
Foundation (MRW laboratory), the Division of Intramural Research of the
National Human Genome Research Institute (NHGRI), the Division of Cancer
Epidemiology and Genetics of the National Cancer Institute's Intramural
Research Program, and in part with federal funds from the National
Cancer Institute, National Institutes of Health. H.B. is a postdoctoral
researcher of the Research Foundation Flanders (FWO) at the KULeuven.
The authors thank Kathleen Freson (Molecular and Vascular Biology,
KULeuven) for GNAS1 mutation analysis. E.L. is supported by the Clinical
Research Foundation of the University Hospitals Leuven and by a grant
from the FWO-Vlaanderen (G057806N).
NR 43
TC 4
Z9 4
U1 0
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 JUN
PY 2014
VL 16
IS 6
BP 448
EP 459
DI 10.1038/gim.2013.163
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AI6UF
UT WOS:000337011800005
PM 24232412
ER
PT J
AU Opoliner, A
Blacker, D
Fitzmaurice, G
Becker, A
AF Opoliner, April
Blacker, Deborah
Fitzmaurice, Garrett
Becker, Anne
TI Challenges in assessing depressive symptoms in Fiji: A psychometric
evaluation of the CES-D
SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY
LA English
DT Article
DE CES-D; Fiji; validity; reliability; cross-cultural
ID GLOBAL MENTAL-HEALTH; EPIDEMIOLOGIC-STUDIES-DEPRESSION; SCALE;
DISORDERS; RELIABILITY; VALIDITY; JAPANESE; SUICIDE
AB Background and Aim: The CES-D is a commonly used self-report assessment for depressive symptomatology. However, its psychometric properties have not been evaluated in Fiji. This study aims to evaluate the reliability and validity of English language and Fijian vernacular versions in ethnic Fijian adolescent schoolgirls.
Methods: As part of the HEALTHY Fiji study, ethnic Fijian female adolescents (N = 523) completed the CES-D. Participants selected to respond in English or the local vernacular. Reliability (internal consistency, item-total score correlation, and test-retest estimates), validity (associations with other proxies for depression) and factor structure were assessed. Evaluations considered differences between language versions.
Results: In this sample, the CES-D had a Cronbach's of 0.81 and item-total score correlation coefficients ranged between 0.2 and 0.63. One week test-retest reliability (ICC(2)) was 0.57. CES-D scores were higher among individuals who endorsed feelings of depression and suicidality compared to those who did not. ROC analyses of the CES-D versus binary depression and suicidality variables produced AUCs around 0.70 and did not support a discrete cut-off for significant disturbance. Findings were similar across the two language groups.
Conclusions: The CES-D has acceptable reliability and validity among ethnic Fijian female adolescents in English and in the Fijian vernacular language. Findings support its utility as a dimensional measure for depressive symptomatology in this study population. Further examination of its clinical utility for case finding for depression in Fijian school-based and community populations is warranted.
C1 [Opoliner, April; Blacker, Deborah] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02155 USA.
[Blacker, Deborah; Becker, Anne] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Fitzmaurice, Garrett] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02155 USA.
[Fitzmaurice, Garrett] McLean Hosp, Belmont, MA 02178 USA.
[Becker, Anne] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA 02155 USA.
RP Opoliner, A (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02155 USA.
EM aopoline@hsph.harvard.edu
FU NIMH NIH HHS [K23MH068575, K23 MH068575]
NR 36
TC 1
Z9 1
U1 1
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0020-7640
EI 1741-2854
J9 INT J SOC PSYCHIATR
JI Int. J. Soc. Psychiatr.
PD JUN
PY 2014
VL 60
IS 4
BP 367
EP 376
DI 10.1177/0020764013490871
PG 10
WC Psychiatry
SC Psychiatry
GA AI3VE
UT WOS:000336792300007
PM 23877336
ER
PT J
AU Barry, MJ
AF Barry, Michael J.
TI Incidentaloma Fatigue
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID NODULES
C1 [Barry, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA.
EM mbarry@partners.org
NR 7
TC 1
Z9 1
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN
PY 2014
VL 174
IS 6
BP 851
EP 852
DI 10.1001/jamainternmed.2014.672
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4OA
UT WOS:000336843500008
PM 24733384
ER
PT J
AU Huffman, JC
Mastromauro, CA
Beach, SR
Celano, CM
DuBois, CM
Healy, BC
Suarez, L
Rollman, BL
Januzzi, JL
AF Huffman, Jeff C.
Mastromauro, Carol A.
Beach, Scott R.
Celano, Christopher M.
DuBois, Christina M.
Healy, Brian C.
Suarez, Laura
Rollman, Bruce L.
Januzzi, James L.
TI Collaborative Care for Depression and Anxiety Disorders in Patients With
Recent Cardiac Events The Management of Sadness and Anxiety in
Cardiology (MOSAIC) Randomized Clinical Trial
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION;
CARDIOVASCULAR EVENTS; MAJOR DEPRESSION; PANIC DISORDER; SADHART-CHF;
RISK-FACTOR; VALIDITY; METAANALYSIS
AB IMPORTANCE Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events. There has been minimal study of collaborative care (CC) management models for mental health disorders in high-risk cardiac inpatients, and no prior CC intervention has simultaneously managed depression and anxiety disorders.
OBJECTIVE To determine the impact of a low-intensity CC intervention for depression, generalized anxiety disorder, and panic disorder among patients hospitalized for an acute cardiac illness.
DESIGN, SETTING, AND PARTICIPANTS Single-blind randomized clinical trial, with study assessors blind to group assignment, from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome, arrhythmia, or heart failure and found to have clinical depression, generalized anxiety disorder, or panic disorder on structured assessment.
INTERVENTIONS Participants were randomized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders (n = 92) or to enhanced usual care (serial notification of primary medical providers; n = 91). The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate.
MAIN OUTCOMES AND MEASURES Improvement in mental health-related quality of life (Short Form-12 Mental Component Score [SF-12MCS]) at 24 weeks, compared between groups using a random-effects model in an intent-to-treat analysis.
RESULTS Patients randomized to CC had significantly greater estimated mean improvements in SF-12MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs 5.53 points [from 36.30 to 41.83] in the control group; estimated mean difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61). Patients receiving CC also had significant improvements in depressive symptoms and general functioning, and higher rates of treatment of a mental health disorder; anxiety scores, rates of disorder response, and adherence did not differ between groups.
CONCLUSIONS AND RELEVANCE A novel telephone-based, low-intensity model to concurrently manage cardiac patients with depression and/or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial.
C1 [Huffman, Jeff C.; Mastromauro, Carol A.; Beach, Scott R.; Celano, Christopher M.; DuBois, Christina M.; Healy, Brian C.; Suarez, Laura; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA.
[Huffman, Jeff C.; Mastromauro, Carol A.; Beach, Scott R.; Celano, Christopher M.; DuBois, Christina M.; Suarez, Laura] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Rollman, Bruce L.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA.
[Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA.
EM jhuffman@partners.org
FU American Heart Association [10GRNT3450015]
FX This research was funded by American Heart Association Grant-in-Aid
10GRNT3450015 (to Dr Huffman).
NR 54
TC 50
Z9 50
U1 6
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN
PY 2014
VL 174
IS 6
BP 927
EP 935
DI 10.1001/jamainternmed.2014.739
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4OA
UT WOS:000336843500026
PM 24733277
ER
PT J
AU Kroenke, K
AF Kroenke, Kurt
TI Are the Harms of False-Positive Screening Test Results Minimal or
Meaningful?
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Kroenke, Kurt] US Dept Vet Affairs, Ctr Hlth Informat & Commun, Hlth Serv Res & Dev, Indianapolis, IN USA.
[Kroenke, Kurt] Regenstrief Inst Inc, Indianapolis, IN 46202 USA.
[Kroenke, Kurt] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
RP Kroenke, K (reprint author), Regenstrief Inst Inc, 1050 Wishard Blvd,Fifth Floor, Indianapolis, IN 46202 USA.
EM kkroenke@regenstrief.org
NR 8
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN
PY 2014
VL 174
IS 6
BP 961
EP 963
DI 10.1001/jamainternmed.2014.160
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4OA
UT WOS:000336843500032
PM 24756378
ER
PT J
AU Li, WQ
Qureshi, AA
Robinson, KC
Han, JL
AF Li, Wen-Qing
Qureshi, Abrar A.
Robinson, Kathleen C.
Han, Jiali
TI Sildenafil Use and Increased Risk of Incident Melanoma in US Men A
Prospective Cohort Study
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID ERECTILE DYSFUNCTION; CARDIAC DYSFUNCTION; MALIGNANT-MELANOMA;
SKIN-CANCER; INHIBITORS; CELLS; METAANALYSIS; MUTATIONS; PATHWAY;
DISEASE
AB IMPORTANCE The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk.
OBJECTIVE To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States.
DESIGN, SETTING, AND PARTICIPANTS Our study is a prospective cohort study. In 2000, participants in the Health Professionals' Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25 848 men remained in the analysis.
MAIN OUTCOMES AND MEASURES The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed.
RESULTS We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95% CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95% CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95% CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95% CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use.
CONCLUSIONS AND RELEVANCE Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association.
C1 [Li, Wen-Qing; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Li, Wen-Qing; Qureshi, Abrar A.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02903 USA.
[Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Network Med,Dept Med, Boston, MA 02115 USA.
[Robinson, Kathleen C.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Robinson, Kathleen C.] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA USA.
[Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Han, Jiali] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA.
[Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Han, Jiali] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China.
RP Han, JL (reprint author), Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, 714 N Senate Ave, Indianapolis, IN 46202 USA.
EM jialhan@iu.edu
RI Li, Wenqing/N-2293-2014
OI Li, Wenqing/0000-0002-1283-4091
FU National Institutes of Health [P01 CA055075]
FX The HPFS is partly supported by grant P01 CA055075 from the National
Institutes of Health.
NR 38
TC 25
Z9 27
U1 1
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN
PY 2014
VL 174
IS 6
BP 964
EP 970
DI 10.1001/jamainternmed.2014.594
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4OA
UT WOS:000336843500033
PM 24710960
ER
PT J
AU Wiener, RS
Gould, MK
Slatore, CG
Fincke, BG
Schwartz, LM
Woloshin, S
AF Wiener, Renda Soylemez
Gould, Michael K.
Slatore, Christopher G.
Fincke, Benjamin G.
Schwartz, Lisa M.
Woloshin, Steven
TI Resource Use and Guideline Concordance in Evaluation of Pulmonary
Nodules for Cancer Too Much and Too Little Care
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID FLEISCHNER SOCIETY GUIDELINES; LUNG-CANCER; MANAGEMENT; RADIOLOGISTS;
CT; COMPLICATIONS; STATEMENT; ADHERENCE; BIOPSY; FRANCE
AB IMPORTANCE Pulmonary nodules are common, and more will be found with implementation of lung cancer screening. How potentially malignant pulmonary nodules are evaluated may affect patient outcomes, health care costs, and effectiveness of lung cancer screening programs. Guidelines for evaluating pulmonary nodules for cancer exist, but little is known about how nodules are evaluated in the usual care setting.
OBJECTIVE To characterize nodule evaluation and concordance with guidelines.
DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted including detailed review of medical records from pulmonary nodule detection through evaluation completion, cancer diagnosis, or study end (December 31, 2012). The participants included 300 adults with pulmonary nodules from 15 Veterans Affairs hospitals.
MAIN OUTCOMES AND MEASURES Resources used for evaluation at any Veterans Affairs facility and guideline-concordant evaluation served as the main outcomes.
RESULTS Twenty-seven of 300 patients (9.0%) with pulmonary nodules ultimately received a diagnosis of lung cancer: 1 of 57 (1.8%) with a nodule of 4 mm or less, 4 of 134 (3.0%) with a nodule of 5 to 8 mm, and 22 of 109 (20.2%) with a nodule larger than 8 mm. Nodule evaluation entailed 1044 imaging studies, 147 consultations, 76 biopsies, 13 resections, and 21 hospitalizations. Radiographic surveillance (n = 277) lasted a median of 13 months but ranged from less than 0.5 months to 8.5 years. Forty-six patients underwent invasive procedures (range per patient, 1-4): 41.3%(19 patients) did not have cancer and 17.4% (8) experienced complications, including 1 death. Notably, 15 of the 300 (5.0%) received no purposeful evaluation and had no obvious reason for deferral, seemingly "falling through the cracks." Among 197 patients with a nodule detected after release of the Fleischner Society guidelines, 44.7% received care inconsistent with guidelines (17.8% overevaluation, 26.9% underevaluation). In multivariable analyses, the strongest predictor of guideline-inconsistent care was inappropriate radiologist recommendations (overevaluation relative risk, 4.6 [95% CI, 2.3-9.2]; underevaluation, 4.3 [2.7-6.8]). Other systems factors associated with underevaluation included receiving care at more than 1 facility (2.0 [1.5-2.7]) and nodule detection during an inpatient or preoperative visit (1.6 [1.1-2.5]).
CONCLUSIONS AND RELEVANCE Pulmonary nodule evaluation is often inconsistent with guidelines, including cases with no workup and others with prolonged surveillance or unneeded procedures that may cause harm. Systems to improve quality (eg, aligning radiologist recommendations with guidelines and facilitating communication across providers) are needed before lung cancer screening is widely implemented.
C1 [Wiener, Renda Soylemez; Fincke, Benjamin G.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA.
[Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA.
[Gould, Michael K.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA.
[Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA.
[Fincke, Benjamin G.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Schwartz, Lisa M.; Woloshin, Steven] Dept Vet Affairs, Vet Affairs Outcomes Grp, White River Jct, VT USA.
RP Wiener, RS (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 Mail Code 152, Bedford, MA 01730 USA.
EM rwiener@bu.edu
OI Wiener, Renda/0000-0001-7712-2135; Slatore,
Christopher/0000-0003-0958-8122
FU Veterans Affairs (VA) Health Services Research and Development (HSRD)
[PPO 08-401]; White River Junction VA Medical Center; Edith Nourse
Rogers Memorial Veterans Hospital; Portland VA Medical Center; National
Cancer Institute [K07 CA138772]; VA HSR&D Career Development Award
FX This study was supported by the Veterans Affairs (VA) Health Services
Research and Development (HSR&D) (PPO 08-401) and with resources from
the White River Junction VA Medical Center, Edith Nourse Rogers Memorial
Veterans Hospital, and Portland VA Medical Center. Dr Wiener is also
supported by career development award K07 CA138772 from the National
Cancer Institute, and Dr Slatore is supported by a VA HSR&D Career
Development Award.
NR 37
TC 20
Z9 20
U1 2
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUN
PY 2014
VL 174
IS 6
DI 10.1001/jamainternmed.2014.561
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4OA
UT WOS:000336843500017
PM 24710850
ER
PT J
AU van Deursen, VM
Edwards, C
Cotter, G
Davison, BA
Damman, K
Teerlink, JR
Metra, M
Felker, GM
Ponikowski, P
Unemori, E
Severin, T
Voors, AA
AF van Deursen, Vincent M.
Edwards, Christopher
Cotter, Gad
Davison, Beth A.
Damman, Kevin
Teerlink, John R.
Metra, Marco
Felker, G. Michael
Ponikowski, Piotr
Unemori, Elaine
Severin, Thomas
Voors, Adriaan A.
TI Liver Function, In-Hospital, and Post-Discharge Clinical Outcome in
Patients With Acute Heart Failure-Results From the Relaxin for the
Treatment of Patients With Acute Heart Failure Study
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE Liver function; acute decompensated heart failure; prognosis
ID FUNCTION TESTS; FUNCTION ABNORMALITIES; MORTALITY; PROGRAM
AB Background: Elevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF.
Methods: We investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality.
Results: Mean age was 70 +/- 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found. for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004).
Conclusions: Abnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.
C1 [van Deursen, Vincent M.; Damman, Kevin; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Edwards, Christopher; Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA.
[Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA.
[Metra, Marco] Univ Brescia, Dept Expt & Appl Sci, Sect Cardiovasc Dis, Brescia, Italy.
[Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
[Ponikowski, Piotr] Med Univ, Dept Hlth Sci, Mil Hosp, Dept Cardiol, Wroclaw, Poland.
[Unemori, Elaine] Corthera, San Mateo, CA USA.
[Severin, Thomas] Novartis Pharmaceut, Basel, Switzerland.
RP Voors, AA (reprint author), Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9700 RB Groningen, Netherlands.
EM a.a.voors@umcg.nl
RI Ponikowski, Piotr/O-6454-2015;
OI Ponikowski, Piotr/0000-0002-3391-7064; Davison,
Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568
FU Corthera (a Novartis affiliate company); Amgen; Bayer; Corthera; Cardio3
Bioscience; Cytokinetics; Merck; Novartis; Takeda; Teva; Trevena; Abbott
Vascular; Medpace; Otsuka; Roche Diagnostics; BG Medicine; Medtronic; St
Jude; National Heart, Lung, and Blood Institute; Abbott; PDL Biopharma;
Alere; Cardio3 Biosciences; Celladon; Ceva; European Commission; Dutch
Heart Foundation; Servier; Torrent; Vifor
FX The Pre-RELAX-AHF study is supported by Corthera (a Novartis affiliate
company). Mr Edwards and Drs Cotter and Davison are employees of
Momentum Research, which has provided consulting and trial management
services to Novacardia, Merck, Corthera, Novartis, Nile Therapeutics,
Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena,
Sorbent Therapeutics, and the National Institutes of Health. Dr Teerlink
has received research grants or consulting fees from Amgen, Bayer,
Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda,
Teva, and Trevena. Dr Metra has received consulting income from Abbott
Vascular, Bayer, Corthera, and Novartis and travel support and honoraria
from Servier and Novartis. Dr Felker has received consulting income from
Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG
Medicine, Medtronic, and St Jude and grant funding from Amgen, Otsuka,
Roche Diagnostics, and the National Heart, Lung, and Blood Institute. Dr
Ponikowski has been a consultant for Astellas, Bayer, EKR Therapeutics,
Johnson and Johnson, The Medicines Company, Medtronic, Novartis, Otsuka,
Palatin Technologies, PDL Biopharma, Pericor Therapeutics, Sigma Tau,
Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere,
Beckman-Coulter, Biogenidec, Corthera, Ikaria, Nile Therapeutics,
Momentum Research, and Overcome; has received research support from
Abbott, Merck and PDL Biopharma; and has received travel support from My
Life and equipment support from Sonosite. Dr Unemori is employed by the
sponsor, Corthera. Dr Severin is an employee and shareholder of Novartis
Pharma. Dr Voors has received consultancy fees and/or research grants
from Alere, Bayer, Cardio3 Biosciences, Celladon, Ceva, the European
Commission, the Dutch Heart Foundation, Novartis, Servier, Torrent, and
Vifor. Dr van Deursen no relationships relevant to the contents of this
paper to disclose.
NR 18
TC 10
Z9 10
U1 0
U2 3
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
EI 1532-8414
J9 J CARD FAIL
JI J. Card. Fail.
PD JUN
PY 2014
VL 20
IS 6
BP 407
EP 413
DI 10.1016/j.cardfail.2014.03.003
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI7LA
UT WOS:000337070900005
PM 24642379
ER
PT J
AU Simonsen, CZ
Sorensen, LH
Karabegovic, S
Mikkelsen, IK
Schmitz, ML
Juul, N
Yoo, AJ
Andersen, G
AF Simonsen, Claus Z.
Sorensen, Leif H.
Karabegovic, Sanja
Mikkelsen, Irene K.
Schmitz, Marie L.
Juul, Niels
Yoo, Albert J.
Andersen, Grethe
TI MRI before intraarterial therapy in ischemic stroke: feasibility,
impact, and safety
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE acute stroke; diffusion-weighted imaging; endovascular therapy; magnetic
resonance imaging; outcome; selection
ID ENDOVASCULAR TREATMENT; TRIAL; THROMBOLYSIS; SELECTION; DIFFUSION;
COHORT; REVASCULARIZATION
AB Intraarterial therapy (IAT) in acute ischemic stroke is effective for opening occlusions of major extracranial or intracranial vessels. Clinical efficacy data are lacking pointing to a need for proper patient selection. We examined feasibility, clinical impact, and safety profile of magnetic resonance imaging (MRI) for patient selection before IAT. In this single-center study, we collected epidemiologic, imaging, and outcome data on all intraarterial-treated patients presenting with anterior circulation occlusions at our center from 2004 to 2011. Magnetic resonance imaging was the first imaging choice. Computer tomography (CT) was performed in the presence of a contraindication. We treated 138 patients. Mean age was 64 years and median National Institutes of Health Stroke Scale (NIHSS) was 17. Major reperfusion (thrombolysis in cerebral infarction (TICI) 2b + 3) was achieved in 52% and good outcome defined as modified Rankin Scale (mRS) score 0 to 2 at 90 days was achieved in 41%. Mortality at 90 days was 10%. There was only one symptomatic hemorrhage. Recanalization, age, and stroke severity were associated with outcome. Preprocedure MRI was obtained in 83%. Good outcome was significantly associated with smaller diffusion-weighted imaging (DWI) lesion size at presentation and not with the size of the perfusion lesion. It is feasible to triage patients for IAT using MRI with acceptable rates of poor outcome and symptomatic hemorrhage.
C1 [Simonsen, Claus Z.; Schmitz, Marie L.; Andersen, Grethe] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus C, Denmark.
[Sorensen, Leif H.; Karabegovic, Sanja] Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus C, Denmark.
[Mikkelsen, Irene K.] Aarhus Univ, Ctr Funct Integrat Neurosci, Aarhus, Denmark.
[Juul, Niels] Aarhus Univ Hosp, Dept Neuroanaestesiol, DK-8000 Aarhus C, Denmark.
[Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Diagnost & Intervent Neuroradiol, Boston, MA 02115 USA.
RP Simonsen, CZ (reprint author), Aarhus Univ Hosp, Dept Neurol, Norrebrogade 44, DK-8000 Aarhus C, Denmark.
EM clasim@rm.dk
RI Demchuk, Andrew/E-1103-2012
OI Demchuk, Andrew/0000-0002-4930-7789
FU Penumbra Inc.; Remedy Pharmaceuticals Inc.
FX AJY has received research support from Penumbra Inc. and Remedy
Pharmaceuticals Inc. Also honorarium from Codman. The remaining authors
have no conflict of interest.
NR 27
TC 6
Z9 7
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2014
VL 34
IS 6
BP 1076
EP 1081
DI 10.1038/jcbfm.2014.57
PG 6
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA AI4JH
UT WOS:000336831000019
PM 24690941
ER
PT J
AU Bauer, CA
Kim, EY
Marangoni, F
Carrizosa, E
Claudio, NM
Mempel, TR
AF Bauer, Christian A.
Kim, Edward Y.
Marangoni, Francesco
Carrizosa, Esteban
Claudio, Natalie M.
Mempel, Thorsten R.
TI Dynamic Treg interactions with intratumoral APCs promote local CTL
dysfunction
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID REGULATORY T-CELLS; DRAINING LYMPH-NODES; ANTIGEN-SPECIFIC CD8; EFFECTOR
FUNCTION; DENDRITIC CELLS; TUMOR MICROENVIRONMENT; MELANOMA PATIENTS;
INFLAMED TISSUES; THYMIC SELECTION; IN-VITRO
AB Tregs control various functions of effector T cells; however, where and how Tregs exert their immunomodulatory effects remain poorly understood. Here we developed a murine model of adoptive T cell therapy and found that Tregs induce a dysfunctional state in tumor-infiltrating CTLs that resembles T cell exhaustion and is characterized by low expression of effector cytokines, inefficient cytotoxic granule release, and coexpression of coinhibitory receptors PD-1 and TIM-3. Induction of CTL dysfunction was an active process, requiring local TCR signals in tumor tissue. Tregs infiltrated tumors only subsequent to Ag-dependent activation and expansion in tumor-draining LNs; however, Tregs also required local Ag reencounter within tumor tissue to induce CTL dysfunction and prevent tumor rejection. Multiphoton intravital microscopy revealed that in contrast to CTLs, Tregs only rarely and briefly interrupted their migration in tumor tissue in an Ag-dependent manner and formed unstable tethering-interactions with CD11c(+) APCs, coinciding with a marked reduction of CD80 and CD86 on APCs. Activation of CTLs by Treg-conditioned CD80/86(lo) DCs promoted enhanced expression of both TIM-3 and PD-1. Based on these data, we propose that Tregs locally change the costimulatory landscape in tumor tissue through transient, Ag-dependent interactions with APCs, thus inducing CTL dysfunction by altering the balance of costimulatory and coinhibitory signals these cells receive.
C1 [Bauer, Christian A.; Kim, Edward Y.; Marangoni, Francesco; Carrizosa, Esteban; Claudio, Natalie M.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Boston, MA USA.
RP Mempel, TR (reprint author), Massachusetts Gen Hosp East, 149 Thirteenth St,Room 8301, Boston, MA 02129 USA.
EM tmempel@mgh.harvard.edu
RI Marangoni, Francesco/I-9087-2012
OI Marangoni, Francesco/0000-0002-2490-849X
FU NIH [AI073457, CA150975, CA179563]; German Research Foundation [BA
3824/1-1]; Fellowship from the Terry Fox Foundation (Canadian Cancer
Society Research Institute) [19726]; Dana Foundation.
FX We thank Ulrich von Andrian and James Moon for critical reading of the
manuscript and helpful comments, and Sean Megason and Jeff Hogan for the
pCS-H2B-Cerulean and pcDNA3.1-HA constructs, respectively. T.R. Mempel
was supported by NIH grants AI073457, CA150975, and CA179563 and by a
grant by the Dana Foundation. C.A. Bauer was supported by a grant from
the German Research Foundation (BA 3824/1-1). E.Y. Kim was supported by
a Fellowship from the Terry Fox Foundation (Canadian Cancer Society
Research Institute award no. 19726).
NR 73
TC 34
Z9 34
U1 0
U2 17
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2425
EP 2440
DI 10.1172/JCI66375
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800019
PM 24812664
ER
PT J
AU Davidowitz, RA
Selfors, LM
Iwanicki, MP
Elias, KM
Karst, A
Piao, HY
Ince, TA
Drage, MG
Dering, J
Konecny, GE
Matulonis, U
Mills, GB
Slamon, DJ
Drapkin, R
Brugge, JS
AF Davidowitz, Rachel A.
Selfors, Laura M.
Iwanicki, Marcin P.
Elias, Kevin M.
Karst, Alison
Piao, Huiying
Ince, Tan A.
Drage, Michael G.
Dering, Judy
Konecny, Gottfried E.
Matulonis, Ursula
Mills, Gordon B.
Slamon, Dennis J.
Drapkin, Ronny
Brugge, Joan S.
TI Mesenchymal gene program-expressing ovarian cancer spheroids exhibit
enhanced mesothelial clearance
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CARCINOMA ASCITES SPHEROIDS; ADVANCED EPITHELIAL OVARIAN; IN-VITRO; CELL
MONOLAYERS; FALLOPIAN-TUBE; PERITONEAL METASTASIS; EXTRACELLULAR-MATRIX;
TUMOR-CELLS; E-CADHERIN; TRANSITION
AB Metastatic dissemination of ovarian tumors involves the invasion of tumor cell clusters into the mesothelial cell lining of peritoneal cavity organs; however, the tumor-specific factors that allow ovarian cancer cells to spread are unclear. We used an in vitro assay that models the initial step of ovarian cancer metastasis, clearance of the mesothelial cell layer, to examine the clearance ability of a large panel of both established and primary ovarian tumor cells. Comparison of the gene and protein expression profiles of clearance-competent and clearance-incompetent cells revealed that mesenchymal genes are enriched in tumor populations that display strong clearance activity, while epithelial genes are enriched in those with weak or undetectable activity. Overexpression of transcription factors SNAI1, TWIST1, and ZEB1, which regulate the epithelial-to-mesenchymal transition (EMT), promoted mesothelial clearance in cell lines with weak activity, while knockdown of the EMT-regulatory transcription factors TWIST1 and ZEB1 attenuated mesothelial clearance in ovarian cancer cell lines with strong activity. These fmdings provide important insights into the mechanisms associated with metastatic progression of ovarian cancer and suggest that inhibiting pathways that drive mesenchymal programs may suppress tumor cell invasion of peritoneal tissues.
C1 [Davidowitz, Rachel A.; Selfors, Laura M.; Iwanicki, Marcin P.; Brugge, Joan S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Elias, Kevin M.; Karst, Alison; Piao, Huiying; Matulonis, Ursula; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA.
[Ince, Tan A.] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Interdisciplinary Stem Cell Inst,Dept Pathol, Miami, FL 33136 USA.
[Ince, Tan A.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Drage, Michael G.; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Dering, Judy; Konecny, Gottfried E.; Slamon, Dennis J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM ronny_drapkin@dfci.harvard.edu; Joan_Brugge@hms.harvard.edu
RI Drapkin, Ronny/E-9944-2016;
OI Drapkin, Ronny/0000-0002-6912-6977; Elias, Kevin/0000-0003-1502-5553
FU Ovarian Cancer Research Fund; Honorable Tina Brozman Foundation; Gamel.
Family Ovarian Cancer Research Fund; Dana-Farber Cancer Institute; NIH
[CA016672]
FX We would like to thank Yiling Lu and Doris Siwak (MD Anderson Cancer
Center) for performing the RPPA studies; Jennifer Waters and the Nikon
Imaging Center at Harvard Medical School for support on the microscopy
studies; and Kong-Jie Kah and Robert Weinberg for donation of the ZEB1
overexpression construct. We also thank Ghassan Mouneimne for review of
the manuscript and helpful discussions and Grace Gao for lab management.
These studies were supported by the Dr. Miriam and Sheldon G. Adelson
Medical Research Foundation (to J.S. Brugge and R. Drapkin), the Ovarian
Cancer Research Fund (to R. Drapkin), the Honorable Tina Brozman
Foundation (to R. Drapkin), the Robert and Debra First Fund (to R.
Drapkin), the Gamel. Family Ovarian Cancer Research Fund (to R.
Drapkin), the Susan F. Smith Center for Women's Cancers at the
Dana-Farber Cancer Institute (to R. Drapkin), and the Men's
Collaborative to Cure Women's Cancer (to J.S. Brugge and R. Drapkin).
RPPA was performed at the MD Anderson RPPA Core Facility (supported by
NIH grant CA016672).
NR 63
TC 25
Z9 25
U1 1
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2611
EP 2625
DI 10.1172/JCI69815
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800034
PM 24762435
ER
PT J
AU Misra, M
Klibanski, A
AF Misra, Madhusmita
Klibanski, Anne
TI Anorexia nervosa and bone
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Review
DE anorexia nervosa; eating disorders; adolescents; adults; bone density;
microarchitecture; strength; fracture; growth hormone; IGF1; estrogen;
testosterone; bisphosphonates; leptin; ghrelin; PYY; adipokines
ID DWELLING ADOLESCENT GIRLS; PREADIPOCYTE FACTOR-I; BROWN ADIPOSE-TISSUE;
MINERAL DENSITY; GROWTH-HORMONE; YOUNG-WOMEN; HEALTHY ADOLESCENTS;
SECRETORY DYNAMICS; EATING-DISORDERS; BULIMIA-NERVOSA
AB Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk. Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiological estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age, given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN.
C1 [Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Misra, Madhusmita; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediatr Endocrine Unit, Boston, MA 02114 USA.
RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA.
EM mmisra@partners.org
FU NIH [1 R01 HD060827, 5 UL1 RR025758, K24HD071843, 2 R01 DK062249]
FX This work was supported in part by NIH grants 1 R01 HD060827, 5 UL1
RR025758, K24HD071843, and 2 R01 DK062249.
NR 92
TC 24
Z9 24
U1 1
U2 8
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
EI 1479-6805
J9 J ENDOCRINOL
JI J. Endocrinol.
PD JUN
PY 2014
VL 221
IS 3
BP R163
EP R176
DI 10.1530/JOE-14-0039
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI7WF
UT WOS:000337111400007
PM 24898127
ER
PT J
AU Doring, AC
Nota, SPFT
Hageman, MGJS
Ring, DC
AF Doering, Anne-Carolin
Nota, Sjoerd P. F. T.
Hageman, Michiel G. J. S.
Ring, David C.
TI Measurement of Upper Extremity Disability Using the Patient-Reported
Outcomes Measurement Information System
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE PROMIS; QuickDASH; upper extremity disability; outcome questionnaires
ID COMPUTERIZED ADAPTIVE TESTS; FUNCTION ITEM BANK; PRIMARY-CARE; PROMIS;
QUESTIONNAIRE; VALIDITY; PAIN; RESPONSIVENESS; RELIABILITY; QUICKDASH
AB Purpose Current questionnaires used to measure upper extremity specific disability can be time-consuming and subject to ceiling effects. The National Institutes of Health developed Patient-Reported Outcomes Measurement Information System (PROMIS) measures based on computer adaptive testing (CAT), a technique that is more efficient and less subject to floor and ceiling effects than traditional questionnaires with a fixed number of,questions. This study tested the correlation of the Physical Function-Upper Extremity CAT with the Quick-Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire.
Methods Patients presenting to our orthopedic outpatient clinic were invited to participate in this observational cross-sectional study between August and October 2013. A study sample of 84 patients completed the QuickDASH and PROMIS Physical Function-Upper Extremity CAT, and 3 other PROMIS measures, as well as the 2-question Pain Self-efficacy Questionnaire and the 2-question Patient Health Questionnaire.
Results A strong correlation was found between QuickDASH and PROMIS Physical Function-Upper Extremity CAT, with a significantly shorter completion time for the latter.
Conclusions We recommend the PROMIS Upper Extremity CAT because it is valid, reliable, and easy to use, and it provides easy reference to population norms (a score of 50 represents the norm in the United States population, and every 10 points represents a standard deviation from the norm). Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved.)
C1 [Doering, Anne-Carolin; Nota, Sjoerd P. F. T.; Hageman, Michiel G. J. S.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
NR 24
TC 13
Z9 13
U1 0
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 0363-5023
EI 1531-6564
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2014
VL 39
IS 6
BP 1160
EP 1165
DI 10.1016/j.jhsa.2014.03.013
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AI6TX
UT WOS:000337011000021
PM 24799143
ER
PT J
AU Menendez, ME
Ring, D
AF Menendez, Mariano E.
Ring, David
TI Disability Versus Impairment
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Letter
ID GRIP STRENGTH; FRACTURES; OUTCOMES
C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
NR 5
TC 0
Z9 0
U1 0
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 0363-5023
EI 1531-6564
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2014
VL 39
IS 6
BP 1231
EP 1231
DI 10.1016/j.jhsa.2014.02.036
PG 1
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AI6TX
UT WOS:000337011000036
PM 24862121
ER
PT J
AU Menendez, ME
Ring, D
AF Menendez, Mariano E.
Ring, David
TI de Quervain Tendinopathy: "Success" and Other Subtleties
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Letter
C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
OI Ring, David/0000-0002-6506-4879
NR 3
TC 0
Z9 0
U1 0
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 0363-5023
EI 1531-6564
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2014
VL 39
IS 6
BP 1232
EP 1233
DI 10.1016/j.jhsa.2014.03.023
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AI6TX
UT WOS:000337011000038
PM 24862123
ER
PT J
AU Kim, BYS
Jiang, W
Beiko, J
Prabhu, SS
DeMonte, F
Gilbert, MR
Sawaya, R
Aldape, KD
Cahill, DP
McCutcheon, IE
AF Kim, Betty Y. S.
Jiang, Wen
Beiko, Jason
Prabhu, Sujit S.
DeMonte, Franco
Gilbert, Mark R.
Sawaya, Raymond
Aldape, Kenneth D.
Cahill, Daniel P.
McCutcheon, Ian E.
TI Diagnostic discrepancies in malignant astrocytoma due to limited small
pathological tumor sample can be overcome by IDH1 testing
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Glioblastoma; Anaplastic astrocytoma; Malignant astrocytoma; Diagnosis;
Surgical resection; Isocitrate dehydrogenase
ID ANAPLASTIC GLIOMAS; DIFFUSE GLIOMA; MUTATION; CLASSIFICATION;
GLIOBLASTOMA; LIMITATIONS; BIOPSY; MANAGEMENT; FRAMELESS; PROGNOSIS
AB The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Patients with > 20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to < 20 cc [odds ratio (OR) 2.57, 95 % confidence interval (CI) 1.6-4.06, P < 0.0001]. The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95 % CI 0.48-1.36, P < 0.43). The rate of GBM diagnosis is twofold greater for individual surgical specimen > 10 cc than those of lower volume (OR 2.48, 95 % CI 1.88-3.28, P < 0.0001). Overall survival for AA patients with > 20 cc tumor resection on MRI is significantly better than those with < 20 cc tumor resected (P < 0.05). No volume-dependent differences were observed in patients with GBM (P < 0.4), IDH1 wild type (P < 0.1) or IDH1 mutation (P < 0.88). IDH1 status should be considered when total resection volume is < 20 cc based on MRI analysis and for surgical specimen < 10 cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone.
C1 [Kim, Betty Y. S.; Prabhu, Sujit S.; DeMonte, Franco; Sawaya, Raymond; McCutcheon, Ian E.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA.
[Jiang, Wen] Stanford Sch Med, Stanford, CA 94305 USA.
[Beiko, Jason] Univ Manitoba, Dept Neurosurg, Winnipeg, MB R3E 3P5, Canada.
[Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Kim, BYS (reprint author), Mayo Clin, Coll Med, Dept Neurosurg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM kim.betty@mayo.edu; imccutch@mdanderson.org
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; Cahill, Daniel/0000-0003-2552-6546;
Jiang, Wen/0000-0001-9154-633X
FU Detweiler Travelling Fellowship from the Royal College of Physicians and
Surgeons of Canada; James and Sarah Kennedy Mayo Clinic Research Career
Development Award; Burroughs-Wellcome Career Award in Medical Sciences;
James S. McDonnell Foundation
FX The authors also wish to thank Dr. Dima Suki for helpful discussions
related to statistical analysis. Financial support was provided by the
Detweiler Travelling Fellowship from the Royal College of Physicians and
Surgeons of Canada and James and Sarah Kennedy Mayo Clinic Research
Career Development Award (B. Y. S. K.), Burroughs-Wellcome Career Award
in Medical Sciences and James S. McDonnell Foundation (D. P. C.).
NR 32
TC 6
Z9 6
U1 0
U2 2
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 JUN
PY 2014
VL 118
IS 2
BP 405
EP 412
DI 10.1007/s11060-014-1451-0
PG 8
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AI6YN
UT WOS:000337024300022
PM 24777756
ER
PT J
AU Alvarez, V
Crary, J
Slick, N
Fry, B
Stein, T
McKee, A
AF Alvarez, Victor
Crary, John
Slick, Nathalie
Fry, Brian
Stein, Thor
McKee, Ann
TI Opthalmological Abnormalities in CTE
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Alvarez, Victor; Slick, Nathalie; Fry, Brian] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Stein, Thor; McKee, Ann] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 24
BP 591
EP 591
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100034
ER
PT J
AU Rose, M
Rashid, A
Jakobiec, F
AF Rose, Matthew
Rashid, Alia
Jakobiec, Frederick
TI Intraocular Medulloepitheliomas in Children and Adults show Markers of
Retinal Development and Glioneuronal Differentiation
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Rose, Matthew] Harvard, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA.
[Rashid, Alia; Jakobiec, Frederick] Harvard, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 23
BP 591
EP 591
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100033
ER
PT J
AU William, C
Saqran, L
Stern, M
Frosch, M
Hyman, B
AF William, Christopher
Saqran, Lubna
Stern, Matthew
Frosch, Matthew
Hyman, Bradley
TI Developmental Synaptic Plasticity Defects in a Mouse Model of Down
Syndrome
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [William, Christopher; Frosch, Matthew] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA.
[Saqran, Lubna; Stern, Matthew] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Hyman, Bradley] MGH, MassGen Inst Neurodegenerat Dis, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 32
BP 593
EP 594
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100042
ER
PT J
AU McGuone, D
Shapiro, K
Staley, K
Stemmer-Rachamimov, A
AF McGuone, Declan
Shapiro, Kevin
Staley, Kevin
Stemmer-Rachamimov, Anat
TI Lack of Findings to Support a Role for HPV in a Cohort of Focal Cortical
Dysplasia, Type IIB
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [McGuone, Declan; Shapiro, Kevin; Staley, Kevin; Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 70
BP 603
EP 604
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100080
ER
PT J
AU McGuone, D
Marciscano, A
Niemierko, A
Curry, W
Barker, F
Martuza, R
Oh, K
Loeffler, J
Shih, H
Stemmer-Rachamimov, A
AF McGuone, Declan
Marciscano, Ariel
Niemierko, Andrzej
Curry, William
Barker, Fred, II
Martuza, Robert
Oh, Kevin
Loeffler, Jay
Shih, Helen
Stemmer-Rachamimov, Anat
TI WHO Grade I Meningiomas with Atypical Features: Correlation of
Histopathology with Clinical Outcome
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [McGuone, Declan; Niemierko, Andrzej; Curry, William; Barker, Fred, II; Martuza, Robert; Oh, Kevin; Loeffler, Jay; Shih, Helen; Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
[Marciscano, Ariel] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 86
BP 607
EP 608
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100096
ER
PT J
AU Suva, M
Patel, A
Bernstein, B
Louis, D
AF Suva, Mario
Patel, Anoop
Bernstein, Bradley
Louis, David
TI Reprogramming Cell Circuits in Glioblastoma
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Suva, Mario; Patel, Anoop; Bernstein, Bradley; Louis, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 108
BP 613
EP 614
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100118
ER
PT J
AU Davidson, C
Liu, CH
Vitte, J
Giovannini, M
McClatchey, A
AF Davidson, Christian
Liu, Ching-Hui
Vitte, Jeremie
Giovannini, Marco
McClatchey, Andrea
TI Altered Receptor Tyrosine Kinase Regulation Promotes Growth Factor
Adaptability in Nf2-mutant Schwann Cells
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Davidson, Christian; Liu, Ching-Hui; McClatchey, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vitte, Jeremie; Giovannini, Marco] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
RI Vitte, Jeremie/B-9874-2017
OI Vitte, Jeremie/0000-0002-2567-7988
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 117
BP 616
EP 616
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100128
ER
PT J
AU Mordes, D
Suzuki, N
Salameh, J
Stewart, M
Maroof, A
Han, S
Brown, R
Eggan, K
AF Mordes, Daniel
Suzuki, Naoki
Salameh, Johnny
Stewart, Morag
Maroof, Asif
Han, Steve
Brown, Robert
Eggan, Kevin
TI A Loss of Function Mutation in the C9ORF72 Mouse Ortholog Results in
Motor System Degeneration
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Mordes, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Suzuki, Naoki; Maroof, Asif] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Salameh, Johnny; Han, Steve; Brown, Robert] Univ Massachusetts, Sch Med, Dept Neurol, Amherst, MA 01003 USA.
[Stewart, Morag] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
[Eggan, Kevin] Harvard Univ, HHMI, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 132
BP 620
EP 620
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100142
ER
PT J
AU Leger, PD
Johnson, DH
Robbins, GK
Shafer, RW
Clifford, DB
Li, J
McLaren, PJ
Haas, DW
AF Leger, Paul D.
Johnson, Daniel H.
Robbins, Gregory K.
Shafer, Robert W.
Clifford, David B.
Li, Jun
McLaren, Paul J.
Haas, David W.
TI Genome-wide association study of peripheral neuropathy with
D-drug-containing regimens in AIDS Clinical Trials Group protocol 384
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE Peripheral neuropathy; HIV-1; Stavudine; Didanosine; Genomics
ID MARIE-TOOTH-DISEASE; ANTIRETROVIRAL THERAPY; MUTATIONS; KIF1A
AB Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naive patients were randomized to d4T/didanosine (ddI)-or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P<5.0x10(-8)) and focused on 46 neuropathy-associated genes (threshold, P<3.5x10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P= 8.4x10(-4)), in LITAF among Blacks (rs13333308, P= 6.0x10(-6)), and in NEFL among Hispanics (rs17763685, P= 5.6x10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect.
C1 [Leger, Paul D.; Johnson, Daniel H.; Haas, David W.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN USA.
[Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Clifford, David B.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Li, Jun] Vanderbilt Univ, Sch Med, Dept Neurol, Nashville, TN 37212 USA.
[Li, Jun] VA Tennessee Valley Healthcare Syst, Nashville, TN USA.
[McLaren, Paul J.] Ecole Polytech Fed Lausanne, Lausanne, Switzerland.
[McLaren, Paul J.] Univ Lausanne, Univ Lausanne Hosp, Lausanne, Switzerland.
[Haas, David W.] Vanderbilt Hlth One Hundred Oaks, Nashville, TN 37204 USA.
RP Haas, DW (reprint author), Vanderbilt Hlth One Hundred Oaks, 719 Thompson Lane,Ste 47183, Nashville, TN 37204 USA.
EM david.w.haas@vanderbilt.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI-068636]; National Institute of Mental Health (NIMH); National
Institute of Dental and Craniofacial Research (NIDCR); [AI-077505];
[AI-038858]; [AI-068634]; [AI038855]; [GM-80178]; [AI-062435];
[AI-069415]; [AI-069419]; [AI-069423]; [AI-069424]; [AI-069428];
[AI-069432]; [AI-069434]; [AI-069450]; [AI069452]; [AI-069465];
[AI-069471]; [AI-069472]; [AI-069474]; [AI-069477]; [AI-069484];
[AI-069495]; [AI-069501]; [AI-069502]; [AI-069511]; [AI069513];
[AI-069532]; [AI-069556]; [AI-25859]; [AI-27661]; [AI-34835];
[AI34853]; [AI-38844]; [AI-46370]; [AI-54999]; [AI-69467];
[AI-69495]; [AL32782]; [HL-087726]; [NS-059330]; [TR-000445]
FX The authors are grateful to the many persons with HIV infection who
volunteered for ACTG 384 and A5128. In addition, they acknowledge the
contributions of study teams and site staff for protocols ACTG 384 and
A5128. This project was supported by grant AI-077505 (DWH). The project
described was also supported by award number U01 AI-068636 from the
National Institute of Allergy and Infectious Diseases (NIAID) and
supported by National Institute of Mental Health (NIMH) and 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. Additional
grant support included AI-038858, AI-068634, AI038855, GM-80178,
AI-062435, AI-069415, AI-069419, AI-069423, AI-069424, AI-069428,
AI-069432, AI-069434, AI-069450, AI069452, AI-069465, AI-069471,
AI-069472, AI-069474, AI-069477, AI-069484, AI-069495, AI-069501,
AI-069502, AI-069511, AI069513, AI-069532, AI-069556, AI-25859,
AI-27661, AI-34835, AI34853, AI-38844, AI-46370, AI-54999, AI-69467,
AI-69495, AL32782, HL-087726, NS-059330, and TR-000445.
NR 16
TC 4
Z9 4
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2014
VL 20
IS 3
BP 304
EP 308
DI 10.1007/s13365-014-0235-9
PG 5
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA AI3ZO
UT WOS:000336804900010
PM 24554482
ER
PT J
AU Liu, PH
Landrum, MB
Weeks, JC
Huskamp, HA
Kahn, KL
He, YL
Mack, JW
Keating, NL
AF Liu, Pang-Hsiang
Landrum, Mary Beth
Weeks, Jane C.
Huskamp, Haiden A.
Kahn, Katherine L.
He, Yulei
Mack, Jennifer W.
Keating, Nancy L.
TI Physicians' Propensity To Discuss Prognosis Is Associated with Patients'
Awareness of Prognosis for Metastatic Cancers
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID CELL LUNG-CANCER; COLORECTAL-CANCER; CHEMOTHERAPY; CARE; COMMUNICATION;
PREFERENCES; SURVIVAL; METAANALYSIS; INFORMATION; PERCEPTIONS
AB Background: Prognosis discussion is an essential component of informed decision-making. However, many terminally ill patients have a limited awareness of their prognosis and the causes are unclear.
Objective: To explore the impact of physicians' propensity to discuss prognosis on advanced cancer patients' prognosis awareness.
Design: Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study, a prospective cohort study with patient and physician surveys.
Setting/Subjects: We investigated 686 patients with metastatic lung or colorectal cancer at diagnosis who participated in the CanCORS study and reported about their life expectancy. Data were linked to the physician survey from 486 physicians who were identified by these patients as filling important roles in their cancer care.
Results: Few patients with metastatic cancers (16.5%) reported an accurate awareness of their prognosis, defined as reporting a life expectancy of less than 2 years for lung cancer or less than 5 years for colorectal cancer. Patients whose most-important-doctor (in helping patient make decisions) reported discussing prognosis with terminally ill patients earlier were more likely than those whose doctors deferred these discussions to have an accurate prognosis awareness (adjusted proportion, 18.5% versus 7.6%; odds ratio, 3.23; 95% confidence interval, 1.39-7.52; p = 0.006).
Conclusions: Few patients with advanced cancer could articulate an accurate prognosis estimate, despite most having received chemotherapy and many physicians reported they would discuss prognosis early. Physicians' propensity to discuss prognosis earlier was associated with more accurate patient reports of prognosis. Enhancing the communication skills of providers with important roles in cancer care may help to improve cancer patients' understanding of their prognosis.
C1 [Liu, Pang-Hsiang; Landrum, Mary Beth; Huskamp, Haiden A.; He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Weeks, Jane C.; Mack, Jennifer W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Santa Monica, CA USA.
[Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
RI Liu, Michael Pang-Hsiang/B-9903-2015
OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264
FU National Cancer Institute [U01-CA093344]; Primary Data Collection and
Research Centers (Dana-Farber Cancer Institute/Cancer Research Network)
[U01-CA093332]; Primary Data Collection and Research Centers (Harvard
Medical School/Northern California Cancer Center) [U01-CA093324];
Primary Data Collection and Research Centers (RAND/UCLA) [U01-CA093348];
Primary Data Collection and Research Centers (University of Alabama at
Birmingham) [U01-CA093329]; Primary Data Collection and Research Centers
(University of Iowa) [U01-CA093339]; Primary Data Collection and
Research Centers (University of North Carolina) [U01-CA093326];
Department of Veteran's Affairs [CRS 02-164]; [1R01CH164021-01A1]
FX This work of the Cancer Care Outcomes Research and Surveillance
(CanCORS) Consortium was supported by the National Cancer Institute
grants to the Statistical Coordinating Center (U01-CA093344) and Primary
Data Collection and Research Centers (Dana-Farber Cancer
Institute/Cancer Research Network U01-CA093332, Harvard Medical
School/Northern California Cancer Center U01-CA093324, RAND/UCLA
U01-CA093348, University of Alabama at Birmingham U01-CA093329,
University of Iowa U01-CA093339, University of North Carolina
U01-CA093326), and a Department of Veteran's Affairs grant to the Durham
VA Medical Center CRS 02-164. The effort of Drs. Keating, Landrum, and
Huskamp was also funded by 1R01CH164021-01A1.
NR 27
TC 15
Z9 15
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUN
PY 2014
VL 17
IS 6
BP 673
EP U49
DI 10.1089/jpm.2013.0460
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AI8HE
UT WOS:000337151100009
PM 24742212
ER
PT J
AU Cooper, Z
Corso, K
Bernacki, R
Bader, A
Gawande, A
Block, S
AF Cooper, Zara
Corso, Katherine
Bernacki, Rachelle
Bader, Angela
Gawande, Atul
Block, Susan
TI Conversations about Treatment Preferences before High-Risk Surgery: A
Pilot Study in the Preoperative Testing Center
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID CONTROLLED-TRIAL; DECISION-MAKING; FAMILY-MEMBERS; LIFE CARE; BUY-IN;
END; DIRECTIVES; SUPPORT
AB Background: It is important to engage patients and surrogates in conversations about goals and preferences for medical treatment before high-risk surgery. However, few interventions have been tested to facilitate these discussions.
Objective: To assess the acceptability and feasibility of a facilitated, structured conversation with patients and surrogates about patient goals and preferences for medical treatment during their visit to a preoperative testing center before high-risk surgery.
Design: A randomized controlled pilot study in the preoperative testing center at a tertiary academic hospital over a 4-month period.
Measurements: We used baseline and preoperative surveys to assess feasibility, and to compare differences in worry, surrogate burden, and patient-surrogate concordance about treatment preferences in conversation and control groups. We assessed acceptability of the conversation qualitatively and through surveys.
Results: Of 146 eligible patients, 79 were approached, and 65 declined to participate. Thirteen completed the study and 8 were randomized to the structured conversation. Major recruitment barriers included lack of time, or surrogate unavailability. Most postconversation patients were less worried, and more hopeful for a good recovery before surgery; 7 of 8 would recommend the conversation. Six of 8 surrogates reported postoperatively that the conversation helped prepare them to be a surrogate. Concordance improved in the intervention group only.
Conclusions: Current processes of care present major barriers to conducting facilitated conversations in the preoperative testing center. Among a small group of patients and surrogates, most found a structured conversation about the patient's goals and preferences for medical treatment helpful before high-risk surgery.
C1 [Cooper, Zara; Gawande, Atul] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Cooper, Zara; Corso, Katherine; Bader, Angela; Gawande, Atul] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Bader, Angela] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Bernacki, Rachelle; Block, Susan] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Gawande, Atul] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Cooper, Z (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM zcooper@partners.org
FU Klarman Family Foundation
FX Funding for this study was generously provided by the Klarman Family
Foundation.
NR 24
TC 7
Z9 7
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUN
PY 2014
VL 17
IS 6
BP 701
EP 707
DI 10.1089/jpm.2013.0311
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AI8HE
UT WOS:000337151100013
PM 24832687
ER
PT J
AU Lareau, CR
Sawyer, GA
Wang, JH
DiGiovanni, CW
AF Lareau, Craig R.
Sawyer, Gregory A.
Wang, Joanne H.
DiGiovanni, Christopher W.
TI Plantar and Medial Heel Pain: Diagnosis and Management
SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
LA English
DT Review
ID SHOCK-WAVE THERAPY; TARSAL TUNNEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL;
CORTICOSTEROID INJECTION; LATERAL PLANTAR; CONTROLLED MULTICENTER;
CLINICAL-TRIAL; 1ST BRANCH; FOLLOW-UP; FASCIITIS
AB Heel pain is commonly encountered in orthopaedic practice. Establishing an accurate diagnosis is critical, but it can be challenging due to the complex regional anatomy. Subacute and chronic plantar and medial heel pain are most frequently the result of repetitive microtrauma or compression of neurologic structures, such as plantar fasciitis, heel pad atrophy, Baxter nerve entrapment, calcaneal stress fracture, and tarsal tunnel syndrome. Most causes of inferior heel pain can be successfully managed nonsurgically. Surgical intervention is reserved for patients who do not respond to nonsurgical measures. Although corticosteroid injections have a role in the management of select diagnoses, they should be used with caution.
C1 [Lareau, Craig R.; Sawyer, Gregory A.; Wang, Joanne H.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Lareau, Craig R.; Sawyer, Gregory A.] Rhode Isl Hosp, Providence, RI USA.
[DiGiovanni, Christopher W.] Harvard Univ, Sch Med, Boston, MA USA.
[DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Lareau, CR (reprint author), Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
FU BioMimetic Therapeutics; Wright Medical Technology
FX Dr. Sawyer or an immediate family member serves as a paid consultant to
Mitek. Dr. DiGiovanni or an immediate family member has received
royalties from Extremity Medical; is a member of a speakers' bureau or
has made paid presentations on behalf of BioMimetic Therapeutics,
Extremity Medical, and Wright Medical Technology; serves as a paid
consultant to BESPA, BioMimetic Therapeutics, Extremity 'Medical, and
Wright Medical Technology; has stock or stock options held in Extremity
Medical and Wright Medical Technology; has received research or
institutional support from BioMimetic Therapeutics and Wright Medical
Technology; and has received nonincome support (such as equipment or
services), commercially derived honoraria, or other non-research-related
funding (such as paid travel) from CuraMedix and Performance Orthotics.
Neither of the following authors nor any immediate family member has
received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the
subject of this article: Dr. Lareau and Ms. Wang.
NR 68
TC 7
Z9 8
U1 4
U2 26
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1067-151X
EI 1940-5480
J9 J AM ACAD ORTHOP SUR
JI J. Am. Acad. Orthop. Surg.
PD JUN
PY 2014
VL 22
IS 6
BP 372
EP 380
DI 10.5435/JAAOS-22-06-372
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AI4JE
UT WOS:000336830700005
PM 24860133
ER
PT J
AU Anatchkova, MD
Barysauskas, CM
Kinney, RL
Kiefe, CI
Ash, AS
Lombardini, L
Allison, JJ
AF Anatchkova, Milena D.
Barysauskas, Constance M.
Kinney, Rebecca L.
Kiefe, Catarina I.
Ash, Arlene S.
Lombardini, Lisa
Allison, Jeroan J.
TI Psychometric Evaluation of the Care Transition Measure in TRACE-CORE: Do
We Need a Better Measure?
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE acute coronary syndromes; care transitions measure; validity; IRT
scoring
ID PATIENT-REPORTED OUTCOMES; ITEM RESPONSE THEORY; QUALITY; PRECISION
AB Background-The quality of transitional care is associated with important health outcomes such as rehospitalization and costs. The widely used Care Transitions Measure (CTM-15) was developed with a classic test theory approach; its short version (CTM-3) was included in the CAHPS Hospital Survey. We conducted a psychometric evaluation of both measures and explored whether item response theory (IRT) could produce a more precise measure.
Methods and Results-As part of the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education, 1545 participants were interviewed during an acute coronary syndrome hospitalization, providing information on general health status (Short Form-36), CTM-15, health utilization, and care process questions at 1 month postdischarge. We used classic and IRT analyses and compared the measurement precision of CTM-15-, CTM-3-, and CTM-IRT-based score using relative validity. Participants were 79% non-Hispanic white and 67% male, with an average age of 62 years. The CTM-15 had good internal consistency (Cronbach's alpha=0.95) but demonstrated acquiescence bias (8.7% participants responded "Strongly agree" and 19% responded "Agree" to all items) and limited score variability. These problems were more pronounced for the CTM-3. The CTM-15 differentiated between patient groups defined by self-reported health status, health care utilization, and care transition process indicators. Differences between groups were small (2 to 3 points). There was no gain in measurement precision from IRT scoring. The CTM-3 was not significantly lower for patients reporting rehospitalization or emergency department visits.
Conclusion-We identified psychometric challenges of the CTM, which may limit its value in research and practice. These results are in line with emerging evidence of gaps in the validity of the measure.
C1 [Anatchkova, Milena D.; Kinney, Rebecca L.; Kiefe, Catarina I.; Ash, Arlene S.; Lombardini, Lisa; Allison, Jeroan J.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA.
[Barysauskas, Constance M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Anatchkova, MD (reprint author), Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, 55 Lake Ave N,ACCES7, Worcester, MA 01655 USA.
EM milena.Anatchkova@umassmed.edu
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[1U01HL105268]; National Center for Research Resources [UL1RR031982];
NIH/NCRR; University of Massachusetts Center for Clinical and
Translational Sciences, Biostatistics, Epidemiology & Research Design
Component (BERD); Center for Health Equity Intervention Research (CHEIR)
[P60 MD006912]; PhRMA Foundation Started Grant
FX TRACE-CORE is supported by the National Institutes of Health, National
Heart, Lung, and Blood Institute grant 1U01HL105268. Research also
supported by UL1RR031982 from the National Center for Research
Resources, NIH/NCRR, University of Massachusetts Center for Clinical and
Translational Sciences, Biostatistics, Epidemiology & Research Design
Component (BERD), and The Center for Health Equity Intervention Research
(CHEIR), grant P60 MD006912. Partial salary support is additionally
provided by the PhRMA Foundation Started Grant (Dr. Anatchkova).
NR 42
TC 2
Z9 2
U1 0
U2 4
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 JUN
PY 2014
VL 3
IS 3
AR e001053
DI 10.1161/JAHA.114.001053
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800043
PM 24901109
ER
PT J
AU Ho, JE
Larson, MG
Ghorbani, A
Cheng, S
Coglianese, EE
Vasan, RS
Wang, TJ
AF Ho, Jennifer E.
Larson, Martin G.
Ghorbani, Anahita
Cheng, Susan
Coglianese, Erin E.
Vasan, Ramachandran S.
Wang, Thomas J.
TI Long-term Cardiovascular Risks Associated With an Elevated Heart Rate:
The Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular disease; epidemiology; heart failure; risk factor
ID PACEMAKER IMPLANTATION; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY;
PROGNOSTIC-FACTOR; PULSE-RATE; MORTALITY; FAILURE; DISEASE; MEN;
ATHEROSCLEROSIS
AB Background-Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow-up.
Methods and Results-Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all-cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001).
Conclusions-Individuals with a higher heart rate are at elevated long-term risk for cardiovascular events, in particular, heart failure, and all-cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation.
C1 [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA.
[Ho, Jennifer E.] Boston Univ, Cardiovasc Med Sect, Sch Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Ghorbani, Anahita] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Cheng, Susan] Harvard Univ, Sch Med, Dept Med, Div Cardiol,Brigham & Womens Hosp, Boston, MA USA.
[Coglianese, Erin E.] Loyola Univ Hlth Syst, Chicago, IL USA.
[Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA.
RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02118 USA.
EM jenho@bu.edu
OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National
Institutes of Health [K23-HL116780]; Boston University School of
Medicine Department of Medicine; Ellison Foundation
FX This work was partially supported by the Framingham Heart Study of the
National Heart, Lung, and Blood Institute (contract N01-HC-25195). Dr Ho
is supported by National Institutes of Health grant K23-HL116780 and a
Boston University School of Medicine Department of Medicine Career
Investment Award. Dr Cheng is supported by an award from the Ellison
Foundation.
NR 37
TC 20
Z9 20
U1 0
U2 6
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 JUN
PY 2014
VL 3
IS 3
AR e000668
DI 10.1161/JAHA.113.000668
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800008
PM 24811610
ER
PT J
AU Ovbiagele, B
Schwamm, LH
Smith, EE
Grau-Sepulveda, MV
Saver, JL
Bhatt, DL
Hernandez, AF
Peterson, ED
Fonarow, GC
AF Ovbiagele, Bruce
Schwamm, Lee H.
Smith, Eric E.
Grau-Sepulveda, Maria V.
Saver, Jeffrey L.
Bhatt, Deepak L.
Hernandez, Adrian F.
Peterson, Eric D.
Fonarow, Gregg C.
TI Patterns of Care Quality and Prognosis Among Hospitalized Ischemic
Stroke Patients With Chronic Kidney Disease
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE chronic kidney disease; glomerular Filtration Rate; guidelines; ischemic
stroke; outcomes; prognosis; quality indicators; renal
ID CORONARY-ARTERY-DISEASE; OF-CARE; THROMBOLYTIC THERAPY;
GUIDELINES-STROKE; RENAL DYSFUNCTION; HEART-FAILURE; OUTCOMES;
ASSOCIATION; RISK; PREVENTION
AB Background-Relatively little is known about the quality of care and outcomes for hospitalized ischemic stroke patients with chronic kidney disease (CKD). We examined quality of care and in-hospital prognoses among patients with CKD in the Get With The Guidelines-Stroke (GWTG-Stroke) program
Methods and Results-We analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. Use of 7 predefined ischemic stroke performance measures, composite "defect-free" care compliance, and in-hospital mortality were examined based on glomerular filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank-ordered variable: normal (>= 90), mild (<= 60 to <90), moderate (>= 30 to <60), severe (>= 15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%) ischemic stroke patients with CKD. Patients with severe renal dysfunction or failure were significantly less likely to receive guideline-based therapies. Compared with patients with normal kidney function (>= 90), those with CKD (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94 [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to 0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely to receive 100% defect-free care measure compliance. Inpatient mortality was higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]), and progressively rose with more severe renal dysfunction.
Conclusions-Despite higher in-hospital mortality rates, ischemic stroke patients with CKD, especially those with greater severity of renal dysfunction, were less likely to receive important guideline-recommended therapies.
C1 [Ovbiagele, Bruce] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA.
[Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA.
[Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA.
[Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ovbiagele, B (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St,CSB 301,MSC 606, Charleston, SC 29425 USA.
EM ovibes@musc.edu
RI Hernandez, Adrian F./A-7818-2016;
OI Hernandez, Adrian F./0000-0003-3387-9616; Smith,
Eric/0000-0003-3956-1668
FU American Heart Association; American Stroke Association; Pfizer (New
York, NY); Merck-Schering Plough Partnership (North Wales, PA)
FX The Get With The Guidelines Program (GWTG) is funded by the American
Heart Association and the American Stroke Association. The program is
also supported in part by unrestricted educational grants to the
American Heart Association by Pfizer (New York, NY) and the
Merck-Schering Plough Partnership (North Wales, PA), who did not
participate in the design, analysis, or manuscript preparation, and did
not require approval of this manuscript for submission.
NR 23
TC 2
Z9 2
U1 0
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 JUN
PY 2014
VL 3
IS 3
AR e000905
DI 10.1161/JAHA.114.000905
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800035
PM 24904017
ER
PT J
AU Sarma, A
Cannon, CP
de Lemos, J
Rouleau, JL
Lewis, EF
Guo, JP
Mega, JL
Sabatine, MS
O'Donoghue, ML
AF Sarma, Amy
Cannon, Christopher P.
de Lemos, James
Rouleau, Jean L.
Lewis, Eldrin F.
Guo, Jianping
Mega, Jessica L.
Sabatine, Marc S.
O'Donoghue, Michelle L.
TI The Incidence of Kidney Injury for Patients Treated With a High-Potency
Versus Moderate-Potency Statin Regimen After an Acute Coronary Syndrome
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE acute coronary syndrome; acute kidney injury; kidney; statins
ID TO-Z TRIAL; MYOCARDIAL-INFARCTION; REDUCTASE INHIBITORS; SHORT-TERM;
SIMVASTATIN; ATORVASTATIN; THERAPY; EXPRESSION; CELLS; RAT
AB Background-Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy.
Methods and Results-PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/dayx1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebox4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or >= 0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78).
Conclusions-For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury.
C1 [Cannon, Christopher P.; Lewis, Eldrin F.; Guo, Jianping; Mega, Jessica L.; Sabatine, Marc S.; O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Sarma, Amy] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[de Lemos, James] UT Southwestern Med Ctr, Dallas, TX USA.
[Rouleau, Jean L.] Univ Montreal, Div Cardiovasc, Montreal, PQ, Canada.
RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM modonoghue@partners.org
FU Bristol-Myers Squibb; Sankyo; Merck
FX The PROVE IT-TIMI 22 trial was supported by Bristol-Myers Squibb and
Sankyo. The A-to-Z trial was supported by Merck. The current analysis
received no financial support.
NR 28
TC 6
Z9 6
U1 0
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 JUN
PY 2014
VL 3
IS 3
AR e000784
DI 10.1161/JAHA.114.000784
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800018
PM 24786143
ER
PT J
AU Madani, N
Princiotto, AM
Schon, A
LaLonde, J
Feng, Y
Freire, E
Park, J
Courter, JR
Jones, DM
Robinson, J
Liao, HX
Moody, MA
Permar, S
Haynes, B
Smith, AB
Wyatt, R
Sodroski, J
AF Madani, Navid
Princiotto, Amy M.
Schoen, Arne
LaLonde, Judith
Feng, Yu
Freire, Ernesto
Park, Jongwoo
Courter, Joel R.
Jones, David M.
Robinson, James
Liao, Hua-Xin
Moody, M. Anthony
Permar, Sallie
Haynes, Barton
Smith, Amos B., III
Wyatt, Richard
Sodroski, Joseph
TI CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to
Vaccine-Elicited Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 ENVELOPE GLYCOPROTEIN; CORECEPTOR BINDING-SITE; STRUCTURE-BASED
DESIGN; NEUTRALIZING ANTIBODY; TYPE-1 ENVELOPE; MONOCLONAL-ANTIBODIES;
GP120 GLYCOPROTEINS; ENTRY INHIBITORS; VARIABLE REGIONS; IMMUNOGEN
DESIGN
AB Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.
C1 [Madani, Navid; Princiotto, Amy M.; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Feng, Yu; Wyatt, Richard] Scripps Res Inst, TSRI, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[LaLonde, Judith] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
[Park, Jongwoo; Courter, Joel R.; Jones, David M.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Robinson, James] Tulane Univ Med Ctr, Dept Pediat, New Orleans, LA USA.
[Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton] Duke Univ Med Ctr, Duke Human Vaccine Inst, Dept Immunol, Dept Med, Durham, NC USA.
[Sodroski, Joseph] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
FU National Institutes of Health [GM56550, AI100645, AI24755];
International AIDS Vaccine Initiative; National Science Foundation
[MCB-1157506]; amfAR [107431-45-RFNT]; NIH [AI090682]; Ragon Institute
Innovation Award
FX This study was supported by the National Institutes of Health (grants
GM56550, AI100645, and AI24755), the International AIDS Vaccine
Initiative, and the late William F. McCarty-Cooper. E. F. thanks the
National Science Foundation for support (MCB-1157506). N.M. was
supported by amfAR grant 107431-45-RFNT, NIH grant AI090682, and a Ragon
Institute Innovation Award.
NR 91
TC 19
Z9 19
U1 1
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 JUN
PY 2014
VL 88
IS 12
BP 6542
EP 6555
DI 10.1128/JVI.00540-14
PG 14
WC Virology
SC Virology
GA AI5HF
UT WOS:000336895600004
PM 24696475
ER
PT J
AU Kasinath, BS
AF Kasinath, Balakuntalam S.
TI Hydrogen sulfide to the rescue in obstructive kidney injury
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID CYSTATHIONINE-GAMMA-LYASE; RENAL ISCHEMIA/REPERFUSION; CELLS
AB Hydrogen sulfide is a gasotransmitter with far-reaching effects on cell function. Studies show that, depending on the context, hydrogen sulfide can function as an ameliorative agent or as a mediator of kidney injury.
C1 [Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM kasinath@uthscsa.edu
FU NIDDK NIH HHS [R01 DK077295]
NR 12
TC 6
Z9 6
U1 0
U2 3
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 JUN
PY 2014
VL 85
IS 6
BP 1255
EP 1258
DI 10.1038/ki.2013.529
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA AI4FG
UT WOS:000336820500002
PM 24875544
ER
PT J
AU George, B
Fan, QF
Dlugos, CP
Soofi, AA
Zhang, JD
Verma, R
Park, TJ
Wong, H
Curran, T
Nihalani, D
Holzman, LB
AF George, Britta
Fan, Qingfeng
Dlugos, Christopher P.
Soofi, Abdulsalam A.
Zhang, Jidong
Verma, Rakesh
Park, Tae-Ju
Wong, Hetty
Curran, Tom
Nihalani, Deepak
Holzman, Lawrence B.
TI Crk1/2 and CrkL form a hetero-oligomer and functionally complement each
other during podocyte morphogenesis
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE cytoskeleton; nephrin; podocyte; signaling
ID ACTIN CYTOSKELETON; SLIT DIAPHRAGM; INTERCELLULAR JUNCTION; TRANSGENIC
MICE; NEPHRIN; EXPRESSION; PROTEINS; GENE; PROMOTES; FAMILY
AB Activation of the slit diaphragm protein nephrin induces actin cytoskeletal remodeling, resulting in lamellipodia formation in podocytes in vitro in a phosphatidylinositol-3 kinase-, focal adhesion kinase-, Cas-, and Crk1/2-dependent fashion. In mice, podocyte-specific deletion of Crk1/2 prevents or attenuates foot process effacement in two models of podocyte injury. This suggests that cellular mechanisms governing lamellipodial protrusion in vitro are similar to those in vivo during foot process effacement. As Crk1/2-null mice developed and aged normally, we tested whether the Crk1/2 paralog, CrkL, functionally complements Crk1/2 in a podocyte-specific context. Podocyte-specific CrkL-null mice, like podocyte-specific Crk1/2-null mice, developed and aged normally but were protected from protamine sulfate-induced foot process effacement. Simultaneous podocyte-specific deletion of Crk1/2 and CrkL resulted in albuminuria detected by 6 weeks postpartum and associated with altered podocyte process architecture. Nephrin-induced lamellipodia formation in podocytes in vitro was CrkL-dependent. CrkL formed a hetero-oligomer with Crk2 and, like Crk2, was recruited to tyrosine phosphorylated nephrin. Thus, Crk1/2 and CrkL are physically linked, functionally complement each other during podocyte foot process spreading, and together are required for developing typical foot process architecture.
C1 [George, Britta; Fan, Qingfeng; Zhang, Jidong; Wong, Hetty; Nihalani, Deepak; Holzman, Lawrence B.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[George, Britta; Dlugos, Christopher P.] Univ Klinikum Munster, Med Klin & Poliklin D, Munster, Germany.
[Soofi, Abdulsalam A.; Verma, Rakesh] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA.
[Park, Tae-Ju; Curran, Tom] Childrens Hosp Philadelphia, Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Holzman, Lawrence B.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
RP Holzman, LB (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, 405 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA.
EM lholzman@upenn.edu
RI Curran, Tom/D-7515-2011;
OI Park, Taeju/0000-0003-3897-3994
FU NIDDK [DK080751]; Department of Veterans Affairs; Deutsche
Forschungsgemeinschaft [GE 2158/1-1, GE 2158/3-1]; Pennsylvania
Department of Health Cure Formulary [4100047628]
FX This work was supported by grants to LBH from the NIDDK (DK080751) and
the Department of Veterans Affairs, and to BG from the Deutsche
Forschungsgemeinschaft (GE 2158/1-1, GE 2158/3-1). This work was also
supported by a Pennsylvania Department of Health Cure Formulary grant to
TC (SAP #4100047628).
NR 32
TC 7
Z9 7
U1 1
U2 5
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 JUN
PY 2014
VL 85
IS 6
BP 1382
EP 1394
DI 10.1038/ki.2013.556
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA AI4FG
UT WOS:000336820500020
PM 24499776
ER
PT J
AU Hunemohr, N
Paganetti, H
Greilich, S
Jakel, O
Seco, J
AF Huenemohr, Nora
Paganetti, Harald
Greilich, Steffen
Jaekel, Oliver
Seco, Joao
TI Tissue decomposition from dual energy CT data for MC based dose
calculation in particle therapy
SO MEDICAL PHYSICS
LA English
DT Article
DE dual energy CT; stoichiometric calibration; Monte Carlo; composition;
WEPL; range uncertainty
ID MONTE-CARLO SIMULATIONS; EFFECTIVE ATOMIC NUMBER; COMPUTED-TOMOGRAPHY;
RANGE UNCERTAINTIES; HOUNSFIELD UNITS; BRACHYTHERAPY; DISTRIBUTIONS;
SINGLE; BEAMS; SEGMENTATION
AB Purpose: The authors describe a novel method of predicting mass density and elemental mass fractions of tissues from dual energy CT (DECT) data for Monte Carlo (MC) based dose planning.
Methods: The relative electron density rho(e) and effective atomic number Z(eff) are calculated for 71 tabulated tissue compositions. For MC simulations, the mass density is derived via one linear fit in the rho(e) that covers the entire range of tissue compositions (except lung tissue). Elemental mass fractions are predicted from the rho(e) and the Z(eff) in combination. Since particle therapy dose planning and verification is especially sensitive to accurate material assignment, differences to the ground truth are further analyzed for mass density, I-value predictions, and stopping power ratios (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12 tissues which showed the largest differences of single energy CT (SECT) to DECT are presented with respect to range uncertainties. The standard approach (SECT) and the new DECT approach are compared to reference Bragg peak positions.
Results: Mean deviations to ground truth in mass density predictions could be reduced for soft tissue from (0.5 +/- 0.6)% (SECT) to (0.2 +/- 0.2)% with the DECT method. Maximum SPR deviations could be reduced significantly for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. Mean I-value deviations could be reduced for soft tissue from (1.1 +/- 1.4%, SECT) to (0.4 +/- 0.3%) with the presented method. Predictions of elemental composition were improved for every element. Mean and maximum deviations from ground truth of all elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. Dose studies showed that most of the 12 selected tissues would profit significantly (up to 2.2%) from DECT material decomposition with no noise present. The rho(e) associated with an absolute noise of +/- 0.01 and Z(eff) associated with an absolute noise of +/- 0.2 resulted in +/- 10% standard variation in the carbon and oxygen mass fraction prediction.
Conclusions: Accurate stopping power prediction is mainly determined by the correct mass density prediction. Theoretical improvements in range predictions with DECT data in the order of 0.1%-2.1% were observed. Further work is needed to quantify the potential improvements from DECT compared to SECT in measured image data associated with artifacts and noise. (C) 2014 American Association of Physicists in Medicine.
C1 [Huenemohr, Nora; Greilich, Steffen; Jaekel, Oliver] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Paganetti, Harald; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Paganetti, Harald; Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Jaekel, Oliver] Univ Heidelberg Hosp, Dept Radiat Oncol & Radiat Therapy, D-69120 Heidelberg, Germany.
RP Hunemohr, N (reprint author), German Canc Res Ctr, D-69120 Heidelberg, Germany.
EM n.huenemohr@dkfz.de
OI Greilich, Steffen/0000-0001-6237-7936
FU NCI NIH HHS [P01 CA21239, P01 CA021239]
NR 34
TC 18
Z9 18
U1 1
U2 13
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2014
VL 41
IS 6
AR 061714
DI 10.1118/1.4875976
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI7UR
UT WOS:000337106300016
PM 24877809
ER
PT J
AU Schaefferkoetter, J
Ouyang, JS
Rakvongthai, Y
Nappi, C
El Fakhri, G
AF Schaefferkoetter, Joshua
Ouyang, Jinsong
Rakvongthai, Yothin
Nappi, Carmela
El Fakhri, Georges
TI Effect of time-of-flight and point spread function modeling on
detectability of myocardial defects in PET
SO MEDICAL PHYSICS
LA English
DT Article
DE time-of-flight; point spread function; myocardial defect; detectability;
channelized Hotelling observer
ID POSITRON-EMISSION-TOMOGRAPHY; LESION DETECTION; HUMAN-OBSERVER; IMPACT;
RECONSTRUCTION; NOISE; DEFINITION; PERFUSION; LROC
AB Purpose: A study was designed to investigate the impact of time-of-flight (TOF) and point spread function (PSF) modeling on the detectability of myocardial defects.
Methods: Clinical FDG-PET data were used to generate populations of defect-present and defect-absent images. Defects were incorporated at three contrast levels, and images were reconstructed by ordered subset expectation maximization (OSEM) iterative methods including ordinary Poisson, alone and with PSF, TOF, and PSF+TOF. Channelized Hotelling observer signal-to-noise ratio (SNR) was the surrogate for human observer performance.
Results: For three iterations, 12 subsets, and no postreconstruction smoothing, TOF improved overall defect detection SNR by 8.6% as compared to its non-TOF counterpart for all the defect contrasts. Due to the slow convergence of PSF reconstruction, PSF yielded 4.4% less SNR than non-PSF. For reconstruction parameters (iteration number and postreconstruction smoothing kernel size) optimizing observer SNR, PSF showed larger improvement for faint defects. The combination of TOF and PSF improved mean detection SNR as compared to non-TOF and non-PSF counterparts by 3.0% and 3.2%, respectively.
Conclusions: For typical reconstruction protocol used in clinical practice, i.e., less than five iterations, TOF improved defect detectability. In contrast, PSF generally yielded less detectability. For large number of iterations, TOF+PSF yields the best observer performance. (C) 2014 American Association of Physicists in Medicine.
C1 [Schaefferkoetter, Joshua] A STAR NUS Clin Imaging & Res Ctr CIRC, Singapore 117599, Singapore.
[Ouyang, Jinsong; Rakvongthai, Yothin; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Ouyang, Jinsong; Rakvongthai, Yothin; Nappi, Carmela; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Nappi, Carmela] Univ Naples Federico II, Dept Adv Biomed Sci, I-80131 Naples, Italy.
[Nappi, Carmela] SDN Fdn, Inst Diagnost & Nucl Dev, I-80142 Naples, Italy.
RP Schaefferkoetter, J (reprint author), A STAR NUS Clin Imaging & Res Ctr CIRC, Singapore 117599, Singapore.
EM dnrjds@nus.edu.sg
FU NCI NIH HHS [R01-CA165221, R01 CA165221]; NHLBI NIH HHS [R01 HL118261,
R01-HL118261, R01-HL110241, R01 HL110241]; NIBIB NIH HHS [T32-EB013180,
T32 EB013180]
NR 34
TC 3
Z9 3
U1 1
U2 10
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2014
VL 41
IS 6
AR 062502
DI 10.1118/1.4875725
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI7UR
UT WOS:000337106300043
PM 24877836
ER
PT J
AU Yip, S
Rottmann, J
Berbeco, R
AF Yip, Stephen
Rottmann, Joerg
Berbeco, Ross
TI The impact of cine EPID image acquisition frame rate on markerless
soft-tissue tracking
SO MEDICAL PHYSICS
LA English
DT Article
DE EPID; markerless tracking; acquisition frame rate stereotactic body
radiotherapy
ID STEREOTACTIC BODY RADIOTHERAPY; RADIATION-THERAPY; LUNG-CANCER;
VERIFICATION; FEASIBILITY; TUMORS
AB Purpose: Although reduction of the cine electronic portal imaging device (EPID) acquisition frame rate through multiple frame averaging may reduce hardware memory burden and decrease image noise, it can hinder the continuity of soft-tissue motion leading to poor autotracking results. The impact of motion blurring and image noise on the tracking performance was investigated.
Methods: Phantom and patient images were acquired at a frame rate of 12.87 Hz with an amorphous silicon portal imager (AS1000, Varian Medical Systems, Palo Alto, CA). The maximum frame rate of 12.87 Hz is imposed by the EPID. Low frame rate images were obtained by continuous frame averaging. A previously validated tracking algorithm was employed for autotracking. The difference between the programmed and autotracked positions of a Las Vegas phantom moving in the superior-inferior direction defined the tracking error (delta). Motion blurring was assessed by measuring the area change of the circle with the greatest depth. Additionally, lung tumors on 1747 frames acquired at 11 field angles from four radiotherapy patients are manually and automatically tracked with varying frame averaging. d was defined by the position difference of the two tracking methods. Image noise was defined as the standard deviation of the background intensity. Motion blurring and image noise are correlated with d using Pearson correlation coefficient (R).
Results: For both phantom and patient studies, the autotracking errors increased at frame rates lower than 4.29 Hz. Above 4.29 Hz, changes in errors were negligible with delta < 1.60 mm. Motion blurring and image noise were observed to increase and decrease with frame averaging, respectively. Motion blurring and tracking errors were significantly correlated for the phantom (R = 0.94) and patient studies (R = 0.72). Moderate to poor correlation was found between image noise and tracking error with R -0.58 and -0.19 for both studies, respectively.
Conclusions: Cine EPID image acquisition at the frame rate of at least 4.29 Hz is recommended. Motion blurring in the images with frame rates below 4.29 Hz can significantly reduce the accuracy of autotracking. (C) 2014 American Association of Physicists in Medicine.
C1 [Yip, Stephen] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Yip, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
EM syip@lroc.harvard.edu
FU NCI NIH HHS [R21 CA156068, R21CA156068]
NR 25
TC 4
Z9 4
U1 0
U2 3
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2014
VL 41
IS 6
AR 061702
DI 10.1118/1.4873322
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI7UR
UT WOS:000337106300004
PM 24877797
ER
PT J
AU Pop, MS
Stransky, N
Garvie, CW
Theurillat, JP
Hartman, EC
Lewis, TA
Zhong, C
Culyba, EK
Lin, F
Daniels, DS
Pagliarini, R
Ronco, L
Koehler, AN
Garraway, LA
AF Pop, Marius S.
Stransky, Nicolas
Garvie, Colin W.
Theurillat, Jean-Philippe
Hartman, Emily C.
Lewis, Timothy A.
Zhong, Cheng
Culyba, Elizabeth K.
Lin, Fallon
Daniels, Douglas S.
Pagliarini, Raymond
Ronco, Lucienne
Koehler, Angela N.
Garraway, Levi A.
TI A Small Molecule That Binds and Inhibits the ETV1 Transcription Factor
Oncoprotein
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DIVERSE SMALL MOLECULES; ETS PROTEIN ER81; PROSTATE-CANCER; CELL
INVASION; IN-VITRO; GENE; ACTIVATION; DISCOVERY; MELANOMA; TARGET
AB Members of the ETS transcription factor family have been implicated in several cancers, where they are often dysregulated by genomic derangement. ETS variant 1 (ETV1) is an ETS factor gene that undergoes chromosomal translocation in prostate cancers and Ewing sarcomas, amplification in melanomas, and lineage dysregulation in gastrointestinal stromal tumors. Pharmacologic perturbation of ETV1 would be appealing in these cancers; however, oncogenic transcription factors are often deemed "undruggable" by conventional methods. Here, we used small-molecule microarray screens to identify and characterize drug-like compounds that modulate the biologic function of ETV1. We identified the 1,3,5-triazine small molecule BRD32048 as a top candidate ETV1 perturbagen. BRD32048 binds ETV1 directly, modulating both ETV1-mediated transcriptional activity and invasion of ETV1-driven cancer cells. Moreover, BRD32048 inhibits p300-dependent acetylation of ETV1, thereby promoting its degradation. These results point to a new avenue for pharmacologic ETV1 inhibition and may inform a general means to discover small molecule perturbagens of transcription factor oncoproteins. (C) 2014 AACR.
C1 [Pop, Marius S.; Theurillat, Jean-Philippe; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pop, Marius S.; Stransky, Nicolas; Garvie, Colin W.; Theurillat, Jean-Philippe; Hartman, Emily C.; Lewis, Timothy A.; Zhong, Cheng; Culyba, Elizabeth K.; Daniels, Douglas S.; Ronco, Lucienne; Koehler, Angela N.; Garraway, Levi A.] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Lin, Fallon; Pagliarini, Raymond] MIT, Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
[Koehler, Angela N.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Koehler, Angela N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Garraway, LA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1542, Boston, MA 02115 USA.
EM levi_garraway@dfci.harvard.edu
OI Daniels, Douglas/0000-0003-0238-9403
FU National Cancer Institute's Initiative for Chemical Genetics (ICG)
[N01-CO-12400]; Cancer Target Discovery and Development (CTD2) Network
[RC2 CA148399]; New Innovator Award from the National Institutes of
Health; Challenge Award from the Prostate Cancer Foundation
FX The project was funded by the National Cancer Institute's Initiative for
Chemical Genetics (ICG) under Contract No. N01-CO-12400, and the Cancer
Target Discovery and Development (CTD2) Network, under RC2
CA148399 (A.N. Koehler), a New Innovator Award from the National
Institutes of Health, and a Challenge Award from the Prostate Cancer
Foundation (L.A. Garraway).
NR 50
TC 12
Z9 12
U1 0
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2014
VL 13
IS 6
BP 1492
EP 1502
DI 10.1158/1535-7163.MCT-13-0689
PG 11
WC Oncology
SC Oncology
GA AI8LX
UT WOS:000337168600010
PM 24737027
ER
PT J
AU Lerner-Ellis, JP
Aldubayan, SH
Hernandez, AL
Kelly, MA
Stuenkel, AJ
Walsh, J
Joshi, VA
AF Lerner-Ellis, Jordan P.
Aldubayan, Saud H.
Hernandez, Amy Lovelette
Kelly, Melissa Allard
Stuenkel, Aaron J.
Walsh, Jennifer
Joshi, Victoria A.
TI The spectrum of FBN1, TGF beta R1, TGF beta R2 and ACTA2 variants in 594
individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or
Thoracic Aortic Aneurysms and Dissections (TAAD)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Marfan Syndrome; Loeys-Dietz Syndrome; Thoracic Aortic Aneurysms and
Dissections; FBN1; Aortic aneurysms
ID TGFBR2 MUTATIONS; FIBRILLIN-1 GENE; FEATURES; UPDATE; GHENT
AB Introduction: In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGF beta R1, TGF beta R2 and ACTA2 genes.
Methods: We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGF beta R1, TGF beta R2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions.
Results: A total of 112 patients had a positive result Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel.
Conclusion: This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Lerner-Ellis, Jordan P.] Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada.
[Lerner-Ellis, Jordan P.] Univ Toronto, Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada.
[Lerner-Ellis, Jordan P.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Lerner-Ellis, Jordan P.; Hernandez, Amy Lovelette; Kelly, Melissa Allard; Joshi, Victoria A.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA.
[Aldubayan, Saud H.] Univ Toronto, Dept Med, Toronto, ON M5G 2C4, Canada.
[Stuenkel, Aaron J.; Walsh, Jennifer] Boston Univ, Boston, MA 02215 USA.
[Joshi, Victoria A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Joshi, Victoria A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Aldubayan, SH (reprint author), Univ Toronto, Dept Med, 190 Elizabeth St,R Fraser Elliott Bldg 3-805, Toronto, ON M5G 2C4, Canada.
EM sdubayan@gmail.com
RI Lerner-Ellis, Jordan/J-5559-2016
NR 37
TC 10
Z9 10
U1 3
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUN
PY 2014
VL 112
IS 2
BP 171
EP 176
DI 10.1016/j.ymgme.2014.03.011
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AI7KF
UT WOS:000337067900010
PM 24793577
ER
PT J
AU Zhang, B
Jia, WH
Matsuda, K
Kweon, SS
Matsuo, K
Xiang, YB
Shin, AS
Jee, SH
Kim, DH
Cai, QY
Long, JR
Shi, JJ
Wen, WQ
Yang, G
Zhang, YF
Li, C
Li, BS
Guo, Y
Ren, ZF
Ji, BT
Pan, ZZ
Takahashi, A
Shin, MH
Matsuda, F
Gao, YT
Oh, JH
Kim, S
Ahn, YO
Chan, AT
Chang-Claude, J
Slattery, ML
Gruber, SB
Schumacher, FR
Stenzel, SL
Casey, G
Kim, HR
Jeong, JY
Park, JW
Li, HL
Hosono, S
Cho, SH
Kubo, M
Shu, XO
Zeng, YX
Zheng, W
AF Zhang, Ben
Jia, Wei-Hua
Matsuda, Koichi
Kweon, Sun-Seog
Matsuo, Keitaro
Xiang, Yong-Bing
Shin, Aesun
Jee, Sun Ha
Kim, Dong-Hyun
Cai, Qiuyin
Long, Jirong
Shi, Jiajun
Wen, Wanqing
Yang, Gong
Zhang, Yanfeng
Li, Chun
Li, Bingshan
Guo, Yan
Ren, Zefang
Ji, Bu-Tian
Pan, Zhi-Zhong
Takahashi, Atsushi
Shin, Min-Ho
Matsuda, Fumihiko
Gao, Yu-Tang
Oh, Jae Hwan
Kim, Soriul
Ahn, Yoon-Ok
Chan, Andrew T.
Chang-Claude, Jenny
Slattery, Martha L.
Gruber, Stephen B.
Schumacher, Fredrick R.
Stenzel, Stephanie L.
Casey, Graham
Kim, Hyeong-Rok
Jeong, Jin-Young
Park, Ji Won
Li, Hong-Lan
Hosono, Satoyo
Cho, Sang-Hee
Kubo, Michiaki
Shu, Xiao-Ou
Zeng, Yi-Xin
Zheng, Wei
CA Genetics Epidemiology Colorectal C
Colorectal Transdisciplinary COREC
Colon Canc Family Registry
TI Large-scale genetic study in East Asians identifies six new loci
associated with colorectal cancer risk
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LYMPHOTOXIN-BETA-RECEPTOR; SUSCEPTIBILITY LOCI;
BREAST-CANCER; COLON-CANCER; CELL-GROWTH; EXPRESSION; MUTATIONS;
VARIANTS; METAANALYSIS
AB Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 x 10(-8) to 9.22 x 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.
C1 [Zhang, Ben; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Jia, Wei-Hua; Pan, Zhi-Zhong; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.
[Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
[Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea.
[Matsuo, Keitaro; Hosono, Satoyo] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan.
[Xiang, Yong-Bing; Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Shin, Aesun] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea.
[Shin, Aesun; Ahn, Yoon-Ok] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Jee, Sun Ha; Kim, Soriul] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea.
[Kim, Dong-Hyun; Jeong, Jin-Young] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea.
[Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Li, Bingshan] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Guo, Yan] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA.
[Ren, Zefang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Takahashi, Atsushi; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
[Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
[Oh, Jae Hwan; Park, Ji Won] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA.
[Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Kim, Hyeong-Rok] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea.
[Park, Ji Won] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea.
[Cho, Sang-Hee] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
EM wei.zheng@vanderbilt.edu
RI Gallinger, Steven/E-4575-2013; Shin, Aesun/E-9145-2014; Hoffmeister,
Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Kubo,
Michiaki/N-7947-2015; zhang, yanfeng/E-6971-2016; Brenner,
Hermann/B-4627-2017;
OI Shin, Aesun/0000-0002-6426-1969; Hoffmeister,
Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; zhang,
yanfeng/0000-0002-3859-3839; Brenner, Hermann/0000-0002-6129-1572;
Bezieau, stephane/0000-0003-0095-1319; Matsuda,
Koichi/0000-0001-7292-2686; Matsuo, Keitaro/0000-0003-1761-6314
FU US National Institutes of Health (NIH) [R37CA070867, R01CA082729,
R01CA124558, R01CA148667, R01CA122364]; Vanderbilt University School of
Medicine. Studies; Asia Colorectal Cancer Consortium include the
Shanghai Women's Health Study (US NIH) [R37CA070867]; Shanghai Men's
Health Study (US NIH) [R01CA082729]; Shanghai Breast and Endometrial
Cancer Studies (US NIH) [R01CA064277, R01CA092585]; Shanghai Colorectal
Cancer Study 3 (US NIH) [R37CA070867]; Guangzhou Colorectal Cancer Study
(National Key Scientific and Technological Project)
[2011ZX09307-001-04]; National Basic Research Program [2011CB504303];
Natural Science Foundation of China [81072383]; Japan BioBank Colorectal
Cancer Study (grant from the Ministry of Education, Culture, Sports,
Science and Technology of the Japanese government); Hwasun Cancer
Epidemiology Study Colon and Rectum Cancer (HCES-CRC); Korea Center for
Disease Control and Prevention; Aichi Colorectal Cancer Study [17015018,
221S0001]; Korea-NCC (National Cancer Center) Colorectal Cancer Study
(Basic Science Research Program through-the National Research Foundation
of Korea [2010-0010276]; National Cancer Center Korea [0910220];
Korea-Seoul Colorectal Cancer Study; KCPS-II Colorectal Cancer Study
(National R&D Program for Cancer Control) [1220180]; Seoul RD Program
[10526]; GECCO; CORECT; CCFR; NIH [R01CA048998]; DACHS (German Federal
Ministry of Education and Research) [BR 1704/6-1, BR 1704/6-3, BR
1704/6-4, CH 117/1-1, 01KH0404, 01ER0814]; HPFS (US NIH) [P01CA055075,
UM1CA167552, R01137178, P50CA127003]; NHS (US NIH) [R01137178,
P50CA127003, P01CA087969]; OFCCR (US NIH) [U01CA074783]; PMH (US NIH)
[R01CA076366]; PHS (US NIH) [R01CA042182]
FX The authors are solely responsible for the scientific content of this
paper. The sponsors of this study had no role in study design, data
collection, analysis or interpretation, writing of the report or the
decision for submission. We thank all study participants and research
staff of all parent studies for their contributions and commitment to
this project, R. Courtney for DNA preparation, J. He for data processing
and analyses, X. Gun for suggestions on bioinformatics analysis, and
M.J. Daly and B.J. Rammer for editing and preparing the manuscript. The
work at the Vanderbilt University School of Medicine was supported by US
National Institutes of Health (NIH) grants R37CA070867, R01CA082729,
R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram
Professorship and Research Reward funds from the Vanderbilt University
School of Medicine. Studies (grant support) participating in the Asia
Colorectal Cancer Consortium include the Shanghai Women's Health Study
(US NIH, R37CA070867), the Shanghai Men's Health Study (US NIH,
R01CA082729), the Shanghai Breast and Endometrial Cancer Studies (US
NIH, R01CA064277 and R01CA092585; contributing only controls), Shanghai
Colorectal Cancer Study 3 (US NIH, R37CA070867 and Ingram Professorship
funds), the Guangzhou Colorectal Cancer Study (National Key Scientific
and Technological Project, 2011ZX09307-001-04; the National Basic
Research Program, 2011CB504303, contributing only controls; the Natural
Science Foundation of China, 81072383, contributing only controls), the
Japan BioBank Colorectal Cancer Study (grant from the Ministry of
Education, Culture, Sports, Science and Technology of the Japanese
government), the Hwasun Cancer Epidemiology Study Colon and Rectum
Cancer (HCES-CRC; grants from the Korea Center for Disease Control and
Prevention and the Jeonnam Regional Cancer Center), the Aichi Colorectal
Cancer Study (Grant-in-Aid for Cancer Research, grant for the Third Term
Comprehensive Control Research for Cancer and Grants-in-Aid for
Scientific Research from the Japanese Ministry of Education, Culture,
Sports, Science and Technology, 17015018 and 221S0001), the Korea-NCC
(National Cancer Center) Colorectal Cancer Study (Basic Science Research
Program through-the National Research Foundation of Korea, 2010-0010276;
National Cancer Center Korea, 0910220), the Korea-Seoul Colorectal
Cancer Study (none reported) and the KCPS-II Colorectal Cancer Study
(National R&D Program for Cancer Control, 1220180; Seoul R&D Program,
10526).; We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik,
R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; and P. Soule, H.
Ranu, I. Devivo, D.J. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS
and PHS, as well as the following state cancer registries for their
help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut,
Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky,
Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New
Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio,
Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee,
Texas, Virginia, Washington and Wyoming. We thank C. Berg and P. Prorok
of PLCO; T. Riley of Information Management Services, Inc.; B. O'Brien
of Westat, Inc.; B. Kopp and W Shao of SAIC-Frederick; the WHI
investigators (see
https://www.whi.org/researchers/SitePages/Write%20a%20Paper. aspx) and
the GECCO Coordinating Center. Participating studies (grant support) in
the GECCO, CORECT and CCFR GWAS meta-analysis are GECCO (US NIH,
U01CA137088 and R01CA059045), DALS (US NIH, R01CA048998), DACHS (German
Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR
1704/6-4, CH 117/1-1,01KH0404 and 01ER0814), HPFS (US NIH, P01CA055075,
UM1CA167552, R01137178 and P50CA127003), NHS (US NIH, R01137178,
P50CA127003 and P01CA087969), OFCCR (US NIH, U01CA074783), PMH (US NIH,
R01CA076366), PHS (US NIH, R01CA042182), VITAL (US NIH, K05CA154337),
WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and
268200764316C) and PLCO (US NIH, Z01CP 010200, U0IHG004446 and U01HG
004438). CORECT is supported by the National Cancer Institute as part of
the GAME-ON consortium (US NIH, U19CA148107) with additional support
from National Cancer Institute grants (R01CA81488 and P30CA014089), the
National Human Genome Research Institute at the US NIH (T32HG000040) and
the National Institute of Environmental Health Sciences at the US NIH
(T32ES013678). CCFR is supported by the National Cancer Institute, US
NIH under RFA CA-95-011 and through cooperative agreements with members
of the Colon Cancer Family Registry and principal investigators of the
Australasian Colorectal Cancer Family Registry (US NIH, U01CA097735),
the Familial Colorectal Neoplasia Collaborative Group (US NIH,
U01CA074799) (University of Southern California), the Mayo Clinic
Cooperative Family Registry for Colon Cancer Studies (US NIH,
U01CA074800), the Ontario Registry for Studies of Familial Colorectal
Cancer (US NIH, U01CA074783), the Seattle Colorectal Cancer Family
Registry (US NIH, U01CA074794) and the University of Hawaii Colorectal
Cancer Family Registry (US NIH, U01CA074806). The GWAS work was
supported by a National Cancer Institute grant (US NIH, U01CA122839).
OFCCR was supported by a GL2 grant from the Ontario Research Fund,
Canadian Institutes of Health Research and a Cancer Risk Evaluation
(CaRE) Program grant from the Canadian Cancer Society Research
Institute. T.J. Hudson and B.W. Zanke are recipients of Senior
Investigator Awards from the Ontario Institute for Cancer Research,
through support from the Ontario Ministry of Economic Development and
Innovation. ASTERISK was funded by a Regional 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).; PLCO data sets were accessed
with approval through dbGaP (CGEMS prostate cancer scan,
phs000207.v1.p1; CGEMS pancreatic cancer scan, phs000206.v4.p3; and GWAS
of Lung Cancer and Smoking, phs000093.v2.p2, which was funded by Z01CP
010200, U01HG004446 and U01HG 004438 from the US NIH).
NR 63
TC 63
Z9 68
U1 2
U2 26
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 JUN
PY 2014
VL 46
IS 6
BP 533
EP 542
DI 10.1038/ng.2985
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700008
PM 24836286
ER
PT J
AU Gong, YX
Zack, TI
Morris, LGT
Lin, K
Hukkelhoven, E
Raheja, R
Tan, IL
Turcan, S
Veeriah, S
Meng, S
Viale, A
Schumacher, SE
Palmedo, P
Beroukhim, R
Chan, TA
AF Gong, Yongxing
Zack, Travis Ian
Morris, Luc G. T.
Lin, Kan
Hukkelhoven, Ellen
Raheja, Radhika
Tan, I-Li
Turcan, Sevin
Veeriah, Selvaraju
Meng, Shasha
Viale, Agnes
Schumacher, Steven E.
Palmedo, Perry
Beroukhim, Rameen
Chan, Timothy A.
TI Pan-cancer genetic analysis identifies PARK2 as a master regulator of
G1/S cyclins
SO NATURE GENETICS
LA English
DT Article
ID COPY-NUMBER ALTERATION; F-BOX PROTEINS; CELL-CYCLE; UBIQUITIN LIGASES;
MITOCHONDRIAL DEPOLARIZATION; COLORECTAL-CANCER; TUMOR-SUPPRESSOR;
BREAST-CANCER; DEGRADATION; D1
AB Coordinate control of different classes of cyclins is fundamentally important for cell cycle regulation and tumor suppression, yet the underlying mechanisms are incompletely understood. Here we show that the PARK2 tumor suppressor mediates this coordination. The PARK2 E3 ubiquitin ligase coordinately controls the stability of both cyclin D and cyclin E. Analysis of approximately 5,000 tumor genomes shows that PARK2 is a very frequently deleted gene in human cancer and uncovers a striking pattern of mutual exclusivity between PARK2 deletion and amplification of CCND1, CCNE1 or CDK4-implicating these genes in a common pathway. Inactivation of PARK2 results in the accumulation of cyclin D and acceleration of cell cycle progression. Furthermore, PARK2 is a component of a new class of cullin-RING-containing ubiquitin ligases targeting both cyclin D and cyclin E for degradation. Thus, PARK2 regulates cyclin-CDK complexes, as does the CDK inhibitor p16, but acts as a master regulator of the stability of G1/S cyclins.
C1 [Gong, Yongxing; Turcan, Sevin; Veeriah, Selvaraju; Meng, Shasha; Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Zack, Travis Ian; Schumacher, Steven E.; Palmedo, Perry; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA.
[Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Characterizat, Boston, MA 02115 USA.
[Zack, Travis Ian] Harvard Univ, Biophys Program, Boston, MA 02115 USA.
[Morris, Luc G. T.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Lin, Kan; Tan, I-Li] Weill Cornell Coll Med, New York, NY USA.
[Hukkelhoven, Ellen; Raheja, Radhika] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA.
[Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core, New York, NY 10021 USA.
[Palmedo, Perry] Harvard Univ, Ctr Biomed Informat, Boston, MA 02115 USA.
[Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA.
[Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA.
RP Chan, TA (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA.
EM chant@mskcc.org
OI Turcan, Sevin/0000-0002-0885-5607; Gong, Yongxing/0000-0003-1071-0375
FU US National Institutes of Health T32 grant [5T32CA160001]; US National
Institutes of Health [RO1 NS086875-01]; Memorial Sloan-Kettering Cancer
Center Brain Tumor Center; Sontag Foundation; Frederick Adler Fund
FX We thank E. Holland, A.C. Koff and J. Huse for helpful advice. S.T. was
a recipient of a US National Institutes of Health T32 grant
(5T32CA160001). This work was supported by the US National Institutes of
Health (RO1 NS086875-01) (T.A.C.), the Memorial Sloan-Kettering Cancer
Center Brain Tumor Center (T.A.C.), the Sontag Foundation (T.A.C.) and
the Frederick Adler Fund (T.A.C.).
NR 53
TC 40
Z9 40
U1 0
U2 10
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 JUN
PY 2014
VL 46
IS 6
BP 588
EP 594
DI 10.1038/ng.2981
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700015
PM 24793136
ER
PT J
AU Wang, YX
Marino-Enriquez, A
Bennett, RR
Zhu, MJ
Shen, YP
Eilers, G
Lee, JC
Henze, J
Fletcher, BS
Gu, ZZ
Fox, EA
Antonescu, CR
Fletcher, CDM
Guo, XQ
Raut, CP
Demetri, GD
van de Rijn, M
Ordog, T
Kunkel, LM
Fletcher, JA
AF Wang, Yuexiang
Marino-Enriquez, Adrian
Bennett, Richard R.
Zhu, Meijun
Shen, Yiping
Eilers, Grant
Lee, Jen-Chieh
Henze, Joern
Fletcher, Benjamin S.
Gu, Zhizhan
Fox, Edward A.
Antonescu, Cristina R.
Fletcher, Christopher D. M.
Guo, Xiangqian
Raut, Chandrajit P.
Demetri, George D.
van de Rijn, Matt
Ordog, Tamas
Kunkel, Louis M.
Fletcher, Jonathan A.
TI Dystrophin is a tumor suppressor in human cancers with myogenic programs
SO NATURE GENETICS
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; DUCHENNE MUSCULAR-DYSTROPHY;
GENE-THERAPY; RHABDOMYOSARCOMA; MUTATIONS; PROTEIN; LEIOMYOSARCOMA;
CHILDHOOD; PRODUCT; TARGETS
AB Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS), feature myogenic differentiation(1-3). Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in the non-neoplastic and benign counterparts of GIST, RMS and LMS tumors, and DMD deletions inactivate larger dystrophin isoforms, including 427-kDa dystrophin, while preserving the expression of an essential 71-kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence and invadopodia formation, and dystrophin inactivation was found in 96%, 100% and 62% of metastatic GIST, embryonal RMS and LMS samples, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in the treatment of cancer.
C1 [Wang, Yuexiang; Marino-Enriquez, Adrian; Zhu, Meijun; Eilers, Grant; Lee, Jen-Chieh; Henze, Joern; Fletcher, Benjamin S.; Fletcher, Christopher D. M.; Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wang, Yuexiang; Marino-Enriquez, Adrian; Zhu, Meijun; Eilers, Grant; Lee, Jen-Chieh; Henze, Joern; Fletcher, Benjamin S.; Gu, Zhizhan; Fletcher, Christopher D. M.; Raut, Chandrajit P.; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA USA.
[Bennett, Richard R.; Kunkel, Louis M.] Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA.
[Shen, Yiping] Childrens Hosp, Dept Lab Med, Genet Diagnost Lab, Boston, MA 02115 USA.
[Shen, Yiping] Jiaotong Univ, Shanghai Childrens Med Ctr, Dept Lab Med, Shanghai, Peoples R China.
[Lee, Jen-Chieh] Natl Taiwan Univ Hosp, Dept Pathol, Taipei 100, Taiwan.
[Gu, Zhizhan] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA.
[Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Guo, Xiangqian; van de Rijn, Matt] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA.
[Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Demetri, George D.] Harvard Univ, Sch Med, Ludwig Ctr Harvard, Boston, MA USA.
[Demetri, George D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ordog, Tamas] Mayo Clin, Ctr Individualized Med, Rochester, MN USA.
[Ordog, Tamas] Mayo Clin, Enter Neurosci Program, Rochester, MN USA.
[Ordog, Tamas] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA.
RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jfletcher@partners.org
OI Lee, Jen-Chieh/0000-0001-7739-5934
FU US National Institutes of Health [1P50CA127003-07, 1P50CA168512-01,
5R01DK058185-12]; Virginia and Daniel K. Ludwig Trust; GIST Cancer
Research Fund; Life Raft Group; Cesarini Pan-Mass Challenge for GIST;
Paul's Posse of the Pan-Mass Challenge; Bernard F. and Alva B. Gimbel
Foundation; Sarcoma Alliance for Research Through Collaboration; Erica
Kaitz LMS Research NOW Fund
FX We thank J. Tremblay (Quebec University Hospital) for the pCR3.1-miniDMD
construct; T. Taguchi (Kochi Medical School) for the GIST-T1 cell line;
Y. Hayashi, M. Bardsley and H. Qiu for their expert technical
assistance; and S. Bauer (West German Cancer Center) for useful
discussions and for funding support of J.H. This work was supported by
grants from the US National Institutes of Health, including
1P50CA127003-07 (J.A.F. and G.D.D.), 1P50CA168512-01 (J.A.F., G.D.D. and
A.M.-E.) and 5R01DK058185-12 (TO.), and by the Virginia and Daniel K.
Ludwig Trust for Cancer Research (J.A.F. and G.D.D.), the GIST Cancer
Research Fund (J.A.F.), the Life Raft Group (J.A.F., TO. and M.v.d.R.),
the Cesarini Pan-Mass Challenge for GIST (J.A.F. and G.D.D.), Paul's
Posse of the Pan-Mass Challenge (JAR and G.D.D.), the Bernard F. and
Alva B. Gimbel Foundation (L.M.K.), the Sarcoma Alliance for Research
Through Collaboration (A.M.-E.) and the Erica Kaitz LMS Research NOW
Fund (J.A.F., A.M.-E. and G.D.D.).
NR 40
TC 27
Z9 27
U1 0
U2 14
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 JUN
PY 2014
VL 46
IS 6
BP 601
EP 606
DI 10.1038/ng.2974
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700017
PM 24793134
ER
PT J
AU Lane, AA
Chapuy, B
Lin, CY
Tivey, T
Li, HB
Townsend, EC
van Bodegom, D
Day, TA
Wu, SC
Liu, HY
Yoda, A
Alexe, G
Schinzel, AC
Sullivan, TJ
Malinge, S
Taylor, JE
Stegmaier, K
Jaffe, JD
Bustin, M
te Kronnie, G
Izraeli, S
Harris, MH
Stevenson, KE
Neuberg, D
Silverman, LB
Sallan, SE
Bradner, JE
Hahn, WC
Crispino, JD
Pellman, D
Weinstock, DM
AF Lane, Andrew A.
Chapuy, Bjoern
Lin, Charles Y.
Tivey, Trevor
Li, Hubo
Townsend, Elizabeth C.
van Bodegom, Diederik
Day, Tovah A.
Wu, Shuo-Chieh
Liu, Huiyun
Yoda, Akinori
Alexe, Gabriela
Schinzel, Anna C.
Sullivan, Timothy J.
Malinge, Sebastien
Taylor, Jordan E.
Stegmaier, Kimberly
Jaffe, Jacob D.
Bustin, Michael
te Kronnie, Geertruy
Izraeli, Shai
Harris, Marian H.
Stevenson, Kristen E.
Neuberg, Donna
Silverman, Lewis B.
Sallan, Stephen E.
Bradner, James E.
Hahn, William C.
Crispino, John D.
Pellman, David
Weinstock, David M.
TI Triplication of a 21q22 region contributes to B cell transformation
through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation
SO NATURE GENETICS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; DOWN-SYNDROME;
EXPRESSION; CHROMATIN; CRLF2; GENE; TRISOMY-21; MUTATIONS; PROTEINS
AB Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL)1, and polysomy 21 is most frequent somatic aneuploidy among all B-ALLs(2). Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chromosome 21q22 confers mouse progenitor B cell self renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL fusion protein or CRLF2 with activated JAK2. Chromosome 21q22 triplication suppresses histone H3 Lys27 trimethylation (H3K27me3) in progenitor B cells and B-ALLs, and 'bivalent' genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Human B-ALLs with polysomy 21 are distinguished by their overexpression of genes marked with H3K27me3 in multiple cell types. Overexpression of HMGN1, a nucleosome remodeling protein encoded on chromosome 21q22 (refs. 3-5), suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo.
C1 [Lane, Andrew A.; Chapuy, Bjoern; Lin, Charles Y.; Tivey, Trevor; Townsend, Elizabeth C.; van Bodegom, Diederik; Day, Tovah A.; Wu, Shuo-Chieh; Liu, Huiyun; Yoda, Akinori; Schinzel, Anna C.; Bradner, James E.; Hahn, William C.; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Li, Hubo; Alexe, Gabriela; Silverman, Lewis B.; Sallan, Stephen E.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Schinzel, Anna C.; Taylor, Jordan E.; Stegmaier, Kimberly; Jaffe, Jacob D.; Hahn, William C.; Weinstock, David M.] Broad Inst, Cambridge, MA USA.
[Sullivan, Timothy J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Microarray Core, Boston, MA 02115 USA.
[Malinge, Sebastien] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France.
[Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[te Kronnie, Geertruy] Univ Padua, Dept Pediat, Padua, Italy.
[Izraeli, Shai] Chaim Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel.
[Izraeli, Shai] Tel Aviv Univ, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Harris, Marian H.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA.
[Stevenson, Kristen E.; Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Crispino, John D.] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA.
[Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Lane, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM andrew_lane@dfci.harvard.edu; dweinstock@partners.org
RI Bustin, Michael/G-6155-2015
OI Crispino, John/0000-0002-8182-8306;
FU Conquer Cancer Foundation; Lauri Strauss Leukemia Foundation; Leukemia
and Lymphoma Society; Alex Lemonade Stand Foundation; US Department of
Defense; Israel Science Foundation; US Israel Binational Foundation;
Stellato Fund; US National Institutes of Health/National Cancer
Institute [CA15198-01, CA172387-A01]
FX We thank N. Kopp and A. Schlauch for technical assistance, M. Busslinger
(Research Institute of Molecular Pathology, Vienna) for the
Pax5+/- mice and M. Oshimura (Tottori University) for A9
cells carrying human chromosome 21. This research was supported by the
Conquer Cancer Foundation (.A.A.L.), the Lauri Strauss Leukemia
Foundation (A.A.L.), the Leukemia and Lymphoma Society (A.A.L.), the
Alex Lemonade Stand Foundation (A.A.L., H. Li and D.P.), the US
Department of Defense (C.Y.L.), the Israel Science Foundation (S.I.),
the US Israel Binational Foundation (J.D.C. and S.I.), the Stellato Fund
(D.M.W.), US National Institutes of Health/National Cancer Institute R01
awards CA15198-01 and CA172387-A01 (D.M.W.) and a Translational Research
Award from the Leukemia and Lymphoma Society (J.D.C. and D.M.W.).
NR 31
TC 27
Z9 27
U1 2
U2 10
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 JUN
PY 2014
VL 46
IS 6
BP 618
EP 623
DI 10.1038/ng.2949
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700020
PM 24747640
ER
PT J
AU Cottini, F
Hideshima, T
Xu, CX
Sattler, M
Dori, M
Agnelli, L
ten Hacken, E
Bertilaccio, MT
Antonini, E
Neri, A
Ponzoni, M
Marcatti, M
Richardson, PG
Carrasco, R
Kimmelman, AC
Wong, KK
Caigaris-Cappio, F
Blandino, G
Kuehl, WM
Anderson, KC
Tonon, G
AF Cottini, Francesca
Hideshima, Teru
Xu, Chunxiao
Sattler, Martin
Dori, Martina
Agnelli, Luca
ten Hacken, Elisa
Bertilaccio, Maria Teresa
Antonini, Elena
Neri, Antonino
Ponzoni, Maurilio
Marcatti, Magda
Richardson, Paul G.
Carrasco, Ruben
Kimmelman, Alec C.
Wong, Kwok-Kin
Caigaris-Cappio, Federico
Blandino, Giovanni
Kuehl, W. Michael
Anderson, Kenneth C.
Tonon, Giovanni
TI Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis
in hematological cancers
SO NATURE MEDICINE
LA English
DT Article
ID YES-ASSOCIATED PROTEIN; ABL TYROSINE KINASE; C-ABL; MULTIPLE-MYELOMA;
TUMOR-SUPPRESSOR; P73; PATHWAY; PHOSPHORYLATION; TUMORIGENESIS;
ACTIVATION
AB Oncogene-induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and the mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies, including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53-independent, proapoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1-induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine-threonine kinase, STK4. Notably, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a new synthetic-lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels.
C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Cottini, Francesca; Dori, Martina; Antonini, Elena; Tonon, Giovanni] Ist Ricovero & Cura Carattere Sci IRCCS San Raffa, Div Mol Oncol, Funct Genom Canc Unit, Milan, Italy.
[Xu, Chunxiao; Sattler, Martin; Carrasco, Ruben; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Xu, Chunxiao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Xu, Chunxiao; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Agnelli, Luca; Neri, Antonino] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hematol Unit, Milan, Italy.
[ten Hacken, Elisa; Bertilaccio, Maria Teresa; Caigaris-Cappio, Federico] IRCCS San Raffaele Sci Inst, Div Mol Oncol, Lab Lymphoid Malignancies, Milan, Italy.
[Ponzoni, Maurilio] IRCCS San Raffaele Sci Inst, Myeloma Unit, Pathol Unit, Milan, Italy.
[Marcatti, Magda] IRCCS San Raffaele Sci Inst, Myeloma Unit, Dept Hematol Oncol, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.
[Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA.
[Caigaris-Cappio, Federico; Tonon, Giovanni] Univ Vita Salute San Raffaele, Milan, Italy.
[Caigaris-Cappio, Federico; Tonon, Giovanni] IRCCS San Raffaele Sci Inst, MAGIC Microenvironm & Genes Canc Blood Interdiv R, Milan, Italy.
[Blandino, Giovanni] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy.
[Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA.
EM kenneth_anderson@dfci.harvard.edu; tonon.giovanni@hsr.it
OI neri, antonino/0000-0001-9047-5912
FU Fondazione CARIPLO, a Marie Curie International Reintegration Grant;
Associazione Raliana per la Ricerca sul Cancro (AIRC); Special Program
Molecular Clinical Oncology [9965]; NIH [P50100707, PO-1 78378, RO-1
50947]
FX We thank M. Sudol (Mount Sinai School of Medicine) for the eGFP-YAP1
construct, W Hahn (Dana-Farber Cancer Institute) for pLKO.1 shRNA
lentiviral vectors and S. Rosen (Northwestern University) and R. Burger
(University of Kiel) for MM.1R and INA-6 MM cells. We also thank E. Di
Cairano and L. Spagnuolo for immunohistochemical stains, F. Ghini and
A.M. Gasparri for technical help, the Dana-Farber Cancer Institute Flow
cytometry facility, D. Kufe and F. Bernassola for insightful
suggestions, C. Brennan for the bioinformatics analysis and members of
the Anderson and Tonon lab for sharing reagents and critical reading of
the manuscript. W.M.K. is supported by the Intramural Research Program
of the US National Institutes of Health (NIH), National Cancer
Institute, Center for Cancer Research. This work was supported by
Fondazione CARIPLO, a Marie Curie International Reintegration Grant and
the Associazione Raliana per la Ricerca sul Cancro (AIRC; AIRC Special
Program Molecular Clinical Oncology, 5 per milk no. 9980 to A.N. and
Investigator Grants and Special Program Molecular Clinical Oncology, 5
per mile no. 9965 to G.T.) (G.T.). K.C.A. is an American Cancer Society
Clinical Research Professor and is supported by NIH grants NIH SPORE
P50100707, PO-1 78378 and RO-1 50947.
NR 38
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U1 4
U2 19
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 JUN
PY 2014
VL 20
IS 6
BP 599
EP 606
DI 10.1038/nm.3562
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA AI7LB
UT WOS:000337071000021
PM 24813251
ER
PT J
AU Van Allen, EM
Wagle, N
Stojanov, P
Perrin, DL
Cibulskis, K
Marlow, S
Jane-Valbuena, J
Friedrich, DC
Kryukov, G
Carter, SL
McKenna, A
Sivachenko, A
Rosenberg, M
Kiezun, A
Voet, D
Lawrence, M
Lichtenstein, LT
Gentry, JG
Huang, FW
Fostel, J
Farlow, D
Barbie, D
Gandhi, L
Lander, ES
Gray, SW
Joffe, S
Janne, P
Garber, J
MacConaill, L
Lindeman, N
Rollins, B
Kantoff, P
Fisher, SA
Gabriel, S
Getz, G
Garraway, LA
AF Van Allen, Eliezer M.
Wagle, Nikhil
Stojanov, Petar
Perrin, Danielle L.
Cibulskis, Kristian
Marlow, Sara
Jane-Valbuena, Judit
Friedrich, Dennis C.
Kryukov, Gregory
Carter, Scott L.
McKenna, Aaron
Sivachenko, Andrey
Rosenberg, Mara
Kiezun, Adam
Voet, Douglas
Lawrence, Michael
Lichtenstein, Lee T.
Gentry, Jeff G.
Huang, Franklin W.
Fostel, Jennifer
Farlow, Deborah
Barbie, David
Gandhi, Leena
Lander, Eric S.
Gray, Stacy W.
Joffe, Steven
Janne, Pasi
Garber, Judy
MacConaill, Laura
Lindeman, Neal
Rollins, Barrett
Kantoff, Philip
Fisher, Sheila A.
Gabriel, Stacey
Getz, Gad
Garraway, Levi A.
TI Whole-exome sequencing and clinical interpretation of formalin-fixed,
paraffin-embedded tumor samples to guide precision cancer medicine
SO NATURE MEDICINE
LA English
DT Article
ID SOMATIC MUTATIONS; LUNG ADENOCARCINOMA; LANDSCAPE; GENOME;
HETEROGENEITY; CARCINOMA; SPECIMENS; PLATFORM; CATALOG; TISSUE
AB Translating whole-exome sequencing (WES) for prospective clinical use may have an impact on the care of patients with cancer; however, multiple innovations are necessary for clinical implementation. These include rapid and robust WES of DNA derived from formalin-fixed, paraffin-embedded tumor tissue, analytical output similar to data from frozen samples and clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival formalin-fixed, paraffin-embedded tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a 'long tail' of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15 out of 16 patients. In one patient, previously undetected findings guided clinical trial enrollment, leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
C1 [Van Allen, Eliezer M.; Wagle, Nikhil; Stojanov, Petar; Marlow, Sara; Jane-Valbuena, Judit; Huang, Franklin W.; Barbie, David; Gandhi, Leena; Gray, Stacy W.; Joffe, Steven; Janne, Pasi; Garber, Judy; MacConaill, Laura; Lindeman, Neal; Rollins, Barrett; Kantoff, Philip; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Van Allen, Eliezer M.; Wagle, Nikhil; Stojanov, Petar; Perrin, Danielle L.; Cibulskis, Kristian; Marlow, Sara; Jane-Valbuena, Judit; Friedrich, Dennis C.; Kryukov, Gregory; Carter, Scott L.; McKenna, Aaron; Sivachenko, Andrey; Rosenberg, Mara; Kiezun, Adam; Voet, Douglas; Lawrence, Michael; Lichtenstein, Lee T.; Gentry, Jeff G.; Huang, Franklin W.; Fostel, Jennifer; Farlow, Deborah; Lander, Eric S.; Fisher, Sheila A.; Gabriel, Stacey; Getz, Gad; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[McKenna, Aaron] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Joffe, Steven] Childrens Hosp Boston, Boston, MA USA.
[MacConaill, Laura; Lindeman, Neal] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM gadgetz@broadinstitute.org; levi_garraway@dfci.harvard.edu
RI Kryukov, Gregory/A-9592-2008;
OI Gandhi, Leena/0000-0002-2398-9179; Joffe, Steven/0000-0002-0667-7384
FU Chair in Oncology at Massachusetts General Hospital; Starr Cancer
Foundation; Prostate Cancer Foundation; US National Institutes of Health
(NIH) NHGRI Clinical Sequencing Exploratory Research grant
[1U01HG006492]; NIH National Cancer Institute [1U24CA126546]; US
Department of Defense; NIH [U24CA143845]; Dana-Farber Leadership Council
FX We thank the patients and clinicians for their participation in this
project. We thank the Broad Genomics Platform (specifically K. Anderka,
A. Cheney, E. Wheeler, T. Mason and C. Crawford). We thank C. Sougnez
for facilitating data deposition. We also thank A. Lane and A. Yoda
(Dana-Farber Cancer Institute), for their contributions to the JAK3
experimental work: A. Lane provided Ba/F3 cells, and A. Yoda provided
murine stem cell virus puromycin vector. G.G. is partially funded by a
Paul C. Zamecnik, MD, Chair in Oncology at Massachusetts General
Hospital. This work was supported by the Starr Cancer Foundation
(L.A.G.), the Prostate Cancer Foundation (E.M.V.A. and L.A.G.), US
National Institutes of Health (NIH) NHGRI Clinical Sequencing
Exploratory Research grant 1U01HG006492 (L.A.G.), the NIH National
Cancer Institute grant 1U24CA126546 (L.A.G. and E.S.L.), the US
Department of Defense (L.A.G.), NIH U24CA143845 grant (G.G.) and the
Dana-Farber Leadership Council (E.M.V.A.).
NR 39
TC 123
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U1 7
U2 37
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 JUN
PY 2014
VL 20
IS 6
BP 682
EP 688
DI 10.1038/nm.3559
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA AI7LB
UT WOS:000337071000033
PM 24836576
ER
PT J
AU Guyette, JP
Gilpin, SE
Charest, JM
Tapias, LF
Ren, X
Ott, HC
AF Guyette, Jacques P.
Gilpin, Sarah E.
Charest, Jonathan M.
Tapias, Luis F.
Ren, Xi
Ott, Harald C.
TI Perfusion decellularization of whole organs
SO NATURE PROTOCOLS
LA English
DT Article
ID STEM-CELL DIFFERENTIATION; LUNG DE-CELLULARIZATION; SODIUM
DODECYL-SULFATE; EXTRACELLULAR-MATRIX; HEART-VALVES; IN-VITRO;
ORTHOTOPIC TRANSPLANTATION; MECHANICAL-PROPERTIES; RE-CELLULARIZATION;
PORCINE KIDNEYS
AB The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.
C1 [Guyette, Jacques P.; Gilpin, Sarah E.; Charest, Jonathan M.; Ren, Xi; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Guyette, Jacques P.; Gilpin, Sarah E.; Tapias, Luis F.; Ren, Xi; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA.
[Tapias, Luis F.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA.
[Ott, Harald C.] Harvard Stem Cell Inst, Boston, MA USA.
RP Ott, HC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
EM hott@mgh.harvard.edu
FU US National Institutes of Health (NIH) [DP2 0D008749-01, R21
HL108663-01, R01 HL108678]; Department of Surgery, Massachusetts General
Hospital; Harvard Stem Cell Institute; United Therapeutics Inc.
FX The present study was supported by the US National Institutes of Health
(NIH) Director's New Innovator Award DP2 0D008749-01, grants R21
HL108663-01 and R01 HL108678, by seed grants by the Department of
Surgery, Massachusetts General Hospital and the Harvard Stem Cell
Institute, and a research grant by United Therapeutics Inc. We thank
D.J. Mathisen and J.P. Vacanti for their mentorship and senior advice on
surgical procedures, tissue engineering aspects and for critical review
of the manuscript.
NR 54
TC 38
Z9 40
U1 4
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD JUN
PY 2014
VL 9
IS 6
BP 1451
EP 1468
DI 10.1038/nprot.2014.097
PG 18
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AI8FS
UT WOS:000337145800018
PM 24874812
ER
PT J
AU Kim, MN
Edlow, BL
Durduran, T
Frangos, S
Mesquita, RC
Levine, JM
Greenberg, JH
Yodh, AG
Detre, JA
AF Kim, Meeri N.
Edlow, Brian L.
Durduran, Turgut
Frangos, Suzanne
Mesquita, Rickson C.
Levine, Joshua M.
Greenberg, Joel H.
Yodh, Arjun G.
Detre, John A.
TI Continuous Optical Monitoring of Cerebral Hemodynamics During
Head-of-Bed Manipulation in Brain-Injured Adults
SO NEUROCRITICAL CARE
LA English
DT Article
DE Diffuse correlation spectroscopy; Near-infrared spectroscopy; Diffuse
optical spectroscopy; Head-of-bed; Cerebral blood flow; Neurocritical
care; Cerebral hemodynamics
ID DIFFUSE CORRELATION SPECTROSCOPY; ANEURYSMAL SUBARACHNOID HEMORRHAGE;
TRANSCRANIAL DOPPLER ULTRASOUND; BLOOD-FLOW; PERFUSION-PRESSURE;
INTRACRANIAL-PRESSURE; AUTOREGULATION; RESPONSES; CIRCULATION;
VALIDATION
AB Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering.
Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30A degrees and then at 0A degrees. Relative CBF (rCBF) and concurrent changes in oxy- (Delta HbO(2)), deoxy- (Delta Hb), and total-hemoglobin concentrations (Delta THC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed.
rCBF, Delta HbO(2), and Delta THC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 +/- A 28.2 %, P = 0.938). rCBF increased in controls (18.6 +/- A 9.4 %, P < 0.001). Delta HbO(2), Delta Hb, and Delta THC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure.
DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.
C1 [Kim, Meeri N.; Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
[Edlow, Brian L.; Levine, Joshua M.; Greenberg, Joel H.; Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Edlow, Brian L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Durduran, Turgut] Mediterranean Technol Pk, ICFO Inst Ciencies Foton, Barcelona 08860, Spain.
[Frangos, Suzanne; Levine, Joshua M.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.
[Mesquita, Rickson C.] Univ Campinas UNICAMP, Inst Phys, BR-13083859 Campinas, SP, Brazil.
[Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RP Kim, MN (reprint author), Univ Penn, Dept Phys & Astron, 209 South 33rd St, Philadelphia, PA 19104 USA.
EM meeri@alumni.upenn.edu
RI FAPESP, BRAINN/J-4049-2015; Durduran, Turgut/N-7768-2015; Inst. of
Physics, Gleb Wataghin/A-9780-2017;
OI Durduran, Turgut/0000-0001-5838-1027; Mesquita,
Rickson/0000-0003-1945-6713
FU National Institute of Heath [NS-054575, NS-060653, NS-045839, HL077699,
RR-02305, R25-NS065743]; Fundacio Cellex Barcelona; Marie Curie IRG
(FP7, RPTAMON); Institute de Salud Carlos III (DOMMON, FIS); Ministerio
de Ciencia e Innovacion (MICINN); Ministerio de Economia y
Comepetitividad; Institucio CERCA (DOCNEURO) [PROVAT-002-11];
Generalitat de Catalunya, European Regional Development Fund
(FEDER/ERDF); LASERLAB (FP7); Photonics4Life (FP7) consortia
FX Sources of Support (if applicable): Name(s) of Grantor(s), Grant or
contract numbers, name of author who received the funding, and specific
material support given: National Institute of Heath: NS-054575 (JAD),
NS-060653 (AGY), NS-045839 (JAD), HL077699 (AGY), RR-02305 (AGY, JAD),
R25-NS065743 (BLE). TD gratefully acknowledged partial support by
Fundacio Cellex Barcelona, Marie Curie IRG (FP7, RPTAMON), Institute de
Salud Carlos III (DOMMON, FIS), Ministerio de Ciencia e Innovacion
(MICINN), Ministerio de Economia y Comepetitividad, Institucio CERCA
(DOCNEURO, PROVAT-002-11), Generalitat de Catalunya, European Regional
Development Fund (FEDER/ERDF) and LASERLAB (FP7) and Photonics4Life
(FP7) consortia. University of Pennsylvania Research Foundation (JHG).
Financial Disclosure AGY, JAD, JHG, TD are co-inventors on patents
related to the optical technology. However, they do not receive any
income or royalties from those patents.
NR 52
TC 12
Z9 12
U1 0
U2 15
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
EI 1556-0961
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD JUN
PY 2014
VL 20
IS 3
BP 443
EP 453
DI 10.1007/s12028-013-9849-7
PG 11
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA AI7RH
UT WOS:000337092900013
PM 23653267
ER
PT J
AU Qureshi, AI
Majidi, S
Gilani, WI
Palesch, YY
Martin, R
Novitzke, J
Cruz-Flores, S
Ehtisham, A
Goldstein, JN
Kirmani, JF
Hussein, HM
Suri, MFK
Tariq, N
AF Qureshi, Adnan I.
Majidi, Shahram
Gilani, Waqas I.
Palesch, Yuko Y.
Martin, Renee
Novitzke, Jill
Cruz-Flores, Salvador
Ehtisham, Asad
Goldstein, Joshua N.
Kirmani, Jawad F.
Hussein, Haitham M.
Suri, M. Fareed K.
Tariq, Nauman
TI Increased Brain Volume Among Good Grade Patients with Intracerebral
Hemorrhage. Results from the Antihypertensive Treatment of Acute
Cerebral Hemorrhage (ATACH) Study
SO NEUROCRITICAL CARE
LA English
DT Article
DE Intracerebral hemorrhage; Edema; Computed tomography; Brain volume
ID PERIHEMATOMAL EDEMA; ACUTE STROKE; RAT MODEL; INJURY
AB We ascertained the occurrence of global cerebral edema manifesting as increased brain volume in subjects with intracerebral hemorrhage (ICH) and explored the relationship between subject characteristics and three month outcomes.
A post-hoc analysis of a multicenter prospective study that recruited patients with ICH, elevated SBP a parts per thousand yen170 mm Hg, and Glasgow Coma Scale (GCS) score a parts per thousand yen8, who presented within 6 h of symptom onset was performed. Computed tomographic (CT) scans at baseline and 24 h, submitted to a core image laboratory, were analyzed to measure total brain, hematoma, and perihematoma edema volumes from baseline and 24-h CT scans using image analysis software. The increased brain volume was determined by subtracting the hematoma and perihematomal edema volumes from the total brain volume.
A total of 18 (44 %) of 41 subjects had increased brain volume that developed between initial CT scan and 24-h CT scan. The median increase in brain volume among the 18 subjects was 35 cc ranging from 0.12 to 296 cc. The median baseline GCS score was 15 in both groups of subjects who experienced increased brain volume and those who did not, and the median hematoma volume was 10.18 and 6.73, respectively. Three of the 18 subjects with increased brain volume underwent concurrent neurological deterioration and one subject died during hospitalization.
We found preliminary evidence of increased cerebral brain volume in subjects with good grade and small ICHs, which may be suggestive of global cerebral edema.
C1 [Qureshi, Adnan I.; Majidi, Shahram; Gilani, Waqas I.; Novitzke, Jill; Suri, M. Fareed K.; Tariq, Nauman] Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, Minneapolis, MN 55455 USA.
[Palesch, Yuko Y.; Martin, Renee] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Cruz-Flores, Salvador] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA.
[Ehtisham, Asad] Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Kirmani, Jawad F.] John F Kennedy Med Ctr, Neurosci Inst, Edison, NJ USA.
[Hussein, Haitham M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
RP Qureshi, AI (reprint author), Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, 420 Delaware St SE,MMC 295, Minneapolis, MN 55455 USA.
EM aiqureshi@hotmail.com
RI Goldstein, Joshua/H-8953-2016
FU National Institutes of Health [RO1-NS44976-01A2]; American Heart
Association [0840053N]; National Institute of Health
[U01-NS062091-01A2]; Minnesota Medical Foundation, Minneapolis, MN
FX Dr. Qureshi has received funding from the National Institutes of Health
RO1-NS44976-01A2 (medication provided by ESP Parma), American Heart
Association Established Investigator Award 0840053N, National Institute
of Health U01-NS062091-01A2, and the Minnesota Medical Foundation,
Minneapolis, MN.
NR 25
TC 5
Z9 5
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
EI 1556-0961
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD JUN
PY 2014
VL 20
IS 3
BP 470
EP 475
DI 10.1007/s12028-013-9842-1
PG 6
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA AI7RH
UT WOS:000337092900017
PM 23609118
ER
PT J
AU Moonen, AJH
Wijers, A
Leentjens, AFG
Christine, CW
Factor, SA
Juncos, J
Lyness, JM
Marsh, L
Panisset, M
Pfeiffer, R
Rottenberg, D
Ramos, CS
Shulman, L
Singer, C
Slevin, J
McDonald, W
Auinger, P
Richard, IH
AF Moonen, A. J. H.
Wijers, A.
Leentjens, A. F. G.
Christine, C. W.
Factor, S. A.
Juncos, J.
Lyness, J. M.
Marsh, L.
Panisset, M.
Pfeiffer, R.
Rottenberg, D.
Ramos, C. Serrano
Shulman, L.
Singer, C.
Slevin, J.
McDonald, W.
Auinger, P.
Richard, I. H.
TI Severity of depression and anxiety are predictors of response to
antidepressant treatment in Parkinson's disease
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease; Depression; Clinical trials randomized controlled;
Venlafaxine; Paroxetine
ID DATABASE; PLACEBO
AB Background: Antidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD). Objective: To identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients.
Methods: A secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables.
Results: In both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response.
Conclusions: Higher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Moonen, A. J. H.; Wijers, A.; Leentjens, A. F. G.] Maastricht Univ, Dept Psychiat, NL-6200 MD Maastricht, Netherlands.
[Christine, C. W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Factor, S. A.; Juncos, J.] Emory Univ, Dept Neurol, Atlanta, GA USA.
[McDonald, W.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Marsh, L.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[Marsh, L.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA.
[Marsh, L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Panisset, M.] Univ Montreal, Dept Neurol, Montreal, PQ, Canada.
[Pfeiffer, R.] Univ Tennessee, Dept Neurol, Hlth Sci Ctr, Memphis, TN USA.
[Rottenberg, D.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA.
[Rottenberg, D.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA.
[Ramos, C. Serrano] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA.
[Shulman, L.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Singer, C.] Univ Miami, Dept Neurol, Leonard M Miller Sch Med, Miami, FL USA.
[Slevin, J.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA.
[Lyness, J. M.; Auinger, P.; Richard, I. H.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
RP Moonen, AJH (reprint author), Maastricht Univ, Dept Psychiat, POB 616, NL-6200 MD Maastricht, Netherlands.
EM anja.moonen@maastrichtuniversity.nl
FU National Institutes of Health/National Institute of Neurological
Disorders and Stroke [R01 N5046487]; General Clinical Research Center at
Johns Hopkins University School of Medicine (National Center for
Research Resources/NIH) [M01-RR00052]
FX This study was funded by National Institutes of Health/National
Institute of Neurological Disorders and Stroke grant R01 N5046487 and
the General Clinical Research Center at Johns Hopkins University School
of Medicine (National Center for Research Resources/NIH M01-RR00052).
Wyeth Pharmaceuticals provided venlafaxine extended release and matching
placebo. Glaxo-Smith-Kline provided paroxetine.
NR 10
TC 5
Z9 6
U1 0
U2 5
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 JUN
PY 2014
VL 20
IS 6
BP 644
EP 646
DI 10.1016/j.parkreldis.2014.02.025
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA AI5AN
UT WOS:000336877900016
PM 24679737
ER
PT J
AU Khodjaev, SD
Teerlink, JR
Malik, FI
AF Khodjaev, Soidjon D.
Teerlink, John R.
Malik, Fady I.
TI Novel drug mechanisms in development for heart failure
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Review
DE BAY 94-8862; Heart failure; LCZ696; Omecamtiv mecarbil; Pharmacologic
therapy; Serelaxin; TRV 027; Ularitide
ID CARDIAC MYOSIN ACTIVATOR; DOUBLE-BLIND; MINERALOCORTICOID RECEPTOR;
OMECAMTIV-MECARBIL; NATRIURETIC PEPTIDES; CONTROLLED-TRIAL; HORMONE
RELAXIN; BAY 94-8862; TASK-FORCE; URODILATIN
AB Heart failure therapy has seen many advances over the last 40 years and has rapidly expanded beyond diuretics and digoxin to include several new mechanisms of action and devices whose efficacy had been demonstrated in large clinical trials. The evidence for their use is thoroughly summarized and discussed in current heart failure treatment guidelines and is not the subject of this review. Despite these advances, the mortality and morbidity in heart failure patients is still substantial, and there remains a need to develop new heart failure therapies. Recognizing that advances in medical therapy are often driven by the introduction of drugs with novel mechanisms of action, here we provide an overview of investigative heart failure drugs with novel mechanisms of action that are the subject of ongoing clinical trials.
C1 [Khodjaev, Soidjon D.; Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA.
[Khodjaev, Soidjon D.; Teerlink, John R.; Malik, Fady I.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Malik, Fady I.] Cytokinet Inc, Res & Early Dev, San Francisco, CA USA.
RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol Sect, 111C,4150 Clement St, San Francisco, CA 94121 USA.
EM john.teerlink@ucsf.edu
NR 42
TC 0
Z9 0
U1 3
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
EI 1432-2013
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD JUN
PY 2014
VL 466
IS 6
BP 1219
EP 1225
DI 10.1007/s00424-014-1528-9
PG 7
WC Physiology
SC Physiology
GA AI4AO
UT WOS:000336807700018
PM 24793049
ER
PT J
AU Yang, ZR
Wang, C
Zhou, QX
An, JL
Hildebrandt, E
Aleksandrov, LA
Kappes, JC
DeLucas, LJ
Riordan, JR
Urbatsch, IL
Hunt, JF
Brouillette, CG
AF Yang, Zhengrong
Wang, Chi
Zhou, Qingxian
An, Jianli
Hildebrandt, Ellen
Aleksandrov, Luba A.
Kappes, John C.
DeLucas, Lawrence J.
Riordan, John R.
Urbatsch, Ina L.
Hunt, John F.
Brouillette, Christie G.
TI Membrane protein stability can be compromised by detergent interactions
with the extramembranous soluble domains
SO PROTEIN SCIENCE
LA English
DT Review
DE CFTR; NBD1; DSC; CD; thermal unfolding; detergent interaction; membrane
protein; extramembrane domain; soluble domain
ID TRANSMEMBRANE CONDUCTANCE REGULATOR; NUCLEOTIDE-BINDING DOMAIN;
DIFFERENTIAL SCANNING CALORIMETRY; CYSTIC-FIBROSIS MUTATION;
CYTOCHROME-C-OXIDASE; FULL-LENGTH CFTR; DELTA-F508 MUTATION; SURFACTANT
INTERACTIONS; ESCHERICHIA-COLI; EFFICIENT PURIFICATION
AB Detergent interaction with extramembranous soluble domains (ESDs) is not commonly considered an important determinant of integral membrane protein (IMP) behavior during purification and crystallization, even though ESDs contribute to the stability of many IMPs. Here we demonstrate that some generally nondenaturing detergents critically destabilize a model ESD, the first nucleotide-binding domain (NBD1) from the human cystic fibrosis transmembrane conductance regulator (CFTR), a model IMP. Notably, the detergents show equivalent trends in their influence on the stability of isolated NBD1 and full-length CFTR. We used differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy to monitor changes in NBD1 stability and secondary structure, respectively, during titration with a series of detergents. Their effective harshness in these assays mirrors that widely accepted for their interaction with IMPs, i.e., anionic>zwitterionic>nonionic. It is noteworthy that including lipids or nonionic detergents is shown to mitigate detergent harshness, as will limiting contact time. We infer three thermodynamic mechanisms from the observed thermal destabilization by monomer or micelle: (i) binding to the unfolded state with no change in the native structure (all detergent classes); (ii) native state binding that alters thermodynamic properties and perhaps conformation (nonionic detergents); and (iii) detergent binding that directly leads to denaturation of the native state (anionic and zwitterionic). These results demonstrate that the accepted model for the harshness of detergents applies to their interaction with an ESD. It is concluded that destabilization of extramembranous soluble domains by specific detergents will influence the stability of some IMPs during purification.
C1 [Yang, Zhengrong; Brouillette, Christie G.] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA.
[Yang, Zhengrong; Zhou, Qingxian; An, Jianli; DeLucas, Lawrence J.; Brouillette, Christie G.] Univ Alabama Birmingham, Struct Biol Ctr, Birmingham, AL USA.
[Wang, Chi; Hunt, John F.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Hildebrandt, Ellen; Urbatsch, Ina L.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA.
[Aleksandrov, Luba A.; Riordan, John R.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA.
[Aleksandrov, Luba A.; Riordan, John R.] Univ N Carolina, Cyst Fibrosis Treatment & Res Ctr, Chapel Hill, NC USA.
[Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA.
[DeLucas, Lawrence J.] Univ Alabama Birmingham, Dept Optometry, Birmingham, AL USA.
[Urbatsch, Ina L.] Texas Tech Univ, Hlth Sci Ctr, Ctr Membrane Prot Res, Lubbock, TX 79430 USA.
RP Brouillette, CG (reprint author), 1025 18th St South,234 CBSE, Birmingham, AL 35294 USA.
EM jfhunt@biology.columbia.edu; christie@uab.edu
FU CFFT; NIH [R01 DK051619, R0 1DK051870, P01 HL110873]; Shared Facility
Program of the UAB Comprehensive Cancer Center [316851]
FX Grant sponsor: CFFT (to C. B., J.H., I. U., J.R., L. D., and J.K.).
Grant sponsor: NIH R01 DK051619; R0 1DK051870; P01 HL110873 (to J.R.).
Grant sponsor: Shared Facility Program of the UAB Comprehensive Cancer
Center; Grant number: 316851.
NR 102
TC 11
Z9 11
U1 2
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD JUN
PY 2014
VL 23
IS 6
BP 769
EP 789
DI 10.1002/pro.2460
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI4NW
UT WOS:000336843100010
PM 24652590
ER
PT J
AU Halpern, EF
AF Halpern, Elkan F.
TI Behind the Numbers: Inverse Probability Weighting
SO RADIOLOGY
LA English
DT Editorial Material
AB Inverse probability weighting is a propensity score-based technique that can be used to compensate for imbalance in study groups. It is an alternative to regression-based adjustment of the outcomes. It has advantages over matching of cases on the basis of propensity scores when there are more than two groups to compare, when finding matches results in insufficient sample sizes, or when the data are censored. However, it can create artificial imbalance unless it is applied carefully. In this article, an introduction to inverse probability weighting is provided by using the Yang et al study published in this issue of Radiology as an example.
C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
RP Halpern, EF (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St, Boston, MA 02114 USA.
EM elk@mgh-ita.org
NR 6
TC 3
Z9 3
U1 0
U2 1
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 JUN
PY 2014
VL 271
IS 3
BP 625
EP 628
DI 10.1148/radiol.14140035
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI5GW
UT WOS:000336894600002
PM 24848956
ER
PT J
AU Kopans, DB
AF Kopans, Daniel B.
TI A New Era in Mammography Screening
SO RADIOLOGY
LA English
DT Editorial Material
ID DIGITAL BREAST TOMOSYNTHESIS; CANCER; WOMEN; CALCIFICATIONS; EXPERIENCE;
VIEWS; TIME
C1 Harvard Univ, Dept Radiol, Breast Imaging Div, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA.
RP Kopans, DB (reprint author), Harvard Univ, Dept Radiol, Breast Imaging Div, Massachusetts Gen Hosp,Sch Med, 15 Parkman St,Ambulatory Care Bldg,Suite 219, Boston, MA 02114 USA.
EM dkopans@partners.org
NR 31
TC 2
Z9 2
U1 0
U2 8
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 JUN
PY 2014
VL 271
IS 3
BP 629
EP 631
DI 10.1148/radiol.14140177
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI5GW
UT WOS:000336894600003
PM 24848957
ER
PT J
AU Sheth, RA
Heidari, P
Esfahani, SA
Wood, BJ
Mahmood, U
AF Sheth, Rahul A.
Heidari, Pedram
Esfahani, Shadi A.
Wood, Bradford J.
Mahmood, Umar
TI Interventional Optical Molecular Imaging Guidance during Percutaneous
Biopsy
SO RADIOLOGY
LA English
DT Article
ID INDOCYANINE GREEN; FLUORESCENCE; ENDOSCOPY
AB Purpose: To investigate indocyanine green (ICG) as a molecular beacon for malignant lesions within the liver and evaluate the ability of a developed handheld imaging system to allow measurement of ICG fluorescence within focal hepatic lesions with high target-to-background ratios in a mouse model.
Materials and Methods: All animal experiments were approved by the institutional animal care committee. A handheld optical molecular imaging device was constructed to pass through the introducer needle of a standard percutaneous biopsy kit. An ex vivo phantom system was constructed to quantify tissue attenuation properties of ICG in liver parenchyma. Subsequently, intrahepatic colorectal cancer metastases were generated in nude mice, and epifluorescence imaging of ICG, as well as histologic analysis of the explanted livers, was performed at 3 weeks after implantation (n = 6). Epifluorescence imaging with the handheld imaging device was then performed on intrahepatic colorectal metastases after the administration of ICG (n = 15) at 3, 6, and 24 hours after injection. Target-to-background ratios were calculated for each time point. Subsequently, a core biopsy of intrahepatic colorectal metastases was performed by using a standard clinical 18-gauge biopsy needle.
Results: There was avid localization of ICG to the focal lesions at all time points. Similarly, fluorescence within the tumors was greater than that within normal liver, as detected with the handheld imaging system (mean target-to-background ratio +/- standard deviation, 3.9 +/- 0.2 at 24 hours). A core biopsy of tumor and normal adjacent liver by using a standard biopsy needle demonstrated a sharp margin of fluorescence intensity at the tumor-liver interface.
Conclusion: The custom-designed molecular imaging device, in combination with ICG, readily allowed differentiation between normal and malignant tissue in a murine model of intrahepatic colorectal metastasis. (C) RSNA, 2014
C1 [Sheth, Rahul A.; Heidari, Pedram; Esfahani, Shadi A.; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA.
[Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD USA.
[Wood, Bradford J.] NCI, NIH, Bethesda, MD 20892 USA.
RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA.
EM umah-mood@mgh.harvard.edu
FU National Institutes of Health [U01CA084301]
FX This research was supported by the National Institutes of Health (grant
U01CA084301).
NR 14
TC 10
Z9 13
U1 0
U2 5
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 JUN
PY 2014
VL 271
IS 3
BP 770
EP 777
DI 10.1148/radiol.14131880
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI5GW
UT WOS:000336894600018
PM 24520946
ER
PT J
AU Davis, LA
Whitfield, E
Cannon, GW
Wolff, RK
Johnson, DS
Reimold, AM
Kerr, GS
Richards, JS
Mikuls, TR
Caplan, L
AF Davis, Lisa A.
Whitfield, Emily
Cannon, Grant W.
Wolff, Roger K.
Johnson, Dannette S.
Reimold, Andreas M.
Kerr, Gail S.
Richards, J. Steuart
Mikuls, Ted R.
Caplan, Liron
TI Association of rheumatoid arthritis susceptibility gene with lipid
profiles in patients with rheumatoid arthritis
SO RHEUMATOLOGY
LA English
DT Article
DE arthritis; rheumatoid; polymorphism; single nucleotide; cholesterol;
HDL; LDL; triglycerides
ID NF-KAPPA-B; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR
RISK-FACTORS; C-REL; DISEASE SUSCEPTIBILITY; MYOCARDIAL-INFARCTION;
VASCULAR-DISEASE; NUCLEAR-FACTOR; POLYMORPHISM; TRANSCRIPTION
AB Objective. RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects.
Methods. Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethyl-glutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF-alpha and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified Charlson-Deyo comorbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels.
Results. The REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI.
Conclusion. The REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry.
C1 [Davis, Lisa A.] Univ Colorado, Sch Med, Dept Med, Div Rheumatol,Denver Hlth Med Ctr, Denver, CO USA.
[Whitfield, Emily; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol,Denver Vet Affairs Med Ctr VAMC, Denver, CO USA.
[Davis, Lisa A.; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Denver, CO USA.
[Whitfield, Emily] Denver VAMC, Dept Res, Div Care Coordinat, Denver, CO USA.
[Cannon, Grant W.] George E Wahlen VAMC, Staff Acad Affiliat, Salt Lake City, UT USA.
[Cannon, Grant W.] Univ Utah, Sch Med, Dept Med, Div Rheumatol, Salt Lake City, UT USA.
[Wolff, Roger K.] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT USA.
[Johnson, Dannette S.] Jackson VAMC, Med Serv, Rheumatol Sect, Jackson, MS USA.
[Johnson, Dannette S.] Univ Mississippi, Dept Internal Med, Div Rheumatol & Mol Immunol, Jackson, MS 39216 USA.
[Reimold, Andreas M.] Dallas VAMC, Med Serv, Rheumatol Sect, Dallas, TX USA.
[Reimold, Andreas M.] Univ Texas Dallas, SW Med Ctr, Dept Internal Med, Dallas, TX USA.
[Kerr, Gail S.; Richards, J. Steuart] VAMC, Med Serv, Rheumatol Sect, Washington, DC USA.
[Kerr, Gail S.; Richards, J. Steuart] Georgetown Univ, Dept Med, Div Rheumatol, Washington, DC USA.
[Mikuls, Ted R.] Omaha VAMC, Med Serv, Rheumatol Sect, Omaha, NE USA.
[Mikuls, Ted R.] Univ Nebraska Med Ctr, Nebraska Arthrit Outcomes Res Ctr, Omaha, NE USA.
RP Davis, LA (reprint author), Denver Hlth & Hosp Author, 777 Bannock St,MC 4000, Denver, CO 80204 USA.
EM lisa.davis@ucdenver.edu
FU Veterans Affairs Health Services Research and Development Grant [SHP
08-172]; University of Colorado Denver, Division of Rheumatology;
National Institutes of Health/National Institute of Arthritis and
Musculoskeletal and Skin Diseases [T32 AR007534-24]; National Institutes
of Health Loan Repayment Award; Rheumatology Research Foundation
Rheumatology Scientist Development Award; Denver Health and Hospital
Authority; University of Colorado; Colorado Clinical and Translational
Science Institute; Veterans Affairs Health Services Research and
Development Career Development Award [CDA 07-221]
FX This work, including the genotyping, was supported by a Veterans Affairs
Health Services Research and Development Grant (SHP 08-172) and the
University of Colorado Denver, Division of Rheumatology. L.D. received
support from the National Institutes of Health/National Institute of
Arthritis and Musculoskeletal and Skin Diseases (T32 AR007534-24),
National Institutes of Health Loan Repayment Award, the Rheumatology
Research Foundation Rheumatology Scientist Development Award, Denver
Health and Hospital Authority, the University of Colorado and the
Colorado Clinical and Translational Science Institute. L.C. received
support from a Veterans Affairs Health Services Research and Development
Career Development Award (CDA 07-221). The funding sources had no role
in the design, collection, analysis, interpretation of data, writing of
the report or decision to submit this article for publication. The views
expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs or US government. All investigators participating in this
research had access to all data. We declare that we (and our spouses,
partners and children under 18 years of age) have no financial or
personal relationships with other people or organizations that could
inappropriately influence (bias) this work, including employment,
consultancies, stock ownership, honoraria, paid expert testimony,
patents or patent applications and travel grants, within 5 years of
beginning the work submitted.
NR 49
TC 5
Z9 5
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD JUN
PY 2014
VL 53
IS 6
BP 1014
EP 1021
DI 10.1093/rheumatology/ket472
PG 8
WC Rheumatology
SC Rheumatology
GA AI6KJ
UT WOS:000336982600008
PM 24489016
ER
PT J
AU Shinozaki, S
Chang, K
Sakai, M
Shimizu, N
Shimokado, K
Stamler, J
Kaneki, M
AF Shinozaki, S.
Chang, K.
Sakai, M.
Shimizu, N.
Shimokado, K.
Stamler, J.
Kaneki, M.
TI S-NITROSYLATION OF THE CXXC ZINC FINGER MOTIF IN SIRT1 MEDIATES AND
ENHANCES NITROSATIVE STRESS IN ENDOTOXIN-INDUCED LIVER APOPTOSIS AND
INFLAMMATION: PROTECTIVE ROLE OF S-NITROSOGLUTATHIONE REDUCTASE
SO SHOCK
LA English
DT Meeting Abstract
CT 37th Annual Conference of the Shock-Society on Shock
CY JUN 07-10, 2014
CL Charlotte, NC
SP Shock Soc
C1 [Shinozaki, S.; Chang, K.; Sakai, M.; Shimizu, N.; Kaneki, M.] Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp, Charlestown, MA USA.
[Shinozaki, S.; Shimokado, K.] Tokyo Med & Dent Univ, Grad Sch, Dept Geriatr & Vasc Med, Tokyo, Japan.
[Chang, K.] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Stamler, J.] Case Western Reserve Univ, Inst Transformat Mol Med, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
SU 2
BP 22
EP 23
PG 2
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AI6ET
UT WOS:000336964600031
ER
PT J
AU Hafner, S
Matallo, J
Groger, M
Wachter, U
McCook, O
Wood, M
Whiteman, M
Georgieff, M
Calzia, E
Radermacher, P
Wepler, M
AF Hafner, S.
Matallo, J.
Groeger, M.
Wachter, U.
McCook, O.
Wood, M.
Whiteman, M.
Georgieff, M.
Calzia, E.
Radermacher, P.
Wepler, M.
TI EFFECTS OF THE SLOW-RELEASING SULFIDE DONOR GYY4137 DURING RESUSCITATED
SEPTIC SHOCK IN ATHEROSCLEROTIC SWINE
SO SHOCK
LA English
DT Meeting Abstract
CT 37th Annual Conference of the Shock-Society on Shock
CY JUN 07-10, 2014
CL Charlotte, NC
SP Shock Soc
C1 [Hafner, S.; Matallo, J.; Groeger, M.; Wachter, U.; McCook, O.; Georgieff, M.; Calzia, E.; Radermacher, P.; Wepler, M.] Univ Ulm Klinikum, Anasthesiol Klin, Sekt APV, Ulm, Germany.
[Wood, M.] Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England.
[Whiteman, M.] Univ Exeter, Sch Med, Exeter, Devon, England.
[Wepler, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RI Whiteman, Matthew/C-6079-2009
OI Whiteman, Matthew/0000-0002-6583-6779
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
SU 2
BP 53
EP 54
PG 2
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AI6ET
UT WOS:000336964600117
ER
PT J
AU Matallo, J
Radermacher, P
McCook, O
Calzia, E
Wepler, M
Hafner, S
AF Matallo, J.
Radermacher, P.
McCook, O.
Calzia, E.
Wepler, M.
Hafner, S.
TI CHARACTERIZATION OF LEFT VENTRICULAR FUNCTION DURING SEPTIC SHOCK IN
ATHEROSCLEROTIC SWINE
SO SHOCK
LA English
DT Meeting Abstract
CT 37th Annual Conference of the Shock-Society on Shock
CY JUN 07-10, 2014
CL Charlotte, NC
SP Shock Soc
C1 [Matallo, J.; Radermacher, P.; McCook, O.; Calzia, E.; Hafner, S.] Univ Ulm, D-89069 Ulm, Germany.
[Wepler, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 5
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
SU 2
BP 60
EP 60
PG 1
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AI6ET
UT WOS:000336964600135
ER
PT J
AU Li, D
Zou, L
Feng, Y
Gong, Y
Cai, J
Chao, W
AF Li, D.
Zou, L.
Feng, Y.
Gong, Y.
Cai, J.
Chao, W.
TI TOLL-LIKE RECEPTORS UP-REGULATE COMPLEMENT FACTOR B VIA NF-kappa B
PATHWAY IN HUMAN KIDNEY TUBULAR CELLS
SO SHOCK
LA English
DT Meeting Abstract
CT 37th Annual Conference of the Shock-Society on Shock
CY JUN 07-10, 2014
CL Charlotte, NC
SP Shock Soc
C1 [Li, D.; Zou, L.; Feng, Y.; Gong, Y.; Cai, J.; Chao, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Li, D.] Xiangya 3rd Hosp, Changsha, Hunan, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
SU 2
BP 71
EP 71
PG 1
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AI6ET
UT WOS:000336964600165
ER
PT J
AU Hafner, S
Wepler, M
Matallo, J
Groger, M
Wagner, K
McCook, O
Huber-Lang, M
Dietl, P
Georgieff, M
Calzia, E
Radermacher, P
Wagner, F
AF Hafner, S.
Wepler, M.
Matallo, J.
Groeger, M.
Wagner, K.
McCook, O.
Huber-Lang, M.
Dietl, P.
Georgieff, M.
Calzia, E.
Radermacher, P.
Wagner, F.
TI PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM
MURINE MODEL OF BLUNT CHEST TRAUMA
SO SHOCK
LA English
DT Meeting Abstract
CT 37th Annual Conference of the Shock-Society on Shock
CY JUN 07-10, 2014
CL Charlotte, NC
SP Shock Soc
C1 [Hafner, S.; Wepler, M.; Matallo, J.; Groeger, M.; Wagner, K.; McCook, O.; Georgieff, M.; Calzia, E.; Radermacher, P.; Wagner, F.] Univ Ulm Klinikum, Anasthesiol Klin, Sekt APV, Ulm, Germany.
[Wepler, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Huber-Lang, M.] Univ Ulm Klinikum, Klin Unfall Hand Plast & Wiederherstellungschirur, Ulm, Germany.
[Dietl, P.] Univ Ulm, Inst Allgemeine Physiol, D-89069 Ulm, Germany.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
SU 2
BP 85
EP 86
PG 2
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AI6ET
UT WOS:000336964600208
ER
PT J
AU de Windt, TS
Hendriks, JAA
Zhao, X
Vonk, LA
Creemers, LB
Dhert, WJA
Randolph, MA
Saris, DBF
AF de Windt, Tommy S.
Hendriks, Jeanine A. A.
Zhao, Xing
Vonk, Lucienne A.
Creemers, Laura B.
Dhert, Wouter J. A.
Randolph, Mark A.
Saris, Daniel B. F.
TI Concise Review: Unraveling Stem Cell Cocultures in Regenerative
Medicine: Which Cell Interactions Steer Cartilage Regeneration and How?
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Review
DE Bone marrow stromal cells; Cellular therapy; Chondrogenesis; Clinical
translation; Marrow stromal stem cells; Mesenchymal stem cells; Skeleton
ID HUMAN ARTICULAR CHONDROCYTES; IMPROVED CHONDROGENIC DIFFERENTIATION;
MESENCHYMAL STROMAL CELLS; QUALITY-OF-LIFE; IN-VITRO; TISSUE
REGENERATION; FOLLOW-UP; OSTEOARTHRITIC CHONDROCYTES; MATURE
CHONDROCYTES; BACK-PAIN
AB Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartilage regeneration in vitro and in vivo. However, there is considerable debate regarding the mechanisms and cellular interactions that lead to chondrogenesis in these models. This review, which included 52 papers, provides a systematic overview of the data presented in the literature and tries to elucidate the mechanisms that lead to chondrogenesis in stem cell cocultures with cartilage cells. It could serve as a basis for research groups and clinicians aiming at designing and implementing combined cellular technologies for single-stage cartilage repair and treatment or prevention of OA.
C1 [de Windt, Tommy S.; Zhao, Xing; Vonk, Lucienne A.; Creemers, Laura B.; Dhert, Wouter J. A.; Saris, Daniel B. F.] Univ Med Ctr Utrecht, Dept Orthopaed, NL-3508 GA Utrecht, Netherlands.
[Hendriks, Jeanine A. A.] CellCoTec, Bilthoven, Netherlands.
[Zhao, Xing; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue Or, Boston, MA USA.
[Zhao, Xing; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA.
[Dhert, Wouter J. A.] Univ Utrecht, Fac Vet Med, Utrecht, Netherlands.
[Saris, Daniel B. F.] Univ Twente, MIRA Inst Biotechnol & Tech Med, NL-7500 AE Enschede, Netherlands.
RP Saris, DBF (reprint author), Univ Med Ctr Utrecht, Dept Orthopaed, POB 85500, NL-3508 GA Utrecht, Netherlands.
EM d.saris@umcutrecht.nl
OI Creemers, Laura/0000-0002-1585-3052
NR 76
TC 17
Z9 17
U1 3
U2 15
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD JUN
PY 2014
VL 3
IS 6
BP 723
EP 733
DI 10.5966/sctm.2013-0207
PG 11
WC Cell & Tissue Engineering
SC Cell Biology
GA AI5WL
UT WOS:000336940000018
PM 24763684
ER
PT J
AU Bockhorn, M
Uzunoglu, FG
Adham, M
Imrie, C
Milicevic, M
Sandberg, AA
Asbun, HJ
Bassi, C
Buchler, M
Charnley, RM
Conlon, K
Cruz, LF
Dervenis, C
Fingerhutt, A
Friess, H
Gouma, DJ
Hartwig, W
Lillemoe, KD
Montorsi, M
Neoptolemos, JP
Shrikhande, SV
Takaori, K
Traverso, W
Vashist, YK
Vollmer, C
Yeo, CJ
Izbicki, JR
AF Bockhorn, Maximilian
Uzunoglu, Faik G.
Adham, Mustapha
Imrie, Clem
Milicevic, Miroslav
Sandberg, Aken A.
Asbun, Horacio J.
Bassi, Claudio
Buechler, Markus
Charnley, Richard M.
Conlon, Kevin
Cruz, Laureano Fernandez
Dervenis, Christos
Fingerhutt, Abe
Friess, Helmut
Gouma, Dirk J.
Hartwig, Werner
Lillemoe, Keith D.
Montorsi, Marco
Neoptolemos, John P.
Shrikhande, Shailesh V.
Takaori, Kyoichi
Traverso, William
Vashist, Yogesh K.
Vollmer, Charles
Yeo, Charles J.
Izbicki, Jakob R.
CA Int Study Grp Pancreatic Surg
TI Borderline resectable pancreatic cancer: A consensus statement by the
International Study Group of Pancreatic Surgery (ISGPS)
SO SURGERY
LA English
DT Article
ID PORTAL-VEIN RESECTION; CELIAC AXIS RESECTION; MARGIN STATUS; VASCULAR
RESECTION; DUCTAL ADENOCARCINOMA; DISTAL PANCREATECTOMY; PREOPERATIVE
THERAPY; ARTERIAL RESECTION; SURVIVAL DURATION; BODY CANCER
AB Background. This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.
Methods. An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.
Results. The International Study Group of Pancreatic Surgery (ISGPS) supports the National,Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection, in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within I mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (I) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers.
Conclusion. Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.
C1 [Bockhorn, Maximilian; Uzunoglu, Faik G.; Vashist, Yogesh K.; Izbicki, Jakob R.] Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, D-20246 Hamburg, Germany.
[Adham, Mustapha] Hop Edouard Herriot, Dept HPB Surg, Lyon, France.
[Imrie, Clem] Univ Glasgow, Acad Surg Unit, Glasgow, Lanark, Scotland.
[Milicevic, Miroslav] Univ Belgrade, Clin Ctr Serbia, Surg Clin 1, Belgrade, Serbia.
[Sandberg, Aken A.] Karolinska Univ Hosp, Karolinska Inst, Dept Surg, Stockholm, Sweden.
[Asbun, Horacio J.] Mayo Clin, Dept Gen Surg, Jacksonville, FL 32224 USA.
[Bassi, Claudio] Univ Verona, Pancreas Inst, Dept Surg & Oncol, I-37100 Verona, Italy.
[Buechler, Markus; Hartwig, Werner] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany.
[Charnley, Richard M.] Freeman Rd Hosp, Dept HPB & Transplant Surg, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
[Conlon, Kevin] Univ Dublin Trinity Coll, Professorial Surg Unit, Dublin 2, Ireland.
[Cruz, Laureano Fernandez] Univ Barcelona, Hosp Clin Barcelona, Dept Surg, Barcelona, Spain.
[Dervenis, Christos] Agia Olga Hosp, Dept Surg 1, Athens, Greece.
[Fingerhutt, Abe] Ctr Hosp Intercommunal, Dept Digest Surg, Poissy, France.
[Friess, Helmut] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-80290 Munich, Germany.
[Gouma, Dirk J.] Univ Amsterdam, Acad Med Ctr, Dept Surg, NL-1105 AZ Amsterdam, Netherlands.
[Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Montorsi, Marco] Univ Milan, Inst Clin Humanitas IRCCS, Dept Gen Surg, Milan, Italy.
[Neoptolemos, John P.] Univ Liverpool, Liverpool Canc Res UK Ctr, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England.
[Shrikhande, Shailesh V.] Tata Mem Hosp, Dept Gastrointestinal & HPB Surg Oncol, Bombay, Maharashtra, India.
[Takaori, Kyoichi] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan.
[Traverso, William] Ctr Pancreat & Liver Dis, St Lukes Clin, Boise, ID USA.
[Vollmer, Charles] Hosp Univ Penn, Dept Gastrointestinal Surg, Philadelphia, PA 19104 USA.
[Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA.
RP Izbicki, JR (reprint author), Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Martinistr 52, D-20246 Hamburg, Germany.
EM izbicki@uke.de
RI Adham, Mustapha/A-1270-2017;
OI Imrie, Clem/0000-0002-1190-7084
NR 75
TC 107
Z9 130
U1 7
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JUN
PY 2014
VL 155
IS 6
BP 977
EP 988
DI 10.1016/j.surg.2014.02.001
PG 12
WC Surgery
SC Surgery
GA AI6RW
UT WOS:000337005700003
PM 24856119
ER
PT J
AU Goldstein, S
Bates, ER
Bhatt, DL
Cao, C
Holmes, D
Kupfer, S
Martinez, F
Spaeder, J
Weitz, JI
Ye, Z
Zannad, F
AF Goldstein, Sidney
Bates, Eric R.
Bhatt, Deepak L.
Cao, Charlie
Holmes, David
Kupfer, Stuart
Martinez, Felipe
Spaeder, Jeffrey
Weitz, Jeffrey I.
Ye, Zhan
Zannad, Faiez
CA AXIOM Investigators
TI Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients
following acute coronary syndrome
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Oral factor Xa inhibitors; acute coronary syndrome; thrombosis
ID MYOCARDIAL-INFARCTION; CONTROLLED TRIAL; DOUBLE-BLIND; ASPIRIN;
WARFARIN; THROMBOSIS; METAANALYSIS; RIVAROXABAN; CLOPIDOGREL; THERAPY
AB TAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose-dependent effect of TAK-442 on major bleeding when added to standard treatment in stabilised patients with acute coronary syndrome (ACS). In this phase II double-blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition to usual care using a three-stage adaptive design. Patients were randomised to placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was started 36 hours after emergent treatment of ACS and within seven days of admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding incidence was low, but higher with the pooled TAK-442 doses than with placebo (17 [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor dose-dependent. However, a dose response was evident when using the modified ISTH scale. The incidence of cardiovascular events was similar among TAK-442 dose groups and placebo. When administered over a wide range of doses after an ACS event, TAK-442 treatment did not result in a dose-dependent increase in TIMI major bleeding, but increased bleeding was observed when a more sensitive bleeding scale was used. There was no evidence for efficacy.
C1 [Goldstein, Sidney] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA.
[Bates, Eric R.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
[Cao, Charlie; Spaeder, Jeffrey; Ye, Zhan] Takeda Global Res & Dev Inc, Stat, Deerfield, IL USA.
[Holmes, David] Mayo Clin, Dept Cardiovasc Dis, Rochester, MN USA.
[Kupfer, Stuart] Takeda Global Res & Dev Ctr Inc, Clin Sci, Deerfield, IL USA.
[Martinez, Felipe] Natl Univ Cordoba, Cordoba, Argentina.
[Weitz, Jeffrey I.] McMaster Univ, Hamilton, ON, Canada.
[Weitz, Jeffrey I.] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada.
[Zannad, Faiez] Henri Poincare Univ Nancy, Nancy, France.
RP Goldstein, S (reprint author), 2799 W Grand Blvd, Detroit, MI 48202 USA.
EM sgoldst1@hfhs.org
RI Zadionchenko, Vladimir/A-7445-2016; Lotufo, Paulo/A-9843-2008
OI Zadionchenko, Vladimir/0000-0003-2377-5266; Lotufo,
Paulo/0000-0002-4856-8450
FU Takeda Global Research & Development, Inc., Deerfield, IL, USA
FX Research funding was provided by Takeda Global Research & Development,
Inc., Deerfield, IL, USA.
NR 21
TC 6
Z9 7
U1 1
U2 11
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUN
PY 2014
VL 111
IS 6
BP 1141
EP 1152
DI 10.1160/TH13-07-0543
PG 12
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AI5CO
UT WOS:000336883200016
PM 24671450
ER
PT J
AU Bang, JW
Khalilzadeh, O
Hamalainen, M
Watanabe, T
Sasaki, Y
AF Bang, Ji Won
Khalilzadeh, Omid
Haemaelaeinen, Matti
Watanabe, Takeo
Sasaki, Yuka
TI Location specific sleep spindle activity in the early visual areas and
perceptual learning
SO VISION RESEARCH
LA English
DT Article
DE Visual perceptual learning; Consolidation; Sleep; Reactivation; Sleep
spindle; Magnetoencephalography (MEG)
ID DECLARATIVE MEMORY CONSOLIDATION; SURFACE-BASED ANALYSIS; SLOW-WAVE
SLEEP; ORIENTATION DISCRIMINATION; MOTOR-SEQUENCE; TIME-COURSE;
TOPOGRAPHIC DISTRIBUTION; TEXTURE-DISCRIMINATION; SYNAPTIC HOMEOSTASIS;
DEPENDENT CHANGES
AB Visual perceptual learning (VPL) is consolidated during sleep. However, the underlying neuronal mechanisms of consolidation are not yet fully understood. It has been suggested that the spontaneous brain oscillations that characterize sleep stages are indicative of the consolidation of learning and memory. We investigated whether sleep spindles and/or slow-waves are associated with consolidation of VPL during non-rapid eye movement (NREM) sleep during the first sleep cycle, using magnetoencephalography (MEG), magnetic resonance imaging (MRI), and polysomnography (PSG). We hypothesized that after training, early visual areas will show an increase in slow sigma, fast sigma and/or delta activity, corresponding to slow/fast sleep spindles and slow-waves, respectively. We found that during sleep stage 2, but not during slow-wave sleep, the slow sigma power within the trained region of early visual areas was larger after training compared to baseline, and that the increase was larger in the trained region than in the untrained region. However, neither fast sigma nor delta band power increased significantly after training in either sleep stage. Importantly, performance gains for the trained task were correlated with the difference of power increases in slow, sigma activity between the trained and untrained regions. This finding suggests that slow sigma activity plays a critical role in the consolidation of VPL, at least in sleep stage 2 during the first sleep cycle. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Bang, Ji Won; Watanabe, Takeo; Sasaki, Yuka] Brown Univ, Dept Cognit Linguist & Psychol Sci, Lab Cognit & Perceptual Learning, Providence, RI 02912 USA.
[Haemaelaeinen, Matti] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Khalilzadeh, Omid] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Khalilzadeh, Omid] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Sasaki, Y (reprint author), Brown Univ, Dept Cognit Linguist & Psychol Sci, BOX 1821,190 Thayer St, Providence, RI 02912 USA.
EM ji_won_bang@brown.edu; o.khalilzadeh@gmail.com; msh@nmr.mgh.harvard.edu;
takeo_watanabe@brown.edu; yuka_sasaki@brown.edu
RI Hamalainen, Matti/C-8507-2013
FU NIH [R21EY018925, R01EY015980, R01EY019466, R01AG031941, R01MH091801,
R01EB0009048]; NSF [BCS-1261765]; National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health; NIH
Shared Instrumentation Grant Program; High-End Instrumentation Grant
Program [S10RR014978, S10RR021110]
FX This work was supported by grants from NIH (R21EY018925, R01EY015980,
R01EY019466, R01AG031941, R01MH091801, R01EB0009048), and NSF
(BCS-1261765). This research was carried out in part at the Athinoula A.
Martinos Center for Biomedical Imaging at the Massachusetts General
Hospital, using resources provided by the Center for Functional
Neuroimaging Technologies, P41RR014075, a P41 Biotechnology Resource
Grant supported by the National Institute of Biomedical Imaging and
Bioengineering (NIBIB), National Institutes of Health. This work also
involved the use of instrumentation supported by the NIH Shared
Instrumentation Grant Program and High-End Instrumentation Grant
Program; specifically, grant numbers S10RR014978, and S10RR021110. We
thank Daniel G. Wakeman for providing analysis tool, Erika Scilipoti for
helping with data collection, Keiko Ogawa, and Masako Tamaki for scoring
sleep stages, Jared Burgess for editing the manuscript.
NR 103
TC 9
Z9 9
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD JUN
PY 2014
VL 99
SI SI
BP 162
EP 171
DI 10.1016/j.visres.2013.12.014
PG 10
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA AI6UL
UT WOS:000337012400019
PM 24380705
ER
PT J
AU Maeder, MMB
Basnyat, B
Harris, NS
AF Maeder, Monika M. Brodmann
Basnyat, Buddha
Harris, N. Stuart
TI From Matterhorn to Mt Everest: Empowering Rescuers and Improving Medical
Care in Nepal
SO WILDERNESS & ENVIRONMENTAL MEDICINE
LA English
DT Article
DE wilderness medicine; emergency medicine; rescue work; public health
AB This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people.
C1 [Maeder, Monika M. Brodmann] Univ Hosp Bern, Inselspital, Dept Emergency Med, CH-3010 Bern, Switzerland.
[Basnyat, Buddha] Nepal Int Clin, Kathmandu, Nepal.
[Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Div Wilderness Med, Boston, MA 02114 USA.
RP Maeder, MMB (reprint author), Univ Hosp Bern, Inselspital, Dept Emergency Med, CH-3010 Bern, Switzerland.
EM monika.brodmannmaeder@insel.ch
FU Alpine Rescue Foundation Zermatt; Nicole Niquille Foundation
FX Financial support was given by Alpine Rescue Foundation Zermatt by
paying wages, travel expenses, and lodging during the instructors' stay
in Nepal. Nicole Niquille Foundation paid the medical instructor's
travel expenses and lodging during her instruction for the staff of
Pasang Lhamu Nicole Niquille Hospital in Lukla, Nepal.
NR 3
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1080-6032
EI 1545-1534
J9 WILD ENVIRON MED
JI Wildern. Environ. Med.
PD SUM
PY 2014
VL 25
IS 2
BP 177
EP 181
PG 5
WC Public, Environmental & Occupational Health; Sport Sciences
SC Public, Environmental & Occupational Health; Sport Sciences
GA AI5YL
UT WOS:000336946800007
PM 24864066
ER
PT J
AU Lee, AM
Engel, LC
Hui, GC
Liew, G
Ferencik, M
Sidhu, MS
Hoffmann, U
Ghoshhajra, BB
AF Lee, Ashley M.
Engel, Leif-Christopher
Hui, Gladwin C.
Liew, Gary
Ferencik, Maros
Sidhu, Manavjot S.
Hoffmann, Udo
Ghoshhajra, Brian B.
TI Coronary computed tomography angiography at 140 kV versus 120 kV:
assessment of image quality and radiation exposure in overweight and
moderately obese patients
SO ACTA RADIOLOGICA
LA English
DT Article
DE Cardiac; CT; CT angiography; adult; dosimetry; radiation safety
ID TUBE POTENTIAL SELECTION; BODY-MASS INDEX; DUAL-SOURCE CT;
DIAGNOSTIC-ACCURACY; ASSOCIATION; ATTENUATION; PROTOCOL; ADULTS; NOISE
AB Background: Although a tube potential of 140 kV is available on most computed tomography (CT) scanners, its incremental diagnostic value versus 120 kV has been controversial.
Purpose: To retrospectively evaluate the image quality and radiation exposure of cardiac computed tomography angiography (CCTA) performed at 140 kV in comparison to CCTA at 120 kV in overweight and moderately obese patients.
Material and Methods: Eighty-eight patients who were referred for CCTA between January 2010 and May 2012 were included. Forty-four patients who were overweight or moderately obese (body mass index [BMI], 25-35 kg/m(2)) underwent CCTA with dual-source CT (DSCT) scanner at 140 kV. Forty-four match controls who underwent CCTA with DSCT at 120 kV were identified per BMI, average heart rate, scan indication, and scan acquisition mode. All scans were performed per routine protocols with direct physician supervision. Quantitative image metrics (CT attenuation, image noise, contrast-to-noise ratio [CNR], and signal-to-noise ratio [SNR] of left main [LM] and proximal right coronary artery [RCA]) were assessed. Effective radiation dose was compared between the two groups.
Results: Overall, all scans were diagnostic without any non-evaluable coronary segment per clinical report. 140 kV had a lower attenuation and image noise versus 120 kV (P<0.01). Both SNR and CNR of proximal coronary arteries were similar between 140 kV and 120 kV (SNR, LM P = 0.93, RCA P = 0.62; CNR, LM P = 0.57, RCA P = 0.77). 140 kV was associated with a 35.3% increase in effective radiation dose as compared with 120 kV (5.1 [3.6-8.2] vs. 3.3 [2.0-5.1] mSv, respectively; P<0.01).
Conclusion: 140 kV CCTA resulted in similar image quality but a higher effective radiation dose in comparison to 120 kV CCTA. Therefore, in overweight and moderately obese patients, a tube potential of 120 kV may be sufficient for CCTA with diagnostic image quality.
C1 [Lee, Ashley M.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA.
Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA.
RP Lee, AM (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM amshlee@hotmail.com
NR 24
TC 3
Z9 4
U1 1
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0284-1851
EI 1600-0455
J9 ACTA RADIOL
JI Acta Radiol.
PD JUN
PY 2014
VL 55
IS 5
BP 554
EP 562
DI 10.1177/0284185113502745
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI3XM
UT WOS:000336799000005
PM 24031049
ER
PT J
AU Kratz, M
Marcovina, S
Nelson, JE
Yeh, MM
Kowdley, KV
Callahan, HS
Song, XL
Di, CZ
Utzschneider, KM
AF Kratz, Mario
Marcovina, Santica
Nelson, James E.
Yeh, Matthew M.
Kowdley, Kris V.
Callahan, Holly S.
Song, Xiaoling
Di, Chongzhi
Utzschneider, Kristina M.
TI Dairy fat intake is associated with glucose tolerance, hepatic and
systemic insulin sensitivity, and liver fat but not beta-cell function
in humans
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID TRANS-PALMITOLEIC ACID; ADIPOSE-TISSUE; PLASMA; VALIDATION; BIOMARKERS;
RESISTANCE; ADULTS; RISK
AB Background: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16: ln-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts.
Objective: The objective was to investigate whether the intake of trans-16: ln-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance.
Design: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n 7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oralglucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess beta-cell function and hepatic and systemic insulin sensitivity.
Results: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, PIA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n 7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with beta-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for beta-cell function.
Conclusion: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat. This trial was registered at clinicaltrials.gov as NCT01289639.
C1 [Kratz, Mario; Song, Xiaoling] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA.
[Di, Chongzhi] Biostat Program, Seattle, WA 98109 USA.
[Kratz, Mario; Utzschneider, Kristina M.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Kratz, Mario] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Marcovina, Santica] Univ Washington, Northwest Lipid Res Labs, Seattle, WA 98195 USA.
[Nelson, James E.; Kowdley, Kris V.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA.
[Callahan, Holly S.] Univ Washington, Inst Translat Hlth Sci, Seattle, WA 98195 USA.
[Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol, Seattle, WA USA.
RP Kratz, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mail Stop M4-B402,1100 Fairview Ave North, Seattle, WA 98109 USA.
EM mkratz@fhcrc.org
FU US Department of Veterans Affairs, Office of Research and Development
Medical Research Service; NIH [UL1RR025014, P30DK017047, P30DK035816,
DK020579, RR000954, DK056341, T32DK007247, U01DK061728, K24DK002957,
R21ES022332]
FX Supported by the US Department of Veterans Affairs, Office of Research
and Development Medical Research Service, and NIH grant nos.
UL1RR025014, P30DK017047, P30DK035816, DK020579, RR000954, DK056341,
T32DK007247, U01DK061728, K24DK002957, and R21ES022332.
NR 20
TC 17
Z9 17
U1 1
U2 15
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 JUN
PY 2014
VL 99
IS 6
BP 1385
EP 1396
DI 10.3945/ajcn.113.075457
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9NW
UT WOS:000336470100011
PM 24740208
ER
PT J
AU Kim, HT
Frederick, D
Armand, P
Andler, E
Kao, G
Cutler, C
Koreth, J
Alyea, EP
Antin, JH
Soiffer, RJ
Ritz, J
Ho, VT
AF Kim, Haesook T.
Frederick, David
Armand, Philippe
Andler, Emily
Kao, Grace
Cutler, Corey
Koreth, John
Alyea, Edwin P., III
Antin, Joseph H.
Soiffer, Robert J.
Ritz, Jerome
Ho, Vincent T.
TI White blood cell recovery after allogeneic hematopoietic cell
transplantation predicts clinical outcome
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID VERSUS-HOST-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; LYMPHOCYTE RECOVERY;
MONOCYTE RECOVERY; BONE-MARROW; MALIGNANCIES; SURVIVAL; IMPACT; RISK;
SCT
AB To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1-3 months after HCT was categorized as low (<2), normal (2-10), and high (>10 x 10(9) cells/L). Overall survival (OS) and progression-free survival (PFS) were lower for patients with low or high WBC at 1-3 months after HCT (P<0.0001). We developed a predictive three-group risk model based on the pattern of WBC recovery early after HCT. Five-year OS was 47, 30, and 15% (P<0.0001) and 5-year PFS was 39, 22, and 14% for patients in the three different risk groups (P<0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression-free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials. Am. J. Hematol. 89:591-597, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Frederick, David; Armand, Philippe; Andler, Emily; Kao, Grace; Cutler, Corey; Koreth, John; Alyea, Edwin P., III; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02215 USA.
RP Kim, HT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM htkimc@jimmy.harvard.edu
OI Ritz, Jerome/0000-0001-5526-4669
FU NCI NIH HHS [P01 CA142106, P01 CA018029]
NR 16
TC 4
Z9 4
U1 0
U2 3
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 JUN
PY 2014
VL 89
IS 6
BP 591
EP 597
DI 10.1002/ajh.23695
PG 7
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600207
PM 24549932
ER
PT J
AU Black, L
Selby, R
Hoffman, S
Chen, D
Meijer, P
Plumhoff, E
Van Cott, E
AF Black, Lesley
Selby, Rita
Hoffman, Suzanne
Chen, Dong
Meijer, Piet
Plumhoff, Elizabeth
Van Cott, Elizabeth
TI ANTI-XA ASSAYS FOR UNFRACTIONATED HEPARIN (UFH) AND LOW MOLECULAR WEIGHT
HEPARIN (LMWH): ANALYSIS OF THE QUALITY OF PERFORMANCE BY NORTH AMERICAN
LABORATORIES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Black, Lesley; Selby, Rita] Univ Toronto, Lab Med Program, Univ Hlth Network, Toronto, ON, Canada.
[Selby, Rita] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Clin Pathol, Toronto, ON, Canada.
[Hoffman, Suzanne] Univ Wisconsin, Madison, WI USA.
[Chen, Dong; Plumhoff, Elizabeth] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands.
[Van Cott, Elizabeth] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 124
BP E60
EP E60
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600122
ER
PT J
AU Chen, D
Selby, R
Meijer, P
Plumhoff, EA
Van Cott, EM
AF Chen, Dong
Selby, Rita
Meijer, Piet
Plumhoff, Elizabeth A.
Van Cott, Elizabeth M.
TI ANTITHROMBIN ACTIVITY AND ANTIGEN ASSAYS: AN ANALYSIS OF LABORATORY
PERFORMANCE
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Chen, Dong; Plumhoff, Elizabeth A.] Mayo Clin, Rochester, MN USA.
[Selby, Rita] Univ Toronto, Toronto, ON, Canada.
[Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 48
BP E23
EP E23
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600047
ER
PT J
AU Grabowski, EF
Paidas, MJ
Buonanno, FS
Thibert, RL
Musolino, PL
Pels, S
Ment, L
Triche, E
Caruso, PA
Roberts, DJ
Sze, G
Van Cott, EM
Murphy, S
Krishnamoorthy, KS
AF Grabowski, Eric F.
Paidas, Michael J.
Buonanno, Ferdinando S.
Thibert, Ronald L.
Musolino, Patricia L.
Pels, Sally
Ment, Laura
Triche, Elizabeth
Caruso, Paul A.
Roberts, Drucilla J.
Sze, Gordon
Van Cott, Elizabeth M.
Murphy, Sarah
Krishnamoorthy, Kalpathy S.
TI PREDICTING LATE AND EARLY PERINATAL STROKE IN HIGH-RISK PREGNANCIES AND
HIGH-RISK NEONATES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Grabowski, Eric F.; Buonanno, Ferdinando S.; Thibert, Ronald L.; Musolino, Patricia L.; Caruso, Paul A.; Roberts, Drucilla J.; Van Cott, Elizabeth M.; Murphy, Sarah; Krishnamoorthy, Kalpathy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Paidas, Michael J.; Pels, Sally; Ment, Laura; Sze, Gordon] Yale Univ, Sch Med, New Haven, CT USA.
[Triche, Elizabeth] Brown Univ, Providence, RI 02912 USA.
RI Triche, Elizabeth/I-4986-2014
NR 0
TC 0
Z9 0
U1 0
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 JUN
PY 2014
VL 89
IS 6
MA 113
BP E55
EP E55
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600111
ER
PT J
AU Hsu, PH
Marlar, RA
Zantek, ND
Smock, KJ
Plumhoff, EA
Meijer, P
Van Cott, EM
AF Hsu, Peihong
Marlar, Richard A.
Zantek, Nicole D.
Smock, Kristi J.
Plumhoff, Elizabeth A.
Meijer, Piet
Van Cott, Elizabeth M.
TI ACTIVATED PROTEIN C RESISTANCE TESTING: ASSESSMENT OF THE QUALITY OF
TESTING PERFORMED BY NORTH AMERICAN SPECIALIZED COAGULATION LABORATORIES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol & Lab Med, Lake Success, NY USA.
[Marlar, Richard A.] Univ Oklahoma, Dept Pathol, Hlth Sci Ctr, Tulsa, OK USA.
[Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA.
[Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 80
BP E38
EP E38
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600078
ER
PT J
AU Marshall, A
Campigotto, F
Neuberg, D
Rowe, B
Connors, J
AF Marshall, Ariela
Campigotto, Federico
Neuberg, Donna
Rowe, Betty
Connors, Jean
TI RATES OF RECURRENT VENOUS THROMBOEMBOLISM AMONGST ONCOLOGY PATIENTS
MANAGED IN A DEDICATED ANTICOAGULATION CLINIC NOT HIGHER WITH WARFARIN
COMPARED TO PARENTERAL ANTICOAGULANTS
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Marshall, Ariela; Campigotto, Federico; Neuberg, Donna; Rowe, Betty; Connors, Jean] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Marshall, Ariela] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rowe, Betty; Connors, Jean] Brigham & Womens Hosp, Boston, MA 02115 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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 138
BP E66
EP E66
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600135
ER
PT J
AU Marshall, A
Drucker, A
Dzik, WH
AF Marshall, Ariela
Drucker, Adrienne
Dzik, Walter H.
TI USE OF AMINOCAPROIC ACID IN PATIENTS WITH HEMATOLOGIC MALIGNANCY: A CASE
SERIES FROM THE MASSACHUSETTS GENERAL HOSPITAL
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Marshall, Ariela] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Marshall, Ariela; Drucker, Adrienne; Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
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 JUN
PY 2014
VL 89
IS 6
MA 91
BP E43
EP E44
PG 2
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600089
ER
PT J
AU Milling, TJ
Refaai, MA
Sarode, R
Lewis, B
Mangione, A
Durn, BL
Goldstein, JN
AF Milling, Truman J.
Refaai, Majed A.
Sarode, Ravi
Lewis, Brandon
Mangione, Antoinette
Durn, Billie L.
Goldstein, Joshua N.
TI SAFETY OF A 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE (4F-PCC) VERSUS
PLASMA FOR VITAMIN K ANTAGONIST REVERSAL: AN INTEGRATED DATA ANALYSIS OF
TWO PHASE III CLINICAL TRIALS
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Milling, Truman J.] Univ Med Ctr Brackenridge, Seton UT Southwestern Clin Res Inst Austin, Dell Childrens Med Ctr, Austin, TX USA.
[Refaai, Majed A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Sarode, Ravi] UT Southwestern Med Ctr, Dallas, TX USA.
[Lewis, Brandon] Texas A&M Hlth Sci Ctr, St Joseph Reg Hlth Ctr, College Stn, TX USA.
[Mangione, Antoinette; Durn, Billie L.] CSL Behring, King Of Prussia, PA USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Goldstein, Joshua/H-8953-2016
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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 54
BP E26
EP E26
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600053
ER
PT J
AU Pruthi, RK
Plumhoff, EA
Nichols, WL
Meijer, P
Van Cott, EM
AF Pruthi, Rajiv K.
Plumhoff, Elizabeth A.
Nichols, William L.
Meijer, Piet
Van Cott, Elizabeth M.
TI QUALITY OF FACTOR VIII INHIBITOR TESTING IN NORTH AMERICAN SPECIALIZED
COAGULATION LABORATORIES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Pruthi, Rajiv K.; Plumhoff, Elizabeth A.; Nichols, William L.] Mayo Clin, Rochester, MN USA.
[Meijer, Piet] ECAT Fdn Netherlands, Leiden, Netherlands.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
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 JUN
PY 2014
VL 89
IS 6
MA 57
BP E27
EP E27
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600055
ER
PT J
AU Smock, KJ
Plumhoff, EA
Meijer, P
Hsu, PH
Zantek, ND
Heikal, NM
Van Cott, EM
AF Smock, Kristi J.
Plumhoff, Elizabeth A.
Meijer, Piet
Hsu, Peihong
Zantek, Nicole D.
Heikal, Nahla M.
Van Cott, Elizabeth M.
TI PROTEIN S: QUALITY OF TESTING IN NORTH AMERICAN SPECIALIZED COAGULATION
LABORATORIES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Smock, Kristi J.; Heikal, Nahla M.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA.
[Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands.
[Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol & Lab Med, Lake Success, NY USA.
[Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
MA 62
BP E29
EP E30
PG 2
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600060
ER
PT J
AU Zantek, ND
Hsu, PH
Meijer, P
Plumhoff, EA
Refaai, MA
Smock, KJ
Van Cott, EM
AF Zantek, Nicole D.
Hsu, Peihong
Meijer, Piet
Plumhoff, Elizabeth A.
Refaai, Majed A.
Smock, Kristi J.
Van Cott, Elizabeth M.
TI QUALITY OF FACTOR XI ACTIVITY TESTING IN NORTH AMERICAN SPECIALIZED
COAGULATION LABORATORIES
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol Lab Med, Lake Success, NY USA.
[Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands.
[Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Refaai, Majed A.] Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY USA.
[Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
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 JUN
PY 2014
VL 89
IS 6
MA 66
BP E31
EP E31
PG 1
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600064
ER
PT J
AU Turner, AP
Williams, RM
Norvell, DC
Henderson, AW
Hakimi, KN
Blake, DJ
Czerniecki, JM
AF Turner, Aaron P.
Williams, Rhonda M.
Norvell, Daniel C.
Henderson, Alison W.
Hakimi, Kevin N.
Blake, Donna Jo
Czerniecki, Joseph M.
TI Prevalence and 1-Year Course of Alcohol Misuse and Smoking in Persons
with Lower Extremity Amputation as a Result of Peripheral Arterial
Disease
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Smoking; Alcohol Misuse; Amputation; Prevalence; Social Support
ID SPINAL-CORD-INJURY; DISORDERS IDENTIFICATION TEST; TYPE-2
DIABETES-MELLITUS; LOWER-LIMB AMPUTATION; 6.5-YEAR FOLLOW-UP;
RISK-FACTORS; SOCIAL SUPPORT; MULTIPLE-SCLEROSIS; CIGARETTE-SMOKING;
UNITED-STATES
AB Objective The aim of this study was to describe prevalence of alcohol misuse and smoking among individuals with amputations as a result of peripheral arterial disease before surgery and 12 mos after surgery, changes in these behaviors over time, and factors associated with change.
Design This is a prospective cohort study of 75 veterans experiencing their first major unilateral amputation. Measures included demographic and general health information, Alcohol Use Disorders Identification Test, smoking behaviors, and social support.
Results Sixteen percent of the participants reported engaging in alcohol misuse at presurgical baseline; and 13% at 12 mos after amputation. Thirty-seven percent of the participants were categorized as smokers at baseline; this number dropped to 29% at 12 mos after amputation. Among those who decreased drinking and quit smoking, there was a trend indicating greater social support.
Conclusions The participants endorsed drinking and smoking behaviors at levels consistent with other types of disability and with veterans using the Veterans Health Administration for their health care. Even with a variety of health concerns, after amputation, most of the smokers and those engaging in alcohol misuse continued to smoke and drink at their preamputation rate. The presence of social support may encourage health behavior change and is an important area for future research and intervention.
C1 [Turner, Aaron P.; Williams, Rhonda M.; Henderson, Alison W.; Hakimi, Kevin N.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA.
[Blake, Donna Jo] Denver VAMC, Denver, CO USA.
[Blake, Donna Jo] Univ Colorado, Denver, CO 80202 USA.
RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA.
OI Turner, Aaron/0000-0001-6897-8003
FU United States Department of Veterans Affairs, Office of Research and
Development, Rehabilitation Research and Development [A41241, B4927W]
FX Supported by the United States Department of Veterans Affairs, Office of
Research and Development, Rehabilitation Research and Development (Merit
Review A41241, Joseph M. Czerniecki, PI, and Career Development Award
B4927W, Aaron P. Turner, PI).
NR 78
TC 1
Z9 1
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
EI 1537-7385
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD JUN
PY 2014
VL 93
IS 6
BP 493
EP 502
DI 10.1097/PHM.0000000000000055
PG 10
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA AI3FC
UT WOS:000336744900005
PM 24508927
ER
PT J
AU Lee, JXW
Yusin, JS
Randhawa, I
AF Lee, Joyce Xiang Wu
Yusin, Joseph Stephen
Randhawa, Inderpal
TI Properdin deficiency-associated bronchiectasis
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Letter
C1 [Lee, Joyce Xiang Wu; Yusin, Joseph Stephen] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol, Los Angeles, CA 90073 USA.
[Randhawa, Inderpal] Long Beach Mem Med Ctr, Long Beach, CA USA.
RP Lee, JXW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol, Los Angeles, CA 90073 USA.
EM joycexianglee@gmail.com
NR 8
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 1081-1206
EI 1534-4436
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD JUN
PY 2014
VL 112
IS 6
BP 557
EP 559
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA AH9XJ
UT WOS:000336498400017
PM 24793003
ER
PT J
AU Carbone, LD
Chin, AS
Lee, TA
Burns, SP
Svircev, JN
Hoenig, HM
Bailey, L
Weaver, FM
AF Carbone, Laura D.
Chin, Amy S.
Lee, Todd A.
Burns, Stephen P.
Svircev, Jelena N.
Hoenig, Helen M.
Bailey, Lauren
Weaver, Frances M.
TI Thiazide Use Is Associated With Reduced Risk for Incident Lower
Extremity Fractures in Men With Spinal Cord Injury
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Fractures, bone; Men; Rehabilitation; Spinal cord injuries; Thiazides
ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; HIP FRACTURE; OLDER-ADULTS;
DIURETIC USE; VITAMIN-D; OSTEOPOROSIS; WORLDWIDE; VETERANS
AB Objective: To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI).
Design: Cohort study from fiscal years 2002 to 2007.
Setting: Medical centers.
Participants: Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides.
Intervention: Thiazide use versus nonuse.
Main Outcome Measure: Incident lower extremity fractures.
Results: Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95).
Conclusions: Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures. (C) 2014 by the American Congress of Rehabilitation Medicine
C1 [Carbone, Laura D.] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA USA.
[Carbone, Laura D.] Georgia Regents Univ, Dept Med, Augusta, GA 30912 USA.
[Chin, Amy S.; Lee, Todd A.; Bailey, Lauren; Weaver, Frances M.] Care of Hines EJ, Jr Vet Affairs Hosp, Hines, IL USA.
[Lee, Todd A.; Bailey, Lauren] Univ Illinois, Chicago, IL USA.
[Burns, Stephen P.; Svircev, Jelena N.] Vet Affairs Puget Sound, Spinal Cord Injury Serv, Seattle, WA USA.
[Burns, Stephen P.; Svircev, Jelena N.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Hoenig, Helen M.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA.
RP Carbone, LD (reprint author), Georgia Regents Univ, Dept Med, Sect Rheumatol & Immunol, 1120 15th St,BI 5086, Augusta, GA 30912 USA.
EM lcarbone@gru.edu
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development [UR 08-033]
FX Supported by the Department of Veterans Affairs, Veterans Health
Administration, Health Services Research and Development (grant no. UR
08-033).
NR 38
TC 2
Z9 2
U1 2
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUN
PY 2014
VL 95
IS 6
BP 1015
EP 1020
DI 10.1016/j.apmr.2013.12.013
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA AI3OY
UT WOS:000336773000002
PM 24378805
ER
PT J
AU Sullivan-Singh, SJ
Sawyer, K
Ehde, DM
Bell, KR
Temkin, N
Dikmen, S
Williams, RM
Hoffman, JM
AF Sullivan-Singh, Sarah J.
Sawyer, Kathryn
Ehde, Dawn M.
Bell, Kathleen R.
Temkin, Nancy
Dikmen, Sureyya
Williams, Rhonda M.
Hoffman, Jeanne M.
TI Comorbidity of Pain and Depression Among Persons With Traumatic Brain
Injury
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Brain injuries; Depression; Pain; Rehabilitation
ID CUT-POINTS; SEVERITY; DISORDERS; PREVALENCE; VALIDITY; OUTCOMES
AB Objective: To assess the prevalence of pain, depression, and comorbid pain and depression among a civilian sample of persons with traumatic brain injury (TBI).
Design: Longitudinal survey design with 1-year follow-up.
Setting: Inpatient rehabilitation and the community.
Participants: Participants (N = 158) admitted to inpatient rehabilitation after moderate to severe TBI.
Interventions: Not applicable.
Main Outcome Measures: Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9); pain was assessed with a numerical rating scale from 0 (no pain) to 10 (worst pain). Participants who reported average pain >= 4 were classified as having pain, and participants with PHQ-9 scores >= 10 were classified as depressed.
Results: Both pain and depression were more prevalent at baseline assessment (pain: 70%; depression: 31%) than at year 1 (pain: 34%; depression: 22%). Comorbid pain and depression declined from 27% at baseline to 18% at year 1. Pain was significantly associated with depression at baseline (relative risk: 2.62, P = .003) and at year 1 (relative risk: 7.98, P<.001).
Conclusions: Pain and depression are common and frequently co-occur in persons with TBI. Although their frequency declined over the first year after injury, the strength of their association increased. Assessment and treatment of both conditions simultaneously may lead to improved outcomes, both early after TBI and over time. (C) 2014 by the American Congress of Rehabilitation Medicine
C1 [Sullivan-Singh, Sarah J.; Sawyer, Kathryn; Ehde, Dawn M.; Bell, Kathleen R.; Temkin, Nancy; Dikmen, Sureyya; Williams, Rhonda M.; Hoffman, Jeanne M.] Univ Washington, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA.
[Temkin, Nancy; Dikmen, Sureyya] Univ Washington, Dept Neurol Surg, Sch Med, Seattle, WA 98104 USA.
[Temkin, Nancy] Univ Washington, Dept Biostat, Sch Med, Seattle, WA 98104 USA.
[Dikmen, Sureyya] Univ Washington, Dept Psychiat & Biobehav Sci, Sch Med, Seattle, WA 98104 USA.
[Williams, Rhonda M.] Vet Affairs Puget Sound Healthcare Syst, Rehabil Care Serv, Seattle, WA USA.
RP Sullivan-Singh, SJ (reprint author), Univ Washington, Dept Rehabil Med, Harborview Med Ctr, 325 Ninth Ave,Box 359612, Seattle, WA 98104 USA.
EM sarahsullivansingh@gmail.com
FU National Institute on Disability and Rehabilitation Research Traumatic
Brain Injury Model Systems [H133A070032]; Department of Defense
Congressionally Directed Medical Research Programs [W81XWH-12-2-0109]
FX Supported by the National Institute on Disability and Rehabilitation
Research Traumatic Brain Injury Model Systems (grant no. H133A070032)
and Department of Defense Congressionally Directed Medical Research
Programs (grant no. W81XWH-12-2-0109).
NR 27
TC 10
Z9 10
U1 1
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 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUN
PY 2014
VL 95
IS 6
BP 1100
EP 1105
DI 10.1016/j.apmr.2014.02.001
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA AI3OY
UT WOS:000336773000014
PM 24561058
ER
PT J
AU Spector, M
Ying, JYR
AF Spector, Myron
Ying, Jackie Yi-Ru
TI An interview with Jackie Yi-Ru Ying: the compleat multi-tasker
SO BIOMEDICAL MATERIALS
LA English
DT Editorial Material
ID FIBERS
C1 [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA.
[Ying, Jackie Yi-Ru] ASTAR, IBN, Singapore, Singapore.
[Ying, Jackie Yi-Ru] Inst New Mat, Saarbrucken, Germany.
[Ying, Jackie Yi-Ru] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA.
NR 9
TC 0
Z9 0
U1 1
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1748-6041
EI 1748-605X
J9 BIOMED MATER
JI Biomed. Mater.
PD JUN
PY 2014
VL 9
IS 3
AR 030401
DI 10.1088/1748-6041/9/3/030401
PG 5
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA AI3DA
UT WOS:000336738000001
ER
PT J
AU Violant, D
Galofre, M
Nart, J
Teles, RP
AF Violant, Deborah
Galofre, Marta
Nart, Jose
Teles, Ricardo Patricio
TI In vitro evaluation of a multispecies oral biofilm on different implant
surfaces
SO BIOMEDICAL MATERIALS
LA English
DT Article
DE checkerboard DNA-DNA hybridization; implant surface; oral biofilm;
periimplantitis
ID DENTAL IMPLANTS; BACTERIAL-COLONIZATION; TITANIUM IMPLANTS; FOLLOW-UP;
PLAQUE; VIVO; HYDROXYAPATITE; EPIDERMIDIS; VALIDATION; OSTEOBLAST
AB Biofilm accumulation on implant surfaces is one of the most important factors for early and late implant failure. Because of the related clinical implications, the aim of this in vitro study was to compare the bacterial cell attachment of a four-species oral biofilm on titanium discs of purity grade 2 and 4, with machined surfaces and etched-thermochemically modified with Avantblast (R). The in vitro biofilm model was composed of early (Actinomyces naeslundii, Streptococcus gordonii), secondary (Veillonella parvula), and intermediate (Fusobacterium nucleatum ssp. polymorphum) colonizers of tooth surfaces. A total of 36 discs were divided into four groups: Tigr2-c (titanium grade 2, machined surface), Tigr2-t (titanium grade 2, modified surface with Avantblast (R)), Tigr4-c (titanium grade 4, machined surface), Tigr4-t (titanium grade 4, modified surface with Avantblast (R)). The experiment was repeated three times. Biofilm viability was tested with 1% 2, 3, 5-triphenyltetrazolium chloride solution and bacterial cell quantification by checkerboard DNA-DNA hybridization. Descriptive analysis was performed to evaluate biofilm composition and differences between groups were checked with the Mann-Whitney test (p < 0.05). After one week, multispecies biofilms showed a similar pattern of bacterial composition on all analyzed implant surfaces. The most prevalent bacterium was V. parvula (similar to 50% of the total biomass), followed by S. gordonii (similar to 30%), F. nucleatum ssp. polymorphum (similar to 10%) and A. naeslundii (<5%). Total bacterial biomass was significantly higher in both grade-4-titanium surfaces (p < 0.05). The results demonstrated that not only implant surface treatment, but also titanium purity, influence early bacterial colonization.
C1 [Violant, Deborah; Galofre, Marta; Nart, Jose] Univ Int Catalunya, Dept Periodont, Barcelona 08195, Spain.
[Violant, Deborah; Teles, Ricardo Patricio] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
RP Violant, D (reprint author), Univ Int Catalunya, Dept Periodont, Josep Trueta S-N, Barcelona 08195, Spain.
EM dviolant@uic.es
OI Violant, Deborah/0000-0002-3292-270X
NR 54
TC 5
Z9 5
U1 2
U2 18
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1748-6041
EI 1748-605X
J9 BIOMED MATER
JI Biomed. Mater.
PD JUN
PY 2014
VL 9
IS 3
AR 035007
DI 10.1088/1748-6041/9/3/035007
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA AI3DA
UT WOS:000336738000008
PM 24770899
ER
PT J
AU Miller, CL
West, JA
Bettini, AC
Koerner, FC
Gudewicz, TM
Freer, PE
Coopey, SB
Gadd, MA
Hughes, KS
Smith, BL
Rafferty, E
Specht, MC
AF Miller, Cynthia L.
West, Jane A.
Bettini, Anna C.
Koerner, Frederick C.
Gudewicz, Thomas M.
Freer, Phoebe E.
Coopey, Suzanne B.
Gadd, Michele A.
Hughes, Kevin S.
Smith, Barbara L.
Rafferty, Elizabeth
Specht, Michelle C.
TI Surgical excision of radial scars diagnosed by core biopsy may help
predict future risk of breast cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Radial scar; Complex sclerosing lesion; Surgical excision; High-risk
lesion; Atypia
ID ATYPICAL DUCTAL HYPERPLASIA; COMPLEX SCLEROSING LESIONS; CARCINOMA
IN-SITU; OF-THE-LITERATURE; NEEDLE-BIOPSY; PATHOLOGICAL CORRELATION;
SCREENING-PROGRAM; ADJUVANT BREAST; FOLLOW-UP; MANAGEMENT
AB Radial scars (RS's) are benign breast lesions known to be associated with carcinomas and other high-risk lesions (HRL's). The upgrade rate to carcinoma after core biopsy revealing RS is 0-40 %. We sought to determine the outcomes of RS with and without HRL diagnosed by core biopsy. Patients who underwent core biopsy revealing RS without carcinoma at our institution between 1/1996 and 11/2012 were identified from a surgical pathology database. Retrospective chart review was utilized to classify patients as RS-no HRL or RS-HRL. HRL was defined as ADH, LCIS, and/or ALH. We determined upgrade rate to carcinoma at surgical excision, and upgrade to HRL for RS-no HRL patients. Univariate analysis was performed to identify risk factors for upgrade in RS-no HRL patients. 156 patients underwent core biopsy revealing RS, 131 RS-no HRL (84 %), and 25 RS-HRL (16 %). The overall rate of upgrade to invasive carcinoma was 0.8 % (1/124). 1.0 % (1/102) of RS-no HRL and 13.6 % (3/22) of RS-HRL patients were upgraded to DCIS (P = 0.0023). The upgrade of RS-no HRL to HRL at excision was 21.6 % (22/102). By univariate analysis, RS-no HRL with radiologic appearance of a mass/architectural distortion had a significantly higher rate of upgrade to HRL or carcinoma compared with calcifications (P = 0.03). Excision of RS to rule out associated invasive carcinoma is not warranted, given a < 1 % rate of upgrade at excision. However, excision to evaluate for non-invasive cancer or HRL may be considered to help guide clinical decision-making about use of chemoprevention.
C1 [Miller, Cynthia L.; Bettini, Anna C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[West, Jane A.; Freer, Phoebe E.; Rafferty, Elizabeth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Koerner, Frederick C.; Gudewicz, Thomas M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Coopey, Suzanne B.; Gadd, Michele A.; Hughes, Kevin S.; Smith, Barbara L.; Specht, Michelle C.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
RP Specht, MC (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
EM mspecht@partners.org
OI Hughes, Kevin/0000-0003-4084-6484; Freer, Phoebe/0000-0001-6886-7100
NR 48
TC 6
Z9 6
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2014
VL 145
IS 2
BP 331
EP 338
DI 10.1007/s10549-014-2958-y
PG 8
WC Oncology
SC Oncology
GA AH8FG
UT WOS:000336370200006
PM 24748568
ER
PT J
AU Chen, WY
Giobbie-Hurder, A
Gantman, K
Savoie, J
Scheib, R
Parker, LM
Schernhammer, ES
AF Chen, Wendy Y.
Giobbie-Hurder, Anita
Gantman, Kathryn
Savoie, Jennifer
Scheib, Rochelle
Parker, Leroy M.
Schernhammer, Eva S.
TI A randomized, placebo-controlled trial of melatonin on breast cancer
survivors: impact on sleep, mood, and hot flashes
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Melatonin; Sleep disturbance; Survivorship; Clinical
trial
ID PINEAL HORMONE MELATONIN; QUALITY-OF-LIFE; EXOGENOUS MELATONIN;
DEPRESSIVE SYMPTOMS; DOUBLE-BLIND; CHEMOTHERAPY; THERAPY; WOMEN;
METAANALYSIS; EFFICACY
AB The purpose is to examine the effects of melatonin supplementation on sleep, mood, and hot flashes in postmenopausal breast cancer survivors. In a randomized, double-blind, placebo-controlled study, 95 postmenopausal women with a prior history of stage 0-III breast cancer, who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 3 mg oral melatonin (n = 48) or placebo daily (n = 47) for 4 months. Sleep, mood, and hot flashes were assessed at baseline and 4 months via self-administered questionnaire using the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiologic Studies-Depression (CES-D), and the North Central Cancer Treatment Group (NCCTG) hot flash diary, respectively. Eighty-six women (91 %) completed the study and provided pre- and post-questionnaires. At baseline, 52 % of participants reported poor sleep in the month prior to enrollment. Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. For example, the mean change in PSQI score was -0.1 in the placebo group compared to -1.9 in the melatonin group (p < 0.001). There were no significant differences in measures of depression or hot flashes. Sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment. This is the first randomized placebo-controlled study among breast cancer survivors to demonstrate that melatonin was associated with an improvement in subjective sleep quality, without any significant adverse effects.
C1 [Chen, Wendy Y.; Schernhammer, Eva S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chen, Wendy Y.; Schernhammer, Eva S.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Wendy Y.; Savoie, Jennifer; Scheib, Rochelle; Parker, Leroy M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Gantman, Kathryn] Mt Auburn Hosp, Cambridge, MA USA.
[Schernhammer, Eva S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Schernhammer, Eva S.] ACR ITR, Vienna, Austria.
[Schernhammer, Eva S.] LBI ACR VIEnna CEADDP, Vienna, Austria.
RP Chen, WY (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM wendy.chen@channing.harvard.edu
FU National Cancer Institute [R03 CA123597]
FX We are grateful to the participants of this trial, as well as to the
staff at the Dana-Farber Cancer Institute that helped facilitate the
trial's conduct. This study was supported by a grant from the National
Cancer Institute (R03 CA123597). The funding source had no role in the
design or analysis of the study or in the decision to submit the
manuscript for publication.
NR 35
TC 12
Z9 13
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2014
VL 145
IS 2
BP 381
EP 388
DI 10.1007/s10549-014-2944-4
PG 8
WC Oncology
SC Oncology
GA AH8FG
UT WOS:000336370200011
PM 24718775
ER
PT J
AU Freedman, RA
Vaz-Luis, I
Barry, WT
Lii, H
Lin, NU
Winer, EP
Keating, NL
AF Freedman, Rachel A.
Vaz-Luis, Ines
Barry, William T.
Lii, Huichuan
Lin, Nancy U.
Winer, Eric P.
Keating, Nancy L.
TI Patterns of chemotherapy, toxicity, and short-term outcomes for older
women receiving adjuvant trastuzumab-based therapy
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Non-standard chemotherapy; Toxicity; Outcomes; Older women
ID HER2-POSITIVE BREAST-CANCER; SEER-MEDICARE DATA; ELDERLY-WOMEN;
COMORBIDITY INDEX; POPULATION; PLUS; HER2; VALIDATION; SELECTION;
SURVIVAL
AB Limited data are available regarding patterns of chemotherapy receipt and treatment-related toxicities for older women receiving adjuvant trastuzumab-based therapy. We used surveillance, epidemiology and end results (SEER)-Medicare data to identify patients a parts per thousand yen66 years with stage I-III breast cancer treated during 2005-2009, who received trastuzumab-based therapy. We examined patterns of chemotherapy receipt, and using multivariable logistic regression, we examined associations of age and comorbidity with non-standard chemotherapy. In propensity-weighted cohorts of women receiving standard and non-standard trastuzumab-based therapy, we also examined rates of (1) hospital events during the first 6 months of chemotherapy and (2) short-term survival. Among 2,106 women, 29.7 % were aged a parts per thousand yen76 and 66 % had a comorbidity score = 0. Overall, 31.3 % of women received non-standard chemotherapy. Compared to patients aged 66-70, older patients more often received non-standard chemotherapy [adjusted odds ratio (OR) = 4.1, 95 % confidence interval (CI) = 3.40-4.92 (ages 76-80); OR = 15.3, 95 %CI = 9.92-23.67 (age a parts per thousand yen 80)]. However, comorbidity was not associated with receipt of non-standard chemotherapy. After propensity score adjustment, hospitalizations were more frequent in the standard (vs. non-standard) group (adjusted OR = 1.7, 95 % CI = 1.29-2.24). With a median follow-up of 2.8 years, 276 deaths occurred; the adjusted hazard ratio (HR) for death was lower in standard versus non-standard treated women (HR = 0.69, 95 % CI = 0.52-0.91). Among a population-based cohort of older women receiving trastuzumab, nearly one-third received non-standard chemotherapy, with the highest rates among the oldest women. Non-standard chemotherapy was associated with fewer toxicity-related hospitalizations but worse survival. Further exploration of treatment toxicities and outcomes for older women with HER2-positive breast cancer is warranted.
C1 [Freedman, Rachel A.; Vaz-Luis, Ines; Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Vaz-Luis, Ines] Inst Med Mol, Lisbon, Portugal.
[Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Lii, Huichuan] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM rafreedman@partners.org
FU National Cancer Institute's Surveillance, Epidemiology and End Results
Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease
Control and Prevention's National Program of Cancer Registries
[U55/CCR921930-02]; National Cancer Institute Specialized Program of
Research Excellence in Breast Cancer [NIH P50 CA089393]; CJL Foundation;
ACT NOW fund; Susan G. Komen for the Cure; Fundacao para a Ciencia e
Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber Cancer Institute Friends
Grant
FX This study used the linked SEER-Medicare database. The interpretation
and reporting of these data are the sole responsibility of the authors.
The authors acknowledge the efforts of the Applied Research Program,
NCI; the Office of Research, Development and Information, CMS;
Information Management Services (IMS), Inc.; and the Surveillance,
Epidemiology, and End Results (SEER) Program tumor registries in the
creation of the SEER-Medicare database. The collection of the California
cancer incidence data used in this study was supported by the California
Department of Public Health as part of the statewide cancer reporting
program mandated by California Health and Safety Code Section 103885;
the National Cancer Institute's Surveillance, Epidemiology and End
Results Program under contract N01-PC-35136 awarded to the Northern
California Cancer Center, contract N01-PC-35139 awarded to the
University of Southern California, and contract N02-PC-15105 awarded to
the Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
#U55/CCR921930-02 awarded to the Public Health Institute. The ideas and
opinions expressed herein are those of the author(s) and endorsement by
the State of California, Department of Public Health the National Cancer
Institute, and the Centers for Disease Control and Prevention or their
Contractors and Subcontractors is not intended nor should be inferred.
The study was supported by the National Cancer Institute Specialized
Program of Research Excellence in Breast Cancer (NIH P50 CA089393), the
CJL Foundation (to W T Barry), ACT NOW fund, Susan G. Komen for the Cure
(to E P Winer and N L Keating), Fundacao para a Ciencia e Tecnologia
(HMSP-ICS/0004/2011, Career Development Award) (to I Vaz-Luis) and a
Dana-Farber Cancer Institute Friends Grant (to R Freedman).
NR 38
TC 10
Z9 10
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2014
VL 145
IS 2
BP 491
EP 501
DI 10.1007/s10549-014-2968-9
PG 11
WC Oncology
SC Oncology
GA AH8FG
UT WOS:000336370200022
PM 24756187
ER
PT J
AU Stanton, AL
Petrie, KJ
Partridge, AH
AF Stanton, Annette L.
Petrie, Keith J.
Partridge, Ann H.
TI Contributors to nonadherence and nonpersistence with endocrine therapy
in breast cancer survivors recruited from an online research registry
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Adherence; Tamoxifen; Aromatase inhibitor; Compliance
ID WORKING ALLIANCE INVENTORY; ADJUVANT HORMONAL-THERAPY; MEDICATION
ADHERENCE; PATIENT-ADHERENCE; OLDER WOMEN; SELF-REPORT; POSTMENOPAUSAL
WOMEN; CLINICAL-PRACTICE; TAMOXIFEN; METAANALYSIS
AB Rates of adherence and persistence with endocrine therapy regimens (i.e., tamoxifen, aromatase inhibitors) by breast cancer survivors are suboptimal, with negative implications for prognosis. This study identified potential contributors to nonadherence and nonpersistence. From an online breast cancer research registry (Army of Women) including approximately 51,000 breast cancer survivors, we recruited 1,371 women who currently were taking endocrine therapy and 94 nonpersisters (i.e., diagnosed during the prior 5 years and on endocrine therapy within the prior 12 months, but no longer taking it). Participants completed an online questionnaire assessing demographic/medical characteristics, general and cancer-related psychosocial variables (i.e., depressive symptoms, anxiety, patient-oncologist relationship quality, cancer recurrence worry, general symptoms), and endocrine therapy-specific variables (i.e., endocrine therapy-related symptoms, perceived endocrine therapy necessity, long-term therapy use concern, endocrine therapy-related emotions). Two weeks later, current users were re-contacted to complete an endocrine therapy adherence measure. In a final regression model, patient-reported nonadherence among current users was significantly associated with lower financial status, a prior switch in endocrine therapies, a poorer relationship with the oncologist, and lower perceived need for and more negative emotions regarding endocrine therapy (adjusted R (2) = 0.15, P < 0.001). In a final logistic regression model, endocrine therapy nonpersisters were significantly more likely than current users to report depressive symptoms, as well as more negative emotions and lower positive emotions related to endocrine therapy (adjusted R (2) = 0.10, P < 0.001). In addition to demographic/medical variables, several potentially modifiable psychosocial characteristics are likely to contribute to endocrine therapy nonadherence and nonpersistence.
C1 [Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, Los Angeles, CA 90095 USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychiat Biobehav Sci, Los Angeles, CA 90095 USA.
[Petrie, Keith J.] Univ Auckland, Dept Psychol Med, Auckland 1, New Zealand.
[Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Stanton, AL (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, 1285 Franz Hall,Box 90095-1563, Los Angeles, CA 90095 USA.
EM astanton@ucla.edu
FU Breast Cancer Research Foundation
FX This research was supported by funding from the Breast Cancer Research
Foundation (Stanton).
NR 52
TC 17
Z9 17
U1 5
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2014
VL 145
IS 2
BP 525
EP 534
DI 10.1007/s10549-014-2961-3
PG 10
WC Oncology
SC Oncology
GA AH8FG
UT WOS:000336370200025
PM 24781972
ER
PT J
AU Kantarjian, HM
Steensma, DP
Light, DW
AF Kantarjian, Hagop M.
Steensma, David P.
Light, Donald W.
TI The Patient Protection and Affordable Care Act: Is it Good or Bad for
Oncology?
SO CANCER
LA English
DT Editorial Material
ID LUNG-CANCER; STAGE
AB The Patient Protection and Affordable Care Act (ACA) has many flaws that need to be addressed, but it is better than what was. Oncologists should advocate for the ACA and work on improving it.
C1 [Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, Houston, TX 77030 USA.
[Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Med, Boston, MA 02115 USA.
[Light, Donald W.] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA.
RP Kantarjian, HM (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, 1400 Holcombe Blvd,Unit 428, Houston, TX 77030 USA.
EM hkantarj@mdanderson.org
OI Steensma, David/0000-0001-5130-9284
FU NCI NIH HHS [P30 CA016672]
NR 21
TC 2
Z9 2
U1 1
U2 2
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 JUN 1
PY 2014
VL 120
IS 11
BP 1600
EP 1603
DI 10.1002/cncr.28673
PG 4
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700004
PM 24643748
ER
PT J
AU Garcia, JA
Hudes, GR
Choueiri, TK
Stadler, WM
Wood, LS
Gurtler, J
Bhatia, S
Joshi, A
Hozak, RR
Xu, YH
Schwartz, JD
Thompson, JA
AF Garcia, Jorge A.
Hudes, Gary R.
Choueiri, Toni K.
Stadler, Walter M.
Wood, Laura S.
Gurtler, Jayne
Bhatia, Shailender
Joshi, Adarsh
Hozak, Rebecca R.
Xu, Yihuan
Schwartz, Jonathan D.
Thompson, John A.
TI A Phase 2, Single-Arm Study of Ramucirumab in Patients With Metastatic
Renal Cell Carcinoma With Disease Progression on or Intolerance to
Tyrosine Kinase Inhibitor Therapy
SO CANCER
LA English
DT Article
DE ramucirumab; renal cell carcinoma; phase 2; metastatic; monoclonal
antibody
ID PROGNOSTIC-FACTORS; III TRIAL; BEVACIZUMAB; SORAFENIB; SUNITINIB;
TUMORS; SELECTION; GROWTH; CANCER
AB BACKGROUNDMultitargeted tyrosine kinase inhibitors (TKIs) have antitumor activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents develops frequently, and their use is often limited by intolerance. Ramucirumab is a recombinant human monoclonal antibody directed against human vascular endothelial growth factor receptor-2. For this study, the authors investigated the clinical efficacy and safety of ramucirumab in patients with TKI-resistant/intolerant mRCC.
METHODSIn this single-arm phase 2 trial, patients received ramucirumab 8 mg/kg every 2 weeks until they developed disease progression or intolerable toxicity. The primary endpoint was the best objective response rate (ORR); additional endpoints included the disease control rate (DCR), progression-free survival (PFS), the median duration of overall response, and safety.
RESULTSThirty-nine patients with RCC received ramucirumab monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was 5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95% CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or higher adverse events that occurred in 5% of patients included grade 3 hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from multiorgan failure.
CONCLUSIONSAlthough the study did not meet its primary endpoint of 15% ORR, ramucirumab was associated with evidence of antitumor activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and well tolerated. Cancer 2014;120:1647-1655. (c) 2014 American Cancer Society.
C1 [Garcia, Jorge A.; Wood, Laura S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA.
[Hudes, Gary R.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Stadler, Walter M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Gurtler, Jayne] Metarie Oncol, Metairie, LA USA.
[Bhatia, Shailender; Thompson, John A.] Seattle Canc Care Alliance, Seattle, WA USA.
[Bhatia, Shailender; Thompson, John A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Joshi, Adarsh; Hozak, Rebecca R.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Xu, Yihuan; Schwartz, Jonathan D.] ImClone Syst Inc, Branchburg, NJ USA.
RP Garcia, JA (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Glickman Urol & Kidney Inst,CCF CWRU Lerner Coll, 9500 Euclid Ave R35, Cleveland, OH 44195 USA.
EM garciaj4@ccf.org
FU ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company
FX This study was supported by ImClone Systems LLC, a wholly owned
subsidiary of Eli Lilly and Company.
NR 28
TC 16
Z9 16
U1 1
U2 5
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 JUN 1
PY 2014
VL 120
IS 11
BP 1647
EP 1655
DI 10.1002/cncr.28634
PG 9
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700013
PM 24577874
ER
PT J
AU Abern, MR
Terris, MK
Aronson, WJ
Kane, CJ
Amling, CL
Cooperberg, MR
Freedland, SJ
AF Abern, Michael R.
Terris, Martha K.
Aronson, William J.
Kane, Christopher J.
Amling, Christopher L.
Cooperberg, Matthew R.
Freedland, Stephen J.
TI The Impact of Pathologic Staging on the Long-Term Oncologic Outcomes of
Patients With Clinically High-Risk Prostate Cancer
SO CANCER
LA English
DT Article
DE prostatic neoplasms; prostatectomy; treatment outcome; pathology
ID RADICAL PROSTATECTOMY; UNITED-STATES; MORTALITY; NOMOGRAM; SURVIVAL;
DISEASE; NG/ML; MEN
AB BACKGROUNDIn the prostate-specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high-risk prostate cancer (PC). However, high-risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high-risk disease stratified on RP pathology.
METHODSA total of 611 men with high-risk PC (PSA level>20 ng/mL, biopsy Gleason sum [bGS]8, or clinical classification ofT3) underwent RP and pelvic lymphadenectomy between 1998 and 2011. Outcomes included biochemical disease recurrence (BCR), receipt of androgen deprivation therapy (ADT), metastases, and PC-specific and overall survival. RP pathology was classified as unfavorable (pathologic Gleason sum8, pathologic classification ofT3, or lymph node-positive disease), or favorable (no unfavorable features). Multivariable analyses tested oncologic outcomes stratified by pathologic classification.
RESULTSOverall, 527 men had complete pathologic data and were included in the current analysis. Of the cohort, 206 of 527 men (39%) had favorable pathology. This finding was more common in men with only 1 clinical high-risk feature, and a lower body mass index, PSA level, bGS, and percentage positive biopsy cores. Favorable pathology was associated with decreased BCR (hazards ratio [HR], 0.34), metastases (HR, 0.17), and PC death (HR, 0.17). After a median follow-up of 82 months (range, 49 months-131 months), 193 of the 527 men (37%) received ADT, including only 35 of the 206 men with favorable pathology (17%). Unfavorable pathology was associated with early ( 5 years) but not late treatment with ADT.
CONCLUSIONSIn a large cohort of men with high-risk PC who were managed with RP, 39% had favorable pathology and superior oncologic outcomes. Cancer 2014;120:1656-1662. (c) 2014 American Cancer Society.
C1 [Abern, Michael R.] Univ Illinois, Dept Urol, Chicago, IL 60612 USA.
[Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA.
[Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA.
[Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA.
[Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA.
[Kane, Christopher J.] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA.
[Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR USA.
[Cooperberg, Matthew R.] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Urol, San Francisco, CA 94143 USA.
[Cooperberg, Matthew R.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA.
[Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA.
[Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC USA.
RP Abern, MR (reprint author), Univ Illinois, Dept Urol, 820 S Wood St,Suite 515, Chicago, IL 60612 USA.
EM mabern1@uic.edu
OI Terris, Martha/0000-0002-3843-7270
NR 23
TC 10
Z9 11
U1 0
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 JUN 1
PY 2014
VL 120
IS 11
BP 1656
EP 1662
DI 10.1002/cncr.28647
PG 7
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700014
PM 24647966
ER
PT J
AU Steensma, DP
Komrokji, RS
Stone, RM
List, AF
Garcia-Manero, G
Huber, JM
Dennison, B
Sekeres, MA
AF Steensma, David P.
Komrokji, Rami S.
Stone, Richard M.
List, Alan F.
Garcia-Manero, Guillermo
Huber, John M.
Dennison, Betsy
Sekeres, Mikkael A.
TI Disparity in Perceptions of Disease Characteristics, Treatment
Effectiveness, and Factors Influencing Treatment Adherence Between
Physicians and Patients With Myelodysplastic Syndromes
SO CANCER
LA English
DT Article
DE myelodysplastic syndromes; therapy adherence; azacitidine; decitabine;
lenalidomide; communication
ID INTERNET-BASED SURVEY; CELL TRANSPLANTATION; AZACITIDINE; CANCER;
IMPACT; DIAGNOSIS; SURVIVAL; LEUKEMIA; OUTCOMES; QUALITY
AB BACKGROUNDPrevious studies have suggested that many patients with myelodysplastic syndromes (MDS) have an incomplete understanding of their disease, which may influence adherence to prescribed regimens and outcomes.
METHODSTo better understand physician and patient perceptions about MDS and MDS therapy, the authors conducted 2 surveys in February 2012: 1 for patients with MDS and 1 for health care professionals (HCPs) who cared for patients with MDS. Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific treatments, barriers to treatment adherence, and treatment experience.
RESULTSIn total, 477 complete patient responses and 120 complete HCP responses were received. Among patient responders, 63% were aged 60 years, and 42% had received at least 1 disease-modifying therapy. Of the 61 physician responders, 57% practiced in an academic setting, and 43% practiced in the community; 71% of the 59 nonphysician HCPs worked in the community setting. Only 10% of patients agreed that MDS represented cancer compared with 59% of physicians and 46% of nonphysician HCPs (P<.001). Only 29% of patients reported that MDS was ever curable compared with 52% of physicians (P<.001). Physicians viewed the potential benefits of active therapy as greater than patients, but patients perceived the actual treatment experience more positively than physicians and differed from physicians in perceived reasons for stopping therapy.
CONCLUSIONSPhysicians, nonphysician HCPs, and patients with MDS have disparate views of MDS characteristics and the value and limitations of treatments for MDS. Improved communication and education may increase understanding and achieve better treatment adherence and patient outcomes. Cancer 2014;120:1670-1676. (c) 2014 American Cancer Society.
C1 [Steensma, David P.; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02215 USA.
[Komrokji, Rami S.; List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Med Oncol, Tampa, FL 33612 USA.
[Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Huber, John M.] Aplast Anemia & Myelodysplast Syndromes Int Fdn, Rockville, MD USA.
[Dennison, Betsy] Clar Commun, Pompton Lakes, NJ USA.
[Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA.
RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, 450 Brookline Ave,D2037, Boston, MA 02215 USA.
EM david_steensma@dfci.harvard.edu
OI Steensma, David/0000-0001-5130-9284
FU Celgene Corporation; Edward P. Evans Foundation
FX This study was funded in part by an unrestricted educational grant to
the Aplastic Anemia & Myelodysplastic Syndromes International Foundation
from Celgene Corporation and by the Edward P. Evans Foundation. The
authors designed and conducted the study and wrote the article without
influence from the sponsor.
NR 23
TC 12
Z9 12
U1 0
U2 0
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 JUN 1
PY 2014
VL 120
IS 11
BP 1670
EP 1676
DI 10.1002/cncr.28631
PG 7
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700016
PM 24577838
ER
PT J
AU Ackerman, A
Klein, O
McDermott, DF
Wang, W
Ibrahim, N
Lawrence, DP
Gunturi, A
Flaherty, KT
Hodi, FS
Kefford, R
Menzies, AM
Atkins, MB
Long, GV
Sullivan, RJ
AF Ackerman, Allison
Klein, Oliver
McDermott, David F.
Wang, Wei
Ibrahim, Nageatte
Lawrence, Donald P.
Gunturi, Anasuya
Flaherty, Keith T.
Hodi, F. Stephen
Kefford, Richard
Menzies, Alexander M.
Atkins, Michael B.
Long, Georgina V.
Sullivan, Ryan J.
TI Outcomes of Patients With Metastatic Melanoma Treated With Immunotherapy
Prior to or After BRAF Inhibitors
SO CANCER
LA English
DT Article
DE vemurafenib; sequencing; ipilimumab; melanoma; BRAF
ID IMPROVED SURVIVAL; MEK INHIBITION; OPEN-LABEL; IPILIMUMAB; SAFETY;
MULTICENTER; VEMURAFENIB; DABRAFENIB; RESPONSES; ANTI-PD-1
AB BACKGROUNDThe immunotherapy (IT) agents ipilimumab and interleukin-2 as well as BRAF inhibitors (BRAFi) vemurafenib and dabrafenib, with or without trametinib (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma, but there are few studies to guide optimal sequencing. This retrospective analysis describes the outcomes of patients treated with either BRAFi before IT or IT before BRAFi.
METHODSA cohort of patients treated with BRAFi alone or with MEK inhibitor was retrospectively identified. Response rate (RR), overall survival (OS), and progression-free survival (PFS) were evaluated for the entire cohort, subdivided by BRAFi prior to or after IT.
RESULTSRR and median PFS and OS calculated from commencement of BRAFi following IT (N=32) were 57%, 6.7 months (95% confidence interval [CI]=4.3-9.1 months), and 19.6 months (95% CI=10.0-undefined months), respectively; whereas for BRAFi initially (N=242) were 66%, 5.6 months (95% CI=4.7-6.8 months), and 13.4 months (95% CI=10.1-17.0 months). Results were similar when controlled for prognostic variables. A total of 193 patients discontinued BRAFi, with OS of 2.9 months (range of 1.8-4.4 months) from day of BRAFi discontinuation. Forty patients subsequently received IT with ipilimumab. Only half could complete 4 doses of ipilimumab; PFS with ipilimumab was 2.7 months (95% CI=1.8-3.1 months) and OS was 5.0 months (95% CI=3.0-8.8 months).
CONCLUSIONSIn this retrospective analysis, prior treatment with IT does not appear to negatively influence response to BRAFi. Outcomes for IT with ipilimumab following BRAFi discontinuation are poor. Randomized controlled trials are needed to define if sequencing IT prior to BRAFi therapy is superior to sequencing BRAFi prior to IT. Cancer 2014;120:1695-1701. (c) 2014 American Cancer Society.
C1 [Ackerman, Allison; McDermott, David F.; Gunturi, Anasuya] Beth Israel Deaconess Med Ctr, Dept Med, Div Oncol, Boston, MA 02215 USA.
[Klein, Oliver; Kefford, Richard] Westmead Hosp, Sydney, NSW, Australia.
[Wang, Wei] Brigham & Womens Hosp, Div Sleep Med, Dept Med, Boston, MA 02115 USA.
[Ibrahim, Nageatte; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Melanoma Dis Ctr, Boston, MA 02115 USA.
[Lawrence, Donald P.; Flaherty, Keith T.; Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA.
[Kefford, Richard; Long, Georgina V.] Westmead Hosp, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW, Australia.
[Kefford, Richard; Menzies, Alexander M.; Long, Georgina V.] Univ Sydney, Discipline Med, Sydney, NSW 2006, Australia.
[Kefford, Richard; Menzies, Alexander M.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia.
[Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA.
EM rsullivan7@partners.org
NR 18
TC 70
Z9 74
U1 3
U2 23
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 JUN 1
PY 2014
VL 120
IS 11
BP 1695
EP 1701
DI 10.1002/cncr.28620
PG 7
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700019
PM 24577748
ER
PT J
AU Meza, R
ten Haaf, K
Kong, CY
Erdogan, A
Black, WC
Tammemagi, MC
Choi, SE
Jeon, J
Han, SS
Munshi, V
van Rosmalen, J
Pinsky, P
McMahon, PM
de Koning, HJ
Eric, J
Hazelton, WD
Plevritis, SK
AF Meza, Rafael
ten Haaf, Kevin
Kong, Chung Yin
Erdogan, Ayca
Black, William C.
Tammemagi, Martin C.
Choi, Sung Eun
Jeon, Jihyoun
Han, Summer S.
Munshi, Vidit
van Rosmalen, Joost
Pinsky, Paul
McMahon, Pamela M.
de Koning, Harry J.
Feuer, Eric J.
Hazelton, William D.
Plevritis, Sylvia K.
TI Comparative Analysis of 5 Lung Cancer Natural History and Screening
Models That Reproduce Outcomes of the NLST and PLCO Trials
SO CANCER
LA English
DT Article
DE Cancer Intervention and Surveillance Modeling Network (CISNET);
comparative modeling analyses; low-dose CT screening; lung cancer
screening; cancer natural history models; smoking and lung cancer;
simulation model
ID MULTISTAGE CARCINOGENESIS; MICROSIMULATION MODELS; POTENTIAL BENEFITS;
COLORECTAL-CANCER; UNITED-STATES; MORTALITY; SMOKING; PROSTATE; HEALTH;
RISK
AB BACKGROUNDThe National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level.
METHODSFive independent LC screening models were developed using common inputs and calibration targets derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Imputation of missing information regarding smoking, histology, and stage of disease for a small percentage of individuals and diagnosed LCs in both trials was performed. Models were calibrated to LC incidence, mortality, or both outcomes simultaneously.
RESULTSInitially, all models were calibrated to the NLST and validated against PLCO. Models were found to validate well against individuals in PLCO who would have been eligible for the NLST. However, all models required further calibration to PLCO to adequately capture LC outcomes in PLCO never-smokers and light smokers. Final versions of all models produced incidence and mortality outcomes in the presence and absence of screening that were consistent with both trials.
CONCLUSIONSThe authors developed 5 distinct LC screening simulation models based on the evidence in the NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO have produced consistent results. The resulting models can be important tools to generate additional evidence to determine the effectiveness of lung cancer screening strategies using low-dose computed tomography. Cancer 2014;120:1713-1724. (c) 2014 American Cancer Society.
C1 [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[ten Haaf, Kevin; van Rosmalen, Joost; de Koning, Harry J.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands.
[Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Erdogan, Ayca; Han, Summer S.; Plevritis, Sylvia K.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
[Black, William C.] Dartmouth Coll, Dept Radiol, Geisel Sch Med Dartmouth, Hanover, NH 03755 USA.
[Tammemagi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Jeon, Jihyoun; Hazelton, William D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA.
[van Rosmalen, Joost] Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands.
[Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Meza, R (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM rmeza@umich.edu
OI van Rosmalen, Joost/0000-0002-9187-244X
FU Agency for Healthcare Research and Quality (AHRQ) [U01-CA152956]
FX This report is based on research conducted by the National Cancer
Institutes (NCI)'s Cancer Intervention and Surveillance Modeling Network
(CISNET) through support from an interagency agreement with the Agency
for Healthcare Research and Quality (AHRQ) (administrative supplement to
NCI grant U01-CA152956).
NR 31
TC 17
Z9 17
U1 1
U2 10
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 JUN 1
PY 2014
VL 120
IS 11
BP 1713
EP 1724
DI 10.1002/cncr.28623
PG 12
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700021
PM 24577803
ER
PT J
AU Slusarz, KM
Merker, VL
Muzikansky, A
Francis, SA
Plotkin, SR
AF Slusarz, Katherine M.
Merker, Vanessa L.
Muzikansky, Alona
Francis, Sanjeev A.
Plotkin, Scott R.
TI Long-term toxicity of bevacizumab therapy in neurofibromatosis 2
patients
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Bevacizumab; Neurofibromatosis 2; Toxicity; Hypertension; Proteinuria
ID BLOOD-PRESSURE; PHASE-III; HYPERTENSION; CANCER; TYPE-2; INHIBITORS;
SYSTEM; TRIAL; RISK
AB Bevacizumab treatment is associated with tumor shrinkage and hearing improvement in about 50 % of neurofibromatosis 2 (NF2) patients with progressive vestibular schwannomas. Hypertension and proteinuria are common side effects of treatment. However, the long-term toxicity of bevacizumab in this population has not been reported.
We reviewed the medical records of all NF2 patients treated with compassionate care bevacizumab at our institution. Hypertension was defined as a systolic blood pressure a parts per thousand yen140 or a diastolic blood pressure a parts per thousand yen90. Proteinuria was measured by urine dipstick. Time-to-event analyses were conducted for hypertension and proteinuria. The relationship of cumulative dose of bevacizumab to mean arterial pressure (MAP) was examined using mixed model analysis, while the relationship to urine protein was examined using generalized estimating equations.
Thirty-three patients (median age 28 years) were included in the study, with a median treatment time of 34.1 months. 15/26 (58 %) patients became hypertensive and 18/29 (62 %) developed proteinuria during treatment. Median time to develop hypertension was 12.8 months. Median time to develop 1+ and 2+ proteinuria was 23.7 and 31.9 months, respectively. Eight patients required treatment holidays for proteinuria (median length 3.2 months). A significant positive relationship existed between cumulative bevacizumab dose and MAP (p < 0.0001) but not between cumulative dose and proteinuria (p > 0.30).
In our cohort of NF2 patients, extended use of bevacizumab was associated with manageable toxicity. However, bevacizumab treatment still requires careful monitoring of blood pressure and proteinuria, and future studies should investigate optimal dosing schedules to minimize long-term toxicity.
C1 [Slusarz, Katherine M.] Massachusetts Gen Hosp, Ctr Neurofibromatosis & Allied Disorders, Ctr Human Genet Res, Boston, MA 02114 USA.
[Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA.
[Francis, Sanjeev A.] Massachusetts Gen Hosp, Serv Cardiol, Boston, MA 02114 USA.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA.
EM splotkin@partners.org
OI Merker, Vanessa/0000-0002-4542-5227
NR 24
TC 13
Z9 15
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD JUN
PY 2014
VL 73
IS 6
BP 1197
EP 1204
DI 10.1007/s00280-014-2456-2
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AH8NV
UT WOS:000336395700012
PM 24710627
ER
PT J
AU Yurgelun, MB
Hornick, JL
Curry, VK
Ukaegbu, CI
Brown, EK
Hiller, E
Chittenden, A
Goldberg, JE
Syngal, S
AF Yurgelun, Matthew B.
Hornick, Jason L.
Curry, Victoriana K.
Ukaegbu, Chinedu I.
Brown, Emily K.
Hiller, Elaine
Chittenden, Anu
Goldberg, Joel E.
Syngal, Sapna
TI Therapy-Associated Polyposis as a Late Sequela of Cancer Treatment
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Polyps; Radiation; Adenomas; Chemotherapy
ID CHILDHOOD-CANCER; HODGKINS-DISEASE; 2ND MALIGNANCY; SURVIVORS; RISK;
ADENOMAS; COHORT
AB Survivors of childhood cancers are at increased risk of developing secondary gastrointestinal cancers, including colorectal cancer, later in life, possibly from exposure to abdominopelvic radiotherapy and/or alkylating chemotherapy. Profuse gastrointestinal polyposis is associated with rare, inherited colorectal cancer predisposition syndromes, most commonly caused by mutations in the adenomatous polyposis coli (APC) or mutY homolog (MUTYH) genes. We describe 5 patients who developed gastrointestinal polyposis many years after radiotherapy and chemotherapy for a childhood cancer. Genetic analysis of all 5 subjects did not identify pathogenic germline mutations in APC or MUTYH. Chemotherapy and/or radiotherapy therefore might cause gastrointestinal polyposis in some patients by undiscovered mechanisms.
C1 [Yurgelun, Matthew B.; Curry, Victoriana K.; Ukaegbu, Chinedu I.; Brown, Emily K.; Hiller, Elaine; Chittenden, Anu] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Yurgelun, Matthew B.; Syngal, Sapna] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Goldberg, Joel E.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Goldberg, Joel E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Yurgelun, MB (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Matthew_Yurgelun@DFCI.Harvard.edu
FU National Institutes of Health (National Cancer Institute) [K24CA113433]
FX Supported by the National Institutes of Health (National Cancer
Institute) (K24CA113433 to S.S.).
NR 15
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 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JUN
PY 2014
VL 12
IS 6
BP 1046
EP 1050
DI 10.1016/j.cgh.2013.11.040
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9ZI
UT WOS:000336504700027
PM 24362051
ER
PT J
AU Pinto, N
Gamazon, ER
Antao, N
Myers, J
Stark, AL
Konkashbaev, A
Im, HK
Diskin, SJ
London, WB
Ludeman, SM
Maris, JM
Cox, NJ
Cohn, SL
Dolan, ME
AF Pinto, N.
Gamazon, E. R.
Antao, N.
Myers, J.
Stark, A. L.
Konkashbaev, A.
Im, H. K.
Diskin, S. J.
London, W. B.
Ludeman, S. M.
Maris, J. M.
Cox, N. J.
Cohn, S. L.
Dolan, M. E.
TI Integrating Cell-Based and Clinical Genome-Wide Studies to Identify
Genetic Variants Contributing to Treatment Failure in Neuroblastoma
Patients
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID HIGH-RISK NEUROBLASTOMA; PHARMACOGENOMIC DISCOVERY; CYCLOPHOSPHAMIDE;
SUSCEPTIBILITY; IDENTIFICATION; ASSOCIATION; STRESS; TRIAL;
CYTOTOXICITY; METABOLITES
AB High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer.
C1 [Pinto, N.] Univ Chicago, Dept Pediat, Sect Pediat Hematol Oncol, Chicago, IL 60637 USA.
[Gamazon, E. R.; Konkashbaev, A.; Cox, N. J.] Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL 60637 USA.
[Antao, N.; Myers, J.; Stark, A. L.; Dolan, M. E.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Im, H. K.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Diskin, S. J.; Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Diskin, S. J.; Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Diskin, S. J.; Maris, J. M.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[London, W. B.] Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[London, W. B.] Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA.
[Ludeman, S. M.] Albany Coll Pharm & Hlth Sci, Dept Basic & Social Sci, Albany, NY USA.
RP Dolan, ME (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA.
EM edolan@medicine.bsd.uchicago.edu
OI Cohn, Susan/0000-0001-5749-7650; Gamazon, Eric/0000-0003-4204-8734
FU National Center For Advancing Translational Sciences of the National
Institutes of Health (NIH) [UL1TR000430]; NIH/National Institute of
General Medical Sciences Pharmacogenomics of Anticancer Agents grant
[U01GM61393]; University of Chicago Breast Cancer SPORE grants [NCI P50
CA125183, NIH/NCI RO1 CA136765, NIH/NCI R01 CA 016783]; St. Baldrick's
Foundation; Cancer Research Foundation
FX Research reported in this publication was supported by the National
Center For Advancing Translational Sciences of the National Institutes
of Health (NIH) under award UL1TR000430, NIH/National Institute of
General Medical Sciences Pharmacogenomics of Anticancer Agents grant
U01GM61393, and by the University of Chicago Breast Cancer SPORE grants
NCI P50 CA125183, NIH/NCI RO1 CA136765, and NIH/NCI R01 CA 016783. In
addition, this research was supported by the St. Baldrick's Foundation
and the Cancer Research Foundation. The authors are grateful to the
Pharmacogenomics of Anticancer Agents Cell Line Core at the University
of Chicago for assistance in maintaining the cell lines. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH. The authors thank Shannon
Delaney for her help in formatting the IKZF3 siRNA results.
NR 47
TC 4
Z9 4
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUN
PY 2014
VL 95
IS 6
BP 644
EP 652
DI 10.1038/clpt.2014.37
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH8VC
UT WOS:000336415300028
PM 24549002
ER
PT J
AU Danilack, VA
Weston, NA
Richardson, CR
Mori, DL
Moy, ML
AF Danilack, Valery A.
Weston, Nicole A.
Richardson, Caroline R.
Mori, DeAnna L.
Moy, Marilyn L.
TI Reasons Persons with COPD Do Not Walk and Relationship with Daily Step
Count
SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
LA English
DT Article
DE exercise; pulmonary disease; accelerometer; physical activity; step
count
ID OBSTRUCTIVE PULMONARY-DISEASE; PHYSICAL-ACTIVITY; OLDER-ADULTS;
BARRIERS; EXERCISE; POPULATION; PARTICIPATION; COHORT; REHABILITATION;
ACCELEROMETER
AB Background: Physical activity (PA) is significantly reduced in persons with COPD. Assessing reasons why persons with COPD do not engage in PA can guide development of effective interventions to promote PA. Methods: We queried 102 participants with stable COPD about disease-related and general reasons why they do not walk more. The StepWatch Activity Monitor (Orthocare Innovations, Mountlake Terrace, WA, USA) assessed daily step count, a direct measure of PA. Regression models assessed daily step count by response categories, adjusting for age and FEV1 % predicted. Results: Subjects had mean age 72 +/- 8 years and mean FEV1 1.48 +/- 0.55 L (52 +/- 19% predicted). COPD-related worries of becoming short of breath (SOB), needing to use inhalers, or oxygen level becoming low were endorsed by 31, 14, and 12 subjects, respectively. Controlling for age and FEV1% predicted, those who worried about becoming SOB walked an average of 1,329 fewer steps per day than those who did not worry (p = 0.020). Those who worried about needing to use inhalers walked an average of 1,806 fewer steps per day than those who did not worry (p = 0.016). Subjects who were the most motivated and confident walked significantly more than those who were the least motivated and confident. Conclusions: Presence of COPD-related reasons and lower motivation and confidence are associated with lower daily step count. Management of dyspnea and education about medication use during exercise, and strategies to increase motivation and confidence could facilitate walking in COPD.
C1 [Danilack, Valery A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
[Danilack, Valery A.; Weston, Nicole A.; Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, West Roxbury, MA 02132 USA.
[Richardson, Caroline R.] Univ Michigan, Sch Med, Dept Family Med, Ann Arbor, MI USA.
[Richardson, Caroline R.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Mori, DeAnna L.] VA Boston Healthcare Syst, Psychol Serv, West Roxbury, MA 02132 USA.
[Mori, DeAnna L.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Moy, Marilyn L.] Vet Hlth Adm, Dept Vet Affairs, Rehabil Res & Dev Serv, Washington, DC USA.
[Moy, Marilyn L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, West Roxbury, MA 02132 USA.
EM marilyn.moy@va.gov
FU Department of Veteran Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service through a VA Career
Development Award; CIMIT: Center for Integration of Medicine and
Innovative Technology, Boston, MA
FX The research reported here was supported by the Department of Veteran
Affairs, Veterans Health Administration, Rehabilitation Research and
Development Service through a VA Career Development Award to Dr. Moy.
Dr. Moy was supported in part by CIMIT: Center for Integration of
Medicine and Innovative Technology, Boston, MA. The authors report no
conflicts of interest.
NR 46
TC 4
Z9 4
U1 3
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1541-2555
EI 1541-2563
J9 COPD
JI COPD-J. Chronic Obstr. Pulm. Dis.
PD JUN
PY 2014
VL 11
IS 3
BP 290
EP 299
DI 10.3109/15412555.2013.841670
PG 10
WC Respiratory System
SC Respiratory System
GA AI0AI
UT WOS:000336507800006
PM 24152213
ER
PT J
AU O'Horo, JC
Maki, DG
Krupp, AE
Safdar, N
AF O'Horo, John C.
Maki, Dennis G.
Krupp, Anna E.
Safdar, Nasia
TI Arterial Catheters as a Source of Bloodstream Infection: A Systematic
Review and Meta-Analysis
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE arterial catheterization; catheter-related infections; critical care;
meta-analysis; nosocomial infections; peripheral; prevalence
ID CRITICALLY-ILL PATIENTS; RANDOMIZED CONTROLLED-TRIAL; CENTRAL VENOUS
CATHETERS; INTENSIVE-CARE UNITS; RADIAL-ARTERY; FEMORAL-ARTERY;
CARDIAC-SURGERY; COLONIZATION; CANNULATION; SEPSIS
AB Objective: Catheter-related bloodstream infections are associated with significant costs and adverse consequences. Arterial catheters are commonly used in the critical care setting and are among the most heavily manipulated vascular access devices. We sought to evaluate the prevalence of arterial catheter-related bloodstream infection.
Data Sources: PubMed, CinAHL, EMBASE, and Web of Science.
Study Selection: Included studies reported prevalence rate of catheter-related bloodstream infection for arterial catheters used for critical illness or postoperative monitoring. For the purposes of this study, catheter-related bloodstream infection was defined as positive blood culture collected from an arterial catheter and from the periphery with the same organism in a patient demonstrating systemic signs of sepsis.
Data Extraction: The study population, site of insertion, antiseptic preparation, catheter days, and prevalence of catheter-related bloodstream infection were abstracted. When data were not available, authors were contacted for further information.
Data Synthesis: Forty-nine studies met criteria including 222 cases of arterial catheter-related bloodstream infection in 30,841 catheters. Pooled incidence was 3.40/1,000 catheters or 0.96/1,000 catheter days. Prevalence was considerably higher in the subgroup of studies that cultured all catheters (1.26/1,000 catheter days) compared with those studies that cultured only when the arterial catheter was suspected as the source for the catheter-related bloodstream infection (0.70/1,000 catheter days). Pooled data also found a significantly increased risk of infection for femoral site of insertion compared with radial artery for arterial catheter placement (relative risk, 1.93; 95% CI, 1.32-2.84; p = 0.001)
Conclusions: Arterial catheters are an underrecognized cause of catheter-related bloodstream infection. Pooled incidence when catheters were systematically cultured and correlated to blood culture results indicated a substantial burden of arterial catheter-related bloodstream infection. Selection of a radial site over a femoral site will help reduce the risk of arterial catheter-related bloodstream infection. Future studies should evaluate technologies applied to preventing central venous catheter-related bloodstream infection to arterial catheters as well.
C1 [O'Horo, John C.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA.
[Maki, Dennis G.; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Krupp, Anna E.; Safdar, Nasia] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Sect Infect Dis, Madison, WI USA.
[Safdar, Nasia] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA.
RP Safdar, N (reprint author), UW Med Fdn Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA.
EM ns2@medicine.wisc.edu
RI O'Horo, John/N-8681-2013
OI O'Horo, John/0000-0002-0880-4498
NR 62
TC 25
Z9 26
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2014
VL 42
IS 6
BP 1334
EP 1339
DI 10.1097/CCM.0000000000000166
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6UM
UT WOS:000336266900016
PM 24413576
ER
PT J
AU Quraishi, SA
Bittner, EA
Blum, L
McCarthy, CM
Bhan, I
Camargo, CA
AF Quraishi, Sadeq A.
Bittner, Edward A.
Blum, Livnat
McCarthy, Caitlin M.
Bhan, Ishir
Camargo, Carlos A., Jr.
TI Prospective Study of Vitamin D Status at Initiation of Care in
Critically III Surgical Patients and Risk of 90-Day Mortality
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE 25-hydroxyvitamin; bioavailable 25-hydroxyvitamin; intensive care unit;
mortality; vitamin D
ID D DEFICIENCY; ILL PATIENTS; HEMODIALYSIS-PATIENTS; MINERAL METABOLISM;
CRITICAL ILLNESS; UNIT; OUTCOMES; CALCIUM; ICU
AB Objectives: 1) To characterize vitamin D status at initiation of critical care in surgical ICU patients and 2) to determine whether this vitamin D status is associated with the risk of prolonged hospital length of stay, 90-day readmission, and 90-day mortality.
Design: Prospective cohort study.
Setting: A teaching hospital in Boston, MA.
Patients: Hundred surgical ICU patients.
Interventions: None.
Measurements and Main Results: Mean ( sd) serum total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were 17 +/- 8 ng/mL and 32 +/- 19 pg/mL, respectively. Mean calculated bioavailable 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were 2.5 +/- 2.0 ng/mL and 6.6 +/- 5.3 pg/mL, respectively. Receiver-operating characteristic curve analysis demonstrated that all of four vitamin D measures predicted the three clinical outcomes; total 25-hydroxyvitamin D was not inferior to the other measures. Median (interquartile range) hospital length of stay was 11 days (8-19 d). Poisson regression analysis, adjusted for biologically plausible covariates, demonstrated an association of total 25-hydroxyvitamin D with hospital length of stay (incident rate ratio per 1 ng/mL, 0.98; 95% CI, 0.97-0.98). The 90-day readmission and mortality rates were 24% and 22%, respectively. Even after adjustment for biologically plausible covariates, there remained significant associations of total 25-hydroxyvitamin D with readmission (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.74-0.95) and mortality (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.73-0.97).
Conclusions: Serum 25-hydroxyvitamin D levels within 24 hours of ICU admission may identify patients at high risk for prolonged hospitalization, readmission, and mortality. Randomized trials are needed to assess whether vitamin D supplementation can improve these clinically relevant outcomes in surgical ICU patients.
C1 [Quraishi, Sadeq A.; Bittner, Edward A.; Blum, Livnat; McCarthy, Caitlin M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Quraishi, Sadeq A.; Bittner, Edward A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
[Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Bhan, Ishir; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Quraishi, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM squraishi@partners.org
FU National Institutes of Health (NIH) [5T32GM007592-33, UL1 RR025758];
Harvard Medical School; NIH [K23 DK081677, R01 AI093723, U01 AI087881];
Massachusetts General Hospital
FX Dr. Quraishi received grant support from the National Institutes of
Health (NIH) (5T32GM007592-33 and UL1 RR025758) and Harvard Medical
School and received support for article research from NIH. His
institution received grant support from the NIH, Massachusetts General
Hospital, and Harvard Medical School. Dr. Bhan received support for
article research from NIH (K23 DK081677). His institution received grant
support from NIH. Dr. Camargo Jr received support for article research
from NIH (grants R01 AI093723 and U01 AI087881). His institution
received grant support from NIH. Dr. Bittner received support for
article research from the NIH. Dr. Blum received support for article
research from the NIH. Dr. McCarthy received support for article
research from the NIH.
NR 24
TC 25
Z9 31
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2014
VL 42
IS 6
BP 1365
EP 1371
DI 10.1097/CCM.0000000000000210
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6UM
UT WOS:000336266900020
PM 24557421
ER
PT J
AU Goverman, J
AF Goverman, Jeremy
TI Our Natural Defense: The Skin!
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE antimicrobial peptides; barrier function; burn; permeability barrier;
stratum corneum
ID BURNS; DEATH; PEPTIDES
C1 Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA.
RP Goverman, J (reprint author), Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA.
NR 13
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2014
VL 42
IS 6
BP 1575
EP 1577
DI 10.1097/CCM.0000000000000356
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6UM
UT WOS:000336266900065
PM 24836807
ER
PT J
AU Saddawi-Konefka, D
Alston, TA
AF Saddawi-Konefka, Daniel
Alston, Theodore A.
TI Tracking the Wily Speckle in Darkest Sepsis
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE bacteremia; Escherichia coli; myocardial edema; sepsis; strain
echocardiography
ID ESCHERICHIA-COLI; LEAKAGE; EDEMA
C1 [Saddawi-Konefka, Daniel; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Saddawi-Konefka, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
NR 14
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2014
VL 42
IS 6
BP 1577
EP 1579
DI 10.1097/CCM.0000000000000353
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6UM
UT WOS:000336266900066
PM 24836808
ER
PT J
AU Dimas, AS
Lagou, V
Barker, A
Knowles, JW
Magi, R
Hivert, MF
Benazzo, A
Rybin, D
Jackson, AU
Stringham, HM
Song, C
Fischer-Rosinsky, A
Boesgaard, TW
Grarup, N
Abbasi, FA
Assimes, TL
Hao, K
Yang, X
Lecoeur, C
Barroso, I
Bonnycastle, LL
Bottcher, Y
Bumpstead, S
Chines, PS
Erdos, MR
Graessler, J
Kovacs, P
Morken, MA
Narisu, N
Payne, F
Stancakova, A
Swift, AJ
Tonjes, A
Bornstein, SR
Cauchi, S
Froguel, P
Meyre, D
Schwarz, PEH
Haring, HU
Smith, U
Boehnke, M
Bergman, RN
Collins, FS
Mohlke, KL
Tuomilehto, J
Quertemous, T
Lind, L
Hansen, T
Pedersen, O
Walker, M
Pfeiffer, AFH
Spranger, J
Stumvoll, M
Meigs, JB
Wareham, NJ
Kuusisto, J
Laakso, M
Langenberg, C
Dupuis, J
Watanabe, RM
Florez, JC
Ingelsson, E
McCarthy, MI
Prokopenko, I
AF Dimas, Antigone S.
Lagou, Vasiliki
Barker, Adam
Knowles, Joshua W.
Maegi, Reedik
Hivert, Marie-France
Benazzo, Andrea
Rybin, Denis
Jackson, Anne U.
Stringham, Heather M.
Song, Ci
Fischer-Rosinsky, Antje
Boesgaard, Trine Wellov
Grarup, Niels
Abbasi, Fahim A.
Assimes, Themistocles L.
Hao, Ke
Yang, Xia
Lecoeur, Cecile
Barroso, Ines
Bonnycastle, Lori L.
Boettcher, Yvonne
Bumpstead, Suzannah
Chines, Peter S.
Erdos, Michael R.
Graessler, Jurgen
Kovacs, Peter
Morken, Mario A.
Narisu, Narisu
Payne, Felicity
Stancakova, Alena
Swift, Amy J.
Toenjes, Anke
Bornstein, Stefan R.
Cauchi, Stephane
Froguel, Philippe
Meyre, David
Schwarz, Peter E. H.
Haering, Hans-Ulrich
Smith, Ulf
Boehnke, Michael
Bergman, Richard N.
Collins, Francis S.
Mohlke, Karen L.
Tuomilehto, Jaakko
Quertemous, Thomas
Lind, Lars
Hansen, Torben
Pedersen, Oluf
Walker, Mark
Pfeiffer, Andreas F. H.
Spranger, Joachim
Stumvoll, Michael
Meigs, James B.
Wareham, Nicholas J.
Kuusisto, Johanna
Laakso, Markku
Langenberg, Claudia
Dupuis, Josee
Watanabe, Richard M.
Florez, Jose C.
Ingelsson, Erik
McCarthy, Mark I.
Prokopenko, Inga
CA MAGIC Investigators
TI Impact of Type 2 Diabetes Susceptibility Variants on Quantitative
Glycemic Traits Reveals Mechanistic Heterogeneity
SO DIABETES
LA English
DT Article
ID BETA-CELL FUNCTION; SCALE ASSOCIATION ANALYSIS; BODY-MASS INDEX; INSULIN
SENSITIVITY; PROINSULIN LEVELS; COMMON VARIANT; TCF7L2 GENE; GLUCOSE;
GENOME; LOCI
AB Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
C1 [Dimas, Antigone S.; Lagou, Vasiliki; Maegi, Reedik; Ingelsson, Erik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Dimas, Antigone S.] Biomed Sci Res Ctr, Athens, Greece.
[Lagou, Vasiliki; Maegi, Reedik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Barker, Adam; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA.
[Maegi, Reedik] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Benazzo, Andrea] Univ Ferrara, Dept Biol & Evolut, I-44100 Ferrara, Italy.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Song, Ci; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
[Song, Ci] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite, Dept Endocrinol & Metab, D-13353 Berlin, Germany.
[Boesgaard, Trine Wellov] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
[Hao, Ke] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA.
[Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA.
[Lecoeur, Cecile; Cauchi, Stephane; Froguel, Philippe; Meyre, David] Univ Lille 2, Inst Pasteur, Inst Biol, CNRS,UMR8199, Lille, France.
[Barroso, Ines; Bumpstead, Suzannah; Payne, Felicity] Wellcome Trust Sanger Inst, Hinxton, England.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England.
[Barroso, Ines] Addenbrookes Hosp, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge, England.
[Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Boettcher, Yvonne; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Med Ctr, IFB AdiposityDis, D-04109 Leipzig, Germany.
[Graessler, Jurgen; Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, Dresden, Germany.
[Kovacs, Peter] Interdisciplinary Ctr Clin Res Leipzig, Leipzig, Germany.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany.
[Froguel, Philippe; Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England.
[Meyre, David] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Vasc Med Nephrol & Clin C, Tubingen, Germany.
[Smith, Ulf] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res,Ctr Excellence Metab & Ca, Gothenburg, Sweden.
[Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia.
[Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden.
[Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
[Pedersen, Oluf] Hagedorn Res Inst, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Pfeiffer, Andreas F. H.] German Inst Human Nutr, Dept Clin Nutr, Nuthetal, Germany.
[Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England.
RP Prokopenko, I (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM rwatanab@usc.edu; jcflorez@partners.org; erik.ingelsson@medsci.uu.se;
mark.mccarthy@drl.ox.ac.uk; i.prokopenko@imperial.ac.uk
RI Grarup, Niels/K-2807-2015; Prokopenko, Inga/H-3241-2014; Schwarz,
Peter/B-5127-2013;
OI Grarup, Niels/0000-0001-5526-1070; Prokopenko, Inga/0000-0003-1624-7457;
Schwarz, Peter/0000-0001-6317-7880; Magi, Reedik/0000-0002-2964-6011;
Song, Ci/0000-0002-0947-9068; Rybin, Denis/0000-0002-3657-4829; Assimes,
Themistocles/0000-0003-2349-0009; Payne, Felicity/0000-0003-4228-581X
FU European Community [HEALTH-F4-2007-201413, LSHM-CT-2004-512013];
Wellcome Trust [WT098051, 098381]; Cambridge Biomedical Research Centre
of the U.K. National Institute for Health Research; Medical Research
Council Centre for Obesity and Related Metabolic Diseases; National
Heart, Lung, and Blood Institute's Framingham Heart Study
[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; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [R01 DK-078616]; NIDDK [K24
DK-080140]; Doris Duke Charitable Foundation Clinical Scientist
Development Award; NIH [DK-069922, U54 DA021519, DK-062370, DK-072193,
RR01066]; National Human Genome Research Institute [1 Z01 HG000024];
Agence Nationale de la Recherche; Conseil Regional Nord-Pas de
Calais/Fonds europeen de developpement economique et regional; Academy
of Finland [124243]; Clinical Research Group [KFO218/1]; Deutsche
Forschungsgemeinschaft (DFG) [SP716/2-1]; German Bundesministerium fur
Bildung und Forschung (BMBF); Mallinckrodt General Clinical Research
Program, National Center for Research Resources; Swedish Research
Council; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic
Research; Royal Swedish Academy of Science; Lundbeck Foundation Centre
of Applied Medical Genomics for Personalized Disease Prediction,
Prevention; Care; Danish Diabetes Association; Danish Research Council;
European Union [QLG1-CT-2001-01252]; AstraZeneca; German Research
Council [SF8-1052]; German Diabetes Association; Diabetes Hi Ifs;
Forschungsfonds Deutschland; Boehringer Ingelheim Foundation; BMBF [FKZ:
01E01001]; European Commission under the Marie Curie Intra-European
Fellowship; European Foundation; National Center for Research Resources,
NIH [2 M01 RR000070]; U.S. Public Health Service; American Heart
Association Fellow [10FTF3360005]
FX The major funding for this meta-analysis was provided through the
Seventh Framework Programme of the European Community (FP7/2007-2013),
the ENGAGE project, and grant agreement HEALTH-F4-2007-201413. As part
of the Ely Study, I.B. was supported by Wellcome Trust grant WT098051,
the Cambridge Biomedical Research Centre of the U.K. National Institute
for Health Research, and the Medical Research Council Centre for Obesity
and Related Metabolic Diseases. The EUGENE2 Study was supported by grant
LSHM-CT-2004-512013 from the European Community FP6 EUGENE2. The
Framingham Heart Study was conducted in part using data and resources
from the Framingham Heart Study of the National Heart, Lung, and Blood
Institute of the National Institutes of Health (NIH) and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource project. This work
was partially supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract no. N01-HC-25195) and its
contract with Affymetrix Inc. for genotyping services (contract no.
N02-HL-6-4278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II), which is funded by the Robert Dawson
Evans Endowment of the Department of Medicine at Boston University
School of Medicine and Boston Medical Center. The Framingham Heart Study
was also supported by National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) grant R01 DK-078616 to J.B.M., J.D., and J.C.F.;
NIDDK grant K24 DK-080140 to J.B.M.; and a Doris Duke Charitable
Foundation Clinical Scientist Development Award to J.C.F. Support for
the Finland-United States Investigation of NIDDM Genetics was provided
by NIH grants DK-069922 (to R.M.W.), U54 DA021519 (to R.M.W.), DK-062370
(to M.B.), and DK-072193 (to K.L.M.). Additional support comes from the
National Human Genome Research Institute intramural project number 1 Z01
HG000024 (to F.S.C.). The Metabolisches Syndrom Berlin Potsdam
(MESYBEPO) Study was supported by grants from Agence Nationale de la
Recherche and Conseil Regional Nord-Pas de Calais/Fonds europeen de
developpement economique et regional. Support for the Metabolic Syndrome
in Men Study was provided by grant 124243 from the Academy of Finland.
In the MESYBEPO Study, J.S. was supported by Clinical Research Group
grant KFO218/1, Heisenberg Professorship SP716/2-1 of the Deutsche
Forschungsgemeinschaft (DFG), and a research group on molecular
nutrition of the German Bundesministerium fur Bildung und Forschung
(BMBF). The Partners/Roche Cohort was supported by the Mallinckrodt
General Clinical Research Program, National Center for Research
Resources, and NIH grant RR01066. In the Prospective Investigation of
the Vasculature in Uppsala Seniors and the Uppsala Longitudinal Study of
Adult Men, the SNP Technology Platform is supported by Uppsala
University, Uppsala University Hospital, and the Swedish Research
Council for Infrastructures. El. was supported by grants from the
Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish
Foundation for Strategic Research, and the Royal Swedish Academy of
Science. The QTL families and UNG92 Study is supported by the Lundbeck
Foundation Centre of Applied Medical Genomics for Personalized Disease
Prediction, Prevention, and Care, The Danish Diabetes Association, and
The Danish Research Council.; The Relationship between Insulin
Sensitivity and Cardiovascular Disease Study is supported by European
Union grant QLG1-CT-2001-01252 and AstraZeneca. The Sorbs Study was
supported by grants from the German Research Council (SF8-1052 "Obesity
mechanisms") and the German Diabetes Association and the Diabetes Hi Ifs
und Forschungsfonds Deutschland. P.K. is funded by the Boehringer
Ingelheim Foundation. The Integrated Research and Treatment Center
Adiposity Diseases is supported by BMBF grant FKZ: 01E01001. I.P. and
V.L. were partially funded through the Seventh Framework Programme of
the European Community (grant FP7/2007-2013) and the ENGAGE project
grant agreement HEALTH-F4-2007-201413. R.M. is funded by the European
Commission under the Marie Curie Intra-European Fellowship and a
European Foundation for the Study of Diabetes New Horizons grant. M.I.M.
is supported by Wellcome Trust grant 098381. Sample collection for the
Stanford IST Cohort was carried out in part in the Clinical and
Translational Research Unit, Stanford University, with funds provided by
the National Center for Research Resources, NIH grant 2 M01 RR000070,
and the U.S. Public Health Service. J.W.K. is supported by American
Heart Association Fellow to Faculty Transition award 10FTF3360005.
NR 44
TC 77
Z9 79
U1 4
U2 32
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 JUN
PY 2014
VL 63
IS 6
BP 2158
EP 2171
DI 10.2337/db13-0949
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1VS
UT WOS:000336643900039
PM 24296717
ER
PT J
AU Vassy, JL
Hivert, MF
Porneala, B
Dauriz, M
Florez, JC
Dupuis, J
Siscovick, DS
Fornage, M
Rasmussen-Torvik, LJ
Bouchard, C
Meigs, JB
AF Vassy, Jason L.
Hivert, Marie-France
Porneala, Bianca
Dauriz, Marco
Florez, Jose C.
Dupuis, Josee
Siscovick, David S.
Fornage, Myriam
Rasmussen-Torvik, Laura J.
Bouchard, Claude
Meigs, James B.
TI Polygenic Type 2 Diabetes Prediction at the Limit of Common Variant
Detection
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS;
DENSITY-LIPOPROTEIN-CHOLESTEROL; LIFE-STYLE INTERVENTION; RISK-FACTORS;
AFRICAN-AMERICANS; GLUCOSE-TOLERANCE; RECLASSIFICATION; POPULATION;
MELLITUS
AB Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRS(t)) improves T2D prediction compared with previous less inclusive GRS(t); 2) separate GRS for beta-cell (GRS(beta)) and insulin resistance (GRS(IR)) independently predict T2D; and 3) the relationships between T2D and GRS(t), GRS(beta), or GRS(IR) do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRS(t) was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRS(t), respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRS(beta) but not GRS(IR) predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants.
C1 [Vassy, Jason L.; Hivert, Marie-France; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA.
[Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA.
[Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada.
[Porneala, Bianca; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA.
[Dauriz, Marco] Univ Verona Med Sch & Hosp Trust Verona, Div Endocrinol & Metab Dis, Dept Med, Verona, Italy.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Dupuis, Josee] Boston Univ Sch Publ Hlth, Depat Biostat, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA.
[Bouchard, Claude] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA.
RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA USA.
EM jmeigs@partners.org
RI Bouchard, Claude/A-7637-2009; Dauriz, Marco/S-5843-2016
OI Dauriz, Marco/0000-0002-5542-5941
FU National Institutes of Health [R01-DK-078616, K24-DK-080140,
U01-HG-006500, L30-DK089597]; National Heart, Lung, and Blood Institute
(NHLBI); University of Alabama at Birmingham [HHSN268201300025C,
HHSN268201300026C]; Northwestern University [HHSN268201300027C];
University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research
Institute [HHSN268201300029C]; Johns Hopkins University School of
Medicine [HHSN268200900041C]; Intramural Research Program of the
National Institute on Aging; NHLBI [N01-HC-25195]; Affymetrix, Inc.
[N02-HL-6-4278]
FX This work was supported by National Institutes of Health grants
(R01-DK-078616 and K24-DK-080140 to J.B.M. and U01-HG-006500 and
L30-DK089597 to J.L.V.). The CARDIA Study is conducted and supported by
the National Heart, Lung, and Blood Institute (NHLBI) in collaboration
with the University of Alabama at Birmingham (HHSN268201300025C and
HHSN268201300026C), Northwestern University (HHSN268201300027C),
University of Minnesota (HHSN268201300028C), Kaiser Foundation Research
Institute (HHSN268201300029C), and Johns Hopkins University School of
Medicine (HHSN268200900041C). CARDIA is also partially supported by the
Intramural Research Program of the National Institute on Aging. This
manuscript was reviewed by CARDIA personnel for scientific content. The
Framingham Heart Study was supported by the NHLBI (contract number
N01-HC-25195) and its contract with Affymetrix, Inc., for genotyping
services (contract number N02-HL-6-4278). A portion of this research was
conducted using the Linux Clusters for Genetic Analysis (LinGA)
computing resources at the Boston University Medical Campus.
NR 44
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U1 0
U2 18
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 JUN
PY 2014
VL 63
IS 6
BP 2172
EP 2182
DI 10.2337/db13-1663
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1VS
UT WOS:000336643900040
PM 24520119
ER
PT J
AU Inoue, T
Higashiyama, M
Kaji, I
Rudenkyy, S
Higuchi, K
Guth, PH
Engel, E
Kaunitz, JD
Akiba, Y
AF Inoue, Takuya
Higashiyama, Masaaki
Kaji, Izumi
Rudenkyy, Sergiy
Higuchi, Kazuhide
Guth, Paul H.
Engel, Eli
Kaunitz, Jonathan D.
Akiba, Yasutada
TI Dipeptidyl Peptidase IV Inhibition Prevents the Formation and Promotes
the Healing of Indomethacin-Induced Intestinal Ulcers in Rats
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Glucagon-like peptide-2; NSAIDs; Taste receptor
ID GLUCAGON-LIKE PEPTIDE-2; SHORT-BOWEL SYNDROME; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-I; INDUCED ENTEROPATHY; ENTERAL
NUTRIENTS; BICARBONATE SECRETION; AMINO-ACID; BLOOD-LOSS; GLP-2
AB We studied the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) as a possible therapy for non-steroidal anti-inflammatory drug (NSAID)-induced intestinal ulcers. Luminal nutrients release endogenous GLP-2 from enteroendocrine L cells. Since GLP-2 is degraded by dipeptidyl peptidase IV (DPPIV), we hypothesized that DPPIV inhibition combined with luminal administration of nutrients potentiates the effects of endogenous GLP-2 on intestinal injury.
Intestinal injury was induced by indomethacin (10 mg/kg, sc) in fed rats. The long-acting DPPIV inhibitor K579 was given intragastrically (ig) or intraperitoneally (ip) before or after indomethacin treatment. l-Alanine (l-Ala) and inosine 5'-monophosphate (IMP) were co-administered ig after the treatment.
Indomethacin treatment induced intestinal ulcers that gradually healed after treatment. Pretreatment with ig or ip K579 given at 1 mg/kg reduced total ulcer length, whereas K579 at 3 mg/kg had no effect. Exogenous GLP-2 also reduced intestinal ulcers. The preventive effect of K579 was dose-dependently inhibited by a GLP-2 receptor antagonist. Daily treatment with K579 (1 mg/kg), GLP-2, or l-Ala + IMP after indomethacin treatment reduced total ulcer length. Co-administration (ig) of K579 and l-Ala + IMP further accelerated intestinal ulcer healing.
DPPIV inhibition and exogenous GLP-2 prevented the formation and promoted the healing of indomethacin-induced intestinal ulcers, although high-dose DPPIV inhibition reversed the preventive effect. Umami receptor agonists also enhanced the healing effects of the DPPIV inhibitor. The combination of DPPIV inhibition and luminal nutrient-induced GLP-2 release may be a useful therapeutic tool for the treatment of NSAIDs-induced intestinal ulcers.
C1 [Inoue, Takuya; Higashiyama, Masaaki; Kaji, Izumi; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Inoue, Takuya; Higuchi, Kazuhide] Osaka Med Coll, Dept Internal Med 2, Osaka, Japan.
[Rudenkyy, Sergiy; Guth, Paul H.; Kaunitz, Jonathan D.; Akiba, Yasutada] Greater Los Angles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
[Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA.
[Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.] West Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA.
RP Kaunitz, JD (reprint author), West Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM jake@ucla.edu
FU Department of Veterans Affairs Merit Review Award, NIH-NIDDK [R01
DK54221]; NIH-NIDDK [P30 DK0413]
FX We thank Coleen and Bea Palileo for their assistance with manuscript
preparation. Supported by the Department of Veterans Affairs Merit
Review Award, NIH-NIDDK R01 DK54221 (J. Kaunitz), and the animal core of
NIH-NIDDK P30 DK0413 (J.E. Rozengurt).
NR 53
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U1 0
U2 7
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 JUN
PY 2014
VL 59
IS 6
BP 1286
EP 1295
DI 10.1007/s10620-013-3001-6
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH8KF
UT WOS:000336386000031
PM 24379150
ER
PT J
AU Hildebrandt, T
Shope, S
Varangis, E
Klein, D
Pfaff, DW
Yehuda, R
AF Hildebrandt, Tom
Shope, Sydney
Varangis, Eleanna
Klein, Diane
Pfaff, Donald W.
Yehuda, Rachel
TI Exercise reinforcement, stress, and beta-endorphins: An initial
examination of exercise in anabolic-androgenic steroid dependence
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Anabolic androgenic steroids; beta-endorphin; Cortisol; ACTH; Compulsive
exercise; Drug dependence
ID HEAVY-RESISTANCE EXERCISE; HEALTHY-YOUNG MEN; ACUTE HORMONAL RESPONSES;
GROWTH-FACTOR RESPONSES; RAT-BRAIN; NANDROLONE DECANOATE;
ANOREXIA-NERVOSA; PLASMA-CORTISOL; DOSE-RESPONSE; MALE HAMSTERS
AB Background: Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer.
Method: Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity x frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, beta-endorphin samples, and measures of mood, compulsive exercise, and body image.
Results: Between group differences indicated that on-cycle AAS users had the highest beta-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest beta-endorphin levels. Exercise value was positively correlated with beta-endorphin and symptoms of AAS dependence.
Conclusion: The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Yehuda, Rachel] Ichan Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Klein, Diane] NYU, Dept Psychiat, New York, NY 10016 USA.
[Pfaff, Donald W.] Rockefeller Univ, New York, NY 10021 USA.
[Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
RP Hildebrandt, T (reprint author), Ichan Sch Med Mt Sinai, Eating & Weight Disorders Program, Dept Psychiat, One Gustave Levy Pl,Box 1230, New York, NY 10029 USA.
EM hildebtb@hotmail.com
OI Hildebrandt, Thomas/0000-0001-7054-9590
FU NIDA K23 grant [DA024043]
FX Funds for this study were provided by NIDA K23 grant DA024043 awarded to
Dr. Hildebrandt. NIDA had no influence over the study design, execution
of the project, interpretation or results, or manuscript preparation.
NR 58
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U1 2
U2 24
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 JUN 1
PY 2014
VL 139
BP 86
EP 92
DI 10.1016/j.drugalcdep.2014.03.008
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AI2SI
UT WOS:000336708000012
PM 24690349
ER
PT J
AU Rautiainen, S
Wang, L
Gaziano, JM
Sesso, HD
AF Rautiainen, Susanne
Wang, Lu
Gaziano, J. Michael
Sesso, Howard D.
TI Who uses multivitamins? A cross-sectional study in the Physicians'
Health Study
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE Multivitamin; Cross-sectional; Cohort; Diet
ID FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; RANDOMIZED
CONTROLLED-TRIAL; DIETARY-SUPPLEMENT USERS; CARDIOVASCULAR-DISEASE;
NATIONAL-HEALTH; BETA-CAROTENE; CANCER; ADULTS; PREVENTION
AB The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins.
Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95 % confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors.
Overall, 36 % of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74 % more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16 % more likely to use multivitamins only. A 14, 24, and 26 % greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05).
Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease.
C1 [Rautiainen, Susanne; Wang, Lu; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA.
[Rautiainen, Susanne; Wang, Lu; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Rautiainen, Susanne] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA.
[Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Rautiainen, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA.
EM susanne.rautiainen@ki.se
FU National Institutes of Health (Bethesda, MD, USA) [CA 097193, CA 34944,
CA 40360, HL 26490, HL 34595]; Swedish Research Council for Health,
Working Life, and Welfare (FORTE) Fellowship
FX This work is supported by CA 097193, CA 34944, CA 40360, HL 26490, and
HL 34595 from the National Institutes of Health (Bethesda, MD, USA) as
well as a Swedish Research Council for Health, Working Life, and Welfare
(FORTE) Fellowship.
NR 24
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U1 3
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
EI 1436-6215
J9 EUR J NUTR
JI Eur. J. Nutr.
PD JUN
PY 2014
VL 53
IS 4
BP 1065
EP 1072
DI 10.1007/s00394-013-0608-5
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AI3YL
UT WOS:000336801700006
PM 24170064
ER
PT J
AU Hoganson, DM
Bassett, EK
Vacanti, JP
AF Hoganson, David M.
Bassett, Erik K.
Vacanti, Joseph P.
TI Lung tissue engineering
SO FRONTIERS IN BIOSCIENCE-LANDMARK
LA English
DT Article
DE Tissue Engineering; Scaffold; Decellularize; Biomimetic; Vascular
Network; Trachea; Review
ID ERYTHROCYTE/HEMOGLOBIN SOLUTION MIXTURES; MICROCHANNEL TECHNOLOGIES;
ARTIFICIAL LUNGS; OXYGEN-TRANSPORT; RECTANGULAR CHANNELS;
INITIAL-EXPERIENCE; BLOOD-VESSELS; STEM-CELLS; TRANSPLANTATION; DESIGN
AB Lung tissue engineering is an emerging field focused on the development of lung replacement devices and tissue to treat patients with end stage lung disease. Microfluidic based lung assist devices have been developed that have biomimetically designed vascular networks that achieve physiologic blood flow. Gas exchange in these devices occurs across a thin respiratory membrane. Designed for intrathoracic implantation as a bridge to transplant or destination therapy, these lung assist devices will allow ambulation and hospital discharge for patients with end stage lung disease. Decellularized lungs subsequently recellularized with epithelial and endothelial cells have been implanted in small animal models with demonstration of initial gas exchange. Further development of these tissues and scaling to large animal models will validate this approach and may be an organ source for lung transplantation. Initial clinical success has been achieved with decellularized tracheal implants using autologous stem cells. Development of microfluidic lung models using similar architecture to the lung assist device technology allows study of lung biology and diseases with manipulation of lung cells and respiratory membrane strain.
C1 [Hoganson, David M.; Bassett, Erik K.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA.
[Hoganson, David M.] Washington Univ, Dept Surg, St Louis, MO USA.
RP Vacanti, JP (reprint author), Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA.
EM jvacanti@partners.org
FU NIH [F32 DK076349-01]
FX The authors gratefully acknowledge support from the NIH (F32
DK076349-01, DMH).
NR 43
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Z9 4
U1 2
U2 15
PU FRONTIERS IN BIOSCIENCE INC
PI IRVINE
PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA
SN 1093-9946
EI 1093-4715
J9 FRONT BIOSCI-LANDMRK
JI Front. Biosci.
PD JUN 1
PY 2014
VL 19
BP 1227
EP 1239
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AI0WA
UT WOS:000336569800003
PM 24896347
ER
PT J
AU Suter, MJ
Gora, MJ
Lauwers, GY
Arnason, T
Sauk, J
Gallagher, KA
Kava, L
Tan, KM
Soomro, AR
Gallagher, TP
Gardecki, JA
Bouma, BE
Rosenberg, M
Nishioka, NS
Tearney, GJ
AF Suter, Melissa J.
Gora, Michalina J.
Lauwers, Gregory Y.
Arnason, Thomas
Sauk, Jenny
Gallagher, Kevin A.
Kava, Lauren
Tan, Khay M.
Soomro, Amna R.
Gallagher, Timothy P.
Gardecki, Joseph A.
Bouma, Brett E.
Rosenberg, Mireille
Nishioka, Norman S.
Tearney, Guillermo J.
TI Esophageal-guided biopsy with volumetric laser endomicroscopy and laser
cautery marking: a pilot clinical study
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; IN-VIVO; INTESTINAL
METAPLASIA; SURVEILLANCE; MICROSCOPY; ENDOSCOPY; DYSPLASIA; CANCER
AB Background: Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites.
Objective: The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo.
Design: A pilot feasibility study.
Setting: Massachusetts General Hospital. Patients: A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants.
Intervention: Volumetric laser endomicroscopy.
Main Outcome Measurements: Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks.
Results: There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations.
Limitations: This is a single-center feasibility study with a limited number of patients.
Conclusion: Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (Clinical trial registration number: NCT01439633.)
C1 [Suter, Melissa J.; Tan, Khay M.] Massachusetts Gen Hosp, Pulmonol & Crit Care Unit, Boston, MA 02114 USA.
[Suter, Melissa J.; Gora, Michalina J.; Gallagher, Kevin A.; Kava, Lauren; Soomro, Amna R.; Gallagher, Timothy P.; Gardecki, Joseph A.; Bouma, Brett E.; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Lauwers, Gregory Y.; Arnason, Thomas; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sauk, Jenny; Nishioka, Norman S.] Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA.
[Bouma, Brett E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA.
RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Fruit St,BHX604A, Boston, MA 02114 USA.
EM gtearney@partners.org
FU National Institutes of Health [R01DK091923, R01CA103769, R21CA141884,
R00CA134920]; NinePoint Medical
FX Study data were collected and managed with REDCap electronic data
capture tools hosted at Massachusetts General Hospital. Funding was
provided by grants from the National Institutes of Health R01DK091923
(G.K.T.), R01CA103769 (G.J.T.), R21CA141884 (G.J.T.), and R00CA134920
(M.J.S.). Massachusetts General Hospital has a licensing arrangement
with NinePoint Medical. M. Suter, B. Bouma, N. Nishioka, and G. Tearney
have the rights to receive royalties from this licensing arrangement. G.
Tearney, N. Nishioka, and B. Bouma consult for NinePoint Medical, and M.
Suter, B. Bouma, and G. Tearney receive sponsored research funding from
NinePoint Medical. All other authors disclosed no financial
relationships relevant to this publication.
NR 22
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U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
EI 1097-6779
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD JUN
PY 2014
VL 79
IS 6
BP 886
EP 896
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9XD
UT WOS:000336497700002
PM 24462171
ER
PT J
AU Attanasio, C
Nord, AS
Zhu, YW
Blow, MJ
Biddie, SC
Mendenhall, EM
Dixon, J
Wright, C
Hosseini, R
Akiyama, JA
Holt, A
Plajzer-Frick, I
Shoukry, M
Afzal, V
Ren, B
Bernstein, BE
Rubin, EM
Visel, A
Pennacchio, LA
AF Attanasio, Catia
Nord, Alex S.
Zhu, Yiwen
Blow, Matthew J.
Biddie, Simon C.
Mendenhall, Eric M.
Dixon, Jesse
Wright, Crystal
Hosseini, Roya
Akiyama, Jennifer A.
Holt, Amy
Plajzer-Frick, Ingrid
Shoukry, Malak
Afzal, Veena
Ren, Bing
Bernstein, Bradley E.
Rubin, Edward M.
Visel, Axel
Pennacchio, Len A.
TI Tissue-specific SMARCA4 binding at active and repressed regulatory
elements during embryogenesis
SO GENOME RESEARCH
LA English
DT Article
ID CHROMATIN-REMODELING COMPLEX; EMBRYONIC STEM-CELLS; MUSCLE DEVELOPMENT;
SWI/SNF COMPLEXES; SELF-RENEWAL; BRG1; ENHANCERS; GENOME; TRANSCRIPTION;
EXPRESSION
AB The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryogenesis remains poorly defined. To investigate the genome-wide binding landscape of SMARCA4 in differentiating tissues, we engineered a Smarca4 FLAG knock-in mouse line. Using ChIP-seq, we identified similar to 51,000 SMARCA4associated regions across six embryonic mouse tissues (forebrain, hindbrain, neural tube, heart, limb, and face) at midgestation (E11.5). The majority of these regions was distal from promoters and showed dynamic occupancy, with most distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To further characterize these regions, we profiled active and repressive histone marks in the same tissues and examined the intersection of informative chromatin states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4-associated elements characterized by activating and repressive chromatin signatures that were associated with tissue-specific up-or down-regulation of gene expression and relevant active/repressed biological pathways. We further demonstrate the predicted active regulatory properties of SMARCA4associated elements by retrospective analysis of tissue-specific enhancers and direct testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate a dual active/repressive function of SMARCA4 at distal regulatory sequences in vivo and support its role in tissue-specific gene regulation during embryonic development.
C1 [Attanasio, Catia; Nord, Alex S.; Zhu, Yiwen; Hosseini, Roya; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Blow, Matthew J.; Biddie, Simon C.; Wright, Crystal; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Biddie, Simon C.] Cambridge Univ NHS Trust, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
[Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, HHMI, Boston, MA 02114 USA.
[Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mendenhall, Eric M.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Dixon, Jesse; Ren, Bing] UCSD Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
RP Pennacchio, LA (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
EM lapennacchio@lbl.gov
RI Blow, Matthew/G-6369-2012; Visel, Axel/A-9398-2009; attanasio,
catia/D-5042-2017;
OI Blow, Matthew/0000-0002-8844-9149; Visel, Axel/0000-0002-4130-7784;
Biddie, Simon/0000-0002-8253-0253; Mendenhall, Eric/0000-0002-7395-6295
FU National Human Genome Research Institute [HG003988, U54HG006997]; Swiss
National Science Foundation (SNSF) Advanced Researcher fellowship;
NIH/NIGMS NRSA F32 [GM105202]; University of California
[DE-AC02-05CH11231]
FX L.A.P. and A.V. were supported by grants HG003988 and U54HG006997 funded
by the National Human Genome Research Institute. C.A. was supported by
the Swiss National Science Foundation (SNSF) Advanced Researcher
fellowship. A.S.N. was supported by NIH/NIGMS NRSA F32 fellowship
GM105202. Research was conducted at the E.O. Lawrence Berkeley National
Laboratory and performed under Department of Energy Contract
DE-AC02-05CH11231, University of California.
NR 52
TC 19
Z9 19
U1 0
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD JUN
PY 2014
VL 24
IS 6
BP 920
EP 929
DI 10.1101/gr.168930.113
PG 10
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA AI2BQ
UT WOS:000336662200004
PM 24752179
ER
PT J
AU Steinberg, BA
Hellkamp, AS
Lokhnygina, Y
Halperin, JL
Breithardt, G
Passman, R
Hankey, GJ
Patel, MR
Becker, RC
Singer, DE
Hacke, W
Berkowitz, SD
Nessel, CC
Mahaffey, KW
Fox, KAA
Califf, RM
Piccini, JP
AF Steinberg, Benjamin A.
Hellkamp, Anne S.
Lokhnygina, Yuliya
Halperin, Jonathan L.
Breithardt, Gunter
Passman, Rod
Hankey, Graeme J.
Patel, Manesh R.
Becker, Richard C.
Singer, Daniel E.
Hacke, Werner
Berkowitz, Scott D.
Nessel, Christopher C.
Mahaffey, Kenneth W.
Fox, Keith A. A.
Califf, Robert M.
Piccini, Jonathan P.
CA ROCKET AF Steering Comm & Investig
TI Use and outcomes of antiarrhythmic therapy in patients with atrial
fibrillation receiving oral anticoagulation: Results from the ROCKET AF
trial
SO HEART RHYTHM
LA English
DT Article
DE Atrial fibrillation; Antiarrhythmic drugs; Rivaroxaban; Warfarin;
Outcomes
ID WARFARIN; RIVAROXABAN; PREDICTION; AMIODARONE; EVENTS
AB BACKGROUND Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment.
OBJECTIVE To study the use and outcomes of AAD therapy in anticoagulated patients with AF.
METHODS Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin).
RESULTS Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were Less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly Lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; P-interaction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; P-inteiaction = .33).
CONCLUSION Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation.
C1 [Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA.
[Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA.
[Breithardt, Gunter] Hosp Univ Munster, Dept Cardiovasc Med, Munster, Germany.
[Passman, Rod] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia.
[Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hacke, Werner] Heidelberg Univ, Heidelberg, Germany.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA.
[Nessel, Christopher C.] Janssen Res & Development LLC, Raritan, NJ USA.
[Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
[Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Medi Inst, Durham, NC USA.
RP Steinberg, BA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM benjamin.steinberg@dm.duke.edu
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
FU Janssen Research & Development LLC, Raritan, NJ; Bayer Health Care AG,
Leverkusen, Germany; NTH T-32 training grant [5 T32 HL 7101-38, R34
HL113404-01]; Boehringer Ingelheim; Bristol-Myers Squibb; Pfizer;
Sanofi-Aventis; Johnson Johnson; Medtronic; Ortho-McNeil-Janssen
Pharmaceuticals; Bayer Health Care; Genzyme; Bayer; AstraZeneca; Daiichi
Sankyo; Eli Lilly; GlaxoSmithKline; Merck; Momenta Pharmaceuticals;
Novartis; Porto la; Pozen; Regado Biotechnologies; Medicines Company;
Ortho/McNeill; Polymedix; ARCA Biopharma; Boston Scientific; GE
Healthcare; ResMed; BMS/Pfizer; Forest Laboratories; Spectranetics
FX This work was supported by Janssen Research & Development LLC, Raritan,
NJ, and Bayer Health Care AG, Leverkusen, Germany.; Dr Steinberg was
funded by NTH T-32 training grant #5 T32 HL 7101-38 However, no
relationships exist related to the analysis presented. Dr Halperin has
received honoraria and served as a consultant and is on an advisory
board for Bayer and Johnson & Johnson. Dr Brcithardt has received
honoraria from Johnson & Johnson and Bayer and advisory board fees from
Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis.
Dr Passman has received speaker's bureau fees from Boehringer ingelheim,
Johnson & Johnson, and Medtronic and research support from Medtronic; he
is also funded by the NIH R34 HL113404-01. Dr Hankcy has received
honoraria for serving on executive committees for Johnson & Johnson and
Bayer. Dr Patel has received honoraria from Johnson & Johnson and Bayer
Health Care for serving on the executive committee of the ROCKET AF
trial; consulting fees from Ortho-McNeil-Janssen Pharmaceuticals and
Bayer Health Care; and advisory board fees from Genzyme. Dr Becker has
received research support from Bayer and Johnson & johnson. Dr Singer is
a consultant and member of a scientific advisory hoard for Bayer,
Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson &.
Johnson, and Pfizer; has an institutional research support contract with
Johnson & Johnson; and served as an unpaid ROCKET AF executive committee
member. Dr Hacke has received honoraria for serving on executive
committees for Johnson & Johnson and Bayer. Dr Berkowitz is a full-time
employee of Bayer Health Care Pharmaceuticals. Dr Nessel is a full-time
employee of Janssen Research & Development LLC. Dr Mahaffey has received
grant support (significant) from AstraZeneca, Bayer, Boehringer
Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly,
GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals,
Novartis, Porto la, Pozen, Regado Biotechnologies, Sanofi-Aventis,
Schering-Plough (now Merck), and The Medicines Company; he has also
received consulting fees (significant) from AstraZeneca and Johnson &
Johnson, (modest) Bayer, Boehringer Ingelheim, Bristol-Myers Squibb,
Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis,
Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plough
(now Merck). Dr Fox has received grant funding and honoraria from Bayer
and Johnson & Johnson. Dr Califf has received consulting fees and
research funding from Johnson & Johnson; all other industry interactions
are listed at www.dcri.org/about-us/conflict-of-interest. Dr Piccini has
received grants for clinical research from ARCA Biopharma, Boston
Scientific, GE Healthcare, Johnson & Johnson, and ResMed; he has also
received consulting fees from BMS/Pfizer, Johnson & Johnson, Forest
Laboratories, Medtronic, and Spectranetics.
NR 15
TC 12
Z9 13
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD JUN
PY 2014
VL 11
IS 6
BP 925
EP 932
DI 10.1016/j.hrthm.2014.03.006
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH8NU
UT WOS:000336395600003
PM 24833235
ER
PT J
AU Macri, V
Mahida, SN
Zhang, ML
Sinner, MF
Dolmatova, EV
Tucker, NR
McLellan, M
Shea, MA
Milan, DJ
Lunetta, KL
Benjamin, EJ
Ellinor, PT
AF Macri, Vincenzo
Mahida, Saagar N.
Zhang, Michael L.
Sinner, Moritz F.
Dolmatova, Elena V.
Tucker, Nathan R.
McLellan, Micheal
Shea, Marisa A.
Milan, David J.
Lunetta, Kathryn L.
Benjamin, Emelia J.
Ellinor, Patrick T.
TI A novel trafficking-defective HCN4 mutation is associated with
early-onset atrial fibrillation
SO HEART RHYTHM
LA English
DT Article
DE HCN4; Mutation; Atrial fibrillation; Electrophysiology
ID FUNCTIONAL EXPRESSION; SINUS BRADYCARDIA; PACEMAKER CHANNEL; DOMAIN;
HAPLOINSUFFICIENCY; DYSFUNCTION; TERMINUS; GENES
AB BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel, and HCN4 mutations are associated with familial sinus bradycardia and AF.
OBJECTIVE The purpose of this study was to determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF.
METHODS We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry, and confocal microscopy to functionally characterize novel variants.
RESULTS We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (7 variants) compared to the referents (3 variants). We determined that of the 7 novel HCN4 variants in our AF cases, 1 (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) did not traffic to cell membrane, whereas the remaining 6 were not functionally different from wild type. In addition, the 3 novel variants in our referents did not alter function compared to wild-type. Coexpression studies showed that the p.Pro257Ser mutant channel failed to colocalize with the wild-type HCN4 channel on the cell membrane.
CONCLUSION Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p. Pro257Ser carrier.
C1 [Macri, Vincenzo; Mahida, Saagar N.; Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Macri, Vincenzo; Mahida, Saagar N.; Dolmatova, Elena V.; Tucker, Nathan R.; Milan, David J.; Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA.
[Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
RP Ellinor, PT (reprint author), Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM ellinor@mgh.harvard.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [1RO1HL104156, 1K2411L105780,
1RO1HL092577]; Established Investigator Award from the American Heart
Association [13EIA14220013]; National Heart, Lung, and Blood Institute
[T32HL007208]; Heart Rhythm Society (The Max Schaldach Fellowship in
Cardiac Pacing and Electrophysiology)
FX Drs. Macri and Mahida contributed equally to this manuscript. The
current work was funded by National Institutes of Health Grants
1RO1HL104156 and 1K2411L105780 to Dr. Elinor and Grant 1RO1HL092577 to
Drs. Benjamin and Elinor. Dr. Ellinor is supported by an Established
Investigator Award from the American Heart Association (13EIA14220013).
Dr. Tucker was supported by award number T32HL007208 from the National
Heart, Lung, and Blood Institute. Dr. Macri is supported by the Heart
Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and
Electrophysiology).
NR 25
TC 9
Z9 9
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD JUN
PY 2014
VL 11
IS 6
BP 1055
EP 1062
DI 10.1016/j.hrthm.2014.03.002
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH8NU
UT WOS:000336395600021
PM 24607718
ER
PT J
AU Tsunemi, T
Krainc, D
AF Tsunemi, Taiji
Krainc, Dimitri
TI Zn2+ dyshomeostasis caused by loss of ATP13A2/PARK9 leads to lysosomal
dysfunction and alpha-synuclein accumulation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID P-TYPE ATPASE; MAMMALIAN ZINC TRANSPORTERS; KUFOR-RAKEB SYNDROME;
PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; CONFERS RESISTANCE;
INTESTINAL-CELLS; HOMEOSTASIS; EXPRESSION; PROTEINS
AB Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome (KRS) characterized by juvenile-onset parkinsonism, pyramidal signs and dementia. PARK9 belongs to type 5 P-type ATPase with its putative function as a cation transporter. Loss of PARK9 leads to lysosomal dysfunction and subsequent alpha-synuclein (alpha-Syn) accumulation. However, the mechanistic link between PARK9 and lysosomal dysfunction remains unclear. Here, we found that patient fibroblasts expressing mutant PARK9 or primary neurons with silenced PARK9 exhibited increased sensitivity to extracellular zinc (Zn2+). This effect was rescued with the Zn2+ chelators clioquinol or TPEN. PARK9-deficient cells showed decreased lysosomal sequestration of Zn2+ and increased expression of zinc transporters. Importantly, increased concentrations of Zn2+ (Zn2+ stress) resulted in lysosomal dysfunction that was partially restored by expression of wild-type PARK9. Zn2+ stress also caused increased expression of alpha-Syn and consequently decreased activity of the lysosomal enzyme glucocerebrosidase. Together, these data suggest that PARK9 loss of function leads to dyshomeostasis of intracellular Zn2+ that in turn contributes to lysosomal dysfunction and accumulation of alpha-Syn. It will be of interest to examine whether therapeutic lowering of zinc may prove beneficial for patients with KRS.
C1 [Tsunemi, Taiji; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
RP Krainc, D (reprint author), MassGen Inst Neurodegenerat Dis, 114 16th St,Room 2008, Charlestown, MA 02129 USA.
EM krainc@helix.mgh.harvard.edu
FU National Institute of Health [R01NS076054]
FX This work was supported by National Institute of Health (R01NS076054 to
D.K.).
NR 57
TC 39
Z9 41
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2014
VL 23
IS 11
BP 2791
EP 2801
DI 10.1093/hmg/ddt572
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AH9ST
UT WOS:000336483200001
PM 24334770
ER
PT J
AU Moayyeri, A
Hsu, YH
Karasik, D
Estrada, K
Xiao, SM
Nielson, C
Srikanth, P
Giroux, S
Wilson, SG
Zheng, HF
Smith, AV
Pye, SR
Leo, PJ
Teumer, A
Hwang, JY
Ohlsson, C
McGuigan, F
Minster, RL
Hayward, C
Olmos, JM
Lyytikainen, LP
Lewis, JR
Swart, KMA
Masi, L
Oldmeadow, C
Holliday, EG
Cheng, SL
van Schoor, NM
Harvey, NC
Kruk, M
Fabiola Del Greco, M
Igl, W
Trummer, O
Grigoriou, E
Luben, R
Liu, CT
Zhou, YH
Oei, L
Medina-Gomez, C
Zmuda, J
Tranah, G
Brown, SJ
Williams, FM
Soranzo, N
Jakobsdottir, J
Siggeirsdottir, K
Holliday, KL
Hannemann, A
Go, MJ
Garcia, M
Polasek, O
Laaksonen, M
Zhu, K
Enneman, AW
McEvoy, M
Peel, R
Sham, PC
Jaworski, M
Johansson, A
Hicks, AA
Pludowski, P
Scott, R
Dhonukshe-Rutten, RAM
van der Velde, N
Kahonen, M
Viikari, JS
Sievanen, H
Raitakari, OT
Gonzalez-Macias, J
Hernandez, JL
Mellstroom, D
Ljunggren, O
Cho, YS
Volker, U
Nauck, M
Homuth, G
Volzke, H
Haring, R
Brown, MA
McCloskey, E
Nicholson, GC
Eastell, R
Eisman, JA
Jones, G
Reid, IR
Dennison, EM
Wark, J
Boonen, S
Vanderschueren, D
Wu, FCW
Aspelund, T
Richards, JB
Bauer, D
Hofman, A
Khaw, KT
Dedoussis, G
Obermayer-Pietsch, B
Gyllensten, U
Pramstaller, PP
Lorenc, RS
Cooper, C
Kung, AWC
Lips, P
Alen, M
Attia, J
Brandi, ML
de Groot, LCPGM
Lehtimaki, T
Riancho, JA
Campbell, H
Liu, YM
Harris, TB
Akesson, K
Karlsson, M
Lee, JY
Wallaschofski, H
Duncan, EL
O'Neill, TW
Gudnason, V
Spector, TD
Rousseau, F
Orwoll, E
Cummings, SR
Wareham, NJ
Rivadeneira, F
Uitterlinden, AG
Prince, RL
Kiel, DP
Reeve, J
Kaptoge, SK
AF Moayyeri, Alireza
Hsu, Yi-Hsiang
Karasik, David
Estrada, Karol
Xiao, Su-Mei
Nielson, Carrie
Srikanth, Priya
Giroux, Sylvie
Wilson, Scott G.
Zheng, Hou-Feng
Smith, Albert V.
Pye, Stephen R.
Leo, Paul J.
Teumer, Alexander
Hwang, Joo-Yeon
Ohlsson, Claes
McGuigan, Fiona
Minster, Ryan L.
Hayward, Caroline
Olmos, Jose M.
Lyytikaeinen, Leo-Pekka
Lewis, Joshua R.
Swart, Karin M. A.
Masi, Laura
Oldmeadow, Chris
Holliday, Elizabeth G.
Cheng, Sulin
van Schoor, Natasja M.
Harvey, Nicholas C.
Kruk, Marcin
Fabiola Del Greco, M.
Igl, Wilmar
Trummer, Olivia
Grigoriou, Efi
Luben, Robert
Liu, Ching-Ti
Zhou, Yanhua
Oei, Ling
Medina-Gomez, Carolina
Zmuda, Joseph
Tranah, Greg
Brown, Suzanne J.
Williams, Frances M.
Soranzo, Nicole
Jakobsdottir, Johanna
Siggeirsdottir, Kristin
Holliday, Kate L.
Hannemann, Anke
Go, Min Jin
Garcia, Melissa
Polasek, Ozren
Laaksonen, Marika
Zhu, Kun
Enneman, Anke W.
McEvoy, Mark
Peel, Roseanne
Sham, Pak Chung
Jaworski, Maciej
Johansson, Asa
Hicks, Andrew A.
Pludowski, Pawel
Scott, Rodney
Dhonukshe-Rutten, Rosalie A. M.
van der Velde, Nathalie
Kaehoenen, Mika
Viikari, Jorma S.
Sievaenen, Harri
Raitakari, Olli T.
Gonzalez-Macias, Jesus
Hernandez, Jose L.
Mellstroem, Dan
Ljunggren, Oesten
Cho, Yoon Shin
Voelker, Uwe
Nauck, Matthias
Homuth, Georg
Voelzke, Henry
Haring, Robin
Brown, Matthew A.
McCloskey, Eugene
Nicholson, Geoffrey C.
Eastell, Richard
Eisman, John A.
Jones, Graeme
Reid, Ian R.
Dennison, Elaine M.
Wark, John
Boonen, Steven
Vanderschueren, Dirk
Wu, Frederick C. W.
Aspelund, Thor
Richards, J. Brent
Bauer, Doug
Hofman, Albert
Khaw, Kay-Tee
Dedoussis, George
Obermayer-Pietsch, Barbara
Gyllensten, Ulf
Pramstaller, Peter P.
Lorenc, Roman S.
Cooper, Cyrus
Kung, Annie Wai Chee
Lips, Paul
Alen, Markku
Attia, John
Luisa Brandi, Maria
de Groot, Lisette C. P. G. M.
Lehtimaeki, Terho
Riancho, Jose A.
Campbell, Harry
Liu, Yongmei
Harris, Tamara B.
Akesson, Kristina
Karlsson, Magnus
Lee, Jong-Young
Wallaschofski, Henri
Duncan, Emma L.
O'Neill, Terence W.
Gudnason, Vilmundur
Spector, Timothy D.
Rousseau, Francois
Orwoll, Eric
Cummings, Steven R.
Wareham, Nick J.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Prince, Richard L.
Kiel, Douglas P.
Reeve, Jonathan
Kaptoge, Stephen K.
TI Genetic determinants of heel bone properties: genome-wide association
meta-analysis and replication in the GEFOS/GENOMOS consortium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; QUANTITATIVE ULTRASOUND; MINERAL DENSITY;
OSTEOPOROSIS; FRACTURE; RISK; DENSITOMETRY; PHENOTYPES; CALCANEUS; WOMEN
AB Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
C1 [Moayyeri, Alireza; Luben, Robert; Khaw, Kay-Tee; Reeve, Jonathan; Kaptoge, Stephen K.] Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge CB1 8RN, England.
[Moayyeri, Alireza; Wilson, Scott G.; Williams, Frances M.; Richards, J. Brent; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Enneman, Anke W.; van der Velde, Nathalie; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Estrada, Karol] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Dept Med, Boston, MA USA.
[Estrada, Karol] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI, Leiden, Netherlands.
[Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China.
[Nielson, Carrie; Srikanth, Priya] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Orwoll, Eric] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA.
[Giroux, Sylvie; Rousseau, Francois] HSFA, Ctr Rech CHU Quebec, Quebec City, PQ, Canada.
[Wilson, Scott G.; Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Wilson, Scott G.; Lewis, Joshua R.; Brown, Suzanne J.; Zhu, Kun; Prince, Richard L.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6000, Australia.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Med, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Human Genet, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Epidemiol, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Biostat, Montreal, PQ, Canada.
[Smith, Albert V.; Jakobsdottir, Johanna; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Pye, Stephen R.; Holliday, Kate L.; O'Neill, Terence W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9WL, Lancs, England.
[Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England.
[Leo, Paul J.; Brown, Matthew A.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Human Genet Grp, Brisbane, Qld, Australia.
[Teumer, Alexander; Voelker, Uwe; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
[Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.
[Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Lab Med, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Hwang, Joo-Yeon; Go, Min Jin; Lee, Jong-Young] NIH, Ctr Genome Sci, Chungcheongbuk, South Korea.
[Ohlsson, Claes; Mellstroem, Dan] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
[McGuigan, Fiona; Akesson, Kristina; Karlsson, Magnus] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Malmo, Sweden.
[Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden.
[Minster, Ryan L.] Univ Pittsburgh, Dept Human Genet, Pitsburgh, PA USA.
[Zmuda, Joseph] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pitsburgh, PA USA.
[Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Univ Cantabria, Dept Med, E-39005 Santander, Spain.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Hosp Univ Marques Valdecilla, Dept Internal Med, Santander, Spain.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Spain.
[Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, Sch Med, FIN-33101 Tampere, Finland.
[Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, Sch Med, FIN-33101 Tampere, Finland.
[Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Lips, Paul] Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands.
[Lips, Paul] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Masi, Laura] Univ Florence, Metab Bone Dis Unit AOUC, Florence, Italy.
[Luisa Brandi, Maria] Univ Florence, Dept Surg & Translat Med, Florence, Italy.
[Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia.
[Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Cheng, Sulin] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland.
[Harvey, Nicholas C.; Dennison, Elaine M.; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Kruk, Marcin; Jaworski, Maciej; Pludowski, Pawel; Lorenc, Roman S.] Childrens Mem Hlth Inst, Dept Biochem Radioimmunol & Expt Med, Warsaw, Poland.
[Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Igl, Wilmar; Johansson, Asa; Gyllensten, Ulf] SciLifeLab, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Ljunggren, Oesten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Trummer, Olivia; Obermayer-Pietsch, Barbara] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria.
[Grigoriou, Efi; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece.
[Liu, Ching-Ti; Zhou, Yanhua] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, Calif Pacif Med Ctr Res Inst, San Francisco, CA 94143 USA.
[Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Soranzo, Nicole] Wellcome Trust Res Labs, Sanger Inst, Cambridge, England.
[Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia.
[Laaksonen, Marika] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.
[Dhonukshe-Rutten, Rosalie A. M.; de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 AP Wageningen, Netherlands.
[van der Velde, Nathalie] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands.
[Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Viikari, Jorma S.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Sievaenen, Harri] UKK Inst Hlth Promot Res, Tampere, Finland.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
[McCloskey, Eugene] Univ Sheffield, Natl Inst Hlth & Res NIHR, Musculoskeletal Biomed Res Unit, Sheffield, S Yorkshire, England.
[McCloskey, Eugene; Eastell, Richard] Univ Sheffield, Acad Unit Bone Metab, Metab Bone Ctr, Sheffield, S Yorkshire, England.
[Nicholson, Geoffrey C.] Univ Queensland, Rural Clin Sch, Toowoomba, Qld, Australia.
[Eisman, John A.] Garvan Inst Med Res, Clin Translat & Adv Educ & Osteoporosis & Bone Bi, Sydney, NSW, Australia.
[Eisman, John A.] Univ New S Wales, Dept ofMedicine, Kensington, NSW 2033, Australia.
[Eisman, John A.] Univ Notre Dame, Sch Med Sydney, Sydney, NSW, Australia.
[Eisman, John A.] St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia.
[Jones, Graeme] Univ Tasmania, Menzies Res Inst, Hobart, Tas, Australia.
[Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand.
[Wark, John] Royal Melbourne Hosp, Dept Clin Sci, Melbourne, Vic, Australia.
[Boonen, Steven] Katholieke Univ Leuven, Div Geriatr Med, Leuven, Belgium.
[Boonen, Steven] Katholieke Univ Leuven, Ctr Metab Bone Dis, Leuven, Belgium.
[Vanderschueren, Dirk] Katholieke Univ Leuven, Dept Androl & Endocrinol, Leuven, Belgium.
[Cooper, Cyrus; Reeve, Jonathan] Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Inst Musculoskeletal Sci, Oxford, England.
[Alen, Markku] Oulu Univ Hosp, Dept Rehabil Med, Oulu, Finland.
[Alen, Markku] Inst Hlth Sci, Oulu, Finland.
[Campbell, Harry] Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA.
[Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Brisbane, Qld, Australia.
[Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada.
[Rousseau, Francois] Univ Laval, APOGEE Net, CanGeneTest Network Genet Hlth Serv & Policy, Quebec City, PQ, Canada.
[Wareham, Nick J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Reeve, Jonathan; Kaptoge, Stephen K.] Strangeways Res Lab, Cambridge CB1 4RN, England.
RP Kaptoge, SK (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England.
EM stephen@srl.cam.ac.uk
RI Lyytikainen, Leo-Pekka/C-8544-2016; Oei, Ling/E-8163-2013; Smith,
Albert/K-5150-2015; Pye, Stephen/D-9236-2011; Hayward,
Caroline/M-8818-2016; Hicks, Andrew/E-9518-2017; Polasek,
Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Duncan,
Emma/L-1224-2013; Aspelund, Thor/C-5983-2008; Pramstaller,
Peter/C-2357-2008; Nicholson, Geoffrey/F-1901-2010; Leo,
Paul/B-3470-2011; Lewis, Joshua/D-5077-2013; Moayyeri,
Alireza/N-3332-2014; Reeve, Jonathan/C-7551-2012; Gudnason,
Vilmundur/K-6885-2015
OI Johansson, Asa/0000-0002-2915-4498; Brown, Matthew
A/0000-0003-0538-8211; de Groot, Lisette /0000-0003-2778-2789; Luben,
Robert/0000-0002-5088-6343; Soranzo, Nicole/0000-0003-1095-3852;
Karasik, David/0000-0002-8826-0530; Medina-Gomez,
Carolina/0000-0001-7999-5538; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Oei, Ling/0000-0003-3523-458X; Smith,
Albert/0000-0003-1942-5845; Pye, Stephen/0000-0002-7263-2897; Hayward,
Caroline/0000-0002-9405-9550; Hicks, Andrew/0000-0001-6320-0411; van der
Velde, Nathalie/0000-0002-6477-6209; Kiel, Douglas/0000-0001-8474-0310;
Williams, Frances/0000-0002-2998-2744; Polasek,
Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441;
Duncan, Emma/0000-0002-8143-4403; Aspelund, Thor/0000-0002-7998-5433;
Nicholson, Geoffrey/0000-0002-0152-1153; Leo, Paul/0000-0001-8325-4134;
Lewis, Joshua/0000-0003-1003-8443; Moayyeri,
Alireza/0000-0002-9143-2161; Reeve, Jonathan/0000-0002-4364-2682;
Gudnason, Vilmundur/0000-0001-5696-0084
FU European Commission [HEALTH-F2-2008-201865-GEFOS]
FX This research and the Genetic Factors for Osteoporosis (GEFOS)
consortium have been funded by the European Commission
(HEALTH-F2-2008-201865-GEFOS). Several other sources of funding and
people have supported work in the contributing cohorts as acknowledged
in Supplementary Material, Table S2.
NR 43
TC 27
Z9 28
U1 2
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2014
VL 23
IS 11
BP 3054
EP 3068
DI 10.1093/hmg/ddt675
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AH9ST
UT WOS:000336483200021
PM 24430505
ER
PT J
AU Kamihara, J
Rana, HQ
Garber, JE
AF Kamihara, Junne
Rana, Huma Q.
Garber, Judy E.
TI Germline TP53 Mutations and the Changing Landscape of Li-Fraumeni
Syndrome
SO HUMAN MUTATION
LA English
DT Review
DE TP53; p53; cancer; Li-Fraumeni syndrome; germline; screening;
management; genetic counseling
ID ADRENAL-CORTICAL CARCINOMA; ONSET BREAST-CANCER; SOFT-TISSUE-SARCOMA;
P53 GENE; SOUTHERN BRAZIL; RELATIVE FREQUENCY; COLORECTAL-CANCER;
FAMILIAL SYNDROME; PEDIATRIC CANCER; R337H MUTATION
AB Since its description by Li and Fraumeni over 40 years ago, Li-Fraumeni syndrome (LFS) remains one of the most striking familial cancer predisposition syndromes. Children and adults are affected by a wide array of cancers that occur predominantly at younger ages. This review discusses LFS, describes its association with TP53, and examines the classic and evolving definitions of the syndrome. The potential implications of multigene assessments of individuals at increased cancer risk, which have already begun to identify those with very little personal or family cancer history carrying germline TP53 mutations, are considered. Newer options in the management of individuals with LFS are also discussed, highlighting the importance of further clinical trials for cancer detection, prevention, and management. Finally, we observe how the clinical criteria for TP53 mutation screening appear to be evolving as our understanding of the impact of germline TP53 mutations continues to expand.
C1 [Kamihara, Junne] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA USA.
[Kamihara, Junne] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA.
[Rana, Huma Q.; Garber, Judy E.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA.
RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Judy_Garber@dfci.harvard.edu
OI Rana, Huma/0000-0002-1598-6752
FU NCI NIH HHS [T32 CA136432]
NR 85
TC 30
Z9 31
U1 1
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD JUN
PY 2014
VL 35
IS 6
SI SI
BP 654
EP 662
DI 10.1002/humu.22559
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AI1NX
UT WOS:000336618900003
PM 24706533
ER
PT J
AU Cornejo, KM
Hutchinson, L
Deng, A
Tomaszewicz, K
Welch, M
Lyle, S
Dresser, K
Cosar, EF
AF Cornejo, Kristine M.
Hutchinson, Lloyd
Deng, April
Tomaszewicz, Keith
Welch, Matthew
Lyle, Stephen
Dresser, Karen
Cosar, Ediz F.
TI BRAF/KRAS gene sequencing of sebaceous neoplasms after mismatch repair
protein analysis
SO HUMAN PATHOLOGY
LA English
DT Article
DE Muir-Torre syndrome; Lynch syndrome; Sebaceous neoplasms; Mismatch
repair genes; KRAS; BRAF; Microsatellite instability
ID MUIR-TORRE-SYNDROME; NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE
INSTABILITY; LYNCH-SYNDROME; ENDOMETRIAL CANCER; KRAS MUTATIONS; BRAF
MUTATION; GLAND TUMORS; CARCINOMAS; IMMUNOHISTOCHEMISTRY
AB Sebaceous neoplasms are cutaneous markers for the autosomal-dominant Muir-Tone syndrome (MTS). This phenotypic variant of Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. Microsatellite instability or loss of protein expression suggests a mutation or promoter hypermethylation in 1 of the MMR. genes. BRAF gene sequencing may help to distinguish between patients with sporadic and LS-associated colorectal carcinomas with loss of MLH1 expression. LS-associated carcinomas are virtually negative for BRAF mutations, but a subset harbors KRAS mutations. The aim of our study was to test sebaceous neoplasms for V600E BRAF or KRAS mutations to determine if these mutations are associated with somatic or germline MMR defects, analogous to colorectal carcinomas. Over a 4-year period, 32 cases comprising 21 sebaceous adenomas, 3 sebaceomas, and 8 sebaceous carcinomas with sufficient material for testing were collected. MMR immunohistochemistry showed that 7 neoplasms had combined loss of MLH1-PMS2, 16 neoplasms had combined loss of MSH2-MSH6, 2 neoplasms had solitary loss of MSH6, and 7 sebaceous neoplasms had intact protein expression. BRAF/KRAS testing revealed all sebaceous neoplasms contained a wild-type BRAF gene. Two (15%) of 13 patients with MTS were found to harbor a KRAS mutation and loss of MLH1 expression. We conclude that a V600E BRAF mutation may not be helpful in distinguishing sporadic from MTS-associated sebaceous neoplasms. Further studies are needed to determine if KRAS mutations are restricted to patients with MTS or are also present in sporadic sebaceous neoplasms. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Cornejo, Kristine M.; Hutchinson, Lloyd; Deng, April; Tomaszewicz, Keith; Welch, Matthew; Lyle, Stephen; Dresser, Karen; Cosar, Ediz F.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Dept Pathol, Worcester, MA 01605 USA.
RP Cornejo, KM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA.
EM kcornejo@partners.org
NR 33
TC 6
Z9 6
U1 0
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 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD JUN
PY 2014
VL 45
IS 6
BP 1213
EP 1220
DI 10.1016/j.humpath.2014.02.001
PG 8
WC Pathology
SC Pathology
GA AI1UG
UT WOS:000336640000013
PM 24767862
ER
PT J
AU Kubiak, DW
Gilmore, ET
Buckley, MW
Lynch, R
Marty, FM
Koo, S
AF Kubiak, David W.
Gilmore, Erin T.
Buckley, Mary W.
Lynch, Robert
Marty, Francisco M.
Koo, Sophia
TI Adjunctive management of central line-associated bloodstream infections
with 70% ethanol-lock therapy
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
DE catheter-related infections; biofilms; salvage therapy
ID IN-VITRO EFFICACIES; INTRAVASCULAR DEVICES; CANDIDA-ALBICANS; CATHETER;
BIOFILMS; METAANALYSIS
AB Ethanol is bactericidal against most pathogens implicated in central line-associated bloodstream infections (CLABSIs) and biofilms. Current Infectious Diseases Society of America guidelines cite insufficient evidence to support adjunctive ethanol-lock therapy (ELT) for central venous catheter (CVC) salvage in patients with CLABSI in combination with systemic antimicrobial treatment. We evaluated the safety and potential efficacy of 70% ELT for CLABSI at our institution after implementation of a hospital ELT protocol.
We collected data on all patients treated with adjunctive 70% ELT for catheter salvage from September 2009 to September 2011 and assessed clinical outcomes and adverse events associated with ELT.
Sixty-eight hospitalized patients received 70% ELT for CVC salvage: 45 (66%) met the criteria for CLABSI. Five (11%) had persistent or recurrent bacteraemia triggering CVC removal; 28 (62%) preserved their CVC long term. There were no documented adverse events associated with ELT.
Adjunctive 70% ELT is an inexpensive, well-tolerated option for CVC salvage in patients with CLABSI and warrants further investigation.
C1 [Kubiak, David W.; Gilmore, Erin T.; Buckley, Mary W.; Lynch, Robert; Marty, Francisco M.; Koo, Sophia] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Marty, Francisco M.; Koo, Sophia] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Marty, Francisco M.; Koo, Sophia] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Kubiak, DW (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM dwkubiak@partners.org
OI Koo, Sophia/0000-0002-4973-7439
FU National Institutes of Health [AI097225]
FX The work was carried out in part with support from the National
Institutes of Health (AI097225 to S. K.).
NR 17
TC 5
Z9 5
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
EI 1460-2091
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD JUN
PY 2014
VL 69
IS 6
BP 1665
EP 1668
DI 10.1093/jac/dku017
PG 4
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA AH9ZU
UT WOS:000336506300035
PM 24526514
ER
PT J
AU Hwang, TJ
Hooper, DC
AF Hwang, Thomas J.
Hooper, David C.
TI Association between fluoroquinolone resistance and resistance to other
antimicrobial agents among Escherichia coli urinary isolates in the
outpatient setting: a national cross-sectional study
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Letter
DE urinary tract infections; ambulatory care; antimicrobial resistance; E.
coli; evidence-based prescribing; public health; surveillance
ID QUINOLONE RESISTANCE; SURVEILLANCE; PLASMID; WOMEN
C1 [Hwang, Thomas J.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA.
[Hwang, Thomas J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Program Regulat Therapeut & Law, Boston, MA 02115 USA.
[Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hwang, TJ (reprint author), Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA.
EM tjhwang@fas.harvard.edu
NR 10
TC 5
Z9 5
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
EI 1460-2091
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD JUN
PY 2014
VL 69
IS 6
BP 1720
EP 1722
DI 10.1093/jac/dku029
PG 3
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA AH9ZU
UT WOS:000336506300048
PM 24521853
ER
PT J
AU Grannan, BL
Yanamadala, V
Walcott, BP
Stapleton, CJ
Ogilvy, CS
AF Grannan, Benjamin L.
Yanamadala, Vijay
Walcott, Brian P.
Stapleton, Christopher J.
Ogilvy, Christopher S.
TI Repeated neurovascular imaging in subarachnoid hemorrhage when initial
studies are negative
SO JOURNAL OF CLINICAL NEUROSCIENCE
LA English
DT Article
DE Angiography; Cerebral angiography; Intracranial aneurysm; Subarachnoid
hemorrhage
ID CATHETER ANGIOGRAPHY; CEREBRAL ANEURYSMS; CLINICAL-COURSE; CT
AB Approximately 15% of patients with non-traumatic subarachnoid hemorrhage have no causative lesion identified on their initial angiogram. We present two patients with non-traumatic subarachnoid hemorrhage with negative initial angiograms who were subsequently found to have small basilar perforator aneurysms on delayed neurovascular imaging. We discuss the possible mechanisms for false negative diagnostic cerebral angiograms. These patients support the current standard of care with repeat angiography in cases of subarachnoid hemorrhage when no causative lesion can be identified on initial neurovascular imaging. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA.
EM walcott.brian@mgh.harvard.edu
FU Brain Aneurysm Foundation
FX Grant support for this work was provided to B.P.W. by the Brain Aneurysm
Foundation. The funders had no role in the design and conduct of the
study, the collection, management, analysis, and interpretation of the
data, or in the preparation, review, or approval of the manuscript.
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0967-5868
EI 1532-2653
J9 J CLIN NEUROSCI
JI J. Clin. Neurosci.
PD JUN
PY 2014
VL 21
IS 6
BP 993
EP 996
DI 10.1016/j.jocn.2013.11.002
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI2QT
UT WOS:000336703800019
PM 24398343
ER
PT J
AU Simon, MV
Sheth, SA
Eckhardt, CA
Kilbride, RD
Braver, D
Williams, Z
Curry, W
Cahill, D
Eskandar, EN
AF Simon, Mirela V.
Sheth, Sameer A.
Eckhardt, Christine A.
Kilbride, Ronan D.
Braver, Diana
Williams, Ziv
Curry, William
Cahill, Dan
Eskandar, Emad N.
TI Phase reversal technique decreases cortical stimulation time during
motor mapping
SO JOURNAL OF CLINICAL NEUROSCIENCE
LA English
DT Article
DE Cortical stimulation; Motor mapping; Phase reversal technique
ID BRAIN-TUMORS; EPILEPSY SURGERY; INTRAOPERATIVE STIMULATION; STIMULUS
THRESHOLDS; SENSORIMOTOR CORTEX; SURGICAL RESECTION; PROGNOSTIC-FACTORS;
EVOKED-POTENTIALS; CENTRAL REGION; LOW-GRADE
AB Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in supratentorial surgery. Electrical cortical stimulation is guided by anatomic landmarks towards the precentral gyms, with recording of the triggered primary motor responses (TPMR) in the contralateral hemibody. Thus, factors such as distortion of the pericentral anatomy, small surgical fields, brain shifts and miscalibrated neuro-navigational systems may lengthen the process and result in unnecessary stimulations, increasing the probability of triggering seizures. We hypothesized that central sulcus localization via the median somatosensory evoked potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon, resulting in prompt identification of the PMC with minimal electrical stimulation. Multivariate Cox regression was used to study the impact of MSSEP PRT on time spent performing electrical cortical stimulation to TPMR. The analysis was adjusted for presence of increased cortical excitability, high motor thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized motor mapping procedures for brain tumor resection and epilepsy surgery. Phase reversal and change morphology of the recorded somatosensory evoked potentials quadrupled (hazard ratio [HR] 4.13, p < 0.0001) and doubled (HR 2.14, p = 0.02) the rate of obtaining TPMR, respectively. A 1 mA increase in motor threshold decreased the rate by 9% (HR 0.91, p = 0.0002). Afterdischarges triggered before TPMR and lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23, p <0.0001) and 48% (HR 0.52, p = 0.04), respectively. Informative PRT decreases stimulation time. Afterdischarges triggered before TPMR, high motor thresholds and lesions close to the PMC increase it. (c) 2014 Elsevier Ltd. All rights reserved.
C1 [Simon, Mirela V.; Kilbride, Ronan D.; Braver, Diana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Simon, Mirela V.; Sheth, Sameer A.; Eckhardt, Christine A.; Kilbride, Ronan D.; Braver, Diana; Williams, Ziv; Curry, William; Cahill, Dan; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Sheth, Sameer A.; Eckhardt, Christine A.; Williams, Ziv; Curry, William; Cahill, Dan; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Sheth, Sameer A.] Columbia Univ, Dept Neurol Surg, New York, NY USA.
[Kilbride, Ronan D.] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA.
EM MVSIMON@mgh.harvard.edu
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0967-5868
EI 1532-2653
J9 J CLIN NEUROSCI
JI J. Clin. Neurosci.
PD JUN
PY 2014
VL 21
IS 6
BP 1011
EP 1017
DI 10.1016/j.jocn.2013.12.015
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI2QT
UT WOS:000336703800023
PM 24679940
ER
PT J
AU Mizutani, K
Park, K
Mima, A
Katagiri, S
King, GL
AF Mizutani, K.
Park, K.
Mima, A.
Katagiri, S.
King, G. L.
TI Obesity-associated Gingival Vascular Inflammation and Insulin Resistance
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE periodontitis; protein kinase C; oxidative stress; endothelial nitric
oxide synthase; periodontal bone loss; NF-kappa B
ID PROTEIN-KINASE-C; PERIODONTAL-DISEASE; NITRIC-OXIDE; RATS; MECHANISMS;
ACTIVATION; BONE; PHOSPHORYLATION; DYSFUNCTION; EXPRESSION
AB Obesity is a risk factor for periodontitis, but the pathogenic mechanism involved is unclear. We studied the effects of insulin in periodontal tissues during the state of obesity-induced insulin resistance. Gingival samples were collected from fatty (ZF) and lean (ZL, control) Zucker rats. Endothelial nitric oxide synthase (eNOS) expression was decreased, and activities of protein kinase C (PKC) alpha, beta 2, delta, and epsilon isoforms were significantly increased in the gingiva from ZF rats compared with those from ZL rats. Expression of oxidative stress markers (mRNA) and the p65 subunit of NF-kappa B was significantly increased in ZF rats. Immunohistochemistry revealed that NF-kappa B activation was also increased in the gingival endothelial cells from transgenic mice overexpressing NF-kappa B-dependent enhanced green fluorescent protein (GFP) and on a high-fat vs. normal chow diet. Analysis of the gingiva showed that insulin-induced phosphorylation of IRS-1, Akt, and eNOS was significantly decreased in ZF rats, but Erk1/2 activation was not affected. General PKC inhibitor and an anti-oxidant normalized the action of insulin on Akt and eNOS activation in the gingiva from ZF rats. This provided the first documentation of obesity-induced insulin resistance in the gingiva. Analysis of our data suggested that PKC activation and oxidative stress may selectively inhibit insulin-induced Akt and eNOS activation, causing endothelial dysfunction and inflammation.
C1 [Mizutani, K.; Park, K.; Mima, A.; Katagiri, S.; King, G. L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02163 USA.
[Mizutani, K.] Tokyo Med & Dent Univ, Dept Periodontol, Grad Sch Med & Dent Sci, Tokyo, Japan.
[Mima, A.] Kinki Univ, Nara Hosp, Fac Med, Dept Nephrol & Hematol, Osaka, Japan.
RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02163 USA.
EM George.King@joslin.harvard.edu
FU National Institutes of Health/NIDDK [RO1 DK053105-13, 5P30 DK 36836];
Hiroo Kaneda Scholarship, Sunstar Foundation, Japan; Japan Society for
the Promotion of Science [25862043, 24890148]; Takeda Science Foundation
FX This work was supported by a National Institutes of Health/NIDDK RO1
DK053105-13 grant to G. L. K. K. M. is the recipient of a Research
Fellowship (Hiroo Kaneda Scholarship, Sunstar Foundation, Japan) and a
Grant-in-Aid for Young Scientists(B) 25862043 from the Japan Society for
the Promotion of Science. A. M. is the recipient of a Grant-in-Aid for
Scientific Research from the Japan Society for the Promotion of Science
(24890148) and the Takeda Science Foundation. This project was also
supported by a National Institutes of Health/NIDDK 5P30 DK 36836 grant
to the Specialized Assay Core of the Joslin Diabetes Center. The authors
declare no potential conflicts of interest with respect to the
authorship and/or publication of this article.
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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 JUN
PY 2014
VL 93
IS 6
BP 596
EP 601
DI 10.1177/0022034514532102
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AH9WP
UT WOS:000336496100011
PM 24744283
ER
PT J
AU Joseph, J
AF Joseph, Jacob
TI Needling the heart to rejuvenate: The promise of intramyocardial
injection of bone marrow stem cells
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Editorial Material
ID DISEASE; METALLOPROTEINASES; INHIBITORS; LEUKEMIA
C1 [Joseph, Jacob] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA.
[Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Joseph, J (reprint author), Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA.
NR 7
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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 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD JUN
PY 2014
VL 33
IS 6
BP 565
EP 566
DI 10.1016/j.healun.2014.02.029
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA AI1TG
UT WOS:000336637100002
PM 24726425
ER
PT J
AU Schwabl, P
Payer, BA
Grahovac, J
Klein, S
Horvatits, T
Mitterhauser, M
Stift, J
Boucher, Y
Trebicka, J
Trauner, M
Angermayr, B
Fuhrmann, V
Reiberger, T
Peck-Radosavljevic, M
AF Schwabl, Philipp
Payer, Berit A.
Grahovac, Jelena
Klein, Sabine
Horvatits, Thomas
Mitterhauser, Markus
Stift, Judith
Boucher, Yves
Trebicka, Jonel
Trauner, Michael
Angermayr, Bernhard
Fuhrmann, Valentin
Reiberger, Thomas
Peck-Radosavljevic, Markus
TI Pioglitazone decreases portosystemic shunting by modulating inflammation
and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Angiogenesis; Inflammation; Portal hypertension; BDL; PPVL;
Pioglitazone; Portosystemic shunting; PPAR gamma
ID ACTIVATED RECEPTOR-GAMMA; HYPERDYNAMIC SPLANCHNIC CIRCULATION;
NITRIC-OXIDE SYNTHASE; NONALCOHOLIC STEATOHEPATITIS; GROWTH-FACTOR;
PRESSURE; ROSIGLITAZONE; INHIBITION; PLACEBO; KINASE
AB Background & Aims: Development of the portal-hypertensive syndrome is mediated by splanchnic inflammation and neoangiogenesis. Since peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists like pioglitazone (PIO) regulate inflammatory response and inhibit angiogenesis in endothelial cells, we evaluated PIO as treatment for experimental portal hypertension.
Methods: PIO (10 mg/kg) or vehicle (VEH) was administered from day 21-28 after bile duct ligation (BDL), from day 0-7 after partial portal vein ligation (PPVL) or sham-operation (SO), respectively. After treatment, systemic hemodynamics, splanchnic blood flow (SMABF), portal pressure (PP), and portosystemic shunting (PSS) were assessed. Splanchnic and hepatic tissues were analyzed for angiogenic and inflammatory markers.
Results: BDL and PPVL showed significantly increased PP, SMABF, and PSS compared to SO-VEH rats. While PIO treatment did not decrease PP or SMABF, PSS was significantly reduced both in cirrhotic (BDL-VEH: 71% to BDL-PIO: 41%; p < 0.001) and non-cirrhotic (PPVL-VEH: 62% to PPVL-PIO: 40%; p = 0.041) rats. PIO (10 mu M, in vitro) inhibited endothelial cell migration and significantly increased PPAR gamma activity in vivo. In BDL rats, PIO decreased hepatic mRNA levels of PPAR gamma (p = 0.01) and PlGF (p = 0.071), and splanchnic mRNA expression of PPAR gamma (p = 0.017), PDGF beta (p = 0.053) and TNF alpha (p = 0.075). Accordingly, splanchnic protein expression of PPAR gamma (p = 0.032), VEGFR2 (p = 0.035), CD31 (p = 0.060) and PDGF beta (p = 0.066) were lower in BDL-PIO vs. BDL-VEH animals. In PPVL rats, PIO treatment decreased splanchnic gene expression of Ang2 (-12.4 fold), eNOS (-9.3 fold), PDGF (-7.0 fold), PlGF (-11.9 fold), TGFb (-8.3 fold), VEGF-A (-11.3 fold), VEGFR1 (-5.9 fold), IL1b (-14.4 fold), and IL6 (-9.6 fold).
Conclusions: Pioglitazone treatment decreases portosystemic shunting via modulation of splanchnic inflammation and neoangiogenesis. Pioglitazone should be assessed for potential beneficial effects in patients with portosystemic collaterals due to portal hypertension. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
C1 [Schwabl, Philipp; Payer, Berit A.; Horvatits, Thomas; Trauner, Michael; Angermayr, Bernhard; Fuhrmann, Valentin; Reiberger, Thomas; Peck-Radosavljevic, Markus] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, A-1090 Vienna, Austria.
[Schwabl, Philipp; Payer, Berit A.; Angermayr, Bernhard; Reiberger, Thomas; Peck-Radosavljevic, Markus] Vienna Hepat Hemodynam Lab, Vienna, Austria.
[Grahovac, Jelena; Boucher, Yves; Reiberger, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Grahovac, Jelena; Boucher, Yves; Reiberger, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
[Klein, Sabine; Trebicka, Jonel] Univ Bonn, Dept Internal Med 1, Div Gastroenterol & Hepatol, Bonn, Germany.
[Mitterhauser, Markus] Med Univ Vienna, Dept Nucl Med, A-1090 Vienna, Austria.
[Stift, Judith] Med Univ Vienna, Dept Pathol, A-1090 Vienna, Austria.
RP Peck-Radosavljevic, M (reprint author), Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM markus.peck@meduniwien.ac.at
OI Grahovac, Jelena/0000-0003-1430-8682; Trebicka,
Jonel/0000-0002-7028-3881
FU Joseph-Skoda-Forschungsforderungspreis of the Austrian Society of
Internal Medicine (OEGIM); Max-Kade Fellowship; Deutsche
Forschungsgemeinschaft [SFB TRR57 P18]; HW & J Hector Stiftung
FX This study and the work of PS were supported by
Joseph-Skoda-Forschungsforderungspreis of the Austrian Society of
Internal Medicine (OEGIM) to VF and TR. The work of TR was partly funded
by a Max-Kade Fellowship. This is study was partly supported by grants
from Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to JT.) and by
grants of the HW & J Hector Stiftung (to JT).
NR 39
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2014
VL 60
IS 6
BP 1135
EP 1142
DI 10.1016/j.jhep.2014.01.025
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9BO
UT WOS:000336434300007
PM 24530596
ER
PT J
AU Op den Dries, S
Westerkamp, AC
Karimian, N
Gouw, ASH
Bruinsma, BG
Markmann, JF
Lisman, T
Yeh, H
Uygun, K
Martins, PN
Porte, RJ
AF Op den Dries, Sanna
Westerkamp, Andrie C.
Karimian, Negin
Gouw, Annette S. H.
Bruinsma, Bote G.
Markmann, James F.
Lisman, Ton
Yeh, Heidi
Uygun, Korkut
Martins, Paulo N.
Porte, Robert J.
TI Injury to peribiliary glands and vascular plexus before liver
transplantation predicts formation of non-anastomotic biliary strictures
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Bile duct injury; Donation after cardiac death; Non-anastomotic biliary
strictures; Biliary complications; Ischemic cholangiopathy;
Regeneration; Ischemic type biliary injury; Liver transplantation
ID BILE-DUCTS; MACHINE PERFUSION; CARDIAC DEATH; COLD-STORAGE; DONOR
LIVERS; CELLS; COMPLICATIONS; CONSEQUENCES; REGENERATION; ISCHEMIA
AB Background & Aims: The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation.
Methods: In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system. Histological severity of injury was subsequently compared in liver grafts that later developed biliary structures vs. uncomplicated liver grafts.
Results: Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p <0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%, respectively; p = 0.004). In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed NAS, compared to grafts without NAS (>50% vascular changes in 57.1% vs. 20.3%; p = 0.006).
Conclusion: Injury of peribiliary glands and vascular plexus before transplantation is strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply may explain the development of biliary strictures. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
C1 [Op den Dries, Sanna; Westerkamp, Andrie C.; Karimian, Negin; Lisman, Ton; Porte, Robert J.] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, Groningen, Netherlands.
[Op den Dries, Sanna; Markmann, James F.; Yeh, Heidi; Martins, Paulo N.] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Gouw, Annette S. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands.
[Bruinsma, Bote G.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA.
[Bruinsma, Bote G.; Uygun, Korkut] Shriners Burns Hosp, Boston, MA USA.
RP Porte, RJ (reprint author), Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, POB 30-001, NL-9700 RB Groningen, Netherlands.
EM r.j.porte@umcg.nl
OI Lisman, Ton/0000-0002-3503-7140
FU Netherlands Digestive Diseases Foundation (Maag Lever Darm Stichting);
European Society for Organ Transplantation; Ubbo Emmius Foundation in
Groningen; National Institutes of Health [R01DK096075, R01EB008678];
Shriners Hospitals for Children
FX This research work was financially supported by grants provided by The
Netherlands Digestive Diseases Foundation (Maag Lever Darm Stichting),
the European Society for Organ Transplantation and the Ubbo Emmius
Foundation in Groningen (all to SODD). For US studies, funding from the
National Institutes of Health (R01DK096075, R01EB008678), and the
Shriners Hospitals for Children are gratefully acknowledged.
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U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2014
VL 60
IS 6
BP 1172
EP 1179
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9BO
UT WOS:000336434300012
PM 24560661
ER
PT J
AU Markowitz, JT
Volkening, LK
Laffel, LMB
AF Markowitz, Jessica T.
Volkening, Lisa K.
Laffel, Lori M. B.
TI Care Utilization in a Pediatric Diabetes Clinic: Cancellations, Parental
Attendance, and Mental Health Appointments
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID GLYCEMIC CONTROL; METABOLIC-CONTROL; YOUNG-ADULTS; PATERNAL INVOLVEMENT;
DEPRESSIVE SYMPTOMS; FAMILY CONFLICT; TYPE-1; ADOLESCENTS; YOUTH;
MANAGEMENT
AB Objective To examine care utilization, family attendance, and hemoglobin A1c levels in a multidisciplinary pediatric diabetes clinic.
Study design This retrospective electronic record review of deidentified data included patients (99% with type 1 diabetes) with established diabetes care, aged <30 years (mean age, 15 +/- 5.2 years), and duration of diabetes >1 year (mean 8.5 +/- 5.1 years) at first visit during a 2-year period. Outcomes included care utilization, family attendance, and glycemic control, as indicated by hemoglobin A1c level. Analyses included t tests, ANOVA, chi(2) tests, ORs and 95% CIs, and multivariate analyses.
Results The study cohort comprised 1771 patients, with a mean of 5.8 +/- 2.8 visits per patient. Roughly 15% of the scheduled appointments resulted in a cancellation or no-show; 61% of patients missed >= 1 visit. Patients with >= 2 missed appointments had higher A1c values and were older than those with <2 missed visits. Almost one-half of visits were attended by mothers alone; fathers attended 22% of visits. Patients whose fathers attended >= 1 visit had lower A1c values than patients whose fathers never attended. Eighteen percent of patients had onsite mental health visits. Patients with >= 1 mental health visit had higher mean A1c values, shorter duration of diabetes, and were younger compared with those with no mental health visits.
Conclusion Our observations suggest the need to encourage attendance at diabetes visits and to include fathers to improve A1c values. The high rate of missed visits, especially in patients with poor glycemic control, identifies wasted provider effort when late cancellations/no-shows result in vacant clinic time. It is important to explore reasons for missed visits and to identify approaches to maximizing attendance, such as extended evening/weekend clinic hours and virtual visits.
C1 [Markowitz, Jessica T.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA.
Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA.
RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA.
EM jessica.markowitz@joslin.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[K23DK092335, P30DK036836]; Eleanor Chesterman Beatson Fund; Katherine
Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund
FX Funded by the National Institute of Diabetes and Digestive and Kidney
Diseases (K23DK092335 and P30DK036836), the Eleanor Chesterman Beatson
Fund, the Katherine Adler Astrove Youth Education Fund, and the Maria
Griffin Drury Pediatric Fund. The authors declare no conflicts of
interest.
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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 JUN
PY 2014
VL 164
IS 6
BP 1384
EP 1389
DI 10.1016/j.jpeds.2014.01.045
PG 6
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200031
PM 24612905
ER
PT J
AU Landsman-Blumberg, PB
Wei, WH
Douglas, D
Smith, DM
Clark, S
Camargo, CA
AF Landsman-Blumberg, Pamela B.
Wei, Wenhui
Douglas, Damon
Smith, David M.
Clark, Sunday
Camargo, Carlos A., Jr.
TI Concordance with Recommended Postdischarge Care Guidelines among
Children with Food-Induced Anaphylaxis
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LONG-TERM MANAGEMENT; ALLERGY
AB Objective To describe patient characteristics, concordance with recommended postdischarge care, and risk of repeat events within a cohort of children discharged from an emergency department (ED) or hospital for food-induced anaphylaxis in the US.
Study design Children (aged <18 years) with an ED visit/hospitalization for food-induced anaphylaxis were identified from the 2002-2008 Truven Health MarketScan databases using an expanded International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithm. The initial identified ED visit/hospitalization was the index event. Claims data for the children with continuous medical and prescription coverage for >= 1 year before and after the index event were evaluated. Analyses included the rates of 1-year postdischarge epinephrine autoinjector (EAI) prescription fills, allergist/immunologist visits, and repeat events.
Results The study cohort comprised 1009 patients with an average age of 7 years, including 58% males, 27% with a history of asthma, and 90% discharged from an ED. Within 1 year postdischarge, 83% had an EAI prescription fill (69% within 1 week postdischarge), 43% had a specialist visit (51% within 4 weeks postdischarge), and 6.4% had evidence of another anaphylaxis-related ED visit/hospitalization.
Conclusion Among children with food-induced anaphylaxis, within 1 year postdischarge from the ED or hospital, concordance was higher for EAI prescription fills than for allergist/immunologist visits. Subsequent ED visits/hospital stays for anaphylactic events were low. More research is needed to identify barriers between recommendations and physician/patient behaviors, as well as the impact of not following the recommendations on patient outcomes and healthcare costs.
C1 [Landsman-Blumberg, Pamela B.; Smith, David M.] Truven Hlth Analyt, Bethesda, MD USA.
[Wei, Wenhui] Sanofi US, Bridgewater, NJ USA.
[Douglas, Damon] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Boston, MA USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA.
RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA.
EM ccamargo@partners.org
FU Sanofi US
FX Funded by Sanofi US. P.L.-B. and D. S. are employees of Truven Health
Analytics (formerly the Healthcare Division of Thomson Reuters). W. W.
is an employee of Sanofi US. D. D. was a Rutgers Fellow on assignment at
Sanofi US until 2011. C. C. is a consultant for Sanofi US and Dey
Pharma.
NR 20
TC 1
Z9 1
U1 0
U2 5
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 JUN
PY 2014
VL 164
IS 6
BP 1444
EP +
DI 10.1016/j.jpeds.2014.02.022
PG 6
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200041
PM 24661339
ER
PT J
AU Vergamini, LB
Frazier, AL
Abrantes, FL
Ribeiro, KB
Rodriguez-Galindo, C
AF Vergamini, Lucas Bonachi
Frazier, A. Lindsay
Abrantes, Fernanda Laurinavicius
Ribeiro, Karina Braga
Rodriguez-Galindo, Carlos
TI Increase in the Incidence of Differentiated Thyroid Carcinoma in
Children, Adolescents, and Young Adults: A Population-Based Study
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID HIGH-INCIDENCE AREA; UNITED-STATES; CANCER INCIDENCE; NEW-CALEDONIA;
TRENDS; RISK; SMOKING; ENGLAND; PEOPLE; IODINE
AB Objective To investigate trends in incidence of differentiated thyroid carcinomas among children and adolescents and young adults.
Study design In this ecological time-trends study, we selected cases of differentiated thyroid carcinomas (19842010) in patients <30 years from Surveillance, Epidemiology, and End Results 9 cancer registries by using International Classification of Diseases for Oncology, 3rd edition, codes for papillary and follicular cancers. Patients with multiple other primary diseases before differentiated thyroid carcinomas were excluded. SEER*Stat software, version 8.0.4 (National Cancer Institute, Bethesda, Maryland) was used to calculate age-standardized rates (estimated per 1 000 000/persons) and annual percentage changes (APCs) were calculated by the Joinpoint model (Joinpoint software, version 4.0.4; National Cancer Institute).
Results Rates ranged from 2.77 (1990) to 9.63 (2009) and from 18.35 (1987) to 50.99 (2009), for male and female subjects, respectively. A significant increasing trend in incidence was observed for both male (APC 3.44; 95% CI 2.60-4.28) and female (APC 3.81; 95% CI 3.38-4.24) patients. When a stratified analysis on the basis of tumor size was performed, significant increasing trends were noted for the following categories: <0.5 cm (females: APC 5.09, 95% CI 3.54-6.65), 0.5-0.9 cm (females: APC 8.45, 95% CI 7.09-9.82), 1.0-1.9 cm (males: APC 5.09, 95% CI 3.20-7.01; females: APC 3.42, 95% CI 2.78-4.07), and >= 2 cm(males: APC 2.62, 95% CI 1.64-3.60; females: APC 2.96, 95% CI 2.34-3.59).
Conclusions Incidence rates for differentiated thyroid carcinomas are increasing among children and adolescents and young adults in the US. The increasing trends for larger tumors rules out diagnostic scrutiny as the only explanation for the observed results. Environmental, dietary, and genetic influences should be investigated.
C1 [Vergamini, Lucas Bonachi; Abrantes, Fernanda Laurinavicius; Ribeiro, Karina Braga] Santa Casa Sao Paulo, Fac Med Sci, Sao Paulo, Brazil.
[Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Dana Farber Boston Childrens Ctr Canc & Blood Dis, Boston, MA USA.
[Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Boston, MA USA.
RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D3-313, Boston, MA 02215 USA.
EM carlos_rodriguez-galindo@dfci.harvard.edu
FU program "Pesquisadores do Futuro"- Faculty of Medicine Sciences of Santa
Casa of Sao Paulo, Brazil
FX L.V. was recipient of a scholarship from the program "Pesquisadores do
Futuro"- Faculty of Medicine Sciences of Santa Casa of Sao Paulo,
Brazil. The authors declare no conflicts of interest.
NR 34
TC 31
Z9 38
U1 0
U2 4
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 JUN
PY 2014
VL 164
IS 6
BP 1481
EP 1485
DI 10.1016/j.jpeds.2014.01.059
PG 5
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200047
PM 24630354
ER
PT J
AU Lin, F
Roiland, R
Heffner, K
Johnson, M
Chen, DG
Mapstone, M
AF Lin, Feng
Roiland, Rachel
Heffner, Kathi
Johnson, Melissa
Chen, Ding-Geng (Din)
Mapstone, Mark
TI Evaluation of objective and perceived mental fatigability in older
adults with vascular risk
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE Mental fatigability; Executive control; History of mental activities;
Reaction time
ID COGNITIVE FATIGUE; SUBSEQUENT SYMPTOMS; MULTIPLE-SCLEROSIS; SUBJECTIVE
FATIGUE; NORMATIVE DATA; HEART-FAILURE; AGE; EDUCATION; SAMPLE; MEMORY
AB Objectives: Mental fatigability refers to the failure to sustain participation in tasks requiring mental effort Older adults with vascular risk are at particular risk for experiencing mental fatigability. The present study (1) tested a new way of measuring objective mental fatigability by examining its association with perceived mental fatigability; and (2) identified associated psychological, physiological, and situational predictors.
Methods: A cross-sectional study was conducted with 49 community-dwelling participants aged 75 + years with vascular risk. A 20-minute fatigability-manipulation task was used to induce mental fatigability and develop objective and perceived mental fatigability measures. Objective fatigability was calculated by the change of reaction time over the course of the task. Perceived fatigability was calculated by the change of fatigue self-reported before and after the task. A set of potential psychological, physiological, and situational predictors were measured.
Results: There was a significant increase in reaction time and self-reported fatigue to the fatigability manipulation task, indicating occurrence of objective and perceived mental fatigability. Reaction time and self-reported fatigue were moderately, but significantly correlated. Higher levels of executive control and having a history of more frequently engaging in mental activities were associated with lower objective mental fatigability. None of the examined factors were associated with perceived mental fatigability.
Conclusion: Objective and perceived mental fatigability were sensitive to our fatigability-manipulation task. While these two measures were correlated, they were not associated with the same factors. These findings need to be validated in studies with a more heterogeneous sample and a greater variety of fatigability-manipulation tasks. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Lin, Feng; Johnson, Melissa; Chen, Ding-Geng (Din)] Univ Rochester, Sch Nursing, Rochester, NY 14642 USA.
[Lin, Feng; Heffner, Kathi] Univ Rochester, Dept Psychiat, Sch Med & Dent, Rochester, NY 14642 USA.
[Roiland, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Chen, Ding-Geng (Din)] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY 14642 USA.
[Mapstone, Mark] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
RP Lin, F (reprint author), Univ Rochester, Med Ctr, HWH 2w128,601 Elmwood Ave, Rochester, NY 14642 USA.
EM vankee_lin@urmc.rochester.edu
OI Heffner, Kathi/0000-0003-1095-1873
FU University of Rochester CTSA from the National Center for Advancing
Translational Sciences of the National Institutes of Health [KL2
TR000095]; Sigma Theta Tau International Small Grants
FX Data collection of the present project was supported by Sigma Theta Tau
International Small Grants to F. Lin. The manuscript preparation was
supported by the University of Rochester CTSA award number KL2 TR000095
from the National Center for Advancing Translational Sciences of the
National Institutes of Health to F. Lin. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 52
TC 0
Z9 0
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
EI 1879-1360
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD JUN
PY 2014
VL 76
IS 6
BP 458
EP 464
DI 10.1016/j.jpsychores.2014.04.001
PG 7
WC Psychiatry
SC Psychiatry
GA AI1UA
UT WOS:000336639300004
PM 24840140
ER
PT J
AU Cox, K
McAdams, DP
AF Cox, Keith
McAdams, Dan P.
TI Meaning making during high and low point life story episodes predicts
emotion regulation two years later: How the past informs the future
SO JOURNAL OF RESEARCH IN PERSONALITY
LA English
DT Article
DE Narrative identity; Emotion regulation; Emotional memory
ID AUTOBIOGRAPHICAL MEMORIES; ADOLESCENCE
AB Memory processes are commonly thought to relate to a host of personality systems. The current study specifies a particular way that memory relates to personality. Highly-valenced, identity-rich memories - high and low point episodes in the life story - were analyzed to see if aspects of these memories predicted self-reports of emotion regulation two years later. Meaning making in high and low points predicted emotion regulation. Moreover, valence mattered. Positive meaning making in high and low point stories predicted positive emotion regulation while negative meaning making in low point stories predicted negative emotion regulation. These relationships held while controlling for baseline extraversion, neuroticism, and memory word count. Limitations due to study design are discussed. Published by Elsevier Inc.
C1 [Cox, Keith] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Cox, Keith] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA.
[McAdams, Dan P.] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA.
[McAdams, Dan P.] Sch Educ & Social Policy, Evanston, IL USA.
RP Cox, K (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA.
EM keith.cox@va.gov
NR 14
TC 9
Z9 9
U1 2
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0092-6566
EI 1095-7251
J9 J RES PERS
JI J. Res. Pers.
PD JUN
PY 2014
VL 50
BP 66
EP 70
DI 10.1016/j.jrp.2014.03.004
PG 5
WC Psychology, Social
SC Psychology
GA AI2TA
UT WOS:000336709800009
ER
PT J
AU Bent, S
Hendren, RL
Zandi, T
Law, K
Choi, JE
Widjaja, F
Kalb, L
Nestle, J
Law, P
AF Bent, Stephen
Hendren, Robert L.
Zandi, Tara
Law, Kiely
Choi, Jae-Eun
Widjaja, Felicia
Kalb, Luther
Nestle, Jay
Law, Paul
TI Internet-Based, Randomized, Controlled Trial of Omega-3 Fatty Acids for
Hyperactivity in Autism
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE autism; nutritional supplement; alternative medicine; hyperactivity
ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED-TRIAL; SPECTRUM
DISORDERS; PARENT REPORT; CHILDREN; METHYLPHENIDATE; SUPPLEMENTATION;
IRRITABILITY; ARIPIPRAZOLE; RISPERIDONE
AB Objective: Preliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder (ASD). We sought to examine the feasibility of a novel, Internet-based clinical trial design to evaluate the efficacy of this supplement. Method: E-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network. All study procedures, including screening, informed consent, and collection of outcome measures took place over the Internet. The primary Outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist (ABC-H). Results: During the 6-week recruitment period, 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks. Outcome assessments were obtained from all 57 participants and 57 teachers, and the study was completed in 3 months. Children in the omega-3 fatty acid group had a greater reduction in hyperactivity (-5.3 points) compared to the placebo group (-2.6 points), but the difference was not statistically significant (1.9-point greater improvement in the omega-3 group, 95% CI = -2.2 to 5.2). Adverse events were rare and not associated with omega-3 fatty acids. Participant feedback was positive. Conclusion: Internet-based, randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials. A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids. Clinical trial registration information-Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder; http://clinicaltrials.gov; NCT 01694667.
C1 [Bent, Stephen; Hendren, Robert L.; Choi, Jae-Eun; Widjaja, Felicia] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Zandi, Tara; Law, Kiely; Kalb, Luther; Nestle, Jay; Law, Paul] Kennedy Krieger Inst, Baltimore, MD USA.
RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA.
EM Stephen.Bent@ucsf.edu
FU Simons Foundation [SFARI 206484]; National Center for Research
Resources; National Center for Advancing Translational Sciences,
National Institutes of Health, through UCSF-CTSI [UL1 RR024131]
FX This work was supported by a grant from the Simons Foundation (SFARI
206484, S.B.) and by the National Center for Research Resources and the
National Center for Advancing Translational Sciences, National
Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131.
NR 25
TC 9
Z9 10
U1 2
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2014
VL 53
IS 6
BP 658
EP 666
DI 10.1016/j.jaac.2014.01.018
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AI0SO
UT WOS:000336560400009
PM 24839884
ER
PT J
AU Kohn, R
Kratz, JR
Markmann, JF
Vagefi, PA
AF Kohn, Rachel
Kratz, Johannes R.
Markmann, James F.
Vagefi, Parsia A.
TI The Migrated Liver Transplantation Candidate: Insight into Geographic
Disparities in Liver Distribution
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article; Proceedings Paper
CT 94th Annual Meeting of the New-England-Surgical-Society
CY SEP, 2013
CL Hartford, CT
SP New England Surg Soc
ID KIDNEY
AB BACKGROUND: A minority of liver transplantation (LT) candidates pursue listing at multiple centers to achieve transplantation. The purpose of this study was to assess the characteristics and outcomes of the migrated LT candidates, that is, those who travel to secondary centers seeking LT.
STUDY DESIGN: Single-center retrospective study from January 1, 2005 to January 1, 2013 at a tertiary care center within United Network for Organ Sharing Region 1. Adult recipients who were listed at the primary center of interest, but subsequently achieved transplantation at a secondary center (Massachusetts General Hospital [MGH]-migrated; n = 44) were compared with recipients who achieved LT at the primary center (MGH-transplanted; n = 279).
RESULTS: The MGH-migrated recipients most frequently traveled to United Network for Organ Sharing Region 3 (70.5%), with a mean (+/- SD) distance traveled of 1,134 (+/- 392) miles. The MGH-migrated patients, when compared with MGH-transplanted recipients, spent more time on the waitlist (907.6 +/- 930.1 days vs 354.9 +/- 533.2 days; p < 0.00001), were more likely to have cholestatic liver disease (22.7% vs 6.8%; p = 0.0006) and private insurance (80.0% vs 51.6%; p = 0.0005), but were less likely to have alcoholic liver disease (2.3% vs 18.6%; p = 0.006) and Model for End-Stage Liver Disease exception points (6.8% vs 50.9%; p < 0.00001). On multivariable analysis, candidates with private insurance who lacked both alcoholic liver disease and Model for End-Stage Liver Disease exception point listing were significantly associated with the odds of pursuing migration. Despite achieving LT, MGH-migrated patients had inferior 5-year patient survival rates (63% vs 80%; p = 0.03).
CONCLUSIONS: A small and distinctive cohort of LT recipients pursue migration to achieve transplantation. Travel patterns of migrated LT recipients appear to reflect the ongoing geographic disparities in liver distribution and underscore the need for alterations in policy to allow for equitable distribution. (C) 2014 by the American College of Surgeons
C1 [Kohn, Rachel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kratz, Johannes R.; Markmann, James F.; Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Kratz, Johannes R.; Markmann, James F.; Vagefi, Parsia A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA.
EM pvagefi@partners.org
NR 7
TC 7
Z9 7
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2014
VL 218
IS 6
BP 1113
EP 1118
DI 10.1016/j.jamcollsurg.2013.12.056
PG 6
WC Surgery
SC Surgery
GA AH9JK
UT WOS:000336458000006
PM 24680570
ER
PT J
AU Kaafarani, HMA
Mavros, MN
Hwabejire, J
Fagenholz, P
Yeh, DD
Demoya, M
King, DR
Alam, HB
Chang, YC
Hutter, M
Antonelli, D
Gervasini, A
Velmahos, GC
AF Kaafarani, Haytham M. A.
Mavros, Michael N.
Hwabejire, John
Fagenholz, Peter
Yeh, Daniel D.
Demoya, Marc
King, David R.
Alam, Hasan B.
Chang, Yuchiao
Hutter, Matthew
Antonelli, Donna
Gervasini, Alice
Velmahos, George C.
TI Derivation and Validation of a Novel Severity Classification for
Intraoperative Adverse Events
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article; Proceedings Paper
CT 94th Annual Meeting of the New-England-Surgical-Society
CY SEP, 2013
CL Hartford, CT
SP New England Surg Soc
ID PATIENT SAFETY INDICATORS; CLAVIEN-DINDO CLASSIFICATION; ABDOMINAL-WALL
REPAIR; SURGICAL COMPLICATIONS; POSTOPERATIVE COMPLICATIONS; GRADING
SYSTEM; ENTEROTOMY; MORBIDITY; SURGERY; UTILITY
AB BACKGROUND: There is currently no systematic approach to evaluating the severity of intraoperative adverse events (iAEs).
STUDY DESIGN: A 3-phase project was designed to develop and validate a novel severity classification scheme for iAEs. Phase 1 created the severity classification using a modified Delphi process. Phase 2 measured the classification's internal consistency by calculating inter-rater reliability among 91 surgeons using standardized iAEs scenarios. Phase 3 measured the classification's construct validity by testing whether major iAEs (severity class >= 3) correlated with worse 30-day postoperative outcomes compared with minor iAEs (severity class <3). This was achieved by creating a matched database using American College of Surgeons NSQIP and administrative data, querying for iAEs using the Patient Safety Indicator #15 (Accidental Puncture/ Laceration), and iAE confirmation by chart review.
RESULTS: Phase 1 resulted in a 6-point severity classification scheme. Phase 2 revealed an inter-rater reliability of 0.882. Of 9,292 patients, phase 3 included 181 confirmed with iAEs. All preoperative/intraoperative variables, including demographics, comorbidities, type of surgery performed, and operative length, were similar between patients with minor (n = 110) vs major iAEs (n = 71). In multivariable logistic analysis, severe iAEs correlated with higher risks of any postoperative complication (odds ratio [OR] 3.8; 95% CI, 1.9-7.4; p < 0.001), surgical site infections (OR 3.7; 95% CI, 1.7-8.2; p 0.001), systemic sepsis (OR 6.0; 95% CI, 2.1-17.2; p 0.001), failure to wean off the ventilator (OR 3.2; 95% CI, 1.2-8.9; p = 0.022), and postoperative length of stay >= 7 days (OR 3.0; 95% CI, 1.5-5.9; p = 0.002). Thirty-day mortalities were similar (4.5% vs 7.1%; p = 0.46).
CONCLUSIONS: We propose a novel iAE severity classification system with high internal consistency and solid construct validity. Our classification scheme might prove essential for benchmarking quality of intraoperative care across hospitals and/or individual surgeons. (C) 2014 by the American College of Surgeons
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM hkaafarani@partners.org
OI King, David/0000-0003-1028-1478
NR 32
TC 11
Z9 12
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2014
VL 218
IS 6
BP 1120
EP 1128
DI 10.1016/j.jamcollsurg.2013.12.060
PG 9
WC Surgery
SC Surgery
GA AH9JK
UT WOS:000336458000008
PM 24702887
ER
PT J
AU Tapias, LF
Morse, CR
AF Tapias, Luis F.
Morse, Christopher R.
TI Minimally Invasive Ivor Lewis Esophagectomy: Description of a Learning
Curve
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article; Proceedings Paper
CT 94th Annual Meeting of the New-England-Surgical-Society
CY SEP, 2013
CL Hartford, CT
SP New England Surg Soc
ID CANCER; OUTCOMES; SURGERY; VOLUME; LYMPHADENECTOMY; MORTALITY
AB BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIE) is gaining popularity for the treatment of esophageal cancer. However, as it is a technically demanding operation, a learning curve should be defined to guide training and allow implementation at institutions not currently using this technique.
STUDY DESIGN: Our study included a retrospective series of the first 80 consecutive patients undergoing MIE by a single surgeon with advanced training in minimally invasive esophageal surgery in independent practice at a high-volume tertiary center. Patients were stratified into 2 groups of 40 patients, with chronological order defining early and late experiences. Primary end points included conversion to open procedure, surgical time, blood loss, chest drainage duration, time to oral intake, hospital stay, postoperative morbidity, and mortality. The cumulative sum methodology was used and analyzed by visually inspecting the plots.
RESULTS: Conversion to open procedure occurred in 2 (5%) patients in the early group and none in the late group (p = 0.49). Comparing early vs late experience, mean surgical time was 364 vs 316 minutes (p < 0.01), estimated blood loss was 205 vs 176 mL (p = 0.14), median hospital stay was 7 vs 6 days (p < 0.01), and morbidity was observed in 16 (40%) and 14 (35%) patients (p = 0.82), respectively. There were no anastomotic leaks or 30-day mortality. Cumulative sum plots showed decreasing surgical time after patient 54 (plateau after patient 31), decreasing chest tube duration after patients 38 and 33, sooner oral intake after patient 35, and decreased hospital stay after patient 33.
CONCLUSIONS: Improved operative and perioperative parameters for MIE were observed in the last 40 patients when compared with the first 40 patients. A reasonable learning curve for MIE would require the operation and perioperative care of 35 to 40 patients. (C) 2014 by the American College of Surgeons
C1 [Tapias, Luis F.; Morse, Christopher R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Morse, CR (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM crmorse@partners.org
NR 21
TC 22
Z9 23
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2014
VL 218
IS 6
BP 1130
EP 1140
DI 10.1016/j.jamcollsurg.2014.02.014
PG 11
WC Surgery
SC Surgery
GA AH9JK
UT WOS:000336458000010
PM 24698488
ER
PT J
AU Ahmad, R
Schmidt, BH
Rattner, DW
Mullen, JT
AF Ahmad, Rima
Schmidt, Benjamin H.
Rattner, David W.
Mullen, John T.
TI Factors Influencing Readmission after Curative Gastrectomy for Gastric
Cancer
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article; Proceedings Paper
CT 94th Annual Meeting of the New-England-Surgical-Society
CY SEP, 2013
CL Hartford, CT
SP New England Surg Soc
ID LENGTH-OF-STAY; FEEDING JEJUNOSTOMY; PATIENT READMISSION; SURGERY;
PLACEMENT; MORTALITY; RESECTION; RATES; TIME
AB BACKGROUND: The incidence of, and associated risk factors for, readmission after potentially curative gastrectomy for patients with gastric cancer has not been well studied. We sought to determine the 30-day readmission rate as well as the potential risk factors for readmission at our institution in patients undergoing gastrectomy for gastric cancer with curative intent.
STUDY DESIGN: We performed a retrospective analysis of all patients undergoing potentially curative gastrectomy for gastric cancer from 1995 to 2011. The 30-day hospital readmission rate was determined, and potential clinicopathologic risk factors for readmission were examined.
RESULTS: Readmission to the hospital within 30 days occurred in 14.6% (61 of 418) of patients, including 6 patients who were readmitted more than once. The most common reasons for readmission included nutritional difficulties (n = 12, 20%), intra-abdominal fluid collections (n = 11, 18%), and small bowel obstruction (n = 6, 10%). Factors associated with a higher 30-day readmission rate included type of resection (total gastrectomy, 23% vs subtotal gastrectomy, 13% vs esophagogastrectomy, 9%, p = 0.016), pre-existing cardiovascular disease (17%, p = 0.05), and history of a major postoperative complication (24%, p < 0.001). Factors not associated with a higher readmission rate included advanced age, preexisting pulmonary disease, T or N stage, extent of lymph node dissection, receipt of neoadjuvant chemotherapy or radiotherapy, length of stay of the index hospitalization, and destination and level of support on discharge.
CONCLUSIONS: Readmission after potentially curative gastrectomy for gastric cancer is common. Patients with pre-existing cardiovascular disease, those who suffer major postoperative complications, and those undergoing total gastric resections are at especially high risk for readmission, and strategies designed to support these high-risk patients on discharge are warranted. (C) 2014 by the American College of Surgeons
C1 [Ahmad, Rima; Schmidt, Benjamin H.; Rattner, David W.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM jmullen@partners.org
NR 11
TC 9
Z9 9
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2014
VL 218
IS 6
BP 1215
EP 1222
DI 10.1016/j.jamcollsurg.2014.02.015
PG 8
WC Surgery
SC Surgery
GA AH9JK
UT WOS:000336458000030
PM 24680567
ER
PT J
AU Jesinkey, SR
Funk, JA
Stallons, LJ
Wills, LP
Megyesi, JK
Beeson, CC
Schnellmann, RG
AF Jesinkey, Sean R.
Funk, Jason A.
Stallons, L. Jay
Wills, Lauren P.
Megyesi, Judit K.
Beeson, Craig C.
Schnellmann, Rick G.
TI Formoterol Restores Mitochondrial and Renal Function after
Ischemia-Reperfusion Injury
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; OXIDANT INJURY; TRANSCRIPTIONAL COACTIVATOR;
PROMOTES RECOVERY; PROXIMAL TUBULES; BIOGENESIS; PGC-1-ALPHA; DISEASE;
EXPRESSION; REGULATOR
AB Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondria! biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting beta(2)-adrenergic agonist, induces renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulated mitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred.
C1 [Jesinkey, Sean R.; Funk, Jason A.; Stallons, L. Jay; Wills, Lauren P.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA.
[Megyesi, Judit K.] Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA.
[Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Schnellmann, RG (reprint author), MUSC MSC 140,280 Calhoun St, Charleston, SC 29425 USA.
EM schnell@musc.edu
FU National Institutes of Health [R01 GM084147, T32 HL007260-35,
F32DK098053, C06 RR015455, P20 GM103542-02, UL1 RR029882]; Biomedical
Laboratory Research and Development Program of the Department of
Veterans Affairs [BX-000851]; South Carolina Clinical and Translational
Research Institute
FX This study was supported by the National Institutes of Health (R01
GM084147 to R.G.S., T32 HL007260-35 to S.R.J and L.J.S., F32DK098053 to
L.J.S., C06 RR015455 and SC COBRE in Oxidants, Redox Balance and Stress
Signaling P20 GM103542-02), and by the Biomedical Laboratory Research
and Development Program of the Department of Veterans Affairs
(BX-000851). This publication was supported, in part, by the South
Carolina Clinical and Translational Research Institute, with an academic
home at the Medical University of South Carolina CTSA, and funded by the
National Institutes of Health (UL1 RR029882).
NR 30
TC 20
Z9 20
U1 0
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUN
PY 2014
VL 25
IS 6
BP 1157
EP 1162
DI 10.1681/ASN.2013090952
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0RS
UT WOS:000336558100007
PM 24511124
ER
PT J
AU Funk, JA
Janech, MG
Dillon, JC
Bissler, JJ
Siroky, BJ
Bell, PD
AF Funk, Jason A.
Janech, Michael G.
Dillon, Joshua C.
Bissler, John J.
Siroky, Brian J.
Bell, P. Darwin
TI Characterization of Renal Toxicity in Mice Administered the Marine
Biotoxin Domoic Acid
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; LIONS ZALOPHUS-CALIFORNIANUS; SEA LIONS; C-FOS;
RECEPTOR ANTAGONIST; TISSUE DISTRIBUTION; SUBCLINICAL AKI;
GENE-EXPRESSION; NMDA RECEPTORS; SHELLFISH
AB Domoic acid (DA), an excitatory amino acid produced by diatoms belonging to the genus Pseudo-nitzschia, is a glutamate analog responsible for the neurologic condition referred to as amnesic shellfish poisoning. To date, the renal effects of DA have been underappreciated, although renal filtration is the primary route of systemic elimination and the kidney expresses ionotropic glutamate receptors. To characterize the renal effects of DA, we administered either a neurotoxic dose of DA or doses below the recognized limit of toxicity to adult Sv128/Black Swiss mice. DA preferentially accumulated in the kidney and elicited marked renal vascular and tubular damage consistent with acute tubular necrosis, apoptosis, and renal tubular cell desquamation, with toxic vacuolization and mitochondrial swelling as hallmarks of the cellular damage. Doses >= 0.1 mg/kg DA elevated the renal injury biomarkers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and doses >= 0.005 mg/kg induced the early response genes c-fos and junb. Coadministration of DA with the broad spectrum excitatory amino acid antagonist kynurenic acid inhibited induction of c-fos, junb, and neutrophil gelatinase-associated lipocalin. These findings suggest that the kidney may be susceptible to excitotoxic agonists, and renal effects should be considered when examining glutamate receptor activation. Additionally, these results indicate that DA is a potent nephrotoxicant, and potential renal toxicity may require consideration when determining safe levels for human exposure.
C1 [Funk, Jason A.; Janech, Michael G.; Dillon, Joshua C.; Bell, P. Darwin] Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA.
[Bissler, John J.; Siroky, Brian J.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA.
[Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Bell, PD (reprint author), Med Univ S Carolina, 70 President St,DDB 514,MSC 629, Charleston, SC 29425 USA.
EM bellpd@musc.edu
OI Janech, Michael/0000-0002-3202-4811
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases [T32DK007752]; Office of Naval Research
[N000140810341]; Veterans Affairs Merit Grant [P30 DK074038]; Dialysis
Clinic
FX J.A.F. was supported by National Institutes of Health/National Institute
of Diabetes and Digestive and Kidney Diseases Training Grant T32DK007752
in Renal Function and Disease. M.G.J. was supported by Office of Naval
Research Award N000140810341. This study was supported by Veterans
Affairs Merit Grant P30 DK074038 and funds from Dialysis Clinic (to
P.D.B.).
NR 58
TC 7
Z9 7
U1 0
U2 14
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUN
PY 2014
VL 25
IS 6
BP 1187
EP 1197
DI 10.1681/ASN.2013080836
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0RS
UT WOS:000336558100010
PM 24511141
ER
PT J
AU Meehan, T
Stecker, MS
Kalva, SP
Oklu, R
Walker, TG
Ganguli, S
AF Meehan, Timothy
Stecker, Michael S.
Kalva, Sanjeeva P.
Oklu, Rahmi
Walker, T. Gregory
Ganguli, Suvranu
TI Outcomes of Transcatheter Arterial Embolization for Acute Hemorrhage
Originating from Gastric Adenocarcinoma
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID UPPER GASTROINTESTINAL HEMORRHAGE; CANCER; MANAGEMENT; SURGERY;
ENDOSCOPY; EMBOLOTHERAPY; MALIGNANCY; SURVIVAL
AB Purpose: To evaluate the indications, complications, and clinical outcomes of transcatheter embolization for acute hemorrhage associated with gastric adenocarcinoma.
Materials and Methods: Ten patients underwent catheter-directed arterial embolization at two institutions for acute gastrointestinal hemorrhage related to pathology-proven gastric adenocarcinoma from March 2002 to March 2012. The electronic medical record for each patient was reviewed for clinical presentation, endoscopy history, procedural complications, and long-term follow-up results.
Results: Between March 2002 and March 2012, 10 patients (eight men; mean age, 61.1 y +/- 15.3) underwent transcatheter arterial embolization for gastrointestinal hemorrhage caused by gastric adenocarcinoma. Endoscopic therapy had failed in all patients before embolization. Embolization involving branches of the left gastric artery was performed in all patients. No deaths or complications related to the procedure were identified. Mean survival was 301 days, but with a wide range, from 1 day to 1,852 days and counting. Those with unresectable disease (n = 7; 70%) had a median survival time of 9 days, significantly worse (P < .01) than those with resectable disease (n = 3; 30%), who had a median survival of 792 days. Six patients, all with unresectable disease, did not live beyond 30 days. Two of the three patients with resectable disease had subsequent curative resection.
conclusions: Transcatheter arterial embolization can be considered for cases of acute hemorrhagic gastric adenocarcinoma, with improved outcomes in patients with localized disease compared with nonresectable gastric adenocarcinoma.
C1 [Meehan, Timothy] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Oklu, Rahmi; Walker, T. Gregory; Ganguli, Suvranu] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA.
[Stecker, Michael S.] Div Angiog & Intervent Radiol, Boston, MA USA.
[Meehan, Timothy; Stecker, Michael S.; Oklu, Rahmi; Walker, T. Gregory; Ganguli, Suvranu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Intervent Radiol, Dallas, TX 75390 USA.
RP Ganguli, S (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM sganguli@partners.org
NR 27
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
EI 1535-7732
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUN
PY 2014
VL 25
IS 6
BP 847
EP 851
DI 10.1016/j.jvir.2014.02.005
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA AI1TY
UT WOS:000336639100004
PM 24657087
ER
PT J
AU Chao, TE
Sharma, K
Mandigo, M
Hagander, L
Resch, SC
Weiser, TG
Meara, JG
AF Chao, Tiffany E.
Sharma, Ketan
Mandigo, Morgan
Hagander, Lars
Resch, Stephen C.
Weiser, Thomas G.
Meara, John G.
TI Cost-effectiveness of surgery and its policy implications for global
health: a systematic review and analysis
SO LANCET GLOBAL HEALTH
LA English
DT Review
ID ADJUSTED LIFE YEARS; SUB-SAHARAN AFRICA; ADULT MALE CIRCUMCISION;
SIERRA-LEONE; ANESTHESIA INFRASTRUCTURE; INCOME COUNTRIES;
CATARACT-SURGERY; TRACHOMA CONTROL; HERNIA SURGERY; 21 REGIONS
AB Background The perception of surgery as expensive and complex might be a barrier to its widespread acceptance in global health efforts. We did a systematic review and analysis of cost-effectiveness studies that assess surgical interventions in low-income and middle-income countries to help quantify the potential value of surgery.
Methods We searched Medline for all relevant articles published between Jan 1, 1996 and Jan 31, 2013, and searched the reference lists of retrieved articles. We converted all results to 2012 US$. We extracted cost-effectiveness ratios (CERs) and appraised economic assessments for their methodological quality using the 10-point Drummond checklist.
Findings Of the 584 identified studies, 26 met full inclusion criteria. Together, these studies gave 121 independent CERs in seven categories of surgical interventions. The median CER of circumcision ($13.78 per disability-adjusted life year [DALY]) was similar to that of standard vaccinations ($12.96-25.93 per DALY) and bednets for malaria prevention ($6.48-22.04 per DALY). Median CERs of cleft lip or palate repair ($47.74 per DALY), general surgery ($82.32 per DALY), hydrocephalus surgery ($108.74 per DALY), and ophthalmic surgery ($136 per DALY) were similar to that of the BCG vaccine ($51.86-220.39 per DALY). Median CERs of caesarean sections ($315.12 per DALY) and orthopaedic surgery ($381.15 per DALY) are more favourable than those of medical treatment for ischaemic heart disease ($500.41-706.54 per DALY) and HIV treatment with multidrug antiretroviral therapy ($453.74-648.20 per DALY).
Interpretation Our findings suggest that many essential surgical interventions are cost-effective or very cost-effective in resource-poor countries. Quantification of the economic value of surgery provides a strong argument for the expansion of global surgery's role in the global health movement. However, economic value should not be the only argument for resource allocation-other organisational, ethical, and political arguments can also be made for its inclusion.
Funding Massachusetts General Hospital Department of Surgery, Boston Children's Hospital, and Stanford University Department of Surgery.
Copyright (C) Chao et al. Open Access article distributed under the terms of CC BY.
C1 [Chao, Tiffany E.; Sharma, Ketan; Mandigo, Morgan; Hagander, Lars; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA.
[Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Sharma, Ketan; Meara, John G.] Washington Univ, Sch Med, Div Plast & Reconstruct Surg, St Louis, MO USA.
[Mandigo, Morgan; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA.
[Mandigo, Morgan] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Hagander, Lars] Lund Univ, Dept Pediat Surg, Childrens Hosp, Lund, Sweden.
[Hagander, Lars] Lund Univ, Dept Clin Sci Lund, Fac Med, Lund, Sweden.
[Resch, Stephen C.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
[Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA.
RP Chao, TE (reprint author), 300 Longwood Ave,Enders 1, Boston, MA 02115 USA.
EM tchao@partners.org
FU Massachusetts General Hospital Department of Surgery
FX Research support was provided to TEC by Massachusetts General Hospital
Department of Surgery, to TEC, KS, MM, LH, amd JGM by Boston Children's
Hospital, and to TGW by Stanford University Department of Surgery. This
study forms part of the work for the forthcoming Lancet Commission on
Surgery.
NR 67
TC 54
Z9 55
U1 8
U2 29
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 JUN
PY 2014
VL 2
IS 6
BP E334
EP E345
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8YW
UT WOS:000336425200017
PM 25103302
ER
PT J
AU Krop, IE
Kim, SB
Gonzalez-Martin, A
LoRusso, PM
Ferrero, JM
Smitt, M
Yu, R
Leung, ACF
Wildiers, H
AF Krop, Ian E.
Kim, Sung-Bae
Gonzalez-Martin, Antonio
LoRusso, Patricia M.
Ferrero, Jean-Marc
Smitt, Melanie
Yu, Ron
Leung, Abraham C. F.
Wildiers, Hans
CA TH3RESA Study Collaborators
TI Trastuzumab emtansine versus treatment of physician's choice for
pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised,
open-label, phase 3 trial
SO LANCET ONCOLOGY
LA English
DT Article
ID CLINICAL-TRIALS; PI3K PATHWAY; LAPATINIB; PROGRESSION; CAPECITABINE;
COMBINATION; RESISTANCE; SURVIVAL; EFFICACY; ANTIBODY
AB Background Patients with progressive disease after two or more HER2-directed regimens for recurrent or metastatic breast cancer have few effective therapeutic options. We aimed to compare trastuzumab emtansine, an antibody-drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, with treatment of physician's choice in this population of patients.
Methods This randomised, open-label, phase 3 trial took place in medical centres in 22 countries across Europe, North America, South America, and Asia-Pacific. Eligible patients (>= 18 years, left ventricular ejection fraction >= 50%, Eastern Cooperative Oncology Group performance status 0-2) with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting, including trastuzumab and lapatinib, and previous taxane therapy in any setting, were randomly assigned (in a 2: 1 ratio) to trastuzumab emtansine (3.6 mg/kg intravenously every 21 days) or physician's choice using a permuted block randomisation scheme by an interactive voice and web response system. Patients were stratified according to world region (USA vs western Europe vs other), number of previous regimens (excluding single-agent hormonal therapy) for the treatment of advanced disease (two to three vs more than three), and presence of visceral disease (any vs none). Coprimary endpoints were investigator-assessed progression-free survival (PFS) and overall survival in the intention-to-treat population. We report the final PFS analysis and the first interim overall survival analysis. This study is registered with ClinicalTrials. gov, number NCT01419197.
Findings From Sept 14, 2011, to Nov 19, 2012, 602 patients were randomly assigned (404 to trastuzumab emtansine and 198 to physician's choice). At data cutoff (Feb 11, 2013), 44 patients assigned to physician's choice had crossed over to trastuzumab emtansine. After a median follow-up of 7.2 months (IQR 5.0-10.1 months) in the trastuzumab emtansine group and 6.5 months (IQR 4.1-9.7) in the physician's choice group, 219 (54%) patients in the trastuzumab emtansine group and 129 (65%) of patients in the physician's choice group had PFS events. PFS was significantly improved with trastuzumab emtansine compared with physician's choice (median 6.2 months [95% CI 5.59-6.87] vs 3.3 months [2.89-4.14]; stratified hazard ratio [HR] 0.528 [0.422-0.661]; p<0.0001). Interim overall survival analysis showed a trend favouring trastuzumab emtansine (stratified HR 0.552 [95% CI 0.369-0.826]; p= 0.0034), but the stopping boundary was not crossed. A lower incidence of grade 3 or worse adverse events was reported with trastuzumab emtansine than with physician's choice (130 events [32%] in 403 patients vs 80 events [43%] in 184 patients). Neutropenia (ten [2%] vs 29 [16%]), diarrhoea (three [<1%] vs eight [4%]), and febrile neutropenia (one [<1%] vs seven [4%]) were grade 3 or worse adverse events that were more common in the physician's choice group than in the trastuzumab emtansine group. Thrombocytopenia (19 [5%] vs three [2%]) was the grade 3 or worse adverse event that was more common in the trastuzumab emtansine group. 74 (18%) patients in the trastuzumab emtansine group and 38 (21%) in the physician's choice group reported a serious adverse event.
Interpretation Trastuzumab emtansine should be considered as a new standard for patients with HER2-positive advanced breast cancer who have previously received trastuzumab and lapatinib.
C1 [Krop, Ian E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kim, Sung-Bae] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea.
[Gonzalez-Martin, Antonio] MD Anderson Canc Ctr, Madrid, Spain.
[LoRusso, Patricia M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Ferrero, Jean-Marc] Ctr Antoine Lacassagne, Dept Med Oncol, F-06054 Nice, France.
[Smitt, Melanie; Yu, Ron; Leung, Abraham C. F.] Genentech Inc, San Francisco, CA 94080 USA.
[Wildiers, Hans] Univ Hosp Leuven, Dept Gen Med Oncol, Louvain, Belgium.
RP Krop, IE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM ikrop@partners.org
FU Genentech
FX Genentech.
NR 31
TC 118
Z9 119
U1 2
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2014
VL 15
IS 7
BP 689
EP 699
DI 10.1016/S1470-2045(14)70178-0
PG 11
WC Oncology
SC Oncology
GA AH9ZR
UT WOS:000336505900037
PM 24793816
ER
PT J
AU Fan, L
Strasser-Weippl, K
Li, JJ
St Louis, J
Finkelstein, DM
Yu, KD
Chen, WQ
Shao, ZM
Goss, PE
AF Fan, Lei
Strasser-Weippl, Kathrin
Li, Jun-Jie
St Louis, Jessica
Finkelstein, Dianne M.
Yu, Ke-Da
Chen, Wan-Qing
Shao, Zhi-Ming
Goss, Paul E.
TI Breast cancer in China
SO LANCET ONCOLOGY
LA English
DT Review
ID MIDDLE-INCOME COUNTRIES; PERIOD-COHORT ANALYSIS; SELF-EXAMINATION;
RECEPTOR STATUS; RISK-FACTORS; COST-EFFECTIVENESS; ESTROGEN-RECEPTOR;
LATIN-AMERICA; BODY-SIZE; HONG-KONG
AB The health burden of cancer is increasing in China, with more than 1 . 6 million people being diagnosed and 1 . 2 million people dying of the disease each year. As in most other countries, breast cancer is now the most common cancer in Chinese women; cases in China account for 12 . 2% of all newly diagnosed breast cancers and 9 . 6% of all deaths from breast cancer worldwide. China's proportional contribution to global rates is increasing rapidly because of the population's rising socioeconomic status and unique reproductive patterns. In this Review we present an overview of present control measures for breast cancer across China, and emphasise epidemiological and socioeconomic diversities and disparities in access to care for various subpopulations. We describe demographic differences between China and high-income countries, and also within geographical and socioeconomic regions of China. These disparities between China and high-income countries include younger age at onset of breast cancer; the unique one-child policy; lower rates of provision and uptake for screening for breast cancer; delays in diagnosis that result in more advanced stage of disease at presentation; inadequate resources; and a lack of awareness about breast cancer in the Chinese population. Finally, we recommend key measures that could contribute to improved health outcomes for patients with breast cancer in China.
C1 [Fan, Lei; Strasser-Weippl, Kathrin; Li, Jun-Jie; St Louis, Jessica; Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Int Breast Canc Program, Boston, MA USA.
[Finkelstein, Dianne M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA.
[Fan, Lei; Li, Jun-Jie; Yu, Ke-Da; Shao, Zhi-Ming] Fudan Univ, Dept Breast Surg, Ctr Canc, Shanghai 200433, Peoples R China.
[Fan, Lei; Li, Jun-Jie; Yu, Ke-Da; Shao, Zhi-Ming] Fudan Univ, Inst Canc, Shanghai 200433, Peoples R China.
[Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, Vienna, Austria.
[Chen, Wan-Qing] Chinese Acad Med Sci, Natl Off Canc Prevent & Control, Beijing 100730, Peoples R China.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,LRH 302, Boston, MA 02114 USA.
EM pgoss@partners.org
FU Avon Foundation New York
FX PEG, LF, J-JL, JSL, and DMF are supported by The Avon Foundation New
York. This funding source had no role in the planning or writing of the
Review.
NR 117
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Z9 233
U1 25
U2 108
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2014
VL 15
IS 7
BP E279
EP E289
PG 11
WC Oncology
SC Oncology
GA AH9ZR
UT WOS:000336505900023
PM 24872111
ER
PT J
AU Spiegel, P
Khalifa, A
Mateen, FJ
AF Spiegel, Paul
Khalifa, Adam
Mateen, Farrah J.
TI Cancer in refugees in Jordan and Syria between 2009 and 2012: challenges
and the way forward in humanitarian emergencies
SO LANCET ONCOLOGY
LA English
DT Review
ID AFGHAN REFUGEES; HEALTH
AB Treatment of non-communicable diseases such as cancer in refugees is neglected in low-income and middle-income countries, but is of increasing importance because the number of refugees is growing. The UNHCR, through exceptional care committees (ECCs), has developed standard operating procedures to address expensive medical treatment for refugees in host countries, to decide on eligibility and amount of payment. We present data from funding applications for cancer treatments for refugees in Jordan between 2010 and 2012, and in Syria between 2009 and 2011. Cancer in refugees causes a substantial burden on the health systems of the host countries. Recommendations to improve prevention and treatment include improvement of health systems through standard operating procedures and innovative financing schemes, balance of primary and emergency care with expensive referral care, development of electronic cancer registries, and securement of sustainable funding sources. Analysis of cancer care in low-income refugee settings, particularly in sub-Saharan Africa, is needed to inform future responses.
C1 [Spiegel, Paul] Off United Nations High Commissioner Refugees, CH-1211 Geneva, Switzerland.
[Khalifa, Adam] Off United Nations High Commissioner Refugees, Damascus, Syria.
[Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Spiegel, P (reprint author), Off United Nations High Commissioner Refugees, CH-1211 Geneva, Switzerland.
EM spiegel@unhcr.org
NR 18
TC 10
Z9 10
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2014
VL 15
IS 7
BP E290
EP E297
PG 8
WC Oncology
SC Oncology
GA AH9ZR
UT WOS:000336505900024
PM 24872112
ER
PT J
AU Decramer, M
Anzueto, A
Kerwin, E
Kaelin, T
Richard, N
Crater, G
Tabberer, M
Harris, S
Church, A
AF Decramer, Marc
Anzueto, Antonio
Kerwin, Edward
Kaelin, Thomas
Richard, Nathalie
Crater, Glenn
Tabberer, Maggie
Harris, Stephanie
Church, Alison
TI Efficacy and safety of umeclidinium plus vilanterol versus tiotropium,
vilanterol, or umeclidinium monotherapies over 24 weeks in patients with
chronic obstructive pulmonary disease: results from two multicentre,
blinded, randomised controlled trials
SO LANCET RESPIRATORY MEDICINE
LA English
DT Article
ID REFERENCE VALUES; COPD PATIENTS; DYSPNEA; SALMETEROL; BRONCHODILATION;
QUESTIONNAIRE; INDACATEROL; SHORTNESS; SAMPLE; BREATH
AB Background Combination long-acting bronchodilator treatment might be more effective than long-acting bronchodilator monotherapy for the treatment of chronic obstructive pulmonary disease (COPD). We aimed to compare the efficacy and safety of umeclidinium (UMEC) plus vilanterol (VI) with tiotropium (TIO) monotherapy, UMEC monotherapy, or VI monotherapy in patients with moderate to very severe COPD.
Methods In two multicentre, randomised, blinded, double-dummy, parallel-group, active-controlled trials, eligible patients (current or former smokers aged 40 years or older with an established clinical history of COPD) were randomly assigned in 1:1:1:1 ratio to UMEC 125 mu g plus VI 25 mu g, UMEC 62.5 mu g plus VI 25 mu g, TIO 18 mu g, and either VI 25 mu g (study 1) or UMEC 125 mu g (study 2). All study drugs were used once daily for 24 weeks. TIO was delivered via the HandiHaler inhaler and all other active treatments were delivered via the ELLIPTA dry powder inhaler. Random assignment (by a validated computer-based system) was done by centre and was not stratified. All patients and physicians were masked to assigned treatment during the studies. The primary efficacy endpoint of both studies was trough forced expiratory volume in 1 s (FEV1) on day 169, which was analysed in the intention-to-treat population. Both studies are registered with ClinicalTrials.gov, numbers NCT01316900 (study 1) and NCT01316913 (study 2).
Findings 1141 participants were recruited in study 1, and 1191 in study 2. For study 1, after exclusions, 208, 209, 214, and 212 patients were included in the intention-to-treat analyses for TIO monotherapy, VI monotherapy, UMEC 125 mu g plus VI 25 mu g, and UMEC 62.5 mu g plus VI 25 mu g, respectively. For study 2, 215, 222, 215, and 217 patients were included in the intention-to-treat analyses for TIO monotherapy, UMEC monotherapy, UMEC 125 mu g plus VI 25 mu g, and UMEC 62.5 mu g plus VI 25 mu g, respectively. In both studies, we noted improvements in trough FEV1 on day 169 for both doses of UMEC plus VI compared with TIO monotherapy (study 1, UMEC 125 mu g plus VI 25 mu g: 0.088 L [95% CI 0.036 to 0.140; p=0.0010]; study 1, UMEC 62.5 mu g plus VI 25 mu g: 0.090 L [0.039 to 0.141; p=0.0006]; study 2, UMEC 125 mu g plus VI 25 mu g: 0.074 L [0.025 to 0.123; p=0.0031]; study 2, UMEC 62.5 mu g plus VI 25 mu g: 0.060 L [0.010 to 0.109; nominal p=0.0182]). Both doses of UMEC plus VI also improved trough FEV1 compared with VI monotherapy (UMEC 125 mu g plus VI 25 mu g: 0.088 L [0.036 to 0.140; p=0.0010]; UMEC 62.5 mu g plus VI 25 mu g: 0.090 L [0.039 to 0.142; p=0.0006], but not compared with UMEC 125 mu g monotherapy (UMEC 125 mu g plus VI 25 mu g: 0.037 L [-0.012 to 0.087; p=0.14]; UMEC 62.5 mu g plus VI 25 mu g: 0.022 L [-0.027 to 0.072; p=0.38]). All treatments produced improvements in dyspnoea and health-related quality of life; we noted no significant differences in symptoms, health status, or risk of exacerbation between UMEC plus VI and TIO. The most common on-treatment, severe-intensity adverse event in both studies was acute exacerbation of COPD (1-4 [<1-2%] patients across treatment groups in study 1 and 1-6 [<1-3%] patients in study 2). We recorded five to 15 (2-7%) on-treatment serious adverse events across treatment groups in study 1, and nine to 22 (4-10%) in study 2. We noted no substantial changes from baseline in vital signs, clinical laboratory findings, or electrocardiography findings in any of the treatment groups.
Interpretation Combination treatment with once-daily UMEC plus VI improved lung function compared with VI monotherapy and TIO monotherapy in patients with COPD. Overall our results suggest that the combination of UMEC plus VI could be beneficial for the treatment of moderate to very severe COPD.
C1 [Decramer, Marc] Univ Louvain, Div Resp, Univ Hosp, B-3000 Louvain, Belgium.
[Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Kerwin, Edward] Clin Res Inst Southern Oregon, Medford, OR USA.
[Kaelin, Thomas] Lowcountry Lung & Crit Care, Charleston, SC USA.
[Richard, Nathalie; Harris, Stephanie; Church, Alison] GlaxoSmithKline, Resp & Immunoinflammat, Res Triangle Pk, NC USA.
[Crater, Glenn] Aerocrine, Clin Dev, Morrisville, NC USA.
[Tabberer, Maggie] GlaxoSmithKline, Uxbridge, Middx, England.
RP Decramer, M (reprint author), Univ Louvain, Div Resp, Univ Hosp, B-3000 Louvain, Belgium.
EM marc.decramer@uzleuven.be
OI Crater, Glenn/0000-0002-1159-1323
FU GlaxoSmithKline
FX The work presented here, including the conduct of the study, data
analysis, and data interpretation, was supported by GlaxoSmithKline.
Editorial assistance in the preparation of the report was provided by
David Griffiths (Fishawack Indicia, Knutsford, UK) and was funded by
GlaxoSmithKline.
NR 34
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U1 0
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-2600
J9 LANCET RESP MED
JI Lancet Resp. Med.
PD JUN
PY 2014
VL 2
IS 6
BP 472
EP 486
DI 10.1016/S2213-2600(14)70065-7
PG 15
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AI2WA
UT WOS:000336717900018
PM 24835833
ER
PT J
AU Brault, M
Ray, J
Gomez, YH
Mantzoros, CS
Daskalopoulou, SS
AF Brault, Marilyne
Ray, Jessica
Gomez, Yessica-Haydee
Mantzoros, Christos S.
Daskalopoulou, Stella S.
TI Statin treatment and new-onset diabetes: A review of proposed mechanisms
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Review
DE HMG-CoA inhibitors; Diabetes mellitus; Lipophilicity; Adipocytes;
Adiponectin; GLUT4; Isoprenoids; Ca2+ channels; Cholesterol
ID PANCREATIC BETA-CELLS; COA REDUCTASE INHIBITORS;
CORONARY-ARTERY-DISEASE; INSULIN-SECRETION; PPAR-GAMMA;
DRUG-INTERACTIONS; GLUCOSE-UPTAKE; CHOLESTEROL ACCUMULATION; NONDIABETIC
PATIENTS; PROTEIN PRENYLATION
AB New-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. To explain this association, three major mechanisms have been proposed and discussed in the literature. First, certain statins affect insulin secretion through direct, indirect Or combined effects on calcium channels in pancreatic (beta-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling. Other possible mechanisms implicated in the effect of statins on new-onset diabetes are: statin interference with intracellular insulin signal transduction pathways via inhibition of necessary phosphorylation events and reduction of small GTPase action; inhibition of adipocyte differentiation leading to decreased peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which are important pathways for glucose homeostasis; decreased leptin causing inhibition of (beta-cells proliferation and insulin secretion; and diminished adiponectin levels. Given that the magnitude of the risk of new-onset diabetes following statin use remains to be fully clarified and the well-established beneficial effect of statins in reducing cardiovascular risk, statins remain the first-choice treatment for prevention of CVD. Elucidation of the mechanisms underlying the development of diabetes in association with statin use may help identify novel preventative or therapeutic approaches to this problem and/or help design a new generation statin without such side-effects. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Brault, Marilyne] McGill Univ, Fac Med, Dept Med, Montreal, PQ H3G 1A4, Canada.
[Ray, Jessica] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3G 1A4, Canada.
[Gomez, Yessica-Haydee; Daskalopoulou, Stella S.] McGill Univ, Fac Med, Div Internal Med, Dept Med, Montreal, PQ H3G 1A4, Canada.
[Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA.
[Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
[Daskalopoulou, Stella S.] McGill Univ, Fac Med, Div Expt Med, Dept Med, Montreal, PQ H3G 1A4, Canada.
RP Daskalopoulou, SS (reprint author), McGill Univ, Ctr Hlth, Div Internal Med, Dept Med, 1650 Cedar Ave,C2-101-4, Montreal, PQ H3G 1A4, Canada.
EM stella.daskalopoulou@mcgill.ca
NR 98
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U2 23
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 2014
VL 63
IS 6
BP 735
EP 745
DI 10.1016/j.metabol.2014.02.014
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1UH
UT WOS:000336640100001
PM 24641882
ER
PT J
AU Hwang, JJ
Thakkar, B
Chamberland, JP
Mantzoros, CS
AF Hwang, Janice J.
Thakkar, Bindiya
Chamberland, John P.
Mantzoros, Christos S.
TI Circulating fetuin-A levels are not affected by short and long-term
energy deprivation and/or by leptin administration
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Fetuin-A; Leptin; Alpha-2-Heremans-Schmid glycoprotein
ID HYPOTHALAMIC AMENORRHEA; METABOLIC SYNDROME; HEALTHY-MEN; WOMEN; HUMANS;
RISK; NEUROENDOCRINE; HYPOLEPTINEMIA
AB Objective. Fetuin-A may mediate cross-talk between the liver and adipose tissue. We studied the physiologic regulation of fetuin-A and explored its potential regulation by leptin.
Design and Methods. Fetuin-A levels were measured in three interventional studies as well as in in vitro experiments. Study 1: 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin (metreleptin) following short term complete caloric deprivation to induce severe hypoleptinemia; Study 2: 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin; Study 3: 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months. In study 4 human hepatoma Hep G2 cells were treated with leptin. Fetuin-A mRNA expression and secretion were measured.
Results. Complete caloric deprivation significantly decreased leptin but had no effect on fetuin-A levels. Normalizing leptin levels with metreleptin in hypoleptinemic subjects had no effect on circulating fetuin-A levels. Leptin treatment had no effect on fetuin-A mRNA expression and secretion in vitro.
Conclusions. Circulating fetuin-A levels are not affected by short and long-term energy deprivation. Furthermore, both in vivo and in vitro experiments confirm that fetuin-A is not regulated by leptin. Published by Elsevier Inc.
C1 [Hwang, Janice J.; Thakkar, Bindiya; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02130 USA.
[Thakkar, Bindiya; Chamberland, John P.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA USA.
[Thakkar, Bindiya; Mantzoros, Christos S.] Boston Univ, Sch Med, Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
RP Thakkar, B (reprint author), Div Endocrinol Diabet & Metab, 150 S Huntington Ave,9B-52A, Boston, MA 02130 USA.
EM Bindiya.Thakkar@bmc.org
FU Harvard Clinical and Translational Science Center [L1 RR025758,
M01-RR-01032]
FX The project described was supported by Grant Number UL1 RR025758 and
M01-RR-01032 Harvard Clinical and Translational Science Center, from the
National Center for Research Resources. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Center for Research Resources or the
National Institutes of Health. Additional support for this research came
from grant-in-aid by Tanita Corporation and from Amgen/Amylin to BIDMC.
Amylin Pharmaceuticals, LLC (a wholly-owned subsidiary of Bristol-Myers
Squibb) supplied metreleptin for this study but had no role in the study
design; conduct of the study; collection, management, analysis, and
interpretation of the data; or the preparation, review, or approval of
the manuscript.
NR 29
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 2014
VL 63
IS 6
BP 754
EP 759
DI 10.1016/j.metabol.2014.02.006
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1UH
UT WOS:000336640100003
PM 24703486
ER
PT J
AU Aronis, KN
Sahin-Efe, A
Chamberland, JP
Spiro, A
Vokonas, P
Mantzoros, CS
AF Aronis, Konstantinos N.
Sahin-Efe, Ayse
Chamberland, John P.
Spiro, Avron, III
Vokonas, Pantel
Mantzoros, Christos S.
TI Chemerin levels as predictor of acute coronary events: A case-control
study nested within the veterans affairs normative aging study
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Chemerin; Acute Coronary Events; Normative Aging Study
ID EPICARDIAL ADIPOSE-TISSUE; MESSENGER-RNA EXPRESSION; FATTY
LIVER-DISEASE; METABOLIC SYNDROME; ARTERY-DISEASE; INSULIN-RESISTANCE;
BARIATRIC SURGERY; RECEPTOR CHEMR23; WEIGHT-LOSS; OBESITY
AB Objective. Chemerin is a recently identified adipocytokine that has been positively correlated with the presence and severity of coronary artery disease (CAD). However, no studies have examined circulating chemerin levels as a predictor of acute coronary syndrome (ACS). The purpose of this study is to evaluate whether chemerin levels predict the onset of ACS.
Materials/Methods. We studied 90 men whose serum had been collected at least 2 years before the development of ACS, and 162 controls matched with the cases in a 1:2 fashion for age and year of collection. The mean age of the cohort was 66.3 +/- 9.6 years (range 34-84 years). Serum chemerin levels were measured with a commercially available enzyme-linked immunosorbent assay.
Results. Age was positively associated with chemerin levels (r = 0.39, p < 0.001). Logistic regression analysis, adjusting for years since blood collection, demonstrated a null association between chemerin levels and the odds ratio for development of ACS (OR: 0.99, 95% CI [0.99-1.001]). This association remained null after adjusting for age (OR: 0.99 95% CI [0.99-1.001]).
Conclusions. Although cross-sectional and case control studies suggest a positive association between chemerin levels and CAD, we demonstrate that chemerin levels do not predict the development of ACS. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Aronis, Konstantinos N.; Sahin-Efe, Ayse; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Endocrinol Sect, Cambridge, MA 02138 USA.
[Aronis, Konstantinos N.; Sahin-Efe, Ayse; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Cambridge, MA 02138 USA.
[Aronis, Konstantinos N.; Mantzoros, Christos S.] Boston Univ, Sch Med, Boston Med Ctr, Dept Med, Boston, MA 02215 USA.
[Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, Normat Aging Study, Jamaica Plain, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Spiro, Avron, III; Vokonas, Pantel] Boston Univ, Sch Med, Boston, MA 02215 USA.
RP Aronis, KN (reprint author), VA Boston Hlth Care Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA.
EM konstantinos.aronis@bmc.org
RI Aronis, Konstantinos/F-3586-2012
OI Aronis, Konstantinos/0000-0001-7189-8434
FU Clinical Science Research and Development Service of the VA Office of
Research and Development [1I01CX000422-01A1]; Cooperative Studies
Program/ERIC, US Department of Veterans Affairs; Massachusetts Veterans
Epidemiology Research and Information Center; Research Career Scientist
award from the Clinical Science Research and Development Service, US
Department of Veterans' Affairs
FX The Mantzoros Laboratory is supported by the Award Number
1I01CX000422-01A1 from the Clinical Science Research and Development
Service of the VA Office of Research and Development. NAS is supported
by Cooperative Studies Program/ERIC, US Department of Veterans Affairs
and is a research component of the Massachusetts Veterans Epidemiology
Research and Information Center. Dr. Spiro is supported by a Research
Career Scientist award from the Clinical Science Research and
Development Service, US Department of Veterans' Affairs.
NR 51
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U1 0
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 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 2014
VL 63
IS 6
BP 760
EP 766
DI 10.1016/j.metabol.2014.02.013
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1UH
UT WOS:000336640100004
PM 24684821
ER
PT J
AU Liu, X
Hamnvik, OPR
Chamberland, JP
Petrou, M
Gong, H
Christophi, CA
Christiani, DC
Kales, SN
Mantzoros, CS
AF Liu, Xiaowen
Hamnvik, Ole-Petter R.
Chamberland, John P.
Petrou, Michael
Gong, Huizhi
Christophi, Costas A.
Christiani, David C.
Kales, Stefanos N.
Mantzoros, Christos S.
TI Circulating alanine transaminase (ALT) and gamma-glutamyl transferase
(GGT), but not fetuin-A, are associated with metabolic risk factors, at
baseline and at two-year follow-up: The prospective Cyprus Metabolism
Study
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Obesity; Insulin resistance; Metabolic syndrome
ID MIDDLE-AGED MEN; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; SERUM
FETUIN; LIVER-ENZYMES; JAPANESE MEN; OBESITY; AMINOTRANSFERASE; DISEASE;
WOMEN
AB Objective. To comparatively evaluate traditional liver tests and fetuin A as predictors of cardiometabolic risk, we studied associations between serum alanine transaminase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters cross-sectionally at baseline, and prospectively, after 2-years of follow-up.
Research Design and Methods. 616 randomly enrolled young healthy participants in the Cyprus Metabolism Study, including all 93 subjects who participated in the follow-up study 2 years after baseline assessment, were included in this study.
Results. In the cross-sectional study, serum ALT and GGT were strongly correlated with anthropometric, cardiovascular, and metabolic variables, while serum AST was only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was correlated with anthropometric variables, systolic blood pressure (SBP), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) in the unadjusted model. In the fully adjusted model, both serum ALT and GGT levels remained positively correlated with total and low-density lipoprotein (LDL) cholesterol. GGT levels also remained correlated with triglycerides. ALT levels remained strongly positively correlated with insulin (r = 0.17, p < .0001) and HOMA-IR (r = 0.16, p = 0.0001). Serum fetuin-A levels were no longer significantly correlated with any variables.
Prospectively, ALT and GGT were predictors of anthropometric variables and LDL cholesterol, while baseline levels of AST and fetuin-A were not predictors of any variables at 2-year follow-up.
Conclusions. We confirmed associations of ALT and GGT levels but failed to demonstrate an independent association between fetuin-A and cardiometabolic risk factors in young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A predictors of metabolic risk factors cross-sectionally and prospectively in young healthy adults. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Liu, Xiaowen; Chamberland, John P.; Gong, Huizhi; Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Liu, Xiaowen; Hamnvik, Ole-Petter R.; Chamberland, John P.; Gong, Huizhi; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston, MA USA.
[Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Petrou, Michael; Christophi, Costas A.] Cyprus Univ Technol, Harvard Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
[Christophi, Costas A.; Christiani, David C.; Kales, Stefanos N.; Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02139 USA.
[Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA.
RP Kales, SN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Macth Bldg 427,1493 Cambridge St, Cambridge, MA 02139 USA.
EM skales@hsph.harvard.edu
RI Hamnvik, Ole-Petter/D-1719-2011
FU Cyprus Research Promotion Foundation [EPE/0205/10]; Beth Israel
Deaconess Medical Center [DK58785, DK79929, DK81913, AG032030]; Harvard
Catalyst \ The Harvard Clinical and Translational Science Center (NIH)
[UL1 RR 025758]; Harvard University
FX The study was supported by the Cyprus Research Promotion Foundation (EP
Upsilon E Xi/0205/10). The Mantzoros Lab is supported by grants DK58785,
DK79929, DK81913, AG032030, a VA Merit award and a discretionary grant
from Beth Israel Deaconess Medical Center. This work was conducted with
support from Harvard Catalyst vertical bar The Harvard Clinical and
Translational Science Center (NIH Award #UL1 RR 025758 and financial
contributions from Harvard University and its affiliated academic health
care centers).
NR 47
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PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 2014
VL 63
IS 6
BP 773
EP 782
DI 10.1016/j.metabol.2014.03.008
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1UH
UT WOS:000336640100006
PM 24726813
ER
PT J
AU Forristal, C
Henley, SA
MacDonald, JI
Bush, JR
Ort, C
Passos, DT
Talluri, S
Ishak, CA
Thwaites, MJ
Norley, CJ
Litovchick, L
DeCaprio, JA
DiMattia, G
Holdsworth, DW
Beier, F
Dick, FA
AF Forristal, Chantal
Henley, Shauna A.
MacDonald, James I.
Bush, Jason R.
Ort, Carley
Passos, Daniel T.
Talluri, Srikanth
Ishak, Charles A.
Thwaites, Michael J.
Norley, Chris J.
Litovchick, Larisa
DeCaprio, James A.
DiMattia, Gabriel
Holdsworth, David W.
Beier, Frank
Dick, Frederick A.
TI Loss of the Mammalian DREAM Complex Deregulates Chondrocyte
Proliferation
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID CELL-CYCLE; GENE-EXPRESSION; B-MYB; RETINOBLASTOMA PROTEIN; HISTONE
DEACETYLASE; IN-VIVO; REPRESS TRANSCRIPTION; TARGETED DISRUPTION; G(2)/M
GENES; MICE LACKING
AB Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes.
C1 [Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, London Reg Canc Program, London, ON, Canada.
[Bush, Jason R.; Beier, Frank; Dick, Frederick A.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada.
[Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, Dept Biochem, London, ON, Canada.
[Bush, Jason R.; Beier, Frank] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada.
[Norley, Chris J.; Holdsworth, David W.] Univ Western Ontario, Dept Med Biophys, London, ON, Canada.
[DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, Dept Oncol, London, ON, Canada.
[Litovchick, Larisa] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
[DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[DeCaprio, James A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Dick, FA (reprint author), Univ Western Ontario, London Reg Canc Program, London, ON, Canada.
EM fdick@uwo.ca
RI Passos, Daniel/K-5520-2012; Holdsworth, David/F-6315-2012; Beier,
Frank/G-4595-2013
OI Passos, Daniel/0000-0002-3530-2821; Beier, Frank/0000-0002-8505-7537
FU SRP award from the Schulich School of Medicine and Dentistry; CaRTT;
CBCF-Ontario; Canadian Cancer Society Research Institute [2011700720];
Canadian Institutes of Health Research [MOP43899]; CIHR postdoctoral
fellowship (Priority Announcement: Epigenetics)
FX C.F. was supported by an SRP award from the Schulich School of Medicine
and Dentistry. S.A.H. and C.A.I. were supported by fellowship awards
from CaRTT, and S.A.H. also acknowledges fellowship support from
CBCF-Ontario. J.R.B. is the recipient of CIHR postdoctoral fellowship
(Priority Announcement: Epigenetics). F.B. is the Canada Research Chair
in musculoskeletal research. F.A.D. is the Wolfe Senior Fellow in Tumor
Suppressor Genes at Western University. Funding for this work was
provided by the Canadian Cancer Society Research Institute (2011700720)
to F.A.D. and the Canadian Institutes of Health Research (MOP43899) to
F.B.
NR 57
TC 7
Z9 8
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2014
VL 34
IS 12
BP 2221
EP 2234
DI 10.1128/MCB.01523-13
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AI3EQ
UT WOS:000336743200010
PM 24710275
ER
PT J
AU Panic, N
Mastrostefano, E
Leoncini, E
Persiani, R
Arzani, D
Amore, R
Ricci, R
Sicoli, F
Sioletic, S
Bulajic, M
D' Ugo, D
Ricciardi, W
Boccia, S
AF Panic, Nikola
Mastrostefano, Elena
Leoncini, Emanuele
Persiani, Roberto
Arzani, Dario
Amore, Rosarita
Ricci, Riccardo
Sicoli, Federico
Sioletic, Stefano
Bulajic, Milutin
D' Ugo, Domenico
Ricciardi, Walter
Boccia, Stefania
TI Susceptibility to Helicobacter pylori infection: results of an
epidemiological investigation among gastric cancer patients
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE Helicobacter pylori; Gastric cancer; Genetic polymorphism; Family
history
ID METHYLENETETRAHYDROFOLATE REDUCTASE C677T; P53 ARG72PRO POLYMORPHISM;
CARDIOVASCULAR EVENTS; A1298C POLYMORPHISMS; ALCOHOL-CONSUMPTION;
ITALIAN POPULATION; GENE POLYMORPHISMS; ALLELE FREQUENCIES; MULTIPLEX
PCR; RISK-FACTORS
AB The aim of this study was to identify the clinical, demographic, lifestyle factors and selected genetic polymorphisms that affect the susceptibility towards Helicobacter pylori (H. pylori) infection in gastric cancer patients. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002 and 2012 were included. Gastric biopsy samples were obtained to determine the H. pylori status, and further cagA status and vacA m and s genotypes by polymerase chain reaction. Patients were interviewed with structured questionnaires, and blood samples were collected for EPHX1, GSTM1, GSTT1, IL1B, IL1-RN, MTHFR and p53 genotyping. Proportions were compared in univariate analysis, while the relation between putative risk factors and H. pylori status and genotype were measured using logistic regression analysis. One hundred forty-nine gastric cancer patients were included, of which 78.5 % were H. pylori positive. Among positive patients 50 % were cagA+, 72.5 % vacA m1 and 80.7 % vacA s1. The presence of cagA was less frequent among vacA m1 (p = 0.031) and vacA s1 (p = 0.052) subtypes. The presence of father history for any cancer was a significant risk factor for H. pylori infection [adjusted odds ratio (OR) = 8.18, 95 % confidence interval (CI) 1.04-64.55]. EPHX1 exon 3 T > C (OR = 0.35, CI 95 % 0.13-0.94), IL1B-511 T > C (OR = 0.38, CI 95 % 0.15-0.97) and IL1-RN VNTR (OR = 0.19, CI 95 % 0.06-0.58) polymorphisms were protective towards H. pylori infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the H. pylori vacA m1 virulent subtype (p = 0.034). Lastly, cardiovascular diseases were less common among cagA positive subjects (p = 0.023). Father history of any cancer is a risk factor for H. pylori infection. Polymorphisms in IL1B-511, IL1-RN and EPHX1 exon 3 genes might be protective towards H. pylori infection.
C1 [Panic, Nikola; Mastrostefano, Elena; Leoncini, Emanuele; Arzani, Dario; Amore, Rosarita; Ricciardi, Walter; Boccia, Stefania] Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy.
[Panic, Nikola; Bulajic, Milutin] Univ Belgrade, Fac Med, Belgrade, Serbia.
[Panic, Nikola; Bulajic, Milutin] Univ Clin Hosp Ctr Dr DragisaMisovic Dedinje, Belgrade, Serbia.
[Persiani, Roberto; Sicoli, Federico; D' Ugo, Domenico] Univ Cattolica Sacro Cuore, Dept Surg, Rome, Italy.
[Ricci, Riccardo] Univ Cattolica Sacro Cuore, Dept Pathol, Rome, Italy.
[Sioletic, Stefano] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA.
[Bulajic, Milutin] Univ Clin Hosp Santa Maria della Misericordia, Udine, Italy.
[Boccia, Stefania] IRCCS San Raffaele, Rome, Italy.
RP Boccia, S (reprint author), Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy.
EM sboccia@rm.unicatt.it
RI Kim, Seongman/N-6910-2014; Ricci, Riccardo/E-4411-2010; Ricci,
Riccardo/A-8195-2017; , emanuele/A-5466-2010
OI Ricci, Riccardo/0000-0002-9089-5084; Ricci,
Riccardo/0000-0002-9089-5084; , emanuele/0000-0002-7669-8535
FU AIRC (Associazione Italiana Ricerca sul Cancro) [IG 2013 N.14220];
Italian Ministry of Health [GR-2011-02347943]; ERAWEB project; European
Community; Fondazione Veronesi
FX This work has been supported by the AIRC (Associazione Italiana Ricerca
sul Cancro) IG 2013 N.14220, and from the Italian Ministry of Health
(GR-2011-02347943). The work of Dr Nikola Panic was supported by the
ERAWEB project, funded with support of the European Community. The work
of Dr Emanuele Leoncini was supported by Fondazione Veronesi.
NR 61
TC 3
Z9 3
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
EI 1573-4978
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD JUN
PY 2014
VL 41
IS 6
BP 3637
EP 3650
DI 10.1007/s11033-014-3228-0
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8QY
UT WOS:000336404500012
PM 24526578
ER
PT J
AU Hooli, BV
Kovacs-Vajna, ZM
Mullin, K
Blumenthal, MA
Mattheisen, M
Zhang, C
Lange, C
Mohapatra, G
Bertram, L
Tanzi, RE
AF Hooli, B. V.
Kovacs-Vajna, Z. M.
Mullin, K.
Blumenthal, M. A.
Mattheisen, M.
Zhang, C.
Lange, C.
Mohapatra, G.
Bertram, L.
Tanzi, R. E.
TI Rare autosomal copy number variations in early-onset familial
Alzheimer's disease
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE Alzheimer's; CNVs; MAPT; CHMP2B; VLDLR
ID COMPARATIVE GENOMIC HYBRIDIZATION; N-CADHERIN; MENTAL-RETARDATION;
DE-NOVO; GRANULOVACUOLAR DEGENERATION; FRONTOTEMPORAL DEMENTIA;
STRUCTURAL VARIATION; ASSOCIATION ANALYSIS; GENETIC ASSOCIATION; LOCUS
DUPLICATION
AB Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using highdensity DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias.
C1 [Hooli, B. V.; Mullin, K.; Blumenthal, M. A.; Zhang, C.; Tanzi, R. E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Kovacs-Vajna, Z. M.] Univ Brescia, Dept Informat Engn, Brescia, Italy.
[Mattheisen, M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Lange, C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mohapatra, G.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Bertram, L.] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, D-14195 Berlin, Germany.
RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA.
EM tanzi@helix.mgh.harvard.edu
RI Mattheisen, Manuel/B-4949-2012; Bertram, Lars/K-3889-2015
OI Mattheisen, Manuel/0000-0002-8442-493X; Bertram,
Lars/0000-0002-0108-124X
FU NIMH; Cure Alzheimer's Fund
FX This study was funded by grants from the NIMH and the Cure Alzheimer's
Fund.
NR 73
TC 15
Z9 15
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2014
VL 19
IS 6
BP 676
EP 681
DI 10.1038/mp.2013.77
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AI2BZ
UT WOS:000336663100009
PM 23752245
ER
PT J
AU Gelernter, J
Sherva, R
Koesterer, R
Almasy, L
Zhao, H
Kranzler, HR
Farrer, L
AF Gelernter, J.
Sherva, R.
Koesterer, R.
Almasy, L.
Zhao, H.
Kranzler, H. R.
Farrer, L.
TI Genome-wide association study of cocaine dependence and related traits:
FAM53B identified as a risk gene
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE cocaine dependence; cocaine-induced paranoia; European-American and
African-American populations; GWAS; population genetics
ID POPULATION-BASED SAMPLE; INDUCED PSYCHOSIS; INDUCED PARANOIA; LINKAGE
SCAN; ABUSE; ALCOHOLISM; TWINS
AB We report a genome-wide association study (GWAS) for cocaine dependence (CD) in three sets of African-and European-American subjects (AAs and EAs, respectively) to identify pathways, genes and alleles important in CD risk. The discovery GWAS data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549 independent subjects. We observed one genome-wide-significant (GWS) result: rs2629540 at the FAM53B (` family with sequence similarity 53, member B') locus. This was supported in both AAs and EAs; P-value (meta-analysis of all samples) 4.28 x 10(-8). The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 2) SNP rs150954431 was associated with P = 1.19 x 10(-9) in the EA discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase 1'), was associated with cocaine-induced paranoia in AAs in the discovery sample only (P-4.68 x 10(-8)). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies.
C1 [Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, New Haven, CT USA.
[Gelernter, J.] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA.
[Gelernter, J.; Zhao, H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA.
[Sherva, R.; Koesterer, R.; Farrer, L.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA.
[Almasy, L.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Zhao, H.] Yale Univ, Dept Biostat, Sch Publ Hlth, New Haven, CT USA.
[Kranzler, H. R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kranzler, H. R.] Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA USA.
[Farrer, L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, L.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, L.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
[Farrer, L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA.
RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, VA CT 116A2,950 Campbell Ave, West Haven, CT 06516 USA.
EM joel.gelernter@yale.edu
OI Farrer, Lindsay/0000-0001-5533-4225
FU National Institutes of Health [N01-HG-65403, RC2 DA028909, R01 DA12690,
R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535]; VA Connecticut and
Philadelphia VA MIRECCs; Study of Addiction: Genetics and Environment
(SAGE) was provided through the NIH Genes, Environment and Health
Initiative [U01 HG004422]; Collaborative Study on the Genetics of
Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of
Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine
Dependence (FSCD) [R01 DA013423]; Johns Hopkins University Center for
Inherited Disease Research; NIH GEI [U01HG004438]; National Institute on
Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH
contract 'High throughput genotyping for studying the genetic
contributions to human disease' [HHSN268200782096C]
FX We appreciate the work in recruitment and assessment provided at McLean
Hospital by Roger Weiss at the Medical University of South Carolina by
Kathleen Brady and Raymond Anton and at the University of Pennsylvania
by David Oslin. Genotyping services for a part of our GWAS study were
provided by the Center for Inherited Disease Research (CIDR) and Yale
University (Center for Genome Analysis). CIDR is fully funded through a
federal contract from the National Institutes of Health to The Johns
Hopkins University (contract number N01-HG-65403). We are grateful to
Ann Marie Lacobelle, Michelle Cucinelli, Christa Robinson and Greg
Dalton-Kay for their excellent technical assistance, to the SSADDA
interviewers, led by Yari Nunez and Michelle Slivinsky, who devoted
substantial time and effort to phenotype the study sample and to John
Farrell for database management assistance. This study was supported by
National Institutes of Health Grants RC2 DA028909, R01 DA12690, R01
DA12849, R01 DA18432, R01 AA11330, R01 AA017535 and the VA Connecticut
and Philadelphia VA MIRECCs. The publicly available data sets used for
the analyses described in this manuscript were obtained from dbGaP at
http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0
00092.v1.p1 through dbGaP accession number phs000092.v1.p. Funding
support for the Study of Addiction: Genetics and Environment (SAGE) was
provided through the NIH Genes, Environment and Health Initiative (GEI;
U01 HG004422). SAGE is one of the genome-wide association studies funded
as part of the Gene Environment Association Studies (GENEVA) under GEI.
Assistance with phenotype harmonization and genotype cleaning, as well
as with general study coordination, was provided by the GENEVA
Coordinating Center (U01 HG004446). Assistance with data cleaning was
provided by the National Center for Biotechnology Information. Support
for collection of data sets and samples was provided by the
Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401),
the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01
CA089392) and the Family Study of Cocaine Dependence (FSCD; R01
DA013423). Funding support for genotyping, which was performed at the
Johns Hopkins University Center for Inherited Disease Research, was
provided by the NIH GEI (U01HG004438), the National Institute on Alcohol
Abuse and Alcoholism, the National Institute on Drug Abuse and the NIH
contract 'High throughput genotyping for studying the genetic
contributions to human disease' (HHSN268200782096C).
NR 31
TC 28
Z9 28
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2014
VL 19
IS 6
BP 717
EP 723
DI 10.1038/mp.2013.99
PG 7
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AI2BZ
UT WOS:000336663100014
PM 23958962
ER
PT J
AU Medland, SE
Jahanshad, N
Neale, BM
Thompson, PM
AF Medland, Sarah E.
Jahanshad, Neda
Neale, Benjamin M.
Thompson, Paul M.
TI Whole-genome analyses of whole-brain data: working within an expanded
search space
SO NATURE NEUROSCIENCE
LA English
DT Review
ID DE-NOVO MUTATIONS; TENSOR-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; WIDE
ASSOCIATION; COMMON VARIANTS; EPILEPTIC ENCEPHALOPATHIES;
APOLIPOPROTEIN-E; GENE; SCHIZOPHRENIA; HERITABILITY
AB Large-scale comparisons of patients and healthy controls have unearthed genetic risk factors associated with a range of neurological and psychiatric illnesses. Meanwhile, brain imaging studies are increasing in size and scope, revealing disease and genetic effects on brain structure and function, and implicating neural pathways and causal mechanisms. With the advent of global neuroimaging consortia, imaging studies are now well powered to discover genetic variants that reliably affect the brain. Genetic analyses of brain measures from tens of thousands of people are being extended to test genetic associations with signals at millions of locations in the brain, and connectome-wide, genome-wide scans can jointly screen brain circuits and genomes; these analyses and others present new statistical challenges. There is a growing need for the community to establish and enforce standards in this developing field to ensure robust findings. Here we discuss how neuroimagers and geneticists have formed alliances to discover how genetic factors affect the brain. The field is rapidly advancing with ultra-high-resolution imaging and whole-genome sequencing. We recommend a rigorous approach to neuroimaging genomics that capitalizes on its recent successes and ensures the reliability of future discoveries.
C1 [Medland, Sarah E.] QIMR Berghofer Med Res Inst, Quantitat Genet, Brisbane, Qld, Australia.
[Jahanshad, Neda; Thompson, Paul M.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90033 USA.
[Jahanshad, Neda; Thompson, Paul M.] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA.
[Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Neale, Benjamin M.] Massachusetts Gen Hosp, Psychiat & Neurodev Unit, Boston, MA 02114 USA.
[Thompson, Paul M.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90033 USA.
[Thompson, Paul M.] Univ So Calif, Dept Engn, Los Angeles, CA 90033 USA.
[Thompson, Paul M.] Univ So Calif, Dept Radiol, Los Angeles, CA 90033 USA.
[Thompson, Paul M.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA.
[Thompson, Paul M.] Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA.
RP Thompson, PM (reprint author), Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90033 USA.
EM pthomp@usc.edu
RI Medland, Sarah/C-7630-2013
OI Medland, Sarah/0000-0003-1382-380X
FU Australian Research Council Future Fellowship [110100548]; US National
Institutes of Health R01 [NS080655, AG040060, EB008432, MH097268,
MH085667, MH089722, MH094343]; [U01 AG024904]; [P41 EB015922]; [R01
MH101244]
FX S.E.M. is supported by an Australian Research Council Future Fellowship,
110100548. N.J. and P.M.T. were supported, in part, by US National
Institutes of Health R01 grants NS080655, AG040060, EB008432, MH097268,
MH085667, MH089722 and MH094343, and grants U01 AG024904 and P41
EB015922. B.M.N. was supported in part by R01 MH101244.
NR 67
TC 37
Z9 40
U1 0
U2 21
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 JUN
PY 2014
VL 17
IS 6
BP 791
EP 800
DI 10.1038/nn.3718
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AI1TO
UT WOS:000336638000012
PM 24866045
ER
PT J
AU Pietrobon, D
Moskowitz, MA
AF Pietrobon, Daniela
Moskowitz, Michael A.
TI Chaos and commotion in the wake of cortical spreading depression and
spreading depolarizations
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID RAT HIPPOCAMPAL SLICES; FAMILIAL HEMIPLEGIC MIGRAINE;
CENTRAL-NERVOUS-SYSTEM; PATENT FORAMEN OVALE; CA1 PYRAMIDAL CELLS;
ASPARTATE RECEPTOR ANTAGONISTS; GLUTAMATE TRANSPORTER GLT-1;
CEREBRAL-BLOOD-FLOW; NEURONS IN-VITRO; ANOXIC DEPOLARIZATION
AB Punctuated episodes of spreading depolarizations erupt in the brain, encumbering tissue structure and function, and raising fascinating unanswered questions concerning their initiation and propagation. Linked to migraine aura and headache, cortical spreading depression contributes to the morbidity in the world's migraine with aura population. Even more ominously, erupting spreading depolarizations accelerate tissue damage during brain injury. The once-held view that spreading depolarizations may not exist in the human brain has changed, largely because of the discovery of migraine genes that confer cortical spreading depression susceptibility, the application of sophisticated imaging tools and efforts to interrogate their impact in the acutely injured human brain.
C1 [Pietrobon, Daniela] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
[Pietrobon, Daniela] Univ Padua, CNR, Inst Neurosci, I-35121 Padua, Italy.
[Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA.
[Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Moskowitz, Michael A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Pietrobon, D (reprint author), Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
EM daniela.pietrobon@unipd.it; Moskowitz@helix.mgh.harvard.edu
FU Italian Ministry of University and Research [PRIN2010]; University of
Padova
FX The support of the Italian Ministry of University and Research
(PRIN2010) and of the University of Padova (Strategic Project 2008 and
Progetto Ateneo 2012) to D.P. is gratefully acknowledged. The authors
gratefully thank A. Tottene for help with the figures.
NR 192
TC 57
Z9 58
U1 6
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD JUN
PY 2014
VL 15
IS 6
BP 379
EP 393
DI 10.1038/nrn3770
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA AI3XX
UT WOS:000336800100012
PM 24857965
ER
PT J
AU Pauls, DL
Abramovitch, A
Rauch, SL
Geller, DA
AF Pauls, David L.
Abramovitch, Amitai
Rauch, Scott L.
Geller, Daniel A.
TI Obsessive-compulsive disorder: an integrative genetic and
neurobiological perspective
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID FAMILY-BASED ASSOCIATION; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED
CONTROLLED-TRIAL; OCD COLLABORATIVE GENETICS; FACTOR-ANALYZED SYMPTOM;
DIRECT INTERVIEW FAMILY; HAN CHINESE POPULATION; GLUCOSE METABOLIC-RATE;
WIDE LINKAGE ANALYSIS; CEREBRAL-BLOOD-FLOW
AB Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.
C1 [Pauls, David L.; Abramovitch, Amitai; Rauch, Scott L.; Geller, Daniel A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Pauls, David L.; Abramovitch, Amitai; Rauch, Scott L.; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
[Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA.
RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
EM dpauls@pngu.mgh.harvard.edu; dan.geller@mgh.harvard.edu
OI Abramovitch, Amitai/0000-0001-9640-0970
FU US National Institutes of Health (NIH) grants [NS16648, NS40024,
MH079489]
FX This work was supported in part by US National Institutes of Health
(NIH) grants NS16648 (to D.L.P.), NS40024 (to D.L.P.) and MH079489 (to
D.L.P.).
NR 208
TC 84
Z9 85
U1 17
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD JUN
PY 2014
VL 15
IS 6
BP 410
EP 424
DI 10.1038/nrn3746
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA AI3XX
UT WOS:000336800100014
PM 24840803
ER
PT J
AU Kaley, T
Barani, I
Chamberlain, M
McDermott, M
Panageas, K
Raizer, J
Rogers, L
Schiff, D
Vogelbaum, M
Weber, D
Wen, P
AF Kaley, Thomas
Barani, Igor
Chamberlain, Marc
McDermott, Michael
Panageas, Katherine
Raizer, Jeffrey
Rogers, Leland
Schiff, David
Vogelbaum, Michael
Weber, Damien
Wen, Patrick
TI Historical benchmarks for medical therapy trials in surgery- and
radiation-refractory meningioma: a RANO review
SO NEURO-ONCOLOGY
LA English
DT Article
DE anaplastic meningioma; atypical meningioma; chemotherapy meningioma;
malignant meningioma; meningioma
ID RECURRENT MALIGNANT GLIOMAS; BRAIN-TUMOR CONSORTIUM; PHASE-II;
UNRESECTABLE MENINGIOMA; BEVACIZUMAB THERAPY; IMATINIB MESYLATE;
INTERFERON-ALPHA; HYDROXYUREA; OCTREOTIDE; REGRESSION
AB The outcomes of patients with surgery- and radiation-refractory meningiomas treated with medical therapies are poorly defined. Published reports are limited by small patient numbers, selection bias, inclusion of mixed histologic grades and stages of illness, and World Health Organization (WHO) criteria changes. This analysis seeks to define outcome benchmarks for future clinical trial design.
A PubMed literature search was performed for all English language publications on medical therapy for meningioma. Reports were tabulated and analyzed for number of patients, histologic grade, prior therapy, overall survival, progression-free survival (PFS), and radiographic response.
Forty-seven publications were identified and divided by histology and prior therapies, including only those that treated patients who were surgery and radiation refractory for further analysis. This included a variety of agents (hydroxyurea, temozolomide, irinotecan, interferon-alpha, mifepristone, octreotide analogues, megestrol acetate, bevacizumab, imatinib, erlotinib, and gefitinib) from retrospective, pilot, and phase II studies, exploratory arms of other studies, and a single phase III study. The only outcome extractable from all studies was the PFS 6-month rate, and a weighted average was calculated separately for WHO grade I meningioma and combined WHO grade II/III meningioma. For WHO I meningioma, the weighted average PFS-6 was 29% (95% confidence interval [CI]: 20.3%-37.7%). For WHO II/III meningioma, the weighted average PFS-6 was 26% (95% CI: 19.3%-32.7%).
This comprehensive review confirms the poor outcomes of medical therapy for surgery- and radiation-refractory meningioma. We recommend the above PFS-6 benchmarks for future trial design.
C1 [Kaley, Thomas] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
[Barani, Igor] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA.
[Chamberlain, Marc] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[McDermott, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA.
[Panageas, Katherine] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 19965 USA.
[Raizer, Jeffrey] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
[Rogers, Leland] Gamma West Canc Serv, Dept Radiat Oncol, Salt Lake City, UT USA.
[Schiff, David] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Vogelbaum, Michael] Cleveland Clin, Dept Neurooncol, Cleveland, OH 44106 USA.
[Weber, Damien] Univ Hosp Geneva, Div Radiat Oncol, Geneva, Switzerland.
[Wen, Patrick] Brigham & Womens Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA.
RP Kaley, T (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA.
EM kaleyt@mskcc.org
OI Kaley, Thomas/0000-0002-2540-8518
FU BrainLab Inc; NCI ACTNOW (Accelerating Clinical Trials and Novel
Oncologic Pathways Initiative); Pfizer; Novartis; Genentech
FX Drs Kaley, Chamberlain, McDermott, Panageas, and Weber have no conflict
of interest. Dr Barani has a BrainLab Inc research grant. Dr Raizer is
on advisory boards for Novartis and Roche/Genentech and on a speakers
bureau for Roche/Genentech. Dr Rogers has received an NCI ACTNOW
(Accelerating Clinical Trials and Novel Oncologic Pathways Initiative)
grant to study meningioma. This was applied to RTOG 0539 and used solely
to increase reimbursement for enrolling institutions. Dr Schiff is on an
advisory board for Genentech. Dr Vogelbaum has received honoraria from
Merck. Dr Wen received research support from Pfizer, Novartis, and
Genentech and is on an advisory board for Novartis and Genentech.
NR 50
TC 31
Z9 31
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
IS 6
BP 829
EP 840
DI 10.1093/neuonc/not330
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AH9WO
UT WOS:000336496000014
PM 24500419
ER
PT J
AU Augustinack, JC
Magnain, C
Reuter, M
van der Kouwe, AJW
Boas, D
Fischl, B
AF Augustinack, Jean C.
Magnain, Caroline
Reuter, Martin
van der Kouwe, Andre J. W.
Boas, David
Fischl, Bruce
TI MRI parcellation of ex vivo medial temporal lobe
SO NEUROIMAGE
LA English
DT Review
DE Entorhinal; Brodmann's area 28; Perirhinal; Brodmann's area 35; Mapping;
Localization
ID HUMAN CEREBRAL-CORTEX; LAMINA-SPECIFIC PATHOLOGY; HUMAN ENTORHINAL
CORTEX; HUMAN PERIRHINAL CORTEX; HIGH-FIELD MRI; ALZHEIMERS-DISEASE;
HUMAN-BRAIN; NEUROFIBRILLARY TANGLES; PARAHIPPOCAMPAL CORTICES;
COGNITIVE IMPAIRMENT
AB Recent advancements in radio frequency coils, field strength and sophisticated pulse sequences have propelled modern brain mapping and have made validation to biological standards - histology and pathology possible. The medial temporal lobe has long been established as a pivotal brain region for connectivity, function and unique structure in the human brain, and reveals disconnection in mild Alzheimer's disease. Specific brain mapping of mesbcortical areas affected with neurofibrillary tangle pathology early in disease progression provides not only an accurate description for location of these areas but also supplies spherical coordinates that allow comparison between other ex vivo cases and larger in vivo datasets. We have identified several cytoarchitectonic features in the medial temporal lobe with high resolution ex vivo MRI, including gray matter structures such as the entorhinal layer II 'islands', perirhinal layer II-III columns, presubicular 'clouds', granule cell layer of the dentate gyms as well as lamina of the hippocampus. Localization of Brodmann areas 28 and 35 (entorhinal and perirhinal, respectively) demonstrates MM based area boundaries validated with multiple methods and histological stains. Based on our findings, both myelin and Nissl staining relate to contrast in ex vivo MM. Precise brain mapping serves to create modern atlases for cortical areas, allowing accurate localization with important applications to detecting early disease processes. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Augustinack, Jean C.; Magnain, Caroline; Reuter, Martin; van der Kouwe, Andre J. W.; Boas, David; Fischl, Bruce] MGH, Dept Radiol, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA.
[Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA.
RP Augustinack, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM jean@nmr.mgh.harvard.edu
RI Reuter, Martin/B-3456-2010
OI Reuter, Martin/0000-0002-2665-9693
FU National Center for Research Resources [P41-RR14075]; NCRR BIRN
Morphometric Project [BIRN002, U24 RR021382]; National Institute for
Biomedical Imaging and Bioengineering [R01EB006758]; National Institute
on Aging [K01AG028521, AG022381, 5R01AG008122-22]; National Center for
Alternative Medicine [RD AT005728-01]; National Institute for
Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01,
1R01NS070963]; Shared Instrumentation Grants [1S1ORR023401,
1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project - Ellison Medical
Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765];
multi-institutional Human Connectome Project
FX The authors would like to thank Kristen Huber and Sita Kakunoori for
technical support. Support for this research was provided in part by the
National Center for Research Resources (P41-RR14075, and the NCRR BIRN
Morphometric Project BIRN002, U24 RR021382), the National Institute for
Biomedical Imaging and Bioengineering (R01EB006758), the National
Institute on Aging (K01AG028521, AG022381, 5R01AG008122-22), the
National Center for Alternative Medicine (RD AT005728-01), the National
Institute for Neurological Disorders and Stroke (R01 NS052585-01,
1R21NS072652-01, 1R01NS070963), and was made possible by the resources
provided by Shared Instrumentation Grants 1S1ORR023401, 1S10RR019307,
and 1S10RR023043. Additional support was provided by The Autism &
Dyslexia Project funded by the Ellison Medical Foundation, and by the
NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the
multi-institutional Human Connectome Project.
NR 71
TC 12
Z9 12
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUN
PY 2014
VL 93
SI SI
BP 252
EP 259
DI 10.1016/j.neuroimage.2013.05.053
PN 2
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AI0RG
UT WOS:000336556500011
PM 23702414
ER
PT J
AU Bludau, S
Eickhoff, SB
Mohlberg, H
Caspers, S
Laird, AR
Fox, PT
Schleicher, A
Zilles, K
Amunts, K
AF Bludau, S.
Eickhoff, S. B.
Mohlberg, H.
Caspers, S.
Laird, A. R.
Fox, P. T.
Schleicher, A.
Zilles, K.
Amunts, K.
TI Cytoarchitecture, probability maps and functions of the human frontal
pole
SO NEUROIMAGE
LA English
DT Article
ID ROSTRAL PREFRONTAL CORTEX; HUMAN ORBITOFRONTAL CORTEX; HUMAN
CEREBRAL-CORTEX; PRIMARY SOMATOSENSORY CORTEX; INTERINDIVIDUAL
VARIABILITY; STEREOTAXIC SPACE; MICROSTRUCTURAL PARCELLATION;
INTERSUBJECT VARIABILITY; QUANTITATIVE APPROACH; PROSPECTIVE MEMORY
AB The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Bludau, S.; Eickhoff, S. B.; Mohlberg, H.; Caspers, S.; Schleicher, A.; Zilles, K.; Amunts, K.] Res Ctr Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany.
[Eickhoff, S. B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, D-40001 Dusseldorf, Germany.
[Laird, A. R.; Fox, P. T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Laird, A. R.; Fox, P. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Fox, P. T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Zilles, K.] RVVTH Univ Aachen, Dept Psychiat Psychotherapy & Psychosomat, D-52074 Aachen, Germany.
[Zilles, K.; Amunts, K.] JARA, Juelich Aachen Res Alliance, Julich, Germany.
[Amunts, K.] Univ Dusseldorf, C&O Vogt Inst Brain Res, D-40001 Dusseldorf, Germany.
[Laird, A. R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA.
RP Bludau, S (reprint author), Res Ctr Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany.
EM s.bludau@fz-juelich.de
RI Amunts, Katrin/I-3470-2013; Zilles, Karl/J-9704-2013; Fox,
Peter/B-4725-2010; Caspers, Svenja/H-9346-2013; Eickhoff,
Simon/K-2061-2013;
OI Amunts, Katrin/0000-0001-5828-0867; Zilles, Karl/0000-0002-4705-4175;
Zilles, Karl/0000-0001-9296-9959; Fox, Peter/0000-0002-0465-2028;
Caspers, Svenja/0000-0001-5083-4669; Eickhoff,
Simon/0000-0001-6363-2759; Bludau, Sebastian/0000-0001-6173-9050
FU BMBF [01GW0612]; Helmholtz Alliance for Mental Health in an Aging
Society (HeIMA); Helmholtz Alliance on Systems Biology (Human Brain
Model)
FX This study was supported by the BMBF (01GW0612, K.A.). Further funding
was granted by the Helmholtz Alliance for Mental Health in an Aging
Society (HeIMA; KA., K.Z.) and by the Helmholtz Alliance on Systems
Biology (Human Brain Model; K.Z., S.B.E.). The authors thank Katerina
Semendeferi for critical review of the manuscript and for helpful
discussions.
NR 104
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Z9 43
U1 5
U2 21
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUN
PY 2014
VL 93
SI SI
BP 260
EP 275
DI 10.1016/j.neuroimage.2013.05.052
PN 2
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AI0RG
UT WOS:000336556500012
PM 23702412
ER
PT J
AU Buckner, RL
Yeo, BTT
AF Buckner, Randy L.
Yeo, B. T. Thomas
TI Borders, map clusters, and supra-areal organization in visual cortex
SO NEUROIMAGE
LA English
DT Review
DE Boundary mapping; Functional connectivity; Resting-state connectivity;
fMRI; Brodmann Area; Visual cortex
ID PRIMATE CEREBRAL-CORTEX; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; FIELD;
ARCHITECTURE; TOPOGRAPHY; REPRESENTATION; EVOLUTION; NETWORKS; STRIATE
AB V1 is a canonical cortical area with clearly delineated architectonic boundaries and a continuous topographic representation of the visual hemifield. It thus serves as a touchstone for understanding what new mapping methods can tell us about cortical organization. By parcellating human cortex using local gradients in functional connectivity, Wig et al. (2014-in this issue) detected the V1 border with V2. By contrast, previously-published clustering methods that focus on global similarity in connectivity reveal a supra-areal organization that emphasizes eccentricity bands spanning V1 and its neighboring extrastriate areas; i.e. in the latter analysis, the V1 border is not evident. Thus the focus on local connectivity gradients emphasizes qualitatively different features of cortical organization than are captured by global similarity measures. What is intriguing to consider is that each kind of information might be telling us something unique about cortical organization. Global similarity measures may be detecting map clusters and other supra-areal arrangements that reflect a fundamental level of organization. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Yeo, B. T. Thomas] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117548, Singapore.
RP Buckner, RL (reprint author), Harvard Univ, 52 Oxford St,Northwest Bldg,280-06, Cambridge, MA 02138 USA.
EM randy_buckner@harvard.edu
OI Yeo, B.T. Thomas/0000-0002-0119-3276
FU National University of Singapore Tier 1 Grant [R-263-000-A91-750];
Center for Functional Neuroimaging Technologies [P41EB015896]; Athinoula
A. Martinos Center for Biomedical Imaging at the Massachusetts General
Hospital [S10RR021110, S10RR023401, S10RR019307]
FX We thank Roger Tootell for his thoughtful comments on an earlier draft,
and Marcello Rosa and Mark Schira for the figures. We also thank the
support of the National University of Singapore Tier 1 Grant
(R-263-000-A91-750). Data were provided by the Brain Genomics
Superstruct Project (Principal Investigators: Randy Buckner, Jordan
Smoller, and Joshua Roffman). This research utilized resources provided
by the Center for Functional Neuroimaging Technologies, P41EB015896 and
instruments supported by S10RR021110, S10RR023401 and S10RR019307 from
the Athinoula A. Martinos Center for Biomedical Imaging at the
Massachusetts General Hospital.
NR 35
TC 11
Z9 11
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUN
PY 2014
VL 93
SI SI
BP 292
EP 297
DI 10.1016/j.neuroimage.2013.12.036
PN 2
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AI0RG
UT WOS:000336556500014
PM 24374078
ER
PT J
AU Hoeppner, BB
Bidwell, LC
Colby, SM
Barnett, NP
AF Hoeppner, Bettina B.
Bidwell, L. Cinnamon
Colby, Suzanne M.
Barnett, Nancy P.
TI Smoking Patterns and Their Relationship to Drinking Among First-Year
College Students
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID CIGARETTE-SMOKING; INTERMITTENT SMOKING; NONDAILY SMOKING;
NATURAL-HISTORY; DAILY SMOKERS; YOUNG-ADULTS; ALCOHOL-USE; LIGHT;
UNIVERSITIES; TRAJECTORIES
AB Unlike older smokers, young adult smokers frequently engage in light and intermittent smoking. It remains unclear how stable such smoking patterns are over time, as substantial variability exists between these smokers. This study identified subgroups of college student smokers based on the trajectory of their smoking frequency during the first year of college, thereby examining stability versus instability over time. We then tested if the interplay between drinking and smoking differed in the identified groups to determine the relative role drinking may play in intermittent versus more regular smoking.
Incoming college students at 3 institutions completed online biweekly surveys of their daily substance use throughout the first year of college. Students who reported smoking at least 1 cigarette during this year (n = 266) were included in analyses (70% female, 74% White).
Group-based trajectory modeling identified 5 groups of smokers, 3 of which maintained their smoking frequency throughout the year (77%), and 2 groups of infrequent smokers showed significant trends (11% increasing, 12% decreasing). Notably, nondaily smoking was maintained at different specific frequencies (e.g., 1 vs. 3 days per week). Identified groups differed in the relationship between drinking and smoking, where cooccurrence was particularly strong among infrequent smokers, and trends in smoking quantity differed between groups.
While there was a diversity of smoking patterns in the sample, patterns of intermittent smoking remain relatively stable for a majority of students throughout the year. Intervention messages targeting drinking and smoking should be tailored on the basis of smoking frequency.
C1 [Hoeppner, Bettina B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA USA.
[Bidwell, L. Cinnamon; Colby, Suzanne M.; Barnett, Nancy P.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
RP Hoeppner, BB (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA.
EM bhoeppner@partners.org
FU National Institute on Alcohol Abuse and Alcoholism [R01AA013970];
National Institute on Drug Abuse [K01DA027097, K23DA033302]
FX This study was supported by grants from the National Institute on
Alcohol Abuse and Alcoholism (R01AA013970) and the National Institute on
Drug Abuse (K01DA027097, K23DA033302).
NR 38
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U1 2
U2 9
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 JUN
PY 2014
VL 16
IS 6
BP 743
EP 752
DI 10.1093/ntr/ntt205
PG 10
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA AH9UX
UT WOS:000336491000014
PM 24415586
ER
PT J
AU Chabner, BA
AF Chabner, Bruce A.
TI Approval After Phase I: Ceritinib Runs the Three-Minute Mile
SO ONCOLOGIST
LA English
DT Editorial Material
ID CANCER
C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Chabner, BA (reprint author), 10 North Grove St,LRH 214, Boston, MA 02114 USA.
EM bchabner@partners.org
FU NCI NIH HHS [K12 CA087723]
NR 4
TC 14
Z9 14
U1 0
U2 4
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 JUN
PY 2014
VL 19
IS 6
BP 577
EP 578
DI 10.1634/theoncologist.2014-0143
PG 2
WC Oncology
SC Oncology
GA AI2WF
UT WOS:000336718500001
PM 24789171
ER
PT J
AU Fathi, AT
Sadrzadeh, H
Comander, AH
Higgins, AJ
Bardia, A
Perry, A
Burke, A
Silver, R
Matulis, CR
Straley, KS
Yen, KE
Agresta, S
Kim, H
Schenkein, DP
Borger, DR
AF Fathi, Amir T.
Sadrzadeh, Hossein
Comander, Amy H.
Higgins, Amichaela J.
Bardia, Aditya
Perry, Ashley
Burke, Ameghan
Silver, Regina
Matulis, Christina R.
Straley, Kimberly S.
Yen, Katharine E.
Agresta, Sam
Kim, Hyeryun
Schenkein, David P.
Borger, Darrell R.
TI Isocitrate Dehydrogenase 1 (IDH1) Mutation in Breast Adenocarcinoma Is
Associated With Elevated Levels of Serum and Urine 2-Hydroxyglutarate
SO ONCOLOGIST
LA English
DT Article
DE Isocitrate dehydrogenase 1; 2-Hydroxyglutarate; Breast adenocarcinoma;
Targeted therapy
ID ACUTE MYELOID-LEUKEMIA; DIFFERENTIATION; FREQUENT; INHIBITION;
PROGNOSIS; NEOPLASMS; CANCERS; GLIOMAS; TUMORS; CELLS
AB Mutations in the IDH1 and IDH2 (isocitrate dehydrogenase) genes have been discovered across a range of solid-organ and hematologic malignancies, including acute myeloid leukemia, glioma, chondrosarcoma, and cholangiocarcinoma. An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies. Wedescribe the first reported case of an IDH1 p.R132L mutation in a patient with hormone receptor-positive (HR+) breast adenocarcinoma. This patient was initially treated for locally advanced disease, but then suffered a relapse and metastasis, at which pointan IDH1-R132 mutation was discovered in an affected lymph node. The mutation was subsequently found in the primary tumor tissue and all metastatic sites, but not in an uninvolved lymph node. In addition, the patient's serum and urine displayed marked elevations in the concentration of 2-HG, significantly higher than that measured in six other patients with metastatic HR+ breast carcinoma whose tumors were found to harbor wild-type IDH1. In summary, IDH1 mutations may impact a rare subgroup of patients with breast adenocarcinoma. This may suggest future avenues for disease monitoring through noninvasive measurement of 2-HG, as well as for the development and study of targeted therapies against the aberrant IDH1 enzyme.
C1 [Fathi, Amir T.; Sadrzadeh, Hossein; Comander, Amy H.; Higgins, Amichaela J.; Bardia, Aditya; Perry, Ashley; Burke, Ameghan; Silver, Regina; Matulis, Christina R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Straley, Kimberly S.; Yen, Katharine E.; Agresta, Sam; Kim, Hyeryun; Schenkein, David P.; Borger, Darrell R.] Agios Pharmaceut, Cambridge, MA USA.
RP Fathi, AT (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA.
EM afathi@partners.org
FU Massachusetts General Hospital Cancer Center Thematic Priority [3]
FX This work was supported in part by a Massachusetts General Hospital
Cancer Center Thematic Priority #3 Grant. Amir T. Fathi, Hossein
Sadrzadeh, and Darrell R. Borger contributed equally to this article.
NR 42
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Z9 12
U1 0
U2 4
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 JUN
PY 2014
VL 19
IS 6
BP 602
EP 607
DI 10.1634/theoncologist.2013-0417
PG 6
WC Oncology
SC Oncology
GA AI2WF
UT WOS:000336718500005
PM 24760710
ER
PT J
AU Wolpin, BM
Rubinson, DA
Wang, XX
Chan, JA
Cleary, JM
Enzinger, PC
Fuchs, CS
McCleary, NJ
Meyerhardt, JA
Ng, K
Schrag, D
Sikora, AL
Spicer, BA
Killion, L
Mamon, H
Kimmelman, AC
AF Wolpin, Brian M.
Rubinson, Douglas A.
Wang, Xiaoxu
Chan, Jennifer A.
Cleary, James M.
Enzinger, Peter C.
Fuchs, Charles S.
McCleary, Nadine J.
Meyerhardt, Jeffrey A.
Ng, Kimmie
Schrag, Deborah
Sikora, Allison L.
Spicer, Beverly A.
Killion, Leah
Mamon, Harvey
Kimmelman, Alec C.
TI Phase II and Pharmacodynamic Study of Autophagy Inhibition Using
Hydroxychloroquine in Patients With Metastatic Pancreatic Adenocarcinoma
SO ONCOLOGIST
LA English
DT Article
AB Background. Autophagy is a catabolic pathway that permits cells to recycle intracellular macromolecules, and its inhibition reduces pancreatic cancer growth in model systems. We evaluated hydoxychloroquine (HCQ), an inhibitor of autophagy, in patients with pancreatic cancer and analyzed pharmacodynamic markers in treated patients and mice.
Methods. Patients with previously treated metastatic pancreatic cancer were administered HCQ at 400 mg (n = 10) or 600 mg (n = 10) twice daily. The primary endpoint was 2-month progression-free survival (PFS). We analyzed peripheral lymphocytes from treated mice to identify pharmacodynamic markers of autophagy inhibition that were then assessed in peripheral lymphocytes from patients.
Results. Among 20 patients enrolled, 2 (10%) were without progressive disease at 2 months. Median PFS and overall survival were 46.5 and 69.0 days, respectively. Treatment-related grade 3/4 adverse events were lymphopenia (n = 1) and elevated alanine aminotransferase (n = 1). Tolerability and efficacy were similar at the two dose levels. Analysis of treated murine lymphocytes suggested that LC3-II expression by Western blot is a reliable marker for autophagy inhibition. Analysis of LC3-II in patient lymphocytes demonstrated inconsistent autophagy inhibition.
Conclusion. Mouse studies identified LC3-II levels in peripheral lymphocytes as a potential pharmacodynamic marker of autophagy inhibition. In patients with previously treated metastatic pancreatic cancer, HCQ monotherapy achieved inconsistent autophagy inhibition and demonstrated negligible therapeutic efficacy.
C1 [Wolpin, Brian M.; Rubinson, Douglas A.; Wang, Xiaoxu; Chan, Jennifer A.; Cleary, James M.; Enzinger, Peter C.; Fuchs, Charles S.; McCleary, Nadine J.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Schrag, Deborah; Sikora, Allison L.; Spicer, Beverly A.; Killion, Leah; Mamon, Harvey; Kimmelman, Alec C.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Wolpin, Brian M.; Rubinson, Douglas A.; Wang, Xiaoxu; Chan, Jennifer A.; Cleary, James M.; Enzinger, Peter C.; Fuchs, Charles S.; McCleary, Nadine J.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Schrag, Deborah; Sikora, Allison L.; Spicer, Beverly A.; Killion, Leah; Mamon, Harvey; Kimmelman, Alec C.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Kimmelman, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM bwolpin@partners.org; akimmelman@partners.org
FU NIH from the National Cancer Institute [K07 CA140790, 1R01CA157490,
1R01CA124908, P50127003]; American Society of Clinical Oncology Career
Development Award; Howard Hughes Medical Institute Early Career
Physician-Scientist Award; Lustgarten Foundation; Promises for Purple;
American Cancer Society [RSG-13-298-01-TBG]; Department of Defense
Discovery Award [W81XWH-12-1-0459]; Lustgarten Foundation for Pancreatic
Cancer Research; Robert T. and Judith B. Hale Fund for Pancreatic Cancer
Research
FX Brian M. Wolpin is supported by NIH Grant K07 CA140790 from the National
Cancer Institute, an American Society of Clinical Oncology Career
Development Award, a Howard Hughes Medical Institute Early Career
Physician-Scientist Award, the Lustgarten Foundation, and Promises for
Purple. Alec C. Kimmelman is supported by NIH Grant 1R01CA157490 from
the National Cancer Institute, American Cancer Society Grant
RSG-13-298-01-TBG, a Department of Defense Discovery Award
(W81XWH-12-1-0459), and the Lustgarten Foundation for Pancreatic Cancer
Research. Charles S. Fuchs is supported by NIH Grant 1R01CA124908 and
P50127003 from the National Cancer Institute and the Robert T. and
Judith B. Hale Fund for Pancreatic Cancer Research.
NR 0
TC 43
Z9 44
U1 0
U2 5
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 JUN
PY 2014
VL 19
IS 6
BP 637
EP 638
DI 10.1634/theoncologist.2014-0086
PG 2
WC Oncology
SC Oncology
GA AI2WF
UT WOS:000336718500010
PM 24821822
ER
PT J
AU Khera, N
Emmert, A
Storer, BE
Sandmaier, BM
Alyea, EP
Lee, SJ
AF Khera, Nandita
Emmert, Amy
Storer, Barry E.
Sandmaier, Brenda M.
Alyea, Edwin P.
Lee, Stephanie J.
TI Costs of Allogeneic Hematopoietic Cell Transplantation Using Reduced
Intensity Conditioning Regimens
SO ONCOLOGIST
LA English
DT Article
DE Economics; Hematopoietic stem cell transplantation; Costs; Allogeneic
transplantation
ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; HIGH-DOSE REGIMENS;
HEMATOLOGIC MALIGNANCIES; OLDER PATIENTS; COMPLICATIONS; PREVENTION;
RECIPIENTS; OUTCOMES; DONOR
AB Reduced intensity conditioning (RIC) regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients and up to 2 years for 311 patients who underwent a RIC HCT at two institutions from January 2008 to December 2010. Multiple linear regression was used to analyze the association between clinical variables, center effect, and costs. Patient and transplant characteristics were comparable between the sites, although differences were seen in pretransplant performance scores. Significant predictors for lower costs for the first 100 days included a diagnosis of lymphoma/myeloma and use of human leukocyte antigen-matched related donors. Grade II-IV acute graft-versus-host disease (GVHD) was associated with higher costs. The overall short-term costs between the two institutions were comparable when adjusted for clinical variables (p = .43). Late costs between 100 days and 2 years after HCT were available for one cohort (n = 311); median costs during this period were $39,000 and accounted for 39% of costs during the first 2 years. Late costs were not associated with any pretransplant variables, but were higher with extensive chronic GVHD and death. After adjustment for clinical characteristics, the overall costs of the RIC transplants were similar between the two institutions despite different management approaches (inpatient vs. outpatient conditioning) and accounting methodologies. Use of unrelated/alternative donors, transplant for diseases other than lymphoma or myeloma, and acute GVHD were predictors for higher early costs, and extensive chronic GVHD and death were associated with higher late costs.
C1 [Khera, Nandita] Mayo Clin Arizona, Div Hematol Oncol, Phoenix, AZ USA.
[Emmert, Amy; Alyea, Edwin P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Storer, Barry E.; Sandmaier, Brenda M.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
RP Khera, N (reprint author), 5777 East Mayo Blvd,C-211, Phoenix, AZ 85054 USA.
EM Khera.Nandita@mayo.edu
FU NIH [CA18029, HL36444, CA78902]
FX This work was supported by NIH Grants CA18029, HL36444, and CA78902.
NR 23
TC 7
Z9 7
U1 0
U2 2
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 JUN
PY 2014
VL 19
IS 6
BP 639
EP 644
DI 10.1634/theoncologist.2013-0406
PG 6
WC Oncology
SC Oncology
GA AI2WF
UT WOS:000336718500011
PM 24797822
ER
PT J
AU Grothey, A
George, S
van Cutsem, E
Blay, JY
Sobrero, A
Demetri, GD
AF Grothey, Axel
George, Suzanne
van Cutsem, Eric
Blay, Jean-Yves
Sobrero, Alberto
Demetri, George D.
TI Optimizing Treatment Outcomes With Regorafenib: Personalized Dosing and
Other Strategies to Support Patient Care
SO ONCOLOGIST
LA English
DT Article
DE Regorafenib; Adverse events; Dose optimization; Supportive management;
Hand-foot skin reaction; Multikinase inhibitor
ID FOOT SKIN REACTION; MULTIKINASE INHIBITOR REGORAFENIB; GASTROINTESTINAL
STROMAL TUMORS; ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA; BAY
73-4506; PHASE-I; COLORECTAL-CANCER; JAPANESE PATIENTS; SUNITINIB
AB Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies. The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary.
C1 [Grothey, Axel] Mayo Clin, Rochester, MN 55905 USA.
[George, Suzanne; Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[George, Suzanne; Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA.
[van Cutsem, Eric] Univ Hosp Gasthuisberg Leuven, Louvain, Belgium.
[Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France.
[Blay, Jean-Yves] Univ Lyon 1, F-69365 Lyon, France.
[Sobrero, Alberto] IRCCS San Martino, Genoa, Italy.
RP Grothey, A (reprint author), Mayo Clin, Div Med Oncol, 200 First St SW, Rochester, MN 55905 USA.
EM grothey.axel@mayo.edu; suzanne_george@dfci.harvard.edu
RI Blay, Jean-Yves/N-3966-2016
OI Blay, Jean-Yves/0000-0001-7190-120X
FU Bayer HealthCare Pharmaceuticals
FX The academic authors take full responsibility for the content of this
review. Sara Black, of Succinct Healthcare Communication, provided
editorial assistance, which was funded by Bayer HealthCare
Pharmaceuticals. BayerHealthCare Pharmaceuticals was allowed to review
the manuscript for factual correctness, but did not influence the
content or decision to publish. Axel Grothey and Suzanne George
contributed equally to this article.
NR 31
TC 16
Z9 16
U1 0
U2 3
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 JUN
PY 2014
VL 19
IS 6
BP 669
EP 680
DI 10.1634/theoncologist.2013-0059
PG 12
WC Oncology
SC Oncology
GA AI2WF
UT WOS:000336718500015
PM 24821824
ER
PT J
AU Skaperdas, E
Tuepker, A
Nicolaidis, C
Robb, JK
Kansagara, D
Hickam, DH
AF Skaperdas, Eleni
Tuepker, Anais
Nicolaidis, Christina
Robb, Jessica K.
Kansagara, Devan
Hickam, David H.
TI Congestive heart failure self-management among US veterans: The role of
personal and professional advocates
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Primary care redesign; Self-management; Qualitative research; Heart
failure; Veterans; US
ID CONTROLLED-TRIAL; CARE MANAGEMENT; EXPERIENCES; ADHERENCE; PATIENT;
PROGRAM; RISK
AB Objective: Understand patients' experiences with primary care services for congestive heart failure (CHF) and explore the relationship between health services and self-management.
Methods: We conducted semi-structured interviews with thirty-nine patients with CHF receiving care at one Veterans Affairs Medical Center (VA). We analyzed data using thematic content analysis.
Results: Participants acknowledged the importance of ongoing engagement in the plan of care for CHF. They attributed success in this effort to be greatly influenced by personal advocates. The advocates included both members of the healthcare team with whom they had a continuity relationship and friends or family members who assisted on a daily basis. Participants also identified psychological symptoms as a major barrier to carrying out self-care.
Conclusion: Patients identify relationships with health care workers, help from family and friends, and mental health problems as major influences on the ability to manage their CHF.
Practice implications: Efforts to optimize CHF self-management should attend to health system and psychosocial barriers to care. Published by Elsevier Ireland Ltd.
C1 [Skaperdas, Eleni; Tuepker, Anais; Robb, Jessica K.; Kansagara, Devan; Hickam, David H.] Vet Hlth Adm, Portland VA Med Ctr Hlth Serv Res & Dev, VISN PACT Demonstrat Lab 20, Portland, OR USA.
[Tuepker, Anais; Kansagara, Devan] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA.
[Nicolaidis, Christina] Portland State Univ, Sch Social Work, Portland, OR 97207 USA.
[Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Hickam, David H.] Patient Centered Outcomes Res Inst, Washington, DC USA.
RP Skaperdas, E (reprint author), Portland VA Med Ctr, Mailcode R&D63,POB 1034, Portland, OR 97207 USA.
EM eleni.skaperdas@va.gov
FU VA Office of Patient Care
FX We thank the Veterans, their family members, and close friends for
sharing their experiences, and gratefully acknowledge the contribution
of all members of the VISN 20 PACT Demonstration Lab. Funding for the
PACT Demonstration Laboratory initiative is provided by the VA Office of
Patient Care.
NR 28
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD JUN
PY 2014
VL 95
IS 3
BP 371
EP 377
DI 10.1016/j.pec.2014.03.002
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA AI3QD
UT WOS:000336776100011
PM 24666772
ER
PT J
AU Koenig, CJ
Maguen, S
Monroy, JD
Mayott, L
Seal, KH
AF Koenig, Christopher J.
Maguen, Shira
Monroy, Jose D.
Mayott, Lindsay
Seal, Karen H.
TI Facilitating culture-centered communication between health care
providers and veterans transitioning from military deployment to
civilian life
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Patient-centered care; Health communication; Culture; Post-deployment
health; Readjustment experience; Military veterans; USA
ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; AFGHANISTAN
VETERANS; MENTAL-HEALTH; DISCOURSE ANALYSIS; COMBAT VETERANS; IRAQ;
HOME; BARRIERS; FAMILY
AB Objective: To describe returning veterans' transition experience from military to civilian life and to educate health care providers about culture-centered communication that promotes readjustment to civilian life.
Methods: Qualitative, in-depth, semi-structured interviews with 17 male and 14 female Iraq and Afghanistan veterans were audio recorded, transcribed verbatim, and analyzed using Grounded Practical Theory.
Results: Veterans described disorientation when returning to civilian life after deployment. Veterans' experiences resulted from an underlying tension between military and civilian identities consistent with reverse culture shock. Participants described challenges and strategies for managing readjustment stress across three domains: intrapersonal, professional/educational, and interpersonal.
Conclusions: To provide patient-centered care to returning Iraq and Afghanistan veterans, health care providers must be attuned to medical, psychological, and social challenges of the readjustment experience, including reverse culture shock. Cultufe-centered communication may help veterans integrate positive aspects of military and civilian identities, which may promote full reintegration into civilian life.
Practice implications: Health care providers may promote culture-centered interactions by asking veterans to reflect about their readjustment experiences. By actively eliciting challenges and helping veterans' to identify possible solutions, health care providers may help veterans integrate military and civilian identities through an increased therapeutic alliance and social support throughout the readjustment process. Published by Elsevier Ireland Ltd.
C1 [Koenig, Christopher J.; Maguen, Shira; Monroy, Jose D.; Mayott, Lindsay; Seal, Karen H.] San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA.
[Koenig, Christopher J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Maguen, Shira; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Koenig, Christopher J.; Mayott, Lindsay; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Monroy, Jose D.] San Francisco State Univ, Dept Psychol, San Francisco, CA 94132 USA.
RP Koenig, CJ (reprint author), San Francisco Vet Adm Med Ctr, Dept Med, 4150 Clement St,111-A1, San Francisco, CA 94121 USA.
EM Christopher.Koenig@va.gov
OI Koenig, Christopher J./0000-0003-0884-4120
FU Department of Defense [W81XWH-08-2-0106]
FX Department of Defense award W81XWH-08-2-0106 funded this study. The
funders had no role in the design, data analysis, writing or approval of
the manuscript.
NR 66
TC 5
Z9 5
U1 8
U2 31
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD JUN
PY 2014
VL 95
IS 3
BP 414
EP 420
DI 10.1016/j.pec.2014.03.016
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA AI3QD
UT WOS:000336776100017
PM 24742536
ER
PT J
AU McCracken, JT
Badashova, KK
Posey, DJ
Aman, MG
Scahill, L
Tierney, E
Arnold, LE
Vitiello, B
Whelan, F
Chuang, SZ
Davies, M
Shah, B
McDougle, CJ
Nurmi, EL
AF McCracken, J. T.
Badashova, K. K.
Posey, D. J.
Aman, M. G.
Scahill, L.
Tierney, E.
Arnold, L. E.
Vitiello, B.
Whelan, F.
Chuang, S. Z.
Davies, M.
Shah, B.
McDougle, C. J.
Nurmi, E. L.
TI Positive effects of methylphenidate on hyperactivity are moderated by
monoaminergic gene variants in children with autism spectrum disorders
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE autism spectrum disorders; dopamine; genetics; hyperactivity;
methylphenidate
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL
DISORDERS; DOPAMINE TRANSPORTER GENOTYPE; ABERRANT BEHAVIOR CHECKLIST;
ADHD CHILDREN; DOSE-RESPONSE; RECEPTOR GENE; SCHIZOPHRENIC CHILDREN;
GENOME BROWSER; ASSOCIATION
AB Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P< 0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.
C1 [McCracken, J. T.; Badashova, K. K.; Whelan, F.; Shah, B.; Nurmi, E. L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci, Los Angeles, CA 90024 USA.
[Posey, D. J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychiat, Columbus, OH 43210 USA.
[Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychol, Columbus, OH 43210 USA.
[Scahill, L.] Yale Univ, Child Study Ctr, New Haven, CT USA.
[Tierney, E.] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA.
[Chuang, S. Z.; Davies, M.] Columbia Univ, Dept Psychiat, New York, NY USA.
[McDougle, C. J.] Massachusetts Gen Hosp, Lurie Autism Ctr, Dept Psychiat, Boston, MA 02114 USA.
RP McCracken, JT (reprint author), UCLA NPI Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA.
EM jmccracken@mednet.ucla.edu
RI Nurmi, Erika/P-4627-2014;
OI Nurmi, Erika/0000-0003-4893-8957; Scahill, Lawrence/0000-0001-5073-1707
FU NIMH [N01 MH-70070, N01 MH-70009, N01 MH-70001, N01 MH 80011, MH-01805,
MH094613, T32MH073517, MH-68627]; NIH Division of Research Resources
General Clinical Research Center [M01 RR-00750, M01 RR-00052, M01
RR-00034, M01 RR-06022]; Korczak Foundation
FX The RUPP Autism Network comprises the following investigators listed by
role and study site: Ohio State University: principal investigator
Michael G Amen, PhD, co-investigators L Eugene Arnold, MEd, MD, Yaser
Ramadan, MD, Andrea Witwer, MA, Ronald Lindsay, MD and Patricia Nash,
MD; University of California at Los Angeles: principal investigator
James T McCracken, MD, co-investigators Bhavik Shah, MD, James Mc Gough,
MD, Pegeen Cronin, PhD, Lisa Lee, BA; Indiana University: principal
investigator Christopher J McDougle, MD, co-investigators David Posey,
MD, Naomi Swiezy, PhD, Arlene Kohn, BA; Yale University: principal
investigator Lawrence Scahill, MSN, PhD, co-investigators Andres Martin,
MD, Kathleen Koenig, MSN, Fred Volkmar, MD, Deirdre Carroll, MSN,
Allison Lancor, BS; Kennedy Krieger Institute: principal investigator
Elaine Tierney, MD, co-investigators Jaswinder Ghuman, MD, Nilda
Gonzalez, MD, Marco Grados, MD; National Institute of Mental Health:
principal investigator Benedetto Vitiello, MD, co-investigator Louise
Ritz, MBA; statisticians: Shirley Z Chuang, MS, Mark Davies, MPH, of
Columbia University; data management: James Robinson, MEd, Don McMahon,
MS, Nathan Kline Institute. Research supported by NIMH contracts N01
MH-70070 (principal investigator: Dr McCracken), N01 MH-70009 (principal
investigator: Dr Scahill), N01 MH-70001 (principal investigator: Dr
McDougle), and N01 MH 80011 (principal investigator: Dr Amen); by NIH
Division of Research Resources General Clinical Research Center grants
M01 RR-00750 (to Indiana University), M01 RR-00052 (to John Hopkins
University), M01 RR-00034 (to Ohio University) and M01 RR-06022 (to Yale
University); by NIMH grants MH-01805 (to Dr McCracken) NIMH grants
MH094613 and T32MH073517 (Dr Nurmi) and MH-68627 (to Dr Posey); and by
funding from the Korczak Foundation (to Dr Scahill). The opinions and
assertions contained in this report are the private views of the authors
and are not to be construed as official or as reflecting the views of
the National Institute of Mental Health, the National Institutes of
Health, or the Department of Health and Human Services.
NR 67
TC 11
Z9 12
U1 3
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
EI 1473-1150
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2014
VL 14
IS 3
BP 295
EP 302
DI 10.1038/tpj.2013.23
PG 8
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA AI0SK
UT WOS:000336560000014
PM 23856854
ER
PT J
AU Clarke, TK
Crist, RC
Ang, A
Ambrose-Lanci, LM
Lohoff, FW
Saxon, AJ
Ling, W
Hillhouse, MP
Bruce, RD
Woody, G
Berrettini, WH
AF Clarke, T-K
Crist, R. C.
Ang, A.
Ambrose-Lanci, L. M.
Lohoff, F. W.
Saxon, A. J.
Ling, W.
Hillhouse, M. P.
Bruce, R. D.
Woody, G.
Berrettini, W. H.
TI Genetic variation in OPRD1 and the response to treatment for opioid
dependence with buprenorphine in European-American females
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE buprenorphine; females; methadone; opioids; OPRD1; pharmacogenetics
ID METHADONE-MAINTENANCE TREATMENT; RECEPTOR GENE; POSTOPERATIVE PAIN;
GENDER-DIFFERENCES; OPIATE DEPENDENCE; RANDOMIZED-TRIAL;
DRUG-DEPENDENCE; ABUSE TREATMENT; SEX-DIFFERENCES; ANALGESIA
AB Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR) = 1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR =2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be usefulwhen considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.
C1 [Clarke, T-K; Crist, R. C.; Ambrose-Lanci, L. M.; Lohoff, F. W.; Berrettini, W. H.] Univ Penn, Sch Med, Translat Res Labs, Dept Psychiat,Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA.
[Ang, A.; Ling, W.; Hillhouse, M. P.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA.
[Saxon, A. J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bruce, R. D.] Yale Univ, Sch Med, New Haven, CT USA.
[Woody, G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Woody, G.] Treatment Res Inst, Philadelphia, PA USA.
RP Clarke, TK (reprint author), Univ Penn, Sch Med, Translat Res Labs, Dept Psychiat,Ctr Neurobiol & Behav, 125 South 31st St,Room 2109, Philadelphia, PA 19104 USA.
EM ctoni@mail.med.upenn.edu
RI Lohoff, Falk/M-7951-2016;
OI Clarke, Toni-Kim/0000-0002-7745-6351
FU National Institute on Drug Abuse through the Clinical Trials Network
(CTN); Pacific Northwest Node [U10 DA01714]; Oregon Hawaii Node [U10
DA013036]; California/Arizona Node [U10 DA015815]; New England Node [U10
DA13038]; Delaware Valley Node [U10 DA13043]; Pacific Region Node [U10
DA13045]; New York Node [U10 DA013046]; Center for Neurobiology and
Behavior, Department of Psychiatry, University of Pennsylvania
[T32MH014654]; NIDA [P20DA025995, P60DA05186]; Veterans Administration
Mental Illness Research Education; Clinical Center MIRECC
FX Main START study funding came from the National Institute on Drug Abuse
through the Clinical Trials Network (CTN) through a series of grants
provided to each participating node: the Pacific Northwest Node (U10
DA01714), the Oregon Hawaii Node (U10 DA013036), the California/Arizona
Node (U10 DA015815), the New England Node (U10 DA13038), the Delaware
Valley Node (U10 DA13043), the Pacific Region Node (U10 DA13045) and the
New York Node (U10 DA013046). Dr Berrettini was also supported by the
Delaware Valley Node (U10 DA13043). This work was supported by the
Center for Neurobiology and Behavior, Department of Psychiatry,
University of Pennsylvania, Training Program in Neuropsychopharmacology
(T32MH014654, PI: I Lucki), NIDA grant P20DA025995 (PI: W Berrettini),
the Veterans Administration Mental Illness Research Education and
Clinical Center MIRECC) at the Philadelphia VAMC (David Oslin, MD, PI)
and NIDA grant P60DA05186 (PI: Charles O'Brien).
NR 51
TC 8
Z9 9
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
EI 1473-1150
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2014
VL 14
IS 3
BP 303
EP 308
DI 10.1038/tpj.2013.30
PG 6
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA AI0SK
UT WOS:000336560000015
PM 24126707
ER
PT J
AU Lopez, J
Prifogle, E
Nyame, TT
Milton, J
May, JW
AF Lopez, Joseph
Prifogle, Erin
Nyame, Theodore T.
Milton, Jacqueline
May, James W., Jr.
TI The Impact of Conflicts of Interest in Plastic Surgery: An Analysis of
Acellular Dermal Matrix, Implant-Based Breast Reconstruction
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID BIOMEDICAL-RESEARCH; ORTHOPEDIC RESEARCH; CLINICAL-TRIALS;
PHARMACEUTICAL-INDUSTRY; ASSOCIATION; COMPLICATIONS; MODEL; SPONSORSHIP;
PHYSICIANS; OUTCOMES
AB Background: Although conflicts of interest in biomedical research have received significant attention, the impact of conflicts of interest on surgical outcomes has not been fully explored.
Methods: A systematic electronic search of the literature was performed for studies that evaluated surgical outcomes in acellular dermal matrix and non acellular dermal matrix implant-based breast reconstruction. Surgical complications, including infection, seroma, hematoma, necrosis, and explantation, were used as outcome metrics and extracted from studies. Surgical outcomes were then pooled and compared between studies that disclosed conflicts of interest and those that did not disclose conflicts of interest.
Results: A total of 776 abstracts were identified, of which only 35 fulfilled the authors' inclusion criteria. Conflicts of interest were reported in 14 of these abstracts (40 percent). The pooled data from studies that reported no conflicts of interest and studies that reported conflicts of interest included a total of 8241 and 5384 breasts and 2852 and 1864 patients, respectively. Considered collectively, surgical complications were less common in studies that reported a conflict of interest than in studies that reported no conflicts of interest. When surgical outcome data were further stratified by acellular dermal matrix use, surgical complications were less common in studies with conflicts of interest when acellular dermal matrix was used. However, when acellular dermal matrix was not used, surgical complications were similar between authors that reported a conflict of interest and those that did not report a conflict of interest.
Conclusions: Self-reported conflicts of interest are common in implant-based breast reconstruction research. Studies authored by groups with conflicts of interest are significantly associated with reporting lower surgical complications and therefore describing positive research findings, especially when industry-marketed products are being used in the study.
C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA.
Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
RP Lopez, J (reprint author), Univ Maryland, Med Ctr, Johns Hopkins Hosp, Dept Plast Surg, 1780 East Fayette St,Bloomberg 7th Floor, Baltimore, MD 21231 USA.
EM jlopez37@jhmi.edu
OI Lopez, Joseph/0000-0003-3001-1109
FU TEI Biosciences
FX Dr. May is a paid consultant for TEI Biosciences. Erin Prifogle, B.S.,
is a former employee of TEI Biosciences. The other authors have no
financial disclosures to report.
NR 26
TC 23
Z9 23
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
EI 1529-4242
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD JUN
PY 2014
VL 133
IS 6
BP 1328
EP 1334
DI 10.1097/PRS.0000000000000172
PG 7
WC Surgery
SC Surgery
GA AI3RK
UT WOS:000336779400002
PM 24867714
ER
PT J
AU Reynolds, CF
Thomas, SB
Morse, JQ
Anderson, SJ
Albert, S
Dew, MA
Begley, A
Karp, JF
Gildengers, A
Butters, MA
Stack, JA
Kasckow, J
Miller, MD
Quinn, SC
AF Reynolds, Charles F., III
Thomas, Stephen B.
Morse, Jennifer Q.
Anderson, Stewart J.
Albert, Steven
Dew, Mary Amanda
Begley, Amy
Karp, Jordan F.
Gildengers, Ariel
Butters, Meryl A.
Stack, Jacqueline A.
Kasckow, John
Miller, Mark D.
Quinn, Sandra C.
TI Early Intervention to Preempt Major Depression Among Older Black and
White Adults
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; PROBLEM-SOLVING
THERAPY; PRIMARY-CARE PATIENTS; PREVENTING DEPRESSION; GERIATRIC
DEPRESSION; RISK-FACTORS; METAANALYSIS; INVENTORY; SYMPTOMS
AB Objective: The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching. Methods: A total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm. Results: The two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome. Conclusions: Both PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nation's increasingly diverse older population.
C1 [Reynolds, Charles F., III; Morse, Jennifer Q.; Dew, Mary Amanda; Begley, Amy; Karp, Jordan F.; Gildengers, Ariel; Butters, Meryl A.; Stack, Jacqueline A.; Kasckow, John; Miller, Mark D.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA.
[Kasckow, John] Vet Affairs Pittsburgh Hlth Care Syst, Dept Behav Hlth, Pittsburgh, PA USA.
[Thomas, Stephen B.; Quinn, Sandra C.] Univ Maryland, Ctr Hlth Equ, College Pk, MD 20742 USA.
[Anderson, Stewart J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Albert, Steven] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA.
RP Reynolds, CF (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA.
EM reynoldscf@upmc.edu
OI Anderson, Stewart/0000-0001-8948-0650; Albert,
Steven/0000-0001-6786-9956
FU National Institute of Mental Health [P60 MD000207, P30 MH090333,
UL1RR024153, UL1TR000005]; National Institutes of Health; University of
Pittsburgh Medical Center Endowment in Geriatric Psychiatry;
Commonwealth of Pennsylvania; Bristol-Myers Squibb; Forest; Pfizer;
Lilly; Robert Bosch Health Care, Inc.
FX This work was supported by grants P60 MD000207, P30 MH090333,
UL1RR024153, and UL1TR000005 from the National Institute of Mental
Health and National Institutes of Health, by the University of
Pittsburgh Medical Center Endowment in Geriatric Psychiatry, and by the
Commonwealth of Pennsylvania. This work is registered on
ClinicalTrials.gov as NCT00326677.; Dr. Reynolds reports receiving
pharmaceutical support for National Institutes of Health sponsored
research studies from Bristol-Myers Squibb, Forest, Pfizer, and Lilly.
He is the co-inventor of Psychometric Analysis of the Pittsburgh Sleep
Quality Index (licensed intellectual property PRO10050447). Dr. Karp
reports receipt of medication supplies from Pfizer and Reckitt Benckiser
for investigator-initiated studies. Dr. Butters has received
remuneration from GlaxoSmithKline for performing neuropsychological
services. Dr. Kasckow has received assistance from Robert Bosch Health
Care, Inc., for software-related costs for a research project. The other
authors report no competing interests.
NR 37
TC 14
Z9 14
U1 0
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUN
PY 2014
VL 65
IS 6
BP 765
EP 773
DI 10.1176/appi.ps.201300216
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA AI3RJ
UT WOS:000336779300009
PM 24632760
ER
PT J
AU Cheung, OS
Bar, M
AF Cheung, Olivia S.
Bar, Moshe
TI The resilience of object predictions: Early recognition across
viewpoints and exemplars
SO PSYCHONOMIC BULLETIN & REVIEW
LA English
DT Article
DE Object recognition; Repetition priming; Spatial frequency
ID UNDERLIE REPETITION SUPPRESSION; TOP-DOWN FACILITATION;
SPATIAL-FREQUENCIES; FUSIFORM CORTEX; NEURAL MECHANISMS; ROTATED
OBJECTS; CATEGORIZATION; SCENE; ORIENTATION; INFORMATION
AB Recognition of everyday objects can be facilitated by top-down predictions. We have proposed that these predictions are derived from rudimentary image information, or gist, extracted rapidly from the low spatial frequencies (LSFs) (Bar Journal of Cognitive Neuroscience 15: 600-609, 2003). Because of the coarse nature of LSF representations, we hypothesized here that such predictions can accommodate changes in viewpoint as well as facilitate the recognition of visually similar objects. In a repetition-priming task, we indeed observed significant facilitation of target recognition that was primed by LSF objects across moderate viewpoint changes, as well as across visually similar exemplars. These results suggest that the LSF representations are specific enough to activate accurate predictions, yet flexible enough to overcome small changes in visual appearance. Such gist representations facilitate object recognition by accommodating changes in visual appearance due to viewing conditions, and help generalize from familiar to novel exemplars.
C1 [Cheung, Olivia S.; Bar, Moshe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Boston, MA USA.
[Bar, Moshe] Bar Ilan Univ, Gonda Ctr Multidisciplinary Brain Res, Ramat Gan, Israel.
[Cheung, Olivia S.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
RP Cheung, OS (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
EM sccheung.olivia@gmail.com
FU NEI NIH HHS [1R01EY019477-01, R01 EY019477]
NR 47
TC 4
Z9 4
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1069-9384
EI 1531-5320
J9 PSYCHON B REV
JI Psychon. Bull. Rev.
PD JUN
PY 2014
VL 21
IS 3
BP 682
EP 688
DI 10.3758/s13423-013-0546-5
PG 7
WC Psychology, Mathematical; Psychology, Experimental
SC Psychology
GA AH8XZ
UT WOS:000336422800012
PM 24234168
ER
PT J
AU Provencher, CDRMT
Makani, A
McNeil, JW
Pomerantz, ML
Golijanin, P
Gross, D
AF Provencher, C. D. R. Matthew T.
Makani, Amun
McNeil, John W.
Pomerantz, M. Lucius
Golijanin, Petar
Gross, Daniel
TI The Role of the Scapula in Throwing Disorders
SO SPORTS MEDICINE AND ARTHROSCOPY REVIEW
LA English
DT Review
DE throwing shoulder; scapular dyskinesis; GIRD; impingement; scapula;
mechanics
ID PROFESSIONAL BASEBALL PITCHERS; INTERNAL-ROTATION DEFICIT; SHOULDER
IMPINGEMENT; MUSCLE FATIGUE; PART 1; MOTION; KINEMATICS; DYSKINESIS;
PROTRACTION; ELEVATION
AB Shoulder injuries in the thrower can prove a challenge to diagnose and treat. Overhead throwing is an intricate motion that places considerable torque on the shoulder. The complex interplay of the scapula with the glenohumeral joint and its surrounding musculature allows elite pitchers to achieve speeds >95 miles per hour. An understanding of scapular motion is integral to diagnose and treat shoulder pathology in these athletes. Treatment is aimed at addressing the underlying cause with a physical rehabilitation program. Although nonoperative care is the most predictable and useful treatment, occasionally operative treatment is necessary. This chapter will outline normal scapular motion during throwing, the effects of common shoulder disorders on throwing mechanics, and the prevention, diagnosis, and treatment of these conditions.
C1 [Provencher, C. D. R. Matthew T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Makani, Amun; Golijanin, Petar; Gross, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McNeil, John W.] Univ Calif San Diego, Sch Med, San Diego, CA USA.
[Pomerantz, M. Lucius] Univ Calif San Diego, Sch Med, Dept Orthoped Surg, San Diego, CA USA.
RP Provencher, CDRMT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 175 Cambridge St,Suite 400, Boston, MA 02114 USA.
NR 39
TC 1
Z9 1
U1 3
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-8592
EI 1538-1951
J9 SPORTS MED ARTHROSC
JI Sports Med. Arthrosc. Rev.
PD JUN
PY 2014
VL 22
IS 2
BP 80
EP 87
DI 10.1097/JSA.0000000000000023
PG 8
WC Sport Sciences
SC Sport Sciences
GA AH9ZS
UT WOS:000336506000003
PM 24787721
ER
PT J
AU Engels, MC
Rajarajan, K
Feistritzer, R
Sharma, A
Nielsen, UB
Schalij, MJ
de Vries, AAF
Pijnappels, DA
Wu, SM
AF Engels, Marc C.
Rajarajan, Kuppusamy
Feistritzer, Rebecca
Sharma, Arun
Nielsen, Ulrik B.
Schalij, Martin J.
de Vries, Antoine A. F.
Pijnappels, Daniel A.
Wu, Sean M.
TI Insulin-Like Growth Factor Promotes Cardiac Lineage Induction In Vitro
by Selective Expansion of Early Mesoderm
SO STEM CELLS
LA English
DT Article
DE Embryonic stem cell; Development; Mesoderm; Cardiac progenitor cell;
Cardiomyocyte; Cardiac differentiation; In vitro screening; Insulin;
Insulin-like growth factor; Akt
ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; CARDIOMYOCYTE PROLIFERATION;
SIGNALING EXERTS; SMOOTH-MUSCLE; DIFFERENTIATION; HEART; BMP;
CARDIOMYOGENESIS; PATHWAY
AB A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5(+) cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e. g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine.
C1 [Engels, Marc C.; Rajarajan, Kuppusamy; Feistritzer, Rebecca; Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA.
[Engels, Marc C.; Schalij, Martin J.; de Vries, Antoine A. F.; Pijnappels, Daniel A.] Leiden Univ, Lab Expt Cardiol, Dept Cardiol, Heart Ctr Leiden,Med Ctr, Leiden, Netherlands.
[Sharma, Arun] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
[Nielsen, Ulrik B.] Silver Creek Pharmaceut Inc, San Francisco, CA USA.
[Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Wu, SM (reprint author), Stanford Univ, Div Cardiovasc Med, Sch Med, Dept Med,Stanford Cardiovasc Inst, 265 Campus Dr, Stanford, CA 94305 USA.
EM smwu@stanford.edu
FU NIH [NS069375]; Netherlands Organization for Scientific Research [NWO
017.007.064]; NWO (VENI grant) [91611070]; NIH/Officer of the Director's
New Innovator Award [OD004411]; NIH/NHLBI [HL099776, HL081086]; Harvard
Stem Cell Institute
FX Laura Prickett-Rice and Katherine Folz-Donahue at the Center for
Regenerative Medicine Harvard Stem Cell Institute Flow Cytometry Core
provided assistance with flow cytometry experiments. Andrew Olson at the
Stanford Neuroscience Microscopy Service (supported by NIH NS069375) at
Stanford School of Medicine provided technical assistance with confocal
microscopy imaging. M.C.E. was supported by a Mosaic grant from the
Netherlands Organization for Scientific Research (NWO 017.007.064).
D.A.P. was supported by NWO (VENI grant 91611070) and S.M.W. was
supported by NIH/Officer of the Director's New Innovator Award
(OD004411), NIH/NHLBI U01 (HL099776) and K08 (HL081086) and by the
Harvard Stem Cell Institute.
NR 38
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD JUN
PY 2014
VL 32
IS 6
BP 1493
EP 1502
DI 10.1002/stem.1660
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA AI3EE
UT WOS:000336741700014
PM 24496962
ER
PT J
AU Seible, DM
Gu, XM
Hyatt, AS
Beard, CJ
Choueiri, TK
Efstathiou, JA
Miyamoto, DT
Mitin, T
Martin, NE
Sweeney, CJ
Trinh, QD
Beckman, JA
Basaria, S
Nguyen, PL
AF Seible, Daniel M.
Gu, Xiangmei
Hyatt, Andrew S.
Beard, Clair J.
Choueiri, Toni K.
Efstathiou, Jason A.
Miyamoto, David T.
Mitin, Timur
Martin, Neil E.
Sweeney, Christopher J.
Trinh, Quoc-Dien
Beckman, Joshua A.
Basaria, Shehzad
Nguyen, Paul L.
TI Weight Gain on Androgen Deprivation Therapy: Which Patients Are at
Highest Risk?
SO UROLOGY
LA English
DT Article
ID PROSTATE-CANCER; BODY-COMPOSITION; MEN; AGE; SUPPRESSION; METAANALYSIS;
CARCINOMA; EXERCISE; HORMONES; MALES
AB OBJECTIVE To identify factors associated with weight gain at 1 year from initiation of androgen deprivation therapy (ADT).
METHODS A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT for at least 6 months. Outcome associations were tested using 2-tailed t tests and linear regression.
RESULTS Men in our cohort had significant weight gain (1.32 kg, P = .0005) in the 1 year after ADT initiation. Three risk factors for weight gain on ADT were identified as follows: age < 65 years (2.72 kg gained, P = .001), body mass index (BMI) < 30 (1.98 kg gained, P = .00002), and nondiabetic status (1.56 kg gained, P = .0003). Multivariable regression found both age < 65 years (beta = 4.01, P = .02) and BMI <30 (beta = 3.57, P = .03) to be independently predictive of weight gain, whereas nondiabetic status was nonsignificantly predictive of weight gain (beta = 2.14, P = .29). Weight change was further stratified by the total number of risk factors present (risk score): scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -1.10, +0.41, +1.34, and +3.79 kg, respectively (P-trend = .0005).
CONCLUSION Age < 65 years and BMI < 30 were both independently associated with weight gain 1 year after starting ADT. Increasing weight gain was also strongly associated with increasing number of baseline risk factors present. Despite traditional concerns about ADT in unhealthy men, these data suggest younger, healthier patients may be at higher risk for gaining weight on ADT and should be counseled accordingly. (C) 2014 Elsevier Inc.
C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Seible, DM (reprint author), Brigham & Womens Hosp, 75 Francis St,ASB1-L2, Boston, MA 02115 USA.
EM daniel_seible@hms.harvard.edu
RI Martin, Neil/E-2193-2014;
OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439
FU Prostate Cancer Foundation; Fitz's Cancer Warriors
FX This work is supported by the Prostate Cancer Foundation, Fitz's Cancer
Warriors, David and Cynthia Chapin, and a grant from an Anonymous Family
Foundation.
NR 28
TC 5
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD JUN
PY 2014
VL 83
IS 6
BP 1316
EP 1321
DI 10.1016/j.urology.2014.02.006
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0DL
UT WOS:000336516300020
PM 24726149
ER
PT J
AU El-Serag, HB
Sweet, S
Winchester, CC
Dent, J
AF El-Serag, Hashem B.
Sweet, Stephen
Winchester, Christopher C.
Dent, John
TI Update on the epidemiology of gastro-oesophageal reflux disease: a
systematic review
SO GUT
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; RISK-FACTORS; CLINICAL
SPECTRUM; GENERAL-POPULATION; BARRETTS-ESOPHAGUS; ADULT-POPULATION;
PRIMARY-CARE; PREVALENCE; SYMPTOMS
AB Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD).
Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include >= 200 individuals, to have response rates >= 50% and recall periods < 12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model.
Results 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%-27.8% in North America, 8.8%-25.9% in Europe, 2.5%-7.8% in East Asia, 8.7%-33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 117 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia.
Conclusions GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.
C1 [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr 152, Sect Gastroenterol & Hepatol, Houston, TX USA.
[Sweet, Stephen; Winchester, Christopher C.] Oxford PharmaGenesis, Res Evaluat Unit, Oxford, England.
[Winchester, Christopher C.] Univ Aberdeen, Ctr Acad Primary Care, Aberdeen, Scotland.
[Dent, John] Royal Adelaide Hosp, Dept Gastroenterol Hepatol & Gen Med, Adelaide, SA 5000, Australia.
RP El-Serag, HB (reprint author), Houston VA Med Ctr, Sect Gastroenterol & Hepatol, 2002 Holcombe Blvd 152, Houston, TX 77030 USA.
EM hasheme@bcm.edu
OI Winchester, Christopher/0000-0003-3267-3990
FU Texas Digestive Disease Center [NIH DK58338, NIDDK K24-04-107]; Houston
VA Health Services R&D Center of Excellence [HFP90-020]; AstraZeneca
R&D, Molndal, Sweden
FX This work was supported in part by Texas Digestive Disease Center grants
NIH DK58338 and NIDDK K24-04-107 to Dr El-Serag and by the Houston VA
Health Services R&D Center of Excellence (HFP90-020). The views
expressed in this article are those of the author(s) and do not
necessarily represent the views of the Department of Veterans Affairs.
Stephen Sweet and Christopher C Winchester are employees of Oxford
PharmaGenesis, which received funding from AstraZeneca R&D, Molndal,
Sweden for its role in the preparation of this systematic review.
NR 49
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Z9 167
U1 3
U2 22
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 JUN
PY 2014
VL 63
IS 6
BP 871
EP 880
DI 10.1136/gutjnl-2012-304269
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AG4AB
UT WOS:000335360000006
PM 23853213
ER
PT J
AU Araki, T
Sholl, LM
Gerbaudo, VH
Hatabu, H
Nishino, M
AF Araki, Tetsuro
Sholl, Lynette M.
Gerbaudo, Victor H.
Hatabu, Hiroto
Nishino, Mizuki
TI Thymic Measurements in Pathologically Proven Normal Thymus and Thymic
Hyperplasia: Intraobserver and Interobserver Variabilities
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Thymus; computed tomography; measurement; intraobserver variability;
interobserver variability
ID CELL LUNG-CANCER; AGE-RELATED-CHANGES; COMPUTED-TOMOGRAPHY; ABNORMAL
THYMUS
AB Rationale and Objectives: To determine the intraobserver and interobserver variabilities of thymic measurements on computed tomography (CT) in patients with pathologic diagnosis of thymic hyperplasia or normal thymus.
Materials and Methods: Thirty-three patients with pathologic diagnosis of thymic hyperplasia (n = 25) or normal thymus (n = 8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraobserver and interobserver agreements.
Results: The intraobserver and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging from 0.73 to 0.89 and from 0.72 to 0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC >= 0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intraobserver and interobserver agreements improved, resulting in CCCs ranging from 0.81 to 0.92 and from 0.77 to 0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging from 0.88 to 0.97. In patients with thymic CT attenuation >30 HU (Hounsfield unit), the attenuation measurements were more reproducible with narrower 95% limits of agreement.
Conclusions: Thymic size measurements had moderate-to-high intraobserver and interobserver agreements, when the instruction for consistent selection of images was provided to the readers. CT attenuation was highly reproducible, with higher reproducibility for thymic glands with >30 HU. Awareness of thymic measurement variability is necessary when interpreting measured values of normal thymus and thymic pathology on CT.
C1 [Araki, Tetsuro; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA.
[Nishino, Mizuki] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02215 USA.
EM Mizuki_Nishino@DFCI.HARVARD.EDU
FU National Cancer Institute [1K23CA157631]
FX The investigator, M.N. was supported by grant 1K23CA157631 from National
Cancer Institute.
NR 21
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUN
PY 2014
VL 21
IS 6
BP 733
EP 742
DI 10.1016/j.acra.2014.02.006
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH8UQ
UT WOS:000336414100006
PM 24809315
ER
PT J
AU Martin, JT
Milby, AH
Chiaro, JA
Kim, DH
Hebela, NM
Smith, LJ
Elliott, DM
Mauck, RL
AF Martin, John T.
Milby, Andrew H.
Chiaro, Joseph A.
Kim, Dong Hwa
Hebela, Nader M.
Smith, Lachlan J.
Elliott, Dawn M.
Mauck, Robert L.
TI Translation of an engineered nanofibrous disc-like angle-ply structure
for intervertebral disc replacement in a small animal model
SO ACTA BIOMATERIALIA
LA English
DT Article
DE Intervertebral disc; Tissue engineering; Electrospinning; Surgical
model; External fixation
ID HUMAN LUMBAR DISC; LOW-BACK-PAIN; ANNULUS FIBROSUS; BIOMECHANICAL
FUNCTION; DYNAMIC COMPRESSION; LOADING IMPROVES; NUCLEUS PULPOSUS;
ANULUS FIBROSUS; NEEDLE PUNCTURE; SCAFFOLDS
AB Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(epsilon-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the pen-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. (C) 2014 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA.
[Martin, John T.; Mauck, Robert L.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA.
[Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Newark, DE 19716 USA.
[Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Hebela, Nader M.; Smith, Lachlan J.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA.
[Smith, Lachlan J.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.
RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 36th St & Hamilton Walk,424 Stemmler Hall, Philadelphia, PA 19104 USA.
EM lemauck@mail.med.upenn.edu
FU Department of Defense [OR090090]; Department of Veterans Affairs
[I01RX000211]
FX We would like to thank the exceptional staff of the Philadelphia VA
Medical Center Animal Research Facility: Debra Pawlowski, Jeffrey House
and Pierina Deritis. In addition we would like to thank Deborah Gorth
and Feini Qu (animal procedures), Alexei Adan (DAPS fabrication and
histology), Subash Poudel (DAPS geometry and mechanical property
measurements), Sophia Stylianos (fabrication of surgical equipment) and
Dr. Thomas Schaer (sterilization facilities). This work was funded by
the Department of Defense (Grant #OR090090) and the Department of
Veterans Affairs (Grant # I01RX000211).
NR 49
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U1 6
U2 17
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
EI 1878-7568
J9 ACTA BIOMATER
JI Acta Biomater.
PD JUN
PY 2014
VL 10
IS 6
BP 2473
EP 2481
DI 10.1016/j.actbio.2014.02.024
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA AH7WK
UT WOS:000336345900012
PM 24560621
ER
PT J
AU Chan, KMC
Li, RH
Chapman, JW
Trac, EM
Kobler, JB
Zeitels, SM
Langer, R
Karajanagi, SS
AF Chan, Ka Man Carmen
Li, Randolph H.
Chapman, Joseph W.
Trac, Eric M.
Kobler, James B.
Zeitels, Steven M.
Langer, Robert
Karajanagi, Sandeep S.
TI Functionalizable hydrogel microparticles of tunable size and stiffness
for soft-tissue filler applications
SO ACTA BIOMATERIALIA
LA English
DT Article
DE Soft-tissue filler; Hydrogel; Microparticles; Suspension
photopolymerization
ID ACID DERMAL FILLERS; HYALURONIC-ACID; SUSPENSION POLYMERIZATION; CALCIUM
HYDROXYLAPATITE; RHEOLOGICAL PROPERTIES; INJECTABLE FILLERS; FLOW
LITHOGRAPHY; IN-VIVO; PARTICLES; CELLS
AB Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 JAM and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Chan, Ka Man Carmen; Li, Randolph H.; Chapman, Joseph W.; Kobler, James B.; Zeitels, Steven M.; Karajanagi, Sandeep S.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Chan, Ka Man Carmen; Li, Randolph H.; Trac, Eric M.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Karajanagi, SS (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 70 Blossom St, Boston, MA 02114 USA.
EM skarajanagi@partners.org
FU Voice Health Institute
FX We thank Matias Porras Paniagua and Keriann Durgin for assistance with
drug release studies and Dr. Jie Zhao for assistance with confocal
microscopy. This work was funded by the Voice Health Institute.
NR 57
TC 8
Z9 8
U1 7
U2 62
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
EI 1878-7568
J9 ACTA BIOMATER
JI Acta Biomater.
PD JUN
PY 2014
VL 10
IS 6
BP 2563
EP 2573
DI 10.1016/j.actbio.2014.02.021
PG 11
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA AH7WK
UT WOS:000336345900020
PM 24561708
ER
PT J
AU Caretti, V
Sewing, ACP
Lagerweij, T
Schellen, P
Bugiani, M
Jansen, MHA
van Vuurden, DG
Navis, AC
Horsman, I
Vandertop, WP
Noske, DP
Wesseling, P
Kaspers, GJL
Nazarian, J
Vogel, H
Hulleman, E
Monje, M
Wurdinger, T
AF Caretti, Viola
Sewing, A. Charlotte P.
Lagerweij, Tonny
Schellen, Pepijn
Bugiani, Marianna
Jansen, Marc H. A.
van Vuurden, Dannis G.
Navis, Anna C.
Horsman, Ilona
Vandertop, W. Peter
Noske, David P.
Wesseling, Pieter
Kaspers, Gertjan J. L.
Nazarian, Javad
Vogel, Hannes
Hulleman, Esther
Monje, Michelle
Wurdinger, Thomas
TI Human pontine glioma cells can induce murine tumors
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Neoplasms; Pontine neoplasms; Animal disease model; Microglia
ID BRAIN-STEM GLIOMAS; HIGH-GRADE GLIOMAS; NUDE-MICE; MALIGNANT
TRANSFORMATION; PEDIATRIC GLIOBLASTOMA; CLINICAL-TRIALS; HISTONE H3.3;
HOST-CELLS; IN-VITRO; FUSION
AB Diffuse intrinsic pontine glioma (DIPG), with a median survival of only 9 months, is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue for research has limited progress in this disease until recently. New experimental models for DIPG research are now emerging. To develop preclinical models of DIPG, two different methods were adopted: cells obtained at autopsy (1) were directly xenografted orthotopically into the pons of immunodeficient mice without an intervening cell culture step or (2) were first cultured in vitro and, upon successful expansion, injected in vivo. Both strategies resulted in pontine tumors histopathologically similar to the original human DIPG tumors. However, following the direct transplantation method all tumors proved to be composed of murine and not of human cells. This is in contrast to the indirect method that included initial in vitro culture and resulted in xenografts comprising human cells. Of note, direct injection of cells obtained postmortem from the pons and frontal lobe of human brains not affected by cancer did not give rise to neoplasms. The murine pontine tumors exhibited an immunophenotype similar to human DIPG, but were also positive for microglia/macrophage markers, such as CD45, CD68 and CD11b. Serial orthotopic injection of these murine cells results in lethal tumors in recipient mice. Direct injection of human DIPG cells in vivo can give rise to malignant murine tumors. This represents an important caveat for xenotransplantation models of DIPG. In contrast, an initial in vitro culture step can allow establishment of human orthotopic xenografts. The mechanism underlying this phenomenon observed with direct xenotransplantation remains an open question.
C1 [Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
[Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
[Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
[Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H. A.; van Vuurden, Dannis G.; Kaspers, Gertjan J. L.; Hulleman, Esther] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol, Amsterdam, Netherlands.
[Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Vandertop, W. Peter; Noske, David P.; Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Amsterdam, Netherlands.
[Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H. A.; van Vuurden, Dannis G.; Noske, David P.; Wesseling, Pieter; Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands.
[Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Bugiani, Marianna; Wesseling, Pieter] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Navis, Anna C.; Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands.
[Horsman, Ilona] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Nazarian, Javad] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA.
[Vogel, Hannes] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands.
[Wurdinger, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
RP Caretti, V (reprint author), Stanford Univ, Sch Med, 265 Campus Dr,Room G3077, Stanford, CA 94305 USA.
EM vcaretti@stanford.edu; e.hulleman@vumc.nl; mmonje@stanford.edu;
t.wurdinger@vumc.nl
RI Wesseling, P./H-8114-2014;
OI Wesseling, P./0000-0001-5453-5201; Lagerweij, Tonny/0000-0003-1043-7452;
Vogel, Otto Hannes/0000-0002-0960-3508; Navis, Anna/0000-0002-5267-4678;
Van Vuurden, Dannis/0000-0002-1364-9007
FU NIH [1S10RR02933801]; Semmy Foundation; KiKa Children Cancer Free; Child
Health Research Institute; Lucile Packard Foundation for Children's
Health; Stanford CTSA [UL1 TR000093]; Stanford University School of
Medicine Dean's Fellowship; National Institutes of Neurological Disease
and Stroke (NINDS) [K08NS070926]; Alex's Lemonade Stand Foundation;
McKenna Claire Foundation; The Cure Starts Now; Lyla Nsouli Foundation;
Connor Johnson Memorial Fund; Dylan Jewett Memorial Fund; Dylan Frick
Memorial Fund; Abigail Jensen Memorial Fund; Zoey Ganesh Memorial Fund;
Wayland Villars Memorial Fund; Musella Foundation
FX We would like to thank the patients and families who so generously
donated tissue for this research. We sincerely thank the architect and
artist Alessandra Luoni for drawing Fig. 1a. We gracefully acknowledge
Alyssa Noll (Departments of Neurology and Pediatrics) for support with
animal experiments, and Patty Lovelace (FACS Core) for her expertise
with flow cytometry experiments; all from Stanford, USA. The flow
cytometer used was purchased using an NIH S10 Shared Instrumentation
Grant (1S10RR02933801). We are thankful to Jacqueline Cloos (Department
of Pediatric Oncology, VU University Medical Center, The Netherlands)
and Dana Bangs (Cytogenetics Laboratory, Stanford, USA) for their
mastery in analyzing metaphase spreads. We are also thankful to Sridevi
Yadavilli for processing postmortem specimens and assisting in murine
injections, Research Center for Genetic Medicine, Children's National
Medical Center, Washington, USA. This work was supported by the Semmy
Foundation, KiKa Children Cancer Free, Child Health Research Institute,
Lucile Packard Foundation for Children's Health, as well as the Stanford
CTSA-award number UL1 TR000093-(V.C.), Stanford University School of
Medicine Dean's Fellowship (V. C.), National Institutes of Neurological
Disease and Stroke (NINDS grant K08NS070926), Alex's Lemonade Stand
Foundation, McKenna Claire Foundation, The Cure Starts Now, Lyla Nsouli
Foundation, Connor Johnson Memorial Fund, Dylan Jewett Memorial Fund,
Dylan Frick Memorial Fund, Abigail Jensen Memorial Fund, Zoey Ganesh
Memorial Fund, Wayland Villars Memorial Fund and Musella Foundation.
NR 54
TC 12
Z9 12
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD JUN
PY 2014
VL 127
IS 6
BP 897
EP 909
DI 10.1007/s00401-014-1272-4
PG 13
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AH6WO
UT WOS:000336273100008
PM 24777482
ER
PT J
AU Scherzer, R
Gandhi, M
Estrella, MM
Tien, PC
Deeks, SG
Grunfeld, C
Peralta, CA
Shlipak, MG
AF Scherzer, Rebecca
Gandhi, Monica
Estrella, Michelle M.
Tien, Phyllis C.
Deeks, Steven G.
Grunfeld, Carl
Peralta, Carmen A.
Shlipak, Michael G.
TI A chronic kidney disease risk score to determine tenofovir safety in a
prospective cohort of HIV-positive male veterans
SO AIDS
LA English
DT Article
DE chronic kidney disease; HIV; risk score; tenofovir
ID INFECTED PATIENTS; RANDOMIZED-TRIAL; RENAL-FAILURE; CYSTATIN-C; THERAPY;
INDIVIDUALS; ALBUMINURIA; ASSOCIATION; DYSFUNCTION; EXPOSURE
AB Objective:Tenofovir disoproxil fumarate is a widely used antiretroviral for HIV infection that has been associated with an increased risk of chronic kidney disease (CKD). Our objective was to derive a scoring system to predict 5-year risk of developing CKD in HIV-infected individuals and to estimate difference in risk associated with tenofovir use.Design:We evaluated time to first occurrence of CKD (estimated glomerular filtration rate <60ml/min per 1.73m(2)) in 21590 HIV-infected men from the Veterans Health Administration initiating antiretroviral therapy from 1997 to 2010.Methods:We developed a point-based score using multivariable Cox regression models. Median follow-up was 6.3 years, during which 2059 CKD events occurred.Results:Dominant contributors to the CKD risk score were traditional kidney risk factors (age, glucose, SBP, hypertension, triglycerides, proteinuria); CD4(+) cell count was also a component, but not HIV RNA. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in nonusers [overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8-2.2]. There was a progressive increase in 5-year CKD risk, ranging from less than 1% (zero points) to 16% (9 points) in nonusers of tenofovir, and from 1.4 to 21.4% among tenofovir users. The estimated number-needed-to-harm (NNH) for tenofovir use ranged from 108 for those with zero points to 20 for persons with at least nine points. Among tenofovir users with at least 1 year exposure, NNH ranged from 68 (zero points) to five (9 points).Conclusion:The CKD risk score can be used to predict an HIV-infected individual's absolute risk of developing CKD over 5 years and may facilitate clinical decision-making around tenofovir use.
C1 [Scherzer, Rebecca; Gandhi, Monica; Tien, Phyllis C.; Deeks, Steven G.; Grunfeld, Carl; Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Gandhi, Monica; Deeks, Steven G.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA.
[Estrella, Michelle M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Shlipak, MG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM michael.shlipak@ucsf.edu
FU National Institutes of Health [K23DK080645-01A1, 1R03AG034871-01,
K24AI069994, R01 DK066488-01, RO1 AI098472]; National Center for
Research Resources [KL2 RR024130]; American Heart Association
Established Investigator Award; VA Public Health Strategic Healthcare
Group; Gilead; Merck; Bristol-Myers Squibb; Abbott; Gilead Sciences; EMD
Serono; Theratechnologies
FX This work was supported by the National Institutes of Health
[K23DK080645-01A1 (A. I. C.), 1R03AG034871-01 (A.I.C./M.G.S.),
K24AI069994, R01 DK066488-01 (M.G.S./A.I.C.), RO1 AI098472 (M. G.)], the
National Center for Research Resources [KL2 RR024130], the American
Heart Association Established Investigator Award (M.G.S.) and the VA
Public Health Strategic Healthcare Group, which were administered by the
Northern California Institute for Research and Education, and with
resources of the Veterans Affairs Medical Center, San Francisco,
California. These funding sources had no involvement in the design or
execution of this study. S. G. D. received grant support from Gilead and
Merck, and honorarium for ad hoc consulting from Gilead and
GlaxoSmithKline. C.G. has received prior research funding and/or
honorarium from Merck, Bristol-Myers Squibb, Abbott, Gilead Sciences,
EMD Serono and Theratechnologies.
NR 30
TC 9
Z9 9
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN 1
PY 2014
VL 28
IS 9
BP 1289
EP 1295
DI 10.1097/QAD.0000000000000258
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AH2SX
UT WOS:000335972500006
PM 24922479
ER
PT J
AU Blashill, AJ
Wilson, JM
Baker, JS
Mayer, KH
Safren, SA
AF Blashill, Aaron J.
Wilson, Johannes M.
Baker, Joshua S.
Mayer, Kenneth H.
Safren, Steven A.
TI Assessing Appearance-Related Disturbances in HIV-Infected Men Who have
Sex with Men (MSM): Psychometrics of the Body Change and Distress
Questionnaire-Short Form (ABCD-SF)
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV; MSM; Body image disturbance; Scale development; Health outcomes
ID QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; STRUCTURAL EQUATION
MODELS; SMALL SAMPLE-SIZES; FACIAL LIPOATROPHY; BISEXUAL MEN; IMAGE;
LIPODYSTROPHY; ADHERENCE; HEALTH
AB Appearance-related disturbances are common among HIV-infected MSM; however, to date, there have been limited options in the valid assessment of this construct. The aim of the current study was to assess the structural, internal, and convergent validity of the assessment of body change distress questionnaire (ABCD) and its short version. Exploratory and confirmatory factor analyses indicated that both versions fit the data well. Four subfactors were revealed measuring the following body disturbance constructs: (1) negative affect about appearance, (2) HIV health-related outcomes and stigma, (3) eating and exercise confusion, and (4) ART non-adherence. The subfactors and total scores revealed bivariate associations with salient health outcomes, including depressive symptoms, HIV sexual transmission risk behaviors, and ART non-adherence. The ABCD and its short form, offer valid means to assess varied aspects of body image disturbance among HIV-infected MSM, and require modest participant burden.
C1 [Blashill, Aaron J.; Wilson, Johannes M.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Blashill, Aaron J.; Mayer, Kenneth H.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
[Blashill, Aaron J.; Baker, Joshua S.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM ablashill@partners.org
FU NIAID NIH HHS [P30 AI060354, 5P30 AI060354-08]; NIMH NIH HHS [K23
MH096647, K24MH094214, K24 MH094214, K23MH096647]
NR 51
TC 1
Z9 1
U1 2
U2 3
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 JUN
PY 2014
VL 18
IS 6
BP 1075
EP 1084
DI 10.1007/s10461-013-0620-z
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA AH5YF
UT WOS:000336206400011
PM 24057934
ER
PT J
AU Mordes, DA
Lynch, K
Campbell, S
Dias-Santagata, D
Nose, V
Louis, DN
Hoang, MP
AF Mordes, Daniel A.
Lynch, Kerry
Campbell, Sharon
Dias-Santagata, Dora
Nose, Vania
Louis, David N.
Hoang, Mai P.
TI VE1 Antibody Immunoreactivity in Normal Anterior Pituitary and Adrenal
Cortex Without Detectable BRAF V600E Mutations
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE VE1; BRAF V600E; Immunohistochemistry; Pituitary gland; Adrenal gland
ID IMMUNOHISTOCHEMISTRY; CANCER; CARCINOMA; ADENOMAS; MELANOMA; TUMORS
AB Objectives: The VE1 monoclonal antibody was developed to recognize the V600E mutation in BRAF, which is found in various tumors.
Methods: We report that the VE1 antibody stains normal anterior pituitary gland and adrenal cortex, which lack detectable BRAF V600E mutations.
Results: Staining with the VE1 antibody was seen in the adenohypophysis and correlated well with adrenocorticotropic hormone (ACTH) positive cells. ACTH-positive cells were typically most concentrated in the central mucoid wedge and pars intermedia, and VE1 staining was strong in these regions. Moreover, VE1 staining was seen in ACTH-expressing pituitary adenomas without detectable BRAF mutations. VE1 staining of the adrenal cortex was also significant, with the strongest staining seen in the inner segment of the zona fasciculata. Parathyroid glands, pancreatic islets, or parafollicular C cells in the thyroid showed no VE1 staining.
Conclusions: Overall, VE1 staining of endocrine tissues strongly suggests limitations on the use of this antibody for the detection of BRAF mutations.
C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA.
EM mhoang@mgh.harvard.edu
NR 19
TC 10
Z9 10
U1 1
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUN
PY 2014
VL 141
IS 6
BP 811
EP 815
DI 10.1309/AJCP37TLZLTUAOJL
PG 5
WC Pathology
SC Pathology
GA AH6KM
UT WOS:000336239800009
PM 24838325
ER
PT J
AU Katz, IR
AF Katz, Ira R.
TI Mental Health Needs of Older Veterans
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Editorial Material
ID NATIONAL-HEALTH; RESILIENCE
C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
RP Katz, IR (reprint author), Philadelphia VA Med Ctr, Univ & Woodland Aves, Philadelphia, PA 19104 USA.
EM Ira.Katz2@va.gov
NR 13
TC 1
Z9 1
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD JUN
PY 2014
VL 22
IS 6
BP 527
EP 530
DI 10.1016/j.jagp.2014.01.014
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4HG
UT WOS:000336087400001
PM 24821286
ER
PT J
AU Garrido, MM
Penrod, JD
Prigerson, HG
AF Garrido, Melissa M.
Penrod, Joan D.
Prigerson, Holly G.
TI Unmet Need for Mental Health Care Among Veterans Receiving Palliative
Care: Assessment is Not Enough
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Veterans; psychotherapy; access to care; anxiety; depression; palliative
care
ID ADVANCED CANCER
AB Objective: To determine whether inpatient palliative care teams' assessments of psychological distress affect receipt of in-hospital mental health care (psychotherapy, psychological support, and health and behavior interventions) for seriously ill veterans. Methods: Retrospective review of medical records from 287 seriously ill veterans who received inpatient palliative care consults between 2008 and 2010 in the NY/NJ Veterans Healthcare Network. Results: Of the veterans who were cognitively or physically able to answer questions on the Condensed Memorial Symptom Assessment Scale, 44% reported psychological distress. Of those with distress, 38% accessed mental health care. In logistic regression models adjusted for sociodemographic and health characteristics, there was no evidence that psychological distress reported during the palliative care consult was associated with subsequent mental health care receipt from any type of provider. Conclusions: Efforts to increase mental health care to psychologically distressed palliative care patients need to convert assessments into receipt of needed care.
C1 [Garrido, Melissa M.; Penrod, Joan D.] James J Peters VAMC, Bronx, NY 10468 USA.
[Garrido, Melissa M.; Penrod, Joan D.] Icahn Sch Med Mt Sinai, New York, NY USA.
[Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Garrido, MM (reprint author), James J Peters VAMC, GRECC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM melissa.garrido@mssm.edu
FU Dept. of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service [CDA 11-201/CDP 12-255];
National Palliative Care Research Center; National Cancer Institute
[CA106370, CA156732]; Atlantic Philanthropies Health & Aging Policy
Fellowship; National Institute of Mental Health [MH63892]
FX The following are the funding sources for this research. MMG: Dept. of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service (CDA 11-201/CDP 12-255); National
Palliative Care Research Center. JDP: The Atlantic Philanthropies Health
& Aging Policy Fellowship. HGP: National Institute of Mental Health
(MH63892) and National Cancer Institute (CA106370; CA156732).
NR 14
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD JUN
PY 2014
VL 22
IS 6
BP 540
EP 544
DI 10.1016/j.jagp.2013.08.008
PG 5
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4HG
UT WOS:000336087400003
PM 24119857
ER
PT J
AU Yeager, DE
Magruder, KM
AF Yeager, Derik E.
Magruder, Kathryn M.
TI PTSD Checklist Scoring Rules for Elderly Veterans Affairs Outpatients
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE PTSD; screening; elderly
ID POSTTRAUMATIC-STRESS-DISORDER; PREVALENCE
AB Objective: To assess the diagnostic performance of the PTSDChecklist (PCL) for three age groups (<50, 50-64, and >= 65 years). Methods: The PCL was compared with the Clinician Administered PTSD Scale, a gold standard for the diagnosis of post-traumatic stress disorder. Receiver operating characteristic curves and the corresponding area under the receiver operating characteristic curve (AUC) and measures of sensitivity and specificity were used to assess the performance of and to determine optimal cutscores for the PCL across the three groups. Analyses were based on 858 randomly selected primary care patients who participated in a study conducted at four Veterans Administration medical centers. Results: AUCs were high for all three age groups (87.55%-88.26%), and there were no significant differences in AUCs across age groups chi(2). Optimal cutscores, however, varied considerably: 24 for the oldest group, 34 for the middle group, and 43 for the youngest group. Conclusion: Recommend use of lower PCL cutscore for older Veterans Administration primary care patients.
C1 [Yeager, Derik E.; Magruder, Kathryn M.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA.
[Yeager, Derik E.; Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
RP Yeager, DE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA.
EM yeagerde@musc.edu
FU Department of Veterans Affairs; Veterans Health Administration; Office
of Research and Development; Health Services Research and Development
[VCR 99-010-2]; National Center for Research Resources [UL1TR000062]
FX Supported by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, and Health Services
Research and Development (VCR 99-010-2). The views expressed in this
report are those of the authors and do not necessarily reflect the
position or policy of the Department of Veteran Affairs or the U.S.
government.; Also supported by award number UL1TR000062 from the
National Center for Research Resources. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Center for Research Resources or the
National Institutes of Health.
NR 13
TC 4
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD JUN
PY 2014
VL 22
IS 6
BP 545
EP 550
DI 10.1016/j.jagp.2013.03.009
PG 6
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4HG
UT WOS:000336087400004
PM 24041524
ER
PT J
AU Covinsky, KE
Cenzer, IS
Yaffe, K
O'Brien, S
Blazer, DG
AF Covinsky, Kenneth E.
Cenzer, Irena Stijacic
Yaffe, Kristine
O'Brien, Sarah
Blazer, Dan G.
TI Dysphoria and Anhedonia as Risk Factors for Disability or Death in Older
Persons: Implications for the Assessment of Geriatric Depression
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Depression; anhedonia; activities of daily living; quality of life;
health status
ID SUBTHRESHOLD DEPRESSION; FUNCTIONAL LIMITATIONS; VASCULAR DEPRESSION;
COMMUNITY SAMPLE; ELDERLY PERSONS; LATER-LIFE; SYMPTOMS; ADULTS;
MORTALITY; DIRECTIONS
AB Objectives: Either dysphoria (sadness) or anhedonia (loss of interest in usually pleasurable activities) is required for a diagnosis of major depression. Although major depression is a known risk factor for disability in older persons, few studies have examined the relationship between the two core symptoms of major depression and disability or mortality. Our objective was to examine the relationship between these two core symptoms and time to disability or death. Methods: In a longitudinal cohort study, we used the nationally representative Health and Retirement Study to examine this relationship in 11,353 persons older than 62 years (mean: 73 years) followed for up to 13 years. Dysphoria and anhedonia were assessed with the Short Form Composite International Diagnostic Interview. Our outcome measure was time to either death or increased disability, defined as the new need for help in a basic activity of daily living. We adjusted for a validated disability risk index and other confounders. Results: Compared with subjects without either dysphoria or anhedonia, the risk for disability or death was not elevated in elders with dysphoria without anhedonia (adjusted hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.91-1.36). The risk was elevated in those with anhedonia without dysphoria (HR: 1.30; 95% CI: 1.06-1.60) and those with both anhedonia and dysphoria (HR: 1.28; 95% CI: 1.13-1.46). Conclusion: Our results highlight the need for clinicians to learn whether patients have lost interest in usually pleasurable activities, even if they deny sadness.
C1 [Covinsky, Kenneth E.; Cenzer, Irena Stijacic; O'Brien, Sarah] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Covinsky, Kenneth E.; Cenzer, Irena Stijacic; Yaffe, Kristine; O'Brien, Sarah] San Francisco VA Med Ctr, San Francisco, CA USA.
[Blazer, Dan G.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
RP Covinsky, KE (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr 181G, 4150 Clement, San Francisco, CA 94121 USA.
EM ken.covinsky@ucsf.edu
FU National Institute on Aging [R01AG028481, K24AG029812]
FX Supported by grants R01AG028481 and K24AG029812 from the National
Institute on Aging. The Health and Retirement Study is funded by the
National Institute on Aging.
NR 34
TC 9
Z9 9
U1 5
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD JUN
PY 2014
VL 22
IS 6
BP 606
EP 613
DI 10.1016/j.jagp.2012.12.001
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4HG
UT WOS:000336087400011
PM 23602308
ER
PT J
AU Merker, VL
Bredella, MA
Cai, W
Kassarjian, A
Harris, GJ
Muzikansky, A
Nguyen, R
Mautner, VF
Plotkin, SR
AF Merker, Vanessa L.
Bredella, Miriam A.
Cai, Wenli
Kassarjian, Ara
Harris, Gordon J.
Muzikansky, Alona
Nguyen, Rosa
Mautner, Victor F.
Plotkin, Scott R.
TI Relationship between whole-body tumor burden, clinical phenotype, and
quality of life in patients with neurofibromatosis
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE neurofibromatosis 1; neurofibromatosis 2; schwannomatosis; quality of
life; pain; nerve sheath tumor; whole-body MRI; SF-36
ID DIAGNOSTIC-CRITERIA; TYPE-1; SCHWANNOMATOSIS; CHILDREN; IMPACT
AB Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis share a predisposition to develop multiple nerve sheath tumors. Previous studies have demonstrated that patients with NF1 and NF2 have reduced quality of life (QOL), but no studies have examined the relationship between whole-body tumor burden and QOL in these patients. We administered a QOL questionnaire (the SF-36) and a visual analog pain scale (VAS) to a previously described cohort of adult neurofibromatosis patients undergoing whole-body MRI. One-sample t-tests were used to compare norm-based SF-36 scores to weighted population means. Spearman correlation coefficients and multiple linear regression analyses controlling for demographic and disease-specific clinical variable were used to relate whole-body tumor volume to QOL scales. Two hundred forty-five patients (142 NF1, 53 NF2, 50 schwannomatosis) completed the study. Subjects showed deficits in selected subscales of the SF-36 compared to adjusted general population means. In bivariate analysis, increased tumor volume was significantly associated with pain in schwannomatosis patients, as measured by the SF-36 bodily pain subscale (rho = -0.287, P = 0.04) and VAS (rho = 0.34, P = 0.02). Regression models for NF2 patients showed a positive relationship between tumor burden and increased pain, as measured by the SF-36 (P = 0.008). Patients with NF1, NF2, and schwannomatosis suffer from reduced QOL, although only pain shows a clear relationship to patient's overall tumor burden. These findings suggest that internal tumor volume is not a primary contributor to QOL and emphasize the need for comprehensive treatment approaches that go beyond tumor-focused therapies such as surgery by including psychosocial interventions. (c) 2014 Wiley Periodicals, Inc.
C1 [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Bredella, Miriam A.; Cai, Wenli; Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kassarjian, Ara] Corades SL, Dept Radiol, Majadahonda, Spain.
[Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Nguyen, Rosa] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA.
[Nguyen, Rosa; Mautner, Victor F.] Univ Hamburg Hosp, Dept Neurol, Hamburg, Germany.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM splotkin@partners.org
OI Merker, Vanessa/0000-0002-4542-5227
FU Department of Defense Neurofibromatosis Research Program [NF050202]
FX Grant sponsor: Department of Defense Neurofibromatosis Research Program;
Grant number: NF050202.
NR 22
TC 15
Z9 15
U1 4
U2 12
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 JUN
PY 2014
VL 164
IS 6
BP 1431
EP 1437
DI 10.1002/ajmg.a.36466
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA AH2BV
UT WOS:000335926600010
PM 24664633
ER
PT J
AU Wakeman, SE
Green, TC
Rich, JD
AF Wakeman, Sarah E.
Green, Traci C.
Rich, Josiah D.
TI From Documenting Death to Comprehensive Care: Applying Lessons from the
HIV/AIDS Epidemic to Addiction
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID EXCEPTIONALISM; AIDS
C1 [Wakeman, Sarah E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Wakeman, Sarah E.] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA.
[Wakeman, Sarah E.] Harvard Univ, Sch Med, Boston, MA USA.
[Wakeman, Sarah E.; Green, Traci C.; Rich, Josiah D.] Ctr Prisoner Hlth & Human Rights, Providence, RI USA.
[Green, Traci C.; Rich, Josiah D.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Green, Traci C.] Rhode Isl Hosp, Dept Emergency Med & Epidemiol, Providence, RI USA.
[Rich, Josiah D.] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA.
RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
FU NCIPC CDC HHS [U01 CE002165, 5 R21 CE002165-02]; NIAID NIH HHS [P30
AI042853, P30-AI42853]; NIDA NIH HHS [K24 DA022112, K24DA022112]
NR 5
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2014
VL 127
IS 6
BP 465
EP 466
DI 10.1016/j.amjmed.2013.12.018
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH8GD
UT WOS:000336374100014
PM 24412918
ER
PT J
AU Venkatesh, KK
Cu-Uvin, S
AF Venkatesh, Kartik K.
Cu-Uvin, Susan
TI Anatomic and Hormonal Changes in the Female Reproductive Tract Immune
Environment during the Life Cycle: Implications for HIV/STI Prevention
Research
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Anatomy; female genital tract; HIV; hormones; STI; women
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED INFECTIONS; UTERINE
EPITHELIAL-CELLS; HUMAN VAGINAL EPITHELIUM; MENSTRUAL-CYCLE; CERVICAL
ECTOPY; POSTMENOPAUSAL WOMEN; HIV-1 TRANSMISSION; MUCOSAL IMMUNITY;
INNATE IMMUNITY
AB The female genital tract undergoes anatomic changes from birth through menopause. Concurrently, the relative levels and roles of estradiol and progesterone dramatically change during the female life cycle. This review provides a conceptual overview of clinically relevant anatomic and hormonal changes in the female genital tract, and how these changes may affect HIV-1 pathogenesis, transmission, and mucosal immunology and protection against HIV and STIs across the female life cycle.
C1 [Venkatesh, Kartik K.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02415 USA.
[Venkatesh, Kartik K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Cu-Uvin, Susan] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Cu-Uvin, Susan] Brown Univ, Alpert Med Sch, Dept Med, Div Infect Dis, Providence, RI 02912 USA.
RP Venkatesh, KK (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02415 USA.
EM kvenkatesh@partners.org
NR 69
TC 2
Z9 2
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUN
PY 2014
VL 71
IS 6
SI SI
BP 495
EP 504
DI 10.1111/aji.12247
PG 10
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AH1YK
UT WOS:000335917600003
PM 24832617
ER
PT J
AU Miller, RG
Brooks, BR
Swain-Eng, RJ
Basner, RC
Carter, GT
Casey, P
Cohen, AB
Dubinsky, R
Forshew, D
Jackson, CE
Kasarskis, E
Procaccini, NJ
Sanjak, M
Tolin, FP
AF Miller, Robert G.
Brooks, Benjamin Rix
Swain-Eng, Rebecca J.
Basner, Robert C.
Carter, Gregory T.
Casey, Patricia
Cohen, Adam B.
Dubinsky, Richard
Forshew, Dallas
Jackson, Carlayne E.
Kasarskis, Ed
Procaccini, Nicholas J.
Sanjak, Mohammed
Tolin, Fredrik P.
TI Quality improvement in neurology: Amyotrophic Lateral Sclerosis Quality
Measures
SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
LA English
DT Editorial Material
ID PRACTICE PARAMETER UPDATE; AMERICAN ACADEMY; STANDARDS SUBCOMMITTEE;
REPORTING SUBCOMMITTEE; MULTIDISCIPLINARY CARE; OF-LIFE; MANAGEMENT;
PATIENT; ALS; SURVIVAL
C1 [Miller, Robert G.; Forshew, Dallas] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA.
[Brooks, Benjamin Rix] Univ N Carolina, Carolinas HealthCare Syst, Carolinas Med Ctr, Carolinas Neuromuscular ALS MDA Ctr,Dept Neurol, Charlotte, NC 28223 USA.
[Swain-Eng, Rebecca J.] Amer Acad Neurol, Minneapolis, MN USA.
[Basner, Robert C.] Columbia Univ, Coll Phys & Surg, Div Pulm Med, New York, NY USA.
[Carter, Gregory T.] St Lukes Rehabil Inst, Spokane, WA USA.
[Casey, Patricia] Northwestern Med Fac Fdn, Dept Neurol, Chicago, IL USA.
[Cohen, Adam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Dubinsky, Richard] Univ Kansas, Dept Neurol, Kansas City, KS USA.
[Jackson, Carlayne E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA.
[Kasarskis, Ed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA.
[Procaccini, Nicholas J.] Swedish Med Ctr, Seattle, WA USA.
[Procaccini, Nicholas J.] Univ Washington, Seattle, WA 98195 USA.
[Sanjak, Mohammed] Univ N Carolina, Carolinas HealthCare Syst, Carolinas Med Ctr, Carolinas Neuromuscular ALS MDA Ctr,Dept Kinesiol, Charlotte, NC 28223 USA.
[Tolin, Fredrik P.] Humana, Chicago, IL USA.
RP Miller, RG (reprint author), Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA.
EM quality@aan.com
NR 30
TC 3
Z9 3
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8421
EI 2167-9223
J9 AMYOTROPH LAT SCL FR
JI Amyotroph. Lateral Scher. Frontotemp. Degenerat.
PD JUN
PY 2014
VL 15
IS 3-4
BP 165
EP 168
DI 10.3109/21678421.2013.875706
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH8KH
UT WOS:000336386200003
PM 24707820
ER
PT J
AU Bruijn, L
Cudkowicz, M
AF Bruijn, Lucie
Cudkowicz, Merit
CA Als Clinical Trials Working Grp
TI Opportunities for improving therapy development in ALS
SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
LA English
DT Review
DE Amyotrophic lateral sclerosis; clinical trials; biomarkers; therapy
ID AMYOTROPHIC-LATERAL-SCLEROSIS; RANDOMIZED SEQUENTIAL TRIAL; PHASE-III;
MULTICENTER; SURVIVAL; LITHIUM; DESIGNS
AB In May 2013, The ALS Association and The Northeast ALS Consortium (NEALS) convened a meeting of stakeholders for a round-table discussion of ways to improve therapy development in ALS. The following overview summarizes issues raised and potential new directions discussed at the meeting. We recommend that future phase II clinical trials in ALS proceed when the proposed treatment is directed at targets that are likely to be involved in ALS pathogenesis in a defined subgroup of patients, and be accompanied by one or more biomarkers to track both clinical progression and pharmacodynamic engagement of the target. Innovations in trial structure and design, and greater involvement of patient advocates, may also improve trials.
C1 [Bruijn, Lucie] ALS Assoc, Washington, DC 20005 USA.
[Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA.
RP Bruijn, L (reprint author), ALS Assoc, 125 K St,Suite 250, Washington, DC 20005 USA.
EM lucie@alsa-national.org
OI Macklin, Eric/0000-0003-1618-3502
NR 15
TC 8
Z9 8
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8421
EI 2167-9223
J9 AMYOTROPH LAT SCL FR
JI Amyotroph. Lateral Scher. Frontotemp. Degenerat.
PD JUN
PY 2014
VL 15
IS 3-4
BP 169
EP 173
DI 10.3109/21678421.2013.872662
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH8KH
UT WOS:000336386200004
PM 24472060
ER
PT J
AU Cote, CJ
Posner, KL
Domino, KB
AF Cote, Charles J.
Posner, Karen L.
Domino, Karen B.
TI Death or Neurologic Injury after Tonsillectomy in Children with a Focus
on Obstructive Sleep Apnea: Houston, We Have a Problem!
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID RESPIRATORY COMPLICATIONS; RECURRENT HYPOXEMIA; MALPRACTICE CLAIMS;
OPIOID RECEPTOR; RISK-FACTORS; ADENOTONSILLECTOMY; CODEINE; OBESITY;
METABOLIZERS; MANAGEMENT
AB BACKGROUND: Obesity is epidemic in the United States and With it comes an increased incidence of obstructive sleep apnea (OSA). Evidence regarding opioid sensitivity, as well as recent descriptions of deaths after tonsillectomy prompted a survey of all members of the Society for Pediatric Anesthesia regarding adverse events in children undergoing tonsillectomy.
METHODS: An electronic survey was sent to 2377 members of the Society for Pediatric Anesthesia. Additionally, data from the American Society of Anesthesiologists Closed Claims Project were obtained. Adverse events during or after tonsillectomy with or without adenoidectomy in children were included. Children at risk for OSA were identified as either having a positive history for OSA or a post hoc application of the American Society of Anesthesiologists OSA practice guidelines. These children were compared with all other children by Fisher exact test for proportions and t test for continuous variables.
RESULTS: A total of 129 cases were identified from the 731 replies to the survey, with 92 meeting inclusion criteria for having adequate data. Another 19 cases with adequate data were identified from the 45 from the American Society of Anesthesiologists Closed Claims Project. A total of 111 cases were included in the final analysis. Death and permanent neurologic injury occurred in 86 (77%) cases and were reported in the operating room, postanesthesia care unit, on the ward, and at home. Sixty-three (57%) children fulfilled American Society of Anesthesiologists criteria to be at risk for OSA. Children categorized as at risk for OSA. were more likely than other children to be obese and to have comorbidities (P < 0.0001). A larger proportion of at risk children had the event attributed to apnea (P = 0.016), whereas all others had a larger proportion of events attributed to hemorrhage (P = 0.006).
CONCLUSIONS: Deaths or neurologic injury after tonsillectomy due to apparent apnea in children suggest that at least 16 children could have been rescued had respiratory monitoring been continued throughout first- and second-stage recovery, as well as on the ward during the first postoperative night. A validated pediatric-specific risk assessment scoring system is needed to assist with identifying children at risk for OSA who are not appropriate to be cared for on an outpatient basis.
C1 [Cote, Charles J.] Harvard Univ, Sch Med, MassGen Hosp Children, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Posner, Karen L.; Domino, Karen B.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
RP Cote, CJ (reprint author), MassGen Hosp Children, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA.
EM cjcote@partners.org
FU American Society of Anesthesiologists (ASA), Park Ridge, IL
FX Funding: Supported in part by the American Society of Anesthesiologists
(ASA), Park Ridge, IL. All opinions expressed are those of the authors
and do not reflect the policy of the ASA.
NR 41
TC 35
Z9 35
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
EI 1526-7598
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUN
PY 2014
VL 118
IS 6
BP 1276
EP 1283
DI 10.1213/ANE.0b013e318294fc47
PG 8
WC Anesthesiology
SC Anesthesiology
GA AH7YZ
UT WOS:000336352600018
PM 23842193
ER
PT J
AU Ting, CK
Johnson, KB
Teng, WN
Synoid, ND
LaPierre, C
Yu, L
Westenskow, DR
AF Ting, Chien-Kun
Johnson, Ken B.
Teng, Wei-Nung
Synoid, Noah D.
LaPierre, Cris
Yu, Lu
Westenskow, Dwayne R.
TI Response Surface Model Predictions of Wake-Up Time During Scoliosis
Surgery
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID ALVEOLAR ANESTHETIC CONCENTRATION; PROPOFOL-REMIFENTANIL ANESTHESIA;
SEVOFLURANE REQUIREMENTS; INHALATION ANESTHESIA; CONCENTRATION-AWAKE;
CONTROLLED INFUSION; SYSTEM MODEL; FENTANYL; MAC; DESFLURANE
AB BACKGROUND: With the use of previously published data, new sevoflurane remifentanil interaction models of various degrees of sedation were created and adapted to desflurane-fentanyl by using minimal alveolar concentration and opioid equivalencies. These models were used to predict return of responsiveness in patients undergoing scoliosis surgery during a wake-up test. Our hypothesis was that one of the interaction models would accurately predict return of responsiveness during a wake-up test.
METHODS: Three new sevoflurane remifentanil interaction models were constructed from previous observations in volunteers by using the Observer's Assessment of Alertness/Sedation (OAA/S) scores. These models included predictions of OAA/S<2 (unresponsive), OAA/S<3, and OAA/S<4 (sedation). Twenty-three patients scheduled for scoliosis surgery received a fentanyl desflurane anesthetic. With the use of published pharmacokinetic models, predictions of fentanyl and desflurane effect-site concentrations were recorded throughout surgery and converted to equivalent remifentanil and sevoflurane effect-site concentrations. Data were recorded every 10 seconds from the time when desflurane was turned off until 10 minutes after the patients responded by moving their hands and toes. Model predictions were compared with observations with graphical and temporal analyses.
RESULTS: The average difference between the time when a patient first responded and the time when the model predicted that there was a 50% probability that the patient would respond were -2.6 +/- 3.6 minutes (mean +/- SD) for the OAA/S<2 model, 2.8 +/- 5.6 minutes for the OAA/S<3 model and 52.6 +/- 32.3 minutes for the OAA/S<4 model.
CONCLUSIONS: The results confirmed our study hypothesis; a sevoflurane remifentanil interaction model built from observations in volunteers and adapted to desflurane and fentanyl accurately predicted patient response during a wake-up test. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic. The OAA/S <2 model most accurately predicted the time patients would respond by moving their fingers and toes. This model may help anesthesiologists better predict return of responsiveness during a wake-up test in patients undergoing spine surgery.
C1 [Ting, Chien-Kun; Teng, Wei-Nung] Taipei Vet Gen Hosp, Dept Anesthesiol, Taipei, Taiwan.
[Ting, Chien-Kun; Teng, Wei-Nung] Natl Yang Ming Univ, Taipei 112, Taiwan.
[Johnson, Ken B.; Synoid, Noah D.; Westenskow, Dwayne R.] Univ Utah, Sch Med, Dept Anesthesiol, Salt Lake City, UT USA.
[Johnson, Ken B.; Westenskow, Dwayne R.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
[LaPierre, Cris] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[LaPierre, Cris] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Yu, Lu] China Med Univ, Dept Biomed Engn, Coll Basic Med Sci, Shenyang, Liaoning, Peoples R China.
RP Ting, CK (reprint author), Taipei Vet Gen Hosp, Dept Anesthesiol, 201,Sect 2,Shi Pai Rd, Taipei, Taiwan.
EM ckting2@gmail.com
RI Ting, Chien-Kun/C-1389-2012
OI Ting, Chien-Kun/0000-0002-3156-8139
NR 40
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
EI 1526-7598
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUN
PY 2014
VL 118
IS 6
BP 1396
EP 1403
DI 10.1213/ANE.0000000000000094
PG 8
WC Anesthesiology
SC Anesthesiology
GA AH7YZ
UT WOS:000336352600040
ER
PT J
AU Kim, J
Won, JS
Singh, AK
Sharma, AK
Singh, I
AF Kim, Jinsu
Won, Je-Seong
Singh, Avtar K.
Sharma, Anand K.
Singh, Inderjit
TI STAT3 Regulation by S-Nitrosylation: Implication for Inflammatory
Disease
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; MEDIATED RECEPTOR-BINDING;
EPIDERMAL-GROWTH-FACTOR; BRAIN MICROGLIAL CELLS; NITRIC-OXIDE; JAK-STAT;
TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; NITROSO-GLUTATHIONE
AB Aims: S-nitrosylation and S-glutathionylation, redox-based modifications of protein thiols, are recently emerging as important signaling mechanisms. In this study, we assessed S-nitrosylation-based regulation of Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway that plays critical roles in immune/inflammatory responses and tumorigenesis. Results: Our studies show that STAT3 in stimulated microglia underwent two distinct redox-dependent modifications, S-nitrosylation and S-glutathionylation. STAT3 S-nitrosylation was associated with inducible nitric oxide synthase (iNOS)-produced nitric oxide (NO) and S-nitrosoglutathione (GSNO), whereas S-glutathionylation of STAT3 was associated with cellular oxidative stress. NO produced by iNOS or treatment of microglia with exogenous GSNO inhibited STAT3 activation via inhibiting STAT3 phosphorylation (Tyr(705)). Consequently, the interleukin-6 (IL-6)-induced microglial proliferation and associated gene expressions were also reduced. In cell-free kinase assay using purified JAK2 and STAT3, STAT3 phosphorylation was inhibited by its selective preincubation with GSNO, but not by preincubation of JAK2 with GSNO, indicating that GSNO-mediated mechanisms inhibit STAT3 phosphorylation through S-nitrosylation of STAT3 rather than JAK2. In this study, we identified that Cys(259) was the target Cys residue of GSNO-mediated S-nitrosylation of STAT3. The replacement of Cys(259) residue with Ala abolished the inhibitory role of GSNO in IL-6-induced STAT3 phosphorylation and transactivation, suggesting the role of Cys(259) S-nitrosylation in STAT3 phosphorylation. Innovation: Microglial proliferation is regulated by NO via S-nitrosylation of STAT3 (Cys(259)) and inhibition of STAT3 (Tyr(705)) phosphorylation. Conclusion: Our results indicate the regulation of STAT3 by NO-based post-translational modification (S-nitrosylation). These findings have important implications for the development of new therapeutics targeting STAT3 for treating diseases associated with inflammatory/immune responses and abnormal cell proliferation, including cancer. Antioxid. Redox Signal. 20, 2514-2527.
C1 [Kim, Jinsu; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Won, Je-Seong; Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC USA.
[Sharma, Anand K.; Singh, Inderjit] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA.
RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave CRI 516, Charleston, SC 29425 USA.
EM singhi@musc.edu
FU NIH; VA [NS072511, BX001062, NS037766, BX001072]
FX This work was supported by grants from NIH and VA (NS072511, BX001062,
NS037766 and BX001072). We also acknowledge Ms. Joyce Bryan and Ms.
Chara Williams for their help in procurement of animals and supplies.
NR 60
TC 13
Z9 13
U1 1
U2 6
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 JUN 1
PY 2014
VL 20
IS 16
BP 2514
EP 2527
DI 10.1089/ars.2013.5223
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AG9SM
UT WOS:000335760000003
PM 24063605
ER
PT J
AU Ballen, KK
AF Ballen, Karen K.
TI The Optimal Donor Source for Acute Myeloid Leukemia: Do We Know the
Answer?
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Editorial Material
ID HEMATOPOIETIC-CELL TRANSPLANTATION; UMBILICAL-CORD BLOOD; UNRELATED
DONOR; GRAFT SOURCE
C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Zero Emerson,Suite 118, Boston, MA 02115 USA.
EM kballen@partners.org
NR 9
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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2014
VL 20
IS 6
BP 749
EP 749
DI 10.1016/j.bbmt.2014.04.002
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA AH8WH
UT WOS:000336418400001
PM 24727331
ER
PT J
AU Wood, WA
Lee, SJ
Brazauskas, R
Wang, ZW
Aljurf, MD
Ballen, KK
Buchbinder, DK
Dehn, J
Freytes, CO
Lazarus, HM
LeMaistre, CF
Mehta, P
Szwajcer, D
Joffe, S
Majhail, NS
AF Wood, William A.
Lee, Stephanie J.
Brazauskas, Ruta
Wang, Zhiwei
Aljurf, Mahmoud D.
Ballen, Karen K.
Buchbinder, David K.
Dehn, Jason
Freytes, Cesar O.
Lazarus, Hillard M.
LeMaistre, Charles F.
Mehta, Paulette
Szwajcer, David
Joffe, Steven
Majhail, Navneet S.
TI Survival Improvements in Adolescents and Young Adults after
Myeloablative Allogeneic Transplantation for Acute Lymphoblastic
Leukemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Adolescent and young adults; Hematopoietic cell transplantation;
Allogeneic; Survival
ID HEMATOPOIETIC-CELL TRANSPLANTATION; UNRELATED DONORS; 1ST REMISSION;
OUTCOMES; CHILDREN
AB Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. (C) 2014 American Society for Blood and Marrow Transplantation.
C1 [Wood, William A.] Univ N Carolina, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA.
[Lee, Stephanie J.] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Div Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Wang, Zhiwei] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia.
[Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Buchbinder, David K.] Childrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USA.
[Dehn, Jason] Natl Marrow Donor Program, Minneapolis, MN USA.
[Freytes, Cesar O.] South Texas Vet Hlth Care Syst, Hematopoiet Stem Cell Transplant Program, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA.
[LeMaistre, Charles F.] Sarah Cannon, Hematol & Bone Marrow Transplant, Nashville, TN USA.
[Mehta, Paulette] Univ Arkansas Med Sci, Dept Hematol & Oncol, Little Rock, AR 72205 USA.
[Szwajcer, David] Univ Manitoba, Sect Haematol Oncol, Dept Internal Med, Winnipeg, MB, Canada.
[Szwajcer, David] CancerCare Manitoba, Winnipeg, MB, Canada.
[Szwajcer, David] Univ Manitoba, Winnipeg, MB, Canada.
[Joffe, Steven] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
[Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Majhail, Navneet S.] Cleveland Clin, Blood & Marrow Transplant Program, Cleveland, OH 44195 USA.
RP Majhail, NS (reprint author), Cleveland Clin, Blood & Marrow Transplant Program, 9500 Euclid Ave R35, Cleveland, OH 44195 USA.
EM nmajhail@nmdp.org
OI Wood, William/0000-0001-7439-2543; Joffe, Steven/0000-0002-0667-7384
FU Public Health Service Grant/Cooperative Agreement from the National
Cancer Institute [U24-CA76518]; National Heart, Lung and Blood
Institute; National Institute of Allergy and Infectious Diseases;
National Heart, Lung and Blood Institute and National Cancer Institute
[5U01HL069294]; Health Resources and Services Administration
[HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704,
N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast
FX Financial disclosure: CIBMTR is supported by Public Health Service
Grant/Cooperative Agreement U24-CA76518 from the National Cancer
Institute, the National Heart, Lung and Blood Institute, and the
National Institute of Allergy and Infectious Diseases; a
Grant/Cooperative Agreement 5U01HL069294 from National Heart, Lung and
Blood Institute and National Cancer Institute; a contract
HHSH234200637015C with Health Resources and Services Administration;
grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval
Research; and grants from Allos, Inc., Amgen, Inc., and Angioblast;
anonymous donation to the Medical College of Wisconsin; Ariad; Be the
Match Foundation; Blue Cross and Blue Shield Association; Buchanan
Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH;
Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis
Pharma; The Leukemia & Lymphoma Society; The Medical College of
Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.;
Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor
Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.;
Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics;
Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord
Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS,
Inc.; and Wellpoint, Inc. The views expressed in this article do not
reflect the official policy or position of the National Institutes of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the US government.
NR 23
TC 4
Z9 4
U1 0
U2 0
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 JUN
PY 2014
VL 20
IS 6
BP 829
EP 836
DI 10.1016/j.bbmt.2014.02.021
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA AH8WH
UT WOS:000336418400015
PM 24607554
ER
PT J
AU Yanik, GA
Horowitz, MM
Weisdorf, DJ
Logan, BR
Ho, VT
Soiffer, RJ
Carter, SL
Wu, J
Wingard, JR
Difronzo, NL
Ferrara, JL
Giralt, S
Madtes, DK
Drexler, R
White, ES
Cooke, KR
AF Yanik, Gregory A.
Horowitz, Mary M.
Weisdorf, Daniel J.
Logan, Brent R.
Ho, Vincent T.
Soiffer, Robert J.
Carter, Shelly L.
Wu, Juan
Wingard, John R.
Difronzo, Nancy L.
Ferrara, James L.
Giralt, Sergio
Madtes, David K.
Drexler, Rebecca
White, Eric S.
Cooke, Kenneth R.
TI Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor
Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of
Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell
Transplantation: Blood and Marrow Transplant Clinical Trials Network
Protocol
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Bone marrow transplantation; IPS; TNF; Pneumonia; Pulmonary
ID LUNG INJURY; RISK
AB Idiopathic pneumonia syndromes (IPS) is a diffuse, noninfectious lung injury that occurs acutely after allogeneic hematopoietic cell transplantation (HCT). JPS-related mortality has been historically high (>50%) despite treatment with systemic corticosteroids and supportive care measures. We have now examined the role of tumor necrosis factor inhibition in a randomized, double-blind, placebo-controlled trial of corticosteroids with etanercept or placebo. Thirty-four subjects (>= 18 years) with IPS after HCT were randomized to receive methylprednisolone (2 mg/kg/day) plus etanercept (0.4 mg/kg twice weekly X 4 weeks; n = 16) or placebo (n = 18). No active infections and a pathogen-negative bronchoscopy were required at study entry. Response (alive, with complete discontinuation of supplemental oxygen support) and overall survival were examined. This study, originally planned to accrue 120 patients, was terminated prematurely due to slow accrual. In the limited number of patients examined, there were no differences in response rates at day 28 of study. Ten of 16 patients (62.5% [95%,confidence interval {CI}, 35.4% to 84.8%]) receiving etanercept and 12 of 18 patients (66.7% [95% CI, 41,0% to 86.7%]) receiving placebo met the day 28 response definition (P = 1.00). The median survival was 170 days (95% CI, 11 to 362) with etanercept versus 64 days (95% CI, 26 to 209) with placebo (P = .51). Among responders, the-median time to discontinuation of supplemental oxygen was 9 days (etanercept) versus 7 days (placebo). Therapy was well tolerated, With 1 toxicity-related death froth infectious pneumonia in the placebo arm. The treatment of IPS with corticosteroids in adult HCT recipients was associated with high early response rates (>60%) compared with historical reports, with poor overall survival. The addition of etanercept did not lead to further increases in response, although the sample size of this truncated trial preclude a definitive conclusion. (C) 2014 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Yanik, Gregory A.; Ferrara, James L.] Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, Dept Pediat & Internal Med, Ann Arbor, MI 48109 USA.
[Horowitz, Mary M.; Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Dept Internal Med, Blood & Marrow Transplantat Program, Minneapolis, MN USA.
[Ho, Vincent T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA.
[Carter, Shelly L.; Wu, Juan] EMMES Corp, Rockville, MD USA.
[Wingard, John R.] Univ Florida, Dept Med, Gainesville, FL USA.
[Difronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat, New York, NY 10021 USA.
[Madtes, David K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA.
[Madtes, David K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Drexler, Rebecca] Natl Marrow Donor Program, Minneapolis, MN USA.
[Drexler, Rebecca] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[White, Eric S.] Univ Michigan, Med Ctr, Dept Internal Med Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA.
RP Yanik, GA (reprint author), Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, 5310 Canc Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM gyanik@umich.edu
FU National Heart, Lung, and Blood Institute [U10HL069294]; Leukemia and
Lymphoma Society; Burroughs Welcome Fund; National Cancer Institute
FX Support for this study was provided by grant U10HL069294 from the
National Heart, Lung, and Blood Institute and the National Cancer
Institute, The Leukemia and Lymphoma Society (to K.R.C.), and the
Burroughs Welcome Fund (to K.R.C.). Immunex Corporation, a wholly owned
subsidiary of Amgen Inc., provided study drug and central pharmacy
support for the trial.
NR 17
TC 13
Z9 13
U1 0
U2 32
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 JUN
PY 2014
VL 20
IS 6
BP 858
EP 864
DI 10.1016/j.bbmt.2014.02.026
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA AH8WH
UT WOS:000336418400019
PM 24607553
ER
PT J
AU Neuhaus, V
Bot, A
Guitton, T
Ring, D
AF Neuhaus, V.
Bot, A.
Guitton, T.
Ring, D.
TI Influence of surgeon and patient factors on distal radius fracture
treatment
SO BRITISH JOURNAL OF SURGERY
LA English
DT Meeting Abstract
CT 101st Annual Congress of the Swiss-Society-of-Surgery
CY MAY 21-23, 2014
CL Berne, SWITZERLAND
SP Swiss Soc Surg
C1 [Neuhaus, V.] Univ Zurich Hosp, Div Trauma Surg, CH-8091 Zurich, Switzerland.
[Neuhaus, V.; Bot, A.; Guitton, T.; Ring, D.] Massachusetts Gen Hosp, Div Hand & Upper Extrem, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1323
EI 1365-2168
J9 BRIT J SURG
JI Br. J. Surg.
PD JUN
PY 2014
VL 101
SU 5
BP 12
EP 12
PG 1
WC Surgery
SC Surgery
GA AH2PM
UT WOS:000335963400038
ER
PT J
AU Pillai, AK
Iqbal, SI
Liu, RW
Rachamreddy, N
Kalva, SP
AF Pillai, Anil Kumar
Iqbal, Shams I.
Liu, Raymond W.
Rachamreddy, Niranjan
Kalva, Sanjeeva P.
TI Segmental Arterial Mediolysis
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
DE Segmental arterial mediolysis; Fibromuscular displasia; Vasculopathy
ID FOLLOW-UP; FIBROMUSCULAR DYSPLASIA; HEPATIC ARTERIES; EMBOLIZATION;
ANEURYSM
AB Segmental arterial mediolysis (SAM) is an uncommon, nonatherosclerotic, noninflammatory, large- to medium-sized arteriopathy first described in 1976. It is characterized histologically by vacuolization and lysis of the outer arterial media leading to dissecting aneurysms and vessel rupture presenting clinically with self-limiting abdominal pain or catastrophic hemorrhages in the abdomen. Patients of all ages are affected with a greater incidence at the fifth and sixth decades. There is a slight male predominance. Imaging findings overlap with inflammatory vasculitis, collagen vascular disease, and fibromuscular dysplasia. The presence of segmental dissections involving the celiac, mesenteric, and/or renal arteries is the key distinguishing features of SAM. Inflammatory markers, genetic tests for collagen vascular disorders, and hypercoagulable studies are negative. Anti-inflammatory agents and immunosuppressants are not effective. A mortality rate of 50 % has been attributed to the acute presentation with aneurysmal rupture necessitating urgent surgical or endovascular treatments; in the absence of the acute presentation, SAM is a self-limiting disease and is treated conservatively. There are no established guidelines on medical therapy, although optimal control of blood pressure is considered the main cornerstone of medical therapy. The long-term prognosis is not known.
C1 [Pillai, Anil Kumar; Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA.
[Iqbal, Shams I.] Lahey Clin Fdn, Dept Radiol, Burlington, MA USA.
[Liu, Raymond W.; Rachamreddy, Niranjan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Pillai, AK (reprint author), Univ Texas SW Med Ctr Dallas, Dept Radiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM anil.pillai@utsouthwestern.edu; rliu@partners.org
NR 25
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
EI 1432-086X
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD JUN
PY 2014
VL 37
IS 3
BP 604
EP 612
DI 10.1007/s00270-014-0859-4
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH7RM
UT WOS:000336331300005
PM 24554198
ER
PT J
AU Antman, EM
AF Antman, Elliott M.
TI Clinical Research and the Development of Medical Therapeutics
SO CIRCULATION JOURNAL
LA English
DT Review
DE Atrial fibrillation; Coagulation; Trials
ID NONVALVULAR ATRIAL-FIBRILLATION; PLURIPOTENT STEM-CELLS; FACTOR XA
INHIBITOR; ORAL ANTICOAGULANTS; NETWORK MEDICINE; WARFARIN; EDOXABAN;
THERAPY; METAANALYSIS; DISCOVERY
AB Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.
C1 [Antman, Elliott M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Antman, EM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA.
EM eantman@rics.bwh.harvard.edu
FU Daiichi Sankyo
FX Research grant from Daiichi Sankyo to Brigham and Women's Hospital (TIMI
Study Group) to conduct a phase 3 trial with edoxaban.
NR 28
TC 2
Z9 2
U1 1
U2 4
PU JAPANESE CIRCULATION SOC
PI TOYKO
PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO,
100-0011, JAPAN
SN 1346-9843
EI 1347-4820
J9 CIRC J
JI Circ. J.
PD JUN
PY 2014
VL 78
IS 6
BP 1267
EP 1271
DI 10.1253/circj.CJ-14-0459
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH8HM
UT WOS:000336378000001
PM 24837573
ER
PT J
AU DeAngelo, DJ
Chen, L
Guerin, A
Styles, A
Giguere-Duval, P
Wu, EQ
AF DeAngelo, Daniel J.
Chen, Lei
Guerin, Annie
Styles, Amy
Giguere-Duval, Philippe
Wu, Eric Q.
TI Impact of Timely Switching From Imatinib to a Second-Generation Tyrosine
Kinase Inhibitor After 12-Month Complete Cytogenetic Response Failure: A
Chart Review Analysis
SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
LA English
DT Review
DE Chart review; Chronic myelogenous leukemia; Dasatinib; Nilotinib;
Treatment response
ID CHRONIC MYELOID-LEUKEMIA; CYTARABINE; INTERFERON; RESISTANCE
AB In patients with chronic myelogenous leukemia in chronic phase (CML-CP), the achievement of a complete cytogenetic response (CCyR) at 1 year is associated with an improved overall survival, therefore, we assessed the outcomes of patients who switched therapy (n = 306) versus those who continued imatinib treatment (n = 287) after failure to achieve CCyR 1 year after imatinib initiation. We found a higher rate of CCyR among patients who switched therapy.
Introduction: In this study, cytogenetic response rate after timely switching to a second-generation tyrosine kinase inhibitor (TKI) was evaluated among patients with CML-CP, after failure to achieve CCyR 1 year after imatinib initiation. Patients and Methods: An online physician-administered medical chart review was used to retrospectively collect information from 108 US-based hematologists and oncologists on CML-CP patients who initiated imatinib as first-line therapy and failed to achieve CCyR at 12 months after imatinib initiation. Patients who switched to a second generation TKI within 3 months after the CCyR failure were defined as timely switchers, and those who continued taking imatinib for at least 3 months after the CCyR failure were defined as nonswitchers. CCyR achievement was compared between timely switchers and nonswitchers using multivariate Cox proportional hazard models. Results: Physicians provided information on 593 patients, with 306 defined as timely switchers and 287 defined as nonswitchers. Among the nonswitchers, 78 switched to a second-generation TKI at a later date. After adjusting for potential confounding factors, timely switchers had statistically significantly greater likelihood of achieving CCyR (hazard ratio, 1.80; P =.002) compared with nonswitchers. Conclusion: Timely switching from imatinib to a second-generation TKI after CCyR failure 1 year after imatinib initiation was associated with a greater likelihood of achieving CCyR compared with delaying the switch or not switching to a second-generation TKI. (C) 2014 Elsevier Inc. All rights reserved.
C1 [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chen, Lei] Novartis Pharmaceut, E Hanover, NJ USA.
[Guerin, Annie; Styles, Amy; Giguere-Duval, Philippe; Wu, Eric Q.] Anal Grp Inc, Montreal, PQ H3B 4W5, Canada.
RP Guerin, A (reprint author), Anal Grp Inc, 1000 Rue Gauchetiere Ouest,Bur 1200, Montreal, PQ H3B 4W5, Canada.
EM aguerin@analysisgroup.com
FU Novartis Pharmaceuticals Corporation
FX This research was sponsored by Novartis Pharmaceuticals Corporation,
which manufactures imatinib and nilotinib.
NR 16
TC 2
Z9 3
U1 0
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 2152-2650
EI 2152-2669
J9 CL LYMPH MYELOM LEUK
JI Clin. Lymphoma Myeloma Leuk.
PD JUN
PY 2014
VL 14
IS 3
BP 245
EP 251
DI 10.1016/j.clml.2013.12.002
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA AH5UC
UT WOS:000336195600010
PM 24393622
ER
PT J
AU Li, LT
Hicks, SC
Davila, JA
Kao, LS
Berger, RL
Arita, NA
Liang, MK
AF Li, L. T.
Hicks, S. C.
Davila, J. A.
Kao, L. S.
Berger, R. L.
Arita, N. A.
Liang, M. K.
TI Circular closure is associated with the lowest rate of surgical site
infection following stoma reversal: a systematic review and multiple
treatment meta-analysis
SO COLORECTAL DISEASE
LA English
DT Review
DE Ostomy; enterostomy; ileostomy; colostomy; takedown; wound
ID HEALTH-CARE INTERVENTIONS; LOOP ILEOSTOMY CLOSURE; ISPOR TASK-FORCE;
COLOSTOMY CLOSURE; COLORECTAL SURGERY; WOUND-INFECTION; METHODOLOGICAL
QUALITY; CONTROLLED-TRIALS; METAANALYSIS; COMPLICATIONS
AB Aim Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal.
Method We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed.
Results Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses.
Conclusion This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions.
C1 [Li, L. T.; Berger, R. L.; Arita, N. A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Boston, MA USA.
[Hicks, S. C.] Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA.
[Davila, J. A.] Univ Texas Hlth Sci Ctr Houston, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX 77030 USA.
[Kao, L. S.; Liang, M. K.] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA.
RP Li, LT (reprint author), 2450 Holcombe,Suite 01Y, Houston, TX 77021 USA.
EM Linday@bcm.edu
RI Liang, Mike/L-8493-2015;
OI Liang, Mike/0000-0001-7063-7291; Hicks, Stephanie/0000-0002-7858-0231
NR 39
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-8910
EI 1463-1318
J9 COLORECTAL DIS
JI Colorectal Dis.
PD JUN
PY 2014
VL 16
IS 6
BP 406
EP 416
DI 10.1111/codi.12556
PG 11
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA AH2GW
UT WOS:000335940500013
PM 24422861
ER
PT J
AU Tyler, KL
AF Tyler, Kenneth L.
TI Current developments in understanding of West Nile virus central nervous
system disease
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Review
DE acute flaccid paralysis; antiviral therapy; encephalitis; meningitis;
vaccine; West Nile virus
ID UNITED-STATES; T-CELLS; ANTIVIRAL RESPONSE; FLACCID PARALYSIS; CHIMERIC
VACCINE; IMMUNE-RESPONSE; INFECTION; ENCEPHALITIS; PATHOGENESIS;
OUTBREAK
AB Purpose of reviewWest Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18months related to the epidemiology, immunology, clinical features, and treatment of this disease.Recent findingsThere was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed.SummaryWNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure.
C1 [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA.
[Tyler, Kenneth L.] Eastern Colorado Healthcare Syst, Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Tyler, KL (reprint author), Univ Colorado, Sch Med, Dept Neurol, Mailstop B-182,12700 East 19th Ave, Aurora, CO 80045 USA.
EM ken.tyler@ucdenver.edu
OI Tyler, Kenneth/0000-0003-3294-5888
FU NINDS [1 R01 NS076512]; NIAID [1 R21 AI01064]; Department of Veterans
Affairs (MERIT) [BX000963]
FX K.L.T. is supported by grants from the NINDS (1 R01 NS076512), NIAID (1
R21 AI01064), and the Department of Veterans Affairs (MERIT Grant
BX000963).
NR 64
TC 7
Z9 7
U1 1
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1350-7540
EI 1473-6551
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD JUN
PY 2014
VL 27
IS 3
BP 342
EP 348
DI 10.1097/WCO.0000000000000088
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH2QQ
UT WOS:000335966500013
PM 24722324
ER
PT J
AU Schwartz, KA
Preer, G
McKeag, H
Newton, AW
AF Schwartz, Kimberly A.
Preer, Genevieve
McKeag, Heather
Newton, Alice W.
TI Child maltreatment: a review of key literature in 2013
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE abusive head trauma; child maltreatment; child neglect; child physical
abuse; child sexual abuse
ID ABUSIVE HEAD TRAUMA; HOME-VISITATION; PHYSICAL ABUSE; YOUNG-CHILDREN;
UNITED-STATES; SEXUAL-ABUSE; OUTCOMES; UPDATE; HEALTH; CARE
AB Purposes of reviewThis review summarizes new findings in the field of maltreatment, addressing epidemiology, physical abuse, abusive head trauma, sexual abuse, sequelae, and prevention.Recent findingsMany articles this year focus on establishing a framework for thinking about how to evaluate a child for maltreatment, the consequences of maltreatment, and the current understanding of prevention efforts. Interestingly, some research has helped to reinforce some concepts that were clinically appreciated, especially related to retinal hemorrhages.SummaryThe volume, quality, and breadth of research relating to child maltreatment continue to improve and expand our understanding of child abuse pediatrics. These authors summarize notable advances in our understanding of child maltreatment over the past year.
C1 [Schwartz, Kimberly A.] Boston Med Ctr, Dept Pediat, Child Protect Team, Boston, MA USA.
[Preer, Genevieve] Boston Med Ctr, Dept Pediat, Div Family Advocacy, Boston, MA USA.
[McKeag, Heather] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA.
[McKeag, Heather] Tufts Floating Hosp Children, Child Protect Program, Boston, MA USA.
[Newton, Alice W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Newton, Alice W.] Massachusetts Gen Hosp, Child Protect Program, Boston, MA 02114 USA.
RP Newton, AW (reprint author), Massachusetts Gen Hosp, Dept Pediat, Room 516,175 Cambridge St, Boston, MA 02114 USA.
EM anewton@partners.org
NR 47
TC 5
Z9 5
U1 5
U2 36
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8703
EI 1531-698X
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD JUN
PY 2014
VL 26
IS 3
BP 396
EP 404
DI 10.1097/MOP.0000000000000102
PG 9
WC Pediatrics
SC Pediatrics
GA AH2MY
UT WOS:000335956800020
PM 24786369
ER
PT J
AU Miller, PS
Evangelista, LS
Giger, JN
Martinez-Maza, O
Corvera-Tindel, T
Magpantay, L
Pena, G
Doering, LV
AF Miller, Pamela S.
Evangelista, Lorraine S.
Giger, Joyce Newman
Martinez-Maza, Otoniel
Corvera-Tindel, Teresita
Magpantay, Larry
Pena, Guadalupe
Doering, Lynn V.
TI Exhaustion, immuno-inflammation, and pathogen burden after cardiac
surgery: An exploratory study
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Article
DE vital exhaustion; inflammation; pathogen burden; Coronary heart disease;
herpesviruses; cytokines
ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; ANTIINFLAMMATORY CYTOKINE
INTERLEUKIN-10; BYPASS GRAFT-SURGERY; VITAL EXHAUSTION;
MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; SOCIOECONOMIC-STATUS;
ADHESION MOLECULES; ANGINA-PECTORIS
AB Background: Exhaustion, a consequence of prolonged stress characterized by unusual fatigue, is associated with increased risk of cardiac morbidity and mortality. In patients recovering from coronary artery bypass (CABG), little is known about the relationship of 1) immune-mediated inflammation and resultant endothelial activation, and 2) cumulative exposure to infectious pathogens (pathogen burden (PB)) implicated in coronary atherosclerosis to exhaustion. Aim: The aim of this exploratory study was to investigate the association of PB, inflammatory markers (interleukin (IL)-6, IL-10) and a marker of endothelial activation (soluble intercellular adhesion molecule-1 (sICAM-1)) to exhaustion. Methods: One to two months post-CABG, 42 individuals who met inclusion criteria were assessed for exhaustion using the Maastricht Interview for Vital Exhaustion. Serum IgG antibodies to herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus, Epstein Barr virus, and inflammatory and endothelial activation markers were measured by enzyme-linked immunosorbent assay. Pathogen burden was defined as the total number of seropositive exposures: low (0-1), moderate (2-3), and high (4). Results: Prevalence of exhaustion was 40.5%. Relative to non-exhausted patients, exhausted patients demonstrated a higher frequency of moderate PB (h=0.73, p=0.04) but lower frequency of high PB (h=1.05, p=0.03). Exhaustion showed a non-significant trend for positive correlations with IL-6 and sICAM-1 levels, and inverse relation to PB. In subgroup analysis, exhausted patients had stronger correlations with IL-6 and IL-6:IL-10 and a tendency towards higher serum IL-10 concentrations compared with their non-exhausted counterparts. Conclusion: This hypothesis-generating study provides preliminary evidence that elevated post-CABG exhaustion may be associated with PB, inflammation, and endothelial activation.
C1 [Miller, Pamela S.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA.
[Miller, Pamela S.; Giger, Joyce Newman; Corvera-Tindel, Teresita; Doering, Lynn V.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
[Evangelista, Lorraine S.] Univ Calif Irvine, Program Nursing Sci, Irvine, CA USA.
[Giger, Joyce Newman] Amer Univ Hlth Sci, Signal Hill, CA USA.
[Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Corvera-Tindel, Teresita] Vet Affairs Greater Los Angeles Hlth Care Syst, Nursing Res Dept, Los Angeles, CA USA.
[Magpantay, Larry; Pena, Guadalupe] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
RP Miller, PS (reprint author), Univ Calif San Francisco, Sch Nursing, 2 Koret Way,N411Y,Box 0606, San Francisco, CA 94143 USA.
EM Pamela.Miller@ucsf.edu
RI Martinez-Maza, Otoniel/B-2667-2009
OI Martinez-Maza, Otoniel/0000-0003-1364-0675
FU American Academy of Nurse Practitioners Foundation; Sigma Theta Tau
International; Veterans Affairs Pre-doctoral Nurse Fellowship; James B.
Pendleton Charitable Trust; McCarthy Family Foundation
FX This work was supported by grants from the American Academy of Nurse
Practitioners Foundation; Sigma Theta Tau International; and Veterans
Affairs Pre-doctoral Nurse Fellowship. This work was carried out in the
facilities of the UCLA AIDS Institute, which were supported, in part, by
funds from the James B. Pendleton Charitable Trust and the McCarthy
Family Foundation.
NR 45
TC 1
Z9 1
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1474-5151
EI 1873-1953
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD JUN
PY 2014
VL 13
IS 3
BP 211
EP 220
DI 10.1177/1474515113482805
PG 10
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA AG8RO
UT WOS:000335686100003
PM 23524631
ER
PT J
AU Kitaoka, T
Miyoshi, Y
Namba, N
Miura, K
Kubota, T
Ohata, Y
Fujiwara, M
Takagi, M
Hasegawa, T
Juppner, H
Ozono, K
AF Kitaoka, Taichi
Miyoshi, Yoko
Namba, Noriyuki
Miura, Kohji
Kubota, Takuo
Ohata, Yasuhisa
Fujiwara, Makoto
Takagi, Masaki
Hasegawa, Tomonobu
Jueppner, Harald
Ozono, Keiichi
TI Two Japanese familial cases of Caffey disease with and without the
common COL1A1 mutation and normal bone density, and review of the
literature
SO EUROPEAN JOURNAL OF PEDIATRICS
LA English
DT Article
DE Cortical bone; Hyperostosis; Type 1 collagen; Mutation; Bone mineral
density; Bone formation
ID INFANTILE CORTICAL HYPEROSTOSIS; HYPER-OSTOSIS; MR FINDINGS; SPECTRUM
AB Caffey disease, also known as infantile cortical hyperostosis, is a rare bone disease characterized by acute inflammation with swelling of soft tissues and hyperostosis of the outer cortical surface in early infancy. The common heterozygous mutation of the COL1A1 gene, p.Arg1014Cys, has been reported in patients with Caffey disease. However, its pathogenesis remains to be elucidated, and the reason for the incomplete penetrance and transient course of the disease is still unclear. In the present study, we performed mutation analysis of the COL1A1 and COL1A2 genes and measured bone mineral density in two Japanese familial cases of Caffey disease. The index case and two clinically healthy members of one family carry the common heterozygous mutation; in contrast, no mutation in COL1A1 or COL1A2 was identified in the affected members of the second family. In addition, we found normal bone mineral density in adult patients of both families who have had an episode of cortical hyperostosis regardless of the presence or absence of the common p.Arg1014Cys mutation. Conclusion: The results reveal that Caffey disease is genetically heterogeneous and that affected and unaffected adult patients with or without the common COL1A1 mutation have normal bone mineral density.
C1 [Kitaoka, Taichi; Miyoshi, Yoko; Namba, Noriyuki; Miura, Kohji; Kubota, Takuo; Ohata, Yasuhisa; Fujiwara, Makoto; Ozono, Keiichi] Osaka Univ, Grad Sch Med, Dept Pediat, Suita, Osaka 5650871, Japan.
[Takagi, Masaki; Hasegawa, Tomonobu] Keio Univ, Dept Pediat, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan.
[Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Pediat, Boston, MA 02114 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Med, Boston, MA 02114 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Pediat, Boston, MA 02114 USA.
[Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ozono, K (reprint author), Osaka Univ, Grad Sch Med, Dept Pediat, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan.
EM keioz@ped.med.osaka-u.ac.jp
FU Ministry of Health, Labour, and Welfare of Japan [KH20Q007a-1]
FX This study was supported in part by grants-in-aid from the Ministry of
Health, Labour, and Welfare (KH20Q007a-1) of Japan.
NR 22
TC 2
Z9 2
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6199
EI 1432-1076
J9 EUR J PEDIATR
JI Eur. J. Pediatr.
PD JUN
PY 2014
VL 173
IS 6
BP 799
EP 804
DI 10.1007/s00431-013-2252-8
PG 6
WC Pediatrics
SC Pediatrics
GA AH8ON
UT WOS:000336397500015
PM 24390061
ER
PT J
AU De Greef, D
Aernouts, J
Aerts, J
Cheng, JT
Horwitz, R
Rosowski, JJ
Dirckx, JJJ
AF De Greef, Daniel
Aernouts, Jef
Aerts, Johan
Cheng, Jeffrey Tao
Horwitz, Rachelle
Rosowski, John J.
Dirckx, Joris J. J.
TI Viscoelastic properties of the human tympanic membrane studied with
stroboscopic holography and finite element modeling
SO HEARING RESEARCH
LA English
DT Article
ID HUMAN MIDDLE-EAR; SOUND-TRANSMISSION; MOTION; SURFACE; TOMOGRAPHY;
EARDRUM; RABBIT; GERBIL
AB A new anatomically-accurate Finite Element (FE) model of the tympanic membrane (TM) and malleus was combined with measurements of the sound-induced motion of the TM surface and the bony manubrium, in an isolated TM-malleus preparation. Using the results, we were able to address two issues related to how sound is coupled to the ossicular chain: (i) Estimate the viscous damping within the tympanic membrane itself, the presence of which may help smooth the broadband response of a potentially highly resonant TM, and (ii) Investigate the function of a peculiar feature of human middle-ear anatomy, the thin mucosal epithelial fold that couples the mid part of the human manubrium to the TM. Sound induced motions of the surface of ex vivo human eardrums and mallei were measured with stroboscopic holography, which yields maps of the amplitude and phase of the displacement of the entire membrane surface at selected frequencies. The results of these measurements were similar, but not identical to measurements made in intact ears. The holography measurements were complemented by laser-Doppler vibrometer measurements of sound-induced umbo velocity, which were made with fine-frequency resolution. Comparisons of these measurements to predictions from a new anatomically accurate FE model with varied membrane characteristics suggest the TM contains viscous elements, which provide relatively low damping, and that the epithelial fold that connects the central section of the human manubrium to the TM only loosely couples the TM to the manubrium. The laser-Doppler measurements in two preparations also suggested the presence of significant variation in the complex modulus of the TM between specimens. (C) 2014 Elsevier B.V. All rights reserved.
C1 [De Greef, Daniel; Aernouts, Jef; Aerts, Johan; Dirckx, Joris J. J.] Univ Antwerp, Lab Biomed Phys, B-2020 Antwerp, Belgium.
[Aernouts, Jef; Cheng, Jeffrey Tao; Horwitz, Rachelle; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Aernouts, Jef; Cheng, Jeffrey Tao; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Horwitz, Rachelle; Rosowski, John J.] Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Boston, MA 02115 USA.
RP De Greef, D (reprint author), Univ Antwerp, Lab Biomed Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
EM daniel.degreef@uantwerpen.be
OI De Greef, Daniel/0000-0003-2631-4211
FU agency for Innovation by Science and Technology in Flanders
(IWT-Vlaanderen); Research Foundation Flanders (FWO); University of
Antwerp; US National Institute of Health
FX Financial support to this project was given by the agency for Innovation
by Science and Technology in Flanders (IWT-Vlaanderen), the Research
Foundation Flanders (FWO), the University of Antwerp and the US National
Institute of Health. We thank Mike Ravicz and Saumil Merchant for the
valuable discussions, Melissa McKinnon for her technical assistance.
NR 35
TC 16
Z9 16
U1 1
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
EI 1878-5891
J9 HEARING RES
JI Hear. Res.
PD JUN
PY 2014
VL 312
BP 69
EP 80
DI 10.1016/j.heares.2014.03.002
PG 12
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA AH8BD
UT WOS:000336358200008
PM 24657621
ER
PT J
AU Halko, MA
Connors, EC
Sanchez, J
Merabet, LB
AF Halko, Mark A.
Connors, Erin C.
Sanchez, Jaime
Merabet, Lotfi B.
TI Real World Navigation Independence in the Early Blind Correlates With
Differential Brain Activity Associated With Virtual Navigation
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE early blind; virtual environments; navigation; way finding; path
integration; posterior parietal cortex; temporal parietal junction
ID FUNCTIONAL MAGNETIC-RESONANCE; SPATIAL NAVIGATION; CAUDATE-NUCLEUS;
PLACE CELLS; ROUTE; ACTIVATION; CORTEX; HIPPOCAMPUS; COMPLEX; ABILITY
AB Navigating is a complex cognitive task that places high demands on spatial abilities, particularly in the absence of sight. Significant advances have been made in identifying the neural correlates associated with various aspects of this skill; however, how the brain is able to navigate in the absence of visual experience remains poorly understood. Furthermore, how neural network activity relates to the wide variability in navigational independence and skill in the blind population is also unknown. Using functional magnetic resonance imaging, we investigated the neural correlates of audio-based navigation within a large scale, indoor virtual environment in early profoundly blind participants with differing levels of spatial navigation independence (assessed by the Santa Barbara Sense of Direction scale). Performing path integration tasks in the virtual environment was associated with activation within areas of a core network implicated in navigation. Furthermore, we found a positive relationship between Santa Barbara Sense of Direction scores and activation within right temporal parietal junction during the planning and execution phases of the task. These findings suggest that differential navigational ability in the blind may be related to the utilization of different brain network structures. Further characterization of the factors that influence network activity may have important implications regarding how this skill is taught in the blind community. Hum Brain Mapp 35:2768-2778, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Halko, Mark A.] Harvard Univ, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Beth Israel Deaconess Med Ctr,Med Sch, Boston, MA 02114 USA.
[Connors, Erin C.; Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Visual Neuroplast,Dept Ophthalmol, Boston, MA 02114 USA.
[Sanchez, Jaime] Univ Chile, Dept Comp Sci, Santiago, Chile.
[Sanchez, Jaime] Univ Chile, CARE, Santiago, Chile.
RP Merabet, LB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA.
EM lotfi_merabet@meei.harvard.edu
OI Halko, Mark/0000-0002-7427-0789
FU NEI NIH HHS [R01 EY019924]
NR 57
TC 6
Z9 7
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD JUN
PY 2014
VL 35
IS 6
BP 2768
EP 2778
DI 10.1002/hbm.22365
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AF2PX
UT WOS:000334555100021
PM 24027192
ER
PT J
AU Falkner, B
Ingelfinger, J
AF Falkner, Bonita
Ingelfinger, Julie
TI Understanding the Power of Perinatal Events and Metabolic Status in
Childhood
SO HYPERTENSION
LA English
DT Editorial Material
ID BLOOD-PRESSURE; BIRTH-WEIGHT; DISEASE; GROWTH; RISK; LIFE
C1 [Falkner, Bonita] Thomas Jefferson Univ, Dept Med & Pediat, Philadelphia, PA 19107 USA.
[Ingelfinger, Julie] Massachusetts Gen Children, MassGen Hosp Children, Pediat Nephrol Unit, Boston, MA USA.
RP Falkner, B (reprint author), Thomas Jefferson Univ, Dept Med & Pediat, 833 Chestnut St,Suite 700, Philadelphia, PA 19107 USA.
EM bonita.falkner@jefferson.edu
NR 11
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2014
VL 63
IS 6
BP 1166
EP 1167
DI 10.1161/HYPERTENSIONAHA.114.03290
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG5XL
UT WOS:000335491900148
PM 24688124
ER
PT J
AU Raz, I
Scirica, BM
Braunwald, E
Mosenzon, O
Hirshberg, B
Wiviott, SD
Frederich, R
Davidson, J
Leiter, LA
Bhatt, DL
AF Raz, I
Scirica, B. M.
Braunwald, E.
Mosenzon, O.
Hirshberg, B.
Wiviott, S. D.
Frederich, R.
Davidson, J.
Leiter, L. A.
Bhatt, D. L.
TI SAXAGLIPTIN AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 35th Annual Scientific Meeting of the
High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual
Scientific Meeting of the Australian-Atherosclerosis-Society (AAS)
CY DEC 05-07, 2013
CL Melbourne, AUSTRALIA
SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc
C1 [Raz, I; Mosenzon, O.] Hadassah Univ Hosp, Dept Med, Diabet Unit, IL-91240 Jerusalem, Israel.
[Scirica, B. M.; Wiviott, S. D.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Scirica, B. M.; Braunwald, E.; Wiviott, S. D.; Bhatt, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Braunwald, E.; Bhatt, D. L.] VA Boston Healthcare Syst, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA USA.
[Hirshberg, B.] AstraZeneca Res & Dev, Wilmington, DE USA.
[Frederich, R.] Bristol Myers Squibb Co, Princeton, NJ USA.
[Davidson, J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA.
[Leiter, L. A.] Univ Toronto, St Michaels Hosp, Div Endocrinol & Metab, Keenan Res Ctr,Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2014
VL 63
IS 6
BP E167
EP E167
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG5XL
UT WOS:000335491900114
ER
PT J
AU Sullivan, D
Raal, F
Giugliano, RP
Koren, MJ
Roth, EM
Weiss, R
Kim, JB
Somaratne, RS
Yang, J
Liu, T
Albizem, M
Scott, R
Wasserman, SM
Stein, EA
AF Sullivan, D.
Raal, F.
Giugliano, R. P.
Koren, M. J.
Roth, E. M.
Weiss, R.
Kim, J. B.
Somaratne, R. S.
Yang, J.
Liu, T.
Albizem, M.
Scott, R.
Wasserman, S. M.
Stein, E. A.
TI EFFICACY AND SAFETY OF AMG 145, A FULLY HUMAN MONOCLONAL ANTIBODY TO
PCSK9: DATA FROM FOUR PHASE 2 STUDIES IN OVER 1200 PATIENTS
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 35th Annual Scientific Meeting of the
High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual
Scientific Meeting of the Australian-Atherosclerosis-Society (AAS)
CY DEC 05-07, 2013
CL Melbourne, AUSTRALIA
SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc
C1 [Sullivan, D.] Univ Witwatersrand, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa.
[Raal, F.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Giugliano, R. P.] Jacksonville Ctr Clin Res, Jacksonville, FL USA.
[Koren, M. J.] Royal Prince Alfred Hosp, Dept Clin Biochem, Camperdown, NSW 2050, Australia.
[Roth, E. M.] Sterling Res Grp, Cincinnati, OH USA.
[Weiss, R.] Maine Res Associates, Auburn, ME USA.
[Kim, J. B.; Somaratne, R. S.; Yang, J.; Liu, T.; Albizem, M.; Scott, R.; Wasserman, S. M.] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Stein, E. A.] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2014
VL 63
IS 6
BP E165
EP E166
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG5XL
UT WOS:000335491900108
ER
PT J
AU Hsiue, PP
Gregson, AL
Injean, P
Vangala, S
Brindis, RG
Shemin, RJ
Shahian, DM
Miller, LG
Shapiro, MF
Benharash, P
McKinnell, JA
AF Hsiue, Peter P.
Gregson, Aric L.
Injean, Patil
Vangala, Sitaram
Brindis, Ralph G.
Shemin, Richard J.
Shahian, David M.
Miller, Loren G.
Shapiro, Martin F.
Benharash, Peyman
McKinnell, James A.
TI Variation in Antibiotic Prophylaxis Selection for Coronary Artery Bypass
Graft Procedures in an Era of Increasing Methicillin-Resistant
Staphylococcus aureus Prevalence
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Letter
ID SURGICAL SITE INFECTION; CARDIAC-SURGERY; METAANALYSIS
C1 [Hsiue, Peter P.; Gregson, Aric L.; Injean, Patil; Vangala, Sitaram] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Dept Med, Los Angeles, CA 90095 USA.
[Brindis, Ralph G.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Shemin, Richard J.; Benharash, Peyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA.
[Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA.
[Miller, Loren G.; McKinnell, James A.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
[Shapiro, Martin F.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA.
RP McKinnell, JA (reprint author), Harbor UCLA Med Ctr, Infect Dis Clin Outcomes Res Unit, Div Infect Dis, Los Angeles Biomed Res Inst, 1124 West Carson St, Torrance, CA 90502 USA.
EM dr.mckinnell@yahoo.com
OI Gregson, Aric/0000-0001-6806-0868
FU NCATS NIH HHS [KL2TR000122, KL2 TR000122]; NHLBI NIH HHS [K23 HL102220,
5K23HL 102220-02]
NR 10
TC 1
Z9 1
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD JUN 1
PY 2014
VL 35
IS 6
BP 737
EP 740
DI 10.1086/676436
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA AG8UK
UT WOS:000335693500018
PM 24799655
ER
PT J
AU Villar, J
Kacmarek, RM
Guerin, C
AF Villar, Jesus
Kacmarek, Robert M.
Guerin, Claude
TI Clinical trials in patients with the acute respiratory distress
syndrome: Burn after reading
SO INTENSIVE CARE MEDICINE
LA English
DT Editorial Material
ID ACUTE LUNG INJURY; DEFINITION
C1 [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
[Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria 35010, Spain.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA.
[Guerin, Claude] Hop Croix Rousse, Serv Reanimat Med, F-69004 Lyon, France.
RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Barranco Ballena S-N,4th Floor,South Wing, Las Palmas Gran Canaria 35010, Spain.
EM jesus.villar54@gmail.com; rkacmarek@partners.org;
claude.guerin@chu-lyon.fr
NR 11
TC 10
Z9 10
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
EI 1432-1238
J9 INTENS CARE MED
JI Intensive Care Med.
PD JUN
PY 2014
VL 40
IS 6
BP 900
EP 902
DI 10.1007/s00134-014-3288-6
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6ZJ
UT WOS:000336281100020
PM 24718644
ER
PT J
AU Labarere, J
Renaud, B
Fine, MJ
AF Labarere, Jose
Renaud, Bertrand
Fine, Michael J.
TI Erratum to: How to derive and validate clinical prediction models for
use in intensive care medicine (vol 40, pg 513, 2014)
SO INTENSIVE CARE MEDICINE
LA English
DT Correction
C1 [Labarere, Jose] Univ Hosp, Qual Care Unit, F-38043 Grenoble, France.
[Labarere, Jose] Univ Grenoble 1, CNRS, TIMC, UMR 5525, Grenoble, France.
[Renaud, Bertrand] Cochin Hosp, AP HP, Emergency Dept, Paris, France.
[Renaud, Bertrand] Hop Hotel Dieu, AP HP, Emergency Dept, F-75181 Paris, France.
[Renaud, Bertrand] Fac Med Paris Descartes, Paris, France.
[Fine, Michael J.] VA Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equity & Res Promot, Pittsburgh, PA USA.
[Fine, Michael J.] Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Pittsburgh, PA USA.
[Labarere, Jose] UQEM, F-38043 Grenoble 9, France.
RP Labarere, J (reprint author), UQEM, Pavillon Taillefer,CHU BP217, F-38043 Grenoble 9, France.
EM JLabarere@chu-grenoble.fr
RI Labarere, Jose/N-1688-2014
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
EI 1432-1238
J9 INTENS CARE MED
JI Intensive Care Med.
PD JUN
PY 2014
VL 40
IS 6
BP 925
EP 925
DI 10.1007/s00134-014-3271-2
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6ZJ
UT WOS:000336281100033
ER
PT J
AU Hinds, O
Wighton, P
Tisdall, MD
Hess, A
Breiter, H
van der Kouwe, A
AF Hinds, Oliver
Wighton, Paul
Tisdall, M. Dylan
Hess, Aaron
Breiter, Hans
van der Kouwe, Andre
TI Neurofeedback Using Functional Spectroscopy
SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
LA English
DT Article
DE biofeedback; spectroscopy; fMRI
ID REAL-TIME FMRI; CORTEX; ACQUISITION; COMBINATION; DEPENDENCE; MOTION;
TESLA; EPI
AB Neurofeedback based on real-time measurement of the blood oxygenation level-dependent (BOLD) signal has potential for treatment of neurological disorders and behavioral enhancement. Commonly used methods are based on functional magnetic resonance imaging (fMRI) sequences that sacrifice speed and accuracy for whole-brain coverage, which is unnecessary in most applications. We present multivoxel functional spectroscopy (MVFS): a system for computing the BOLD signal from multiple volumes of interest (VOI) in real-time that improves speed and accuracy of neurofeedback. MVFS consists of a FS pulse sequence, a BOLD reconstruction component, a neural activation estimator, and a stimulus system. The FS pulse sequence is a single-voxel, magnetic resonance spectroscopy sequence without water suppression that has been extended to allow acquisition of a different VOI at each repetition and real-time subject head motion compensation. The BOLD reconstruction component determines the T2* decay rate, which is directly related to BOLD signal strength. The neural activation estimator discounts nuisance signals and scales the activation relative to the amount of ROI noise. Finally, the neurofeedback system presents neural activation-dependent stimuli to experimental subjects with an overall delay of less than 1 s. Here, we present the MVFS system, validation of certain components, examples of its usage in a practical application, and a direct comparison of FS and echo-planar imaging BOLD measurements. We conclude that in the context of realtime BOLD imaging, MVFS can provide superior accuracy and temporal resolution compared with standard fMRI methods. (c) 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 138-148, 2014
C1 [Hinds, Oliver] MIT, McGovern Inst Brain Res, Athinoula A Martinos Imaging Ctr, Cambridge, MA 02139 USA.
[Wighton, Paul; Tisdall, M. Dylan; van der Kouwe, Andre] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Charlestown, MA 02129 USA.
[Wighton, Paul; Tisdall, M. Dylan; van der Kouwe, Andre] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hess, Aaron] Univ Cape Town, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, Western Cape, South Africa.
[Breiter, Hans] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
[Breiter, Hans] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chigaco, IL USA.
RP Wighton, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Charlestown, MA 02129 USA.
EM pwighton@nmr.mgh.harvard.edu
OI Hess, Aaron/0000-0002-9289-5619
FU NIH [R33DA026104, R21MH096559, R01HD071664, P41RR014075, S10RR021110];
Ellison Medical Foundation
FX NIH grants (R33DA026104, R21MH096559, R01HD071664, P41RR014075,
S10RR021110 and the Ellison Medical Foundation)
NR 29
TC 0
Z9 0
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-9457
EI 1098-1098
J9 INT J IMAG SYST TECH
JI Int. J. Imaging Syst. Technol.
PD JUN
PY 2014
VL 24
IS 2
BP 138
EP 148
DI 10.1002/ima.22088
PG 11
WC Engineering, Electrical & Electronic; Optics; Imaging Science &
Photographic Technology
SC Engineering; Optics; Imaging Science & Photographic Technology
GA AG8JY
UT WOS:000335665900003
PM 24999293
ER
PT J
AU Sunpath, H
Winternheimer, P
Cohen, S
Tennant, I
Chelin, N
Gandhi, RT
Murphy, RA
AF Sunpath, H.
Winternheimer, P.
Cohen, S.
Tennant, I.
Chelin, N.
Gandhi, R. T.
Murphy, R. A.
TI Double-dose lopinavir-ritonavir in combination with rifampicin-based
anti-tuberculosis treatment in South Africa
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE second-line ART; toxicity; co-infection
ID HEALTHY-VOLUNTEERS; LOPINAVIR/RITONAVIR; THERAPY
AB BACKGROUND: The optimal treatment for tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients in resource-poor settings receiving lopinavir-ritonavir (LPV/r) based second-line antiretroviral therapy (ART) has yet to be determined. In South Africa, clinicians are advised to use 'double-dose' LPV/r dosed at 800 mg/200 mg twice daily during anti-tuberculosis treatment.
METHODOLOGY AND PRINCIPLE FINDINGS: We conducted a retrospective study of HIV-infected patients who received >= 2 months of double-dose LPV/r-based ART during concomitant rifampicin-containing anti-tuberculosis treatment. We used standard definitions for TB and HIV outcomes; virological failure was defined as a viral load >1000 copies/ml. During co-administration, gastro-intestinal toxicity occurred in 9/25 (36%) patients, a symptomatic rise in aspartate aminotransferase or alanine aminotransferase of any grade was noted in 3 (12%), with two Grade 3 events, and 3 (12%) patients required treatment discontinuation. Outcomes were favourable, with 20/25 (80%) patients achieving TB treatment success and virological failure observed among 3 (12%) patients during co-administration.
CONCLUSION: We found the use of double-dose LPV/r during simultaneous standard anti-tuberculosis treatment to be an effective and reasonably well tolerated interim strategy.
C1 [Sunpath, H.; Chelin, N.] McCord Hosp, Durban, South Africa.
[Sunpath, H.; Winternheimer, P.] St Vincent Hosp, Indianapolis, IN USA.
[Cohen, S.] NYU, Sch Med, Dept Med, New York, NY USA.
[Tennant, I.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Gandhi, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gandhi, R. T.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
[Murphy, R. A.] Albert Einstein Coll Med, New York, NY USA.
[Murphy, R. A.] Doctors Borders, New York, NY USA.
RP Sunpath, H (reprint author), McCord Hosp, Durban, South Africa.
EM henrysunpath@yebo.co.za
FU Global Health Development, New York University School of Medicine, New
York, NY, USA
FX Funding for SC was provided by the Global Health Development, New York
University School of Medicine, New York, NY, USA.
NR 13
TC 3
Z9 3
U1 0
U2 3
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JUN
PY 2014
VL 18
IS 6
BP 689
EP 693
DI 10.5588/ijtld.13.0492
PG 5
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA AH5VH
UT WOS:000336198700013
PM 24903940
ER
PT J
AU Shipherd, JC
Clum, G
Suvak, M
Resick, PA
AF Shipherd, Jillian C.
Clum, Gretchen
Suvak, Michael
Resick, Patricia A.
TI Treatment-related reductions in PTSD and changes in physical health
symptoms in women
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Health; Cognitive behavioral therapy; Health habits; Allostatic load;
Posttraumatic stress disorder
ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; PROLONGED
EXPOSURE THERAPY; SELF-REPORTED HEALTH; QUALITY-OF-LIFE; CHRONIC PAIN;
ALLOSTATIC LOAD; PRIMARY-CARE; INTERPERSONAL VIOLENCE; SEXUAL-HARASSMENT
AB This study examined the relationship between change in posttraumatic stress disorder (PTSD) symptoms over the course of PTSD treatment and the association with changes in general physical health symptoms. Both positive health habits (e.g., exercise) and negative (e.g., smoking), were examined to determine if they accounted for the association between changes in PTSD severity over time and changes in physical health. Participants were 150 women seeking treatment for PTSD. Latent growth curve modeling indicated a substantial relationship (R (2) = 34 %) between changes in PTSD and changes in physical health that occurred during and shortly following treatment for PTSD. However, there was no evidence to suggest that changes in health behaviors accounted for this relationship. Thus, PTSD treatment can have beneficial effects on self-reported physical health symptoms, even without direct treatment focus on health per se, and is not accounted for by shifts in health behavior.
C1 [Shipherd, Jillian C.; Suvak, Michael; Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, Boston, MA 02130 USA.
[Shipherd, Jillian C.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA.
[Clum, Gretchen] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70112 USA.
[Suvak, Michael] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA.
RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA.
EM Jillian.Shipherd@va.gov; gclum@tulane.edu; msuvak@suffolk.edu;
Patricia.Resick@va.gov
FU NIMH NIH HHS [R01 MH051509, 2-R01-MH51509]
NR 65
TC 3
Z9 3
U1 7
U2 25
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
EI 1573-3521
J9 J BEHAV MED
JI J. Behav. Med.
PD JUN
PY 2014
VL 37
IS 3
BP 423
EP 433
DI 10.1007/s10865-013-9500-2
PG 11
WC Psychology, Clinical
SC Psychology
GA AH7SE
UT WOS:000336333300007
PM 23471544
ER
PT J
AU Carper, MM
Traeger, L
Gonzalez, JS
Wexler, DJ
Psaros, C
Safren, SA
AF Carper, Matthew M.
Traeger, Lara
Gonzalez, Jeffrey S.
Wexler, Deborah J.
Psaros, Christina
Safren, Steven A.
TI The differential associations of depression and diabetes distress with
quality of life domains in type 2 diabetes
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Diabetes; T2DM; Quality of life; QOLI; Depression; Diabetes distress
ID GLYCEMIC CONTROL; METAANALYSIS; ADULTS; SCALE; SATISFACTION;
INSTRUMENTS; MORTALITY; SYMPTOMS; MELLITUS
AB The present investigation aimed to understand quality of life domains relevant to adults with type 2 diabetes mellitus (T2DM), and the relative associations of depression and diabetes distress with these domains. Participants were 146 individuals with T2DM who were recruited for entry into a randomized controlled trial of cognitive behavioral therapy for adherence and depression. We conducted an exploratory factor analysis on the Quality of Life Inventory (QOLI) to establish domains of quality of life relevant to this patient population. Hierarchical multiple regression models were evaluated for each domain that emerged to determine independent associations of depression severity and diabetes distress with quality of life independent of demographic and illness factors. Results suggested four quality of life domains: achievement, psychosocial growth, interpersonal relationships, and environment, accounting for 60.1 % of variance in total QOLI scores. Depression severity was associated with poorer quality of life on the achievement, psychosocial growth, and environment domains (p's < 0.01), while diabetes distress was associated with poorer quality of life on the achievement (p < 0.001) domain and marginally associated with quality of life on the psychosocial growth (p < 0.10) domain. Interventions designed to address both depression and diabetes distress may lead to better quality of life outcomes than a generalized depression intervention or an intervention for diabetes alone.
C1 [Carper, Matthew M.; Traeger, Lara; Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA.
[Traeger, Lara; Wexler, Deborah J.; Psaros, Christina; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10461 USA.
[Wexler, Deborah J.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA.
[Carper, Matthew M.] Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, Philadelphia, PA 19122 USA.
RP Carper, MM (reprint author), Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, 1701 N 13th St, Philadelphia, PA 19122 USA.
EM matthew.carper@temple.edu
OI Carper, Matthew/0000-0001-7125-9851
FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758]; NIDDK NIH HHS [P30 DK020541,
P60 DK020541, DK 020541]; NIMH NIH HHS [R01MH078571, K24 MH094214, R01
MH078571]
NR 34
TC 9
Z9 10
U1 3
U2 23
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
EI 1573-3521
J9 J BEHAV MED
JI J. Behav. Med.
PD JUN
PY 2014
VL 37
IS 3
BP 501
EP 510
DI 10.1007/s10865-013-9505-x
PG 10
WC Psychology, Clinical
SC Psychology
GA AH7SE
UT WOS:000336333300014
PM 23515932
ER
PT J
AU Yu, EW
Kumbhani, R
Siwila-Sackman, E
DeLelys, M
Preffer, FI
Leder, BZ
Wu, JY
AF Yu, Elaine W.
Kumbhani, Ruchit
Siwila-Sackman, Erica
DeLelys, Michelle
Preffer, Frederic I.
Leder, Benjamin Z.
Wu, Joy Y.
TI Teriparatide ( PTH1-34) Treatment Increases Peripheral Hematopoietic
Stem Cells in Postmenopausal Women
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE HEMATOPOIETIC STEM CELL NICHE; PARATHYROID HORMONE; TERIPARATIDE; B CELL
LYMPHOPOIESIS
ID PARATHYROID-HORMONE; BONE-MARROW; PROGENITOR CELLS; LINING CELLS; NICHE;
OSTEOCYTES; TRIAL; MICE; MOBILIZATION; OSTEOBLASTS
AB Cells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B-cell development in animal models, perhaps via parathyroid hormone (PTH)-dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women. Twenty-three postmenopausal women at high risk of fracture received teriparatide 20 mcg sc daily for 24 months as part of a prospective longitudinal trial. Whole blood measurements were obtained at baseline, 3, 6, 12, and 18 months. Flow cytometry was performed to identify hematopoietic subpopulations, including HSCs (CD34+/CD45(moderate); ISHAGE protocol) and early transitional B cells (CD19+, CD27-, IgD+, CD24[hi], CD38[hi]). Serial measurements of spine and hip bone mineral density (BMD) as well as serum P1NP, osteocalcin, and CTX were also performed. The average age of study subjects was 64 +/- 5 years. We found that teriparatide treatment led to an early increase in circulating HSC number of 40%+/- 14% (p=0.004) by month 3, which persisted to month 18 before returning to near baseline by 24 months. There were no significant changes in transitional B cells or total B cells over the course of the study period. In addition, there were no differences in complete blood count profiles as quantified by standard automated flow cytometry. Interestingly, the peak increase in HSC number was inversely associated with increases in bone markers and spine BMD. Daily teriparatide treatment for osteoporosis increases circulating HSCs by 3 to 6 months in postmenopausal women. This may represent a proliferation of marrow HSCs or increased peripheral HSC mobilization. This clinical study establishes the importance of PTH in the regulation of the HSC niche within humans. (c) 2014 American Society for Bone and Mineral Research.
C1 [Yu, Elaine W.; Kumbhani, Ruchit; Siwila-Sackman, Erica; Leder, Benjamin Z.; Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[DeLelys, Michelle; Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Wu, Joy Y.] Stanford Univ, Sch Med, Div Endocrinol, Stanford, CA 94305 USA.
RP Wu, JY (reprint author), 300 Pasteur Dr,S-025, Stanford, CA 94305 USA.
EM bzleder@partners.org; jywu1@stanford.edu
FU NIH [AR54741, OD008466, AR61228]; Amgen Inc.; Eli Lilly Co.
FX We thank Dr Henry Kronenberg for his helpful discussion and critical
review of the manuscript. This work was supported by NIH grants AR54741
and OD008466 (to JYW) and AR61228, and funding support from Amgen Inc.
and Eli Lilly Co. The clinical trial registration number is NCT00926380.
NR 28
TC 6
Z9 6
U1 0
U2 3
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 JUN
PY 2014
VL 29
IS 6
BP 1380
EP 1386
DI 10.1002/jbmr.2171
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AH3DJ
UT WOS:000336001500010
PM 24420643
ER
PT J
AU Bianchi, MT
Westover, MB
AF Bianchi, Matt T.
Westover, Michael Brandon
TI Insomnia and Morning Motor Vehicle Accidents A Decision Analysis of the
Risk of Hypnotics Versus the Risk of Untreated Insomnia
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Letter
ID DRIVING IMPAIRMENT; BENZODIAZEPINES; ALCOHOL; IMPACT
C1 [Bianchi, Matt T.; Westover, Michael Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM mtbianchi@partners.org
NR 17
TC 0
Z9 0
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD JUN
PY 2014
VL 34
IS 3
BP 400
EP 402
DI 10.1097/JCP.0000000000000134
PG 3
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA AH3AR
UT WOS:000335994100034
PM 24743722
ER
PT J
AU Siddiqui, A
Nagy, PG
Bonekamp, D
Dreyer, KJ
AF Siddiqui, Adeel
Nagy, Paul G.
Bonekamp, David
Dreyer, Keith J.
TI Changes to Stage 1 Meaningful Use in 2014: Impact on Radiologists
SO JOURNAL OF DIGITAL IMAGING
LA English
DT Article
DE Meaningful Use; Stage 2; 2014 Base EHR; Certified electronic health
record; Complete EHR; Electronic health records; Meaningful Use in
radiology
AB The goal of this work is to provide radiologists an update regarding changes to stage 1 of meaningful use in 2014. These changes were promulgated in the final rulemaking released by the Centers for Medicare and Medicaid Services and the Office of the National Coordinator for Health Information Technology in September 2012. Under the new rules, radiologists are exempt from meaningful use penalties provided that they are listed as radiologists under the Provider Enrollment, Chain and Ownership System (PECOS). A major caveat is that this exemption can be removed at any time. Additional concerns are discussed in the main text. Additional changes discussed include software editions independent of meaningful use stage (i.e., 2011 edition versus 2014 edition), changes to the definition of certified electronic health record technology (CEHRT), and changes to specific measures and exemptions to those measures. The new changes regarding stage 1 add complexity to an already complex program, but overall make achieving meaningful use a win-win situation for radiologists. There are no penalties for failure and incentive payments for success. The cost of upgrading to CEHRT may be much less than the incentive payments, adding a potential new source of revenue. Additional benefits may be realized if the radiology department can build upon a modern electronic health record to improve their practice and billing patterns. Meaningful use and electronic health records represent an important evolutionary step in US healthcare, and it is imperative that radiologists are active participants in the process.
C1 [Siddiqui, Adeel] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Nagy, Paul G.; Bonekamp, David; Dreyer, Keith J.] Johns Hopkins Univ, Russell H Morgan Dept Radiol, Ellicott City, MD USA.
[Dreyer, Keith J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Siddiqui, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
EM adeelsiddiquimd@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0897-1889
EI 1618-727X
J9 J DIGIT IMAGING
JI J. Digit. Imaging
PD JUN
PY 2014
VL 27
IS 3
BP 292
EP 296
DI 10.1007/s10278-014-9673-4
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH8PN
UT WOS:000336400300002
PM 24682743
ER
PT J
AU Underhill, ML
Crotser, CB
AF Underhill, Meghan L.
Crotser, Cheryl B.
TI Seeking Balance: Decision Support Needs of Women Without Cancer and a
Deleterious BRCA1 or BRCA2 Mutation
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Article
DE Decision support; Hereditary breast and ovarian cancer syndrome; Patient
centered care
ID RANDOMIZED-TRIAL; BREAST-CANCER; HEREDITARY BREAST; RISK-ASSESSMENT;
CARRIERS; AID; OOPHORECTOMY; INTERVENTION; PERSPECTIVES; MASTECTOMY
AB Recommendations for women with a deleterious BRCA1 or BRCA2 gene mutation include complex medical approaches related to cancer risk reduction and detection. Current science has not yet fully elucidated decision support needs that women face when living with medical consequences associated with known hereditary cancer risk. The purpose of this study was to describe health communication and decision support needs in healthy women with BRCA1/2 gene mutations. The original researchers completed an interpretive secondary qualitative data analysis of 23 phenomenological narratives collected between 2008 and 2010. The Ottawa Decision Support and Patient Centered Communication frameworks guided the study design and analysis. Women described a pattern wherein breast and ovarian cancer risk, health related recommendations and decisions, and personal values were prioritized over time based on life contexts. Knowing versus acting on cancer risk was not a static process but an ongoing balancing act of considering current and future personal and medical values, further compounded by the complexity of recommendations. Women shared stories of anticipatory, physical and psychosocial consequences of the decision making experience. The findings have potential to generate future research questions and guide intervention development. Importantly, findings indicate a need for ongoing, long-term, support from genetics professionals and decision support interventions, which challenges the current practice paradigm.
C1 [Underhill, Meghan L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA.
[Crotser, Cheryl B.] Roberts Wesleyan Coll, Sch Nursing, Rochester, NY USA.
RP Underhill, ML (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, 450 Brookline Ave,L522, Boston, MA 02115 USA.
EM meghanl_underhill@dfci.harvard.edu
FU National Cancer Institute through University of Massachusetts Boston
[NCIU54CA156732]; National Cancer Institute through Dana Farber Cancer
Institute; National Cancer Institute through Phyllis F. Cantor Center
FX Funding for Dr. Underhill to complete data analysis was provided by the
National Cancer Institute Cancer & Health Disparities Fellowship Funding
(NCIU54CA156732) through the University of Massachusetts Boston and Dana
Farber Cancer Institute and through the Phyllis F. Cantor Center. Dr.
Cheryl Crotser is the Charles S. Gallaher Chair for in the Department of
Nursing at Roberts Wesleyan College.
NR 36
TC 1
Z9 2
U1 2
U2 6
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 JUN
PY 2014
VL 23
IS 3
BP 350
EP 362
DI 10.1007/s10897-013-9667-2
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA AH7SQ
UT WOS:000336334600008
PM 24271037
ER
PT J
AU Mills, R
Barry, W
Haga, SB
AF Mills, Rachel
Barry, William
Haga, Susanne B.
TI Public Trust in Genomic Risk Assessment for Type 2 Diabetes Mellitus
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Article
DE Genetic counseling; Genomic testing; Type 2 diabetes; Patient trust;
Personalized medicine
ID BREAST-CANCER SUSCEPTIBILITY; RANDOMIZED CONTROLLED-TRIAL; ONLINE HEALTH
INFORMATION; NATIONAL TRENDS SURVEY; ETHNIC DISPARITIES;
AFRICAN-AMERICANS; BEHAVIORAL-RESPONSE; RACIAL-DIFFERENCES; GENETICS
SERVICES; CARE PROVIDERS
AB Patient trust in personal medical information is critical to increasing adherence to physician recommendations and medications. One of the anticipated benefits of learning of one's genomic risk for common diseases is the increased adoption of screening, preventive care and lifestyle changes. However, the equivocal results thus far reported of the positive impact of knowledge of genomic risk on behavior change may be due to lack of patients' trust in the results. As part of a clinical study to compare two methods of communication of genomic risk results for Type 2 diabetes mellitus (T2DM), we assessed patients' trust and preferred methods of delivery of genomic risk information. A total of 300 participants recruited from the general public in Durham, NC were randomized to receive their genomic risk for T2DM in-person from a genetic counselor or online through the testing company's web-site. Participants completed a baseline survey and three follow-up surveys after receiving results. Overall, participants reported high levels of trust in the test results. Participants who received their results in-person from the genetic counselor were significantly more likely to trust their results than those who reviewed their results on-line (p = 0.005). There was not a statistically significant difference in levels of trust among participants with increased genetic risk, as compared to other those with decreased or same as population risk (p = 0.1154). In the event they undergo genomic risk testing again, 55 % of participants overall indicated they would prefer to receive their results online compared to 28 % that would prefer to receive future results in-person. Of those participants preferring to receive results online, 77 % indicated they would prefer to have the option to speak to someone if they had questions with the online results (compared to accessing results online without the option of professional consultation). This is the first study to assess satisfaction with genomic risk testing by the method of delivery of the test result. The higher rate of trust in results delivered in-person suggests that online access reports may not result in serious consideration of results and lack of adoption of recommended preventive recommendations.
C1 [Mills, Rachel; Haga, Susanne B.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27708 USA.
[Barry, William] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Mills, R (reprint author), Duke Univ, Duke Inst Genome Sci & Policy, 304 Res Dr,Box 90141, Durham, NC 27708 USA.
EM r.mills@duke.edu
OI Mills, Rachel/0000-0003-4420-9503
FU U.S. National Institutes of Health [1R21HL096573-01A1]
FX This work was funded by the U.S. National Institutes of Health
(1R21HL096573-01A1) and was partially presented as a poster presentation
at the 2012 National Society of Genetic Counselors Annual Education
Conference. We are grateful for the statistical support provided by Dr.
Sunil Suchindran. Disclosures: R.M provides contracting services for the
laboratory testing company GeneDx. W. B. declares no conflict of
interest. S. B. H. serves as a consultant to the Inova Translational
Medicine Institute of Inova Health Care Services (non-profit).
NR 72
TC 0
Z9 0
U1 2
U2 10
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 JUN
PY 2014
VL 23
IS 3
BP 401
EP 408
DI 10.1007/s10897-013-9674-3
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AH7SQ
UT WOS:000336334600012
PM 24292896
ER
PT J
AU Goveas, JS
Espeland, MA
Hogan, PE
Tindle, HA
Shih, RA
Kotchen, JM
Robinson, JG
Barnes, DE
Resnick, SM
AF Goveas, Joseph S.
Espeland, Mark A.
Hogan, Patricia E.
Tindle, Hilary A.
Shih, Regina A.
Kotchen, Jane M.
Robinson, Jennifer G.
Barnes, Deborah E.
Resnick, Susan M.
TI Depressive Symptoms and Longitudinal Changes in Cognition: Women's
Health Initiative Study of Cognitive Aging
SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY
LA English
DT Article
DE depression; cognitive decline; vascular risk factors; cardiovascular
disease; women; dementia; depressive symptoms
ID LATE-LIFE DEPRESSION; APOLIPOPROTEIN-E GENOTYPE; PRIMARY-CARE PATIENTS;
GERIATRIC DEPRESSION; VASCULAR DEPRESSION; POSTMENOPAUSAL WOMEN;
ALZHEIMER-DISEASE; IMPAIRMENT; DEMENTIA; RISK
AB Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N = 204) and without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline.
C1 [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Espeland, Mark A.; Hogan, Patricia E.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Tindle, Hilary A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Shih, Regina A.] RAND Corp, Arlington, VA USA.
[Kotchen, Jane M.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Kotchen, Jane M.] Med Coll Wisconsin, Clin & Translat Sci Inst, Milwaukee, WI 53226 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat & Epidemiol, San Francisco, CA 94143 USA.
[Barnes, Deborah E.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Barnes, Deborah E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM jgoveas@mcw.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services [N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, 44221]; Department of Health and Human Services;
National Institute on Aging [NO1-AG-1-2106]; Intramural Research
Program, National Institute on Aging; National Institutes of Health;
Alzheimer's Association [NIRG-11-204070]; Extendicare Foundation; Brain
& Behavior Research Foundation (NARSAD); Wyeth Pharmaceuticals; Brain
and Behavior Research Foundation (previously NARSAD) young investigator
award
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: The
Women's Health Initiative (WHI) program is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, US Department
of Health and Human Services through contracts N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. The WHI Study of Cognitive Aging (WHISCA)
was supported by the Department of Health and Human Services and the
National Institute on Aging (NO1-AG-1-2106). SMR is supported by the
Intramural Research Program, National Institute on Aging, and National
Institutes of Health. JSG is supported by the Alzheimer's Association
New Investigator NIRG-11-204070 and Extendicare Foundation, and
previously by Brain & Behavior Research Foundation (NARSAD) young
investigator, and Research for a Healthier Tomorrow, a Component of the
Advancing a Healthier Wisconsin Endowment at MCW. The Women's Health
Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as
an ancillary study to the WHI. DB's contributions were supported in part
by Brain and Behavior Research Foundation (previously NARSAD) young
investigator award.
NR 46
TC 11
Z9 11
U1 3
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0891-9887
EI 1552-5708
J9 J GERIATR PSYCH NEUR
JI J. Geriatr. Psychiatry Neurol.
PD JUN
PY 2014
VL 27
IS 2
BP 94
EP 102
DI 10.1177/0891988714522697
PG 9
WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry
SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry
GA AH6DG
UT WOS:000336220300004
PM 24584465
ER
PT J
AU Hay, RJ
Johns, NE
Williams, HC
Bolliger, IW
Dellavalle, RP
Margolis, DJ
Marks, R
Naldi, L
Weinstock, MA
Wulf, SK
Michaud, C
Murray, CJL
Naghavi, M
AF Hay, Roderick J.
Johns, Nicole E.
Williams, Hywel C.
Bolliger, Ian W.
Dellavalle, Robert P.
Margolis, David J.
Marks, Robin
Naldi, Luigi
Weinstock, Martin A.
Wulf, Sarah K.
Michaud, Catherine
Murray, Christopher J. L.
Naghavi, Mohsen
TI The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence
and Impact of Skin Conditions
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID SYSTEMATIC ANALYSIS; DISABILITY WEIGHTS; COMMUNITY; SCABIES; ECZEMA;
DERMATOLOGY; ETHIOPIA; CRITERIA
AB The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.
C1 [Hay, Roderick J.] Int Fdn Dermatol, London W1T 5HQ, England.
[Johns, Nicole E.; Bolliger, Ian W.; Wulf, Sarah K.; Murray, Christopher J. L.; Naghavi, Mohsen] Univ Washington, Inst Hlth Metr & Evaluat, Washington, DC USA.
[Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England.
[Dellavalle, Robert P.] Denver VA Med Ctr, Dermatol Serv, Denver, CO USA.
[Margolis, David J.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Margolis, David J.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Marks, Robin] Skin & Canc Fdn, Melbourne, Vic, Australia.
[Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Dept Dermatol, Bergamo, Italy.
[Weinstock, Martin A.] Brown Univ, Div Dermatoepidemiol, Providence, RI 02912 USA.
[Michaud, Catherine] China Med Board, Cambridge, MA USA.
RP Hay, RJ (reprint author), Int Fdn Dermatol, 4 Fitzroy Sq, London W1T 5HQ, England.
EM roderick.hay@ifd.org
RI Bolliger, Ian/C-4207-2016; Naldi, Luigi/K-6343-2016;
OI Bolliger, Ian/0000-0001-8055-297X; Naldi, Luigi/0000-0002-3160-2835;
Johns, Nicole/0000-0003-4513-4582
NR 29
TC 109
Z9 111
U1 46
U2 88
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2014
VL 134
IS 6
BP 1527
EP 1534
DI 10.1038/jid.2013.446
PG 8
WC Dermatology
SC Dermatology
GA AH5TJ
UT WOS:000336193700010
PM 24166134
ER
PT J
AU Ginat, DT
Swearingen, B
Curry, W
Cahill, D
Madsen, J
Schaefer, PW
AF Ginat, Daniel Thomas
Swearingen, Brooke
Curry, William
Cahill, Daniel
Madsen, Joseph
Schaefer, Pamela W.
TI 3 Tesla Intraoperative MRI for Brain Tumor Surgery
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Review
DE 3T; intraoperative MRI; glioma; pituitary tumor; laser ablation
ID LOW-GRADE GLIOMA; TRANSSPHENOIDAL PITUITARY SURGERY;
GLIOBLASTOMA-MULTIFORME; PRELIMINARY EXPERIENCE; INTERVENTIONAL MRI;
CLINICAL ARTICLE; IMAGING GUIDANCE; RESECTION; EXTENT; SURVIVAL
AB Implementation of intraoperative magnetic resonance imaging (iMRI) has been shown to optimize the extent of resection and safety of brain tumor surgery. In addition, iMRI can help account for the phenomenon of brain shift and can help to detect complications earlier than routine postoperative imaging, which can potentially improve patient outcome. The higher signal-to-noise ratio offered by 3 Tesla (T) iMRI compared with lower field strength systems is particularly advantageous. The purpose of this article is to review the imaging protocols, imaging findings, and technical considerations related to 3T iMRI. To maximize efficiency, iMRI sequences can be tailored to particular types of tumors and procedures, including nonenhancing brain tumor surgery, enhancing brain tumor surgery, transsphenoidal pituitary tumor surgery, and laser ablation. Unique imaging findings on iMRI include the presence of surgically induced enhancement, which can be a potential confounder for residual enhancing tumor, and hyperacute hemorrhage, which tends to have intermediate signal on T1-weighted sequences and high signal on T2-weighted sequences due to the presence of oxyhemoglobin. MR compatibility and radiofrequency shielding pose particularly stringent technical constraints at 3T and influence the design and usage of the surgical suite with iMRI. J. Magn. Reson. Imaging 2014;39:1357-1365. (c) 2013 Wiley Periodicals, Inc.
C1 [Ginat, Daniel Thomas] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Swearingen, Brooke; Curry, William; Cahill, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA.
[Madsen, Joseph; Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Neurosurg, Boston Childrens Hosp, Boston, MA USA.
RP Ginat, DT (reprint author), 55 Fruit St, Boston, MA 02114 USA.
EM ginatd01@gmail.com
OI Cahill, Daniel/0000-0003-2552-6546
NR 56
TC 7
Z9 7
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2014
VL 39
IS 6
BP 1357
EP 1365
DI 10.1002/jmri.24380
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG5LM
UT WOS:000335460500003
PM 24921066
ER
PT J
AU Bot, AGJ
Becker, SJE
Bruijnzeel, H
Mulders, MAM
Ring, D
Vranceanu, AM
AF Bot, Arjan G. J.
Becker, Stephanie J. E.
Bruijnzeel, Hanneke
Mulders, Marjolein A. M.
Ring, David
Vranceanu, Ana-Maria
TI Creation of the Abbreviated Measures of the Pain Catastrophizing Scale
and the Short Health Anxiety Inventory: The PCS-4 and SHAI-5
SO JOURNAL OF MUSCULOSKELETAL PAIN
LA English
DT Article
DE Health anxiety; pain catastrophizing; short form questionnaires
ID RANDOMIZED CONTROLLED-TRIAL; ARM PAIN; MUSCULOSKELETAL PAIN;
POSTOPERATIVE PAIN; BACK-PAIN; HYPOCHONDRIASIS; ASSOCIATION; DISABILITY;
DEPRESSION; THERAPY
AB Objective: In patients with arm and upper extremity illness, pain catastrophizing and health anxiety are important factors in disability, pain and patient satisfaction. The aim of this study was to develop a shorter version of the 13-item Pain Catastrophizing Scale [PCS] and 18-item Short Health Anxiety Inventory [SHAI].
Methods: One hundred and sixty-four patients [54% women, mean age of 51 years] with a variety of upper extremity diagnoses enrolled in this study. Patients completed the PCS, the SHAI, the Disabilities of Arm Shoulder and Hand questionnaire [DASH] for disability, the Patient Health Questionnaire-9 [PHQ-9] for depressive symptoms and a scale to measure pain. Inter-correlation analyses were conducted on each of the subscales of the PCS and the SHAI and questions were selected based on the magnitude of their inter-item correlation.
Results: Questions 3, 6, 8 and 11 remained in the PCS-4 and showed good internal consistency [alpha = 0.86] and correlated highly with the original PCS [r = 0.96]. Questions 2, 3, 12, 15 and 17 were chosen for the SHAI-5. The SHAI-5 had alpha = 0.67 and had a correlation or r = 0.87 with the SHAI-18. Both the SHAI-5 and PCS-4 had equal correlations with DASH, PHQ and pain as the original questionnaires.
Conclusions: We found that the PCS-4 and SHAI-5 were comparable to the original questionnaires, but further studies should be conducted in order to confirm our findings. This study provides preliminary evidence that the PCS-4 and SHAI-5 could be used to screen for health anxiety and pain catastrophizing in busy orthopedic settings.
C1 [Bot, Arjan G. J.; Becker, Stephanie J. E.; Bruijnzeel, Hanneke; Mulders, Marjolein A. M.; Ring, David] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
[Bot, Arjan G. J.; Becker, Stephanie J. E.; Ring, David; Vranceanu, Ana-Maria] Harvard Univ, Sch Med, Boston, MA USA.
[Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Benson Henry Mind Body Inst, Dept Behav Med, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
RI Becker, Stephanie/N-5761-2014
FU VSB fonds; Prins Bernhard CultuurFonds/Banning de Jong Fonds; Anna Fonds
travel grant; Anna Fonds; Genootschap Noorthey; Vreedefonds''; Wright
Medical Technology Inc.; Biomet; Skeletal Dynamics; Hand Surgery
Fellowship from AO North America; Orthopedic Association of Trauma (OTA)
FX Arjan G.J. Bot has received grants from "VSB fonds'', "Prins Bernhard
CultuurFonds/Banning de Jong Fonds'', both non-medical grants and the
orthopaedic: "Anna Fonds travel grant''; Stephanie J.E. Becker has
received grants from "Anna Fonds'', "Genootschap Noorthey'' and
"Vreedefonds''.; Hanneke Bruijnzeel has received a grant from "Anna
Fonds".; Marjolein A. M. Mulders has received a grant from "Anna
Fonds''.; David Ring receives royalties from Wright Medical Technology
Inc.; is consultant for Wright Medical, Skeletal Dynamics, Biomet;
received honoraria from AO North America, AO International; has
royalties contracted with Biomet, Skeletal Dynamics; has stock Options
in Illuminos; received study specific grants from Skeletal Dynamics
(Pending); received funding for Hand Surgery Fellowship from AO North
America and is Deputy Editor for Review Articles, Journal of Hand
Surgery Am., Deputy Editor for Hand and Wrist, Journal of Orthopaedic
Trauma, Assistant Editor, Journal of Shoulder and Elbow Surgery.
Ana-Maria Vranceanu received a grant from the Orthopedic Association of
Trauma (OTA).
NR 44
TC 3
Z9 3
U1 0
U2 5
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1058-2452
J9 J MUSCULOSKELET PAIN
JI J. Musculoskelet. Pain
PD JUN
PY 2014
VL 22
IS 2
BP 145
EP 151
DI 10.3109/10582452.2014.883020
PG 7
WC Rehabilitation; Rheumatology
SC Rehabilitation; Rheumatology
GA AH8OE
UT WOS:000336396600005
ER
PT J
AU Panizzi, P
Stone, JR
Nahrendorf, M
AF Panizzi, Peter
Stone, James R.
Nahrendorf, Matthias
TI Endocarditis and molecular imaging
SO JOURNAL OF NUCLEAR CARDIOLOGY
LA English
DT Review
ID STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; EXPERIMENTAL INFECTIVE ENDOCARDITIS;
IN-VIVO; BACTERIAL-ENDOCARDITIS; MEDICAL PROGRESS; DIAGNOSIS;
MANAGEMENT; ANTIBODY; BIOLUMINESCENCE; PROTHROMBIN
C1 [Panizzi, Peter] Auburn Univ, Dept Drug Discovery & Dev, Harrison Sch Pharm, Auburn, AL 36849 USA.
[Stone, James R.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Stone, James R.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM mnahrendorf@mgh.harvard.edu
OI Panizzi, Peter/0000-0003-0141-8807
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[R00HL094533, R01HL114477]; National Institute of Allergy and Infectious
Diseases Grant [2R44AI085840-02]
FX This work was supported by the National Institutes of Health through
grants provided by the National Heart, Lung, and Blood Institute,
R00HL094533 (to P. P.) & R01HL114477 (to P. P. and M.N.), the National
Institute of Allergy and Infectious Diseases Grant 2R44AI085840-02 (to
P.P.).
NR 65
TC 4
Z9 4
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-3581
EI 1532-6551
J9 J NUCL CARDIOL
JI J. Nucl. Cardiol.
PD JUN
PY 2014
VL 21
IS 3
BP 486
EP 495
DI 10.1007/s12350-014-9902-8
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH6YI
UT WOS:000336278000008
PM 24797384
ER
PT J
AU Hage, FG
Garcia, EV
AF Hage, Fadi G.
Garcia, Ernest V.
TI The independent prognostic value of left ventricular dyssynchrony
SO JOURNAL OF NUCLEAR CARDIOLOGY
LA English
DT Editorial Material
ID PHASE-ANALYSIS; MECHANICAL DYSSYNCHRONY; CARDIOMYOPATHY; DEATH; ERA
C1 [Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA.
[Garcia, Ernest V.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA.
RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA.
EM fadihage@uab.edu
OI Hage, Fadi/0000-0002-1397-4942
NR 18
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-3581
EI 1532-6551
J9 J NUCL CARDIOL
JI J. Nucl. Cardiol.
PD JUN
PY 2014
VL 21
IS 3
BP 541
EP 543
DI 10.1007/s12350-014-9878-4
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH6YI
UT WOS:000336278000013
PM 24623398
ER
PT J
AU Abramowicz, S
Simon, LE
Susarla, HK
Lee, EY
Cheon, JE
Kim, S
Kaban, LB
AF Abramowicz, Shelly
Simon, Lisa E.
Susarla, Harlyn K.
Lee, Edward Y.
Cheon, Jung-Eun
Kim, Susan
Kaban, Leonard B.
TI Are Panoramic Radiographs Predictive of Temporomandibular Joint
Synovitis in Children With Juvenile Idiopathic Arthritis?
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID INVOLVEMENT; PREVALENCE; ULTRASOUND; SIGNS
AB Purpose: To identify specific panoramic radiographic findings associated with temporomandibular joint (TMJ) synovitis in children with juvenile idiopathic arthritis (JIA).
Materials and Methods: This was a retrospective study of children with JIA evaluated at Boston Children's Hospital. Patients were included if they had a confirmed diagnosis of JIA, a panoramic radiograph, and a contemporaneous TMJ magnetic resonance imaging (MRI) study with contrast. Medical records and imaging studies were reviewed to document demographic, panoramic (accentuated antegonial notch, short ramus and condyle unit [RCU] length, and abnormal condyle morphology: decreased condyle anteroposterior or superoinferior dimension) and MRI findings. The outcome variable was the presence or absence of TMJ synovitis on MRI. Descriptive and bivariate statistics and logistic regression models were used to identify associations (significant at P <= .05).
Results: Thirty patients (21 girls) with a mean age of 11.1 years (range, 5 to 16 yr) met the inclusion criteria. Of these, 15 patients had MRI scans positive for synovitis (bilateral in 18 joints in 9 patients and unilateral in 6 joints in 6 patients). The remaining 15 patients did not have evidence of synovitis on MRI. In the synovitis group, 18 of 24 joints (75%) showed abnormal panoramic findings (abnormal condyle morphology in 18 joints, accentuated antegonial notch in 9 joints, or short RCU length in 5 joints). In the nonsynovitis group, 15 of 36 joints (42%) showed abnormal panoramic findings (abnormal condyle morphology in 12 joints, accentuated antegonial notch in 6 joints, or short RCU length in 4 joints). Abnormal condyle morphology and accentuated antegonial notching on panoramic radiographs were found to be significantly correlated with synovitis (P = .0005 and .044, respectively). In a logistic regression model, abnormal condyle morphology was significantly associated with an increase in likelihood of TMJ synovitis versus those joints with normal condyle morphology (P = .007). Joints with abnormal condyle morphology and accentuated antegonial notching were 7.5 times as likely to have synovitis (P = .009) versus those joints without abnormal panoramic findings.
Conclusion: Results of this preliminary study indicate that in this sample of children with JIA, the combination of abnormal condyle morphology and accentuated antegonial notching on a panoramic radiograph correlates with TMJ synovitis on MRI. (C) 2014 American Association of Oral and Maxillofacial Surgeons
C1 [Abramowicz, Shelly; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Abramowicz, Shelly] Boston Childrens Hosp, Boston, MA USA.
[Simon, Lisa E.; Susarla, Harlyn K.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Lee, Edward Y.] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Cheon, Jung-Eun] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul, South Korea.
[Cheon, Jung-Eun] Childrens Hosp, Seoul, South Korea.
[Kim, Susan] Harvard Univ, Sch Med, Dept Pediat, Rheumatol Program,Boston Childrens Hosp, Boston, MA 02115 USA.
[Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Abramowicz, S (reprint author), 1365 Clifton Rd,Bldg B,Suite 2300, Atlanta, GA 30322 USA.
EM sabram5@emory.edu
FU Oral and Maxillofacial Surgery Foundation/American Association of
Maxillofacial Surgeons Faculty Educator Development Award; Massachusetts
General Hospital Oral and Maxillofacial Surgery Education and Research
Fund; Harvard Medical School's Scholars in Medicine
FX This project was supported in part by the Oral and Maxillofacial Surgery
Foundation/American Association of Maxillofacial Surgeons Faculty
Educator Development Award (to S. A.), the Massachusetts General
Hospital Oral and Maxillofacial Surgery Education and Research Fund, and
Harvard Medical School's Scholars in Medicine (to L.S.).
NR 16
TC 4
Z9 4
U1 1
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 0278-2391
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD JUN
PY 2014
VL 72
IS 6
BP 1063
EP 1069
DI 10.1016/j.joms.2013.11.021
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AH3NZ
UT WOS:000336032200008
PM 24742698
ER
PT J
AU Oral, E
Neils, A
Yabannavar, P
Muratoglu, OK
AF Oral, Ebru
Neils, Andrew
Yabannavar, Pooja
Muratoglu, Orhun K.
TI The Effect of an Additional Phosphite Stabilizer on the Properties of
Radiation Cross-Linked Vitamin E Blends of UHMWPE
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE synergy; antioxidant; total joint replacement; hip; knee
ID MOLECULAR-WEIGHT POLYETHYLENE; CRACK PROPAGATION RESISTANCE; TOTAL
HIP-ARTHROPLASTY; IRRADIATED UHMWPE; ALPHA-TOCOPHEROL; FATIGUE
RESISTANCE; WEAR-RESISTANCE; OXIDATION; OSTEOLYSIS; COMPONENTS
AB Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of an antioxidant with UHMWPE resin powder followed by consolidation and radiation cross-linking has been cleared by the FDA for use in both total hips and total knees for designs incorporating two antioxidants, namely vitamin E and Covernox (a medical grade version of Irganox 1010). The antioxidants in the polymer are expected to protect the polymer during consolidation, during radiation cross-linking, on the shelf before implantation, and in vivo after implantation. To maximize the protection of the polymer afforded by the antioxidant in vivo, a novel approach may be the use of multiple antioxidants, especially to protect the primary antioxidant for a longer period of time. We hypothesized that the addition of a phosphite stabilizer (Irgafos 168) commonly used in conjunction with hindered phenolic antioxidants in polymer processing could improve the oxidative stability of radiation cross-linked blends of vitamin E. To test our hypothesis, we prepared UHMWPE blends with 0.05wt% Irgafos and 0.05wt% vitamin E and compared its cross-link density, wear resistance, tensile properties, and impact strength to control blends containing only vitamin E. Our hypothesis was not supported; the cross-link density of UHMWPE was significantly decreased by the additive without additional benefit to oxidative stability. To our knowledge, this was the first attempt at using multiple stabilizers in medical grade UHMWPE. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:757-761, 2014.
C1 [Oral, Ebru; Neils, Andrew; Yabannavar, Pooja; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA.
[Yabannavar, Pooja] MIT, Dept Mat Sci & Engn, Boston, MA USA.
RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
EM eoral@partners.org
FU Aston Medical; Corin Ltd.; Corin Ltd., Iconacy; Zimmer; Renovis;
Conformis; Mako; Biomet
FX No external funds were used for this study. One or more the authors
received royalties from Aston Medical, Corin Ltd., Iconacy, Zimmer,
Renovis, Conformis, Mako, and Biomet on implant material technology not
related to the technology discussed in this study. One of the authors is
an unpaid consultant for Biomet.
NR 42
TC 1
Z9 1
U1 2
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD JUN
PY 2014
VL 32
IS 6
BP 757
EP 761
DI 10.1002/jor.22597
PG 5
WC Orthopedics
SC Orthopedics
GA AE1GC
UT WOS:000333716100004
PM 24536024
ER
PT J
AU Winter, H
Heyman, M
AF Winter, Harland
Heyman, Melvin
TI Value of Endoscopic Mucosal Biopsies in Normal-Appearing Colonic Mucosa
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Editorial Material
C1 [Winter, Harland; Heyman, Melvin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Winter, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM hwinter@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
EI 1536-4801
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD JUN
PY 2014
VL 58
IS 6
BP 676
EP 677
DI 10.1097/MPG.0000000000000384
PG 2
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA AH6SS
UT WOS:000336261600008
PM 24866780
ER
PT J
AU Gosselin, KB
Feldman, HA
Sonis, AL
Bechard, LJ
Kellogg, MD
Gura, K
Venick, R
Gordon, CM
Guinan, EC
Duggan, C
AF Gosselin, Kerri B.
Feldman, Henry A.
Sonis, Andrew L.
Bechard, Lori J.
Kellogg, Mark D.
Gura, Kathleen
Venick, Robert
Gordon, Catherine M.
Guinan, Eva C.
Duggan, Christopher
TI Serum Citrulline as a Biomarker of Gastrointestinal Function During
Hematopoietic Cell Transplantation in Children
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE biomarker; citrulline; gastrointestinal function; hematopoietic cell
transplantation
ID SHORT-BOWEL SYNDROME; PLASMA CITRULLINE; INTESTINAL FAILURE; ENTEROCYTE
MASS; PARENTERAL-NUTRITION; MUCOSITIS; DISEASE; MARKER; PATHOBIOLOGY;
CHEMOTHERAPY
AB Objectives:We sought to determine whether serum citrulline (CIT), an amino acid produced by small bowel enterocytes, was associated with clinical and biochemical markers of gastrointestinal function in children undergoing hematopoietic cell transplantation (HCT).Methods:We conducted a multicenter, prospective cohort study of 26 children to define time-related changes in serum CIT during the course of HCT. Markers of gastrointestinal function including oral energy intake, emesis, stool volume, presence of graft-versus-host disease (GVHD), oral mucositis severity, and cytokine and neurohormone levels were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT.Results:Mean baseline CIT concentration was 22.7mol/L (95% confidence interval [CI] 17.7-27.6) on day -10, which decreased to a nadir of 7.5mol/L (95% CI 3.1-18.0, P=0.017) on day 8 following HCT before returning to baseline by day 30. After adjustment for IL-6 level (1.0% lower CIT per 10% increase in interleukin-6, P=0.004), presence of acute GVHD (27% lower CIT, P=0.025), and oral energy intake (2.1% lower CIT per 10% decrease in energy intake, P=0.018), the nadir shifted to day 10, when mean CIT concentration was lower in patients with severe oral mucositis (6.7mol/L, 95% CI 3.4-13.1) than in those without severe mucositis (11.9mol/L, 95% CI 5.8-24.4, P=0.003). Change in CIT was not correlated with stool volume, C-reactive protein, tumor necrosis factor-, leptin, or ghrelin.Conclusions:In children undergoing HCT, serum CIT correlates with measures of gastrointestinal function (oral mucositis severity, dietary intake, acute GVHD) and may reflect mucosal injury to the gastrointestinal tract.
C1 [Gosselin, Kerri B.; Feldman, Henry A.; Sonis, Andrew L.; Bechard, Lori J.; Kellogg, Mark D.; Gura, Kathleen; Duggan, Christopher] Boston Childrens Hosp, Boston, MA USA.
[Venick, Robert] UCLA Mattel Childrens Hosp, Los Angeles, CA USA.
[Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA.
[Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Duggan, C (reprint author), Boston Childrens Hosp, Ctr Nutr, Div Gastroenterol Hepatol & Nutr, 300 Longwood Ave, Boston, MA 02115 USA.
EM christopher.duggan@childrens.harvard.edu
FU Massachusetts Vitamin Litigation Grant; Harvard Clinical and
Translational Science Center [UL1 RR-025758]; National Institutes of
Health [K24 HD 058795, T32 DK 7477-30]; Bill and Melinda Gates
Foundation [OPP1066203]
FX The present study was supported by the Massachusetts Vitamin Litigation
Grant, the Harvard Clinical and Translational Science Center UL1
RR-025758, and National Institutes of Health grants K24 HD 058795 and
T32 DK 7477-30. C. D. was supported in part by Bill and Melinda Gates
Foundation Award OPP1066203.
NR 29
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-2116
EI 1536-4801
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD JUN
PY 2014
VL 58
IS 6
BP 709
EP 714
DI 10.1097/MPG.0000000000000335
PG 6
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA AH6SS
UT WOS:000336261600015
PM 24614125
ER
PT J
AU Erickson, MA
Morofuji, Y
Owen, JB
Banks, WA
AF Erickson, Michelle A.
Morofuji, Yoichi
Owen, Joshua B.
Banks, William A.
TI Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional
Variation and Importance of Blood Cells
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MICROVASCULAR ENDOTHELIAL-CELLS; COGNITIVE FUNCTION; RAT-BRAIN; EOTAXIN;
CAPILLARY; MOUSE; CHEMOKINE; RECEPTOR; PLASMA; NEUROGENESIS
AB Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.
C1 [Erickson, Michelle A.] Univ Penn, Dept Pathol, Sch Dent Med, Philadelphia, PA 19104 USA.
[Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.; Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA.
[Owen, Joshua B.] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA.
[Morofuji, Yoichi] Nagasaki Univ, Dept Neurosurg, Nagasaki 852, Japan.
RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 Columbian Way, Seattle, WA 98108 USA.
EM wabanks1@u.washington.edu
FU National Institutes of Health National Institute on Aging
[R01-AG029839]; National Institutes of Health National Institute of
Neurological Disorders and Stroke [R01NS051334]
FX This work was supported by the National Institutes of Health National
Institute on Aging [Grant R01-AG029839]; and National Institutes of
Health National Institute of Neurological Disorders and Stroke [Grant
R01NS051334].
NR 42
TC 13
Z9 13
U1 0
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2014
VL 349
IS 3
BP 497
EP 507
DI 10.1124/jpet.114.213074
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH5GJ
UT WOS:000336156200014
PM 24706984
ER
PT J
AU Neuhaus, V
Bot, AGJ
Swellengrebel, CHJ
Jain, NB
Warner, JJP
Ring, DC
AF Neuhaus, Valentin
Bot, Arjan G. J.
Swellengrebel, Christiaan H. J.
Jain, Nitin B.
Warner, Jon J. P.
Ring, David C.
TI Treatment choice affects inpatient adverse events and mortality in older
aged inpatients with an isolated fracture of the proximal humerus
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE Comorbidity; complication; operation; proximal humerus fracture;
surgery; arthroplasty; open reduction and internal fixation
ID SURGICAL-TREATMENT; NONOPERATIVE TREATMENT; CLASSIFICATION;
COMPLICATIONS; ARTHROPLASTY; SURGERY; HEMIARTHROPLASTY; EPIDEMIOLOGY;
OBESITY; TRENDS
AB Background: This study tests the null hypothesis that, among patients aged 65 and older admitted to a United States hospital with an isolated fracture of the proximal humerus (no other injuries or fractures), there are no differences between operative (fixation or arthroplasty) and nonoperative treatments with respect to inpatient adverse events, inpatient mortality, and discharge to a long-term care facility rates accounting for comorbidities.
Methods: Using a large national database representing an estimated 132,005 patients aged 65 and older admitted to a US hospital with an isolated proximal humerus fracture between 2003 and 2007. Sixty-one percent did not have surgery, 22% were treated with open reduction and internal fixation (ORIF), and 17% were treated with arthroplasty.
Results: The risk of an in hospital adverse event was 21% overall and was 4.4 times greater with arthroplasty and 2.7 times greater with ORIF compared to nonoperative treatment. The risk of in hospital death was 1.8% overall and was 2.8 times greater with ORIF compared to nonoperative treatment. Patients treated operatively were less likely to be discharged to a long-term facility compared to patients treated nonoperatively.
Conclusion: In spite of a tendency to treat the most infirm patients (those that are not discharged to home) nonoperatively, operative treatment (open reduction and internal fixation in particular) is an independent risk factor for inpatient adverse events and mortality in older-aged patients admitted to the hospital with an isolated fracture of the proximal humerus and should perhaps be offered more judiciously. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Neuhaus, Valentin; Bot, Arjan G. J.; Swellengrebel, Christiaan H. J.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Jain, Nitin B.] Harvard Univ, Sch Med, Boston, MA USA.
[Jain, Nitin B.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA.
[Jain, Nitin B.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA.
RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
OI Neuhaus, Valentin/0000-0003-4012-5628
FU "Gottfried und Julia Bangerter-Rhyner-Stiftung", Switzerland; Prins
Bernhard Cultuurfonds/Banning- de Jong fonds; VSB fonds; Anna Fonds, the
Netherlands; National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS) [1K23AR059199]; Foundation for PMR; Biomedical
Research Institute at Brigham and Women's Hospital
FX Valentin Neuhaus, MD, was supported by the "Gottfried und Julia
Bangerter-Rhyner-Stiftung", Switzerland, for Scientific Research. Arjan
G.J. Bot, MD, was supported by the Prins Bernhard Cultuurfonds/Banning-
de Jong fonds, VSB fonds and the Anna Fonds, the Netherlands. Nitin B.
Jain, MD, MSPH, is supported by funding from National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) project number
1K23AR059199, Foundation for PM&R, and Biomedical Research Institute at
Brigham and Women's Hospital. The other authors their immediate
families, and any research foundation with which they are affiliated
received no financial payments or other benefits from any commercial
entity related to the subject of this article.
NR 29
TC 7
Z9 7
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1058-2746
J9 J SHOULDER ELB SURG
JI J. Shoulder Elbow Surg.
PD JUN
PY 2014
VL 23
IS 6
BP 800
EP 806
DI 10.1016/j.jse.2013.09.006
PG 7
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA AH8XS
UT WOS:000336422100010
PM 24135421
ER
PT J
AU Vogel, LA
Moen, TC
Macaulay, AA
Arons, RR
Cadet, ER
Ahmad, CS
Levine, WN
AF Vogel, Laura A.
Moen, Todd C.
Macaulay, Alec A.
Arons, Raymond R.
Cadet, Edwin R.
Ahmad, Christopher S.
Levine, William N.
TI Superior labrum anterior-to-posterior repair incidence: a longitudinal
investigation of community and academic databases
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE SLAP lesion; incidence; SPARCS; OSHPD; ABOS
ID II SLAP LESIONS; GLENOID LABRUM; IISLAP LESIONS; ARTHROSCOPIC TREATMENT;
SNYDER CLASSIFICATION; RISING INCIDENCE; LONG HEAD; TEARS; OUTCOMES;
BICEPS
AB Background: Superior labrum anterior-to-posterior (SLAP) lesion repair is controversial regarding indications and potential complications.
Methods: Databases were used to determine the SLAP repair incidence compared with all orthopaedic procedures over a period of 10 years. In part A, the New York Statewide Planning and Research Cooperative System ambulatory surgery database was investigated from 2002 to 2009. In part B, the California Office of Statewide Health Planning and Development ambulatory surgery database was investigated from 2005 to 2009. In part C, the American Board of Orthopaedic Surgery (ABOS) database was investigated from 2003 to 2010.
Results: In part A, from 2002 to 2009, there was a 238% increase in SLAP repair volume compared with a 125% increase in all orthopaedic procedures. In part B, from 2005 to 2009, there was a 20.17% increase in SLAP repair volume compared with a decrease of 13.64% in all orthopaedic procedures. In part C, among candidates performing at least 1 SLAP repair, there was no statistically significant difference in likelihood of performing a SLAP repair (95% confidence interval, 0.973-1.003) in 2010 as compared with 2003 (P > .10).
Conclusions: There has been a significant increase in the incidence of SLAP repairs in the past 10 years in statewide databases. This pattern was not seen in the ABOS database, in which the annual volume of SLAP repairs remained stable over the same period. This suggests that SLAP lesions have been over-treated with surgical repair but that part II ABOS candidates are becoming more aware of the need to narrow indications. Level of evidence: Epidemiology Study, Database Analysis. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Vogel, Laura A.; Arons, Raymond R.; Cadet, Edwin R.; Ahmad, Christopher S.; Levine, William N.] New York Presbyterian Columbia Univ Med Ctr, Ctr Shoulder Elbow & Sports Med, Dept Orthopaed Surg, New York, NY 10032 USA.
[Moen, Todd C.] WB Carrell Mem Clin, Dallas, TX USA.
[Macaulay, Alec A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Levine, WN (reprint author), New York Presbyterian Columbia Univ Med Ctr, Ctr Shoulder Elbow & Sports Med, Dept Orthopaed Surg, 622 W 168th St,PH 1117, New York, NY 10032 USA.
EM wnl1@columbia.edu
NR 47
TC 5
Z9 5
U1 1
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1058-2746
J9 J SHOULDER ELB SURG
JI J. Shoulder Elbow Surg.
PD JUN
PY 2014
VL 23
IS 6
BP E119
EP E126
DI 10.1016/j.jse.2013.11.002
PG 8
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA AH8XS
UT WOS:000336422100001
PM 24496049
ER
PT J
AU Sung, S
Kimball, AB
AF Sung, Sarah
Kimball, Alexa B.
TI An evaluation of educational debt levels in dermatology residents and
effects on career choices
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
C1 [Sung, Sarah; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Suite 240, Boston, MA 02141 USA.
EM Harvardskinstudies@partners.org
NR 4
TC 1
Z9 1
U1 0
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 JUN
PY 2014
VL 70
IS 6
BP 1141
EP 1142
DI 10.1016/j.jaad.2013.09.060
PG 3
WC Dermatology
SC Dermatology
GA AH3NJ
UT WOS:000336030400039
PM 24831320
ER
PT J
AU Benavidez, OJ
Gauvreau, K
Geva, T
AF Benavidez, Oscar J.
Gauvreau, Kimberlee
Geva, Tal
TI Diagnostic Errors in Congenital Echocardiography: Importance of Study
Conditions
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Congenital echocardiography; Diagnostic error; Quality; Outcomes
ID HEART-DISEASE; ACCURACY
AB Background: Diagnostic errors are unwanted clinical events that place patients at risk for injury. The authors have previously reported that a majority of congenital echocardiography errors have clinical impacts and, on the basis of a small cohort, identified factors associated with diagnostic error. The objectives of this study were (1) to evaluate patient risk factors for diagnostic errors in a large contemporary cohort and (2) to identify risk factors for situation-related diagnostic errors.
Methods: Diagnostic errors were identified at a large academic pediatric cardiac center from 2004 to 2011. Clinical and situational variables were collected from diagnostic error cases and controls.
Results: Among the 254 diagnostic error cases, 66% affected clinical management or patients experienced adverse events; 77% of errors were preventable or possibly preventable. Coronary arteries, pulmonary veins, and the aortic arch were most commonly involved with diagnostic errors. Multivariate analysis identified the following patient-related risk factors: rare or very rare diagnoses (adjusted odds ratio [AOR], 6.3; P < .001), high anatomic complexity (AOR, 3.4; P < .001), and weight < 5 kg (AOR, 2.7; P < .001). Risk factors related to the setting of the echocardiographic study included evening or night (7 PM to 6: 59 AM) study interpretation (AOR, 2.6; P = .005) and weekend studies (Friday through Sunday) (AOR, 1.6; P = .04). The model area under the receiver operating characteristic curve was 0.833.
Conclusions: In addition to patient risk factors, the setting of an echocardiographic study and interpretation contribute to risk for a diagnostic error. Studies interpreted overnight or performed during a weekend should be considered for a quality improvement activity to reduce diagnostic errors or their impact.
C1 [Benavidez, Oscar J.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA.
[Benavidez, Oscar J.; Gauvreau, Kimberlee; Geva, Tal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Congenital Cardiol, Boston, MA USA.
[Benavidez, Oscar J.; Gauvreau, Kimberlee; Geva, Tal] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Benavidez, OJ (reprint author), Massachusetts Gen Hosp, Div Pediat Congenital Cardiol, 175 Cambridge St, Boston, MA 02114 USA.
EM ojbenavidez@partners.org
FU Robert Wood Johnson Foundation's Harold Amos Medical Faculty Program
FX Dr Benavidez is supported a grant from the Robert Wood Johnson
Foundation's Harold Amos Medical Faculty Program.
NR 11
TC 9
Z9 9
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD JUN
PY 2014
VL 27
IS 6
BP 616
EP 623
DI 10.1016/j.echo.2014.03.001
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH8PD
UT WOS:000336399300009
PM 24709004
ER
PT J
AU Della Corte, A
Body, SC
Booher, AM
Schaefers, HJ
Milewski, RK
Michelena, HI
Evangelista, A
Pibarot, P
Mathieu, P
Limongelli, G
Shekar, PS
Aranki, SF
Ballotta, A
Di Benedetto, G
Sakalihasan, N
Nappi, G
Eagle, KA
Bavaria, JE
Frigiola, A
Sundt, TM
AF Della Corte, Alessandro
Body, Simon C.
Booher, Anna M.
Schaefers, Hans-Joachim
Milewski, Rita K.
Michelena, Hector I.
Evangelista, Arturo
Pibarot, Philippe
Mathieu, Patrick
Limongelli, Giuseppe
Shekar, Prem S.
Aranki, Sary F.
Ballotta, Andrea
Di Benedetto, Giuseppe
Sakalihasan, Natzi
Nappi, Gianantonio
Eagle, Kim A.
Bavaria, Joseph E.
Frigiola, Alessandro
Sundt, Thoralf M.
CA Int Bicuspid Aortic Valve Consorti
TI Surgical treatment of bicuspid aortic valve disease: Knowledge gaps and
research perspectives
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Review
ID DILATED ASCENDING AORTA; PRACTICE GUIDELINES; AMERICAN-COLLEGE;
NATURAL-HISTORY; EARLIER STAGE; REPLACEMENT; STENOSIS; AORTOPATHY; RISK;
DISSECTION
C1 [Della Corte, Alessandro; Nappi, Gianantonio] Univ Naples 2, Dept Cardiothorac Sci, Div Cardiac Surg, I-80131 Naples, Italy.
[Body, Simon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Booher, Anna M.; Eagle, Kim A.] Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48109 USA.
[Schaefers, Hans-Joachim] Univ Saarland, Med Ctr, Dept Thorac & Cardiovasc Surg, Homburg, Germany.
[Milewski, Rita K.; Bavaria, Joseph E.] Hosp Univ Penn, Dept Cardiovasc Surg, Philadelphia, PA 19104 USA.
[Michelena, Hector I.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Evangelista, Arturo] Hosp Valle De Hebron, Dept Cardiol, Barcelona, Spain.
[Pibarot, Philippe; Mathieu, Patrick] Univ Laval, Quebec City, PQ, Canada.
[Limongelli, Giuseppe] Univ Naples 2, Monaldi Hosp, Div Cardiol, I-80131 Naples, Italy.
[Shekar, Prem S.; Aranki, Sary F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02115 USA.
[Ballotta, Andrea; Frigiola, Alessandro] IRCCS Policlin San Donato, Dept Cardiac Surg, Milan, Italy.
[Di Benedetto, Giuseppe] Univ Hosp, Heart Dept, Salerno, Italy.
[Sakalihasan, Natzi] Univ Hosp, Cardiovasc Surg Serv, Liege, Belgium.
[Sundt, Thoralf M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA.
RP Della Corte, A (reprint author), Univ Naples 2, V Monaldi Hosp, Dept Cardiothorac Sci, Via L Bianchi, I-80131 Naples, Italy.
EM aledellacorte@libero.it
RI Di Salvo, Giovanni/O-7033-2015;
OI Di Salvo, Giovanni/0000-0002-0305-0113; Pluchinotta, Francesca
Romana/0000-0001-7185-7157; Della Corte, Alessandro/0000-0002-4636-3339;
LImongelli, Giuseppe/0000-0002-8291-9517
FU AbbVie; Thrasos Therapeutics, Inc.
FX Simon C. Body reports consulting fees from AbbVie. Kim A. Eagle reports
a research grant from Gore. Thoralf M. Sundt reports consulting fees
from Thrasos Therapeutics, Inc. All other authors have nothing to
disclose with regard to commercial support.
NR 75
TC 19
Z9 21
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2014
VL 147
IS 6
BP 1749
EP U78
DI 10.1016/j.jtcvs.2014.01.021
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AH9HF
UT WOS:000336452000014
PM 24534676
ER
PT J
AU Coselli, JS
Volguina, IV
LeMaire, SA
Sundt, TM
Connolly, HM
Stephens, EH
Schaff, HV
Milewicz, DM
Vricella, LA
Dietz, HC
Minard, CG
Miller, DC
AF Coselli, Joseph S.
Volguina, Irina V.
LeMaire, Scott A.
Sundt, Thoralf M.
Connolly, Heidi M.
Stephens, Elizabeth H.
Schaff, Hartzell V.
Milewicz, Dianna M.
Vricella, Luca A.
Dietz, Harry C.
Minard, Charles G.
Miller, D. Craig
CA Aortic Valve Operative Outcomes M
TI Early and 1-year outcomes of aortic root surgery in patients with Marfan
syndrome: A prospective, multicenter, comparative study
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID VALVE-SPARING OPERATION; ASCENDING AORTA; REPLACEMENT; REGURGITATION;
GUIDELINES; MORBIDITY; MORTALITY; ANEURYSM
AB Objective: To compare the 1-year results after aortic valve-sparing (AVS) or valve-replacing (AVR) aortic root replacement from a prospective, international registry of 316 patients with Marfan syndrome (MFS).
Methods: Patients underwent AVS (n = 239, 76%) or AVR (n = 77, 24%) aortic root replacement at 19 participating centers from 2005 to 2010. One-year follow-up data were complete for 312 patients (99%), with imaging findings available for 293 (94%). The time-to-events were compared between groups using Kaplan-Meier curves and Cox proportional hazards models.
Results: Two patients (0.6%)-1 in each group-died within 30 days. No significant differences were found in early major adverse valve-related events (MAVRE; P = .6). Two AVS patients required early reoperation for coronary artery complications. The 1-year survival rates were similar in the AVR (97%) and AVS (98%) groups; the procedure type was not significantly associated with any valve-related events. At 1 year and beyond, aortic regurgitation of at least moderate severity (>= 2+) was present in 16 patients in the AVS group (7%) but in no patients in the AVR group (P = .02). One AVS patient required late AVR.
Conclusions: AVS aortic root replacement was not associated with greater 30-day mortality or morbidity rates than AVR root replacement. At 1 year, no differences were found in survival, valve- related morbidity, or MAVRE between the AVS and AVR groups. Of concern, 7% of AVS patients developed grade >= 2+ aortic regurgitation, emphasizing the importance of 5 to 10 years of follow-up to learn the long-term durability of AVS versus AVR root replacement in patients with MFS.
C1 [Coselli, Joseph S.; Volguina, Irina V.; LeMaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77584 USA.
[Coselli, Joseph S.; Volguina, Irina V.; LeMaire, Scott A.] Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX 77025 USA.
[Sundt, Thoralf M.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA.
[Connolly, Heidi M.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Stephens, Elizabeth H.; Miller, D. Craig] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Stanford, CA 94305 USA.
[Schaff, Hartzell V.] Mayo Clin, Dept Surg, Div Cardiovasc Surg, Rochester, MN USA.
[Milewicz, Dianna M.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Med Genet, Houston, TX 77030 USA.
[Vricella, Luca A.] Johns Hopkins Univ Hosp, Dept Surg, Div Cardiac Surg, Baltimore, MD 21287 USA.
[Dietz, Harry C.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Minard, Charles G.] Baylor Coll Med, Dan L Duncan Inst Clin & Translat Res, Houston, TX 77584 USA.
RP Volguina, IV (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, One Baylor Plaza,BCM 390, Houston, TX 77584 USA.
EM volguina@bcm.edu
OI Schaff, Hartzell/0000-0003-0994-027X
FU National Marfan Foundation; Michael E. DeBakey Department of Surgery,
Baylor College of Medicine, Houston, Tex; Vascutek Ltd, St Jude Medical,
Inc; Macquet Cardiovascular/Getinge Group; Dan L. Duncan Institute for
Clinical and Translational Research, Baylor College of Medicine,
Houston, Tex
FX The present study was sponsored by the National Marfan Foundation and
Michael E. DeBakey Department of Surgery, Baylor College of Medicine,
Houston, Tex. The National Marfan Foundation received unrestricted
support from Vascutek Ltd, St Jude Medical, Inc, and the Macquet
Cardiovascular/Getinge Group. Dr Minard is supported by the Dan L.
Duncan Institute for Clinical and Translational Research, Baylor College
of Medicine, Houston, Tex.
NR 20
TC 20
Z9 21
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2014
VL 147
IS 6
BP 1758
EP 1766
DI 10.1016/j.jtcvs.2014.02.021
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AH9HF
UT WOS:000336452000015
PM 24655904
ER
PT J
AU Antczak, C
Trinh, VQ
Sood, A
Ravi, P
Roghmann, F
Trudeau, V
Chang, SL
Karakiewicz, PI
Kibel, AS
Krishna, N
Nguyen, PL
Saad, F
Sammon, JD
Sukumar, S
Zorn, KC
Sun, M
Trinh, QD
AF Antczak, Carina
Trinh, Vincent Q.
Sood, Akshay
Ravi, Praful
Roghmann, Florian
Trudeau, Vincent
Chang, Steven L.
Karakiewicz, Pierre I.
Kibel, Adam S.
Krishna, Nandita
Nguyen, Paul L.
Saad, Fred
Sammon, Jesse D.
Sukumar, Shyam
Zorn, Kevin C.
Sun, Maxine
Trinh, Quoc-Dien
TI The Health Care Burden of Skeletal Related Events in Patients with Renal
Cell Carcinoma and Bone Metastasis
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; carcinoma, renal cell; bone and bones; neoplasm metastasis;
hospital charges
ID ZOLEDRONIC ACID; PROSTATE-CANCER; UNITED-STATES; SURVIVAL;
COMPLICATIONS; SECONDARY; PATTERNS; THERAPY; DISEASE
AB Purpose: We examined temporal trends in skeletal related events and associated charges in patients with renal cell carcinoma metastatic to bone. We also identified patient and hospital characteristics associated with skeletal related events and related mortality.
Materials and Methods: Using the Nationwide Inpatient Sample we abstracted data on patients with renal cell carcinoma who were diagnosed with concomitant bone metastasis between 1998 and 2010. Patients who experienced a skeletal related event were identified and hospital charges were calculated. Multivariate regression models fitted with generalized estimating equations were used to examine predictors of skeletal related events and related in-hospital mortality.
Results: Between 1998 and 2010 a weighted estimate of 144,889 renal cell carcinoma hospital visits of patients with bone metastasis was identified in the Nationwide Inpatient Sample, of which 20.8% involved a skeletal related event. In these cases from 1998 to 2010 the inflation adjusted mean yearly costs associated with hospital admission increased by 207% in 2013 United States dollars (estimated annual percent change 8.94%, p < 0.001). Conversely, the rates of skeletal related events and skeletal related event associated mortality decreased significantly (estimated annual percent change -1.11% and -2.9%, respectively, each p < 0.001).
Conclusions: The prevalence and in-hospital mortality of skeletal related event associated hospitalization for metastatic renal cell carcinoma is decreasing but such charges to health care in the United States are increasing at an alarming rate. These findings highlight the need for cost-effective treatment strategies to prevent or treat these morbid complications.
C1 [Antczak, Carina; Trinh, Vincent Q.; Roghmann, Florian; Trudeau, Vincent; Karakiewicz, Pierre I.; Zorn, Kevin C.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada.
[Saad, Fred] Univ Montreal, Ctr Hlth, Div Urol, Montreal, PQ, Canada.
[Sood, Akshay; Ravi, Praful; Sammon, Jesse D.] Vattikuti Urol Inst, Henry Ford Hlth Syst, Detroit, MI USA.
[Roghmann, Florian] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany.
[Sood, Akshay; Chang, Steven L.; Kibel, Adam S.; Krishna, Nandita; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Urol Surg, Boston, MA 02115 USA.
[Sood, Akshay; Chang, Steven L.; Kibel, Adam S.; Krishna, Nandita; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA.
[Sukumar, Shyam] Univ Minnesota, Dept Urol, Minneapolis, MN USA.
RP Antczak, C (reprint author), 1058 St Denis, Montreal, PQ H2X 3J4, Canada.
EM carina.antczak@gmail.com
NR 20
TC 4
Z9 4
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2014
VL 191
IS 6
BP 1678
EP 1684
DI 10.1016/j.juro.2013.12.042
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0IS
UT WOS:000336531100010
PM 24384157
ER
PT J
AU Gray, PJ
Fedewa, SA
Shipley, WU
Efstathiou, JA
Lin, CC
Zietman, AL
Virgo, KS
AF Gray, P. J.
Fedewa, S. A.
Shipley, W. U.
Efstathiou, J. A.
Lin, C. C.
Zietman, A. L.
Virgo, K. S.
TI Re: Use of Potentially Curative Therapies for Muscle-Invasive Bladder
Cancer in the United States: Results from the National Cancer Data Base
Editorial Comment
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Gray, P. J.; Fedewa, S. A.; Shipley, W. U.; Efstathiou, J. A.; Lin, C. C.; Zietman, A. L.; Virgo, K. S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Gray, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2014
VL 191
IS 6
BP 1731
EP 1732
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0IS
UT WOS:000336531100023
ER
PT J
AU Saunders, RS
Fernandes-Taylor, S
Kind, AJH
Engelbert, TL
Greenberg, CC
Smith, MA
Matsumura, JS
Kent, KC
AF Saunders, Richard S.
Fernandes-Taylor, Sara
Kind, Amy J. H.
Engelbert, Travis L.
Greenberg, Caprice C.
Smith, Maureen A.
Matsumura, Jon S.
Kent, K. Craig
TI Rehospitalization to primary versus different facilities following
abdominal aortic aneurysm repair
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID RURAL PATIENTS; SURGERY; VOLUME; CARE; REGIONALIZATION; READMISSIONS;
HOSPITALS; MORTALITY; RESECTION; FAILURE
AB Objective: Reducing readmissions represents a unique opportunity to improve care and reduce health care costs and is the focus of major payers. A large number of surgical patients are readmitted to hospitals other than where the primary surgery was performed, resulting in clinical decisions that do not incorporate the primary surgeon and potentially alter outcomes. This study characterizes readmission to primary vs different hospitals after abdominal aortic aneurysm (AAA) repair and examines the implications with regard to mortality and cost.
Methods: Patients who underwent open or endovascular aneurysm repair for AAA were identified from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse, a random 5% national sample of Medicare beneficiaries from 2005 to 2009. Outcomes for patients who underwent AAA repair and were readmitted within 30 days of initial discharge were compared based on readmission location (primary vs different hospital).
Results: A total of 885 patients underwent AAA repair and were readmitted within 30 days. Of these, 626 (70.7%) returned to the primary facility, and 259 (29.3%) returned to a different facility. Greater distance from patient residence to the primary hospital was the strongest predictor of readmission to a different facility. Patients living 50 to 100 miles from the primary hospital were more likely to be readmitted to a different hospital compared with patients living <10 miles away (odds ratio, 8.50; P < .001). Patients with diagnoses directly related to the surgery (eg, wound infection) were more likely to be readmitted to the primary hospital, whereas medical diagnoses (eg, pneumonia and congestive heart failure) were more likely to be treated at a different hospital. There was no statistically significant difference in mortality between patients readmitted to a different or the primary hospital. Median total 30-day payments were significantly lower at different vs primary hospitals (primary, $11,978 vs different, $11,168; P = .04).
Conclusions: Readmission to a different facility after AAA repair is common and occurs more frequently than for the overall Medicare population. Patients travelling a greater distance for AAA repair are more likely to return to different vs the primary hospital when further care is required. For AAA repair, quality healthcare may be achieved at marginally lower cost and with greater patient convenience for selected readmissions at hospitals other than where the initial procedure was performed.
C1 [Saunders, Richard S.; Fernandes-Taylor, Sara; Engelbert, Travis L.; Greenberg, Caprice C.; Matsumura, Jon S.; Kent, K. Craig] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Surg Outcomes Res Program WiSOR, Dept Surg, Madison, WI USA.
[Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Geriatr, Madison, WI USA.
[Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
[Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA.
[Kind, Amy J. H.] William S Middleton Hosp, GRECC, US Dept Vet Affairs, Madison, WI USA.
RP Kent, KC (reprint author), H4 710 Clin Sci Ctr, 600 Highland Ave, Madison, WI 53792 USA.
EM kent@surgery.wisc.edu
FU Health Innovation Program; University of Wisconsin School of Medicine
and Public Health from The Wisconsin Partnership Program;
Community-Academic Partnerships core of the University of Wisconsin
Institute for Clinical and Translational Research (UW ICTR) through the
National Center for Advancing Translational Sciences (NCATS)
[UL1TR000427]
FX This project was supported in part by the Health Innovation Program, the
University of Wisconsin School of Medicine and Public Health from The
Wisconsin Partnership Program, and the Community-Academic Partnerships
core of the University of Wisconsin Institute for Clinical and
Translational Research (UW ICTR) through the National Center for
Advancing Translational Sciences (NCATS), grant UL1TR000427.
NR 27
TC 12
Z9 12
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD JUN
PY 2014
VL 59
IS 6
BP 1502
EP +
DI 10.1016/j.jvs.2013.12.015
PG 11
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA AH8DH
UT WOS:000336363800004
PM 24491237
ER
PT J
AU Lombardi, JV
Cambria, RP
Nienaber, CA
Chiesa, R
Mossop, P
Haulon, S
Zhou, Q
Jia, FY
AF Lombardi, Joseph V.
Cambria, Richard P.
Nienaber, Christoph A.
Chiesa, Roberto
Mossop, Peter
Haulon, Stephan
Zhou, Qing
Jia, Feiyi
CA STABLE Investigators
TI Aortic remodeling after endovascular treatment of complicated type B
aortic dissection with the use of a composite device design
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS)
CY MAY 29-JUN 01, 2013
CL San Francisco, CA
SP Soc Vasc Surg
ID STENT-GRAFT PLACEMENT; INTERNATIONAL REGISTRY; THORACIC AORTA; FALSE
LUMEN; REPAIR; MANAGEMENT; IRAD; MULTICENTER; INSIGHTS; OUTCOMES
AB Objective: The purpose of this study is to report updated clinical and aortic remodeling results from the Study for the Treatment of complicated Type B Aortic Dissection using Endoluminal repair (STABLE) trial, a prospective, multicenter study evaluating safety and effectiveness of a pathology-specific endovascular system (proximal stent graft and distal bare metal stent) for the treatment of complicated type B aortic dissection.
Methods: All 86 enrolled patients (mean age, 59 years; 73.3% men) were treated within 90 days of symptom onset (55 with acute dissections and 31 with nonacute dissections). Inclusion criteria were branch vessel obstruction/compromise, impending rupture as evidenced by periaortic effusion/hematoma, resistant hypertension, persistent pain/symptoms, or aortic growth >= 5 mm within 3 months (or transaortic diameter >= 40 mm). Remodeling of the dissected aorta, including thrombosis of the false lumen and changes in the true lumen, false lumen, and transaortic diameter, were assessed in patients with available computed tomographic imaging through 2 years.
Results: The 30-day mortality rate was 4.7% (4/86) in the overall patient group (5.5% in acute patients and 3.2% in nonacute patients). Freedom from all-cause mortality was 88.3% at 1 year and 84.7% at 2 years (no significant difference between acute and nonacute patients). From baseline to 2 years, the true lumen diameter increased significantly in the descending thoracic aorta and the more distal abdominal aorta, along with a decrease in the false lumen diameter in both aortic segments. A majority of patients had either a stable or shrinking transaortic diameter in the thoracic (80.3% at 1 year and 73.9% at 2 years) or abdominal aorta (79.1% at 1 year and 66.7% at 2 years). Transaortic growth (>5 mm) occurred predominantly in acute dissections. Consistently, a shorter time from symptom onset to treatment was found to predict transaortic growth in the abdominal aorta (P = .03).
Conclusions: Endovascular repair of complicated type B aortic dissection with the use of a composite construct demonstrates favorable early clinical outcomes and aortic remodeling. However, patients treated in the acute setting may be prone to aortic growth and may require close observation. Follow-up through 5 years is ongoing.
C1 [Lombardi, Joseph V.] Cooper Univ Hosp, Dept Surg, Camden, NJ 08103 USA.
[Cambria, Richard P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Nienaber, Christoph A.] Univ Hosp Rostock, Dept Med, Rostock, Germany.
[Chiesa, Roberto] Hosp San Raffaele, Dept Surg, I-20132 Milan, Italy.
[Mossop, Peter] St Vincents Hosp, Dept Radiol, Melbourne, Vic, Australia.
[Haulon, Stephan] CHRU Lille, Hosp Cardiol, Dept Surg, F-59037 Lille, France.
[Zhou, Qing; Jia, Feiyi] MED Inst, W Lafayette, IN USA.
RP Lombardi, JV (reprint author), Cooper Univ Hosp, Div Vasc & Endovasc Surg, Three Cooper Plaza,Ste 411, Camden, NJ 08103 USA.
EM lombardi-joseph@CooperHealth.edu
NR 26
TC 18
Z9 21
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD JUN
PY 2014
VL 59
IS 6
BP 1544
EP 1554
DI 10.1016/j.jvs.2013.12.038
PG 11
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA AH8DH
UT WOS:000336363800010
PM 24560244
ER
PT J
AU Kougias, P
Sharath, S
Barshes, NR
Lowery, B
Garcia, A
Pak, T
Bechara, CF
Pisimisis, G
AF Kougias, Panos
Sharath, Sherene
Barshes, Neal R.
Lowery, Briauna
Garcia, Andrea
Pak, Taemee
Bechara, Carlos F.
Pisimisis, George
TI Impact of cumulative intravascular contrast exposure on renal function
in patients with occlusive and aneurysmal vascular disease
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 38th Annual Spring Meeting of the Peripheral-Vascular-Surgery-Society
CY MAY 29, 2013
CL San Francisco, CA
SP Peripheral Vasc Surg Soc
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; RISK-FACTORS;
INDUCED NEPHROPATHY; PROXIMAL FIXATION; REPAIR; DYSFUNCTION;
CONSEQUENCES; TERM
AB Objective: Patients with occlusive or aneurysmal vascular disease are repeatedly exposed to intravascular (IV) contrast for diagnostic or therapeutic purposes. We sought to determine the long-term impact of cumulative iodinated IV contrast exposure (CIVCE) on renal function; the latter was defined by means of National Kidney Foundation (NKF) criteria.
Methods: We performed a longitudinal study of consecutive patients without renal insufficiency at baseline (NFK stage I or II) who underwent interventions for arterial occlusive or aneurysmal disease. We collected detailed data on any IV iodinated contrast exposure (including diagnostic or therapeutic angiography, cardiac catheterization, IV pyelography, computed tomography with IV contrast, computed tomographic angiography); medication exposure throughout the observation period; comorbidities; and demographics. The primary end point was the development of renal failure (RF) (defined as NFK stage 4 or 5). Analysis was performed with the use of a shared frailty model with clustering at the patient level.
Results: Patients (n = 1274) had a mean follow-up of 5.8 (range, 2.2-14) years. In the multivariate model with RF as the dependent variable and after adjusting for the statistically significant covariates of baseline renal function (hazard ratio [HR], 0.95; P < .001), diabetes (HR, 1.8; P = .007), use of an angiotensin-converting enzyme inhibitor (HR, 0.63; P = .03), use of antiplatelets (HR, 0.5; P = .01), cumulative number of open vascular operations performed (HR, 1.2; P = .001), and congestive heart failure (HR, 3.2; P < .001), CIVCE remained an independent predictor for RF development (HR, 1.1; P < .001). In the multivariate survival analysis model and after adjusting for the statistically significant covariates of perioperative myocardial infarction (HR, 3.9; P < .001), age at entry in the cohort (HR, 1.05; P = .035), total number of open operations (HR, 1.51; P < .001), and serum albumin (HR, 0.47; P < .001), CIVCE was an independent predictor of death (HR, 1.07; P < .001).
Conclusions: Cumulative IV contrast exposure is an independent predictor of RF and death in patients with occlusive and aneurysmal vascular disease.
C1 [Kougias, Panos; Sharath, Sherene; Barshes, Neal R.; Lowery, Briauna; Bechara, Carlos F.; Pisimisis, George] Michael E DeBakey VA Med Ctr, Dept Surg, Houston, TX USA.
[Kougias, Panos; Barshes, Neal R.; Garcia, Andrea; Pak, Taemee; Bechara, Carlos F.; Pisimisis, George] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA.
RP Kougias, P (reprint author), Houston VAMC, Dept Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA.
EM pkougias@bcm.edu
NR 17
TC 3
Z9 3
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD JUN
PY 2014
VL 59
IS 6
BP 1644
EP 1650
DI 10.1016/j.jvs.2013.12.039
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA AH8DH
UT WOS:000336363800025
PM 24560864
ER
PT J
AU Lee, LC
Ge, L
Zhang, ZH
Pease, M
Nikolic, SD
Mishra, R
Ratcliffe, MB
Guccione, JM
AF Lee, Lik Chuan
Ge, Liang
Zhang, Zhihong
Pease, Matthew
Nikolic, Serjan D.
Mishra, Rakesh
Ratcliffe, Mark B.
Guccione, Julius M.
TI Patient-specific finite element modeling of the Cardiokinetix
Parachute(A (R)) device: effects on left ventricular wall stress and
function
SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
LA English
DT Article
DE Myocardial infarction; Remodeling; Finite element method; Surgical
ventricular restoration
ID CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; MRI; RESTORATION;
MECHANICS; ANEURYSM
AB The Parachute(A (R)) (Cardiokinetix, Inc., Menlo Park, California) is a catheter-based device intended to reverse left ventricular (LV) remodeling after antero-apical myocardial infarction. When deployed, the device partitions the LV into upper and lower chambers. To simulate its mechanical effects, we created a finite element LV model based on computed tomography (CT) images from a patient before and 6 months after Parachute(A (R)) implantation. Acute mechanical effects were determined by in silico device implantation (VIRTUAL-Parachute). Chronic effects of the device were determined by adjusting the diastolic and systolic material parameters to better match the 6-month post-implantation CT data and LV pressure data at end-diastole (ED) (POST-OP). Regional myofiber stress and pump function were calculated in each case. The principal finding is that VIRTUAL-Parachute was associated with a 61.2 % reduction in the lower chamber myofiber stress at ED. The POST-OP model was associated with a decrease in LV diastolic stiffness and a larger reduction in myofiber stress at the upper (27.1 %) and lower chamber (78.4 %) at ED. Myofiber stress at end-systole and stroke volume was little changed in the POST-OP case. These results suggest that the primary mechanism of Parachute(A (R)) is a reduction in ED myofiber stress, which may reverse eccentric post-infarct LV hypertrophy.
C1 [Lee, Lik Chuan; Ge, Liang; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Lee, Lik Chuan; Ge, Liang; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
[Lee, Lik Chuan; Ge, Liang; Zhang, Zhihong; Mishra, Rakesh; Ratcliffe, Mark B.; Guccione, Julius M.] San Francisco VA Med Ctr, Div Surg Serv 112, San Francisco, CA 94121 USA.
[Pease, Matthew; Nikolic, Serjan D.] Cardiokinetix Inc, Menlo Pk, CA USA.
[Mishra, Rakesh] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA.
EM mark.ratcliffe@va.gov
FU NIH [R01-HL-084431, R01-HL-077921, R01-HL-118627]
FX This study was supported by an unrestricted gift from Cardiokinetix and
NIH grants R01-HL-084431 (Dr. Ratcliffe), R01-HL-077921 and
R01-HL-118627 (Dr. Guccione).
NR 23
TC 15
Z9 17
U1 0
U2 6
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0140-0118
EI 1741-0444
J9 MED BIOL ENG COMPUT
JI Med. Biol. Eng. Comput.
PD JUN
PY 2014
VL 52
IS 6
BP 557
EP 566
DI 10.1007/s11517-014-1159-5
PG 10
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Mathematical & Computational Biology; Medical Informatics
SC Computer Science; Engineering; Mathematical & Computational Biology;
Medical Informatics
GA AH8HO
UT WOS:000336378200005
PM 24793158
ER
PT J
AU Hess, AT
Jacobson, SW
Jacobson, JL
Molteno, CD
van der Kouwe, AJW
Meintjes, EM
AF Hess, Aaron T.
Jacobson, Sandra W.
Jacobson, Joseph L.
Molteno, Christopher D.
van der Kouwe, Andre J. W.
Meintjes, Ernesta M.
TI A comparison of spectral quality in magnetic resonance spectroscopy data
acquired with and without a novel EPI-navigated PRESS sequence in
school-aged children with fetal alcohol spectrum disorders
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE Magnetic resonance spectroscopy; Motion correction; B0 correction; EPI
navigator; Fetal alcohol spectrum disorders; South Africa
ID RISK-FACTORS; SIGNAL LOSS; EXPOSURE; MOTION; CAPE; FEATURES; WOMEN;
FMRI; IQ
AB Single voxel spectroscopy (SVS) can generate useful information regarding metabolite concentrations provided that the MR signal can be averaged over several minutes during which the subject remains stationary. This requirement can be particularly challenging for children who cannot otherwise be scanned without sedation. To address this problem we developed an EPI volume navigated (vNav) SVS PRESS sequence, which applies real-time head pose (location and orientation), frequency, and first-order B0 shim adjustments. A water-independent preprocessing algorithm removes residual frequency and phase shifts resulting from within-TR movements. We compare results and performance of the standard and vNav PRESS sequences in a sample of 9- to 10-year-olds from a South African cohort of children with fetal alcohol spectrum disorders (FASD) and healthy controls. Magnetic resonance spectroscopy (MRS) data in the deep cerebellar nuclei were initially acquired with the standard PRESS sequence. The children were re-scanned 1 year later with the vNav PRESS sequence. Good quality data were acquired in 73 % using the vNav PRESS sequence, compared to only 50 % for the standard PRESS sequence. Additionally, tighter linewidths and smaller variances in the measured concentrations were observed. These findings confirm previous reports demonstrating the efficacy of our innovative vNav sequence with healthy volunteers and young children with HIV and expand its application to a school-aged population with FASD-disorders often associated with attention problems and hyperactivity. This study provides the most direct evidence to date regarding degree to which these new methods can improve data quality in research studies employing MRS.
C1 [Hess, Aaron T.; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, South Africa.
[Hess, Aaron T.; Jacobson, Sandra W.; Jacobson, Joseph L.; Meintjes, Ernesta M.] Univ Cape Town, Dept Human Biol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[Hess, Aaron T.] Univ Oxford, Ctr Clin Magnet Resonance Res, Oxford, England.
[Jacobson, Sandra W.; Jacobson, Joseph L.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA.
[Jacobson, Sandra W.; Jacobson, Joseph L.; Molteno, Christopher D.] Univ Cape Town, Dept Psychiat & Mental Hlth, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Meintjes, EM (reprint author), Univ Cape Town, Dept Human Biol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
EM sandra.jacobson@wayne.edu; ernesta.meintjes@gmail.com
FU South African Research Chairs Initiative of the Department of Science
and Technology; National Research Foundation of South Africa; Medical
Research Council of South Africa; NIH/National Institute on Alcohol
Abuse and Alcoholism [R21AA017410, R01AA016781, R01 AA09524, U01
AA014790, U24 AA014815]; University of Cape Town; Wayne State
University; Joseph Young, Sr., Fund from the State of Michigan;
Collaborative Initiative on Fetal Alcohol Spectrum Disorders [U01, U24]
FX This research was funded by grants from the South African Research
Chairs Initiative of the Department of Science and Technology and
National Research Foundation of South Africa, Medical Research Council
of South Africa, NIH/National Institute on Alcohol Abuse and Alcoholism
(R21AA017410, R01AA016781, R01 AA09524, U01 AA014790, and U24 AA014815)
and the University of Cape Town, Wayne State University, and Joseph
Young, Sr., Fund from the State of Michigan. We thank Siemens, Bruce
Spottiswoode, Ph.D., the CUBIC radiographers Marie-Louise de Villiers
and Nailah Maroof, Lindie du Plessis for assistance with LCModel
analyses, Mathematician/Physicist M. Dylan Tisdall, our UCT and WSU
research staff Maggie September, Nicolette Hamman, Mariska Pienaar, Emma
Makin, and Neil Dodge. We also thank the dysmorphologists, H. Eugene
Hoyme, Luther K. Robinson, and Nathanial Khaole, who conducted the
dysmorphology diagnostic examinations of the children for FASD, funded
by U01 and U24 grants from the Collaborative Initiative on Fetal Alcohol
Spectrum Disorders (listed above). We also greatly appreciate the
participation of the mothers and children in the longitudinal study.
NR 33
TC 2
Z9 2
U1 1
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
EI 1573-7365
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD JUN
PY 2014
VL 29
IS 2
SI SI
BP 323
EP 332
DI 10.1007/s11011-014-9487-6
PG 10
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA AH7SU
UT WOS:000336335200012
PM 24488204
ER
PT J
AU Heatwole, C
Bode, R
Johnson, N
Dekdebrun, J
Dilek, N
Heatwole, M
Hilbert, JE
Luebbe, E
Martens, W
Mcdermott, MP
Rothrock, N
Thornton, C
Vickrey, BG
Victorson, D
Moxley, R
AF Heatwole, Chad
Bode, Rita
Johnson, Nicholas
Dekdebrun, Jeanne
Dilek, Nuran
Heatwole, Mark
Hilbert, James E.
Luebbe, Elizabeth
Martens, William
Mcdermott, Michael P.
Rothrock, Nan
Thornton, Charles
Vickrey, Barbara G.
Victorson, David
Moxley, Richard, III
TI MYOTONIC DYSTROPHY HEALTH INDEX: INITIAL EVALUATION OF A
DISEASE-SPECIFIC OUTCOME MEASURE
SO MUSCLE & NERVE
LA English
DT Article
DE pain management; pain assessment; myotonic dystrophy type 1;
facioscapulohumeral muscular dystrophy; rehabilitation
ID PATIENT-REPORTED OUTCOMES; QUALITY-OF-LIFE; MUSCULAR-DYSTROPHY; DRUG
DEVELOPMENT; CTG REPEAT; PERSPECTIVE; VALIDITY; TYPE-1; TRIALS; GENE
AB Introduction: We examined the effects of pain site and intensity on function in patients with myotonic dystrophy type 1 (DM1) and facioscapulohumeral muscular dystrophy (FSHD) and chronic pain. Methods: Questionnaires assessing pain sites, pain extent (number of sites), pain intensity, and pain interference were completed by 182 individuals with DM1 (43%) or FSHD (57%) and chronic pain. Results: There was a positive association between pain extent and intensity with pain interference, and a negative association with psychological functioning in both DM1 and FSHD. Pain intensity at specific sites had differential impact beyond the effects of pain intensity alone. Head pain intensity independently affected psychological functioning, whereas leg, foot, hip, and knee pain contributed independently to the prediction of pain interference. Conclusions: Pain site and intensity differentially modulates the effect of chronic pain on function in DM1 and FSHD patients. Researchers and clinicians should consider these factors when assessing and treating pain. Muscle Nerve 49: 900-905, 2014
C1 [Heatwole, Chad; Dekdebrun, Jeanne; Dilek, Nuran; Hilbert, James E.; Luebbe, Elizabeth; Martens, William; Mcdermott, Michael P.; Thornton, Charles; Moxley, Richard, III] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
[Bode, Rita] Psychometr Consultant, Chicago, IL USA.
[Johnson, Nicholas] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Mcdermott, Michael P.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA.
[Rothrock, Nan; Victorson, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Vickrey, Barbara G.] Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Vickrey, Barbara G.] Greater Los Angeles VA HealthCare Syst, Los Angeles, CA USA.
RP Heatwole, C (reprint author), Univ Rochester, Med Ctr, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA.
EM chad_heatwole@urmc.rochester.edu
FU National Institute of Arthritis and Musculoskeletal and Skin Disorders
[1K23AR055947]; Senator Paul D. Wellstone Muscular Dystrophy Cooperative
Research Center [NINDS U54NS48843]; Muscular Dystrophy Association;
Saunders Family Fund; University of Rochester CTSA award from the
National Center for Research Resources [UL1 RR024160]; National Center
for Advancing Translational Sciences of the National Institutes of
Health
FX Partial support for this research was provided by the National Institute
of Arthritis and Musculoskeletal and Skin Disorders (1K23AR055947), the
Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center
(NINDS U54NS48843), the Muscular Dystrophy Association, and the Saunders
Family Fund. The project described in this publication was also
supported by the University of Rochester CTSA award number UL1 RR024160
from the National Center for Research Resources and the National Center
for Advancing Translational Sciences of the National Institutes of
Health. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes
of Health. Additional information regarding the MDHI is available at the
Neuromuscular Institute of Quality-of-Life Studies and Outcome Measure
Development website www.QOLINSTITUTE.com and MDHI licensing
opportunities can be reviewed at: www.urmc.rochester.edu/techtransfer.
NR 27
TC 5
Z9 5
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
EI 1097-4598
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUN
PY 2014
VL 49
IS 6
BP 906
EP 914
DI 10.1002/mus.24079
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH2MA
UT WOS:000335954400016
PM 24142420
ER
PT J
AU Peng, ZC
Zhang, NH
Chandra, D
Homanics, GE
Olsen, RW
Houser, CR
AF Peng, Zechun
Zhang, Nianhui
Chandra, Dave
Homanics, Gregg E.
Olsen, Richard W.
Houser, Carolyn R.
TI Altered Localization of the delta Subunit of the GABA(A) Receptor in the
Thalamus of alpha 4 Subunit Knockout Mice
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Immunohistochemistry; Non-synaptic GABA receptors; Plasticity; Receptor
trafficking; Tonic inhibition; Ventrobasal nucleus
ID TEMPORAL-LOBE EPILEPSY; AMINOBUTYRIC ACID(A) RECEPTORS; INTERMITTENT
ETHANOL TREATMENT; CEREBELLAR GRANULE CELLS; ADULT-RAT BRAIN; TONIC
INHIBITION; PHARMACOLOGICAL CHARACTERIZATION; IMMUNOCYTOCHEMICAL
DISTRIBUTION; ENDOPLASMIC-RETICULUM; BEHAVIORAL-RESPONSES
AB The alpha 4 subunit of the GABA(A) receptor (GABA(A)R) is highly expressed in the thalamus where receptors containing the alpha 4 and delta subunits are major mediators of tonic inhibition. The alpha 4 subunit also exhibits considerable plasticity in a number of physiological and pathological conditions, raising questions about the expression of remaining GABA(A)R subunits when the alpha 4 subunit is absent. Immunohistochemical studies of an alpha 4 subunit knockout (KO) mouse revealed a substantial decrease in delta subunit expression in the ventrobasal nucleus of the thalamus as well as other forebrain regions where the alpha 4 subunit is normally expressed. In contrast, several subunits associated primarily with phasic inhibition, including the alpha 1 and gamma 2 subunits, were moderately increased. Intracellular localization of the delta subunit was also altered. While delta subunit labeling was decreased within the neuropil, some labeling remained in the cell bodies of many neurons in the ventrobasal nucleus. Confocal microscopy demonstrated co-localization of this labeling with an endoplasmic reticulum marker, and electron microscopy demonstrated increased immunogold labeling near the endoplasmic reticulum in the alpha 4 KO mouse. These results emphasize the strong partnership of the delta and alpha 4 subunit in the thalamus and suggest that the alpha 4 subunit of the GABA(A)R plays a critical role in trafficking of the delta subunit to the neuronal surface. The findings also suggest that previously observed reductions in tonic inhibition in the alpha 4 subunit KO mouse are likely to be related to alterations in delta subunit expression, in addition to loss of the alpha 4 subunit.
C1 [Peng, Zechun; Zhang, Nianhui; Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Chandra, Dave; Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol & Pharmacol & Chem Biol, Pittsburgh, PA USA.
[Olsen, Richard W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Houser, Carolyn R.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235, Los Angeles, CA 90095 USA.
EM houser@mednet.ucla.edu
FU National Institutes of Health [NS075245, AA14022, AA13004, AA007680];
Veterans Affairs Medical Research Funds
FX We thank Drs. Jean-Marc Fritschy and Werner Sieghart for generously
sharing their GABAAR subunit-specific antisera that have made
these studies possible. We also thank Christine Huang and Yliana Cetina
for outstanding assistance with tissue processing and figure
preparation. This work was supported by National Institutes of Health
Grants NS075245 (CRH), AA14022 and AA13004 (GEH), AA007680 (RWO), and
Veterans Affairs Medical Research Funds (CRH).
NR 72
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUN
PY 2014
VL 39
IS 6
SI SI
BP 1104
EP 1117
DI 10.1007/s11064-013-1202-1
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AH6WJ
UT WOS:000336272500013
PM 24352815
ER
PT J
AU Kim, WH
Singh, V
Chung, MK
Hinrichs, C
Pachauri, D
Okonkwo, OC
Johnson, SC
AF Kim, Won Hwa
Singh, Vikas
Chung, Moo K.
Hinrichs, Chris
Pachauri, Deepti
Okonkwo, Ozioma C.
Johnson, Sterling C.
CA Alzheimer's Dis Neuroimaging Initi
TI Multi-resolutional shape features via non-Euclidean wavelets:
Applications to statistical analysis of cortical thickness
SO NEUROIMAGE
LA English
DT Article
DE Non-Euclidean wavelet; Multi-resolution analysis; Graph wavelets; Shape
analysis; Cortical thickness discrimination; Alzheimer's disease
ID ALZHEIMERS-DISEASE; SURFACE-AREA; GRAY-MATTER; HEAT KERNEL; CHILDREN;
CT; ADOLESCENTS; MRI; REPRESENTATION; SCHIZOPHRENIA
AB Statistical analysis on arbitrary surface meshes such as the cortical surface is an important approach to understanding brain diseases such as Alzheimer's disease (AD). Surface analysis may be able to identify specific cortical patterns that relate to certain disease characteristics or exhibit differences between groups. Our goal in this paper is to make group analysis of signals on surfaces more sensitive. To do this, we derive multi-scale shape descriptors that characterize the signal around each mesh vertex, i.e., its local context, at varying levels of resolution. In order to define such a shape descriptor, we make use of recent results from harmonic analysis that extend traditional continuous wavelet theory from the Euclidean to a non-Euclidean setting (i.e., a graph, mesh or network). Using this descriptor, we conduct experiments on two different datasets, the Alzheimer's Disease NeuroImaging Initiative (ADNI) data and images acquired at the Wisconsin Alzheimer's Disease Research Center (W-ADRC), focusing on individuals labeled as having Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. In particular, we contrast traditional univariate methods with our multi-resolution approach which show increased sensitivity and improved statistical power to detect a group-level effects. We also provide an open source implementation. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Kim, Won Hwa; Singh, Vikas; Hinrichs, Chris; Pachauri, Deepti] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA.
[Singh, Vikas; Chung, Moo K.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA.
[Kim, Won Hwa; Singh, Vikas; Okonkwo, Ozioma C.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA.
[Okonkwo, Ozioma C.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA.
RP Kim, WH (reprint author), Univ Wisconsin, Dept Comp Sci, 1210 W Dayton St, Madison, WI 53706 USA.
EM wonhwa@cs.wisc.edu; vsingh@biostat.wisc.edu
OI Kim, Won Hwa/0000-0001-5393-0883; Johnson, Sterling/0000-0002-8501-545X
FU NIH [R01AG040396, R01AG021155, P30 AG010129, K01 AG030514]; NSF [RI
1116584]; NSF CAREER award [1252725]; UW ADRC [P50 AG033514]; Wisconsin
Partnership Program; UW ICTR [1UL1RR025011]; CIBM pre-doctoral
fellowship via NLM grant [5T15LM007359]; Alzheimer's Disease
Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01
AG024904]; National Institute on Aging; National Institute of Biomedical
Imaging and Bioengineering; Canadian Institutes of Health Research
FX We provide a freely downloadable implementation of this framework at
http://pages.cs.wisc.edu/-wonhwa/CTA_toolbox/. This research was
supported by funding from NIH R01AG040396, NIH R01AG021155, NSF RI
1116584, NSF CAREER award 1252725, UW ADRC (P50 AG033514), the Wisconsin
Partnership Program, UW ICTR (1UL1RR025011)and Chris Hinrichs was
supported by a CIBM pre-doctoral fellowship via NLM grant 5T15LM007359.
We appreciate N. Maritza Dowling, Jennifer Oh, Vamsi Ithapu, Joon H. Lee
and Gun W. Park for their help in processing the data and/or the
preparation of this manuscript.; Data collection and sharing for this
project were funded by the Alzheimer's Disease Neuroimaging Initiative
(ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is
funded by the National Institute on Aging, the National Institute of
Biomedical Imaging and Bioengineering, and through generous
contributions from the following: 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.; Mesa 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 is providing funds to support ADNI clinical sites in
Canada. Private sector contributions are facilitated by the Foundation
for the National Institutes of Health (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 disseininated by the Laboratory for Neuro Imaging at the University
of California, Los Angeles. This research was also supported by NIH
grants P30 AG010129 and K01 AG030514.
NR 52
TC 11
Z9 11
U1 0
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUN
PY 2014
VL 93
BP 107
EP 123
DI 10.1016/j.neuroimage.2014.02.028
PN 1
PG 17
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AH7WW
UT WOS:000336347100010
PM 24614060
ER
PT J
AU Portelius, E
Holtta, M
Soininen, H
Bjerke, M
Zetterberg, H
Westerlund, A
Herukka, SK
Blennow, K
Mattsson, N
AF Portelius, Erik
Holtta, Mikko
Soininen, Hilkka
Bjerke, Maria
Zetterberg, Henrik
Westerlund, Anni
Herukka, Sanna-Kaisa
Blennow, Kaj
Mattsson, Niklas
TI Altered Cerebrospinal Fluid Levels of Amyloid beta and Amyloid
Precursor-Like Protein 1 Peptides in Down's Syndrome
SO NEUROMOLECULAR MEDICINE
LA English
DT Article
DE Down's syndrome; Amyloid beta; Amyloid precursor-like protein 1; Mass
spectrometry; Cerebrospinal fluid
ID ALZHEIMERS-DISEASE; BRAIN; BIOMARKER; CLEAVAGE; SYSTEM
AB Down's syndrome (DS) patients develop early Alzheimer's disease pathology with abundant cortical amyloid plaques, likely due to overproduction of the amyloid precursor protein (APP), which subsequently leads to amyloid beta (A beta) aggregation. This is reflected in cerebrospinal fluid (CSF) levels of the 42-amino acid long A beta peptide (A beta 1-42), which are increased in young DS patients and decreases with age. However, it is unclear whether DS also affects other aspects of A beta metabolism, including production of shorter C- and N-terminal truncated A beta peptides, and production of peptides from the amyloid precursor-like protein 1 (APLP1), which is related to APP, and cleaved by the same enzymatic processing machinery. APLP1-derived peptides may be surrogate markers for A beta 1-42 production in the brain. Here, we used hybrid immunoaffinity-mass spectrometry and enzyme-linked immunosorbent assays to monitor several A beta and APLP1 peptides in CSF from DS patients (n = 12) and healthy controls (n = 20). CSF levels of A beta 1-42 and three endogenous peptides derived from APLP1 (APL1 beta 25, APL1 beta 27 and APL1 beta 28) were decreased in DS compared with controls, while a specific A beta peptide, A beta 1-28, was increased in a majority of the DS individuals. This study indicates that DS causes previously unknown specific alterations of APP and APLP1 metabolism.
C1 [Portelius, Erik; Holtta, Mikko; Bjerke, Maria; Zetterberg, Henrik; Westerlund, Anni; Blennow, Kaj; Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden.
[Soininen, Hilkka; Herukka, Sanna-Kaisa] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Soininen, Hilkka; Herukka, Sanna-Kaisa] Univ Eastern Finland, Inst Clin Med Neurol, Sch Med, Kuopio 70211, Finland.
[Zetterberg, Henrik] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Mattsson, Niklas] Univ Calif San Francisco, San Francisco VA Med Ctr, CIND, San Francisco, CA USA.
[Mattsson, Niklas] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
RP Portelius, E (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden.
EM erik.portelius@neuro.gu.se
FU Swedish Research Council [14002, K2010-63P-21562-01-4,
K2011-61X-20401-05-6]; Stiftelsen Gamla Tjanarinnor; Magn. Bergvalls
Stiftelse; Gun och Bertil Stohnes Stiftelse; Swedish Brain Fund;
Alzheimer Foundation, Sweden; Dementia Association, Sweden; Wenner-gren
foundation; Strategic for UEF-BRAIN; JPND Project BIOMARKAPD; Goteborgs
Lakaresallskap; Svenska Lakaresallskapet; Klinisk Biokemi i Norden;
Carl-Bertil Laurells fond
FX The study was supported by the Swedish Research Council (Project Nos.
14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6), Stiftelsen Gamla
Tjanarinnor, Magn. Bergvalls Stiftelse, Gun och Bertil Stohnes
Stiftelse, the Swedish Brain Fund, the Alzheimer Foundation, Sweden, the
Dementia Association, Sweden, Wenner-gren foundation, Strategic for
UEF-BRAIN and the JPND Project BIOMARKAPD, Goteborgs Lakaresallskap,
Svenska Lakaresallskapet, Klinisk Biokemi i Norden, Carl-Bertil Laurells
fond.
NR 26
TC 7
Z9 7
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
EI 1559-1174
J9 NEUROMOL MED
JI Neuromol. Med.
PD JUN
PY 2014
VL 16
IS 2
BP 510
EP 516
DI 10.1007/s12017-014-8302-1
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA AH6EW
UT WOS:000336224500022
PM 24740518
ER
PT J
AU Borsook, D
Aasted, CM
Burstein, R
Becerra, L
AF Borsook, David
Aasted, Christopher M.
Burstein, Rami
Becerra, Lino
TI Migraine Mistakes: Error Awareness
SO NEUROSCIENTIST
LA English
DT Article
DE headache; pain; insula; basal ganglia; neural networks
ID MEDIAL PREFRONTAL CORTEX; BASAL GANGLIA; PREDICTION ERRORS; CINGULATE
CORTEX; ORBITOFRONTAL CORTEX; REWARD PREDICTION; DOPAMINE NEURONS;
BRAIN; ANXIETY; INSULA
AB Error awareness or detection is the conscious and subconscious processing to evaluate physiological signals that are different from a baseline or homeostatic level. Migraine is a unique neurological disorder in which there are repeated attacks interspersed by attack-free periods. These attacks are dynamic and multidimensional in the sense that sensory, affective, autonomic, and cognitive functions are altered and these changes evolve differently before (pre-ictal), during (ictal), and immediately after (post-ictal) an attack. Thus migraine serves as a model disease to understand how the brain monitors and react to the presence of errors.
C1 [Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston, MA USA.
[Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, PAIN Grp,Boston Childrens Hosp, Boston, MA USA.
[Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA.
[Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Boston, MA USA.
RP Borsook, D (reprint author), Boston Childrens Hosp, Ctr Pain & Brain, 9 Hope Ave,Box 26, Waltham, MA 02453 USA.
EM dborsook@partners.org
FU National Institute of Neurological Disorders and Stroke (NINDS) [R01
NS073997, R01 NS075018, K24 NS064050, R01 NS069847, R37 079778]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the National Institute of Neurological Disorders and
Stroke (NINDS) (R01 NS073997, R01 NS075018, and K24 NS064050) to DB, and
R01 NS069847 and R37 079778 to RB.
NR 93
TC 3
Z9 3
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-8584
EI 1089-4098
J9 NEUROSCIENTIST
JI Neuroscientist
PD JUN
PY 2014
VL 20
IS 3
BP 291
EP 304
DI 10.1177/1073858413503711
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH6TZ
UT WOS:000336265200013
PM 24047609
ER
PT J
AU Kemmerly, T
Vuong, C
Kaunitz, JD
AF Kemmerly, Thomas
Vuong, Carolyn
Kaunitz, Jonathan D.
TI A Novel Phosphorus Repletion Strategy in a Patient With Duodenal
Perforation
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Article
DE adult; nutrition; phosphates; duodenum; drug shortage; parenteral
formulas/compounding; GI access; phosphorus;
fluids-electrolytes/acid-base; enteral access; parenteral nutrition;
enema; life cycle; minerals/trace elements
ID SEVERE HYPOPHOSPHATEMIA; ENEMA; HYPERPHOSPHATEMIA; NUTRITION
AB We describe a case in which a patient receiving parenteral nutrition (PN) developed hypophosphatemia. Due to lack of availability of parenteral phosphate supplements, we chose to restore phosphate using diluted hypertonic sodium phosphate enemas. Due to the recent shortages of parenteral minerals and vitamins, such an alternate means of repletion is of increasing importance. Diluted hypertonic sodium phosphate enemas are inexpensive, easy to administer, and effective since phosphate is readily absorbed across the rectal mucosa. We hope that through this type of repletion, life-threatening hypophosphatemia among patients receiving PN can be avoided.
C1 [Kemmerly, Thomas] Cedars Sinai Med Residency Program, Los Angeles, CA USA.
[Vuong, Carolyn] WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Vuong, Carolyn] WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Dept Pharm, Los Angeles, CA USA.
[Kaunitz, Jonathan D.] UCLA Sch Med, Dept Med, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.] UCLA Sch Med, Dept Surg, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA.
RP Kaunitz, JD (reprint author), UCLA Sch Med, West Los Angeles VAMC, Bldg 114,Room 217E, Los Angeles, CA 90073 USA.
EM jake@ucla.edu
FU NIDDK NIH HHS [R01 DK054221]
NR 17
TC 1
Z9 1
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0884-5336
EI 1941-2452
J9 NUTR CLIN PRACT
JI Nutr. Clin. Pract.
PD JUN
PY 2014
VL 29
IS 3
BP 402
EP 405
DI 10.1177/0884533614529997
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH0FP
UT WOS:000335794900020
PM 24743045
ER
PT J
AU Fox, E
Mosse', YP
Meany, HM
Gurney, JG
Khanna, G
Jackson, HA
Gordon, G
Shusterman, S
Park, JR
Cohn, SL
Adamson, PC
London, WB
Maris, JM
Balis, FM
AF Fox, Elizabeth
Mosse', Yael P.
Meany, Holly M.
Gurney, James G.
Khanna, Geetika
Jackson, Hollie A.
Gordon, Gary
Shusterman, Suzanne
Park, Julie R.
Cohn, Susan L.
Adamson, Peter C.
London, Wendy B.
Maris, John M.
Balis, Frank M.
TI Time to Disease Progression in Children With Relapsed or Refractory
Neuroblastoma Treated With ABT-751: A Report from the Children's
Oncology Group (ANBL0621)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE childhood cancer; clinical trial; microtubule inhibitor; neuroblastoma;
time to progression
ID BIOAVAILABLE TUBULIN INHIBITOR; PEDIATRIC-PATIENTS; SOLID TUMORS;
RELIABILITY; POPULATION; VALIDITY; CANCER
AB BackgroundABT-751, an orally bioavailable sulfonamide binds the colchicine site of beta-tubulin and inhibits microtubule polymerizaton. Prior phase I studies established the recommended dose in children with solid tumors as 200mg/m(2) PO dailyx7 days every 21 days and subjects with neuroblastoma experienced prolonged stable disease. We conducted a phase 2 study (NCT00436852) in children and adolescents with progressive neuroblastoma to determine if ABT-751 prolonged the time to progression (TTP) compared to a hypothesized standard based on a historical control population.
ProcedureChildren and adolescents (n=91) with a median (range) age 7.7 (2.3-21.5) years and progressive neuroblastoma were enrolled and stratified by disease status into disease measureable by CT/MRI (n=47) or disease assessable by I-123-metaiodobenzylguanine scintigraphy (MIBG, n=44). Response was evaluated using RECIST for measureable disease and the Curie score for MIBG-avid disease.
ResultsABT-751 was well tolerated. The objective response rate was 7%. The median TTP was 42 days (95% CI: 36, 56) in the measureable disease stratum and 45 days (95% CI: 42, 85) in the MIBG-avid disease stratum. TTP was similar to the historical control group (n=136, median TTP 42 days). For the combined strata (n=91), 1-year progression free survival (PFS) was 134% and overall survival (OS) was 48 +/- 5%.
ConclusionsThe low objective response rate and failure to prolong TTP indicate that ABT-751 is not sufficiently active to warrant further development for neuroblastoma. However, this trial demonstrates the utility of TTP as the primary endpoint in phase 2 trials in children and adolescents with neuroblastoma. Pediatr Blood Cancer 2014;61:990-996. (c) 2013 Wiley Periodicals, Inc.
C1 [Fox, Elizabeth; Mosse', Yael P.; Adamson, Peter C.; Maris, John M.; Balis, Frank M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Meany, Holly M.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gurney, James G.] Univ Memphis, Sch Publ Hlth, Memphis, TN 38152 USA.
[Gurney, James G.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Khanna, Geetika] Washington Univ, Sch Med, St Louis, MO USA.
[Jackson, Hollie A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Gordon, Gary] Abbott Labs, Abbott Pk, IL 60064 USA.
[Shusterman, Suzanne; London, Wendy B.] Boston Childrens Hosp, Boston, MA USA.
[Shusterman, Suzanne; London, Wendy B.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
[Park, Julie R.] Seattle Childrens Hosp, Seattle, WA USA.
[Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA.
[London, Wendy B.] Children Oncol Grp Stat & Data Ctr, Gainesville, FL USA.
RP Fox, E (reprint author), Childrens Hosp Philadelphia, CTRB4016,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM foxe@email.chop.edu
OI Cohn, Susan/0000-0001-5749-7650
FU Abbott Laboratories (Abbott Park, IL); National Cancer Institute of the
NIH [U10 CA 098453, U10 CA98413]
FX Grant sponsor: Abbott Laboratories (Abbott Park, IL); Grant sponsor:
National Cancer Institute of the NIH; Grant numbers: U10 CA 098453; U10
CA98413
NR 15
TC 7
Z9 8
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2014
VL 61
IS 6
BP 990
EP 996
DI 10.1002/pbc.24900
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AE9IC
UT WOS:000334320100010
PM 24347462
ER
PT J
AU Hitzler, JK
He, WS
Doyle, J
Cairo, M
Camitta, BM
Chan, KW
Perez, MAD
Fraser, C
Gross, TG
Horan, JT
Kennedy-Nasser, AA
Kitko, C
Kurtzberg, J
Lehmann, L
O'Brien, T
Pulsipher, MA
Smith, FO
Zhang, MJ
Eapen, M
Carpenter, PA
AF Hitzler, Johann K.
He, Wensheng
Doyle, John
Cairo, Mitchell
Camitta, Bruce M.
Chan, Ka Wah
Diaz Perez, Miguel A.
Fraser, Christopher
Gross, Thomas G.
Horan, John T.
Kennedy-Nasser, Alana A.
Kitko, Carrie
Kurtzberg, Joanne
Lehmann, Leslie
O'Brien, Tracey
Pulsipher, Michael A.
Smith, Franklin O.
Zhang, Mei-Jie
Eapen, Mary
Carpenter, Paul A.
CA CIBMTR Pediat Canc Working Comm
TI Outcome of Transplantation for Acute Lymphoblastic Leukemia in Children
With Down Syndrome
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE acute lymhoblastic leukemia; Down syndrome; hematopoietic stem cell
transplantation; pediatric; relapse; trisomy 21
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; 2ND REMISSION;
TOXICITY; FAILURE; REGIMEN; RELAPSE
AB We report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL. Pediatr Blood Cancer 2014;61:1126-1128. (c) 2014 Wiley Periodicals, Inc.
C1 [Hitzler, Johann K.; Doyle, John] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[He, Wensheng; Zhang, Mei-Jie; Eapen, Mary] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Cairo, Mitchell] New York Med Coll, Valhalla, NY 10595 USA.
[Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA.
[Chan, Ka Wah] Texas Transplant Inst, San Antonio, TX USA.
[Diaz Perez, Miguel A.] Hosp Nino Jesus, Madrid, Spain.
[Fraser, Christopher] Royal Childrens Hosp, Herston, Qld, Australia.
[Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA.
[Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA.
[Kennedy-Nasser, Alana A.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Kitko, Carrie] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kurtzberg, Joanne] Duke Univ, Durham, NC USA.
[Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Brien, Tracey] Sydney Childrens Hosp, Sydney, NSW, Australia.
[Pulsipher, Michael A.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Smith, Franklin O.] Univ Cincinnati, Inst Canc, Cincinnati, OH USA.
[Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
RP Carpenter, PA (reprint author), Fred Hutchinson Canc Res Ctr, Mailstop D5-290,1024 Fairview Ave N, Seattle, WA 98109 USA.
EM pcarpent@fhcrc.org
FU Public Health Service [U24-CA76518]; National Cancer Institute; National
Heart Lung and Blood Institute; National Institute of Allergy and
Infectious Diseases and Heath Resources and Services Administration
[HHSH234200637015C]
FX Grant sponsor: Public Health Service; Grant number: U24-CA76518; Grant
sponsor: National Cancer Institute; Grant sponsor: National Heart Lung
and Blood Institute; Grant sponsor: National Institute of Allergy and
Infectious Diseases and Heath Resources and Services Administration;
Grant number: HHSH234200637015C
NR 18
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2014
VL 61
IS 6
BP 1126
EP 1128
DI 10.1002/pbc.24918
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AE9IC
UT WOS:000334320100036
PM 24391118
ER
PT J
AU Nowak, J
Seidel, C
Pietsch, T
Friedrich, C
von Hoff, K
Rutkowski, S
Warmuth-Metz, M
AF Nowak, Johannes
Seidel, Carolin
Pietsch, Torsten
Friedrich, Carsten
von Hoff, Katja
Rutkowski, Stefan
Warmuth-Metz, Monika
TI Ependymoblastoma of the Brainstem: MRI Findings and Differential
Diagnosis
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE atypical teratoid; rhabdoid tumor; diffuse intrinsic pontine glioma;
embryonal tumor with abundant neuropil and true rosettes;
ependymoblastoma; medulloblastoma; primitive neuroectodermal tumor
ID CENTRAL-NERVOUS-SYSTEM; TRUE ROSETTES ETANTR; OF-THE-LITERATURE;
CASE-BASED UPDATE; ABUNDANT NEUROPIL; EMBRYONAL TUMOR
AB Ependymoblastoma (EBL) is a rare malignant CNS tumor of early childhood, listed as a subgroup of primitive neuroectodermal tumors (PNET) in the 2007 WHO Classification of Tumours of the Central Nervous System. Histologically, EBL can be defined by multilayered, mitotically active ependymoblastic rosettes with central lumen as a histological hallmark. The prognosis seems to be far inferior to other embryonal CNS tumors, and known clinical and MRI characteristics of EBL are based on scattered case reports. We present and discuss two uncommon cases of histopathologically confirmed ependymoblastoma that both seem to originate from the brainstem. Pediatr Blood Cancer 2014;61:1132-1134. (c) 2014 Wiley Periodicals, Inc.
C1 [Nowak, Johannes; Seidel, Carolin; Warmuth-Metz, Monika] Univ Hosp Wurzburg, Reference Ctr Neuroradiol, D-97080 Wurzburg, Germany.
[Seidel, Carolin] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Pietsch, Torsten] Univ Bonn, Dept Neuropathol, Bonn, Germany.
[Friedrich, Carsten; von Hoff, Katja; Rutkowski, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany.
RP Warmuth-Metz, M (reprint author), Univ Hosp Wurzburg, Reference Ctr Neuroradiol, Josef Schneider Str 11, D-97080 Wurzburg, Germany.
EM warmuth_m@ukw.de
FU Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation)
FX Grant sponsor: Deutsche Kinderkrebsstiftung (German Childhood Cancer
Foundation)
NR 20
TC 3
Z9 4
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2014
VL 61
IS 6
BP 1132
EP 1134
DI 10.1002/pbc.24915
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AE9IC
UT WOS:000334320100038
PM 24464920
ER
PT J
AU Goldberg, J
Magruder, KM
Forsberg, CW
Kazis, LE
Ustun, TB
Friedman, MJ
Litz, BT
Vaccarino, V
Heagerty, PJ
Gleason, TC
Huang, GD
Smith, NL
AF Goldberg, Jack
Magruder, Kathryn M.
Forsberg, Christopher W.
Kazis, Lewis E.
Uestuen, T. Bedirhan
Friedman, Matthew J.
Litz, Brett T.
Vaccarino, Viola
Heagerty, Patrick J.
Gleason, Theresa C.
Huang, Grant D.
Smith, Nicholas L.
TI The association of PTSD with physical and mental health functioning and
disability (VA Cooperative Study #569: the course and consequences of
posttraumatic stress disorder in Vietnam-era Veteran twins)
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE PTSD; Vietnam-era Veterans; VR-36; WHODAS 2.0
ID QUALITY-OF-LIFE; COMBAT EXPOSURE; SYMPTOMS; REGISTRY; ORGANIZATION;
COMORBIDITY; VERSION; SF-36; CIDI
AB To assess the relationship of posttraumatic stress disorder (PTSD) with health functioning and disability in Vietnam-era Veterans.
A cross-sectional study of functioning and disability in male Vietnam-era Veteran twins. PTSD was measured by the Composite International Diagnostic Interview; health functioning and disability were assessed using the Veterans RAND 36-Item Health Survey (VR-36) and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). All data collection took place between 2010 and 2012.
Average age of the 5,574 participating Veterans (2,102 Vietnam theater and 3,472 non-theater) was 61.0 years. Veterans with PTSD had poorer health functioning across all domains of VR-36 and increased disability for all subscales of WHODAS 2.0 (all p < .001) compared with Veterans without PTSD. Veterans with PTSD were in poorer overall health on the VR-36 physical composite summary (PCS) (effect size = 0.31 in theater and 0.47 in non-theater Veterans; p < .001 for both) and mental composite summary (MCS) (effect size = 0.99 in theater and 0.78 in non-theater Veterans; p < .001 for both) and had increased disability on the WHODAS 2.0 summary score (effect size = 1.02 in theater and 0.96 in non-theater Veterans; p < .001 for both). Combat exposure, independent of PTSD status, was associated with lower PCS and MCS scores and increased disability (all p < .05, for trend). Within-pair analyses in twins discordant for PTSD produced consistent findings.
Vietnam-era Veterans with PTSD have diminished functioning and increased disability. The poor functional status of aging combat-exposed Veterans is of particular concern.
C1 [Goldberg, Jack; Forsberg, Christopher W.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr S152E, Seattle, WA 98108 USA.
[Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Magruder, Kathryn M.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA.
[Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Kazis, Lewis E.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA USA.
[Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Uestuen, T. Bedirhan] WHO, Classificat & Terminol Team, CH-1211 Geneva, Switzerland.
[Friedman, Matthew J.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, White River Jct, VT USA.
[Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Psychiat, Hanover, NH USA.
[Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Toxicol, Hanover, NH USA.
[Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr, Boston, MA USA.
[Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Vaccarino, Viola] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Gleason, Theresa C.; Huang, Grant D.] VA Off Res & Dev, Cooperat Studies Program, Washington, DC USA.
RP Goldberg, J (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr S152E, 1600 South Columbian Way, Seattle, WA 98108 USA.
EM jack.goldberg@va.gov
FU Cooperative Studies Program (CSP) of the Office of Research and
Development, Clinical Science Research and Development of the United
States Department of Veterans Affairs (VA) [569]; National Institutes of
Health [K24 HL077506]
FX Dr. Goldberg had full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. The funding source was involved in the design and conduct
of the study, and the interpretation, preparation, review, and approval
of the manuscript. The authors were responsible for the collection,
management, analysis, and interpretation of the data and for the
preparation of the manuscript and its submission for publication. The
authors gratefully acknowledge the continued cooperation and
participation of the members of the VET Registry: without their
contribution this research would not have been possible. The authors
would also like to thank the members of the Department of Veterans
Affairs Cooperative Study #569 Group (in addition to the authors): I.
Curtis, A. Ali, B. Majerczyk, B. Harp, K. Moore, A. Fox, M. Tsai, A.
Mori, J. Sporleder, P. Terry, Seattle, WA; D. Yeager, Charleston, SC.
Executive Committee: S. Eisen, Washington, DC; A. Snodgrass,
Albuquerque, NM. Data Monitoring Committee: J. Vasterling, Boston, MA;
M. Stein, La Jolla, CA; B. Booth, Little Rock, AR; J. Westermeyer,
Minneapolis, MN. Planning Committee: M. McFall, Seattle, WA; T. O'Leary,
S. Eisen, Washington, DC; M. Smith, Palo Alto, CA; K. Swanson,
Albuquerque, NM. SF-36 (R) is a registered trademark of the Medical
Outcomes Trust. The Cooperative Studies Program (CSP) of the Office of
Research and Development, Clinical Science Research and Development, of
the United States Department of Veterans Affairs (VA), has provided
financial support for Cooperative Study #569 and the development and
maintenance of the Vietnam Era Twin (VET) Registry. Dr. Viola Vaccarino
was supported in part by a National Institutes of Health award, K24
HL077506
NR 41
TC 12
Z9 12
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD JUN
PY 2014
VL 23
IS 5
BP 1579
EP 1591
DI 10.1007/s11136-013-0585-4
PG 13
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AH8YD
UT WOS:000336423200017
PM 24318083
ER
PT J
AU Conhaim, RL
Watson, KE
Dovi, WF
Bates, ML
AF Conhaim, Robert L.
Watson, Kal E.
Dovi, William F.
Bates, Melissa L.
TI INHALED THROMBOLYTICS REDUCE LUNG MICROCLOT AND LEUKOCYTE INFILTRATION
AFTER ACUTE BLOOD LOSS
SO SHOCK
LA English
DT Article
DE Acute lung injury; neutrophils; thromboembolism; shock lung; pulmonary
circulation; fibrinolysis
ID NEBULIZED ANTICOAGULANTS; INTERALVEOLAR PERFUSION; FIBRIN; RATS; INJURY;
MICROVESSELS; COAGULOPATHY; INFLAMMATION; EDEMA
AB We showed previously that a 30% blood loss in rats, without resuscitation, caused significant accumulation of microthrombi and leukocytes within the pulmonary circulation by 24 h. We hypothesized that the microthrombi formed spontaneously as a consequence of hemorrhage-induced stasis within the low-pressure pulmonary circuit and that the leukocytes were attracted to them. This suggested that elimination of the microthrombi, using an inhaled thrombolytic agent, could prevent the neutrophil sequestration after blood loss. To test this hypothesis, we removed 30% of the calculated blood volume from isoflurane-anesthetized, male Sprague-Dawley rats (350-500 g) over 5 min and allowed them to recover. Six hours later, we reanesthetized the rats and nebulized tissue plasminogen activator (80 or 320 mu g/kg), lactated Ringer's solution (LRS), or ipratropium bromide (i-bromide) into their lungs. We used i-bromide as a control after we discovered that nebulized LRS had thrombolytic properties. At 24 h, we removed and fixed the lungs and prepared sections for immunohistochemistry using antibodies against fibrinogen (microthrombi) and CD16 (leukocytes). Digital images of each section were obtained using a confocal microscope. Pixel counts of the images showed significantly less accumulation of microthrombi and leukocytes in lungs nebulized with tissue plasminogen activator or LRS than in nonnebulized lungs or in lungs nebulized with i-bromide (P 0.05). Lactated Ringer's solution becomes positively charged when nebulized (unlike i-bromide), suggesting that it eliminated microthrombi by fibrin depolymerization. We confirmed this using an in vitro assay. Our results demonstrate that lyses of microthrombi that accumulate in the lung after acute blood loss prevent subsequent leukocyte sequestration.
C1 [Conhaim, Robert L.; Watson, Kal E.] Univ Wisconsin, Dept Surg, Sch Med & Publ Heath, Madison, WI USA.
[Conhaim, Robert L.; Dovi, William F.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Bates, Melissa L.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Heath, Madison, WI USA.
RP Conhaim, RL (reprint author), H5-301-BX3236,600 Highland Ave, Madison, WI 53792 USA.
EM rconhaim@wisc.edu
FU Veterans Health Administration, Office of Research and Development,
Department of Veterans Affairs, Biomedical Laboratory Research and
Development Service
FX This study was supported by the Veterans Health Administration, Office
of Research and Development, Department of Veterans Affairs, Biomedical
Laboratory Research and Development Service (R. L. C., principal
investigator).
NR 24
TC 1
Z9 1
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD JUN
PY 2014
VL 41
IS 6
BP 528
EP 536
DI 10.1097/SHK.0000000000000149
PG 9
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AH6CI
UT WOS:000336217900010
PM 24837203
ER
PT J
AU Dunn, EC
Masyn, KE
Yudron, M
Jones, SM
Subramanian, SV
AF Dunn, Erin C.
Masyn, Katherine E.
Yudron, Monica
Jones, Stephanie M.
Subramanian, S. V.
TI Translating multilevel theory into multilevel research: challenges and
opportunities for understanding the social determinants of psychiatric
disorders
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Article
DE Multilevel; Social determinants; Social and physical environments;
Ecological; Context; Composition; Psychiatric disorders
ID MENTAL-HEALTH; NEIGHBORHOOD CHARACTERISTICS; BIOLOGICAL SENSITIVITY;
SYSTEMS SCIENCE; FUTURE-RESEARCH; MODELS; DEPRESSION; ENVIRONMENT; VIEW;
EPIDEMIOLOGY
AB The observation that features of the social environment, including family, school, and neighborhood characteristics, are associated with individual-level outcomes has spurred the development of dozens of multilevel or ecological theoretical frameworks in epidemiology, public health, psychology, and sociology, among other disciplines. Despite the widespread use of such theories in etiological, intervention, and policy studies, challenges remain in bridging multilevel theory and empirical research.
This paper set out to synthesize these challenges and provide specific examples of methodological and analytical strategies researchers are using to gain a more nuanced understanding of the social determinants of psychiatric disorders, with a focus on children's mental health. To accomplish this goal, we begin by describing multilevel theories, defining their core elements, and discussing what these theories suggest is needed in empirical work. In the second part, we outline the main challenges researchers face in translating multilevel theory into research. These challenges are presented for each stage of the research process. In the third section, we describe two methods being used as alternatives to traditional multilevel modeling techniques to better bridge multilevel theory and multilevel research. These are (1) multilevel factor analysis and multilevel structural equation modeling; and (2) dynamic systems approaches.
Through its review of multilevel theory, assessment of existing strategies, and examination of emerging methodologies, this paper offers a framework to evaluate and guide empirical studies on the social determinants of child psychiatric disorders as well as health across the life course.
C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02144 USA.
[Masyn, Katherine E.; Yudron, Monica; Jones, Stephanie M.] Harvard Univ, Harvard Grad Sch Educ, Cambridge, MA 02138 USA.
[Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02144 USA.
EM erindunn@pngu.mgh.harvard.edu
FU NIMH NIH HHS [F31 MH088074, K01 MH102403]
NR 86
TC 8
Z9 8
U1 3
U2 28
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 JUN
PY 2014
VL 49
IS 6
BP 859
EP 872
DI 10.1007/s00127-013-0809-5
PG 14
WC Psychiatry
SC Psychiatry
GA AH7BR
UT WOS:000336287900003
PM 24469555
ER
PT J
AU Manchikanti, L
Falco, FJE
Hirsch, JA
AF Manchikanti, Laxmaiah
Falco, Frank J. E.
Hirsch, Joshua A.
TI Evidence-based guidelines improperly assessed epidural injections
SO SPINE JOURNAL
LA English
DT Letter
ID LUMBAR DISC HERNIATION; DOUBLE-BLIND TRIAL; RANDOMIZED CONTROLLED-TRIAL;
RADICULAR PAIN; PERIRADICULAR INFILTRATION; STEROID INJECTIONS; SUBGROUP
ANALYSIS; FOLLOW-UP; SCIATICA; INTERLAMINAR
C1 [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Paducah, KY 42003 USA.
[Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE 19713 USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, 2831 Lone Oak Rd, Paducah, KY 42003 USA.
NR 20
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-9430
EI 1878-1632
J9 SPINE J
JI Spine Journal
PD JUN
PY 2014
VL 14
IS 6
BP 1086
EP 1087
DI 10.1016/j.spinee.2014.01.029
PG 3
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA AH8UA
UT WOS:000336412500047
PM 24851737
ER
PT J
AU Barrisford, GW
Gershman, B
Blute, ML
AF Barrisford, Glen W.
Gershman, Boris
Blute, Michael L., Sr.
TI The role of lymphadenectomy in the management of renal cell carcinoma
SO WORLD JOURNAL OF UROLOGY
LA English
DT Article
DE Renal cell carcinoma; Renal cancer; Lymphadenectomy; Lymph node
dissection
ID LYMPH-NODE DISSECTION; PROSPECTIVE CLINICAL-TRIALS; RADICAL NEPHRECTOMY;
STRATIFICATION TOOL; SURGICAL RESECTION; SURVIVAL; CANCER; PROGRESSION;
METASTASES; PREDICTION
AB The role of lymphadenectomy in the management of renal cell carcinoma has been established in staging but is less well defined as a therapeutic maneuver. Level one evidence suggests no survival benefit or increased complication rate with lymphadenectomy when performed concurrently with radical nephrectomy. However, several retrospective studies have identified a survival benefit when patients with increased risk of micrometastatic lymph node disease undergo lymphadenectomy. We perform a selective review of the literature and present the historical basis, risk assessment, use and development of nodal templates, and therapeutic benefits associated with the use of lymphadenectomy in the management of renal cell carcinoma.
C1 [Barrisford, Glen W.; Gershman, Boris; Blute, Michael L., Sr.] Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, Boston, MA 02114 USA.
RP Blute, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM gbarrisford@partners.org; mblute@partners.org
NR 28
TC 1
Z9 1
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-4983
EI 1433-8726
J9 WORLD J UROL
JI World J. Urol.
PD JUN
PY 2014
VL 32
IS 3
BP 643
EP 649
DI 10.1007/s00345-014-1294-5
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AH8RL
UT WOS:000336405800010
PM 24723269
ER
PT J
AU Sammon, JD
Sharma, P
Rahbar, H
Roghmann, F
Ghani, KR
Sukumar, S
Karakiewicz, PI
Peabody, JO
Elder, JS
Menon, M
Sun, M
Trinh, QD
AF Sammon, Jesse D.
Sharma, Pranav
Rahbar, Haider
Roghmann, Florian
Ghani, Khurshid R.
Sukumar, Shyam
Karakiewicz, Pierre I.
Peabody, James O.
Elder, Jack S.
Menon, Mani
Sun, Maxine
Quoc-Dien Trinh
TI Predictors of admission in patients presenting to the emergency
department with urinary tract infection
SO WORLD JOURNAL OF UROLOGY
LA English
DT Article
DE Urinary tract infection; Emergency department; Predictors of admission;
Nationwide Emergency Department Sample (NEDS)
ID ACUTE PYELONEPHRITIS; UROLOGIC DISEASES; AMERICA PROJECT; RESOURCE USE;
WOMEN; HOSPITALIZATION; BEHAVIOR; THERAPY; ADULTS; TRENDS
AB Previous studies examining the management of urinary tract infections (UTI) showed marked variability in the economical burden of care, with a tenfold increase in costs when patients require admission to the hospital. We sought to examine the patient and emergency department (ED) characteristics associated with hospitalization in patients presenting to the ED with UTI.
An estimate of 10,798,343 patients with a primary diagnosis of UTI was presented to the ED from 2006 to 2009 and was abstracted from the Nationwide Emergency Department Sample. Univariable and multivariable analyses examined patient and hospital characteristics of those admitted with UTI.
Between 2006 and 2009, 10.8 million patients presented to the ED in the United States for the treatment of UTI and 1.8 million patients (16.7 %) were admitted to the hospital for further management. Admitted patients were older, and a higher proportion had pyelonephritis, was male, and had Medicare. Admitted patients were also more likely to be seen at urban teaching hospitals, and/or treated at zip codes with higher median incomes. Following multivariable analysis, the independent predictors of admission included pyelonephritis (OR 5.29, 95 % CI 5.23-5.35), male gender (OR 1.58, 95 % CI 1.56-1.59), and advancing age (OR 1.037, 95 % CI 1.037-1.037).
Expansion in ED utilization for the management of UTI has exceeded previous estimates. While the preponderance of patients presenting to the ED for UTI is discharged home, 16.7 % are admitted for further management. Predictors of inpatient admission on multivariable analyses included pyelonephritis, advancing age, and male gender.
C1 [Sammon, Jesse D.; Sharma, Pranav; Ghani, Khurshid R.; Sukumar, Shyam; Peabody, James O.; Elder, Jack S.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA.
[Sammon, Jesse D.; Sharma, Pranav; Ghani, Khurshid R.; Sukumar, Shyam] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA.
[Rahbar, Haider] Wayne State Univ, Sch Med, Detroit, MI USA.
[Roghmann, Florian; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada.
[Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol,Dept Surg,Med Sch, Boston, MA 02115 USA.
RP Sammon, JD (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA.
EM jsammon79@gmail.com
NR 25
TC 2
Z9 3
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-4983
EI 1433-8726
J9 WORLD J UROL
JI World J. Urol.
PD JUN
PY 2014
VL 32
IS 3
BP 813
EP 819
DI 10.1007/s00345-013-1167-3
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AH8RL
UT WOS:000336405800031
PM 24072010
ER
PT J
AU Paruch, JL
Merkow, RP
Bentrem, DJ
Ko, CY
Posner, MC
Cohen, ME
Bilimoria, KY
Weber, SM
AF Paruch, Jennifer L.
Merkow, Ryan P.
Bentrem, David J.
Ko, Clifford Y.
Posner, Mitchell C.
Cohen, Mark E.
Bilimoria, Karl Y.
Weber, Sharon M.
TI Impact of Hepatectomy Surgical Complexity on Outcomes and Hospital
Quality Rankings
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID RISK-ADJUSTMENT; IMPROVEMENT PROGRAM; LIVER RESECTION; NSQIP; SURGERY;
MODELS
AB There is substantial variation in the surgical complexity of hepatectomy. Currently, the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk adjusts for hospital quality comparisons using only the primary procedure code. Our objectives were to (1) assess the association between secondary procedures and complications; (2) assess model performance with inclusion of surgical complexity adjustment; and (3) examine whether secondary procedures affect hospital quality rankings.
Using ACS NSQIP (2007-2012), patients undergoing hepatectomy were identified. Secondary procedure codes and total work relative value units (RVUs) were used to approximate procedural complexity. The effect of procedural complexity variables on outcomes and hospital quality rankings were examined using hierarchical models.
Among 11,826 patients who underwent hepatectomy at 261 hospitals, 32.8 % underwent at least one secondary procedure. Serious morbidity occurred in 18.0 % of patients. Seven of nine secondary procedures were significantly associated with death or serious morbidity on multivariable analysis. Model performance improved when secondary procedure categories were included, and secondary procedure categories outperformed total RVUs. The C-statistic for death or serious morbidity was 0.689 in the standard NSQIP model, 0.703 when total RVU was included, and 0.718 when secondary procedure categories were included. Of the 26 hospitals that were poor performers for death or serious morbidity using the standard ACS NSQIP model, three became average performers when secondary procedure categories were included in the model.
Secondary procedures are associated with an increased risk of postoperative complications. Inclusion of secondary procedure code categories in research and risk prediction models should be considered for hepatectomy.
C1 [Paruch, Jennifer L.; Merkow, Ryan P.; Ko, Clifford Y.; Cohen, Mark E.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA.
[Paruch, Jennifer L.; Merkow, Ryan P.; Posner, Mitchell C.] Univ Chicago, Dept Surg, Pritzker Sch Med, Chicago, IL 60637 USA.
[Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
[Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Northwestern Inst Comparat Effectiveness Res Onco, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA.
[Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Weber, Sharon M.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA.
RP Paruch, JL (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA.
EM jlparuch@gmail.com
FU American Cancer Society; National Comprehensive Cancer Network
FX This work was supported in part by the American Cancer Society (Drs.
Merkow and Bilimoria) and the National Comprehensive Cancer Network (Dr.
Bilimoria).
NR 20
TC 8
Z9 8
U1 0
U2 5
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 JUN
PY 2014
VL 21
IS 6
BP 1773
EP 1780
DI 10.1245/s10434-014-3500-5
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA AG9GH
UT WOS:000335726900005
PM 24558060
ER
PT J
AU Thompson, PM
Stein, JL
Medland, SE
Hibar, DP
Vasquez, AA
Renteria, ME
Toro, R
Jahanshad, N
Schumann, G
Franke, B
Wright, MJ
Martin, NG
Agartz, I
Alda, M
Alhusaini, S
Almasy, L
Almeida, J
Alpert, K
Andreasen, NC
Andreassen, OA
Apostolova, LG
Appel, K
Armstrong, NJ
Aribisala, B
Bastin, ME
Bauer, M
Bearden, CE
Bergmann, O
Binder, EB
Blangero, J
Bockholt, HJ
Boen, E
Bois, C
Boomsma, DI
Booth, T
Bowman, IJ
Bralten, J
Brouwer, RM
Brunner, HG
Brohawn, DG
Buckner, RL
Buitelaar, J
Bulayeva, K
Bustillo, JR
Calhoun, VD
Cannon, DM
Cantor, RM
Carless, MA
Caseras, X
Cavalleri, GL
Chakravarty, MM
Chang, KD
Ching, CRK
Christoforou, A
Cichon, S
Clark, VP
Conrod, P
Coppola, G
Crespo-Facorro, B
Curran, JE
Czisch, M
Deary, IJ
de Geus, EJC
den Braber, A
Delvecchio, G
Depondt, C
de Haan, L
de Zubicaray, GI
Dima, D
Dimitrova, R
Djurovic, S
Dong, HW
Donohoe, G
Duggirala, R
Dyer, TD
Ehrlich, S
Ekman, CJ
Elvsashagen, T
Emsell, L
Erk, S
Espeseth, T
Fagerness, J
Fears, S
Fedko, I
Fernandez, G
Fisher, SE
Foroud, T
Fox, PT
Francks, C
Frangou, S
Frey, EM
Frodl, T
Frouin, V
Garavan, H
Giddaluru, S
Glahn, DC
Godlewska, B
Goldstein, RZ
Gollub, RL
Grabe, HJ
Grimm, O
Gruber, O
Guadalupe, T
Gur, RE
Gur, RC
Goring, H
Hagenaars, S
Hajek, T
Hall, GB
Hall, J
Hardy, J
Hartman, CA
Hass, J
Hatton, SN
Haukvik, UK
Hegenscheid, K
Heinz, A
Hickie, IB
Ho, BC
Hoehn, D
Hoekstra, PJ
Hollinshead, M
Holmes, AJ
Homuth, G
Hoogman, M
Hong, LE
Hosten, N
Hottenga, JJ
Pol, HEH
Hwang, KS
Jack, CR
Jenkinson, M
Johnston, C
Jonsson, E
Kahn, R
Kasperaviciute, D
Kelly, S
Kim, S
Kochunov, P
Koenders, L
Kramer, B
Kwok, JBJ
Lagopoulos, J
Laje, G
Landen, M
Landman, BA
Lauriello, J
Lawrie, SM
Lee, PH
Le Hellard, S
Lemaitre, H
Leonardo, CD
Li, CS
Liberg, B
Liewald, DC
Liu, XM
Lopez, LM
Loth, E
Lourdusamy, A
Luciano, M
Macciardi, F
Machielsen, MWJ
MacQueen, GM
Malt, UF
Mandl, R
Manoach, DS
Martinot, JL
Matarin, M
Mather, KA
Mattheisen, M
Mattingsdal, M
Meyer-Lindenberg, A
McDonald, C
McIntosh, AM
McMahon, FJ
McMahon, KL
Meisenzahl, E
Melle, I
Milaneschi, Y
Mohnke, S
Montgomery, GW
Morris, DW
Moses, EK
Mueller, BA
Munoz Maniega, S
Muhleisen, T
Muller-Myhsok, B
Mwangi, B
Nauck, M
Nho, K
Nichols, TE
Nilsson, LG
Nugent, AC
Nyberg, L
Olvera, RL
Oosterlaan, J
Ophoff, RA
Pandolfo, M
Papalampropoulou-Tsiridou, M
Papmeyer, M
Paus, T
Pausova, Z
Pearlson, GD
Penninx, BW
Peterson, CP
Pfennig, A
Phillips, M
Pike, GB
Poline, JB
Potkin, SG
Putz, B
Ramasamy, A
Rasmussen, J
Rietschel, M
Rijpkema, M
Risacher, SL
Roffman, JL
Roiz-Santianez, R
Romanczuk-Seiferth, N
Rose, EJ
Royle, NA
Rujescu, D
Ryten, M
Sachdev, PS
Salami, A
Satterthwaite, TD
Savitz, J
Saykin, AJ
Scanlon, C
Schmaal, L
Schnack, HG
Schork, AJ
Schulz, SC
Schur, R
Seidman, L
Shen, L
Shoemaker, JM
Simmons, A
Sisodiya, SM
Smith, C
Smoller, JW
Soares, JC
Sponheim, SR
Sprooten, E
Starr, JM
Steen, VM
Strakowski, S
Strike, L
Sussmann, J
Samann, PG
Teumer, A
Toga, AW
Tordesillas-Gutierrez, D
Trabzuni, D
Trost, S
Turner, J
Van den Heuvel, M
Van der Wee, NJ
van Eijk, K
van Erp, TGM
van Haren, NEM
Van 't Ent, D
van Tol, MJ
Hernandez, MCV
Veltman, DJ
Versace, A
Volzke, H
Walker, R
Walter, H
Wang, L
Wardlaw, JM
Weale, ME
Weiner, MW
Wen, W
Westlye, LT
Whalley, HC
Whelan, CD
White, T
Winkler, AM
Wittfeld, K
Woldehawariat, G
Wolf, C
Zilles, D
Zwiers, MP
Thalamuthu, A
Schofield, PR
Freimer, NB
Lawrence, NS
Drevets, W
AF Thompson, Paul M.
Stein, Jason L.
Medland, Sarah E.
Hibar, Derrek P.
Vasquez, Alejandro Arias
Renteria, Miguel E.
Toro, Roberto
Jahanshad, Neda
Schumann, Gunter
Franke, Barbara
Wright, Margaret J.
Martin, Nicholas G.
Agartz, Ingrid
Alda, Martin
Alhusaini, Saud
Almasy, Laura
Almeida, Jorge
Alpert, Kathryn
Andreasen, Nancy C.
Andreassen, Ole A.
Apostolova, Liana G.
Appel, Katja
Armstrong, Nicola J.
Aribisala, Benjamin
Bastin, Mark E.
Bauer, Michael
Bearden, Carrie E.
Bergmann, Orjan
Binder, Elisabeth B.
Blangero, John
Bockholt, Henry J.
Boen, Erlend
Bois, Catherine
Boomsma, Dorret I.
Booth, Tom
Bowman, Ian J.
Bralten, Janita
Brouwer, Rachel M.
Brunner, Han G.
Brohawn, David G.
Buckner, Randy L.
Buitelaar, Jan
Bulayeva, Kazima
Bustillo, Juan R.
Calhoun, Vince D.
Cannon, Dara M.
Cantor, Rita M.
Carless, Melanie A.
Caseras, Xavier
Cavalleri, Gianpiero L.
Chakravarty, M. Mallar
Chang, Kiki D.
Ching, Christopher R. K.
Christoforou, Andrea
Cichon, Sven
Clark, Vincent P.
Conrod, Patricia
Coppola, Giovanni
Crespo-Facorro, Benedicto
Curran, Joanne E.
Czisch, Michael
Deary, Ian J.
de Geus, Eco J. C.
den Braber, Anouk
Delvecchio, Giuseppe
Depondt, Chantal
de Haan, Lieuwe
de Zubicaray, Greig I.
Dima, Danai
Dimitrova, Rali
Djurovic, Srdjan
Dong, Hongwei
Donohoe, Gary
Duggirala, Ravindranath
Dyer, Thomas D.
Ehrlich, Stefan
Ekman, Carl Johan
Elvsashagen, Torbjorn
Emsell, Louise
Erk, Susanne
Espeseth, Thomas
Fagerness, Jesen
Fears, Scott
Fedko, Iryna
Fernandez, Guillen
Fisher, Simon E.
Foroud, Tatiana
Fox, Peter T.
Francks, Clyde
Frangou, Sophia
Frey, Eva Maria
Frodl, Thomas
Frouin, Vincent
Garavan, Hugh
Giddaluru, Sudheer
Glahn, David C.
Godlewska, Beata
Goldstein, Rita Z.
Gollub, Randy L.
Grabe, Hans J.
Grimm, Oliver
Gruber, Oliver
Guadalupe, Tulio
Gur, Raquel E.
Gur, Ruben C.
Goering, Harald H. H.
Hagenaars, Saskia
Hajek, Tomas
Hall, Geoffrey B.
Hall, Jeremy
Hardy, John
Hartman, Catharina A.
Hass, Johanna
Hatton, Sean N.
Haukvik, Unn K.
Hegenscheid, Katrin
Heinz, Andreas
Hickie, Ian B.
Ho, Beng-Choon
Hoehn, David
Hoekstra, Pieter J.
Hollinshead, Marisa
Holmes, Avram J.
Homuth, Georg
Hoogman, Martine
Hong, L. Elliot
Hosten, Norbert
Hottenga, Jouke-Jan
Pol, Hilleke E. Hulshoff
Hwang, Kristy S.
Jack, Clifford R., Jr.
Jenkinson, Mark
Johnston, Caroline
Joensson, Erik G.
Kahn, Rene S.
Kasperaviciute, Dalia
Kelly, Sinead
Kim, Sungeun
Kochunov, Peter
Koenders, Laura
Kraemer, Bernd
Kwok, John B. J.
Lagopoulos, Jim
Laje, Gonzalo
Landen, Mikael
Landman, Bennett A.
Lauriello, John
Lawrie, Stephen M.
Lee, Phil H.
Le Hellard, Stephanie
Lemaitre, Herve
Leonardo, Cassandra D.
Li, Chiang-shan
Liberg, Benny
Liewald, David C.
Liu, Xinmin
Lopez, Lorna M.
Loth, Eva
Lourdusamy, Anbarasu
Luciano, Michelle
Macciardi, Fabio
Machielsen, Marise W. J.
MacQueen, Glenda M.
Malt, Ulrik F.
Mandl, Rene
Manoach, Dara S.
Martinot, Jean-Luc
Matarin, Mar
Mather, Karen A.
Mattheisen, Manuel
Mattingsdal, Morten
Meyer-Lindenberg, Andreas
McDonald, Colm
McIntosh, Andrew M.
McMahon, Francis J.
McMahon, Katie L.
Meisenzahl, Eva
Melle, Ingrid
Milaneschi, Yuri
Mohnke, Sebastian
Montgomery, Grant W.
Morris, Derek W.
Moses, Eric K.
Mueller, Bryon A.
Munoz Maniega, Susana
Muehleisen, Thomas W.
Mueller-Myhsok, Bertram
Mwangi, Benson
Nauck, Matthias
Nho, Kwangsik
Nichols, Thomas E.
Nilsson, Lars-Goeran
Nugent, Allison C.
Nyberg, Lars
Olvera, Rene L.
Oosterlaan, Jaap
Ophoff, Roel A.
Pandolfo, Massimo
Papalampropoulou-Tsiridou, Melina
Papmeyer, Martina
Paus, Tomas
Pausova, Zdenka
Pearlson, Godfrey D.
Penninx, Brenda W.
Peterson, Charles P.
Pfennig, Andrea
Phillips, Mary
Pike, G. Bruce
Poline, Jean-Baptiste
Potkin, Steven G.
Puetz, Benno
Ramasamy, Adaikalavan
Rasmussen, Jerod
Rietschel, Marcella
Rijpkema, Mark
Risacher, Shannon L.
Roffman, Joshua L.
Roiz-Santianez, Roberto
Romanczuk-Seiferth, Nina
Rose, Emma J.
Royle, Natalie A.
Rujescu, Dan
Ryten, Mina
Sachdev, Perminder S.
Salami, Alireza
Satterthwaite, Theodore D.
Savitz, Jonathan
Saykin, Andrew J.
Scanlon, Cathy
Schmaal, Lianne
Schnack, Hugo G.
Schork, Andrew J.
Schulz, S. Charles
Schuer, Remmelt
Seidman, Larry
Shen, Li
Shoemaker, Jody M.
Simmons, Andrew
Sisodiya, Sanjay M.
Smith, Colin
Smoller, Jordan W.
Soares, Jair C.
Sponheim, Scott R.
Sprooten, Emma
Starr, John M.
Steen, Vidar M.
Strakowski, Stephen
Strike, Lachlan
Sussmann, Jessika
Saemann, Philipp G.
Teumer, Alexander
Toga, Arthur W.
Tordesillas-Gutierrez, Diana
Trabzuni, Daniah
Trost, Sarah
Turner, Jessica
Van den Heuvel, Martijn
van der Wee, Nic J.
van Eijk, Kristel
van Erp, Theo G. M.
van Haren, Neeltje E. M.
van 't Ent, Dennis
van Tol, Marie-Jose
Hernandez, Maria C. Valdes
Veltman, Dick J.
Versace, Amelia
Voelzke, Henry
Walker, Robert
Walter, Henrik
Wang, Lei
Wardlaw, Joanna M.
Weale, Michael E.
Weiner, Michael W.
Wen, Wei
Westlye, Lars T.
Whalley, Heather C.
Whelan, Christopher D.
White, Tonya
Winkler, Anderson M.
Wittfeld, Katharina
Woldehawariat, Girma
Wolf, Christiane
Zilles, David
Zwiers, Marcel P.
Thalamuthu, Anbupalam
Schofield, Peter R.
Freimer, Nelson B.
Lawrence, Natalia S.
Drevets, Wayne
CA Alzheimer's Dis Neuroimaging
EPIGEN Consortium
IMAGEN Consortium
Saguenay Youth Study SYS Grp
TI The ENIGMA Consortium: large-scale collaborative analyses of
neuroimaging and genetic data
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Genetics; MRI; GWAS; Consortium; Meta-analysis; Multi-site
ID GENOME-WIDE ASSOCIATION; CORTICAL SURFACE-AREA; WHITE-MATTER
MICROSTRUCTURE; MULTIVARIATE PARALLEL ICA; TENSOR-BASED MORPHOMETRY;
QUANTITATIVE TRAIT LOCI; VOXEL-BASED MORPHOMETRY; HUMAN BRAIN STRUCTURE;
DISEASE RISK VARIANT; BODY-MASS INDEX
AB The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
C1 [Thompson, Paul M.; Hibar, Derrek P.; Jahanshad, Neda; Bowman, Ian J.; Ching, Christopher R. K.; Dong, Hongwei; Leonardo, Cassandra D.; Toga, Arthur W.] Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, Los Angeles, CA 90033 USA.
[Montgomery, Grant W.; Strike, Lachlan] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Lee, Phil H.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Boston, MA USA.
[Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Brunner, Han G.; Hoogman, Martine] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Buitelaar, Jan; Fisher, Simon E.; Francks, Clyde; Rijpkema, Mark; Zwiers, Marcel P.] Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands.
[Toro, Roberto] Inst Pasteur, Human Genet & Cognit Funct, Paris, France.
[Toro, Roberto] Inst Pasteur, CNRS URA Genes Synapses & Cognit 2182, Paris, France.
[Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
[Glahn, David C.] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06115 USA.
[Glahn, David C.; Li, Chiang-shan; Pearlson, Godfrey D.; Winkler, Anderson M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Appel, Katja; Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, NORMENT, KG Jebsen Ctr Psychosis Res, Oslo Univ Hosp, Oslo, Norway.
[Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Alhusaini, Saud; Cavalleri, Gianpiero L.; Whelan, Christopher D.] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland.
[Almasy, Laura; Blangero, John; Carless, Melanie A.; Curran, Joanne E.; Duggirala, Ravindranath; Dyer, Thomas D.; Goering, Harald H. H.; Moses, Eric K.; Peterson, Charles P.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Andreasen, Nancy C.; Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Apostolova, Liana G.; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Aribisala, Benjamin; Bastin, Mark E.; Booth, Tom; Deary, Ian J.; Liewald, David C.; Lopez, Lorna M.; Luciano, Michelle; Munoz Maniega, Susana; Royle, Natalie A.; Starr, John M.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Aribisala, Benjamin; Munoz Maniega, Susana; Wardlaw, Joanna M.] Scottish Imaging Network, St Andrews, Fife, Scotland.
[Aribisala, Benjamin; Bastin, Mark E.; Munoz Maniega, Susana; Royle, Natalie A.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.
[Binder, Elisabeth B.; Czisch, Michael; Hoehn, David; Mueller-Myhsok, Bertram; Puetz, Benno; Saemann, Philipp G.; Wolf, Christiane] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Calhoun, Vince D.; Shoemaker, Jody M.; Turner, Jessica] Mind Res Network, Albuquerque, NM USA.
[Boomsma, Dorret I.; de Geus, Eco J. C.; den Braber, Anouk; Fedko, Iryna; Hottenga, Jouke-Jan; van 't Ent, Dennis] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
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[Muehleisen, Thomas W.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
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[Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany.
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RP Thompson, PM (reprint author), Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, 2001 N Soto St, Los Angeles, CA 90033 USA.
EM pthomp@usc.edu; wdrevets@its.jnj.com
RI Nyberg, Lars/C-2514-2009; Weale, Michael/F-2587-2010; de Zubicaray,
Greig/B-1763-2008; Walter, Henrik/O-2612-2013; Bralten,
Janita/D-4647-2011; Hoogman, Martine/G-8958-2015; Roiz-Santianez,
Roberto/H-6462-2015; Tordesillas-Gutierrez, Diana/H-6893-2015; Turner,
Jessica/H-7282-2015; Rijpkema, Mark/D-1974-2010; Zwiers,
Marcel/D-2968-2009; Alda, Martin/F-5812-2010; Cavalleri,
Gianpiero/A-6632-2010; Rose, Emma/A-9960-2010; Brunner, Han/C-9928-2013;
Hoekstra, Pieter/O-4396-2014; Savitz, Jonathan/C-3088-2009; Fox,
Peter/B-4725-2010; Fisher, Simon/E-9130-2012; Ho,
Beng-Choon/D-6959-2011; Lourdusamy, Anbarasu/P-6606-2014; Franke,
Barbara/D-4836-2009; Ramasamy, Adaikalavan/G-2632-2010; Medland,
Sarah/C-7630-2013; Jack, Clifford/F-2508-2010; Simmons,
Andrew/B-8848-2008; Pike, Bruce/K-5562-2014; Binder,
Elisabeth/K-8905-2014; Hardy, John/C-2451-2009; Laje,
Gonzalo/L-2654-2014; McDonald, Colm/C-1430-2009; Dima,
Danai/H-4342-2014; Hulshoff Pol, Hilleke/B-4795-2014; Munoz Maniega,
Susana/I-8730-2014; Fernandez, Guillen/B-3771-2009; Montgomery,
Grant/B-7148-2008; Mattheisen, Manuel/B-4949-2012; Wright,
Margaret/A-4560-2016; Arias Vasquez, Alejandro/E-4762-2012; McMahon,
Katie/C-6440-2009; Macciardi, Fabio/N-3768-2014; Frodl,
Thomas/D-8118-2012; Li, Chiang-Shan/J-2813-2016; Matarin,
Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Karen, Mather/O-9795-2016;
Putz, Benno/P-2630-2016; Delvecchio, Giuseppe/J-7721-2016; Trabzuni,
Daniah/C-4034-2012; Winkler, Anderson/P-7773-2016; Luciano,
Michelle/F-7277-2010; Meyer-Lindenberg, Andreas/H-1076-2011; Clark,
Vincent/B-3343-2010; Almeida, Jorge/O-5185-2014;
OI Cavalleri, Gianpiero/0000-0002-9802-0506; Jonsson,
Erik/0000-0001-8368-6332; Donohoe, Gary/0000-0003-3037-7426; Sachdev,
Perminder/0000-0002-9595-3220; Mwangi, Benson/0000-0002-1717-4395; Shen,
Li/0000-0002-5443-0503; Schur, Remmelt/0000-0002-2840-2592; Hatton,
Sean/0000-0002-9149-8726; Westlye, Lars T./0000-0001-8644-956X; de Geus,
Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; McIntosh,
Andrew/0000-0002-0198-4588; Nyberg, Lars/0000-0002-3367-1746; Weale,
Michael/0000-0003-4593-1186; de Zubicaray, Greig/0000-0003-4506-0579;
Hoogman, Martine/0000-0002-1261-7628; Roiz-Santianez,
Roberto/0000-0002-5176-2983; Tordesillas-Gutierrez,
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Rijpkema, Mark/0000-0002-8495-4703; Zwiers, Marcel/0000-0001-5483-2935;
Alda, Martin/0000-0001-9544-3944; Rose, Emma/0000-0001-5365-4794;
Savitz, Jonathan/0000-0001-8143-182X; Fox, Peter/0000-0002-0465-2028;
Fisher, Simon/0000-0002-3132-1996; Ho, Beng-Choon/0000-0003-3976-1555;
Franke, Barbara/0000-0003-4375-6572; Ramasamy,
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Jack, Clifford/0000-0001-7916-622X; Simmons, Andrew/0000-0003-2306-5811;
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Dima, Danai/0000-0002-2598-0952; Hulshoff Pol,
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Fernandez, Guillen/0000-0002-5522-0604; Montgomery,
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Wright, Margaret/0000-0001-7133-4970; Arias Vasquez,
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Macciardi, Fabio/0000-0003-0537-4266; Li,
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Putz, Benno/0000-0002-2208-209X; Delvecchio,
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Gollub, Randy L./0000-0002-9434-4044; McMahon,
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Andreassen, Ole A./0000-0002-4461-3568; Romanczuk-Seiferth,
Nina/0000-0002-6931-269X; Emsell, Louise/0000-0003-0011-4158; Potkin,
Steven/0000-0003-1028-1013; Nugent, Allison/0000-0003-2569-2480;
Trabzuni, Daniah/0000-0003-4826-9570; Stein, Jason/0000-0003-4829-0513;
Frodl, Thomas/0000-0002-8113-6959; Lawrence,
Natalia/0000-0003-1969-6637; Caseras, Xavier/0000-0002-8490-6891;
Winkler, Anderson/0000-0002-4169-9781; Luciano,
Michelle/0000-0003-0935-7682; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123; Clark, Vincent/0000-0002-9151-2102;
Almeida, Jorge/0000-0002-1213-1986; Bulayeva,
Kazima/0000-0003-4830-5383; Lemaitre, Herve/0000-0002-5952-076X; Toro,
Roberto/0000-0002-6671-858X; van den Heuvel,
Martijn/0000-0003-1570-1195; Whelan, Christopher/0000-0003-0308-5583
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Medical Research Council [G0701120, G0600429, G0700704, G0802462,
G0901254, G1001245, MR/J006742/1, MR/K01417X/1, MR/K026992/1,
MR/L010305/1, MR/L016400/1]; NCATS NIH HHS [UL1 TR001108]; NIA NIH HHS
[P30 AG010133, P50 AG005134, R01 AG019771, R01 AG040770, U01 AG024904,
U19 AG010483, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846,
R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367];
NLM NIH HHS [K99 LM011384, R00 LM011384, R01 LM011360]; Parkinson's UK
[G-0907]; Wellcome Trust [100309, 104036]
NR 195
TC 84
Z9 85
U1 9
U2 82
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 JUN
PY 2014
VL 8
IS 2
SI SI
BP 153
EP 182
DI 10.1007/s11682-013-9269-5
PG 30
WC Neuroimaging
SC Neurosciences & Neurology
GA AG9UP
UT WOS:000335765700003
PM 24399358
ER
PT J
AU Cohen, MG
Ghatak, A
Kleiman, NS
Naidu, SS
Massaro, JM
Kirtane, AJ
Moses, J
Ohman, EM
Dzavik, V
Palacios, IF
Heldman, AW
Popma, JJ
O'Neill, WW
AF Cohen, Mauricio G.
Ghatak, Abhijit
Kleiman, Neal S.
Naidu, Srihari S.
Massaro, Joseph M.
Kirtane, Ajay J.
Moses, Jeffrey
Ohman, E. Magnus
Dzavik, Vladimir
Palacios, Igor F.
Heldman, Alan W.
Popma, Jeffrey J.
O'Neill, William W.
TI Optimizing Rotational Atherectomy in High-Risk Percutaneous Coronary
Interventions: Insights from the PROTECT II Study
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE atherectomy; percutaneous coronary intervention; ventricular support
device
ID INTRAAORTIC BALLOON PUMP; MYOCARDIAL-INFARCTION; HEMODYNAMIC SUPPORT;
TASK-FORCE; FOLLOW-UP; REVASCULARIZATION; ASSOCIATION; GUIDELINES;
ELEVATION; OUTCOMES
AB ObjectiveTo study rotational atherectomy (RA) outcomes in patients undergoing high-risk PCI randomized to receive hemodynamic support using either IABP or Impella 2.5 in the PROTECT II trial.
BackgroundRA of heavily calcified lesions is often necessary for complex PCI but can be associated with slow-flow, hypotension, and higher risk of periprocedural MI.
MethodsWe compared baseline, angiographic, procedural characteristics, and outcomes of patients treated with and without RA. We examined also RA technique and outcomes.
ResultsRA was used in 52 of 448 patients (32 with Impella vs 20 with IABP, P=0.08). RA patients were older (72 vs. 67 yo, P=0.0009), more likely to have prior CABG (48 vs. 32%, P=0.017), higher STS (8.1 vs. 5.7, P=0.012) and higher SYNTAX scores (37 vs. 29, P<0.0001). At 90 days, RA use was associated with higher incidence of MI but no mortality difference. RA was used more aggressively with Impella resulting in higher rate of periprocedural MI (P<0.01), with no difference in mortality between groups (P=0.78). Repeat revascularization occurred less frequently with Impella (P<0.001). There were no differences in 90-day major adverse events between IABP and Impella in patients undergoing RA (P=0.29). In patients not treated with RA, fewer MAEs were observed with Impella compared with IABP (P=0.03).
ConclusionsPatients who were treated with RA had more comorbidities, and more complex and extensive coronary artery disease. In patients with Impella, more aggressive RA use resulted in fewer revascularization events but higher incidence of periprocedural MI. (c) 2013 Wiley Periodicals, Inc.
C1 [Cohen, Mauricio G.; Ghatak, Abhijit; Heldman, Alan W.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Kleiman, Neal S.] Methodist DeBakey Heart & Vasc Inst, Houston, TX USA.
[Naidu, Srihari S.] Winthrop Univ Hosp, New York, NY USA.
[Massaro, Joseph M.] Harvard Clin Res Inst, Boston, MA USA.
[Kirtane, Ajay J.; Moses, Jeffrey] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA.
[Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA.
[Dzavik, Vladimir] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada.
[Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Popma, Jeffrey J.] Beth Israel Med Deaconess Harvard Med Sch, Boston, MA USA.
[O'Neill, William W.] Henry Ford Hosp, Detroit, MI 48202 USA.
RP Cohen, MG (reprint author), Univ Miami Hosp, 1400 NW 12 th Ave,Suite 1179, Miami, FL 33136 USA.
EM mgcohen@med.miami.edu
OI Cohen, Mauricio/0000-0003-2038-6070
FU Abiomed, Inc.
FX Contract grant sponsor: Abiomed, Inc.
NR 28
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD JUN 1
PY 2014
VL 83
IS 7
BP 1057
EP 1064
DI 10.1002/ccd.25277
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH2LV
UT WOS:000335953900018
PM 24174321
ER
PT J
AU Shenouda, MN
Sadek, BT
Goldberg, SI
Keruakous, AR
Croft, BJ
Raad, RFA
Taghian, AG
AF Shenouda, Mina N.
Sadek, Betro T.
Goldberg, Saveli I.
Keruakous, Amany R.
Croft, Brandon J.
Raad, Rita F. Abi
Taghian, Alphonse G.
TI Clinical Outcome of Isolated Locoregional Recurrence in Patients With
Breast Cancer According to Their Primary Local Treatment
SO CLINICAL BREAST CANCER
LA English
DT Article
DE Breast cancer; Isolated locoregional recurrence; Local breast treatment;
Long-term clinical outcome Prognostic variables
ID CONSERVATIVE SURGERY; REGIONAL RECURRENCE; TUMOR RECURRENCE; CONSERVING
TREATMENT; RANDOMIZED-TRIALS; SYSTEMIC THERAPY; FOLLOW-UP; MASTECTOMY;
PROGNOSIS; RADIATION
AB The long-term clinical outcome was studied for 220 patients with breast cancer who developed isolated locoregional recurrence. Based on a multivariate analysis including multiple pathologic and clinical parameters, the results suggest that patients who had breast-conserving surgery and radiation therapy for their primary tumor have a significantly better clinical outcome compared with those who had mastectomy with no radiation therapy.
Introduction: This study assessed the clinical outcome and prognostic factors in patients with breast cancer who presented with isolated locoregional recurrence (ILRR) as a first event. Materials and Methods: Between 1970 and 2008, 2960 patients with pT1-2, N0-3, M0 primary invasive breast cancer had either breast-conserving therapy (BCT) using lumpectomy and radiation therapy (RT) (group A = 1849 patients) or mastectomy without RT (group B = 1111 patients). Out of groups A and B, 117 and 103 patients, respectively, developed ILRR as a first event. Those 220 patients served as the basis for this study. A multivariate analysis was performed to estimate the clinical outcome of both groups, taking into account clinically relevant variables for the primary tumor and ILRR. Results: The median follow-up after ILRR was 83 months. The median disease-free interval (DFI) was 79 and 38 months for groups A and B, respectively. The overall survival (OS) for group A was 81% and 69% at 5 and 8 years, respectively. For group B, it was 61% and 46%, respectively. The distant metastasis-free survival (DMFS) for group A was 84% at 5 years and remained 84% at 8 years. The DMFS for group B was 60% at 5 years and 52% at 8 years. In multivariate analysis, initial local treatment (BCT vs. mastectomy without RT), pathologic T stage, locoregional recurrence site (local vs. regional), and DFI (<= 4 years vs. > 4 years) were significant prognostic variables for both OS and DMFS. Conclusion: Patients with breast cancer who developed ILRR after BCT as their initial local treatment have better clinical outcome compared with those who had mastectomy without RT. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Shenouda, Mina N.; Sadek, Betro T.; Goldberg, Saveli I.; Keruakous, Amany R.; Croft, Brandon J.; Raad, Rita F. Abi; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Goldberg, Saveli I.] Massachusetts Gen Hosp, Stat Sect, Boston, MA 02114 USA.
RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3 Bldg,100 Blossom St, Boston, MA 02114 USA.
EM ataghian@partners.org
RI Sadek, Betro/I-7734-2013
OI Sadek, Betro/0000-0003-0119-7207
FU National Cancer Institute [R01CA139118, P50CA089393]
FX This project was supported by Award Number R01CA139118 (AGT) and Award
Number P50CA089393 (AGT) from the National Cancer Institute. The content
is solely the responsibility of the authors and does not necessarily
represent the views of the National Cancer Institute or the National
Institutes of Health. All authors state that they have no conflicts of
interest.
NR 33
TC 3
Z9 3
U1 0
U2 3
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
EI 1938-0666
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD JUN
PY 2014
VL 14
IS 3
BP 198
EP 204
DI 10.1016/j.clbc.2013.12.007
PG 7
WC Oncology
SC Oncology
GA AH3JM
UT WOS:000336019500008
PM 24485702
ER
PT J
AU Matulis, S
Resick, PA
Rosner, R
Steil, R
AF Matulis, Simone
Resick, Patricia A.
Rosner, Rita
Steil, Regina
TI Developmentally Adapted Cognitive Processing Therapy for Adolescents
Suffering from Posttraumatic Stress Disorder after Childhood Sexual or
Physical Abuse: A Pilot Study
SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW
LA English
DT Article
DE Posttraumatic stress; Sexual abuse; Physical abuse; Adolescents
ID RANDOMIZED-CONTROLLED-TRIAL; BORDERLINE PERSONALITY-DISORDER;
DIALECTICAL BEHAVIOR-THERAPY; ADMINISTERED PTSD SCALE; LONG-TERM
SEQUELAE; CLINICAL-TRIAL; PSYCHOMETRIC PROPERTIES; INTERRATER
RELIABILITY; PROLONGED EXPOSURE; ASSAULT VICTIMS
AB Although childhood sexual abuse and childhood physical abuse (CSA and CPA) have severe psychopathological consequences, there is little evidence supporting psychotherapeutic interventions for adolescents who have experienced CSA or CPA. To provide a treatment tailored to the specific needs of adolescents suffering from abuse-related posttraumatic stress disorder (PTSD), we modified Cognitive Processing Therapy (CPT) by adding new treatment modules and changing the therapy setting. To evaluate the feasibility and efficacy of Developmentally Adapted CPT (D-CPT), we treated 12 adolescents suffering from PTSD secondary to CSA or CPA. Patients were assessed prior to treatment (t0), post-treatment (t1), and 6 weeks after treatment (t2). Assessments included the Clinician-Administered PTSD Scale (CAPS), the UCLA PTSD Index (UCLA), the Children's Depression Inventory (CDI), the Adolescent Dissociative Experiences Scale (A-DES), and the Borderline Symptom List (BSL-23). MANOVAs revealed that posttraumatic stress measurements and associated symptom measurements significantly differed across time points. When comparing t0 with t2, Cohen's d was large with respect to the CAPS scores (d = 1.45, p < .001) and the UCLA scores (d = 1.91, p < .001). Cohen's d had a medium magnitude with respect to the CDI scores (d = .78, p < .001), the A-DES scores (d = 0.64, p < .05), and the BSL-23 scores (d = 0.74, p < .01). D-CPT has the potential to reduce PTSD symptoms and comorbid psychopathology in adolescents with histories of CSA or CPA.
C1 [Matulis, Simone; Steil, Regina] Goethe Univ Frankfurt, Inst Psychol, Dept Clin Psychol & Psychotherapy, D-60054 Frankfurt, Germany.
[Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA.
[Rosner, Rita] Catholic Univ Eichstatt Ingolstadt, Eichstatt, Ingolstadt, Germany.
RP Matulis, S (reprint author), Goethe Univ Frankfurt, Inst Psychol, Dept Clin Psychol & Psychotherapy, Postbox 11 19 32-120, D-60054 Frankfurt, Germany.
EM matulis@psych.uni-frankfurt.de
NR 112
TC 15
Z9 15
U1 3
U2 35
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1096-4037
EI 1573-2827
J9 CLIN CHILD FAM PSYCH
JI Clin. Child Fam. Psychol. Rev.
PD JUN
PY 2014
VL 17
IS 2
BP 173
EP 190
DI 10.1007/s10567-013-0156-9
PG 18
WC Psychology, Clinical
SC Psychology
GA AH0NZ
UT WOS:000335818200004
PM 24101403
ER
PT J
AU Bragg, DC
Sharma, N
AF Bragg, D. Cristopher
Sharma, Nutan
TI Update on Treatments for Dystonia
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Dystonia; Treatment; Medication; Deep brain stimulation
ID DEEP-BRAIN-STIMULATION; CERVICAL DYSTONIA; BOTULINUM TOXIN;
MOVEMENT-DISORDERS; TARDIVE DYSTONIA; TRIHEXYPHENIDYL; NEUROTOXIN;
NEUROLOGY; EFFICACY; HISTORY
AB Oral medication, botulinum toxin injections, and deep brain stimulation are the current mainstays of treatment for dystonia. In addition, physical and other supportive therapies may help prevent further complications (eg, contractures) and improve function. This review discusses evidence-based medical treatment of dystonia with an emphasis on recent advances in treatment. We will also review the current treatment approaches and suggest ways in which these therapies can be applied to individuals with dystonia.
C1 [Bragg, D. Cristopher; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Sharma, N (reprint author), 149 13th St,Room 6407, Charlestown, MA 02129 USA.
EM nsharma@partners.org
FU Merz Pharmaceuticals; Allergan; NIH [NIH/NINDS P50NS037409]; American
Academy of Neurology; Oakstone Publishing
FX D. Cristopher Bragg declares that he has no conflict of interest. Nutan
Sharma has received consultancy fees from Merz Pharmaceuticals and
Allergan; a grant from NIH (NIH/NINDS P50NS037409); honorarium payment
from The American Academy of Neurology; and payment for development of
an educational presentation from Oakstone Publishing.
NR 31
TC 3
Z9 3
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
EI 1534-6293
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD JUN
PY 2014
VL 14
IS 6
AR 454
DI 10.1007/s11910-014-0454-8
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AG9FK
UT WOS:000335724600007
PM 24744022
ER
PT J
AU Desai, NS
Khandelwal, A
Virmani, V
Kwatra, NS
Ricci, JA
Saboo, SS
AF Desai, Naman S.
Khandelwal, Ashish
Virmani, Vivek
Kwatra, Neha S.
Ricci, Joseph A.
Saboo, Sachin S.
TI Imaging in laparoscopic cholecystectomy-What a radiologist needs to know
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Review
DE Laparoscopic cholecystectomy; Cholelithiasis; Biliary tract surgical
procedure; Post-cholecystectomy syndrome
ID BILIARY COMPLICATIONS; LIVER-TRANSPLANTATION; PERSONAL-EXPERIENCE;
VASCULAR INJURIES; CYSTIC DUCT; MANAGEMENT; GALLBLADDER; MECHANISMS;
GALLSTONES; SURGERY
AB Laparoscopic cholecystectomy is the gold standard treatment option for cholelithiasis. In order to properly assess for the complications related to the procedure, an understanding of the normal biliary anatomy, its variants and the normal postoperative imaging is essential. Radiologist must be aware of benefits and limitations of multiple imaging modalities in characterizing the complications of this procedure as each of these modalities have a critical role in evaluating a symptomatic post-cholecystectomy patient. The purpose of this article is describe the multi-modality imaging of normal biliary anatomy and its variants, as well as to illustrate the imaging features of biliary, vascular, cystic duct, infectious as well as miscellaneous complications of laparoscopic cholecystectomy. We focus on the information that the radiologist needs to know about the radiographic manifestations of potential complications of this procedure. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Desai, Naman S.; Khandelwal, Ashish; Kwatra, Neha S.; Saboo, Sachin S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Virmani, Vivek] Dr Everett Chalmers Hosp, Dept Radiol, Fredericton, NB E3B 5N5, Canada.
[Ricci, Joseph A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
RP Khandelwal, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
EM nsdesai@partners.org; drashish83@gmail.com;
drvivek.virmani@horizonnb.ca; nkwatra@partners.org;
jaricci@partners.org; ssaboo@partners.org
NR 46
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0720-048X
EI 1872-7727
J9 EUR J RADIOL
JI Eur. J. Radiol.
PD JUN
PY 2014
VL 83
IS 6
BP 867
EP 879
DI 10.1016/j.ejrad.2014.02.016
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH1UJ
UT WOS:000335906400001
PM 24657107
ER
PT J
AU Citrome, L
Karagianis, J
Maguire, GA
Nierenberg, AA
AF Citrome, L.
Karagianis, J.
Maguire, G. A.
Nierenberg, A. A.
TI Pharmaism: a tale of two perspectives
SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
LA English
DT Editorial Material
AB Linked Comment: . Linked Comment: .
C1 [Citrome, L.] New York Med Coll, Valhalla, NY 10595 USA.
[Karagianis, J.] Univ Toronto, Toronto, ON, Canada.
[Karagianis, J.] Waypoint Ctr Mental Hlth Care, Penetanguishene, ON, Canada.
[Maguire, G. A.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA.
[Nierenberg, A. A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Citrome, L (reprint author), New York Med Coll, Valhalla, NY 10595 USA.
OI Citrome, Leslie/0000-0002-6098-9266
NR 3
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1368-5031
EI 1742-1241
J9 INT J CLIN PRACT
JI Int. J. Clin. Pract.
PD JUN
PY 2014
VL 68
IS 6
BP 659
EP 661
DI 10.1111/ijcp.12460
PG 3
WC Medicine, General & Internal; Pharmacology & Pharmacy
SC General & Internal Medicine; Pharmacology & Pharmacy
GA AH2JN
UT WOS:000335947400001
PM 24837087
ER
PT J
AU Baldwin, MR
Reid, MC
Westlake, AA
Rowe, JW
Granieri, EC
Wunsch, H
Dam, TT
Rabinowitz, D
Goldstein, NE
Maurer, MS
Lederer, DJ
AF Baldwin, Matthew R.
Reid, M. Cary
Westlake, Amanda A.
Rowe, John W.
Granieri, Evelyn C.
Wunsch, Hannah
Thuy-Tien Dam
Rabinowitz, Daniel
Goldstein, Nathan E.
Maurer, Mathew S.
Lederer, David J.
TI The feasibility of measuring frailty to predict disability and mortality
in older medical intensive care unit survivors
SO JOURNAL OF CRITICAL CARE
LA English
DT Article
DE Aged; Critically Ill; Frailty; Disability; Mortality
ID PROLONGED MECHANICAL VENTILATION; CHRONIC CRITICAL ILLNESS; ACQUIRED
WEAKNESS; FUNCTIONAL STATUS; RANDOMIZED-TRIAL; MUSCLE STRENGTH;
SKELETAL-MUSCLE; CRITICALLY-ILL; ADULTS; OUTCOMES
AB Purpose: To determine whether frailty can be measured within 4 days prior to hospital discharge in older intensive care unit (ICU) survivors of respiratory failure and whether it is associated with post-discharge disability and mortality.
Materials and Methods: We performed a single-center prospective cohort study of 22 medical ICU survivors age 65 years or older who had received noninvasive or invasive mechanical ventilation for at least 24 hours. Frailty was defined as a score of >= 3 using Fried's 5-point scale. We measured disability with the Katz Activities of Daily Living. We estimated unadjusted associations between Fried's frailty score and incident disability at 1-month and 6-month mortality using Cox proportional hazard models.
Results: The mean (SD) age was 77 (9) years, mean Acute Physiology and Chronic Health Evaluation II score was 27 (9.7), mean frailty score was 3.4 (1.3), and 18 (82%) were frail. Nine subjects (41%) died within 6 months, and all were frail. Each 1-point increase in frailty score was associated with a 90% increased rate of incident disability at 1-month (rate ratio: 1.9, 95% CI 0.7-4.9) and a threefold increase in 6-month mortality (rate ratio: 3.0, 95% CI 1.4-6.3).
Conclusions: Frailty can be measured in older ICU survivors near hospital discharge and is associated with 6-month mortality in unadjusted analysis. Larger studies to determine if frailty independently predicts outcomes are warranted. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Baldwin, Matthew R.; Westlake, Amanda A.; Lederer, David J.] Columbia Univ, Coll Phys & Surg, Div Pulm & Crit Care, New York, NY USA.
[Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr, New York, NY USA.
[Rowe, John W.] Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy, New York, NY USA.
[Granieri, Evelyn C.] Columbia Univ, Coll Phys & Surg, Div Geriatr Med & Aging, New York, NY USA.
[Wunsch, Hannah; Thuy-Tien Dam; Lederer, David J.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Wunsch, Hannah] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, New York, NY USA.
[Rabinowitz, Daniel] Columbia Univ, Dept Stat, New York, NY 10027 USA.
[Goldstein, Nathan E.] Mt Sinai Sch Med, Div Geriatr & Palliat Med, New York, NY USA.
[Goldstein, Nathan E.] James J Peters VA Med Ctr, Clin Ctr, New York, NY USA.
[Maurer, Mathew S.] Columbia Univ, Coll Phys & Surg, Div Cardiol, New York, NY USA.
RP Baldwin, MR (reprint author), 622 W 168th St,PH-8,Room 101, New York, NY 10032 USA.
EM mrb45@columbia.edu
OI Reid, Cary/0000-0001-8117-662X
FU National Institute on Aging (NIA) [3P30AG022845-078]
FX The authors of this manuscript have no conflicts of interest to disclose
as described by the Journal of Critical Care. This study was funded by a
sub-contract pilot grant from grant 3P30AG022845-078 from the National
Institute on Aging (NIA), and the NIA had no role in the study design,
analysis, or manuscript approval.
NR 51
TC 10
Z9 10
U1 5
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0883-9441
EI 1557-8615
J9 J CRIT CARE
JI J. Crit. Care
PD JUN
PY 2014
VL 29
IS 3
BP 401
EP 408
DI 10.1016/j.jcrc.2013.12.019
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA AH0OA
UT WOS:000335818300016
PM 24559575
ER
PT J
AU Li, HY
Yang, XJ
Yang, GB
Hong, Z
Zhou, LY
Yin, PQ
Xiao, Y
Chen, LY
Chung, RT
Zhang, LL
AF Li, Hongyan
Yang, Xiaojie
Yang, Guangbo
Hong, Zhi
Zhou, Liya
Yin, Peiqi
Xiao, Yan
Chen, Lingyi
Chung, Raymond T.
Zhang, Leiliang
TI Hepatitis C Virus NS5A Hijacks ARFGAP1 To Maintain a
Phosphatidylinositol 4-Phosphate-Enriched Microenvironment
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SECRETORY PATHWAY; RNA REPLICATION; PROTEIN; RECRUITMENT; PHOSPHATASE;
TRANSPORT; COATOMER; PROMOTES; BINDING
AB Phosphatidylinositol 4-phosphate (PI4P) is well known to be upregulated during hepatitis C virus (HCV) replication. The role of PI4 kinases in HCV has been extensively investigated. Whether the PI4P phosphatase Sac1 is altered by HCV remains unclear. Here, we identified ARFGAP1 to be a novel host factor for HCV replication. We further show that Sac1 interacts with ARFGAP1 and inhibits HCV replication. The elevation of PI4P induced by HCV NS5A is abrogated when the coatomer protein I (COPI) pathway is inhibited. We also found an interaction between NS5A and ARFGAP1. Furthermore, we identified a conserved cluster of positively charged amino acids in NS5A critical for interaction between NS5A and ARFGAP1, induction of PI4P, and HCV replication. Our data demonstrate that ARFGAP1 is a host factor for HCV RNA replication. ARFGAP1 is hijacked by HCV NS5A to remove COPI cargo Sac1 from the site of HCV replication to maintain high levels of PI4P. Our findings provide an additional mechanism by which HCV enhances formation of a PI4P-rich environment.
C1 [Li, Hongyan; Yang, Xiaojie; Yang, Guangbo; Hong, Zhi; Zhou, Liya; Yin, Peiqi; Xiao, Yan; Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China.
[Li, Hongyan; Yang, Xiaojie; Yang, Guangbo; Hong, Zhi; Zhou, Liya; Yin, Peiqi; Xiao, Yan; Zhang, Leiliang] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Li, Hongyan; Chen, Lingyi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
[Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA.
RP Zhang, LL (reprint author), Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China.
EM zhangll@ipbcams.ac.cn
FU National Natural Science Foundation of China [81271832]; Beijing Natural
Science Foundation [7132140]; National Science and Technology Major
Project of China [2013ZX10004-601]; Program for Changjiang Scholars and
Innovative Research Team in University [IRT13007]; Youth Fund of PUMC
[2012J03]; Fundamental Research Funds for the Central Universities;
Research Fund for the Doctoral Program of Higher Education of China
[20121106120058]; Intramural Research Program of the Institute of
Pathogen Biology; CAMS [2012IPB101]; NIH [AI082630]; Rising Star of PUMC
FX This work was supported by grants from the National Natural Science
Foundation of China (81271832), the Beijing Natural Science Foundation
(7132140), the National Science and Technology Major Project of China
(2013ZX10004-601), the Program for Changjiang Scholars and Innovative
Research Team in University (IRT13007), the Youth Fund of PUMC
(2012J03), the Fundamental Research Funds for the Central Universities,
Rising Star of PUMC, the Research Fund for the Doctoral Program of
Higher Education of China (20121106120058), the Intramural Research
Program of the Institute of Pathogen Biology, and the CAMS (2012IPB101)
to L.Z. and the NIH (AI082630) to R.T.C.
NR 36
TC 15
Z9 15
U1 2
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 JUN
PY 2014
VL 88
IS 11
BP 5956
EP 5966
DI 10.1128/JVI.03738-13
PG 11
WC Virology
SC Virology
GA AH2SB
UT WOS:000335970300006
PM 24623438
ER
PT J
AU Cagnetta, A
Adamia, S
Acharya, C
Patrone, F
Miglino, M
Nencioni, A
Gobbi, M
Cea, M
AF Cagnetta, Antonia
Adamia, Sophia
Acharya, Chirag
Patrone, Franco
Miglino, Maurizio
Nencioni, Alessio
Gobbi, Marco
Cea, Michele
TI Role of genotype-based approach in the clinical management of adult
acute myeloid leukemia with normal cytogenetics
SO LEUKEMIA RESEARCH
LA English
DT Review
DE AML; Genomic heterogeneity; Prognosis; Mutations; Minimal residual
disease
ID MINIMAL RESIDUAL DISEASE; CYTOPLASMIC MUTATED NUCLEOPHOSMIN; INTERNAL
TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; AML STUDY-GROUP; TUMOR
GENE WT1; CHRONIC MYELOMONOCYTIC LEUKEMIA; INTERMEDIATE-RISK KARYOTYPE;
FAVORABLE PROGNOSTIC IMPACT; ISOCITRATE-DEHYDROGENASE 1
AB Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CNAML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinicpathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genomewide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current antiAML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Cagnetta, Antonia; Adamia, Sophia; Acharya, Chirag; Cea, Michele] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cagnetta, Antonia; Patrone, Franco; Miglino, Maurizio; Nencioni, Alessio; Gobbi, Marco; Cea, Michele] IRCCS AOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy.
RP Cagnetta, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02115 USA.
EM antonia_cagnetta@dfci.harvard.edu; michele_cea@dfci.harvard.edu
OI patrone, franco/0000-0003-4170-9131
FU Associazione Cristina Bassi; American-Italian Cancer Foundation;
Fondazione Italiana perla Ricerca sul Cancro
FX This study is supported by Associazione Cristina Bassi (A.C.),
American-Italian Cancer Foundation and Fondazione Italiana perla Ricerca
sul Cancro (M.C.).
NR 175
TC 13
Z9 14
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD JUN
PY 2014
VL 38
IS 6
BP 649
EP 659
DI 10.1016/j.leukres.2014.03.006
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA AH1YY
UT WOS:000335919000001
PM 24726781
ER
PT J
AU Schilero, GJ
Radulovic, M
Wecht, JM
Spungen, AM
Bauman, WA
Lesser, M
AF Schilero, Gregory J.
Radulovic, Miroslav
Wecht, Jill M.
Spungen, Ann M.
Bauman, William A.
Lesser, Marvin
TI A Center's Experience: Pulmonary Function in Spinal Cord Injury
SO LUNG
LA English
DT Review
DE Spinal cord injury; Tetraplegia; Pulmonary function; Respiratory muscle
function; Nonspecific airway hyperreactivity; Airway inflammation;
Obstructive sleep apnea
ID GASTROESOPHAGEAL-REFLUX DISEASE; OBSTRUCTIVE SLEEP-APNEA; AIR-FLOW
OBSTRUCTION; RIB CAGE MOTION; BRONCHIAL HYPERRESPONSIVENESS; INDUCED
BRONCHOCONSTRICTION; RESPIRATORY MECHANICS; TETRAPLEGIC SUBJECTS;
IPRATROPIUM BROMIDE; VITAL CAPACITY
AB Traumatic spinal cord injury (SCI) is associated with significant psychological and physical challenges. A multidisciplinary approach to management is essential to ensure recovery during the acute phase, and comprehensive rehabilitative strategies are necessary to foster independence and quality of life throughout the chronic phase of injury. Complications that beset these individuals are often a unique consequence of SCI, and knowledge of the effects of SCI upon organ systems is essential for appropriate management. According to the National SCI Statistical Center (NSCISC), as of 2010 there were an estimated 265,000 persons living with SCI in the United States, with approximately 12,000 incidence cases annually. Although life expectancy for newly injured individuals with SCI is markedly reduced, persons with chronic SCI are expected to live about as long as individuals without SCI; however, longevity varies inversely with level of injury. Since 2005, 56 % of persons with SCI are tetraplegic, and due to paralysis of respiratory muscles, these individuals may be especially prone to pulmonary complications, which remain a major cause of mortality among persons with chronic SCI. We at the VA Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI at the James J. Peters VA Medical Center have devoted more than 25 years to the study of secondary medical conditions that complicate SCI. Herein, we review pulmonary research at the Center, both our past and future endeavors, which form an integral part of our multidisciplinary approach toward achieving a greater understanding of and improving care for veterans with SCI.
C1 [Schilero, Gregory J.; Radulovic, Miroslav; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.; Lesser, Marvin] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Schilero, Gregory J.; Radulovic, Miroslav; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Schilero, GJ (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA.
EM greg.schilero@va.gov
NR 63
TC 2
Z9 2
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0341-2040
EI 1432-1750
J9 LUNG
JI Lung
PD JUN
PY 2014
VL 192
IS 3
BP 339
EP 346
DI 10.1007/s00408-014-9575-8
PG 8
WC Respiratory System
SC Respiratory System
GA AH3LU
UT WOS:000336025900001
PM 24723067
ER
PT J
AU Smith, DF
Maleki, Z
Coughlan, D
Gooi, Z
Akpeng, B
Ogawa, T
Bishop, JA
Frick, KD
Agrawal, N
Gourin, CG
Ha, PK
Koch, WM
Richmon, JD
Westra, WH
Pai, SI
AF Smith, David F.
Maleki, Zahra
Coughlan, Diarmuid
Gooi, Zhen
Akpeng, Belinda
Ogawa, Takenori
Bishop, Justin A.
Frick, Kevin D.
Agrawal, Nishant
Gourin, Christine G.
Ha, Patrick K.
Koch, Wayne M.
Richmon, Jeremy D.
Westra, William H.
Pai, Sara I.
TI Human papillomavirus status of head and neck cancer as determined in
cytologic specimens using the hybrid-capture 2 assay
SO ORAL ONCOLOGY
LA English
DT Article
DE HPV; Head and neck cancer; Squamous cell carcinoma; Hybrid capture 2;
Fine needle aspiration; Cytology
ID SQUAMOUS-CELL CARCINOMA; OROPHARYNGEAL CANCER; TUMOR-ORIGIN;
ORAL-CANCER; RISK; ASSOCIATION; SURVIVAL
AB Objective: A standardized assay to determine the HPV status of head and neck squamous cell carcinoma (HNSCC) specimens has not yet been established, particularly for cytologic samples. The goal of this study was to determine whether the hybrid capture-2 (HC-2) assay, already widely used for the detection of high risk HPV in cervical brushings, is applicable to cytologic specimens obtained from patients with suspected HNSCCs.
Materials and methods: Fine needle aspirates (FNA) of cervical lymph nodes were pre-operatively obtained from patients with suspected HNSCCs and evaluated for the presence of HPV using the HC-2 assay. HPV analysis was performed on the corresponding resected tissue specimens using p16 immunohistochemistry (IHC) and HR-HPV in situ hybridization (ISH). A cost analysis was performed using the Center for Medicare & Medicaid Services.
Results: HPV status of the cervical lymph node metastases was correctly classified using the HC-2 assay in 84% (21/25) of cases. Accuracy was improved to 100% when cytologic evaluation confirmed the presence of cancer cells in the test samples. The estimated cost savings to CMS using the HC-2 assay ranged from $113.74 to $364.63 per patient.
Conclusions: HC-2 is a reliable method for determining the HPV status of HNSCCs. Its application to HNSCCs may reduce costs by helping to localize the primary site during the diagnostic work-up as well as decrease the interval time of determining the HPV status which would be relevant for providing prognostic information to the patient as well as determining eligibility for clinical trials targeting this unique patient population. (c) 2014 Elsevier Ltd. All rights reserved.
C1 [Smith, David F.; Gooi, Zhen; Akpeng, Belinda; Ogawa, Takenori; Agrawal, Nishant; Gourin, Christine G.; Ha, Patrick K.; Koch, Wayne M.; Richmon, Jeremy D.; Westra, William H.; Pai, Sara I.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
[Maleki, Zahra; Bishop, Justin A.; Westra, William H.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Coughlan, Diarmuid; Frick, Kevin D.] Natl Univ Ireland, Dept Econ, Galway, Ireland.
[Ogawa, Takenori] Tohoku Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Sendai, Miyagi 980, Japan.
[Frick, Kevin D.] Johns Hopkins Carey Business Sch, Baltimore, MD 21202 USA.
[Ha, Patrick K.] Greater Baltimore Med Ctr, Milton J Dance Jr Head & Neck Ctr, Baltimore, MD 21204 USA.
[Westra, William H.; Pai, Sara I.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21287 USA.
RP Pai, SI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
EM sipai@mgh.harvard.edu
OI Maleki, Zahra/0000-0003-3273-4802
FU NIH/NCI [1R21CA176332-01]
FX This work was funded by the NIH/NCI Grant 1R21CA176332-01 (SIP).
NR 19
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
EI 1879-0593
J9 ORAL ONCOL
JI Oral Oncol.
PD JUN
PY 2014
VL 50
IS 6
BP 600
EP 604
DI 10.1016/j.oraloncology.2014.02.011
PG 5
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA AH1NY
UT WOS:000335889000012
PM 24630260
ER
PT J
AU Mardirossian, V
Karmali, F
Merfeld, D
AF Mardirossian, Vartan
Karmali, Faisal
Merfeld, Daniel
TI Thresholds for Human Perception of Roll Tilt Motion: Patterns of
Variability Based on Visual, Vestibular, and Mixed Cues
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Roll tilt; Sinusoidal acceleration motion; Vestibular; Vestibular
thresholds; Visual; Visual-vestibular conditions; Visual-vestibular
integration
ID QUALITATIVELY DIFFERENT MECHANISMS; VERTICAL AXIS; TRANSLATION;
RESPONSES; FREQUENCY; VOR
AB Hypothesis: Visual and vestibular cues provide complementary information about spatial orientation.
Background: A previous study we performed showed that visual and vestibular cues are fused when the brain judges the roll-tilt direction. However, it was unclear if the motion perception threshold measured in visual-vestibular conditions will be better than visual or vestibular thresholds at high frequencies.
Methods: An innovative method of vestibular evaluation, the measurement of vestibular thresholds, was used. We used a Moog mobile platform with dedicated software. Four subjects were tested at 1, 2, 3, 4, and 5 Hz with adaptively decreasing amplitude. Subjects were asked to indicate the direction of motion in three conditions: vestibular only, subjects roll tilted in the dark; visual only, a visual scene was tilted in front of the subjects; and combined visual + vestibular, subjects rotated while watching a stationary visual scene. For each subject, we calculated the percentage difference between the threshold for combined visual/vestibular stimuli and the best of either the vestibular or visual threshold.
Results: Visual and vestibular thresholds significantly differed in function of frequency.
Conclusion: Vestibular and visual thresholds at different frequencies are significantly different, which support the fact that they use different perception pathways. The brain may determine the body motion in space during roll tilt motion by integration of vestibular and visual inputs: the combined estimate of motion is better than the vestibular input and is not significantly better than the visual cues alone. This research may be useful in the workup of vertiginous disorders with impaired integration of vestibular and visual cues (motion sickness and migraine dizziness).
C1 [Mardirossian, Vartan] Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02218 USA.
[Karmali, Faisal; Merfeld, Daniel] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA.
RP Mardirossian, V (reprint author), Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, 1 BMC Pl,FGH Bldg,4th Floor, Boston, MA 02218 USA.
EM vartan74@gmail.com
FU National Institutes of Health/National Institute on Deafness and Other
Communication Disorders [DC04158, IRB MEEI 98-09-027]
FX This study was supported by grant DC04158 from the National Institutes
of Health/National Institute on Deafness and Other Communication
Disorders (IRB MEEI 98-09-027).
NR 6
TC 2
Z9 2
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
EI 1537-4505
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD JUN
PY 2014
VL 35
IS 5
BP 857
EP 860
PG 4
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA AH6CQ
UT WOS:000336218700024
PM 24691502
ER
PT J
AU Lepage, JF
Clouchoux, C
Lassonde, M
Evans, AC
Deal, CL
Theoret, H
AF Lepage, Jean-Francois
Clouchoux, Cedric
Lassonde, Maryse
Evans, Alan C.
Deal, Cheri L.
Theoret, Hugo
TI Cortical thickness correlates of socioemotional difficulties in adults
with Turner syndrome
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Emotional Quotient Inventory; Social cognition; Turner syndrome;
X-monosomy; Sex-chromosome aneuploidy
ID EMOTIONAL INTELLIGENCE; X MONOSOMY; RECOGNITION; AMYGDALA; CORTEX; BRAIN
AB Turner syndrome (TS) is a non-inherited genetic disorder associated with a specific cognitive phenotype and socioemotional impairments. The present study aimed at characterizing the neuroanatomical basis of socioemotional dysfunctions in TS using the Emotional Quotient inventory (EQ-I) and cortical morphology analysis in 17 individuals with TS (45,X) and 17-age and verbal IQ matched healthy females. Individuals with TS reported significantly greater socioemotional impairment than controls. Cortical thickness analysis showed that participants with TS had an overall thicker cortex than controls, with extensive alterations in the temporal, frontal, parietal and insular regions bilaterally. Using the total EQ-I score as regressor in the cortical thickness analysis revealed a number of brain regions where the relationship between cortical thickness and EQ-I score differed between groups; these areas included brain regions critically involved in socioemotional processes, such as bilateral insula, the anterior cingulate and the orbitofrontal cortex. These results show that socioemotional dysfunctions seen in women with TS are associated with significant alterations in brain morphology. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Lepage, Jean-Francois; Lassonde, Maryse; Theoret, Hugo] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada.
[Clouchoux, Cedric; Evans, Alan C.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Lassonde, Maryse; Deal, Cheri L.; Theoret, Hugo] Univ St Justine, Ctr Rech Ctr Hosp, Montreal, PQ, Canada.
RP Lepage, JF (reprint author), Massachusetts Gen Hosp, Spaulding Rehabil Hosp, 79-96 13th St, Charlestown, MA 02129 USA.
EM jf.lepage@gmail.com
FU Canadian Institutes of Health Research (CIHR) [MOP-74608]; postdoctoral
fellowship from the CIHR
FX This work was supported by grants from the Canadian Institutes of Health
Research (CIHR) (MOP-74608). JFL is supported by a postdoctoral
fellowship from the CIHR.
NR 18
TC 2
Z9 2
U1 3
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD JUN
PY 2014
VL 44
BP 30
EP 34
DI 10.1016/j.psyneun.2014.02.017
PG 5
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA AH3IN
UT WOS:000336017000004
PM 24767617
ER
PT J
AU Kirchhoff, AC
Montenegro, RE
Warner, EL
Wright, J
Fluchel, M
Stroup, AM
Park, ER
Kinney, AY
AF Kirchhoff, Anne C.
Montenegro, Roberto E.
Warner, Echo L.
Wright, Jennifer
Fluchel, Mark
Stroup, Antoinette M.
Park, Elyse R.
Kinney, Anita Y.
TI Childhood cancer survivors' primary care and follow-up experiences
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Childhood cancer survivors; Primary care; Risk-based care; Survivor care
plans
ID YOUNG-ADULT SURVIVORS; HEALTH-CARE; PHYSICIANS; KNOWLEDGE; PERSPECTIVES;
PROVIDERS; VIEWS
AB Although most childhood cancer survivors see a primary care provider (PCP), little is known about these encounters. We explored themes related to survivors' (1) experiences with primary care, (2) communication with their PCPs about their cancer, and (3) their knowledge and impressions about follow-up care, including their interest in a survivor care plan (SCP).
From April to July 2012, we conducted in-depth, semi-structured telephone interviews with 53 adult survivors recruited from the Utah Cancer Surveillance, Epidemiology, and End Results (SEER) Registry. Participants were randomly selected from sex, age, and rural/urban strata and were younger than 21 years at the time of diagnosis. Participants were asked if they had a PCP and whether they discussed their cancer history with their provider and their interest in a SCP. Interviews were recorded, transcribed, and content-analyzed.
The average age at interview was 39.1 years (SD = 11.2). Most survivors had a current PCP (83.0 %). Almost half were not worried about their health despite having had cancer. Detailed discussions about cancer history with PCPs were generally rare. Few survivors had a follow-up care plan, but over half thought a SCP could empower their medical decision making. However, one-third of the survivors were skeptical about the usefulness of a SCP and some were worried about health-care costs.
Childhood cancer survivors need better care coordination. Of concern is that many do not discuss their cancer history with their current PCPs and most have no SCP.
C1 [Kirchhoff, Anne C.; Warner, Echo L.; Fluchel, Mark] Huntsman Canc Inst, Canc Control & Populat Sci Res Program, Salt Lake City, UT 84112 USA.
[Kirchhoff, Anne C.; Wright, Jennifer; Fluchel, Mark] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Kirchhoff, Anne C.; Wright, Jennifer; Fluchel, Mark] Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT 84112 USA.
[Montenegro, Roberto E.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA.
[Stroup, Antoinette M.] Rutgers State Univ, Sch Publ Hlth, Trenton, NJ USA.
[Stroup, Antoinette M.] Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Park, Elyse R.] Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Park, Elyse R.] Dept Psychiat, Boston, MA 02114 USA.
[Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Kinney, Anita Y.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Kinney, Anita Y.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
RP Kirchhoff, AC (reprint author), Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT 84112 USA.
EM anne.kirchhoff@hci.utah.edu
FU Huntsman Cancer Institute's Cancer Control and Population Sciences Pilot
Grant Program; Primary Children's Medical Foundation; National Cancer
Institute [HHSN261201000026C]; Utah State Department of Health;
University of Utah
FX Support for this research comes from the Huntsman Cancer Institute's
Cancer Control and Population Sciences Pilot Grant Program and the
Cancer Center Support Grant and Primary Children's Medical Foundation
Career Development Award. We also acknowledge the use of shared
resources supported by P30 CA042014 awarded to Huntsman Cancer
Institute. Additional support for the Utah Cancer Registry provided by
the National Cancer Institute's Surveillance, Epidemiology, and End
Results (SEER) Contract # HHSN261201000026C, the Utah State Department
of Health, and the University of Utah.
NR 27
TC 6
Z9 6
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUN
PY 2014
VL 22
IS 6
BP 1629
EP 1635
DI 10.1007/s00520-014-2130-6
PG 7
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA AG9YC
UT WOS:000335775000023
PM 24496759
ER
PT J
AU Lee, V
Singh, G
Trasatti, JP
Bjornsson, C
Xu, XW
Tran, TN
Yoo, SS
Dai, GH
Karande, P
AF Lee, Vivian
Singh, Gurtej
Trasatti, John P.
Bjornsson, Chris
Xu, Xiawei
Thanh Nga Tran
Yoo, Seung-Schik
Dai, Guohao
Karande, Pankaj
TI Design and Fabrication of Human Skin by Three-Dimensional Bioprinting
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID RECONSTRUCTED HUMAN EPIDERMIS; TISSUE-ENGINEERING SCAFFOLDS;
TRANSCUTANEOUS IMMUNIZATION; PENETRATION ENHANCERS; FREEFORM
FABRICATION; LANGERHANS CELLS; IN-VITRO; KERATINOCYTES; CULTURE; MODELS
AB Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.
C1 [Lee, Vivian; Dai, Guohao] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA.
[Lee, Vivian; Singh, Gurtej; Trasatti, John P.; Dai, Guohao; Karande, Pankaj] Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
[Singh, Gurtej; Karande, Pankaj] Rensselaer Polytech Inst, Howard P Isermann Dept Chem & Biol Engn, Troy, NY 12180 USA.
[Trasatti, John P.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Troy, NY 12180 USA.
[Bjornsson, Chris] Neural Stem Cell Inst, Rensselaer, NY USA.
[Xu, Xiawei] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Thanh Nga Tran] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Yoo, Seung-Schik] Harvard Univ, Sch Med, Boston, MA USA.
RP Dai, GH (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA.
EM daig@rpi.edu
OI Dai, Guohao/0000-0001-7346-2685
NR 50
TC 47
Z9 54
U1 14
U2 203
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
EI 1937-3392
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD JUN 1
PY 2014
VL 20
IS 6
BP 473
EP 484
DI 10.1089/ten.tec.2013.0335
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AH2YE
UT WOS:000335987200003
PM 24188635
ER
PT J
AU Winslow, V
Vaivoda, R
Vasilyev, A
Dombkowski, D
Douaidy, K
Stark, C
Drake, J
Guilliams, E
Choudhary, D
Preffer, F
Stoilov, I
Christmas, P
AF Winslow, Valeria
Vaivoda, Rachel
Vasilyev, Aleksandr
Dombkowski, David
Douaidy, Karim
Stark, Christopher
Drake, Justin
Guilliams, Evin
Choudhary, Dharamainder
Preffer, Frederic
Stoilov, Ivaylo
Christmas, Peter
TI Altered leukotriene B-4 metabolism in CYP4F18-deficient mice does not
impact inflammation following renal ischemia
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Cytochrome P450; Neutrophil; Leukotriene B4; omega-Hydroxylase;
Inflammation
ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INNATE IMMUNE-SYSTEM; HUMAN
LIVER-CELLS; REPERFUSION INJURY; DENDRITIC CELLS; TARGETED DISRUPTION;
DIHYDRO METABOLITES; CYP4F SUBFAMILY; DEFICIENT MICE; KIDNEY INJURY
AB Inflammatory responses to infection and injury must be restrained and negatively regulated to minimize damage to host tissue. One proposed mechanism involves enzymatic inactivation of the pro-inflammatory mediator leukotriene B-4, but it is difficult to dissect the roles of various metabolic enzymes and pathways. A primary candidate for a regulatory pathway is omega oxidation of leukotriene B-4 in neutrophils, presumptively by CYP4F3A in humans and CYP4F18 in mice. This pathway generates omega, omega-1, and omega-2 hydroxylated products of leukotriene B4, depending on species. We created mouse models targeting exons 8 and 9 of the Cyp4f18 allele that allows both conventional and conditional knockouts of Cyp4f18. Neutrophils from wild-type mice convert leukotriene B-4 to 19-hydroxy leukotriene B-4, and to a lesser extent 18-hydroxy leukotriene B-4, whereas these products were not detected in neutrophils from conventional Cyp4f18 knockouts. A mouse model of renal ischemia-reperfusion injury was used to investigate the consequences of loss of CYP4F18 in vivo. There were no significant changes in infiltration of neutrophils and other leukocytes into kidney tissue as determined by flow cytometry and immunohistochemistry, or renal injury as assessed by histological scoring and measurement of blood urea nitrogen. It is concluded that CYP4F18 is necessary for omega oxidation of leukotriene B-4 in neutrophils, and is not compensated by other CYP enzymes, but loss of this metabolic pathway is not sufficient to impact inflammation and injury following renal ischemia-reperfusion in mice. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Winslow, Valeria; Vaivoda, Rachel; Vasilyev, Aleksandr; Douaidy, Karim; Stark, Christopher; Christmas, Peter] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Charlestown, MA 02129 USA.
[Dombkowski, David; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Drake, Justin; Guilliams, Evin; Christmas, Peter] Radford Univ, Dept Biol, Radford, VA 24142 USA.
[Choudhary, Dharamainder; Stoilov, Ivaylo] Univ Connecticut, Ctr Hlth, Dept Surg, Farmington, CT 06030 USA.
RP Christmas, P (reprint author), Radford Univ, Dept Biol, Radford, VA 24142 USA.
EM pchristma2@radford.edu
FU National Institutes of Health Grant [R0IDK074821]; National Center for
Research Resources, National Institutes of Health Grant [S10RR027926]
FX This project was supported by the National Institutes of Health Grant
R0IDK074821 (to P. Christmas). LC-MS/MS analysis was performed at the
Wayne State University Lipidomics Core Facility and was supported in
part by the National Center for Research Resources, National Institutes
of Health Grant S10RR027926; we thank Dr. Krishnarao Maddipati for help
with the analysis.
NR 53
TC 2
Z9 2
U1 1
U2 4
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 JUN
PY 2014
VL 1841
IS 6
BP 868
EP 879
DI 10.1016/j.bbalip.2014.03.002
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AG7SI
UT WOS:000335618300005
PM 24632148
ER
PT J
AU Partridge, AH
Pagani, O
Abulkhair, O
Aebi, S
Amant, F
Azim, HA
Costa, A
Delaloge, S
Freilich, G
Gentilini, OD
Harbeck, N
Kelly, CM
Loibl, S
Meirow, D
Peccatori, F
Kaufmann, B
Cardoso, F
AF Partridge, Ann H.
Pagani, Olivia
Abulkhair, Omalkhair
Aebi, Stefan
Amant, Frederic
Azim, Hatem A., Jr.
Costa, Alberto
Delaloge, Suzette
Freilich, Gloria
Gentilini, Oreste Davide
Harbeck, Nadia
Kelly, Catherine M.
Loibl, Sibylle
Meirow, Dror
Peccatori, Fedro
Kaufmann, Bella
Cardoso, Fatima
TI First international consensus guidelines for breast cancer in young
women (BCY1)
SO BREAST
LA English
DT Article
DE Breast cancer; Guidelines; BCY1
ID BRCA2 MUTATION CARRIERS; ADJUVANT ENDOCRINE THERAPY; GOSERELIN PLUS
ANASTROZOLE; NIPPLE-SPARING MASTECTOMY; POPULATION-BASED COHORT;
BONE-MINERAL DENSITY; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; CONSERVING
TREATMENT; FOLLOW-UP
AB The 1st International Consensus Conference for Breast Cancer in Young Women (BCY1) took place in November 2012, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for management of breast cancer in young women were developed and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA). (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pagani, Olivia] Oncol Inst Southern Switzerland, Bellinzona, Switzerland.
[Pagani, Olivia] Breast Unit Southern Switzerland, Bellinzona, Switzerland.
[Abulkhair, Omalkhair] King Abdulaziz Med City Natl Guard, Riyadh, Saudi Arabia.
[Aebi, Stefan] Luzerner Kantonsspital, Luzern, Switzerland.
[Amant, Frederic] Univ Hosp Leuven, Louvain, Belgium.
[Azim, Hatem A., Jr.] Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium.
[Costa, Alberto; Peccatori, Fedro] European Sch Oncol, Milan, Italy.
[Delaloge, Suzette] Inst Gustave Roussy, Villejuif, France.
[Freilich, Gloria] Europa Donna, London, England.
[Gentilini, Oreste Davide; Peccatori, Fedro; Cardoso, Fatima] European Inst Oncol, Milan, Italy.
[Harbeck, Nadia] Univ Munich LMU, Dept OB&GYN, Breast Ctr, Munich, Germany.
[Kelly, Catherine M.] Mater Misericordiae Univ Hosp, Dublin, Ireland.
[Loibl, Sibylle] GBG Forschungs GmbH, German Breast Grp, Neu Isenburg, Germany.
[Loibl, Sibylle] Sana Klinikum Offenbach, Offenbach, Germany.
[Meirow, Dror] Sheba Med Ctr, Ramat Gan, Israel.
[Kaufmann, Bella] Sheba Med Ctr, Tel Hashomer, Israel.
[Cardoso, Fatima] Champalimaud Canc Ctr, Breast Unit, Lisbon, Portugal.
RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Unit, Av Brasilia,S-N, P-1400038 Lisbon, Portugal.
EM fatimacardoso@fundacaochampalimaud.pt
RI Aebi, Stefan/F-2004-2010;
OI Aebi, Stefan/0000-0002-3383-9449; Cardoso, Fatima/0000-0002-6692-2249
NR 129
TC 40
Z9 40
U1 1
U2 11
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
EI 1532-3080
J9 BREAST
JI Breast
PD JUN
PY 2014
VL 23
IS 3
BP 209
EP 220
DI 10.1016/j.breast.2014.03.011
PG 12
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA AG6DV
UT WOS:000335509600003
PM 24767882
ER
PT J
AU Roper, J
Sinnamon, MJ
Coffee, EM
Belmont, P
Keung, L
Georgeon-Richard, L
Wang, WV
Faber, AC
Yun, J
Yilmaz, OH
Bronson, RT
Martin, ES
Tsichlis, PN
Hung, KE
AF Roper, Jatin
Sinnamon, Mark J.
Coffee, Erin M.
Belmont, Peter
Keung, Lily
Georgeon-Richard, Larissa
Wang, Wei Vivian
Faber, Anthony C.
Yun, Jihye
Yilmaz, Oemer H.
Bronson, Roderick T.
Martin, Eric S.
Tsichlis, Philip N.
Hung, Kenneth E.
TI Combination PI3K/MEK inhibition promotes tumor apoptosis and regression
in PIK3CA wild-type, KRAS mutant colorectal cancer
SO CANCER LETTERS
LA English
DT Article
DE PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cancer
ID SYNTHETIC LETHAL INTERACTION; COLON-CANCER; LUNG ADENOCARCINOMA; MEK
INHIBITORS; BRAF MUTATIONS; MOUSE MODEL; RAS; PATHWAY; GROWTH;
CARCINOMAS
AB PI3K inhibition in combination with other agents has not been studied in the context of P1K3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of P1K3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Roper, Jatin; Georgeon-Richard, Larissa; Wang, Wei Vivian] Tufts Med Ctr, Div Gastroenterol, Dept Med, Boston, MA 02111 USA.
[Sinnamon, Mark J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Coffee, Erin M.; Faber, Anthony C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Belmont, Peter] Celgene, Discovery, Oncol Res, San Diego, CA USA.
[Roper, Jatin; Keung, Lily; Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA.
[Yun, Jihye] Weill Cornell Med Coll, New York, NY USA.
[Yun, Jihye] New York Presbyterian Hosp, Dept Med, New York, NY USA.
[Yilmaz, Oemer H.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Bronson, Roderick T.; Martin, Eric S.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA.
[Hung, Kenneth E.] Pfizer Biotherapeut Clin Res, Cambridge, MA USA.
RP Roper, J (reprint author), Tufts Med Ctr, Div Gastroenterol, Dept Med, Boston, MA 02111 USA.
EM jroper@tuftsmedicalcenter.org
FU American Gastroenterological Association
FX American Gastroenterological Association (Fellowship to Faculty
Transition Award to J.R.).
NR 50
TC 18
Z9 19
U1 1
U2 16
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD JUN 1
PY 2014
VL 347
IS 2
BP 204
EP 211
DI 10.1016/j.canlet.2014.02.018
PG 8
WC Oncology
SC Oncology
GA AG7WJ
UT WOS:000335629200007
PM 24576621
ER
PT J
AU Marien, P
Ackermann, H
Adamaszek, M
Barwood, CHS
Beaton, A
Desmond, J
De Witte, E
Fawcett, AJ
Hertrich, I
Kuper, M
Leggio, M
Marvel, C
Molinari, M
Murdoch, BE
Nicolson, RI
Schmahmann, JD
Stoodley, CJ
Thurling, M
Timmann, D
Wouters, E
Ziegler, W
AF Marien, Peter
Ackermann, Herman
Adamaszek, Michael
Barwood, Caroline H. S.
Beaton, Alan
Desmond, John
De Witte, Elke
Fawcett, Angela J.
Hertrich, Ingo
Kueper, Michael
Leggio, Maria
Marvel, Cherie
Molinari, Marco
Murdoch, Bruce E.
Nicolson, Roderick I.
Schmahmann, Jeremy D.
Stoodley, Catherine J.
Thuerling, Markus
Timmann, Dagmar
Wouters, Ellen
Ziegler, Wolfram
TI Consensus Paper: Language and the Cerebellum: an Ongoing Enigma
SO CEREBELLUM
LA English
DT Article
DE Cerebellum; Language; Speech; Speech perception; Apraxia of speech;
Working memory; Verbal fluency; Syntax; Phonology; Semantics; Aphasia;
Imaging; Agraphia; Dyslexia; Functional topography; Imaging; fMRI; SPECT
ID VERBAL WORKING-MEMORY; COGNITIVE-AFFECTIVE SYNDROME;
POSITRON-EMISSION-TOMOGRAPHY; FOREIGN ACCENT SYNDROME; FOSSA TUMOR
RESECTION; SPEECH PRODUCTION; BRAIN ACTIVATION; FUNCTIONAL MRI; BASAL
GANGLIA; TEMPORAL-LOBE
AB In less than three decades, the concept "cerebellar neurocognition" has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the "linguistic cerebellum" in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.
C1 [Marien, Peter; De Witte, Elke; Wouters, Ellen] Vrije Univ Brussel, Dept Clin & Expt Neurolinguist, CLIN, Brussels, Belgium.
[Marien, Peter; Wouters, Ellen] ZNA Middelheim Gen Hosp, Dept Neurol, B-2020 Antwerp, Belgium.
[Marien, Peter] Royal Flemish Acad Belgium Sci & Arts, Vlaams Acad Centrum VLAC, Inst Adv Studies, Brussels, Belgium.
[Ackermann, Herman; Hertrich, Ingo] Univ Tubingen, Dept Gen Neurol, Ctr Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany.
[Adamaszek, Michael] Univ Leipzig, Ctr Neurol Rehabil, Bennewitz, Germany.
[Barwood, Caroline H. S.; Murdoch, Bruce E.] Univ Queensland, Ctr Neurogen Commun Disorders Res, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia.
[Beaton, Alan] Swansea Univ, Dept Psychol, Aberystwyth, Dyfed, Wales.
[Beaton, Alan] Dept Psychol, Aberystwyth, Dyfed, Wales.
[Desmond, John; Marvel, Cherie] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Fawcett, Angela J.] Univ Swansea, Ctr Child Res, Swansea, W Glam, Wales.
[Kueper, Michael; Thuerling, Markus; Timmann, Dagmar] Univ Duisburg Essen, Dept Neurol, Essen, Germany.
[Leggio, Maria] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy.
[Leggio, Maria; Molinari, Marco] IRCCS Santa Lucia Fdn, Rome, Italy.
[Nicolson, Roderick I.] Univ Sheffield, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England.
[Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Ataxia Unit, Cognit & Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA.
[Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA.
[Stoodley, Catherine J.] Amer Univ, Dept Psychol, Washington, DC 20016 USA.
[Ziegler, Wolfram] City Hosp, Clin Neuropsychol Res Grp, Clin Neuropsychol, Munich, Germany.
[Ziegler, Wolfram] Univ Munich, Inst Phonet & Speech Proc, Munich, Germany.
RP Marien, P (reprint author), ZNA Middelheim Gen Hosp, Dept Neurol, Lindendreef 1, B-2020 Antwerp, Belgium.
EM peter.marien5@telenet.be
RI Molinari, Marco/A-9624-2010; Stoodley, Catherine/P-2081-2016;
OI Molinari, Marco/0000-0001-9808-9688; Stoodley,
Catherine/0000-0003-2629-0213; Leggio, Maria /0000-0003-3750-2760
FU NIH [K01 DA0304425, R01 AA018694]; DFG TI [239/9-1]
FX This study is supported by NIH grants K01 DA0304425 (Dr. Marvel) and R01
AA018694 (Dr. Desmond) and by DFG TI 239/9-1. The editorial assistance
of Mrs. Tine D'aes is greatly acknowledged.
NR 267
TC 51
Z9 52
U1 12
U2 66
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1473-4222
EI 1473-4230
J9 CEREBELLUM
JI Cerebellum
PD JUN
PY 2014
VL 13
IS 3
BP 386
EP 410
DI 10.1007/s12311-013-0540-5
PG 25
WC Neurosciences
SC Neurosciences & Neurology
GA AG9LB
UT WOS:000335739600011
PM 24318484
ER
PT J
AU Tang, HY
Sayers, SL
Weissinger, G
Riegel, B
AF Tang, Hsin-Yi (Jean)
Sayers, Steven L.
Weissinger, Guy
Riegel, Barbara
TI The Role of Depression in Medication Adherence Among Heart Failure
Patients
SO CLINICAL NURSING RESEARCH
LA English
DT Article
DE heart failure; depression; major depressive disorders; medication
adherence
ID SELF-REPORT; NONADHERENCE; DISEASE; ANXIETY; RECOMMENDATIONS;
NONCOMPLIANCE; INTERVENTION; METAANALYSIS; ASSOCIATION; PREVALENCE
AB The purpose of the study was to explore the association between depression and medication adherence in heart failure (HF) patients. Studies have shown that people with depression are likely to be nonadherent to their prescribed medication treatment. But other studies suggest that nonadherence may be overestimated by people with depression. A total of 244 adults with Stage C HF completed the study. Self-reported medication adherence was obtained using the Basel Assessment of Adherence Scale (BAAS); objective data on medication adherence were collected using the electronic Medication Event Monitoring System (MEMS). Depression was measured via self-report with the Patient Health Questionnaire (PHQ-9). There was a significant difference between depressed and nondepressed participants in self-reported medication nonadherence (p = .008), but not in objectively measured medication nonadherence (p = .72). The depressed sample was 2.3 times more likely to self-report poor medication adherence than those who were nondepressed (p = .006).
C1 [Tang, Hsin-Yi (Jean)] Seattle Univ, Coll Nursing, Seattle, WA 98125 USA.
[Sayers, Steven L.] Vet Affairs Med Ctr, Philadelphia, PA USA.
[Weissinger, Guy] Univ Penn, Perelman Sch Med, Aaron T Beck Ctr Psychopathol Res, Philadelphia, PA 19104 USA.
[Riegel, Barbara] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA.
RP Tang, HY (reprint author), Seattle Univ, Coll Nursing, 901 12th Ave POB 222000, Seattle, WA 98125 USA.
EM jeantang@u.washington.edu
FU National Heart, Lung & Blood Institute [RO1 HL084394-01A1]; Philadelphia
Veterans Affairs Medical Center, VISN 4 Mental Illness Research,
Education, and Clinical Center (MIREC); Hope Heart Institute, Seattle,
Washington
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
funded by (a) National Heart, Lung & Blood Institute (RO1
HL084394-01A1), (b) Philadelphia Veterans Affairs Medical Center, VISN 4
Mental Illness Research, Education, and Clinical Center (MIREC) [the
opinions expressed herein do not represent the official policy of the
Department of Veterans Affairs], and (c) Hope Heart Institute, Seattle,
Washington.
NR 40
TC 5
Z9 5
U1 2
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1054-7738
EI 1552-3799
J9 CLIN NURS RES
JI Clin. Nurs. Res.
PD JUN
PY 2014
VL 23
IS 3
BP 231
EP 244
DI 10.1177/1054773813481801
PG 14
WC Nursing
SC Nursing
GA AG7EF
UT WOS:000335580200001
PM 23548500
ER
PT J
AU Gavigan, A
Cain, C
Carroll, DL
AF Gavigan, Anne
Cain, Carolyn
Carroll, Diane L.
TI Effects of Informational Sessions on Anxiety Precardiovascular Procedure
SO CLINICAL NURSING RESEARCH
LA English
DT Article
DE patient education; anxiety assessment; percutaneous coronary
intervention; patient satisfaction
ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC PATIENTS; IMPACT; EDUCATION;
HEALTH; LIFE
AB To measure the effect of an informational video intervention (IVI) compared to standard care (SC) preparation on anxiety and satisfaction prior to percutaneous cardiovascular procedure (PCVP). A quasi-experimental, randomized, prepost design was used to measure the effect of IVI, provided pre-PCVP, compared with SC only preparation on admission anxiety compared with post the IVI and SC preparation. There were 113 males/72 females, mean age of 61.8 years, assigned to IVI (n = 94) or SC group (n = 91). After the preparatory information session, there was no difference between groups on state anxiety (37.6 +/- 11.7 vs. 36.3 +/- 10.7; z = -.500, p = .617). There was a significant improvement in satisfaction in IVI group (54.23 +/- 5.5 vs. 50.7 +/- 6.6 (z = -2.9, p = .003). IVI session improved satisfaction with preparation. Viewing the IVI within hours of a PCVP did not reduce measurable anxiety. Further research may reveal a more ideal viewing time.
C1 [Gavigan, Anne; Cain, Carolyn; Carroll, Diane L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Carroll, DL (reprint author), Massachusetts Gen Hosp, POB 426, Boston, MA 02114 USA.
EM dcarroll3@partners.org
FU Yvonne L. Munn Nursing Research Award, Patient Care Services,
Massachusetts General Hospital, Boston MA
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Yvonne L. Munn
Nursing Research Award, Patient Care Services, Massachusetts General
Hospital, Boston MA.
NR 28
TC 0
Z9 0
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1054-7738
EI 1552-3799
J9 CLIN NURS RES
JI Clin. Nurs. Res.
PD JUN
PY 2014
VL 23
IS 3
BP 281
EP 295
DI 10.1177/1054773813483138
PG 15
WC Nursing
SC Nursing
GA AG7EF
UT WOS:000335580200004
PM 23548501
ER
PT J
AU Greene, ME
Rolfson, O
Nemes, S
Gordon, M
Malchau, H
Garellick, G
AF Greene, Meridith E.
Rolfson, Ola
Nemes, Szilard
Gordon, Max
Malchau, Henrik
Garellick, Goran
TI Education Attainment is Associated With Patient-reported Outcomes:
Findings From the Swedish Hip Arthroplasty Register
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID KNEE-JOINT REPLACEMENT; IMPORTANT DIFFERENCE; FUNCTIONAL STATUS; MODEL
SELECTION; OSTEOARTHRITIS; OCCUPATION; SURGERY; HEALTH; INCOME; NEED
AB Age, sex, and medical comorbidities may be associated with differences in patient-reported outcome scores after THA. Highest level of education may be a surrogate for socioeconomic status, but the degree to which this is associated with patient-reported outcomes after THA is not known.
We investigated the national Swedish Hip Arthroplasty Register for the association of education attainment on patient-reported outcomes 1 year after THA; specifically, we evaluated level of education attainment against health-related quality of life (HRQoL), pain reduction, and satisfaction with treatment 1 year after THA.
All THAs for osteoarthritis performed from 2005 through 2007 with complete patient-reported outcome measures (representing 49% of the THAs performed for this diagnosis) were selected from the Swedish Hip Arthroplasty Register. These cases were merged with national databases containing education attainment, marital status, and comorbidities (n = 11,464; mean age of patients, 64 years). The patient-reported outcome measure protocol included the HRQoL measure EuroQol five-dimension scale (EQ-5D), a VAS for pain, the Charnley classification survey, and a VAS addressing THA satisfaction. Linear regression analyses determined the association of preoperative patient factors with patient-reported outcomes.
High education attainment was associated with higher HRQoL (EQ-5D index (high) = 0.03 +/- A 0.01; EQ VAS (high) = 2.6 +/- A 0.5) after THA, whereas those with low and medium education were at risk for lower HRQoL. High education was associated with less pain after treatment ((high) = -3.3 +/- A 0.05). Individuals with low or medium education were at risk for less satisfaction with THA (p < 0.001).
Our results suggest clinicians should support patients with low and medium education to a greater extent. Identification of patients who will benefit most from THA and educating those at risk for poorer outcomes, like patients with low and medium education, ultimately may improve patient satisfaction, HRQoL, pain, and the cost utility of THA.
C1 [Greene, Meridith E.; Rolfson, Ola; Nemes, Szilard; Gordon, Max; Malchau, Henrik; Garellick, Goran] Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
[Greene, Meridith E.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Greene, Meridith E.; Rolfson, Ola; Malchau, Henrik; Garellick, Goran] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
[Gordon, Max] Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
RP Greene, ME (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA.
EM megreene@partners.org
RI Gordon, Max/M-4330-2014;
OI Gordon, Max/0000-0002-8080-5815; Nemes, Szilard/0000-0002-4145-1786;
Rolfson, Ola/0000-0001-6534-1242
FU Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Harris
Orthopaedic Laboratory, Boston, MA, USA; Dr Felix Neuberghs Foundation,
Gothenburg, Sweden
FX This study was funded by the Swedish Hip Arthroplasty Register,
Gothenburg, Sweden (GG), the Harris Orthopaedic Laboratory, Boston, MA,
USA (HM), and research grants from Dr Felix Neuberghs Foundation,
Gothenburg, Sweden (OR).
NR 27
TC 20
Z9 20
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD JUN
PY 2014
VL 472
IS 6
BP 1868
EP 1876
DI 10.1007/s11999-014-3504-2
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AG8KY
UT WOS:000335668500029
PM 24549772
ER
PT J
AU Flinterman, HJA
Doornberg, JN
Guitton, TG
Ring, D
Goslings, JC
Kloen, P
AF Flinterman, Hendrik J. A.
Doornberg, Job N.
Guitton, Thierry G.
Ring, David
Goslings, J. Carel
Kloen, Peter
TI Long-term Outcome of Displaced, Transverse, Noncomminuted Olecranon
Fractures
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID SURGICAL-TREATMENT; ELBOW FUNCTION; PROXIMAL ULNA; HEALTH-STATUS;
TENSION; FIXATION; STABILITY; WIRES; HEAD
AB Operative treatment of a displaced, transverse, noncomminuted fracture of the olecranon is associated with good to excellent elbow function in retrospective short-term followup studies. However, to our knowledge, no studies have evaluated objective and subjective outcomes using standardized outcome instruments (ie, DASH and Mayo Elbow Performance Index [MEPI]) to quantify long-term outcome of these specific fractures.
We evaluated (1) factors associated with disability, as measured with the DASH questionnaire; (2) factors associated with ulnohumeral motion; (3) factors associated with pain intensity; and (4) general descriptive findings for posttraumatic arthrosis, MEPI, ulnar neuropathy symptoms, and return to work between 10 and 32 years after open reduction and internal fixation (ORIF) of a transverse, noncomminuted fracture of the olecranon.
Between 1977 and 1997, we performed ORIFs of transverse, noncomminuted olecranon fractures in 109 patients, of whom 35 had died, 14 had incomplete data in our registry, and 19 were lost to followup or declined participation, leaving 41 patients available for followup at a minimum of 10 years after surgery. During that time, our general indication for performing ORIF was greater than 2 mm displacement. The average age of these patients at the time of injury was 35 years (range, 18-73 years). Patient-reported outcome was quantified using the DASH questionnaire, and physician-based outcome was evaluated using the MEPI. To identify factors associated with disability (DASH), impairment (MEPI), ulnohumeral motion, and pain, we examined demographic and clinical data in bivariate analyses, and subsequently significant factors in multivariate analysis to identify independent predictors of outcome.
The sole factor associated with higher DASH scores in multivariable analysis was age at surgery, explaining 20% of the variability, with younger patients performing better. The mean arc of elbow flexion was 142A degrees (range, 110A degrees-160A degrees), and the variation was associated with arthrosis alone (ie, a greater arc of motion was associated with a lesser grade of arthrosis according to the system of Broberg and Morrey). Pain was uncommon and generally was correlated with adverse events.
The good results of operative fixation (tension-band wiring) of a transverse, displaced olecranon fracture are durable with time. Patient-reported outcomes are excellent in the majority of patients. Residual patient-rated disability does not correlate with arthrosis or loss of extension.
C1 [Flinterman, Hendrik J. A.; Doornberg, Job N.] Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands.
[Doornberg, Job N.; Guitton, Thierry G.] Univ Amsterdam, Orthopaed Residency Program, Amsterdam, Netherlands.
[Ring, David] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Med Sch,Orthopaed Hand & Upper Extrem Serv, Boston, MA USA.
[Goslings, J. Carel] Acad Med Ctr Amsterdam, Dept Surg, Trauma Unit, NL-1100 DD Amsterdam, Netherlands.
[Doornberg, Job N.; Kloen, Peter] Acad Med Ctr Amsterdam, Dept Orthopaed Surg, NL-1100 DD Amsterdam, Netherlands.
RP Doornberg, JN (reprint author), Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands.
EM jdoornberg@partners.org
OI Guitton, Thierry/0000-0002-2599-1985
FU Keuning-Marti-Eckhardt Foundation, Amsterdam, The Netherlands
FX One of the authors (JND) received funding from the
Keuning-Marti-Eckhardt Foundation, Amsterdam, The Netherlands.
NR 30
TC 4
Z9 6
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD JUN
PY 2014
VL 472
IS 6
BP 1955
EP 1961
DI 10.1007/s11999-014-3481-5
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AG8KY
UT WOS:000335668500040
PM 24522384
ER
PT J
AU Rana, HQ
Rainville, IR
Vaidya, A
AF Rana, Huma Q.
Rainville, Irene R.
Vaidya, Anand
TI Genetic testing in the clinical care of patients with pheochromocytoma
and paraganglioma
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Review
DE counselling; genetic testing; inheritance; next-generation sequencing;
paraganglioma; pheochromocytoma
ID ENDOCRINE NEOPLASIA TYPE-2; MITOCHONDRIAL COMPLEX II;
HIPPEL-LINDAU-DISEASE; GASTROINTESTINAL STROMAL TUMORS;
GENOTYPE-PHENOTYPE CORRELATIONS; MEDULLARY-THYROID CANCER; COWDEN-LIKE
SYNDROME; SUCCINATE-DEHYDROGENASE; GERMLINE MUTATIONS; NEUROFIBROMATOSIS
TYPE-1
AB Purpose of reviewParaganglioma and pheochromocytoma (PGL/PCC) are tumours of neural crest origin that can present along a clinical spectrum ranging from apparently sporadic, isolated tumours to a more complex phenotype of one or multiple tumours in the context of other clinical features and family history suggestive of a defined hereditary syndrome. Genetic testing for hereditary PGL/PCC can help to confirm a genetic diagnosis for sporadic and syndromic cases. Informative genetic testing serves to clarify future risks for the patient and family members.Recent findingsGenetic discovery in the last decade has identified new PGL/PCC susceptibility loci. We summarize a contemporary approach adopted in our programme for genetic evaluation, testing and prospective management involving biochemical monitoring and imaging for hereditary PGL/PCC. A clinical vignette is presented to illustrate our practice.SummaryCurrent estimates that up to 40% of PGL/PCC are associated with germline mutations have implications for genetic testing recommendations. Prospective management of patients with defined hereditary susceptibility is based on established guidelines for well characterized syndromes. Management of tumour risk for rare syndromes, newly defined genetic associations and undefined genetic susceptibility in the setting of significant family history presents a challenge. Sustained discovery of new PGL/PCC genes underscores the need for a practice of continued genetic evaluation for patients with uninformative results. All patients with PGL/PCC should undergo genetic testing to identify potential hereditary tumour susceptibility.
C1 [Rana, Huma Q.; Rainville, Irene R.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Canc Genet & Prevent,Dept Med Oncol, Boston, MA 02115 USA.
[Vaidya, Anand] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Adrenal Disorders,Div Endocrinol Diabet & Hyp, Boston, MA 02115 USA.
RP Rana, HQ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02115 USA.
EM HumaQ_Rana@dfci.harvard.edu
OI Rana, Huma/0000-0002-1598-6752
FU NHLBI NIH HHS [L30 HL104553]
NR 97
TC 2
Z9 2
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD JUN
PY 2014
VL 21
IS 3
BP 166
EP 176
DI 10.1097/MED.0000000000000059
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AG5FS
UT WOS:000335445500004
PM 24739310
ER
PT J
AU Shores, MM
Matsumoto, AM
AF Shores, Molly M.
Matsumoto, Alvin M.
TI Testosterone, aging and survival: biomarker or deficiency
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Review
DE aging; androgens; biomarker; mortality; testosterone
ID LOW SERUM TESTOSTERONE; ALL-CAUSE MORTALITY; CORONARY-HEART-DISEASE;
PLACEBO-CONTROLLED TRIALS; ENDOGENOUS SEX-HORMONES; POPULATION-BASED
COHORT; LIFE-STYLE FACTORS; QUALITY-OF-LIFE; OLDER MEN;
CARDIOVASCULAR-DISEASE
AB Purpose of reviewThe purpose of this study is to review recent studies that examined the association of endogenous and exogenous testosterone and mortality in older men.Recent findingsOver the past several years, there has been a steep rise in testosterone prescriptions. The increased use of testosterone occurred in the context of several studies that reported an association between low serum testosterone and increased cardiovascular events and mortality. In contrast, recent studies have reported an association between testosterone treatment and adverse events. A testosterone treatment trial of mobility-impaired elderly men with prevalent cardiovascular disease was stopped due to increased cardiovascular events in the T-treated men and a meta-analysis reported increased cardiovascular events in T-treated men. In two recent large observational studies, testosterone treatment was associated with an increased risk for serious adverse cardiovascular events.SummaryLow testosterone is associated with mortality in multiple cohort studies; however, it is unclear if this is a causal association or due to low testosterone being a biomarker of poor health. Given recent reports of adverse outcomes associated with testosterone treatment, a conservative use of testosterone is warranted in men with cardiovascular disease who may be at greater risk for adverse outcomes.
C1 [Shores, Molly M.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA.
[Shores, Molly M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Matsumoto, Alvin M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA.
[Matsumoto, Alvin M.] GRECC, Seattle, WA USA.
RP Shores, MM (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,S-116A, Seattle, WA 98108 USA.
EM molly.shores@va.gov
FU VA Research Service; VA Geriatric Research Education and Clinical Center
(GRECC); 1R01 AG042934-01; AbbVie; GSK Pharmaceuticals; Advisory Board
for Abbott; Advisory Board for Endo; Forendo Pharmaceuticals; UpToDate.
FX The research was supported by the VA Research Service, the VA Geriatric
Research Education and Clinical Center (GRECC) and by 1R01 AG042934-01.;
Disclosure summary: Dr Matsumoto has the following disclosures to make -
Research support from AbbVie and GSK Pharmaceuticals; Advisory Board for
Abbott, Endo, and Forendo Pharmaceuticals; and Editor for UpToDate.
NR 80
TC 4
Z9 4
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD JUN
PY 2014
VL 21
IS 3
BP 209
EP 216
DI 10.1097/MED.0000000000000057
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AG5FS
UT WOS:000335445500009
PM 24722173
ER
PT J
AU Brownell, AL
AF Brownell, Anna-Liisa
TI Prognostic imaging of neuroblastoma
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Editorial Material
ID PEDIATRIC NEUROBLASTOMA; DIAGNOSIS; TUMORS; PET
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Expt PET Lab,Athinoula A Martinos Biomed Imaging, Charlestown, MA 02129 USA.
RP Brownell, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Expt PET Lab,Athinoula A Martinos Biomed Imaging, Charlestown, MA 02129 USA.
EM abrownell@partners.org
NR 13
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
EI 1619-7089
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUN
PY 2014
VL 41
IS 6
BP 1043
EP 1045
DI 10.1007/s00259-014-2749-z
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG7BI
UT WOS:000335572600001
PM 24668276
ER
PT J
AU Adriaanse, SM
van Dijk, KRA
Ossenkoppele, R
Reuter, M
Tolboom, N
Zwan, MD
Yaqub, M
Boellaard, R
Windhorst, AD
van der Flier, WM
Scheltens, P
Lammertsma, AA
Barkhof, F
van Berckel, BNM
AF Adriaanse, Sofie M.
van Dijk, Koene R. A.
Ossenkoppele, Rik
Reuter, Martin
Tolboom, Nelleke
Zwan, Marissa D.
Yaqub, Maqsood
Boellaard, Ronald
Windhorst, Albert D.
van der Flier, Wiesje M.
Scheltens, Philip
Lammertsma, Adriaan A.
Barkhof, Frederik
van Berckel, Bart N. M.
TI The effect of amyloid pathology and glucose metabolism on cortical
volume loss over time in Alzheimer's disease
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Alzheimer's disease; Amyloid plaques; Hypometabolism; Atrophy;
Longitudinal study
ID MILD COGNITIVE IMPAIRMENT; 2-YEAR FOLLOW-UP; HIPPOCAMPAL ATROPHY; BETA
DEPOSITION; IN-VIVO; A-BETA; ASSOCIATION WORKGROUPS; DIAGNOSTIC
GUIDELINES; NATIONAL INSTITUTE; STRUCTURAL MRI
AB Purpose The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls.
Methods Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [C-11] PIB to assess amyloid-beta plaque load and [18F]FDG to assess glucose metabolism. [11C] PIB binding and [18F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. Results While amyloid-beta plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho=0.56, p<0.05).
Conclusion The present study shows that in a group of AD patients amyloid-beta plaque load as measured by [11C] PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [18F] FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.
C1 [Adriaanse, Sofie M.; Yaqub, Maqsood; Boellaard, Ronald; Windhorst, Albert D.; Lammertsma, Adriaan A.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, NL-1007 MB Amsterdam, Netherlands.
[van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Adriaanse, Sofie M.; Ossenkoppele, Rik; Tolboom, Nelleke; Zwan, Marissa D.; Barkhof, Frederik; van Berckel, Bart N. M.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Radiol & Nucl Med, NL-1007 MB Amsterdam, Netherlands.
[van Dijk, Koene R. A.; Reuter, Martin] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Reuter, Martin] MIT, Div Hlth Sci & Technol, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[van der Flier, Wiesje M.; Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands.
RP Adriaanse, SM (reprint author), Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Radiol & Nucl Med, Neurosci Campus Amsterdam,POB 7057, NL-1007 MB Amsterdam, Netherlands.
EM s.adriaanse@vumc.nl
RI Reuter, Martin/B-3456-2010; Van Dijk, Koene/G-3317-2012;
OI Reuter, Martin/0000-0002-2665-9693; Van Dijk, Koene/0000-0001-6137-4282;
Boellaard, Ronald/0000-0002-0313-5686; Windhorst,
Albert/0000-0002-1250-7656
FU Internationale Stichting Alzheimer Onderzoek (ISAO) [11539];
Hersenstichting Nederland [KS2011(1)-24]
FX This study was sponsored by Internationale Stichting Alzheimer Onderzoek
(ISAO; project number #11539) and Hersenstichting Nederland
(KS2011(1)-24).
NR 57
TC 1
Z9 1
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
EI 1619-7089
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUN
PY 2014
VL 41
IS 6
BP 1190
EP 1198
DI 10.1007/s00259-014-2704-z
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG7BI
UT WOS:000335572600017
PM 24615466
ER
PT J
AU Kroeger, N
Choueiri, TK
Lee, JL
Bjarnason, GA
Knox, JJ
MacKenzie, MJ
Wood, L
Srinivas, S
Vaishamayan, UN
Rha, SY
Pal, SK
Yuasa, T
Donskov, F
Agarwal, N
Tan, MH
Bamias, A
Kollmannsberger, CK
North, SA
Rini, BI
Heng, DYC
AF Kroeger, Nils
Choueiri, Toni K.
Lee, Jae-Lyn
Bjarnason, Georg A.
Knox, Jennifer J.
MacKenzie, Mary J.
Wood, Lori
Srinivas, Sandy
Vaishamayan, Ulka N.
Rha, Sun-Young
Pal, Sumanta K.
Yuasa, Takeshi
Donskov, Frede
Agarwal, Neeraj
Tan, Min-Han
Bamias, Aristotelis
Kollmannsberger, Christian K.
North, Scott A.
Rini, Brian I.
Heng, Daniel Y. C.
TI Survival Outcome and Treatment Response of Patients with Late Relapse
from Renal Cell Carcinoma in the Era of Targeted Therapy
SO EUROPEAN UROLOGY
LA English
DT Article
DE Late recurrence; Targeted therapies; Treatment response; Survival
outcome; Renal cell carcinoma
ID NEPHRECTOMY; PROGRESSION; FEATURES; CRITERIA; AGE
AB Background: A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence >= 5 yr after initial nephrectomy. Objective: To characterize the clinical outcome of patients with late recurrence beyond 5 yr.
Design, setting, and participants: Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease > 3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr.
Outcome measurements and statistical analysis: Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses.
Results and limitations: Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p < 0.0001), fewer with sarcomatoid features (p < 0.0001), more clear cell histology (p = 0.001), and lower Fuhrman grade (p < 0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p = 0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5mo; p = 0.005) and overall survival (OS; 34.0mo vs 27.4 mo; p = 0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols.
Conclusions: A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Kroeger, Nils; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada.
[Kroeger, Nils] Univ Med Greifswald, Dept Urol, Greifswald, Germany.
[Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lee, Jae-Lyn] Univ Ulsan, Coll Med, Asan, South Korea.
[Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Knox, Jennifer J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[MacKenzie, Mary J.] London Hlth Sci Ctr, London, ON, Canada.
[Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
[Srinivas, Sandy] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
[Vaishamayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
[Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA USA.
[Yuasa, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan.
[Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark.
[Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Tan, Min-Han] Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore.
[Tan, Min-Han] Inst Bioengn & Nanotechnol, Singapore, Singapore.
[Bamias, Aristotelis] Univ Athens, Dept Clin Therapeut, Athens, Greece.
[Kollmannsberger, Christian K.] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada.
[North, Scott A.] Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada.
[Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada.
EM daniel.heng@albertahealthservices.ca
OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov,
Frede/0000-0002-8449-863X
FU Novartis; Bayer; Pfizer; GlaxoSmithKline; Bayer Korea
FX Daniel Y.C. Heng certifies that all conflicts of interest, including
specific financial interests and relationships and affiliations relevant
to the subject matter or materials discussed in the manuscript (eg,
employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents
filed, received, or pending), are the following: Jae-Lyn Lee receives
honoraria from Novartis, Bayer, and Pfizer, and research funding from
Bayer. Mary J. MacKenzie is an adviser at Novartis and Pfizer and has
received research funding from both. Georg A. Bjarnason is a consultant
and adviser for Pfizer. He receives honoraria and research funding from
Pfizer. Jennifer J. Knox is a consultant and adviser for AVEO and has
received research funding from Pfizer. Lori Wood is an adviser for
Pfizer and Novartis and has received research funding from Pfizer,
Novartis, and GlaxoSmithKline. Ulka N. Vaishamayan has received
honoraria and research funding from Pfizer, Novartis, and
GlaxoSmithKline. Sun-Young Rha is an adviser for Novartis, Pfizer, and
GlaxoSmithKline and has received research funding from Novartis and
Bayer Korea. Frede Donskov has received research funding from Novartis.
Christian K. Kollmannsberger is an adviser for Pfizer, Novartis, and
GlaxoSmithKline. Scott A North is a consultant and adviser for Novartis,
Bayer, GlaxoSmithKline, and Pfizer. Brian I. Rini is an adviser for
Pfizer, GlaxoSmithKline, Bayer, and Onyx, and he has received research
funding from GlaxoSmithKline and Pfizer. Toni K. Choueiri has received
research funding from Pfizer and is an adviser for AVEO, Pfizer,
Novartis, GlaxoSmithKline, Genentech, Bayer, and Onyx. Daniel Y.C. Heng
is an adviser for AVEO, Pfizer, Novartis, and Bayer. Nils Kroeger, Sandy
Srinivas, Sumanta K. Pal, Takeshi Yuasa, Neeraj Agarwal, and Min-Han Tan
have nothing to disclose.
NR 18
TC 28
Z9 28
U1 0
U2 3
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 JUN
PY 2014
VL 65
IS 6
BP 1086
EP 1092
DI 10.1016/j.eururo.2013.07.031
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AG4JV
UT WOS:000335386700029
PM 23916693
ER
PT J
AU Punnen, S
Freedland, SJ
Presti, JC
Aronson, WJ
Terris, MK
Kane, CJ
Amling, CL
Carroll, PR
Cooperberg, MR
AF Punnen, Sanoj
Freedland, Stephen J.
Presti, Joseph C., Jr.
Aronson, William J.
Terris, Martha K.
Kane, Christopher J.
Amling, Christopher L.
Carroll, Peter R.
Cooperberg, Matthew R.
TI Multi-institutional Validation of the CAPRA-S Score to Predict Disease
Recurrence and Mortality After Radical Prostatectomy
SO EUROPEAN UROLOGY
LA English
DT Article
DE Nomogram; Outcomes; Prostate cancer; Radical prostatectomy
ID RANDOMIZED CLINICAL-TRIAL; UNIVERSITY-OF-CALIFORNIA; RISK-ASSESSMENT
SCORE; BIOCHEMICAL RECURRENCE; ADJUVANT RADIOTHERAPY; EXTERNAL
VALIDATION; CANCER RECURRENCE; SAN-FRANCISCO; MODELS; SURVIVAL
AB Background: The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally.
Objective: To validate CAPRA-S in a large, multi-institutional, external database.
Design, setting, and participants: The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670men(92%) had complete data to calculate a CAPRA-S score. Intervention: RP.
Outcome measurements and statistical analysis: The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index. Results and limitations: The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The cindex for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events.
Conclusions: In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index > 0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Punnen, Sanoj; Carroll, Peter R.; Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Freedland, Stephen J.] Duke Univ, Dept Surg, Div Urol, Durham, NC USA.
[Freedland, Stephen J.] Durham Vet Adm Med Ctr, Urol Sect, Durham, NC USA.
[Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA.
[Presti, Joseph C., Jr.] Vet Adm Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA.
[Aronson, William J.] Vet Adm Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA.
[Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA.
[Terris, Martha K.] Vet Adm Med Ctr, Dept Surg, Urol Sect, Augusta, GA 30904 USA.
[Terris, Martha K.] Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA.
[Kane, Christopher J.] Univ Calif San Diego, Dept Urol, San Diego, CA 92103 USA.
[Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR USA.
[Cooperberg, Matthew R.] Vet Adm Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA.
RP Cooperberg, MR (reprint author), Univ Calif San Francisco, Dept Urol, 1600 Divisadero St,Box 1695, San Francisco, CA 94143 USA.
EM mcooperberg@urology.ucsf.edu
OI Terris, Martha/0000-0002-3843-7270
FU US Department of Veterans Affairs; US Department of Defense; Prostate
Cancer Research Program; NIH [R01CA100938]; NIH Specialized Programs of
Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition;
American Urological Association Foundation/Astellas Rising Star in
Urology Award
FX Funding for the collection and management of the data was from the US
Department of Veterans Affairs, the US Department of Defense, Prostate
Cancer Research Program (C.J.K., S.J.F), NIH R01CA100938 (W.J.A), NIH
Specialized Programs of Research Excellence Grant P50 CA92131-01A1
(W.J.A), Georgia Cancer Coalition (M.K.T), and the American Urological
Association Foundation/Astellas Rising Star in Urology Award (S.J.E).
Views and opinions of and endorsements by the authors do not reflect
thsoe of the US Army or the Department of Defense.
NR 26
TC 40
Z9 41
U1 1
U2 4
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 JUN
PY 2014
VL 65
IS 6
BP 1171
EP 1177
DI 10.1016/j.eururo.2013.03.058
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AG4JV
UT WOS:000335386700044
PM 23587869
ER
PT J
AU Han, LC
Delpe, S
Shah, ND
Ziegenfuss, JY
Tilburt, JC
Karnes, RJ
Nguyen, PL
Gross, CP
Yu, JB
Trinh, QD
Sun, M
Ranasinghe, WKB
Kim, SP
AF Han, Leona C.
Delpe, Sophia
Shah, Nilay D.
Ziegenfuss, Jeanette Y.
Tilburt, Jon C.
Karnes, R. Jeffrey
Nguyen, Paul L.
Gross, Cary P.
Yu, James B.
Quoc-Dien Trinh
Sun, Maxine
Ranasinghe, Weranja K. B.
Kim, Simon P.
TI Perceptions of Radiation Oncologists and Urologists on Sources and Type
of Evidence to Inform Prostate Cancer Treatment Decisions
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RADICAL PROSTATECTOMY; LOW-RISK; RANDOMIZED-TRIAL; MANAGEMENT; TRENDS;
GUIDELINES; ADJUVANT
AB Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer.
Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome.
Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly used resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P <.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer ( 85% vs 77%; P=.009).
Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer. (C) 2014 Elsevier Inc.
C1 [Han, Leona C.; Shah, Nilay D.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN USA.
[Delpe, Sophia; Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT 06517 USA.
[Ziegenfuss, Jeanette Y.] HealthPartners, Minneapolis, MN USA.
[Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN USA.
[Tilburt, Jon C.] Mayo Clin, Biomed Eth Program, Rochester, MN USA.
[Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA.
[Karnes, R. Jeffrey] Mayo Clin, Dept Urol, Rochester, MN USA.
[Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gross, Cary P.; Yu, James B.; Kim, Simon P.] Yale Univ, Canc Outcomes & Publ Policy Effectiveness Res Ctr, New Haven, CT 06517 USA.
[Gross, Cary P.] Yale Univ, Dept Internal Med, New Haven, CT 06517 USA.
[Yu, James B.] Yale Univ, Dept Radiat Oncol, New Haven, CT 06517 USA.
[Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA.
[Sun, Maxine] Univ Montreal, Ctr Hlth, Montreal, PQ, Canada.
[Ranasinghe, Weranja K. B.] Alfred Hosp, Div Urol, Melbourne, Vic, Australia.
RP Kim, SP (reprint author), Yale Univ, Dept Urol, 310 Cedar St,BML 238B, New Haven, CT 06517 USA.
EM simkim@me.com
NR 29
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2014
VL 89
IS 2
BP 277
EP 283
DI 10.1016/j.ijrobp.2014.02.001
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AG6FG
UT WOS:000335513800010
PM 24685153
ER
PT J
AU Hattangadi-Gluth, JA
Chapman, PH
Kim, D
Niemierko, A
Bussiere, MR
Stringham, A
Daartz, J
Ogilvy, C
Loeffler, JS
Shih, HA
AF Hattangadi-Gluth, Jona A.
Chapman, Paul H.
Kim, Daniel
Niemierko, Andrzej
Bussiere, Marc R.
Stringham, Alison
Daartz, Juliane
Ogilvy, Christopher
Loeffler, Jay S.
Shih, Helen A.
TI Single-Fraction Proton Beam Stereotactic Radiosurgery for Cerebral
Arteriovenous Malformations
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID GAMMA-KNIFE SURGERY; TERM-FOLLOW-UP; GRADING SYSTEM; BRAIN-STEM;
OBLITERATION; THALAMUS; COMPLICATIONS; RADIATION; OUTCOMES; THERAPY
AB Purpose/Objective(s): To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs).
Methods and Materials: From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage.
Results: At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P <.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P <.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P <.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%).
Conclusions: The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Posttreatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment. (C) 2014 Elsevier Inc.
C1 [Hattangadi-Gluth, Jona A.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, San Diego, CA 92103 USA.
[Chapman, Paul H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Kim, Daniel; Niemierko, Andrzej; Bussiere, Marc R.; Stringham, Alison; Daartz, Juliane; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Ogilvy, Christopher] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA.
RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA.
EM hshih@partners.org
NR 34
TC 7
Z9 7
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2014
VL 89
IS 2
BP 338
EP 346
DI 10.1016/j.ijrobp.2014.02.030
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AG6FG
UT WOS:000335513800017
PM 24726288
ER
PT J
AU Grassberger, C
Daartz, J
Dowdell, S
Ruggieri, T
Sharp, G
Paganetti, H
AF Grassberger, Clemens
Daartz, Juliane
Dowdell, Stephen
Ruggieri, Thomas
Sharp, Greg
Paganetti, Harald
TI Quantification of Proton Dose Calculation Accuracy in the Lung
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID PENCIL BEAM ALGORITHM; MONTE-CARLO; HETEROGENEOUS MEDIA; THERAPY;
CANCER; RADIOTHERAPY; TUMORS; OUTCOMES; PHOTON; ISSUES
AB Purpose: To quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC)-based dose calculation through measurements and to assess the clinical impact in a cohort of patients with tumors located in the lung.
Methods and Materials: A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in the lung, and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm.
Results: MC increased dose calculation accuracy in lung tissue compared with the TPS and reproduced dose measurements in the target to within +/- 2%. The average difference between measured and predicted dose in a plane through the center of the target was 5.6% for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors, MC also predicted consistently higher V5 and V10 to the normal lung, because of a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target could show large deviations, although this effect was highly patient specific. Range measurements showed that MC can reduce range uncertainty by a factor of similar to 2: the average (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm (17 mm) for the TPS in lung tissue.
Conclusion: Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. In addition, the ability to confidently reduce range margins would benefit all patients by potentially lowering toxicity. (C) 2014 Elsevier Inc.
C1 [Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA.
[Grassberger, Clemens] Paul Scherrer Inst, Ctr Proton Radiotherapy, Villigen, Switzerland.
RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA.
EM Grassberger.Clemens@mgh.harvard.edu
FU National Cancer Institute [R01CA111590]
FX Supported by National Cancer Institute grant R01CA111590.
NR 25
TC 10
Z9 10
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2014
VL 89
IS 2
BP 424
EP 430
DI 10.1016/j.ijrobp.2014.02.023
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AG6FG
UT WOS:000335513800028
PM 24726289
ER
PT J
AU Lichtenhan, JT
Hartsock, JJ
Gill, RM
Guinan, JJ
Salt, AN
AF Lichtenhan, J. T.
Hartsock, J. J.
Gill, R. M.
Guinan, J. J., Jr.
Salt, A. N.
TI The Auditory Nerve Overlapped Waveform (ANOW) Originates in the Cochlear
Apex
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE auditory nerve neurophonic; compound action potential; low-frequency
hearing; neural synchrony; phase locking
ID GUINEA-PIG; LOW-FREQUENCY; ROUND WINDOW; TRANSMITTER RELEASE;
HAIR-CELLS; INNER-EAR; HEARING; PERILYMPH; SYNAPSE; FIBERS
AB Measurements of cochlear function with compound action potentials (CAPs), auditory brainstem responses, and otoacoustic emissions work well with high-frequency sounds but are problematic at low frequencies. We have recently shown that the auditory nerve overlapped waveform (ANOW) can objectively quantify low-frequency (< 1 kHz) auditory sensitivity, as thresholds for ANOW at low frequencies and for CAP at high frequencies relate similarly to single auditory nerve fiber thresholds. This favorable relationship, however, does not necessarily mean that ANOW originates from auditory nerve fibers innervating low-frequency regions of the cochlear apex. In the present study, we recorded the cochlear response to tone bursts of low frequency (353, 500, and 707 Hz) and high frequency (2 to 16 kHz) during administration of tetrodotoxin (TTX) to block neural function. TTX was injected using a novel method of slow administration from a pipette sealed into the cochlear apex, allowing real-time measurements of systematic neural blocking from apex to base. The amplitude of phase-locked (ANOW) and onset (CAP) neural firing to moderate-level, low-frequency sounds were markedly suppressed before thresholds and responses to moderate-level, high-frequency sounds were affected. These results demonstrate that the ANOW originates from responses of auditory nerve fibers innervating cochlear apex, confirming that ANOW provides a valid physiological measure of low-frequency auditory nerve function.
C1 [Lichtenhan, J. T.; Hartsock, J. J.; Gill, R. M.; Salt, A. N.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA.
[Guinan, J. J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA.
[Guinan, J. J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Lichtenhan, JT (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, Box 8115660 South Euclid Ave, St Louis, MO 63110 USA.
EM jlichtenhan@gmail.com
FU National Institutes of Health, National Institute on Deafness and Other
Communication Disorders [R03 DC012844, R01 DC000235, R01 DC001368]
FX We thank Doctors Ann E. Hickox, Mark A. Rutherford, Christopher A.
Shera, and Mrs. Uzma S. Wilson for helpful discussion on this research.
Two anonymous reviewers and Associate Editor Dr. Nigel Cooper provided
productive criticisms that improved this report. This work was supported
by grants R03 DC012844 (J.T.L.), R01 DC000235 (J.J.G.), and R01 DC001368
(A.N.S.) from the National Institutes of Health, National Institute on
Deafness and Other Communication Disorders.
NR 44
TC 11
Z9 11
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
EI 1438-7573
J9 JARO-J ASSOC RES OTO
JI JARO
PD JUN
PY 2014
VL 15
IS 3
BP 395
EP 411
DI 10.1007/s10162-014-0447-y
PG 17
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA AH0LN
UT WOS:000335811500005
PM 24515339
ER
PT J
AU Vaina, LM
Soloviev, S
Calabro, FJ
Buonanno, F
Passingham, R
Cowey, A
AF Vaina, Lucia M.
Soloviev, Sergei
Calabro, Finnegan J.
Buonanno, Ferdinando
Passingham, Richard
Cowey, Alan
TI Reorganization of Retinotopic Maps after Occipital Lobe Infarction
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID HUMAN CEREBRAL-CORTEX; HUMAN VISUAL-CORTEX; PRIMATE SOMATOSENSORY
CORTEX; PERIPHERAL-NERVE INJURY; SURFACE-BASED ANALYSIS; NEW-WORLD
MONKEYS; MOTION PERCEPTION; STRIATE CORTEX; FUNCTIONAL REORGANIZATION;
ISCHEMIC LESIONS
AB We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT(+)) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.
C1 [Vaina, Lucia M.; Buonanno, Ferdinando] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vaina, Lucia M.; Buonanno, Ferdinando] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Vaina, Lucia M.; Soloviev, Sergei; Calabro, Finnegan J.; Buonanno, Ferdinando; Cowey, Alan] Boston Univ, Boston, MA 02215 USA.
[Passingham, Richard; Cowey, Alan] Univ Oxford, Oxford OX1 2JD, England.
RP Vaina, LM (reprint author), Boston Univ, Dept Biomed, Room 315,44 Cummington St, Boston, MA 02215 USA.
EM vaina@bu.edu
OI Calabro, Finnegan/0000-0002-8092-3942
FU NIH [R01NS064100]
FX This work was supported by NIH grant R01NS064100 to L. M. V. Lucia M.
Vaina dedicates this article to Charlie Gross, who has been a long-time
collaborator and friend. I met him at the INS meeting in Beaune
(France), and since then we often discussed the relationship between
several aspects of high-level visual processing described in his work in
monkeys physiology and my work in neuropsychology. In particular, his
pioneering study of biological motion in monkeys' superior temporal lobe
has influenced my own work on biological motion and has led us to
coauthor a paper on this topic. Working with Charlie was a uniquely
enjoyable experience. Alan Cowey and I often spoke fondly about Charlie,
a dear friend and close colleague to us both, whose work, exquisite
sense of humor, and unbound zest of living we both deeply admired and
loved.
NR 58
TC 3
Z9 3
U1 0
U2 12
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
EI 1530-8898
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUN
PY 2014
VL 26
IS 6
SI SI
BP 1266
EP 1282
DI 10.1162/jocn_a_00538
PG 17
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA AG6CM
UT WOS:000335506100007
PM 24345177
ER
PT J
AU Noh, GT
Kim, MH
Suh, JY
Song, Y
Lee, CK
Baek, JH
Lee, YS
Cho, G
Kim, E
Kim, YR
Cho, HJ
Lim, D
Kim, JK
AF Noh, Gwang Tae
Kim, Mi-hyun
Suh, Ji-Yeon
Song, Youngkyu
Lee, Chang Kyung
Baek, Jin Hee
Lee, Yong Seok
Cho, Gyunggoo
Kim, EunJu
Kim, Young Ro
Cho, Hyung Joon
Lim, Dongyeol
Kim, Jeong Kon
TI Sunitinib-CLIO Conjugate: A VEGFR/PDGFR-Targeting Active MR Probe
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE MR probe; VEGFR; PDGFR; Iron oxide; Angiogenesis
ID IRON-OXIDE NANOPARTICLES; CONTRAST AGENTS; INHIBITOR; THERAPY;
ANGIOGENESIS; SORAFENIB; SU11248
AB This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe.
VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven Delta R (2) was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates.
Delta R (2) between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater Delta R (2) in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R (2) changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %).
Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.
C1 [Noh, Gwang Tae; Lim, Dongyeol] Sejong Univ, Dept Chem, Seoul 143747, South Korea.
[Kim, Mi-hyun; Suh, Ji-Yeon; Lee, Chang Kyung; Baek, Jin Hee; Lee, Yong Seok; Kim, Jeong Kon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, Seoul 138736, South Korea.
[Suh, Ji-Yeon; Song, Youngkyu; Lee, Chang Kyung; Baek, Jin Hee; Lee, Yong Seok; Cho, Gyunggoo; Kim, Jeong Kon] Korea Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chungbuk, South Korea.
[Kim, EunJu] Philips Healthcare, Seoul 260199, South Korea.
[Kim, Young Ro] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Cho, Hyung Joon] Ulsan Natl Inst Sci & Technol, Ulsan 689798, South Korea.
RP Kim, JK (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, 388-1 Poongnap Dong, Seoul 138736, South Korea.
EM kim.jeongkon@gmail.com
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Education, Science and Technology
[2010-0015389, 2011-0028826]; Korea Basic Science Institute [T3222K]
FX This work was supported by Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (2010-0015389 and 2011-0028826) and by
a grant from Korea Basic Science Institute (T3222K). We specially thank
to Dr. Eun Kyoung Ryu for manuscript preparation.
NR 18
TC 2
Z9 2
U1 1
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2014
VL 16
IS 3
BP 340
EP 349
DI 10.1007/s11307-013-0697-9
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG9JH
UT WOS:000335734900006
PM 24185817
ER
PT J
AU Tichauer, KM
Deharvengt, SJ
Samkoe, KS
Gunn, JR
Bosenberg, MW
Turk, MJ
Hasan, T
Stan, RV
Pogue, BW
AF Tichauer, Kenneth M.
Deharvengt, Sophie J.
Samkoe, Kimberley S.
Gunn, Jason R.
Bosenberg, Marcus W.
Turk, Mary-Jo
Hasan, Tayyaba
Stan, Radu V.
Pogue, Brian W.
TI Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer
Fluorescence Molecular Imaging
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Tracer kinetic modeling; Cancer; Mouse model; PV1
ID IN-VIVO; FENESTRATED ENDOTHELIA; COMPARTMENTAL MODEL; RECEPTOR; BINDING;
EXPRESSION; DIAPHRAGMS; KINETICS; ANTIBODY; CANCER
AB Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations.
Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system.
The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors.
This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo.
C1 [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
[Deharvengt, Sophie J.; Stan, Radu V.] Geisel Sch Med Dartmouth, Dept Pathol, Hanover, NH 03755 USA.
[Samkoe, Kimberley S.; Pogue, Brian W.] Geisel Sch Med Dartmouth, Dept Surg, Hanover, NH 03755 USA.
[Turk, Mary-Jo; Stan, Radu V.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH 03755 USA.
[Samkoe, Kimberley S.; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
[Bosenberg, Marcus W.] Yale Univ, New Haven, CT 06520 USA.
[Turk, Mary-Jo; Pogue, Brian W.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA.
[Hasan, Tayyaba; Pogue, Brian W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Tichauer, KM (reprint author), IIT, Dept Biomed Engn, Chicago, IL 60616 USA.
EM tichauer@iit.edu
RI Stan, Radu/E-8876-2011
OI Stan, Radu/0000-0003-2969-1725
FU NIH [R01 CA109558, U54 CA151662, R21 CA175592]; CIHR
FX This work was sponsored by NIH research grants R01 CA109558, U54
CA151662, and R21 CA175592, as well as a CIHR Postdoctoral Fellowship
for KMT.
NR 35
TC 6
Z9 6
U1 0
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2014
VL 16
IS 3
BP 372
EP 382
DI 10.1007/s11307-013-0692-1
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG9JH
UT WOS:000335734900009
PM 24217944
ER
PT J
AU Clarke, SE
Kang, JX
Ma, DWL
AF Clarke, Shannon E.
Kang, Jing X.
Ma, David W. L.
TI The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment
both in vitro and in vivo
SO TRANSGENIC RESEARCH
LA English
DT Article
DE fat-1; n-3 Desaturase; Cre-recombinase; loxP
ID FATTY-ACID DESATURASE; ADENOVIRAL GENE-TRANSFER; FAT-1 MICE; CANCER
CELLS; HPRT LOCUS; EXPRESSION; MOUSE; RATIO; RECOMBINATION; GENERATION
AB Fat-1 transgenic mice, which endogenously convert n-6 PUFA to n-3 PUFA, are a useful tool in health research; however with this model timing of n-3 PUFA enrichment cannot be directly controlled. To add such capability, the novel Cre-recombinase inducible fat-1 (iFat1) transgenic mouse has been developed. The aim of this study was to characterize the utility of the iFat1 transgene as a model of Cre-inducible endogenous n-3 PUFA enrichment. Functionality of the iFat1 transgene was screened both in vitro and in vivo. In the presence of Cre, the iFat1 transgene resulted in a balancing (p < 0.01) of the n-6/n-3 PUFA ratio within phospholipids in the human embryonic kidney 293T cell line. For in vivo analysis, iFat1 transgenic mice were crossed with the R26-Cre-ERT2 (Tam-Cre) mouse line, a tamoxifen inducible Cre-expression model. Tam-Cre/iFat1 double hybrids were transiently treated with tamoxifen at 6-7 weeks, then terminated 3 weeks later. Tamoxifen treated mice had increased (p < 0.05) tissue n-3 PUFA and a parts per thousand yentwo-fold reduction (p < 0.05) in the n-6/n-3 PUFA ratio of liver, kidney and muscle phospholipids relative to vehicle treated controls. Collectively these findings suggest that the iFat1 transgenic mouse may be a promising tool to help elucidate the temporal effects through which n-3 PUFA impacts health related outcomes.
C1 [Clarke, Shannon E.; Ma, David W. L.] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada.
[Kang, Jing X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA.
RP Ma, DWL (reprint author), Univ Guelph, Dept Human Hlth & Nutr Sci, 50 Stone Rd East, Guelph, ON N1G 2W1, Canada.
EM davidma@uoguelph.ca
FU Canadian Institutes of Health Research [89971]; Canada Foundation for
Innovation Leaders Opportunity Fund; Ontario Research Fund; Canadian
Institute of Health Research Federick Banting; Canadian Institute of
Charles Best Canada Graduate Scholarship
FX This work was supported by the Canadian Institutes of Health Research
(Grant #89971 to D. W. L. Ma) and the Canada Foundation for Innovation
Leaders Opportunity Fund with matching from the Ontario Research Fund.
S. E. Clarke is funded by a Canadian Institutes of Health Research
Federick Banting and Charles Best Canada Graduate Scholarship. The
authors would like to acknowledge Lyn Hillyer and Colin Stringer for
their technical assistance in this as well as Dr. Nina Jones (Department
of Molecular and Cellular Biology, University of Guelph) for provision
of the HEK 293T and expertise in the in vitro experiments.
NR 39
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U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
EI 1573-9368
J9 TRANSGENIC RES
JI Transgenic Res.
PD JUN
PY 2014
VL 23
IS 3
BP 489
EP 501
DI 10.1007/s11248-014-9788-x
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA AH0SV
UT WOS:000335831600008
PM 24622775
ER
PT J
AU Byers, AL
Yaffe, K
AF Byers, Amy L.
Yaffe, Kristine
TI Depression and dementias among military veterans
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Dementia; Alzheimer's disease; Cognitive impairment; Depression;
Posttraumatic stress disorder; Traumatic brain injury; Older veterans
ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MILD COGNITIVE
IMPAIRMENT; LATE-LIFE DEPRESSION; WHITE-MATTER HYPERINTENSITIES;
CARDIOVASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME;
MAJOR DEPRESSION; GERIATRIC DEPRESSION
AB Depression is very common throughout the course of veterans' lives, and dementia is common in late life. Previous studies suggest an association between depression and dementia in military veterans. The most likely biologic mechanisms that may link depression and dementia among military veterans include vascular disease, changes in glucocorticoid steroids and hippocampal atrophy, deposition of beta-amyloid plaques, inflammatory changes, and alterations of nerve growth factors. In addition, military veterans often have depression comorbid with posttraumatic stress disorder or traumatic brain injury. Therefore, in military veterans, these hypothesized biologic pathways going from depression to dementia are more than likely influenced by trauma-related processes. Treatment strategies for depression, posttraumatic stress disorder, or traumatic brain injury could alter these pathways and as a result decrease the risk for dementia. Given the projected increase of dementia, as well as the projected increase in the older segment of the veteran population, in the future, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize the principal mechanisms of this relationship and discuss treatment implications in military veterans. (C) 2014 The Alzheimer's Association. All rights reserved.
C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
EM Amy.Byers@ucsf.edu
FU United States Army Medical Research and Materiel Command
FX Publication of this article was supported by the United States Army
Medical Research and Materiel Command.
NR 114
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Z9 5
U1 5
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S166
EP S173
DI 10.1016/j.jalz.2014.04.007
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700011
PM 24924668
ER
PT J
AU Durazzo, TC
Mattsson, N
Weiner, MW
AF Durazzo, Timothy C.
Mattsson, Niklas
Weiner, Michael W.
CA Alzheimer's Dis Neuroimaging
TI Smoking and increased Alzheimer's disease risk: A review of potential
mechanisms
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Alzheimer's disease; Cigarette smoking; Tobacco; Risk; Amyloid; Tau;
Military; Oxidative stress; US Armed Services
ID CHRONIC CIGARETTE-SMOKING; MILD COGNITIVE IMPAIRMENT; ALCOHOL-DEPENDENT
INDIVIDUALS; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY;
NICOTINIC ACETYLCHOLINE-RECEPTOR; TRAUMATIC BRAIN-INJURY; PITTSBURGH
COMPOUND-B; FREE-RADICAL DAMAGE; STRESS IN-VIVO
AB Background: Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians.
Methods: A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD-related neuropathology was conducted. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented.
Results: Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD.
Conclusions: A reduction in the incidence of smoking will likely reduce the future prevalence of AD. (C) 2014 The Alzheimer's Association. All rights reserved.
C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA.
[Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA.
EM timothy.durazzo@ucsf.edu
FU National Institutes of Health [NIH DA24136, P30 AG010129, K01 AG030514,
R01 AG010897, R01 AG012435]; ADNI; National Institute on Aging [U01
AG024904]; National Institute of Biomedical Imaging and Bioengineering;
Dana Foundation
FX T.C.D. was responsible for the concept and design of the review,
completed all statistical analyses on the original data presented, and
wrote the original and revised versions of the manuscript. N.M. and
M.W.W. were involved in manuscript editing, data interpretation, and
manuscript draft revisions. T.C.D. had full access to all the original
data presented study and takes responsibility for the integrity of the
data and the accuracy of the data analyses. This work was supported by
the National Institutes of Health (NIH DA24136 to T.C.D.) and by the use
of resources and facilities at the San Francisco Veterans Administration
Medical Center. Florbetapir data collection and sharing for this project
was funded by ADNI. ADNI is funded by the National Institute on Aging
(U01 AG024904), the National Institute of Biomedical Imaging and
Bioengineering, and through generous contributions from the following:
Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb;
Eisai Global Clinical Development; Elan Corporation; Genentech; GE
Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli
Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer
Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; and Wyeth, as
well as nonprofit partners such as the Alzheimer's Association and
Alzheimer Drug Discovery Foundation, with participation from the U.S.
Food and Drug Administration. Private sector contributions to ADNI are
facilitated by the Foundation for the National Institutes of Health
(www.fnih.org; http://www.fnih.org; http://www.fnih.org;
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 for Neuro Imaging at the University Southern California. This
research was also supported by National Institutes of Health grants P30
AG010129, K01 AG030514, R01 AG010897, and R01 AG012435, and The Dana
Foundation and by resources by resources and the use of facilities at
the San Francisco Veterans Administration Medical Center, San Francisco,
CA. The aforementioned funding agencies had no role in the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, or approval of the
manuscript. Original data used in preparation of this article were
obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the
investigators within the ADNI contributed to the design and
implementation of ADNI and/or provided data but did not participate in
analysis or writing of this report. A complete listing of ADNI
investigators can be found at:
http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Authorship
_List. pdf
NR 260
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Z9 41
U1 5
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S122
EP S145
DI 10.1016/j.jalz.2014.04.009
PG 24
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700008
PM 24924665
ER
PT J
AU Greenberg, MS
Tanev, K
Marin, MF
Pitman, RK
AF Greenberg, Mark S.
Tanev, Kaloyan
Marin, Marie-France
Pitman, Roger K.
TI Stress, PTSD, and dementia
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Stress; Dementia; Posttraumatic stress disorder; PTSD; Alzheimer's
disease; Vascular dementia
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; PSYCHOLOGICAL DISTRESS;
HIPPOCAMPAL ATROPHY; PSYCHIATRIC-DISORDERS; OXIDATIVE STRESS; TAU
PATHOLOGY; LIFE STRESS; GREY-MATTER; BRAIN
AB The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals. (C) 2014 The Alzheimer's Association. All rights reserved.
C1 [Greenberg, Mark S.; Tanev, Kaloyan; Marin, Marie-France; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Greenberg, MS (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM mark_greenberg@hms.harvard.edu
FU United States Army Medical Research and Materiel Command
FX Publication of this article was supported by the United States Army
Medical Research and Materiel Command.
NR 77
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Z9 12
U1 5
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S155
EP S165
DI 10.1016/j.jalz.2014.04.008
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700010
PM 24924667
ER
PT J
AU McKee, AC
Robinson, ME
AF McKee, Ann C.
Robinson, Meghan E.
TI Military-related traumatic brain injury and neurodegeneration
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Chronic traumatic encephalopathy; Veterans; Neurodegeneration; Traumatic
brain injury; Tauopathy; TDP-43; Alzheimer's disease
ID POSTTRAUMATIC-STRESS-DISORDER; FOOTBALL-LEAGUE PLAYER; HEAD-INJURY;
ALZHEIMERS-DISEASE; WHITE-MATTER; CEREBRAL VASOSPASM; EXPLOSIVE BLAST;
AXONAL INJURY; WAR VETERANS; ENCEPHALOPATHY
AB Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. (C) 2014 Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [McKee, Ann C.; Robinson, Meghan E.] VA Boston Healthcare Syst, Boston, MA 02114 USA.
[McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA.
[McKee, Ann C.] Boston Univ, Sch Med, Alzheimer Dis Ctr, Boston, MA 02118 USA.
RP McKee, AC (reprint author), VA Boston Healthcare Syst, Boston, MA 02114 USA.
EM amckee@bu.edu
RI Meijer, Anna/K-5118-2016
FU Department of Veterans Affairs; Veterans Affairs Biorepository [CSP
501]; Translational Research Center for Traumatic Brain Injury and
Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and
Development Traumatic Brain Injury Center of Excellence [B6796-C];
National Institute of Neurological Disorders and Stroke; National
Institute of Biomedical Imaging and Bioengineering [UO1NS086659-01];
National Institute of Aging Boston University Alzheimer's Disease Center
[P30AG13846, 0572063345-5]; Sports Legacy Institute; National Operating
Committee on Standards for Athletic Equipment
FX The authors gratefully acknowledge the use of resources and facilities
at the Boston VA Healthcare System (Boston, MA) and Edith Nourse Rogers
Memorial Veterans Hospital (Bedford, MA), as well as all of the
individuals whose participation and contributions made this work
possible. This work was supported by the Department of Veterans Affairs;
Veterans Affairs Biorepository (CSP 501); the Translational Research
Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans
Affairs Rehabilitation Research and Development Traumatic Brain Injury
Center of Excellence (B6796-C); the National Institute of Neurological
Disorders and Stroke, National Institute of Biomedical Imaging and
Bioengineering UO1NS086659-01), National Institute of Aging Boston
University Alzheimer's Disease Center [P30AG13846; supplement
0572063345-5]; the Sports Legacy Institute; and the National Operating
Committee on Standards for Athletic Equipment. This work was also
supported by unrestricted gifts from the National Football League, the
Andlinger Foundation, and the WWE.
NR 75
TC 41
Z9 41
U1 6
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S242
EP S253
DI 10.1016/j.jalz.2014.04.003
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700018
PM 24924675
ER
PT J
AU Meziab, O
Kirby, KA
Williams, B
Yaffe, K
Byers, AL
Barnes, DE
AF Meziab, Omar
Kirby, Katharine A.
Williams, Brie
Yaffe, Kristine
Byers, Amy L.
Barnes, Deborah E.
TI Prisoner of war status, posttraumatic stress disorder, and dementia in
older veterans
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Dementia; Risk factors; Veterans; Aged; POW; Posttraumatic stress
disorder
ID FOLLOW-UP; PLASMA-CORTISOL; HUMAN-MEMORY; FAR-EAST; RISK; DISABILITY;
DISEASE; HEALTH; MALNUTRITION; PREVALENCE
AB Background: It is not known whether prisoners of war (POWs) are more likely to develop dementia independently of the effects of posttraumatic stress disorder (PTSD).
Methods: We performed a retrospective cohort study in 182,879 U.S. veterans age 55 years and older, and examined associations between POW status and PTSD at baseline (October 1, 2000-September 30, 2003), and incident dementia during follow-up (October 1, 2003-September 30, 2012).
Results: A total of 484 veterans (0.3%) reported being POWs, of whom 150 (31.0%) also had PTSD. After adjusting for demographics, medical and psychiatric comorbidities, period of service, and the competing risk of death, the risk of dementia was increased in veterans who were POWs only (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.30-1.98) or had PTSD only (HR, 1.52; 95% CI, 1.41-1.64) and was greatest in veterans who were POWs and also had PTSD (HR, 2.24; 95% CI, 1.72-2.92).
Conclusions: POW status and PTSD increase risk of dementia in an independent, additive manner in older veterans. (C) 2014 Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [Meziab, Omar] Univ Arizona, Sch Med, Tucson, AZ USA.
[Kirby, Katharine A.; Williams, Brie] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
[Kirby, Katharine A.; Williams, Brie; Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Barnes, DE (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
EM Deborah.barnes@ucsf.edu
FU Department of Defense/NCIRE (The Veterans Health Research Institute)
[W81XWH-11-2-0189, 1610, 1614, W81XWH-12-1-0581]; National Institutes of
Health [K24 AG031155]
FX This study was supported by the Department of Defense/NCIRE (The
Veterans Health Research Institute) (Barnes: W81XWH-11-2-0189, project
1610; Byers: W81XWH-11-2-0189, project 1614; Yaffe: W81XWH-12-1-0581)
and the National Institutes of Health (Yaffe: K24 AG031155). The views
expressed do not necessarily reflect those of the U.S. government.
NR 40
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U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S236
EP S241
DI 10.1016/j.jalz.2014.04.004
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700017
PM 24924674
ER
PT J
AU Tanner, CM
Goldman, SM
Ross, GW
Grate, SJ
AF Tanner, Caroline M.
Goldman, Samuel M.
Ross, G. Webster
Grate, Stephen J.
TI The disease intersection of susceptibility and exposure: Chemical
exposures and neurodegenerative disease risk
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Neurodegeneration; Parkinson's disease; Alzheimer's disease; Motor
neuron disease; Military; Risk factors; Pesticides; Traumatic brain
injury; Solvents; Gene-environment interaction
ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON-DISEASE;
METHYLAMINO-L-ALANINE; GULF-WAR VETERANS; STRIATAL DOPAMINE TRANSPORTER;
CUMULATIVE LEAD-EXPOSURE; PERIOD-COHORT ANALYSIS; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE; POLYCHLORINATED-BIPHENYLS
AB Alzheimer's disease, Parkinson's disease, and motor neuron disease, the most common of the late-life neurodegenerative disorders, are in most cases thought to have complex etiologies. Common features among these disorders include insidious onset, pathological findings of protein aggregates and selected neuronal degeneration, and resulting characteristic clinical syndromes. The number of elders in the United States, including aging veterans, is increasing. Investigation of causes and preventive interventions for neurodegenerative disorders is increasingly relevant. Recent epidemiological and laboratory studies suggest that exposures years or decades before diagnosis can trigger the processes that ultimately result in a neurodegenerative disease. If this is correct, preventive measures may be needed in midlife or earlier. This article will focus on putative risk factors relevant to military service. Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [Tanner, Caroline M.; Goldman, Samuel M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA.
[Tanner, Caroline M.; Goldman, Samuel M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Tanner, Caroline M.; Goldman, Samuel M.] Parkinsons Inst, Sunnyvale, CA USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Grate, Stephen J.] MSAMRMC, Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA.
RP Tanner, CM (reprint author), San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA.
EM caroline.tanner@ucsf.edu
FU United States Army Medical Research and Materiel Command
FX Publication of this article was supported by the United States Army
Medical Research and Materiel Command.
NR 176
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U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S213
EP S225
DI 10.1016/j.jalz.2014.04.014
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700015
PM 24924672
ER
PT J
AU Yaffe, K
Hoang, TD
Byers, AL
Barnes, DE
Friedl, KE
AF Yaffe, Kristine
Hoang, Tina D.
Byers, Amy L.
Barnes, Deborah E.
Friedl, Karl E.
TI Lifestyle and health-related risk factors and risk of cognitive aging
among older veterans
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Veterans; Dementia; Cognitive aging; Lifestyle behaviors; Health-related
risk factors
ID POSTTRAUMATIC-STRESS-DISORDER; OBSTRUCTIVE SLEEP-APNEA; CEREBRAL
WHITE-MATTER; US ARMY SOLDIERS; ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY;
METABOLIC SYNDROME; BLOOD-PRESSURE; SOCIAL NETWORK; MENTAL-HEALTH
AB Lifestyle and health-related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health-related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them. Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine; Friedl, Karl E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM kristine.yaffe@ucsf.edu
FU United States Army Medical Research and Materiel Command
FX Publication of this article was supported by the United States Army
Medical Research and Materiel Command.
NR 160
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U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUN
PY 2014
VL 10
IS 3
SU 1
BP S111
EP S121
DI 10.1016/j.jalz.2014.04.010
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA CP8GM
UT WOS:000360130700007
PM 24924664
ER
PT J
AU Mannix, R
Iverson, GL
Maxwell, B
Atkins, JE
Zafonte, R
Berkner, PD
AF Mannix, Rebekah
Iverson, Grant L.
Maxwell, Bruce
Atkins, Joseph E.
Zafonte, Ross
Berkner, Paul D.
TI Multiple prior concussions are associated with symptoms in high school
athletes
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
AB Objectives: The purpose of this study was to evaluate the association of prior concussion on baseline computerized neurocognitive testing in a large cohort of high school athletes. Methods: This is a retrospective cohort study of student athletes from 49 Maine High Schools in 2010 who underwent baseline computerized neurocognitive evaluation with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT (R)). As part of the ImPACT (R), subjects reported a prior history of concussion as well as demographic information and a symptom questionnaire. We used linear regression to evaluate the association of prior concussion with baseline: (1) ImPACT (R) composite scores; and (2) symptom scores. Results: Six thousand seventy-five subjects were included in the study, of whom 57% were boys. The majority of student athletes (85.3%) reported no prior history of concussion while 4.6% reported having sustained two or more prior concussions. On simple linear regression, increasing number of concussions was related to worse performance in verbal memory (P = 0.039) and greater symptoms scores (P < 0.001). On multivariate modeling, only the association with baseline symptoms remained (P < 0.001). Other factors associated with baseline symptom reporting in the multivariate model included mental health history, headache/migraine history, gender, developmental and/or learning problems, and number of prior concussions. Interpretation: In this large-scale, retrospective survey study, history of multiple prior concussions was associated with higher symptom burden but not baseline computerized neurocognitive testing. The association between baseline symptom reporting and clinical and demographic factors was greater than the association with a history of multiple concussions.
C1 [Mannix, Rebekah] Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA.
[Mannix, Rebekah; Iverson, Grant L.; Zafonte, Ross] Harvard Med Sch, Boston, MA USA.
[Iverson, Grant L.; Zafonte, Ross] Harvard Med Sch, Dept Phys Med & Rehabil, Boston, MA USA.
[Iverson, Grant L.; Zafonte, Ross] Red Sox Fdn, Boston, MA USA.
[Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA.
[Iverson, Grant L.; Zafonte, Ross] Spaulding Rehabil Hosp, Boston, MA USA.
[Maxwell, Bruce] Colby Coll, Dept Comp Sci, Waterville, ME 04901 USA.
[Atkins, Joseph E.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA.
[Berkner, Paul D.] Colby Coll, Hlth Serv, Waterville, ME 04901 USA.
RP Mannix, R (reprint author), Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM rebekah.mannix@childrens.harvard.edu
NR 24
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U1 2
U2 2
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 JUN
PY 2014
VL 1
IS 6
BP 433
EP 438
DI 10.1002/acn3.70
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V45KI
UT WOS:000209815100006
PM 25356413
ER
PT J
AU U, KP
Subramanian, V
Nicholas, AP
Thompson, PR
Ferretti, P
AF U, Kin Pong
Subramanian, Venkataraman
Nicholas, Antony P.
Thompson, Paul R.
Ferretti, Patrizia
TI Modulation of calcium-induced cell death in human neural stem cells by
the novel peptidylarginine deiminase-AIF pathway
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Apoptosis inducing factor (ALF); Cell death; Citrullination-deimination;
Human neural stem cell; Peptidylarginine deiminase (PAD,PADI); Vimentin
ID CHICK SPINAL-CORD; CITRULLINATED PROTEINS; MULTIPLE-SCLEROSIS;
TRANSCRIPTIONAL REGULATION; RHEUMATOID-ARTHRITIS; NUCLEAR-LOCALIZATION;
HUMAN KERATINOCYTES; CALPAIN-I; APOPTOSIS; MOUSE
AB PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required for AIF (apoptosis inducing factor)-mediated apoptosis. PAD inhibition prevents association of PAD3 with AIF and AIF cleavage required for its translocation to the nucleus. Finally, PAD inhibition also hinders calcium-induced cytoskeleton disassembly and association of PAD3 with vimentin, that we show to be associated also with AIF; together this suggests that PAD-dependent cytoskeleton disassembly may play a role in AIF translocation to the nucleus. This is the first study highlighting a role of PAD activity in balancing hNSC survival/death, identifying PAD3 as an important upstream regulator of calciuminduced apoptosis, which could be targeted to reduce neural loss, and shedding light on the mechanisms involved. (C) 2014 The Authors. Published by Elsevier B.V.
C1 [U, Kin Pong; Ferretti, Patrizia] UCL Inst Child Hlth, Dev Biol Unit, 30 Guilford St, London WC1N LEH, England.
[Subramanian, Venkataraman; Thompson, Paul R.] Scripps Res Inst, Dept Chem, Scripps Florida, FL 33458 USA.
[Nicholas, Antony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Nicholas, Antony P.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
RP Ferretti, P (reprint author), UCL Inst Child Hlth, Dev Biol Unit, 30 Guilford St, London WC1N LEH, England.
EM p.ferretti@ucl.ac.uk
OI Ferretti, Patrizia/0000-0002-3590-6772
FU Child Research Appeal Trust [08DB04]; Biotechnology and Biological
Sciences Research Council; National Institutes of Health [GM079357];
Medical Research Council [G070089]; Wellcome Trust [GR082557]
FX This work was supported by grants from the Child Research Appeal Trust
(grant 08DB04 to PF), the Biotechnology and Biological Sciences Research
Council (PF) and the National Institutes of Health (grant GM079357 to
PRT). The human embryonic and fetal material was provided by the Human
Developmental Biology Resource (http://lidbr.org) jointly funded by the
Medical Research Council (grant G070089) and The Wellcome Trust (grant
GR082557). We are grateful to J. Ham, JP Brockes and JC Sowden for
reading the manuscript. The authors declare no competing financial
interests.
NR 68
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U1 3
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUN
PY 2014
VL 1843
IS 6
BP 1162
EP 1171
DI 10.1016/j.bbamcr.2014.02.018
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AG7VW
UT WOS:000335627900011
PM 24607566
ER
PT J
AU Palaganas, JC
AF Palaganas, Janice C.
TI "This is not a Simulation''-A Necessary Phrase
SO CLINICAL SIMULATION IN NURSING
LA English
DT Editorial Material
C1 [Palaganas, Janice C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA.
RP Palaganas, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA.
EM jpalaganas@mgh.harvard.edu
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 1876-1399
EI 1876-1402
J9 CLIN SIMUL NURS
JI Clin. Simul. Nurs.
PD JUN
PY 2014
VL 10
IS 6
BP E283
EP E283
DI 10.1016/j.ecns.2014.04.001
PG 1
WC Nursing
SC Nursing
GA V42OY
UT WOS:000209624300001
ER
PT J
AU Hofmann, SG
Hinton, DE
AF Hofmann, Stefan G.
Hinton, Devon E.
TI Cross-Cultural Aspects of Anxiety Disorders
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Review
DE Culture; Anxiety disorders; DSM-5; Cross culture; Taijin kyofusho;
Ataques de nervios
ID LIFETIME PREVALENCE; SELF
AB A person's cultural background influences the experience and expression of emotions. In reviewing the recent literature on cross-cultural aspects of anxiety disorders, we identified some culturally related ethnopsychology/ethnophysiology factors (the culture's conceptualizations of how the mind and body function) and contextual factors that influence anxiety disorders. Ethnopsychology/ethnophysiology factors include the person's ideas about the mental and bodily processes (and their interaction), whereas contextual factors are associated with the social norms and rules that may contribute to anxiety, including individualism vs. collectivism and self-construals. From the perspective of ethnopsychology/ethnophysiology and contextual factors, we will discuss "khyal cap" ("wind attacks"), taijin kyofusho, and ataques de nervios, three prominent examples of culture-specific expressions of anxiety disorders that have all been included in the DSM-5 list of cultural concepts of distress.
C1 [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Hinton, Devon E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA.
EM shofmann@bu.edu
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
FU NIH [R-1AT007257]
FX Dr. Hofmann's work is supported by NIH grant R-1AT007257.
NR 15
TC 6
Z9 6
U1 3
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
EI 1535-1645
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD JUN
PY 2014
VL 16
IS 6
AR 450
DI 10.1007/s11920-014-0450-3
PG 5
WC Psychiatry
SC Psychiatry
GA CY1QK
UT WOS:000366182300002
PM 24744049
ER
PT J
AU Ahern, T
Khattak, A
Reece, R
Kilbane, M
Smith, TP
Lehane, C
McKenna, MJ
O'Shea, D
Hayes, FJ
AF Ahern, Tomas
Khattak, Aftab
Reece, Roland
Kilbane, Mark
Smith, Thomas P.
Lehane, Ciannait
McKenna, Malachi J.
O'Shea, Donal
Hayes, Frances J.
TI Contrasting Effects of Aromatase Inhibition and Testosterone Therapy in
Men with Severe Obesity: A Randomised Clinical Trial
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ahern, Tomas; Khattak, Aftab; Reece, Roland; Kilbane, Mark; Smith, Thomas P.; Lehane, Ciannait; McKenna, Malachi J.; O'Shea, Donal] St Vincents Univ Hosp, Dublin 4, Ireland.
[Hayes, Frances J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0013
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104165
ER
PT J
AU Babwah, AV
Calder, MD
Chan, YM
Raj, R
Elbert, A
Noonan, M
Caligioni, C
Berube, N
Bhattacharya, M
Seminara, SB
AF Babwah, Andy Videsh
Calder, Michele Dawn
Chan, Yee-Ming
Raj, Renju
Elbert, Adrienne
Noonan, Michelle
Caligioni, Claudia
Berube, Nathalie
Bhattacharya, Moshmi
Seminara, Stephanie Beth
TI Implantation Failure in Female Kiss1-/- Mice Is Independent of Their
Hypogonadic State and Can be Partially Rescued By Leukemia Inhibitory
Factor
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Babwah, Andy Videsh; Calder, Michele Dawn; Elbert, Adrienne; Noonan, Michelle; Berube, Nathalie; Bhattacharya, Moshmi] Univ Western Ontario, London, ON, Canada.
[Chan, Yee-Ming] Massachusetts Gen Hosp, Quincy, MA USA.
[Raj, Renju] Univ Vermont, Coll Med, Burlington, VT 05405 USA.
[Caligioni, Claudia; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA LB-OR01-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107228
ER
PT J
AU Bachmann, KN
Fazeli, PK
Lawson, EA
Russell, BM
Riccio, AD
Meenaghan, E
Gerweck, AV
Bredella, MA
Klibanski, A
Miller, KK
AF Bachmann, Katherine Neubecker
Fazeli, Pouneh K.
Lawson, Elizabeth A.
Russell, Brian M.
Riccio, Ariana D.
Meenaghan, Erinne
Gerweck, Anu V.
Bredella, Miriam A.
Klibanski, Anne
Miller, Karen K.
TI Comparison of Hip Geometry, Strength, and Estimated Fracture Risk in
Women with Anorexia Nervosa and Overweight/Obese Women
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bachmann, Katherine Neubecker; Lawson, Elizabeth A.; Meenaghan, Erinne; Bredella, Miriam A.; Klibanski, Anne; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Fazeli, Pouneh K.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA.
[Russell, Brian M.; Riccio, Ariana D.; Gerweck, Anu V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0255
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105252
ER
PT J
AU Baudrand, R
Wiinberg, L
Adler, GK
Barletta, J
Chan, J
Choueiri, T
Dluhy, RG
Elfiky, A
Hamnvik, OPR
Kulke, M
Rainville, I
Rana, HQ
Ruan, DT
Saxena, A
Seely, EW
Shyn, P
Steele, AE
Williams, GH
Vaidya, A
AF Baudrand, Rene
Wiinberg, Linda
Adler, Gail Kurr
Barletta, Justine
Chan, Jennifer
Choueiri, Toni
Dluhy, Robert G.
Elfiky, Aymen
Hamnvik, Ole-Petter Riksfjord
Kulke, Matthew
Rainville, Irene
Rana, Huma Q.
Ruan, Daniel T.
Saxena, Aditi
Seely, Ellen W.
Shyn, Paul
Steele, Amy E.
Williams, Gordon H.
Vaidya, Anand
TI Evaluation of Quality of Life and Well-Being of Patients with Adrenal
Disorders in the Setting of an Integrated Multi-Disciplinary Care Model
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Baudrand, Rene] Pontificia Univ Catolica Chile, Santiago, Chile.
[Wiinberg, Linda; Adler, Gail Kurr; Barletta, Justine; Dluhy, Robert G.; Ruan, Daniel T.; Shyn, Paul; Steele, Amy E.; Williams, Gordon H.; Vaidya, Anand] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Chan, Jennifer; Choueiri, Toni; Kulke, Matthew; Rainville, Irene; Rana, Huma Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hamnvik, Ole-Petter Riksfjord; Saxena, Aditi; Seely, Ellen W.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0779
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103150
ER
PT J
AU Bauman, WA
Swonger, KN
Rivera, DR
LaFountaine, MF
AF Bauman, William A.
Swonger, Kirsten N.
Rivera, Dwindally Rosado
LaFountaine, Michael F.
TI HOMA beta-Cell Function Negatively Correlates to the Vasodilatory
Response of Insulin in the Cutaneous Microvasculature
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bauman, William A.; Swonger, Kirsten N.; Rivera, Dwindally Rosado] James J Peters VA Med Ctr, Bronx, NY USA.
[LaFountaine, Michael F.] Seton Hall Univ, S Orange, NJ 07079 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-1029
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107120
ER
PT J
AU Bolo, NR
Hager, B
Musen, G
Jacobson, AM
Keshavan, M
Simonson, DC
AF Bolo, Nicolas R.
Hager, Brandon
Musen, Gail
Jacobson, Alan M.
Keshavan, Matcheri
Simonson, Donald C.
TI Hyperglycemia Disrupts Regional Brain Functional Connectivity and
Increases Glutamate Neurotransmitter Levels in Type 1 Diabetes: A Link
to the Development of Depression?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bolo, Nicolas R.; Hager, Brandon; Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Musen, Gail] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Jacobson, Alan M.] Winthrop Univ Hosp, Mineola, NY 11501 USA.
[Simonson, Donald C.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR23-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100109
ER
PT J
AU Bowlin, SJ
Sadowski, T
Vokes, TJ
Bilezikian, JP
Clarke, BL
Mannstadt, M
Shoback, DM
Lagast, H
AF Bowlin, Steven J.
Sadowski, Tara
Vokes, Tamara J.
Bilezikian, John P.
Clarke, Bart Lyman
Mannstadt, Michael
Shoback, Dolores M.
Lagast, Hjalmar
TI Paradighm (TM): A Natural History Registry for Patients with Chronic
Hypoparathyroidism
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bowlin, Steven J.] NPS Pharma, Bedminster, NJ USA.
[Sadowski, Tara; Lagast, Hjalmar] NPS Pharmaceut Inc, Bedminster, NJ USA.
[Vokes, Tamara J.] Univ Chicago, Chicago, IL 60637 USA.
[Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Clarke, Bart Lyman] Mayo Clin Rochester, Rochester, MN USA.
[Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mannstadt, Michael] Harvard Med Sch, Boston, MA USA.
[Shoback, Dolores M.] Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0197
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105103
ER
PT J
AU Christensen, JD
Lungu, AO
Cochran, E
Collins, MT
Gafni, RI
Reynolds, JC
Gorden, P
Brown, RJ
AF Christensen, John D.
Lungu, Andreea O.
Cochran, Elaine
Collins, Michael T.
Gafni, Rachel I.
Reynolds, James C.
Gorden, Phillip
Brown, Rebecca J.
TI Increased Bone Mineral Content in Patients with Congenital Generalized
Lipodystrophy Is Unaffected By Metreleptin Replacement Therapy
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Christensen, John D.; Cochran, Elaine; Gorden, Phillip; Brown, Rebecca J.] NIDDK, NIH, Bethesda, MD USA.
[Lungu, Andreea O.] Joslin Diabet Ctr, Brookline, MA USA.
[Collins, Michael T.; Gafni, Rachel I.] NIDCR, NIH, Bethesda, MD USA.
[Reynolds, James C.] NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR43-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105097
ER
PT J
AU Cox, KH
Oliveira, LMB
Plummer, LC
Balasubramanian, R
Crowley, WF
AF Cox, Kimberly H.
Oliveira, Luciana Mattos Barros
Plummer, Lacey C.
Balasubramanian, Ravikumar
Crowley, William F.
TI Heterozygous PROKR2 Mutations in Isolated GnRH Deficiency: False
Positives or Dominant Negatives?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Cox, Kimberly H.; Oliveira, Luciana Mattos Barros; Plummer, Lacey C.; Balasubramanian, Ravikumar; Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0609
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101227
ER
PT J
AU Cunningham, GR
Rosen, RC
Wang, C
Stephens, A
Ellenberg, S
Matsumoto, AM
Bhasin, S
Molitch, ME
Farrar, JT
Cella, D
Gill, TM
Barrett-Connor, EL
Cauley, JA
Cifelli, D
Crandall, JP
Ensrud, KE
Fluharty, L
Hadley, E
Lewis, CE
Pahor, M
Resnick, SM
Romashkan, S
Swerdloff, RS
Snyder, PJ
AF Cunningham, Glenn R.
Rosen, Raymond C.
Wang, Christina
Stephens, Alisa
Ellenberg, Susan
Matsumoto, Alvin M.
Bhasin, Shalender
Molitch, Mark E.
Farrar, John T.
Cella, David
Gill, Thomas M.
Barrett-Connor, Elizabeth Louise
Cauley, Jane A.
Cifelli, Denise
Crandall, Jill P.
Ensrud, Kristine E.
Fluharty, Laura
Hadley, Evan
Lewis, Cora E.
Pahor, Marco
Resnick, Susan M.
Romashkan, Sergei
Swerdloff, Ronald S.
Snyder, Peter J.
TI Free Testosterone but Not Total Testosterone or Estradiol Is Associated
with Sexual Function in Symptomatic Older Hypogonadal Men in the Sexual
Function Trial of the Testosterone Trials
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA.
[Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA.
[Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Stephens, Alisa; Ellenberg, Susan; Farrar, John T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bhasin, Shalender] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Molitch, Mark E.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gill, Thomas M.] Yale Sch Med, New Haven, CT USA.
[Barrett-Connor, Elizabeth Louise] Univ CA San Diego, La Jolla, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA.
[Hadley, Evan; Romashkan, Sergei] NIA, Bethesda, MD 20892 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Pahor, Marco] Univ Florida, Gainesville, FL USA.
[Resnick, Susan M.] NIA, Baltimore, MD 21224 USA.
[Swerdloff, Ronald S.] Harbor Univ Calif Med Ctr, Torrance, CA USA.
[Snyder, Peter J.] Univ PA, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0084
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107199
ER
PT J
AU da Silva, PPB
Bhatnagar, S
Herman, S
Zafonte, R
Klibanski, A
Miller, KK
Tritos, NA
AF da Silva, Paula Paes Batista
Bhatnagar, Saurabha
Herman, Seth
Zafonte, Ross
Klibanski, Anne
Miller, Karen K.
Tritos, Nicholas A.
TI Predictors of Pituitary Hormone Deficiencies in Adults with History of
Traumatic Brain Injury
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [da Silva, Paula Paes Batista; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[da Silva, Paula Paes Batista] Harvard Med Sch, Boston, MA USA.
[Bhatnagar, Saurabha; Herman, Seth; Zafonte, Ross] Harvard Med Sch, Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Boston, MA USA.
[Tritos, Nicholas A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0732
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102096
ER
PT J
AU Dankel, SN
Ramirez, A
Xue, RD
Lee, KYS
Thomou, T
Kasif, S
Tseng, YH
Kahn, CR
AF Dankel, Simon Nitter
Ramirez, Alfred
Xue, Ruidan
Lee, Kevin Yu-sun
Thomou, Thomas
Kasif, Simon
Tseng, Yu-Hua
Kahn, C. Ronald
TI Preadipocyte and Adipocyte Heterogeneity within a Single White Fat Depot
in Humans
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Dankel, Simon Nitter; Ramirez, Alfred; Xue, Ruidan; Lee, Kevin Yu-sun; Thomou, Thomas; Tseng, Yu-Hua] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
[Kasif, Simon] Boston Univ, Boston, MA 02215 USA.
[Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA.
[Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR46-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103191
ER
PT J
AU Delaney, A
Lalonde, FM
Blumenthal, JD
Clasen, LS
Hicks, RL
Denker, AH
Giedd, JN
Crowley, WF
Balasubramanian, R
AF Delaney, Angela
Lalonde, Francois M.
Blumenthal, Jonathan D.
Clasen, Liv S.
Hicks, Rebecca L.
Denker, Alexander H.
Giedd, Jay N.
Crowley, William F.
Balasubramanian, Ravikumar
TI Delayed Sex Hormone Exposure during Puberty Is Associated with
Differences in Brain Cortical Thickness, Spatial Ability, and
Recognition Memory
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Delaney, Angela; Lalonde, Francois M.; Blumenthal, Jonathan D.; Clasen, Liv S.; Hicks, Rebecca L.; Denker, Alexander H.; Giedd, Jay N.] NIH, Bethesda, MD 20892 USA.
[Crowley, William F.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR11-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104109
ER
PT J
AU Dichtel, LE
Yuen, KCJ
Bredella, MA
Gerweck, AV
Russell, BM
Riccio, AD
Gurel, MH
Legg, SE
Sluss, PM
Biller, BMK
Miller, KK
AF Dichtel, Laura E.
Yuen, Kevin C. J.
Bredella, Miriam A.
Gerweck, Anu V.
Russell, Brian M.
Riccio, Ariana D.
Gurel, Michelle H.
Legg, Stacy E.
Sluss, Patrick M.
Biller, Beverly M. K.
Miller, Karen K.
TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak
Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST)
to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0676
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101168
ER
PT J
AU Dichtel, LE
Yuen, KCJ
Bredella, MA
Gerweck, AV
Russell, BM
Riccio, AD
Gurel, MH
Legg, SE
Sluss, PM
Biller, BMK
Miller, KK
AF Dichtel, Laura E.
Yuen, Kevin C. J.
Bredella, Miriam A.
Gerweck, Anu V.
Russell, Brian M.
Riccio, Ariana D.
Gurel, Michelle H.
Legg, Stacy E.
Sluss, Patrick M.
Biller, Beverly M. K.
Miller, Karen K.
TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak
Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST)
to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP03-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109323
ER
PT J
AU Dichtel, LE
Yuen, KCJ
Bredella, MA
Gerweck, AV
Russell, BM
Riccio, AD
Gurel, MH
Legg, SE
Sluss, PM
Biller, BMK
Miller, KK
AF Dichtel, Laura E.
Yuen, Kevin C. J.
Bredella, Miriam A.
Gerweck, Anu V.
Russell, Brian M.
Riccio, Ariana D.
Gurel, Michelle H.
Legg, Stacy E.
Sluss, Patrick M.
Biller, Beverly M. K.
Miller, Karen K.
TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak
Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST)
to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP03-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109324
ER
PT J
AU Ding, SA
Simonson, DC
Halperin, F
Wewalka, M
Foster, K
Kelly, K
Panosian, J
Goebel-Fabbri, A
Hamdy, O
Clancy, K
Lautz, D
Vernon, A
Goldfine, AB
AF Ding, Su Ann
Simonson, Donald C.
Halperin, Florencia
Wewalka, Marlene
Foster, Kathleen
Kelly, Katherine
Panosian, Jennifer
Goebel-Fabbri, Ann
Hamdy, Osama
Clancy, Kerni
Lautz, David
Vernon, Ashley
Goldfine, Allison B.
TI Comparative Effectiveness for Cardiometabolic Outcomes of Roux-En-Y
Gastric Bypass with Intensive Diabetes and Weight Management in Obese
Type 2 Diabetes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ding, Su Ann; Wewalka, Marlene; Foster, Kathleen; Kelly, Katherine; Panosian, Jennifer; Goebel-Fabbri, Ann; Hamdy, Osama; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Simonson, Donald C.; Halperin, Florencia; Vernon, Ashley] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Clancy, Kerni; Lautz, David] Emerson Hosp, Concord, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR40-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100124
ER
PT J
AU Faje, AT
Sullivan, R
Lawrence, D
Tritos, NA
Klibanski, A
Nachtigall, LB
AF Faje, Alexander Terence
Sullivan, Ryan
Lawrence, Donald
Tritos, Nicholas A.
Klibanski, Anne
Nachtigall, Lisa B.
TI Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a
Large Cohort of Patients with Metastatic Melanoma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA.
[Sullivan, Ryan; Lawrence, Donald] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tritos, Nicholas A.; Klibanski, Anne; Nachtigall, Lisa B.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0674
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102009
ER
PT J
AU Fazeli, PK
Faje, AT
Cross, E
Rosen, CJ
Bouxsein, ML
Klibanski, A
AF Fazeli, Pouneh K.
Faje, Alexander Terence
Cross, Ela
Rosen, Clifford J.
Bouxsein, Mary Larsen
Klibanski, Anne
TI FGF-21 Is Associated with Worsened Bone Microarchitecture and Decreased
Bone Strength in Anorexia Nervosa
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA.
[Cross, Ela; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA.
[Bouxsein, Mary Larsen] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0229
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105200
ER
PT J
AU Garcia-Caceres, C
Kim, JG
Gao, YQ
Wang, H
Fuente-Martin, E
Legutko, B
Meyer, C
Pfluger, PT
Kahn, CR
Magnan, C
Luquet, S
Eckel, RH
Vaccarino, FM
Shanabrough, M
Yi, CX
Horvath, TL
Tschop, MH
AF Garcia-Caceres, Cristina
Kim, Jae Geun
Gao, Yuanqing
Wang, Hong
Fuente-Martin, Esther
Legutko, Beata
Meyer, Carola
Pfluger, Paul T.
Kahn, C. Ronald
Magnan, Christophe
Luquet, Serge
Eckel, Robert H.
Vaccarino, Flora M.
Shanabrough, Marya
Yi, Chun-Xia
Horvath, Tamas L.
Tschoep, Matthias H.
TI Astrocytes Co-Regulate Systemic Metabolism in Response to Hormones and
Nutrients
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Garcia-Caceres, Cristina; Gao, Yuanqing; Fuente-Martin, Esther; Legutko, Beata; Meyer, Carola; Pfluger, Paul T.; Yi, Chun-Xia; Tschoep, Matthias H.] Tech Univ Munich, Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Munich, Germany.
[Garcia-Caceres, Cristina; Gao, Yuanqing; Fuente-Martin, Esther; Legutko, Beata; Meyer, Carola; Pfluger, Paul T.; Yi, Chun-Xia; Tschoep, Matthias H.] Tech Univ Munich, Div Metab Dis, Munich, Germany.
[Kim, Jae Geun; Shanabrough, Marya; Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA.
[Wang, Hong; Eckel, Robert H.] Univ Colorado, Dept Internal Med, Div Metab Endocrinol & Diabet, Aurora, CO USA.
[Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA.
[Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA.
[Magnan, Christophe; Luquet, Serge] Univ Paris Diderot Paris 7, CNRS, EAC 4413, Unite Biol Fonct & Adaptat, F-75205 Paris 13, France.
[Vaccarino, Flora M.] Yale Univ, Dept Neurobiol, Child Study Ctr, New Haven, CT 06520 USA.
[Vaccarino, Flora M.] Yale Univ, Kavli Inst Neurosci, New Haven, CT 06520 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR45-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103148
ER
PT J
AU Grimes, MC
Mathew, I
Bandi, A
Martin, E
Codario, R
Rao, RH
AF Grimes, Michael C.
Mathew, Indu
Bandi, Archana
Martin, Emily
Codario, Ronald
Rao, R. Harsha
TI Impact of U-500 Insulin on Glycemic Control, Risk of Hypoglycemia, and
Mortality in Patients with Extreme Insulin Resistance: The VA Pittsburgh
Experience
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Grimes, Michael C.; Mathew, Indu] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA.
[Bandi, Archana] VAPHS Oakland, Wexford, PA USA.
[Martin, Emily] VA Pittsburgh Healthcare Syst, Munhall, PA USA.
[Codario, Ronald] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Rao, R. Harsha] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR54-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100135
ER
PT J
AU Hattersley, G
Dean, T
Gardella, TJ
AF Hattersley, Gary
Dean, Thomas
Gardella, Thomas James
TI Differential Binding Selectivity of Abaloparatide (BA058) Compared to
PTH and PTHrP for PTH Type 1 Receptor Conformations
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Hattersley, Gary] Radius Hlth Inc, Cambridge, MA USA.
[Dean, Thomas; Gardella, Thomas James] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR31-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105215
ER
PT J
AU Hershman, JM
Liwanpo, L
Ro, C
ul Haq, MS
AF Hershman, Jerome M.
Liwanpo, Llanyee
Ro, Cynthia
ul Haq, Muhammd Salman
TI Sunitinib Does Not Inhibit Thyroid Peroxidase in Patients
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Hershman, Jerome M.] VA Greater LA Healthcare Syst, Los Angeles, CA USA.
[Liwanpo, Llanyee; Ro, Cynthia] VA Greater Los Angeles, Los Angeles, CA USA.
[ul Haq, Muhammd Salman] Sansum Clin, Santa Barbara, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0507
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109004
ER
PT J
AU Huynh, J
Lee, H
Clish, CB
Nathan, DM
Thadhani, R
Gerszten, RE
Bentley-Lewis, R
AF Huynh, Jennifer
Lee, Hang
Clish, Clary B.
Nathan, David M.
Thadhani, Ravi
Gerszten, Robert E.
Bentley-Lewis, Rhonda
TI Metabolomic Profiling in the Prediction of Gestational Diabetes Mellitus
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Huynh, Jennifer; Lee, Hang; Nathan, David M.; Thadhani, Ravi; Gerszten, Robert E.; Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Clish, Clary B.] Broad Inst MIT & Harvard, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR20-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100028
ER
PT J
AU Iacovazzo, D
Morrison, PJ
Foulkes, W
Ross, DS
Lugli, F
Gabrovska, P
Lucci-Cordisco, E
De Marinis, L
Korbonits, M
AF Iacovazzo, Donato
Morrison, Patrick J.
Foulkes, William
Ross, Douglas S.
Lugli, Francesca
Gabrovska, Plamena
Lucci-Cordisco, Emanuela
De Marinis, Laura
Korbonits, Marta
TI Four Families with RET-Mutation Negative Familial Medullary Thyroid
Carcinoma: What Lies Beyond RET?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Iacovazzo, Donato; Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England.
[Morrison, Patrick J.] Belfast City Hosp, Belfast, Antrim, North Ireland.
[Foulkes, William] McGill Univ, Montreal, PQ, Canada.
[Ross, Douglas S.] Mass Gen Hosp, Boston, MA USA.
[Lugli, Francesca; Lucci-Cordisco, Emanuela; De Marinis, Laura] Catholic Univ, Rome, Italy.
[Korbonits, Marta] Queen Mary Univ London, Bails & London Sch Med, William Harvey Res Inst, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0546
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109226
ER
PT J
AU Iacovazzo, D
Morrison, PJ
Foulkes, W
Ross, DS
Lugli, F
Gabrovska, P
Lucci-Cordisco, E
De Marinis, L
Korbonits, M
AF Iacovazzo, Donato
Morrison, Patrick J.
Foulkes, William
Ross, Douglas S.
Lugli, Francesca
Gabrovska, Plamena
Lucci-Cordisco, Emanuela
De Marinis, Laura
Korbonits, Marta
TI Four Families with RET-Mutation Negative Familial Medullary Thyroid
Carcinoma: What Lies Beyond RET?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Iacovazzo, Donato; Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England.
[Morrison, Patrick J.] Belfast City Hosp, Belfast, Antrim, North Ireland.
[Foulkes, William] McGill Univ, Montreal, PQ, Canada.
[Ross, Douglas S.] Mass Gen Hosp, Boston, MA USA.
[Lugli, Francesca; Lucci-Cordisco, Emanuela; De Marinis, Laura] Catholic Univ, Rome, Italy.
[Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP39-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109148
ER
PT J
AU Jain, R
Izquierdo, RE
McGrath, M
Rosenbaum, P
AF Jain, Rohit
Izquierdo, Roberto Emilio
McGrath, Mary
Rosenbaum, Paula
TI Poor RAI Treatment Outcomes in Persistent/Recurrent Follicular Cell-
Derived Thyroid Cancer with Negative Diagnostic Whole Body Scans (DxWBS)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Jain, Rohit; McGrath, Mary; Rosenbaum, Paula] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Izquierdo, Roberto Emilio] Joslin Diabet Ctr, Syracuse, NY USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0577
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109218
ER
PT J
AU Jensen, T
Wang, CCL
AF Jensen, Thomas
Wang, Cecilia C. Low
TI Double Trouble: A Case of Primary Hyperparathyroidism and Humoral
Hypercalcemia of Malignancy
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Jensen, Thomas] Univ Colorado, Sch Med, Aurora, CO USA.
[Wang, Cecilia C. Low] Denver VAMC, Denver, CO USA.
[Wang, Cecilia C. Low] Univ Colorado Sh, Denver, CO USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0202
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105128
ER
PT J
AU Kievit, P
Pound, L
Hobbs, T
Martin, D
Johnson, C
Escalona, A
Bader, L
Valleau, J
Elmquist, JK
Seeley, R
Kaplan, L
Grove, KL
AF Kievit, Paul
Pound, Lynley
Hobbs, Theodore
Martin, Drew
Johnson, Chris
Escalona, Alex
Bader, Lindsay
Valleau, Jeanette
Elmquist, Joel Keith
Seeley, Randy
Kaplan, Lee
Grove, Kevin L.
TI Caloric Intake Reduction Following Roux-En-Y Gastric Bypass Surgery
Drives Rapid Improvements in Glucose Homeostasis and Beta Cell Function
in Obese Rhesus Macaques
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kievit, Paul; Pound, Lynley; Hobbs, Theodore; Martin, Drew; Johnson, Chris; Bader, Lindsay; Valleau, Jeanette; Grove, Kevin L.] Oregon Natl Primate Res Ctr, Beaverton, OR USA.
[Escalona, Alex; Kaplan, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Elmquist, Joel Keith] UT Southwestern Med Ctr, Dallas, TX USA.
[Seeley, Randy] Univ Cincinnati, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0921
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103246
ER
PT J
AU Kim, SC
Glynn, R
Liu, J
Everett, BM
Goldfine, AB
AF Kim, Seoyoung C.
Glynn, Robert
Liu, Jun
Everett, Brendan M.
Goldfine, Allison B.
TI Dipeptidyl Peptidase-4 Inhibitors Do Not Increase the Risk of
Cardiovascular Events in Type 2 Diabetes: A Population-Based Cohort
Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kim, Seoyoung C.; Glynn, Robert; Liu, Jun; Everett, Brendan M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR34-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100082
ER
PT J
AU Kocarnik, BM
Kahn, SE
Fujimoto, WY
Hayashi, T
McNeely, MJ
Leonetti, D
Boyko, EJ
AF Kocarnik, Beverly M.
Kahn, Steven E.
Fujimoto, Wilfred Y.
Hayashi, Tomoshige
McNeely, Marguerite J.
Leonetti, Donna
Boyko, Edward J.
TI Estradiol Levels in Men Are Not Correlated Cross-Sectionally with
Intra-Abdominal Fat Area and Do Not Predict Change in This Fat Depot
Longitudinally
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kocarnik, Beverly M.; Kahn, Steven E.; McNeely, Marguerite J.; Leonetti, Donna] Univ Washington, Seattle, WA 98195 USA.
[Kahn, Steven E.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Fujimoto, Wilfred Y.] Univ Washington, Kailua Kona, HI USA.
[Hayashi, Tomoshige] Osaka Univ, Osaka, Japan.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0905
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103097
ER
PT J
AU Lawson, EA
Fazeli, PK
Marengi, DA
Cross, E
Bouxsein, ML
Miller, KK
Faje, AT
Klibanski, A
AF Lawson, Elizabeth A.
Fazeli, Pouneh K.
Marengi, Dean A.
Cross, Ela
Bouxsein, Mary L.
Miller, Karen K.
Faje, Alexander Terence
Klibanski, Anne
TI Oxytocin Levels Are Associated with Trabecular Microarchitecture in
Healthy Women, but Not in Women with Anorexia Nervosa
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lawson, Elizabeth A.; Marengi, Dean A.; Cross, Ela; Miller, Karen K.; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA.
[Bouxsein, Mary L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0228
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105198
ER
PT J
AU Lawson, EA
Fazeli, PK
Marengi, DA
Cross, E
Faje, AT
Rosen, CJ
Breggia, AC
Miller, KK
Klibanski, A
AF Lawson, Elizabeth A.
Fazeli, Pouneh K.
Marengi, Dean A.
Cross, Ela
Faje, Alexander Terence
Rosen, Clifford J.
Breggia, Anne C.
Miller, Karen K.
Klibanski, Anne
TI Irisin Levels Are High in Anorexia Nervosa and Inversely Associated with
Resting Energy Expenditure
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lawson, Elizabeth A.; Marengi, Dean A.; Cross, Ela; Miller, Karen K.; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA.
[Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA.
[Breggia, Anne C.] Maine Med Ctr, Rsrch Inst, Scarborough, ME USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0920
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103245
ER
PT J
AU Li, YB
Fortin, J
Boehm, U
Lin, HY
Bernard, DJ
AF Li, Yining
Fortin, Jerome
Boehm, Ulrich
Lin, Herbert Y.
Bernard, Daniel J.
TI Enhanced Fertility and FSH Synthesis in Mice Lacking the Inhibin
Co-Receptor TGFBR3 (betaglycan) in Pituitary Gonadotropes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Li, Yining; Fortin, Jerome; Bernard, Daniel J.] McGill Univ, Montreal, PQ, Canada.
[Boehm, Ulrich] Univ Saarland, Sch Med, Homburg, Germany.
[Lin, Herbert Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lin, Herbert Y.] Harvard Med Sch, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0361
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100269
ER
PT J
AU Lippincott, MF
Chan, YM
Seminara, SB
AF Lippincott, Margaret Flynn
Chan, Yee-Ming
Seminara, Stephanie Beth
TI Responses to Continuous Kisspeptin-10 Infusions: Influences of Sex and
Sex Steroids
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lippincott, Margaret Flynn; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0640
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101261
ER
PT J
AU Lippincott, MF
Chan, YM
Seminara, SB
AF Lippincott, Margaret Flynn
Chan, Yee-Ming
Seminara, Stephanie Beth
TI Responses to Continuous Kisspeptin-10 Infusions: Influences of Sex and
Sex Steroids
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lippincott, Margaret Flynn; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0640
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101260
ER
PT J
AU Liu, XH
Collier, L
Ma, RS
Latif, R
Davies, TF
Bauman, WA
Cardozo, CP
AF Liu, Xin-Hua
Collier, Lauren
Ma, Risheng
Latif, Rauf
Davies, Terry F.
Bauman, William A.
Cardozo, Christopher Pratt
TI Androgens Promote Differentiation of Induced Pluripotent Stem Cells to
Mesenchymal Progenitor Cells through Embryoid Body Formation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Liu, Xin-Hua; Collier, Lauren; Bauman, William A.; Cardozo, Christopher Pratt] JJ Peter VA Med Ctr, Bronx, NY USA.
[Ma, Risheng] Mt Sinai Sch Med, Bronx, NY USA.
[Latif, Rauf; Davies, Terry F.] Mt Sinai Sch Med, New York, NY USA.
[Bauman, William A.] James J Peters VA Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0262
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105285
ER
PT J
AU Lombardi, A
Inabnet, WB
Owen, R
Tomer, Y
AF Lombardi, Angela
Inabnet, William B.
Owen, Randall
Tomer, Yaron
TI A New Mechanism for Iodine Independent Amiodarone-Induced Thyroiditis
with Translational Implications
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lombardi, Angela; Inabnet, William B.; Owen, Randall; Tomer, Yaron] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Tomer, Yaron] James J Peters VA Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR12-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109054
ER
PT J
AU Malhotra, S
Gupta, N
Galiveeti, S
Milekic, B
Greenberg, PD
AF Malhotra, Sheetal
Gupta, Namita
Galiveeti, Sneha
Milekic, Bojana
Greenberg, Pietra Dale
TI Sleeve Gastrectomy Outcomes in Veterans with Type II Diabetes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Malhotra, Sheetal; Galiveeti, Sneha; Milekic, Bojana] JJ Peters VA Med Ctr, Bronx, NY USA.
[Gupta, Namita] Univ Nebraska Med Ctr, Omaha, NE USA.
[Greenberg, Pietra Dale] James J Peters VA Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR40-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100127
ER
PT J
AU Mannstadt, M
Vokes, TJ
Watts, NB
Denham, D
Shoback, DM
Clarke, BL
Lagast, H
Bilezikian, JP
AF Mannstadt, Michael
Vokes, Tamara J.
Watts, Nelson B.
Denham, Douglas
Shoback, Dolores M.
Clarke, Bart Lyman
Lagast, Hjalmar
Bilezikian, John P.
TI Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone
(rhPTH[1-84]) for the Treatment of Adults with Hypoparathyroidism:
Interim Data from the Race Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mannstadt, Michael] Harvard Med Sch, Boston, MA USA.
[Vokes, Tamara J.] Univ Chicago, Chicago, IL 60637 USA.
[Watts, Nelson B.] Mercy Hlth Osteoporosis Serv, Cincinnati, OH USA.
[Watts, Nelson B.] Mercy Bone Hlth Serv, Cincinnati, OH USA.
[Denham, Douglas] Clin Trials Texas Inc, San Antonio, TX USA.
[Shoback, Dolores M.] Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA.
[Clarke, Bart Lyman] Mayo Clin Rochester, Rochester, MN USA.
[Lagast, Hjalmar] NPS Pharmaceut, Bedminster, NJ USA.
[Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0210
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105117
ER
PT J
AU Manzano, A
Fernandez-Castro, GL
Nose, V
Ayala, A
AF Manzano, Alex
Fernandez-Castro, Gustavo L.
Nose, Vania
Ayala, Alejandro
TI Recurrent Primary Adrenal Leiomyosarcoma: A Case of a Rare Adrenal Tumor
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Manzano, Alex; Fernandez-Castro, Gustavo L.; Ayala, Alejandro] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Nose, Vania] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0759
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105232
ER
PT J
AU Mathew, I
Grimes, MC
Rao, RH
Cunningham, CA
Muder, R
Perreiah, PL
AF Mathew, Indu
Grimes, Michael C.
Rao, R. Harsha
Cunningham, Candace Ann
Muder, Robert
Perreiah, Peter L.
TI Eliminating Deaths from Mediastinitis after Cardiac Surgery Using
Aggressive Glycemic Intervention to Maintain Blood Glucose 80-140mg/DI:
The VA Pittsburgh Experience
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mathew, Indu; Grimes, Michael C.; Muder, Robert] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA.
[Rao, R. Harsha; Cunningham, Candace Ann; Perreiah, Peter L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0956
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106240
ER
PT J
AU Mehta, SN
Niewczas, MA
McMullen, WJ
Gruener, AH
Doria, A
AF Mehta, Sanjeev N.
Niewczas, Monika A.
McMullen, William J.
Gruener, Alf H.
Doria, Alessandro
TI Factors Associated with Choice of Incretin-Based Medication Class in
Adults with Type 2 Diabetes (T2D)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mehta, Sanjeev N.; Niewczas, Monika A.; McMullen, William J.; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Gruener, Alf H.] Sanofi, Bridgewater, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-1007
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106295
ER
PT J
AU Min, L
Hodi, FS
Carroll, RS
Kaiser, UB
AF Min, Le
Hodi, F. Stephen
Carroll, Rona S.
Kaiser, Ursula B.
TI Hypophysitis Associated with Ipilimumab, a Novel Immunotherapy for
Metastatic Melanoma: Analysis of 26 Cases
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Min, Le] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Carroll, Rona S.; Kaiser, Ursula B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Carroll, Rona S.; Kaiser, Ursula B.] Harvard Med Sch, Div Endocrinol Diabet, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0675
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102010
ER
PT J
AU Misra, M
Eguiguren, MD
Singhal, V
Ackerman, KE
Clarke, H
Slattery, M
Eddy, KT
AF Misra, Madhusmita
Eguiguren, Maria de Lourdes
Singhal, Vibha
Ackerman, Kathryn Elizabeth
Clarke, Hannah
Slattery, Meghan
Eddy, Kamryn T.
TI Increased Cognitive Restraint in Amenorrheic Adolescent and Young Adults
Athletes Is Associated with Higher Cortisol Secretion and Trunk Fat and
Lower Bone Density
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Misra, Madhusmita; Eguiguren, Maria de Lourdes; Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Eddy, Kamryn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Misra, Madhusmita; Eguiguren, Maria de Lourdes; Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan] Harvard Med Sch, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0648
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101269
ER
PT J
AU Mitchell, DM
Jueppner, HW
Burnett-Bowie, SAM
AF Mitchell, Deborah Michelle
Jueppner, Harald W.
Burnett-Bowie, Sherri-Ann M.
TI Fibroblast Growth Factor 23 Is Not Associated with Age-Related Changes
in Phosphate Handling in Children
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mitchell, Deborah Michelle; Jueppner, Harald W.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR43-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105094
ER
PT J
AU Muram, D
Matsumoto, AM
Zhang, X
Cui, ZLL
AF Muram, David
Matsumoto, Alvin M.
Zhang, Xiang
Cui, Zhanglin Lin
TI Application of the Endocrine Society Clinical Guidelines on Testosterone
Therapy in Men with Androgen Deficiency Syndromes in Clinical Practice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Muram, David; Zhang, Xiang; Cui, Zhanglin Lin] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0021
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104173
ER
PT J
AU O-Sullivan, I
Li, K
Wasserman, D
Kahn, CR
Schwartz, MW
Unterman, TG
AF O-Sullivan, InSug
Li, Kang
Wasserman, David
Kahn, C. Ronald
Schwartz, Michael W.
Unterman, Terry G.
TI Disruption of FoxO1 Restores the Ability of Insulin to Regulate Hepatic
Glucose Production in Liver-Specific Insulin Receptor Knockout (LIRKO)
Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [O-Sullivan, InSug; Unterman, Terry G.] Univ Illinois, Chicago, IL USA.
[O-Sullivan, InSug; Unterman, Terry G.] Jesse Brown VAMC, Chicago, IL USA.
[Li, Kang; Wasserman, David] Vanderbilt Univ, Nashville, TN 37235 USA.
[Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Schwartz, Michael W.] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-1042
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100008
ER
PT J
AU Pau, CT
Kasippillai, T
Keefe, C
Welt, CK
AF Pau, Cindy Ta
Kasippillai, Thushiga
Keefe, Candace
Welt, Corrine K.
TI Response to Metformin in Women with PCOS: The Role of Variants
Regulating Metformin Transport and Action
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Pau, Cindy Ta; Keefe, Candace; Welt, Corrine K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kasippillai, Thushiga] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR47-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107224
ER
PT J
AU Pivonello, R
Fleseriu, M
Young, J
Bertagna, X
Hamrahian, AH
Molitch, ME
Shimizu, C
Tanaka, T
Shimatsu, A
White, T
Hilliard, A
Tian, C
Sauter, N
Biller, BMK
AF Pivonello, Rosario
Fleseriu, Maria
Young, Jacques
Bertagna, Xavier
Hamrahian, Amir H.
Molitch, Mark E.
Shimizu, Chikara
Tanaka, Tomoaki
Shimatsu, Akira
White, Tracy
Hilliard, Annie
Tian, Chuan
Sauter, Nicholas
Biller, Beverly M. K.
TI LCI699, a Potent 11 beta-Hydroxylase Inhibitor, Normalizes Urinary Free
Cortisol Levels in Patients with Cushing's Disease: 22-Week,
Multicenter, Open-Label Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Pivonello, Rosario] Univ Naples Federico II, Naples, Italy.
[Fleseriu, Maria] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Young, Jacques] Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Paris, France.
[Bertagna, Xavier] Univ Paris 05, Hop Cochin, Fac Med Paris Descartes, Ctr Reference Malad Rares Surrenale, Paris, France.
[Hamrahian, Amir H.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Molitch, Mark E.] Northwestern Univ, Chicago, IL 60611 USA.
[Shimizu, Chikara] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan.
[Tanaka, Tomoaki] Chiba Univ Hosp, Chiba, Japan.
[Shimatsu, Akira] Natl Hosp Org, Kyoto Med Ctr, Kyoto, Japan.
[White, Tracy; Hilliard, Annie; Tian, Chuan; Sauter, Nicholas] Novartis Pharmaceut, E Hanover, NJ USA.
[Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR17-4
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101137
ER
PT J
AU Qin, WP
Pan, JP
Bauman, WA
Cardozo, CP
AF Qin, Weiping
Pan, Jianping
Bauman, William A.
Cardozo, Christopher Pratt
TI Molecular Crosstalk Between Calcineurin and mTORC1 Signaling Pathways
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Qin, Weiping; Pan, Jianping; Bauman, William A.; Cardozo, Christopher Pratt] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0351
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100258
ER
PT J
AU Rietman, A
Stanley, TL
Clish, CB
Mootha, VK
Mensink, M
Grinspoon, SK
Makimura, H
AF Rietman, Annemarie
Stanley, Takara Leah
Clish, Clary B.
Mootha, Vamsi K.
Mensink, Marco
Grinspoon, Steven Kyle
Makimura, Hideo
TI Novel Association Between Branched Chain Amino Acids,
eta-Arninoisobutyric Acid and Abdominal Visceral Adiposity: A
Metabolomics Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Rietman, Annemarie; Mensink, Marco] Wageningen Univ, Wageningen, Netherlands.
[Stanley, Takara Leah; Grinspoon, Steven Kyle; Makimura, Hideo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Clish, Clary B.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Mootha, Vamsi K.] Harvard Med Sc, MIT Broad last, Cambridge, MA USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0934
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103166
ER
PT J
AU Russell, SJ
El-Khatib, FH
Magyar, KL
Sinha, M
Goergen, LG
Balliro, C
McKeon, K
Nathan, DM
Damiano, ER
AF Russell, Steven Jon
El-Khatib, Firas H.
Magyar, Kendra L.
Sinha, Manasi
Goergen, Laura G.
Balliro, Courtney
McKeon, Katherine
Nathan, David M.
Damiano, Edward R.
TI Multiday Outpatient Glycemic Control in Adults with Type 1 Diabetes
Using a Bihormonal Bionic Pancreas: The Beacon Hill Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Russell, Steven Jon; Magyar, Kendra L.; Sinha, Manasi; Goergen, Laura G.; Balliro, Courtney; Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[El-Khatib, Firas H.; McKeon, Katherine; Damiano, Edward R.] Boston Univ, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR26-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100117
ER
PT J
AU Shaw, ND
Srouji, S
Welt, CK
Cox, KH
Fox, JH
Adamss, JM
Sluss, PM
Hall, JE
AF Shaw, Natalie D.
Srouji, Serene
Welt, Corrine K.
Cox, Kimberly H.
Fox, Janis H.
Adamss, Judith Mary
Sluss, Patrick M.
Hall, Janet Elizabeth
TI Evidence That Ovarian Aromatase Action Is Preserved with Aging in
Regularly Cycling Women
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shaw, Natalie D.] Boston Childrens Hosp, Boston, MA USA.
[Srouji, Serene; Fox, Janis H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Welt, Corrine K.; Cox, Kimberly H.; Sluss, Patrick M.; Hall, Janet Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Adamss, Judith Mary] MA Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR04-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104222
ER
PT J
AU Shaw, ND
Butler, JP
Kangarloo, T
Hall, JE
AF Shaw, Natalie D.
Butler, James P.
Kangarloo, Tairmae
Hall, Janet Elizabeth
TI Deep Sleep Disruption Does Not Diminish Pulsatile LH Secretion in
Pubertal Children
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shaw, Natalie D.] Boston Childrens Hosp, Boston, MA USA.
[Butler, James P.] Harvard Sch Publ Hlth, Boston, MA USA.
[Kangarloo, Tairmae] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hall, Janet Elizabeth] Massachusetts Gen, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0158
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104071
ER
PT J
AU Shi, Y
Kim, MS
Shu, ZJ
Salmon, A
Kamat, A
AF Shi, Yun
Kim, Margaret S.
Shu, Zhen-Ju
Salmon, Adam
Kamat, Amrita
TI Positive Association Between Beta(2)-Adrenergic Receptor (beta(2)-AR)
Signaling and Cide Family Proteins in Hepatic Steatosis
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shi, Yun; Kim, Margaret S.; Shu, Zhen-Ju] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Salmon, Adam; Kamat, Amrita] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR15-2
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106048
ER
PT J
AU Shores, MM
Fox, AE
Moore, KP
Matsumoto, AM
Forsberg, CW
Smith, NL
Heckbert, SR
Thompson, ML
Walsh, TJ
AF Shores, Molly M.
Fox, Alexandra E.
Moore, Kathryn P.
Matsumoto, Alvin M.
Forsberg, Christopher W.
Smith, Nicholas L.
Heckbert, Susan R.
Thompson, Mary Lou
Walsh, Thomas J.
TI Characteristics of Treated and Untreated Middle-Aged and Older Men with
Low Testosterone and Testosterone Use in a National Veterans Affairs
(VA) Cohort
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shores, Molly M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA.
[Fox, Alexandra E.] Seattle VA Epidemiol Res & Informat Ctr ERIC, Seattle, WA USA.
[Moore, Kathryn P.; Forsberg, Christopher W.] Seattle VA ERIC, Seattle, WA USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syste, Seattle, WA USA.
[Smith, Nicholas L.; Heckbert, Susan R.; Thompson, Mary Lou; Walsh, Thomas J.] Univ Washington, Seattle, WA 98195 USA.
[Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0077
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107192
ER
PT J
AU Simonson, DC
Ding, SA
Halperin, F
Wewalka, M
Foster, K
Kelly, K
Panosian, J
Goebel-Fabbri, A
Hamdy, O
Clancy, K
Lautz, D
Vernon, A
Goldfine, AB
AF Simonson, Donald C.
Ding, Su Ann
Halperin, Florencia
Wewalka, Marlene
Foster, Kathleen
Kelly, Katherine
Panosian, Jennifer
Goebel-Fabbri, Ann
Hamdy, Osama
Clancy, Kerni
Lautz, David
Vernon, Ashley
Goldfine, Allison B.
TI Changes in Patient-Reported Outcomes up to Two Years after Roux-En-Y
Gastric Bypass Vs. Intensive Medical Weight Management in Obese Patients
with Type 2 Diabetes Mellitus
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Simonson, Donald C.; Halperin, Florencia; Vernon, Ashley] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ding, Su Ann; Wewalka, Marlene; Foster, Kathleen; Kelly, Katherine; Panosian, Jennifer; Goebel-Fabbri, Ann; Hamdy, Osama; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Clancy, Kerni; Lautz, David] Emerson Hosp, Concord, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR40-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100125
ER
PT J
AU Singhal, V
Bredella, MA
Ackerman, KE
Clarke, H
Slattery, M
Misra, M
AF Singhal, Vibha
Bredella, Miriam A.
Ackerman, Kathryn Elizabeth
Clarke, Hannah
Slattery, Meghan
Misra, Madhusmita
TI Bone Marrow Fat in Relation to Bone Density in Young Oligo-Amenorrheic
Athletes and Eumenorrheic Controls
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA.
[Bredella, Miriam A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0227
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105197
ER
PT J
AU Singhal, V
Bredella, MA
Ackerman, KE
Clarke, H
Slattery, M
Misra, M
AF Singhal, Vibha
Bredella, Miriam A.
Ackerman, Kathryn Elizabeth
Clarke, Hannah
Slattery, Meghan
Misra, Madhusmita
TI Bone Marrow Fat in Relation to Bone Density in Young Oligo-Amenorrheic
Athletes and Eumenorrheic Controls
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA.
[Bredella, Miriam A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP31-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105044
ER
PT J
AU Singhal, V
Ackerman, KE
Clarke, H
Slattery, M
Weiner, L
Kolodny, G
Cypess, AM
Misra, M
AF Singhal, Vibha
Ackerman, Kathryn Elizabeth
Clarke, Hannah
Slattery, Meghan
Weiner, Lauren
Kolodny, Gerald
Cypess, Aaron Martin
Misra, Madhusmita
TI Cold Induced Brown Adipose Tissue Activity in Young Oligo-Amenorrheic
Athletes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Weiner, Lauren; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA.
[Weiner, Lauren; Cypess, Aaron Martin] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kolodny, Gerald] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0884
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103033
ER
PT J
AU Somm, E
Xu, C
Miraoui, H
Kinnunen, T
Preitner, N
Dwyer, A
Sykiotis, G
Quinton, R
Crowley, WF
Hauschild, M
Phan-Hug, F
Sidis, Y
Mohammadi, M
Pitteloud, N
AF Somm, Emmanuel
Xu, Cheng
Miraoui, Hichem
Kinnunen, Tarja
Preitner, Nadia
Dwyer, Andrew
Sykiotis, Gerasimos
Quinton, Richard
Crowley, William F.
Hauschild, Michael
Phan-Hug, Franziska
Sidis, Yisrael
Mohammadi, Moosa
Pitteloud, Nelly
TI Klb, Encoding the Co-Receptor for FGF21, Is Mutated in Congenital GnRH
Deficiency
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Somm, Emmanuel; Xu, Cheng; Miraoui, Hichem; Preitner, Nadia; Dwyer, Andrew; Sykiotis, Gerasimos; Hauschild, Michael; Phan-Hug, Franziska; Sidis, Yisrael; Pitteloud, Nelly] CHU Vaudois, Lausanne, Switzerland.
[Kinnunen, Tarja] Univ Huddersfield, Huddersfield, W Yorkshire, England.
[Quinton, Richard] Univ Newcastle On Tyne, Newcastle Upon Tyne, Tyne & Wear, England.
[Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mohammadi, Moosa] NYU, Sch Med, New York, NY USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0602
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101218
ER
PT J
AU Somm, E
Xu, C
Miraoui, H
Kinnunen, T
Preitner, N
Dwyer, A
Sykiotis, G
Quinton, R
Crowley, WF
Hauschild, M
Phan-Hug, F
Sidis, Y
Mohammadi, M
Pitteloud, N
AF Somm, Emmanuel
Xu, Cheng
Miraoui, Hichem
Kinnunen, Tarja
Preitner, Nadia
Dwyer, Andrew
Sykiotis, Gerasimos
Quinton, Richard
Crowley, William F.
Hauschild, Michael
Phan-Hug, Franziska
Sidis, Yisrael
Mohammadi, Moosa
Pitteloud, Nelly
TI Klb, Encoding the Co-Receptor for FGF21, Is Mutated in Congenital GnRH
Deficiency
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Somm, Emmanuel; Xu, Cheng; Miraoui, Hichem; Preitner, Nadia; Dwyer, Andrew; Sykiotis, Gerasimos; Hauschild, Michael; Phan-Hug, Franziska; Sidis, Yisrael; Pitteloud, Nelly] CHU Vaudois, Lausanne, Switzerland.
[Kinnunen, Tarja] Univ Huddersfield, Huddersfield, W Yorkshire, England.
[Quinton, Richard] Univ Newcastle On Tyne, Newcastle Upon Tyne, Tyne & Wear, England.
[Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mohammadi, Moosa] NYU, Sch Med, New York, NY USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP30-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101194
ER
PT J
AU Srinivasa, S
Fitch, KV
Wong, K
Petrow, E
Grinspoon, SK
AF Srinivasa, Suman
Fitch, Kathleen V.
Wong, Kimberly
Petrow, Eva
Grinspoon, Steven Kyle
TI Effects of Lifestyle Modification and Metformin on Irisin and FGF21
Among HIV-Infected Patients with the Metabolic Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Srinivasa, Suman; Fitch, Kathleen V.; Wong, Kimberly; Petrow, Eva] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Grinspoon, Steven Kyle] Mass Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP05-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103265
ER
PT J
AU Srinivasa, S
Fitch, KV
Wong, K
Petrow, E
Grinspoon, SK
AF Srinivasa, Suman
Fitch, Kathleen V.
Wong, Kimberly
Petrow, Eva
Grinspoon, Steven Kyle
TI Effects of Lifestyle Modification and Metformin on Irisin and FGF21
Among HIV-Infected Patients with the Metabolic Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Srinivasa, Suman; Fitch, Kathleen V.; Wong, Kimberly; Petrow, Eva] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Grinspoon, Steven Kyle] Mass Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0924
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103155
ER
PT J
AU Stanley, TL
Feldpausch, MN
Oh, J
Branch, KL
Lee, H
Torriani, M
Grinspoon, SK
AF Stanley, Takara Leah
Feldpausch, Meghan N.
Oh, Jinhee
Branch, Karen L.
Lee, Hang
Torriani, Martin
Grinspoon, Steven Kyle
TI Growth Hormone Releasing Hormone Analogue Reduces Liver Fat in
HIV-Infected Patients
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Stanley, Takara Leah; Feldpausch, Meghan N.; Oh, Jinhee; Branch, Karen L.; Lee, Hang; Torriani, Martin; Grinspoon, Steven Kyle] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR05-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103147
ER
PT J
AU Tela, GH
Dougher, CE
Katz, ML
Laffel, LM
AF Tela, Gabriela H.
Dougher, Carly E.
Katz, Michelle L.
Laffel, Lori M.
TI Dynamic Changes in Total Daily Insulin Dose (U/kg/D) during Childhood
and Adolescence in Youth with Type 1 Diabetes (T1D): Impact of Age, Sex,
Regimen, and Weight Status
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Tela, Gabriela H.; Dougher, Carly E.; Katz, Michelle L.; Laffel, Lori M.] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0952
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106215
ER
PT J
AU Teng, XC
Jin, T
Brent, GA
Wu, AH
Teng, WP
Shan, ZY
AF Teng, Xiaochun
Jin, Ting
Brent, Gregory A.
Wu, An-hua
Teng, Weiping
Shan, Zhongyan
TI A Girl with Resistance to Thyroid Hormone (P453T) and a Suspected
Thyrotropin-Secreting Pituitary Microadenoma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Teng, Xiaochun; Jin, Ting; Shan, Zhongyan] Inst Endocrinol, Shenyang, Peoples R China.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab,Dept Med, Tarzana, CA USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Tarzana, CA USA.
[Wu, An-hua] Dept Neurosurg, Shenyang, Peoples R China.
[Teng, Weiping] Endocrine Inst, Shenyang, Peoples R China.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0488
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108315
ER
PT J
AU Thomou, T
Mori, MA
Kahn, CR
AF Thomou, Thomas
Mori, Marcelo A.
Kahn, C. Ronald
TI Adipose Tissue Micrornas Account for a Major Fraction of Circulating
Exosomal microRNAs and Regulate mRNA Expression in Other Tissues
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Thomou, Thomas] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
[Mori, Marcelo A.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0381
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100296
ER
PT J
AU Townsend, KL
Chen, W
Huang, TL
Lessard, S
Goodyear, LJ
Babitt, J
Lin, H
Tseng, YH
AF Townsend, Kristy L.
Chen, Wenjie
Huang, TianLian
Lessard, Sarah
Goodyear, Laurie J.
Babitt, Jodie
Lin, Herb
Tseng, Yu-Hua
TI Loss of BMP Co-Receptor Hemojuvelin Leads to Increased Brown
Adipogenesis in Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Townsend, Kristy L.; Huang, TianLian; Lessard, Sarah; Tseng, Yu-Hua] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
[Chen, Wenjie; Babitt, Jodie; Lin, Herb] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Goodyear, Laurie J.] Harvard Med Sch, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0909
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103051
ER
PT J
AU Tritos, NA
Johannsson, G
Korbonits, M
Miller, KK
Feldt-Rasmussen, U
Yuen, KCJ
King, D
Mattsson, AF
Jonsson, PJ
Koltowska-Haggstrom, M
Klibanski, A
Biller, BMK
AF Tritos, Nicholas A.
Johannsson, Gudmundur
Korbonits, Marta
Miller, Karen K.
Feldt-Rasmussen, Ulla
Yuen, Kevin C. J.
King, Donna
Mattsson, Anders F.
Jonsson, Peter J.
Koltowska-Haggstrom, Maria
Klibanski, Anne
Biller, Beverly M. K.
TI Long-Term Safety of Growth Hormone (GH) Replacement in Adults with GH
Deficiency (GHD) Following Cure of Acromegaly a Kims (Pfizer
International Metabolic Database) Analysis
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Tritos, Nicholas A.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Johannsson, Gudmundur] Sahlgrens Univ Hosp, Gothenburg, Sweden.
[Korbonits, Marta] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London, England.
[Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Copenhagen, Denmark.
[Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[King, Donna] Pfizer Inc, New York, NY USA.
[Mattsson, Anders F.; Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, Sollentuna, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP17-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102107
ER
PT J
AU Tritos, NA
Johannsson, G
Korbonits, M
Miller, KK
Feldt-Rasmussen, U
Yuen, KCJ
King, D
Mattsson, AF
Jonsson, PJ
Koltowska-Haggstrom, M
Klibanski, A
Biller, BMK
AF Tritos, Nicholas A.
Johannsson, Gudmundur
Korbonits, Marta
Miller, Karen K.
Feldt-Rasmussen, Ulla
Yuen, Kevin C. J.
King, Donna
Mattsson, Anders F.
Jonsson, Peter J.
Koltowska-Haggstrom, Maria
Klibanski, Anne
Biller, Beverly M. K.
TI Long-Term Safety of Growth Hormone (GH) Replacement in Adults with GH
Deficiency (GHD) Following Cure of Acromegaly - a Kims (Pfizer
International Metabolic Database) Analysis
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Tritos, Nicholas A.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Johannsson, Gudmundur] Sahlgrens Univ Hosp, Gothenburg, Sweden.
[Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, Wlliam Harvey Res Inst, London, England.
[Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Copenhagen, Denmark.
[Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[King, Donna] Pfizer Inc, New York, NY USA.
[Mattsson, Anders F.; Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, Sollentuna, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0589
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100317
ER
PT J
AU True, C
Chan, YM
Seminara, SB
AF True, Cadence
Chan, Yee-Ming
Seminara, Stephanie Beth
TI Estradiol Treatment Improves Estrous Cycling but Does Not Rescue All
Reproductive Defects in Neurokinin B Receptor Deficient Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [True, Cadence; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0672
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109281
ER
PT J
AU Vaidya, A
Baudrand, R
Winberg, L
Ruan, DT
Shyn, P
Dluhy, RG
McKay, R
Choueiri, T
Elfiky, A
AF Vaidya, Anand
Baudrand, Rene
Winberg, Linda
Ruan, Daniel T.
Shyn, Paul
Dluhy, Robert G.
McKay, Rana
Choueiri, Toni
Elfiky, Aymen
TI The Impact of Repeated Cytoreduction in Combination with Maximal Medical
Therapy on Clinical Outcomes and Quality of Life in Advanced Adrenal
Cortical Carcinoma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Vaidya, Anand; Winberg, Linda; Ruan, Daniel T.; Shyn, Paul; Dluhy, Robert G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Baudrand, Rene] Pontificia Univ Catolica Chile, Santiago, Chile.
[McKay, Rana; Choueiri, Toni; Elfiky, Aymen] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0801
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101112
ER
PT J
AU von Eynatten, M
Ross, S
Caballero, E
Del Prato, S
Gallwitz, B
Lewis-D'Agostino, D
Bailes, Z
Thiemannt, S
Patel, S
Woerle, HJ
AF von Eynatten, Maximilian
Ross, Stuart
Caballero, Enrique
Del Prato, Stefano
Gallwitz, Baptist
Lewis-D'Agostino, Diane
Bailes, Zelie
Thiemannt, Sandra
Patel, Sanjay
Woerle, Hans-Juergen
TI Linagliptin Monotherapy Versus Initial Combination Therapy with
Metformin in Patients with Newly Diagnosed Type 2 Diabetes (T2D): A
Randomized Controlled Trial
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [von Eynatten, Maximilian] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
[Ross, Stuart] Univ Calgary, Calgary, AB, Canada.
[Caballero, Enrique] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Del Prato, Stefano] Univ Pisa, Pisa, Italy.
[Gallwitz, Baptist] Univ Klinikum Tuebingen, Tubingen, Germany.
[Lewis-D'Agostino, Diane] Boeheringer Ingelheim, Ridgefield, CT USA.
[Bailes, Zelie] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England.
[Thiemannt, Sandra] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.
[Patel, Sanjay] Boehringer Ingelheim Ltd, Bracknell, Berks, England.
[Woerle, Hans-Juergen] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0987
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106201
ER
PT J
AU Yu, EW
Bouxsein, ML
Monis, E
Roy, A
Butsch, WS
Finkelstein, JS
AF Yu, Elaine W.
Bouxsein, Mary L.
Monis, Elizabeth
Roy, Adam
Butsch, W. Scott
Finkelstein, Joel Stephen
TI Bariatric Surgery Patients Have Continued Bone Loss for 2 Years after
Surgery Despite Weight Stabilization
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Yu, Elaine W.; Bouxsein, Mary L.; Monis, Elizabeth; Roy, Adam; Butsch, W. Scott; Finkelstein, Joel Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0194
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105056
ER
PT J
AU Walker, RJ
Smalls, BL
Hernandez-Tejada, MA
Campbell, JA
Egede, LE
AF Walker, Rebekah J.
Smalls, Brittany L.
Hernandez-Tejada, Melba A.
Campbell, Jennifer A.
Egede, Leonard E.
TI EFFECT OF DIABETES SELF-EFFICACY ON GLYCEMIC CONTROL, MEDICATION
ADHERENCE, SELF-CARE BEHAVIORS, AND QUALITY OF LIFE IN A PREDOMINANTLY
LOW-INCOME, MINORITY POPULATION
SO ETHNICITY & DISEASE
LA English
DT Article
DE Diabetes Self-efficacy; Glycemic Control; Medication Adherence;
Self-care Behaviors; Quality of Life; Low-income Population; Type 2
Diabetes
ID AFRICAN-AMERICAN; FOOD INSECURITY; SOCIOECONOMIC-STATUS; HEALTH
LITERACY; MANAGEMENT; ADULTS; INTERVENTION; ASSOCIATION; PERCEPTIONS;
STRATEGIES
AB Objective: This study examined the effect of self-efficacy on glycemic control, self-care behaviors, and quality of life in low-income, minority adults with diabetes.
Methods: Data on 378 participants were examined. Multiple linear regression assessed associations between self-efficacy, hemoglobin A1c, medication adherence, diabetes knowledge, self-care behaviors and quality of life.
Results: Self-efficacy had modest correlations with glycemic control (r = -2.250, P < .001), medication adherence (r = -.352, P < .001), diabetes knowledge (r = -.118, P < .039), diet (r = -.420, P < .001), exercise (r = -.220, P < .001), blood sugar testing (r = -.213, P < .001), foot care (r = .121, P < .032), and mental health related quality of life (r = .137, P < .017). In the regression model, self-efficacy was significantly associated with glycemic control (beta = -.104, 95% CI: - .157, - .051), medication adherence (beta = -.067, 95% CI: - .090, - .044), diet (beta = .150, 95% CI:.108,.191), exercise (beta = -.113, 95% CI:.065,.161), blood sugar testing (beta = .107, 95% CI:.049,.164) and mental health related quality of life (beta = .112, 95% CI:.051,.173).
Conclusion: Higher self-efficacy was associated with improved glycemic control, medication adherence, self-care behavior and mental health related quality of life.
Practice Implications: Emphasis on self-efficacy is relevant for educational interventions developed for low-income, minority populations.
C1 [Walker, Rebekah J.; Smalls, Brittany L.; Hernandez-Tejada, Melba A.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA.
[Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston VA COIN, Charleston, SC USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU National Institute for Diabetes, Digestive and Kidney Disease
[T35DK007431]
FX Supported by Grant #T35DK007431 from the National Institute for
Diabetes, Digestive and Kidney Disease.
NR 53
TC 9
Z9 10
U1 1
U2 9
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
EI 1945-0826
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2014
VL 24
IS 3
BP 349
EP 355
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU7KT
UT WOS:000363717300013
PM 25065078
ER
PT J
AU Boehme, AK
McGwin, G
Andes, DR
Lyon, GM
Chiller, T
Pappas, PG
Baddley, JW
AF Boehme, Amelia K.
McGwin, Gerald
Andes, David R.
Lyon, G. Marshall
Chiller, Tom
Pappas, Peter G.
Baddley, John W.
TI RACE AND INVASIVE FUNGAL INFECTION IN SOLID ORGAN TRANSPLANT RECIPIENTS
SO ETHNICITY & DISEASE
LA English
DT Article
DE Invasive Fungal Infection; Solid Organ Transplant; Aspergillosis;
Candidiasis; Cryptococcosis
ID SURVEILLANCE NETWORK TRANSNET; LIVER-TRANSPLANTATION; ETHNIC
DISPARITIES; RISK-FACTORS; COCCIDIOIDOMYCOSIS; SURVIVAL; ACCESS
AB Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n=1,214) and controls (n=16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR=.97, 95% CI 0.82-1.15, P=.7125), while participants who identified as other ethnicity were less likely to develop IFI (OR=.56, 95% CI .41-.75, P<.001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95%CI 1.35-3.54, P=.002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients.
C1 [Boehme, Amelia K.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Andes, David R.] Univ Wisconsin, Madison, WI 53706 USA.
[Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Chiller, Tom] Ctr Dis Control, Atlanta, GA 30333 USA.
[Pappas, Peter G.; Baddley, John W.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA.
RP Baddley, JW (reprint author), Univ Alabama Birmingham, Div Infect Dis, 1900 Univ Blvd,THT 229, Birmingham, AL 35294 USA.
EM jbaddley@uab.edu
FU CDC; Astellas; Pfizer; Merck; Schering Plough
FX TRANSNET was sponsored by the CDC, Astellas, Pfizer, Merck, and Schering
Plough. We would like to thank the following TRANSNET Investigators:
Barbara Alexander, MD, Duke University; Elias Anaissie, MD, University
of Arkansas; Michael Boeckh, MD, Fred Hutchinson Cancer Research Center;
Janice Brown, MD, Stanford University; Lisa Brumble, MD, Mayo
Clinic-Jacksonville; Alison Freifeld, MD, University of Nebraska; Yoav
Golan, MD, and Susan Hadley, MD, Tufts University; Loreen Herwaldt, MD,
University of Iowa; James Ito, MD, City of Hope National Medical Center;
Carol Kauffman, MD, University of Michigan; Katherine Knapp, MD, St.
Jude Children's Hospital; Dimitrios Kontoyiannis, MD, MD Anderson Cancer
Center; Kieren Marr, MD and Trish Perl, MD, Johns Hopkins Medical
Institute; Vicki Morrison, MD, University of Minnesota; Genovefa
Papanicolaou, MD, Memorial Sloan-Kettering Cancer Center; Tom Patterson,
MD, University of Texas HSC-San Antonio; Mindy Schuster, MD, University
of Pennsylvania; Randall Walker, MD, Mayo Clinic-Rochester; Tom Walsh,
MD, Weill Cornell Medical College; John Wingard, MD, University of
Florida.
NR 17
TC 1
Z9 1
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
EI 1945-0826
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2014
VL 24
IS 3
BP 382
EP 385
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU7KT
UT WOS:000363717300018
PM 25065083
ER
PT J
AU Khamis, RY
Woollard, KJ
Hyde, GD
Boyle, JJ
Bicknell, C
Hara, T
Mauskapf, A
Granger, DW
Johnson, JL
Ntziachristos, V
Matthews, PM
Jaffer, FA
Haskard, DO
AF Khamis, Ramzi Y.
Woollard, Kevin J.
Hyde, Gareth D.
Boyle, Joseph J.
Bicknell, Colin
Hara, Tetsuya
Mauskapf, Adam
Granger, David W.
Johnson, Jason L.
Ntziachristos, Vasilis
Matthews, Paul M.
Jaffer, Farouc A.
Haskard, Dorian O.
TI DEVELOPMENT OF WHOLE BODY AND INTRAVASCULAR NEAR-INFRARED OPTICAL
MOLECULAR IMAGING OF MARKERS OF PLAQUE VULNERABLITY IN ATHEROSCLEROSIS
SO HEART
LA English
DT Meeting Abstract
CT Annual Conference of the British-Cardiovascular-Society
CY JUN 02-04, 2014
CL Manchester, ENGLAND
SP British Cardiovascular Soc
C1 [Khamis, Ramzi Y.; Hyde, Gareth D.; Boyle, Joseph J.; Haskard, Dorian O.] Univ London Imperial Coll Sci Technol & Med, Natl Hearth & Lung Inst, Vasc Sci Sect, London SW7 2AZ, England.
[Woollard, Kevin J.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England.
[Bicknell, Colin] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
[Hara, Tetsuya; Mauskapf, Adam; Ntziachristos, Vasilis; Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA 02138 USA.
[Hara, Tetsuya; Mauskapf, Adam; Ntziachristos, Vasilis; Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA.
[Granger, David W.] GlaxoSmithKline, Biopharm R&D, Stevenage, Herts, England.
[Johnson, Jason L.] Univ Bristol, Bristol Heart Inst, Bristol, Avon, England.
OI Khamis, Ramzi /0000-0003-4119-5193
FU British Heart Foundation [FS/07/053/24069]
NR 0
TC 0
Z9 0
U1 1
U2 4
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 JUN
PY 2014
VL 100
SU 3
MA C
BP A128
EP A128
DI 10.1136/heartjnl-2014-306118.231
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP5UR
UT WOS:000359951000233
ER
PT J
AU Chatterjee, NA
Upadhyay, GA
Singal, G
Parks, KA
Dec, GW
Singh, JP
Lewis, GD
AF Chatterjee, Neal A.
Upadhyay, Gaurav A.
Singal, Gaurav
Parks, Kimberly A.
Dec, G. William
Singh, Jagmeet P.
Lewis, Gregory D.
TI Pre-Capillary Pulmonary Hypertension and Right Ventricular Dilation
Predict Clinical Outcome in Cardiac Resynchronization Therapy
SO JACC-HEART FAILURE
LA English
DT Article
DE cardiac resynchronization therapy; pulmonary hypertension; right
ventricle
ID CHRONIC HEART-FAILURE; ARTERY PRESSURE; EJECTION FRACTION; SYSTOLIC
PRESSURE; MORTALITY; CARDIOMYOPATHY; EXERCISE; RISK; ECHOCARDIOGRAPHY;
TRANSPLANTATION
AB Objectives This study examined the prognostic significance of pre- and post-capillary components of pulmonary hypertension (PH) in patients receiving cardiac resynchronization therapy (CRT).
Background PH is common in patients with left ventricular systolic dysfunction (LVSD) receiving CRT. The impact of PH subtype on clinical outcome in CRT is unknown.
Methods The study population consisted of 101 patients (average age 66 +/- 13 years, left ventricular ejection fraction 0.23 +/- 0.07, and New York Heart Association functional class 3.2 +/- 0.4) who underwent right heart catheterization in the 6 months before CRT. PH was defined as a mean pulmonary artery pressure >= 25 mm Hg; a significant pre-capillary contribution to elevated mean pulmonary artery pressure was defined as a transpulmonary gradient (TPG) >= 12 mm Hg. Clinical endpoints were assessed at 2 years and included all-cause mortality and a composite of death, left ventricular assist device, or cardiac transplantation.
Results Patients with TPG >= 12 mm Hg were more likely to experience all-cause mortality (hazard ratio [HR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4; p = 0.009) and the composite outcome (HR: 3.0; 95% CI: 1.4 to 6.3; p = 0.004) compared with patients with TPG <12 mm Hg. After multivariate adjustment for hemodynamic, clinical, and echocardiographic variables, only TPG >= 12 mm Hg and baseline right ventricular (RV) dilation (RV end-diastolic dimension >42 mm) were associated with the composite clinical outcome (p = 0.05 and p = 0.04, respectively).
Conclusions High TPG PH and RV dilation are independent predictors of adverse outcomes in patients with LVSD who are receiving CRT. RV pulmonary vascular dysfunction may be a therapeutic target in select patients receiving CRT. (C) 2014 by the American College of Cardiology Foundation
C1 [Chatterjee, Neal A.; Upadhyay, Gaurav A.; Singal, Gaurav; Parks, Kimberly A.; Dec, G. William; Singh, Jagmeet P.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Upadhyay, Gaurav A.; Singal, Gaurav; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA.
[Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA.
RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA.
EM glewis@partners.org
FU National Heart Lung and Blood Institute (National Institutes of Health)
[K23HL091106]; Heart Failure Innovation Fund
FX Dr. Lewis has received support from the National Heart Lung and Blood
Institute (National Institutes of Health K23HL091106) and the Heart
Failure Innovation Fund. All other authors have reported they have no
relationships relevant to the contents of this paper to disclose.
NR 39
TC 10
Z9 11
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD JUN
PY 2014
VL 2
IS 3
BP 230
EP 237
DI 10.1016/j.jchf.2014.02.004
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CX4DC
UT WOS:000365647600005
PM 24952689
ER
PT J
AU Krezanoski, PJ
Tsai, AC
Hamer, DH
Comfort, AB
Bangsberg, DR
AF Krezanoski, Paul J.
Tsai, Alexander C.
Hamer, Davidson H.
Comfort, Alison B.
Bangsberg, David R.
TI Household malaria knowledge and its association with bednet ownership in
settings without large-scale distribution programs: Evidence from rural
Madagascar
SO JOURNAL OF GLOBAL HEALTH
LA English
DT Article
AB Background Insecticide-treated bednets are effective at preventing malaria. This study focuses on household-level factors that are associated with bednet ownership in a rural area of Madagascar which had not been a recipient of large-scale ITN distribution.
Methods Data were gathered on individual and household characteristics, malaria knowledge, household assets and bednet ownership. Principal components analysis was used to construct both a wealth index based on household assets and a malaria knowledge index based on responses to questions about malaria. Bivariate and multivariate regressions were used to determine predictors of household bednet ownership and malaria knowledge.
Results Forty-seven of 560 households (8.4%) owned a bednet. In multivariate analysis, higher level of malaria knowledge among household members was the only variable significantly associated with bednet ownership (odds ratio 3.72, P < 0.001). Among respondents, predictors of higher malaria knowledge included higher education levels, female sex and reporting fever as the most frequent or dangerous illness in the community. Household wealth was not a significant predictor of bednet ownership or respondent malaria knowledge.
Conclusion In this setting of limited supply of affordable bednets, malaria knowledge was associated with an increased probability of household bednet ownership. Further studies should determine how such malaria knowledge evolves and if malaria-specific education programs could help overcome the barriers to bednet ownership among at-risk households living outside the reach of large-scale bednet distribution programs.
C1 [Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
[Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Tsai, Alexander C.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA.
[Hamer, Davidson H.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA.
[Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA USA.
[Hamer, Davidson H.] ZCAHRD, Lusaka, Zambia.
[Hamer, Davidson H.] Boston Univ, Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA.
[Comfort, Alison B.] Abt Associates Inc, Int Hlth Div, Cambridge, MA USA.
[Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA.
[Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda.
RP Krezanoski, PJ (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
EM pkrezanoski@partners.org
FU NIH [K23MH096620]
FX All authors have completed the Unified Competing Interest form at
www.icmje.org/coi_disclosure.pdf (available on request from the
corresponding author) and declare that Dr A. C. Tsai reports grant from
NIH for the research outside the submitted work (grant No. K23MH096620).
Other authors declare no support from any organization for the submitted
work; no financial relationships with other organizations that might
have an interest in the submitted work in the previous 3 years, and no
other relationships or activities that could appear to have influenced
the submitted work.
NR 29
TC 2
Z9 2
U1 0
U2 3
PU UNIV EDINBURGH, GLOBAL HEALTH SOC
PI EDINBURGH
PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG,
ENGLAND
SN 2047-2978
EI 2047-2986
J9 J GLOB HEALTH
JI J. Glob. Health
PD JUN
PY 2014
VL 4
IS 1
AR 010401
DI 10.7189/jogh.04.010401
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V42SJ
UT WOS:000209633200006
PM 24976960
ER
PT J
AU Ferry, JA
AF Ferry, Judith A.
TI The diversity of diffuse large B-cell lymphoma in extranodal sites:
overview and update
SO JOURNAL OF HEMATOPATHOLOGY
LA English
DT Review
DE B-cell lymphomas; Diffuse large B-cell lymphoma; Primary central nervous
system; Extranodal; Skin; Mediastinum; EBV; HHV8
ID CENTRAL-NERVOUS-SYSTEM; PRIMARY-EFFUSION-LYMPHOMA; SARCOMA-ASSOCIATED
HERPESVIRUS; CLASSICAL HODGKIN LYMPHOMA; NEGATIVE PLASMABLASTIC
LYMPHOMA; GRAY ZONE LYMPHOMA; INTRAVASCULAR LYMPHOMA; KAPOSIS-SARCOMA;
CLINICAL PRESENTATION; CHRONIC INFLAMMATION
AB Extranodal lymphomas are a diverse group of low and high grade neoplasms of B-, T-, and NK-cell lineage, each with characteristic sites of origin, morphology, immunophenotype, genetic features, patterns of spread, and prognosis. The diversity is sometimes seen even within a single histologic type of lymphoma. This phenomenon is especially striking in the category of diffuse large B-cell lymphoma (DLBCL). DLBCLs as classified in the WHO Classification are clinically and pathologically heterogeneous (Swerdlow et al. 2008; Stein et al. 2008). Since the publication of the most recent edition of the WHO Classification of tumours of haematopoietic and lymphoid tissues (Swerdlow et al. 2008), a number of advances in the understanding of these lymphomas have been made. This review provides an overview of extranodal DLBCLs and describes recent updates regarding these lymphomas.
C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM jferry@partners.org
NR 115
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1868-9256
EI 1865-5785
J9 J HEMATOP
JI J. Hematop.
PD JUN
PY 2014
VL 7
IS 2
BP 57
EP 70
DI 10.1007/s12308-014-0202-7
PG 14
WC Hematology; Pathology
SC Hematology; Pathology
GA CU7YQ
UT WOS:000363758200003
ER
PT J
AU Weingart, SN
Zhu, JY
Young-Hong, J
Vermilya, HB
Hassett, M
AF Weingart, Saul N.
Zhu, Junya
Young-Hong, Joanne
Vermilya, Holly Barr
Hassett, Michael
TI Do drug interaction alerts between a chemotherapy order- entry system
and an electronic medical record affect clinician behavior?
SO JOURNAL OF ONCOLOGY PHARMACY PRACTICE
LA English
DT Article
DE Oral antineoplastic therapy; medication safety; electronic medical
record; alerts and reminders
ID AMBULATORY-CARE; SAFETY; ERRORS; CANCER; PREVENTION; CHILDREN; EVENTS
AB Introduction We developed an enhancement to a chemotherapy order-entry system that alerted prescribers to potential drug interactions between patients' usual outpatient medications and those prescribed for onsite cancer treatment. This report summarizes the interactions and analyzes the impact of alerts on clinician behavior.
Methods We studied electronic orders created from November 2010 to December 2011 by oncology clinicians at two comprehensive cancer centers who shared a chemotherapy order-entry system and an ambulatory electronic medical record. The enhancement generated an alert if a new chemotherapy system order for an antineoplastic agent or supportive care medication interacted with an existing medication in the ambulatory record, and tracked prescribers' responses.
Results New chemotherapy system orders triggered 29,592 drug interaction alerts. New orders for antineoplastic agents accounted for 495 (32.6%) of 1518 high- and medium-severity alerts. Interactions with antibiotics accounted for the majority of these alerts. New chemotherapy system orders for antiemetics triggered 352 (23.2%) alerts and more than two-thirds were attributed to interactions with analgesic opioids. High- and medium-severity alerts changed prescriber behavior in 224 (14.8%) occurrences, including potentially fatal interactions between meperidine and monoamine oxidase inhibitors. Clinicians who overrode alerts indicated that they would monitor the patient (54.6%), the patient already tolerated the combination (24.5%), and they would adjust the dose (15.1%).
Conclusion Cancer patients are at risk of serious interactions between medications ordered for cancer care and those provided for general medical care. Organizations and order-entry applications should develop countermeasures to identify and prevent potentially serious drug interactions.
RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA.
EM saul_weingart@dfci.harvard.edu
NR 19
TC 0
Z9 0
U1 1
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1078-1552
EI 1477-092X
J9 J ONCOL PHARM PRACT
JI J. Oncol. Pharm. Pract.
PD JUN
PY 2014
VL 20
IS 3
BP 163
EP 171
DI 10.1177/1078155213487395
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AG1XR
UT WOS:000335210000001
PM 23804625
ER
PT J
AU Ali, SF
Viswanathan, A
Singhal, AB
Rost, NS
Forducey, PG
Davis, LW
Schindler, J
Likosky, W
Schlegel, S
Solenski, N
Schwamm, LH
AF Ali, Syed F.
Viswanathan, Anand
Singhal, Aneesh B.
Rost, Natalia S.
Forducey, Pamela G.
Davis, Lawrence W.
Schindler, Joseph
Likosky, William
Schlegel, Sherene
Solenski, Nina
Schwamm, Lee H.
CA Partners Telestroke Network
TI The TeleStroke Mimic (TM)-Score: A Prediction Rule for Identifying
Stroke Mimics Evaluated in a Telestroke Network
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cerebrovascular disease; stroke mimics; telestroke; thrombolysis
AB Background-Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation.
Methods and Results-We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England-based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver-operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM-Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM-Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77).
Conclusions-SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision-support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time-critical telestroke evaluations.
C1 [Ali, Syed F.; Viswanathan, Anand; Singhal, Aneesh B.; Rost, Natalia S.; Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Forducey, Pamela G.; Davis, Lawrence W.] INTEGRIS Hlth, Oklahoma City, OK USA.
[Schindler, Joseph] Yale New Haven Stroke Ctr, New Haven, CT USA.
[Likosky, William; Schlegel, Sherene] Swedish Med Ctr, Seattle, WA USA.
[Solenski, Nina] Univ Virginia, Charlottesville, VA USA.
RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MGH Stroke Serv, 55 Fruit St, Boston, MA 02114 USA.
EM lschwamm@partners.org
FU Principal Investigator of an National Institute of Neurological
Disorders and Stroke; Health Resource Services Administration
Requisition [09-HRS9923-AB]
FX Syed F. Ali, Anand Viswanathan, Aneesh B. Singhal, Natalia S. Rost,
Pamela G. Forducey, Lawrence W. Davis, Joseph Schindler, William
Likosky, Sherene Schlegel, and Nina Solenski all report no disclosures.
Dr Schwamm serves as a consultant to the Massachusetts Department of
Public Health, and is the Medical Director of the Mass General
TeleHealth program and the Partners TeleStroke Center. Massachusetts
General Hospital provides telehealth services to hospitals in the New
England region, including telestroke. Dr Schwamm is the Principal
Investigator of an National Institute of Neurological Disorders and
Stroke-funded SPOTRIAS center clinical trial, MR WITNESS, for which
Genentech provides alteplase and additional funding. His work is
supported in part by Health Resource Services Administration Requisition
09-HRS9923-AB (Stroke and Traumatic Brain Injury Telehealth Services).
NR 27
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U1 1
U2 2
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 JUN
PY 2014
VL 3
IS 3
AR e000838
DI 10.1161/JAHA.114.000838
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400001
PM 24958778
ER
PT J
AU Coelho, OR
Shah, RV
Neilan, TG
Mitchell, R
Moreno, H
Kwong, R
Jerosch-Herold, M
AF Coelho-Filho, Otavio R.
Shah, Ravi V.
Neilan, Tomas G.
Mitchell, Richard
Moreno, Heitor, Jr.
Kwong, Raymond
Jerosch-Herold, Michael
TI Cardiac Magnetic Resonance Assessment of Interstitial Myocardial
Fibrosis and Cardiomyocyte Hypertrophy in Hypertensive Mice Treated With
Spironolactone
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiac magnetic resonance imaging; hypertension; hypertrophy/remodeling
AB Background-Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR).
Methods and Results-Mice were randomized to L-nitro-omega-methyl ester (L-NAME, 3 mg/mL in water; n=22), or L-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (sic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of L-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and sic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and L-NAME ("L-NAME+S") showed less concentric remodeling, and a lower myocardial ECV and sic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 +/- 0.09 for L-NAME versus 0.25 +/- 0.03 for L-NAME+S, P<0.001; tau(ic): 0.42 +/- 0.11 for L-NAME groups versus 0.12 +/- 0.05 for L-NAME+S group). Mice treated with a combination of L-NAME and spironolactone were similar to placebo-treated controls at 7 weeks.
Conclusions-Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.
C1 [Coelho-Filho, Otavio R.; Shah, Ravi V.; Neilan, Tomas G.; Kwong, Raymond] Harvard Univ, Sch Med, Dept Med, Div Cardiovasc, Boston, MA USA.
[Jerosch-Herold, Michael] Harvard Univ, Sch Med, Dept Radiol, Div Cardiovasc, Boston, MA 02115 USA.
[Mitchell, Richard] Harvard Univ, Sch Med, Dept Pathol, Div Cardiovasc, Boston, MA 02115 USA.
[Coelho-Filho, Otavio R.; Moreno, Heitor, Jr.] State Univ Campinas UNICAMP, Dept Internal Med, Sao Paulo, Brazil.
[Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Radiol,Dept Med, Boston, MA USA.
[Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
[Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
RP Jerosch-Herold, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,Radiol BWH Box 22, Boston, MA 02115 USA.
EM mjerosch-herold@partners.org
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [R01HL090634]; American Heart Association [AHA 11POST5550053, AHA
11POST110033]; American Heart Association Fellow-to-Faculty grant
[12FTF12060588]
FX The Research reported in this publication was supported by the National
Heart, Lung, and Blood Institute of the National Institutes of Health
under Award Number R01HL090634. Drs Coelho-Filho and Shah are supported
by Post-Doctoral Fellowships from the American Heart Association (AHA
11POST5550053 to OCF and AHA 11POST110033 to RVS). Dr Neilan is
supported by an American Heart Association Fellow-to-Faculty grant
(12FTF12060588).
NR 46
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U1 0
U2 2
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 JUN
PY 2014
VL 3
IS 3
AR e000790
DI 10.1161/JAHA.114.000790
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400009
PM 24965024
ER
PT J
AU Liu, Y
Syed, Z
Scirica, BM
Morrow, DA
Guttag, JV
Stultz, CM
AF Liu, Yun
Syed, Zeeshan
Scirica, Benjamin M.
Morrow, David A.
Guttag, John V.
Stultz, Collin M.
TI ECG Morphological Variability in Beat Space for Risk Stratification
After Acute Coronary Syndrome
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE morphological variability; risk stratification acute coronary syndrome
AB Background-Identification of patients who are at high risk of adverse cardiovascular events after an acute coronary syndrome (ACS) remains a major challenge in clinical cardiology. We hypothesized that quantifying variability in electrocardiogram (ECG) morphology may improve risk stratification post-ACS.
Methods and Results-We developed a new metric to quantify beat-to-beat morphologic changes in the ECG: morphologic variability in beat space (MVB), and compared our metric to published ECG metrics (heart rate variability [HRV], deceleration capacity [DC], T-wave alternans, heart rate turbulence, and severe autonomic failure). We tested the ability of these metrics to identify patients at high risk of cardiovascular death (CVD) using 1082 patients (1-year CVD rate, 4.5%) from the MERLIN-TIMI 36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. DC, HRV/low frequency-high frequency, and MVB were all associated with CVD (hazard ratios [HRs] from 2.1 to 2.3 [P<0.05 for all] after adjusting for the TIMI risk score [TRS], left ventricular ejection fraction [LVEF], and B-type natriuretic peptide [BNP]). In a cohort with low-to-moderate TRS (N=864; 1-year CVD rate, 2.7%), only MVB was significantly associated with CVD (HR, 3.0; P=0.01, after adjusting for LVEF and BNP).
Conclusions-ECG morphological variability in beat space contains prognostic information complementary to the clinical variables, LVEF and BNP, in patients with low-to-moderate TRS. ECG metrics could help to risk stratify patients who might not otherwise be considered at high risk of CVD post-ACS.
C1 [Liu, Yun; Stultz, Collin M.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
[Liu, Yun; Stultz, Collin M.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
[Syed, Zeeshan] Univ Michigan, Elect & Comp Engn, Ann Arbor, MI 48109 USA.
[Scirica, Benjamin M.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
[Scirica, Benjamin M.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA.
[Guttag, John V.; Stultz, Collin M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
RP Stultz, CM (reprint author), Room 36-796,77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM cmstultz@mit.edu
FU Agency of Science, Technology and Research (A*STAR), Singapore; Quanta
Computer, Taiwan; General Electric; Gilead Sciences
FX This work was funded by the Agency of Science, Technology and Research
(A*STAR), Singapore, Quanta Computer, Taiwan, and General Electric, USA
MERLIN-TIMI 36 was supported by CV Therapeutics (now Gilead Sciences).
NR 40
TC 3
Z9 3
U1 0
U2 0
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 JUN
PY 2014
VL 3
IS 3
AR e000981
DI 10.1161/JAHA.114.000981
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400018
PM 24963105
ER
PT J
AU McCabe, JM
Kennedy, KF
Yeh, RW
AF McCabe, James M.
Kennedy, Kevin F.
Yeh, Robert W.
TI Defining Unavoidable Delays in Primary Percutaneous Coronary
Intervention: Discordance Among Patients Excluded From National
Cardiovascular Quality Registries
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE Centers for Medicare and Medicaid Services; NCDR; nonsystems delays;
primary percutaneous coronary intervention
AB Background-The Centers for Medicaid and Medicare Services (CMS) and the National Cardiovascular Data Registry (NCDR) track primary percutaneous coronary intervention (PCI) performance in the form of door-to-balloon time. For quality assessment, exceptions are made for patients with "unavoidable delays" in both registries, yet it remains unclear how consistently such patients are identified.
Methods and Results-All primary PCI patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) from 2009 to 2011 were evaluated for CMS inclusion/exclusion and NCDR nonsystems delay (NSD) status. We subsequently analyzed patient characteristics and outcomes based on these strata. Among 456 total patients, 128 (28%) were excluded from CMS reporting, whereas 56 (12%) were listed in the NCDR registry as having an NSD. Forty of 56 (71%) patients with NSD were also excluded from CMS reporting, whereas 312 of 400 (78%) patients reported without NSD were included in CMS reports. Between-registry agreement on patients with unavoidable delays was modest (kappa=0.32). Among CMS-included patients without NSD, 94% received PCI within 90 minutes compared with 29% of CMS-excluded patients with NSD (P<0.001). Likewise, CMS-included patients without NSD had a 4-fold better 1-year mortality rate compared with CMS-excluded patients with NSD (P<0.001).
Conclusions-More than twice as many primary PCI patients are excluded from CMS quality analyses compared with NCDR. With the use of currently available cardiovascular quality registries, it is unclear how many patients truly require unavoidable delays during primary PCI. Patients with NSD had the worst outcomes regardless of CMS status.
C1 [McCabe, James M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Kennedy, Kevin F.] St Lukes Mid Amer Heart Inst, Div Cardiol, Kansas City, MO USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP McCabe, JM (reprint author), Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA.
EM mccabe@aya.yale.edu
FU Long-term Outcomes Registry; American Heart Association
FX Funding for this project was provided via the Long-term Outcomes
Registry and a grant from the American Heart Association. Neither
funding source participated in the design, conduct, analysis, or
interpretation of the data.
NR 12
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 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUN
PY 2014
VL 3
IS 3
AR e000944
DI 10.1161/JAHA.114.000944
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400021
PM 24965027
ER
PT J
AU Wimmer, NJ
Spertus, JA
Kennedy, KF
Anderson, HV
Curtis, JP
Weintraub, WS
Singh, M
Rumsfeld, JS
Masoudi, FA
Yeh, RW
AF Wimmer, Neil J.
Spertus, John A.
Kennedy, Kevin F.
Anderson, H. Vernon
Curtis, Jeptha P.
Weintraub, William S.
Singh, Mandeep
Rumsfeld, John S.
Masoudi, Frederick A.
Yeh, Robert W.
TI Clinical Prediction Model Suitable for Assessing Hospital Quality for
Patients Undergoing Carotid Endarterectomy
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE carotid endarterectomy; risk prediction; stroke
AB Background-Assessing hospital quality in the performance of carotid endarterectomy (CEA) requires appropriate risk adjustment across hospitals with varying case mixes. The aim of this study was to develop and validate a prediction model to assess the risk of in-hospital stroke or death after CEA that could aid in the assessment of hospital quality.
Methods and Results-Patients from National Cardiovascular Data Registry (NCDR)'s Carotid Artery Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute evolving stroke from 2005 to 2013 were included. In-hospital stroke or death was modeled using hierarchical logistic regression with 20 candidate variables and accounting for hospital-level clustering. Internal validation was achieved with bootstrapping; model discrimination and calibration were assessed. A total of 213 (1.7%) primary end point events occurred during 12 889 procedures. Independent predictors of stroke or death included age, prior peripheral artery disease, diabetes mellitus, prior coronary artery disease, having a symptomatic carotid lesion, having a contralateral carotid occlusion, or having New York Heart Association Class III or IV heart failure. The model was well calibrated and demonstrated moderate discriminative ability (c-statistic 0.65). The NCDR CEA score was then developed to support simple, prospective risk quantification in the clinical setting.
Conclusions-The NCDR CEA score, comprising 7 clinical variables, predicts in-hospital stroke or death after CEA. This model can be used to estimate hospital risk-adjusted outcomes for CEA and to assist with the assessment of hospital quality.
C1 [Wimmer, Neil J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wimmer, Neil J.; Yeh, Robert W.] Harvard Univ, Sch Med, Boston, MA USA.
[Spertus, John A.; Kennedy, Kevin F.] St Lukes Midamer Heart Inst, Kansas City, MO USA.
[Anderson, H. Vernon] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Curtis, Jeptha P.] Yale Univ, Sch Med, New Haven, CT USA.
[Weintraub, William S.] Christiana Hlth Care, Newark, DE USA.
[Singh, Mandeep] Mayo Clin, Rochester, MN USA.
[Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Masoudi, Frederick A.] Univ Colorado, Aurora, CO USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM ryeh@partners.org
FU American College of Cardiology Foundation's NCDR; CARE Registry is an
initiative of the American College of Cardiology Foundation (ACCF);
Society for Cardiovascular Angiography and Interventions; Society of
Interventional Radiology; American Academy of Neurology; American
Association of Neurological Surgeons/Congress of Neurological Surgeons;
Society for Vascular Medicine; Society of Vascular and Interventional
Neurology
FX This research was supported by the American College of Cardiology
Foundation's NCDR. The views expressed in this manuscript represent
those of the author(s) and do not necessarily represent the official
views of the NCDR or its associated professional societies identified at
www.ncdr.com. Partners and Sponsors: CARE Registry is an initiative of
the American College of Cardiology Foundation (ACCF), The Society for
Cardiovascular Angiography and Interventions, the Society of
Interventional Radiology, the American Academy of Neurology, the
American Association of Neurological Surgeons/Congress of Neurological
Surgeons, the Society for Vascular Medicine, and the Society of Vascular
and Interventional Neurology.
NR 24
TC 5
Z9 5
U1 0
U2 0
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 JUN
PY 2014
VL 3
IS 3
AR e000728
DI 10.1161/JAHA.113.000728
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400033
PM 24938712
ER
PT J
AU Molina, Y
Lehavot, K
Beadnell, B
Simoni, J
AF Molina, Yamile
Lehavot, Keren
Beadnell, Blair
Simoni, Jane
TI Racial Disparities in Health Behaviors and Conditions Among Lesbian and
Bisexual Women: The Role of Internalized Stigma
SO LGBT HEALTH
LA English
DT Article
DE bisexual; health disparities; lesbian/gay; physical health;
race/ethnicity; women
ID FEMINIST IDENTITY DEVELOPMENT; ACTIVITY QUESTIONNAIRE IPAQ; BODY-FAT
DISTRIBUTION; SEXUAL ORIENTATION; AFRICAN-AMERICAN; PHYSICAL-ACTIVITY;
US ADULTS; GAY MEN; PSYCHOLOGICAL DISTRESS; VEGETABLE INTAKE
AB There are documented disparities in physical health behaviors and conditions, such as physical activity and obesity, with regard to both race/ethnicity and sexual orientation. However, physical health disparities for lesbian and bisexual (LB) women who are also racial minorities are relatively unexplored. Minority stressors, such as internalized stigma, may account for disparities in such multiply marginalized populations. We sought to (1) characterize inequalities among non-Hispanic white and African American LB women and (2) examine the roles of internalized sexism and homophobia in disparities. Data on health behaviors (diet, physical activity); physical health (hypertension, diabetes, overweight/obesity); internalized sexism; and internalized homophobia were collected via a web-based survey. Recruitment ads were sent electronically to over 200 listservs, online groups, and organizations serving the lesbian, gay, and bisexual community in all 50 U.S. states. The analytic sample consisted of 954 white and 75 African American LB women. African American participants were more likely than white participants to report low fruit/vegetable intake and physical activity, a higher body mass index, and a history of diabetes and hypertension. There were no racial differences in internalized homophobia, but African American women reported higher levels of internalized sexism. Internalized sexism partially mediated racial disparities in physical activity and diabetes, but not in the other outcomes. Findings suggest that African American LB women may be at greater risk than their white counterparts for poor health and that internalized sexism may be a mediator of racial differences for certain behaviors and conditions.
C1 [Molina, Yamile] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Molina, Yamile] Univ Illinois, Epidemiol & Biostat Div, Chicago, IL USA.
[Molina, Yamile] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Beadnell, Blair] Univ Washington, Sch Social Work, Seattle, WA 98195 USA.
[Simoni, Jane] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Lehavot, Keren] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Molina, Y (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA.
EM ymolina@fhcrc.org
OI Simoni, Jane/0000-0002-8711-1576
FU Centers for Disease Control Grant for Public Health Research
Dissertation [R36 CD000996]; National Cancer Institute Supplement to
Promote Diversity in Health-Related Research [P50CA148143];
Biobehavioral Cancer Prevention and Control Training Program at the
University of Washington [R25CA92408]
FX This research was supported by a Centers for Disease Control Grant for
Public Health Research Dissertation (R36 CD000996) award to K.L.
Manuscript preparation was supported by funding to Y.M. through a
National Cancer Institute Supplement to Promote Diversity in
Health-Related Research (P50CA148143) and a postdoctoral fellowship
through the Biobehavioral Cancer Prevention and Control Training Program
at the University of Washington (R25CA92408).
NR 89
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U1 3
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2325-8292
EI 2325-8306
J9 LGBT HEALTH
JI LGBT Health
PD JUN
PY 2014
VL 1
IS 2
BP 131
EP 139
DI 10.1089/lgbt.2013.0007
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR9PV
UT WOS:000361689800012
PM 25364769
ER
PT J
AU Robbins, NM
Swanson, RA
AF Robbins, Nathaniel M.
Swanson, Raymond A.
TI Opposing Effects of Glucose on Stroke and Reperfusion Injury Acidosis,
Oxidative Stress, and Energy Metabolism
SO STROKE
LA English
DT Article
DE acidosis; hemorrhage; hyperglycemia; hypoglycemia; reactive oxygen
species; superoxides
C1 [Robbins, Nathaniel M.; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA.
[Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA USA.
RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA.; Swanson, RA (reprint author), Dept Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
EM raymond.swanson@ucsf.edu
OI Swanson, Raymond/0000-0002-3664-5359
FU National Institutes of Health [NS041421, NS081149]; Department of
Veterans Affairs
FX This review was supported by National Institutes of Health grants
NS041421 and NS081149 to R.A. Swanson and by the Department of Veterans
Affairs.
NR 48
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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 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUN
PY 2014
VL 45
IS 6
BP 1881
EP 1886
DI 10.1161/STROKEAHA.114.004889
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA V42VQ
UT WOS:000209641700001
PM 24743441
ER
PT J
AU Banerjee, SC
Hay, JL
Geller, AC
Gagne, JJ
Frazier, AL
AF Banerjee, Smita C.
Hay, Jennifer L.
Geller, Alan C.
Gagne, Joshua J.
Frazier, A. Lindsay
TI Quitting the "Cancer Tube": a qualitative examination of the process of
indoor tanning cessation
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Health belief model; Indoor tanning; Tanning cessation; Tanning
quitting; Qualitative research
ID APPEARANCE-FOCUSED INTERVENTION; PREVENT SKIN-CANCER;
MALIGNANT-MELANOMA; COLLEGE-STUDENTS; SUNBED USE; RISK; EXPOSURE;
BEHAVIOR; HEALTH; METAANALYSIS
AB This study examined health belief model (HBM) relevant constructs in the context of indoor tanning cessation. Telephone interviews were conducted between December 2011 and April 2012 with participants drawn from the Growing Up Today Study (GUTS) population, specifically, former tanning bed users (N= 14, all females; mean age, 25.65 years) who reported frequent use in 2007, but had quit by 2010. Participants identified important motivations for quitting including health and financial reasons and the central role of family and friends in providing encouragement for indoor tanning cessation. However, participants also noted substantial barriers to maintaining indoor tanning quitting (e.g., social pressures to look good, tanning salon incentives). Participants' experience of withdrawal highlighted psychological factors more often than physical factors; some were open to resuming use in the future. The findings will be useful in intervention development to encourage cessation, the strengthening of policies to regulate the indoor tanning industry, as well as public health messaging to raise awareness of this prevalent, easily accessible cancer risk behavior.
C1 [Banerjee, Smita C.; Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA.
[Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Gagne, Joshua J.] Dana Farber Canc Inst, Survey & Data Management Core, Boston, MA 02115 USA.
[Frazier, A. Lindsay] Dana Farber Childrens Canc Care, Pediat, Boston, MA USA.
RP Banerjee, SC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA.
EM banerjes@mskcc.org
FU National Cancer Institute Specialized Programs of Research Excellence
(SPORE) in Skin Cancer
FX This work was supported by the National Cancer Institute Specialized
Programs of Research Excellence (SPORE) in Skin Cancer (Thomas Kupper
PI, Brigham and Women's Hospital).
NR 41
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U1 1
U2 5
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 JUN
PY 2014
VL 4
IS 2
BP 209
EP 219
DI 10.1007/s13142-014-0257-0
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CL2PL
UT WOS:000356786400012
PM 24904705
ER
PT J
AU Liao, KP
Diogo, D
Cui, J
Cai, TX
Okada, Y
Gainer, VS
Murphy, SN
Gupta, N
Mirel, D
Ananthakrishnan, AN
Szolovits, P
Shaw, SY
Raychaudhuri, S
Churchill, S
Kohane, I
Karlson, EW
Plenge, RM
AF Liao, Katherine P.
Diogo, Dorothee
Cui, Jing
Cai, Tianxi
Okada, Yukinori
Gainer, Vivian S.
Murphy, Shawn N.
Gupta, Namrata
Mirel, Daniel
Ananthakrishnan, Ashwin N.
Szolovits, Peter
Shaw, Stanley Y.
Raychaudhuri, Soumya
Churchill, Susanne
Kohane, Isaac
Karlson, Elizabeth W.
Plenge, Robert M.
TI Association between low density lipoprotein and rheumatoid arthritis
genetic factors with low density lipoprotein levels in rheumatoid
arthritis and non-rheumatoid arthritis controls
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LIPID-LEVELS; COMMON VARIANTS; RISK; LOCI;
DISEASE; ATHEROSCLEROSIS; INFLAMMATION; CHOLESTEROL; CONTRIBUTE
AB Objectives While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine the association of established LDL and RA genetic alleles with LDL levels in RA cases compared with non-RA controls.
Methods Using data from electronic medical records, we linked validated RA cases and non-RA controls to discarded blood samples. For each individual, we extracted data on: first LDL measurement, age, gender and year of LDL measurement. We genotyped subjects for 11 LDL and 44 non-HLA RA alleles, and calculated RA and LDL genetic risk scores (GRS). We tested the association between each GRS and LDL level using multivariate linear regression models adjusted for age, gender, year of LDL measurement and RA status.
Results Among 567 RA cases and 979 controls, 80% were female and mean age at the first LDL measurement was 55 years. RA cases had significantly lower mean LDL levels than controls (117.2 vs 125.6 mg/dl, respectively, p<0.0001). Each unit increase in LDL GRS was associated with 0.8 mg/dl higher LDL levels in both RA cases and controls (p=3.0x10(-7)). Each unit increase in RA GRS was associated with 4.3 mg/dl lower LDL levels in both groups (p=0.01).
Conclusions LDL alleles were associated with higher LDL levels in RA. RA alleles were associated with lower LDL levels in both RA cases and controls. As RA cases carry more RA alleles, these findings suggest a genetic basis for epidemiological observations of lower LDL levels in RA.
C1 [Liao, Katherine P.; Diogo, Dorothee; Cui, Jing; Okada, Yukinori; Raychaudhuri, Soumya; Karlson, Elizabeth W.; Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Diogo, Dorothee; Okada, Yukinori; Raychaudhuri, Soumya; Plenge, Robert M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[Diogo, Dorothee; Okada, Yukinori; Gupta, Namrata; Mirel, Daniel; Plenge, Robert M.] Broad Inst, Med & Populat Genet Program, Cambridge, MA USA.
[Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Gainer, Vivian S.; Murphy, Shawn N.; Churchill, Susanne; Kohane, Isaac] Partners Healthcare, Res Comp, Charlestown, MA USA.
[Murphy, Shawn N.] Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Szolovits, Peter] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Raychaudhuri, Soumya] Partners Ctr Personalised Genet Med, Boston, MA USA.
[Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England.
[Kohane, Isaac] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA.
RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA.
EM kliao@partners.org
OI Szolovits, Peter/0000-0001-8411-6403
FU NIH [U54-LM008748, K08-AR060257, K08 AR055688, U01HG0070033,
K24-AR052403, R01-AR049880, P60-AR047782, R01-AR057108, R01-AR056768,
U01-GM092691, R01-AR059648]; Harold and Duval Bowen Fund; Arthritis
Foundation; Burroughs Wellcome Fund
FX The Informatics for Integrating Biology and the Bedside project is
funded by the NIH grant U54-LM008748. KPL is supported by the NIH
K08-AR060257 and the Harold and Duval Bowen Fund; SR by the NIH K08
AR055688, U01HG0070033 and the Arthritis Foundation; and EWK by the NIH
K24-AR052403, R01-AR049880 and P60-AR047782, RMP NIH R01-AR057108,
R01-AR056768, U01-GM092691, R01-AR059648 and the Career Award for
Medical Scientists from the Burroughs Wellcome Fund.
NR 27
TC 5
Z9 4
U1 0
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 JUN
PY 2014
VL 73
IS 6
BP 1170
EP 1175
DI 10.1136/annrheumdis-2012-203202
PG 6
WC Rheumatology
SC Rheumatology
GA AG4AW
UT WOS:000335362100039
PM 23716066
ER
PT J
AU Lee, J
Hwang, YJ
Ryu, H
Kowall, NW
Ryu, H
AF Lee, Junghee
Hwang, Yu Jin
Ryu, Hyun
Kowall, Neil W.
Ryu, Hoon
TI Nucleolar dysfunction in Huntington's disease
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Huntington's disease; Nucleolus; Upstream binding factor (UBF); rDNA
transcription; Acetylation and methylation; Epigenetics
ID RIBOSOMAL-RNA GENES; WILD-TYPE HUNTINGTIN; TRANSCRIPTION FACTOR;
POLYMERASE-I; HISTONE ACETYLTRANSFERASE; NEUROLOGICAL PHENOTYPE;
STRIATAL NEURONS; SPINY NEURONS; MOUSE MODELS; CAG REPEATS
AB Huntington's disease (HD) is a fatal genetic disorder characterized by triad clinical symptoms of chorea, emotional distress, and cognitive decline. Genetic mutation in HD is identified by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin (htt) gene. The exact mechanism on how mutant htt leads to the selective loss of medium spiny neurons (MSNs) in the striatum is still unknown. Recent studies suggest that nucleolar stress and dysfunction are linked to the pathogenesis of HD. Alterations of the nucleolar activity and integrity contribute to deregulation of ribosomal DNA (rDNA) transcription in HD pathogenesis. Furthermore, epigenetic modifications in the nucleolus are associated with neuronal damage in HD. In this review, we discuss about how post-translational modifications of upstream binding factor (UBF) are affected by histone acetyltransferase and histone methyltransferase and involved in the transcriptional regulation of rDNA in HD. The understanding of epigenetic modulation of UBF-dependent rDNA transcription in the nucleolus may lead to the identification of novel pathological markers and new therapeutic targets to treat HD. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. (C) 2013 Elsevier BM. All rights reserved.
C1 [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Lee, Junghee; Ryu, Hyun; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Boston, MA 02118 USA.
[Hwang, Yu Jin] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, WCU Neurocyt Grp, Seoul 110799, South Korea.
[Ryu, Hoon] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul, South Korea.
RP Ryu, H (reprint author), VA Boston Healthcare Syst, Bldg 1A,Rm 109,150 S Huntington Ave, Boston, MA 02130 USA.
EM hoonryu@bu.edu
RI Kowall, Neil/G-6364-2012
OI Kowall, Neil/0000-0002-6624-0213
FU NIH [NS 067283]; Brain Science Flagship from Korea Institute of Science
and Technology [2E24380]
FX This study was supported by NIH NS 067283 (H.R) and Brain Science
Flagship Grant (2E24380) (H.R.) from Korea Institute of Science and
Technology.
NR 67
TC 15
Z9 15
U1 0
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 0006-3002
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD JUN
PY 2014
VL 1842
IS 6
SI SI
BP 785
EP 790
DI 10.1016/j.bbadis.2013.09.017
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AG5AP
UT WOS:000335431800006
PM 24184605
ER
PT J
AU Chen, Y
Won, SJ
Xu, Y
Swanson, RA
AF Chen, Y.
Won, S. J.
Xu, Y.
Swanson, R. A.
TI Targeting Microglial Activation in Stroke Therapy: Pharmacological Tools
and Gender Effects
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Brain; corticosteroid; female; HDAC; inflammation; ischemia;
minocycline; PARP
ID FOCAL CEREBRAL-ISCHEMIA; HISTONE DEACETYLASE INHIBITORS;
TUMOR-NECROSIS-FACTOR; GROUP BOX1-INHIBITING MECHANISM; BRAIN-INJURY;
RAT-BRAIN; POLY(ADP-RIBOSE) POLYMERASE-1; GENE-EXPRESSION; FACTOR-ALPHA;
CELL-DEATH
AB Ischemic stroke is caused by critical reductions in blood flow to brain or spinal cord. Microglia are the resident immune cells of the central nervous system, and they respond to stroke by assuming an activated phenotype that releases cytotoxic cytokines, reactive oxygen species, proteases, and other factors. This acute, innate immune response may be teleologically adapted to limit infection, but in stroke this response can exacerbate injury by further damaging or killing nearby neurons and other cell types, and by recruiting infiltration of circulating cytotoxic immune cells. The microglial response requires hours to days to fully develop, and this time interval presents a clinically accessible time window for initiating therapy. Because of redundancy in cytotoxic microglial responses, the most effective therapeutic approach may be to target the global gene expression changes involved in microglial activation. Several classes of drugs can do this, including histone deacetylase inhibitors, minocycline and other PARP inhibitors, corticosteroids, and inhibitors of TNF alpha and scavenger receptor signaling. Here we review the pre-clinical studies in which these drugs have been used to suppress microglial activation after stroke. We also review recent advances in the understanding of sex differences in the CNS inflammatory response, as these differences are likely to influence the efficacy of drugs targeting post-stroke brain inflammation.
C1 [Chen, Y.; Xu, Y.] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China.
[Chen, Y.; Won, S. J.; Swanson, R. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Chen, Y.; Won, S. J.; Swanson, R. A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA.
RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA.
EM raymond.swanson@ucsf.edu
OI Swanson, Raymond/0000-0002-3664-5359
FU Chinese Research Scholarship Council; U.S. National Institutes of Health
[NS041421]; U.S. Department of Veterans Affairs
FX This work was supported by the Chinese Research Scholarship Council
(Y.C.) the U.S. National Institutes of Health (grant # NS041421,
R.A.S.), and the U.S. Department of Veterans Affairs.
NR 132
TC 18
Z9 18
U1 0
U2 15
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD JUN
PY 2014
VL 21
IS 19
BP 2146
EP 2155
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AG4MF
UT WOS:000335393300005
PM 24372213
ER
PT J
AU Fitten, LJ
Ortiz, F
Fairbanks, L
Bartzokis, G
Lu, P
Klein, E
Coppola, G
Ringman, J
AF Fitten, L. Jaime
Ortiz, Freddy
Fairbanks, Lynn
Bartzokis, George
Lu, Po
Klein, Eric
Coppola, Giovanni
Ringman, John
TI Younger age of dementia diagnosis in a Hispanic population in southern
California
SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE diagnosis; Hispanic; onset; Alzheimer's disease; Latino; age; dementia;
vascular dementia; APOE genotype; diagnosis
ID APOLIPOPROTEIN-E EPSILON-4; MINI-MENTAL-STATE; OLDER MEXICAN-AMERICANS;
ALZHEIMERS-DISEASE; DIABETES-MELLITUS; AFRICAN-AMERICANS; CARIBBEAN
HISPANICS; NORTHERN MANHATTAN; RISK; ONSET
AB Objective
Prior studies of US Hispanics, largely performed on the East Coast, have found a younger age of dementia onset than in White non-Hispanics. We performed a cross-sectional study to examine clinical and sociodemographic variables associated with age of dementia diagnosis in older Hispanics and White, non-Hispanics in southern California.
Methods
Two hundred ninety (110 Hispanic and 180 White non-Hispanic) community dwelling, cognitively symptomatic subjects, aged 50 years and older, were assessed and diagnosed with probable Alzheimer's disease or probable vascular dementia. Apolipoprotein E (APOE) genotype was assessed in a subset of cases. Analysis of variance and multiple stepwise linear regression were used to assess main effects and interactions of ethnicity with dementia severity (indexed by mini mental state examination scores) and other sociodemographic and clinical variables on age of dementia diagnosis.
Results
Hispanics were younger by an average of 4 years at the time of diagnosis, regardless of dementia subtype, despite a similar prevalence of the APOE epsilon 4 genotype. The earlier age at diagnosis for Hispanics was not explained by gender, dementia severity, years of education, history of hypercholesterolemia, hypertension, or diabetes. Only ethnicity was significantly associated with age of onset.
Conclusions
These findings confirm that US Hispanics living in the southwestern USA tend to be younger at the time of dementia diagnosis than their White non-Hispanic counterparts. As this is not explained by the presence of the APOE epsilon 4 genotype, further studies should explore other cultural, medical, or genetic risk factors influencing the age of dementia onset in this population. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Fitten, L. Jaime; Ortiz, Freddy; Fairbanks, Lynn; Bartzokis, George; Lu, Po; Coppola, Giovanni; Ringman, John] Univ Calif Los Angeles, David Geffen Sch Med, Easton Ctr Alzheimer Dis Res, Los Angeles, CA 90095 USA.
[Fitten, L. Jaime; Ortiz, Freddy] US Dept Vet Affairs, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA.
[Fitten, L. Jaime; Ortiz, Freddy] Univ Calif Los Angeles, Med Ctr, Dept Psychiat Olive View, Los Angeles, CA 90024 USA.
[Fitten, L. Jaime; Fairbanks, Lynn; Bartzokis, George; Lu, Po; Klein, Eric; Coppola, Giovanni] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Ortiz, Freddy; Lu, Po; Ringman, John] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Bartzokis, George] Greater Los Angeles VA Healthcare Syst, West Los Angeles, CA USA.
RP Fitten, LJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Easton Ctr Alzheimer Dis Res, Los Angeles, CA 90095 USA.
EM jfitten@ucla.edu
FU NIA-UCLA ADRC [P50 AG16570]; State of California Alzheimer's Disease
Center at UCLA, the Easton Consortium for Alzheimer's Disease Drug
Discovery and Biomarker Development; Olive View-UCLA Medical Center,
Sylmar, CA, USA; VA Greater Los Angeles Healthcare System, Sepulveda,
CA, USA
FX This study was supported by funding from the NIA-UCLA ADRC (P50
AG16570); by the State of California Alzheimer's Disease Center at UCLA,
the Easton Consortium for Alzheimer's Disease Drug Discovery and
Biomarker Development; by the Olive View-UCLA Medical Center, Sylmar,
CA, USA; and by the VA Greater Los Angeles Healthcare System, Sepulveda,
CA, USA.
NR 37
TC 6
Z9 6
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6230
EI 1099-1166
J9 INT J GERIATR PSYCH
JI Int. J. Geriatr. Psychiatr.
PD JUN
PY 2014
VL 29
IS 6
BP 586
EP 593
DI 10.1002/gps.4040
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AG2ND
UT WOS:000335252300005
PM 24478258
ER
PT J
AU Raskind, MA
Wang, LY
AF Raskind, Murray A.
Wang, Lucy Y.
TI Antipsychotic drugs for psychosis and agitation in dementia: efficacy,
safety, and a possible noradrenergic mechanism of action
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Editorial Material
ID PLACEBO-CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE;
DOUBLE-BLIND; LOCUS-COERULEUS; BEHAVIORAL DISTURBANCES; SENILE DEMENTIA;
CLINICAL-TRIAL; TYROSINE-HYDROXYLASE; COMPENSATORY CHANGES
AB The first patient described by Alzheimer in 1907 had both progressive cognitive deterioration and prominent comorbid signs and symptoms of psychosis and agitation (Alzheimer, 1907, 1987). In this editorial, we use "psychosis" to denote delusions and hallucinations and "agitation" to denote irritability, aggression, pressured motor activity, and active resistance to necessary care. Although advances have been made in the treatment of these non-cognitive symptoms, these psychosis and agitation symptoms continued to be burdensome and costly for dementia patients, caregivers, and society. Among the pharmacologic treatments available for psychosis and agitation, antipsychotic drugs are the drug class most consistently demonstrated effective for psychosis and agitation in dementia (Lyketsos et al., 2006; APA Work Group on Alzheimer's Disease and Other Dementias et al., 2007). These are widely prescribed for these behavioral problems, but their use remains controversial and their mechanism of action unclear.
C1 [Raskind, Murray A.] Univ Washington, Vet Affairs Northwest Network VISN 20, Mental Illness Res Educ & Clin Ctr, Mental Hlth Serv,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Raskind, MA (reprint author), Univ Washington, Vet Affairs Northwest Network VISN 20, Mental Illness Res Educ & Clin Ctr, Mental Hlth Serv,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
EM murray.raskind@va.gov
NR 45
TC 1
Z9 1
U1 1
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
EI 1741-203X
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD JUN
PY 2014
VL 26
IS 6
BP 879
EP 883
AR PII S1041610214000477
DI 10.1017/S1041610214000477
PG 5
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA AG4RK
UT WOS:000335407700001
PM 24703502
ER
PT J
AU Vatsavayi, AVV
Kofler, J
DeMichele-Sweet, MAA
Murray, PS
Lopez, OL
Sweet, RA
AF Vatsavayi, Anil Varma V.
Kofler, Julia
DeMichele-Sweet, Mary Ann A.
Murray, Patrick S.
Lopez, Oscar L.
Sweet, Robert A.
TI TAR DNA-binding protein 43 pathology in Alzheimer's disease with
psychosis
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Article
DE Alzheimer's disease; TDP-43; psychosis
ID FRONTOTEMPORAL LOBAR DEGENERATION; NEUROPATHOLOGIC ASSESSMENT; TDP-43
IMMUNOREACTIVITY; HIPPOCAMPAL SCLEROSIS; RISK-FACTORS; DELUSIONS;
SYMPTOMS; PHENOTYPE; DEMENTIA; BEHAVIOR
AB Background:
TAR DNA-binding protein 43 (TDP-43) has been identified as a major disease protein in frontotemporal lobar degeneration. More recently, TDP-43 proteinopathy has also been observed in Alzheimer's disease (AD) with a characteristic distribution of TDP-43 predominantly in the mesial temporal lobe, and to a lesser degree in the neocortical areas. AD subjects with psychotic symptoms (AD+P) represent a subgroup characterized by greater impairment of frontal cortex-dependent cognitive functions and more severe frontal cortical neuropathology. The aim of this study is to determine whether there is an association between TDP-43 pathology and AD+P. We hypothesized that TDP-43 pathology would be more frequent in AD+P than in AD without psychosis.
Methods:
We studied the presence and distribution of TDP-43 pathology by immunohistochemistry in the dentate gyrus (DG) and prefrontal cortex (FC) of postmortem brain specimens from 68 subjects with a primary neuropathologic diagnosis of AD as determined by the Neuropathology Core of the University of Pittsburgh Alzheimer's Disease Research Center.
Results:
Forty-five (66%) subjects were classified as AD+P. Fourteen (20.6%) subjects had TDP-43 pathology in DG, eight (11.8%) had TDP-43 pathology in FC, and six (8.8%) had TDP-43 pathology in both regions. TDP-43 in DG was not significantly associated with AD+P. However, TDP-43 in FC demonstrated a trend toward reduced likelihood of psychosis (p = 0.068). TDP-43 pathology in DG, but not FC, was significantly associated with greater age at death and longer duration of illness.
Conclusions:
Our findings indicate that there was no association between concomitant TDP-43 pathology in DG or FC and AD+P.
C1 [Vatsavayi, Anil Varma V.; Murray, Patrick S.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Translat Neurosci Program, Pittsburgh, PA USA.
[Vatsavayi, Anil Varma V.; DeMichele-Sweet, Mary Ann A.; Murray, Patrick S.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Vatsavayi, Anil Varma V.; Murray, Patrick S.; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA.
[Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Kofler, Julia] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
RP Sweet, RA (reprint author), Biomed Sci Tower,W1645 3811,OHara St, Pittsburgh, PA 15213 USA.
EM sweetra@upmc.edu
OI Murray, Patrick/0000-0002-6525-2888
FU National Institute of Aging [AG05133, AG027224]; VA Pittsburgh
Healthcare System (VAPHS) [BX000452]
FX This work was supported in part by the National Institute of Aging
grants AG05133 (OLL) and AG027224 (RAS), and the VA Pittsburgh
Healthcare System (VAPHS) grant BX000452 (RAS). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institute of Mental Health, the National
Institutes of Health, the Department of Veterans Affairs, or the United
States Government.
NR 40
TC 3
Z9 3
U1 2
U2 11
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
EI 1741-203X
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD JUN
PY 2014
VL 26
IS 6
BP 987
EP 994
DI 10.1017/S1041610214000246
PG 8
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA AG4RK
UT WOS:000335407700013
PM 24588894
ER
PT J
AU Abuelo, CE
Levinson, KL
Salmeron, J
Sologuren, CV
Fernandez, MJV
Belinson, JL
AF Abuelo, Carolina E.
Levinson, Kimberly L.
Salmeron, Jorge
Vallejos Sologuren, Carlos
Vallejos Fernandez, Maria Jose
Belinson, Jerome L.
TI The Peru Cervical Cancer Screening Study (PERCAPS): The Design and
Implementation of a Mother/Daughter Screen, Treat, and Vaccinate Program
in the Peruvian Jungle
SO JOURNAL OF COMMUNITY HEALTH
LA English
DT Article
DE Human papillomavirus; Cervical cancer screening; Community based
participatory; Research techniques; Peru
ID SELF-COLLECTED SAMPLES; HUMAN-PAPILLOMAVIRUS; HPV; ACCEPTABILITY;
CYTOLOGY; PART
AB Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100 % of participants gave an HPV sample and 99.7 % reported high satisfaction; 81 % of HPV + women were treated, and 57 % returned for 6-month followup. Vaccine intervention: 98 % of girls received the 1st vaccine, 88 % of those received the 2nd, and 65 % the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions.
C1 [Abuelo, Carolina E.] Massachusetts Gen Hosp, Charlestown HealthCare Ctr, Charlestown, MA 02445 USA.
[Levinson, Kimberly L.] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA.
[Salmeron, Jorge] Inst Mexicano Seguro Social, Cuernavaca, Morelos, Mexico.
[Vallejos Sologuren, Carlos; Vallejos Fernandez, Maria Jose] Oncosalud, Lima, Peru.
[Belinson, Jerome L.] Prevent Oncol Int, Cleveland, OH USA.
RP Abuelo, CE (reprint author), Massachusetts Gen Hosp, Charlestown HealthCare Ctr, 73 High St, Charlestown, MA 02445 USA.
EM cabuelo@partners.org
FU FIC NIH HHS [R24 TW007988]
NR 17
TC 4
Z9 4
U1 7
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0094-5145
EI 1573-3610
J9 J COMMUN HEALTH
JI J. Community Health
PD JUN
PY 2014
VL 39
IS 3
BP 409
EP 415
DI 10.1007/s10900-013-9786-6
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AG4LY
UT WOS:000335392600001
PM 24276617
ER
PT J
AU Peters, AT
Peckham, AD
Stange, JP
Sylvia, LG
Hansen, NS
Salcedo, S
Rauch, SL
Nierenberg, AA
Dougherty, DD
Deckersbach, T
AF Peters, Amy T.
Peckham, Andrew D.
Stange, Jonathan P.
Sylvia, Louisa G.
Hansen, Natasha S.
Salcedo, Stephanie
Rauch, Scott L.
Nierenberg, Andrew A.
Dougherty, Darin D.
Deckersbach, Thilo
TI Correlates of real world executive dysfunction in bipolar I disorder
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Executive function; Bipolar; Cognition
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; QUALITY-OF-LIFE;
NEUROCOGNITIVE IMPAIRMENT; FUNCTIONAL IMPAIRMENT; COGNITIVE
REHABILITATION; EMPLOYMENT STATUS; EUTHYMIC PATIENTS; RATING-SCALE;
DSM-IV; SCHIZOPHRENIA
AB Background: Bipolar disorder is characterized by impairments in cognitive functioning, both during acute mood episodes and periods of euthymia, which interfere with functioning. Cognitive functioning is typically assessed using laboratory-based tests, which may not capture how cognitive dysfunction is experienced in real-life settings. Little is known about the specific illness characteristics of bipolar disorder that contribute to cognitive dysfunction in everyday life.
Methods: Participants met DSM-IV criteria for bipolar I disorder (n = 68) in a depressed or euthymic state. Everyday executive functioning was evaluated using the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Frontal Systems Behavior Rating Scale (FrSBe). Participants completed clinician rated measures of mood state (Hamilton Depression Rating Scale, Young Mania Rating Scale), prior illness course and co-morbidities (Mini International Neuropsychiatric Interview), as well as self-report measures of psychotropic medication use and medical co-morbidity.
Results: Individuals in this study reported significant impairment in every domain of executive functioning. These deficits were associated with a multitude of illness factors, some directly impacted by mood symptoms and others shaped by illness chronicity, psychiatric comorbidity, medical co-morbidity, and medication use.
Discussion: Executive functioning problems observed in everyday functioning in bipolar disorder are not entirely mood-state dependent. Cognitive rehabilitation for executive dysfunction should be considered an important adjunctive treatment for many individuals with bipolar disorder. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Peters, Amy T.] Univ Illinois, Chicago, IL USA.
[Peckham, Andrew D.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Stange, Jonathan P.] Temple Univ, Philadelphia, PA 19122 USA.
[Sylvia, Louisa G.; Hansen, Natasha S.; Salcedo, Stephanie; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA USA.
[Sylvia, Louisa G.; Rauch, Scott L.; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA.
[Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA.
RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149-2628,Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA.
EM tdeckersbach@partners.org
FU K-23 NIMH Career Award [1K23MH074895-01A2]
FX This work was supported by a K-23 NIMH Career Award 1K23MH074895-01A2 to
Thilo Deckersbach, PhD.
NR 53
TC 9
Z9 9
U1 3
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUN
PY 2014
VL 53
BP 87
EP 93
DI 10.1016/j.jpsychires.2014.02.018
PG 7
WC Psychiatry
SC Psychiatry
GA AG0KK
UT WOS:000335104200013
PM 24655587
ER
PT J
AU Carl, JR
Fairholme, CP
Gallagher, MW
Thompson-Hollands, J
Barlow, DH
AF Carl, Jenna R.
Fairholme, Christopher P.
Gallagher, Matthew W.
Thompson-Hollands, Johanna
Barlow, David H.
TI The Effects of Anxiety and Depressive Symptoms on Daily Positive Emotion
Regulation
SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT
LA English
DT Article
DE Positive emotion; Anxiety; Depression; Emotion regulation; Daily diary
ID IMPAIRMENT SCALE OASIS; INDIVIDUAL-DIFFERENCES; NEGATIVE EMOTIONS; MAJOR
DEPRESSION; DAILY-LIFE; DISORDER; REACTIVITY; EXPERIENCE; VALIDATION;
EVENTS
AB Individuals with anxiety and depressive symptoms exhibit disturbances in positive emotion regulation, which may hinder full recovery. By comparison, individuals with strong beliefs regarding their capacity to "savor" or maintain positive emotions (i.e., savoring beliefs) display more adaptive positive emotion regulation. The present daily diary study explores three momentary processes involved in positive emotion regulation, namely positive emotion reactivity, regulatory goals, and regulatory effectiveness, and examines the comparative effects of baseline anxiety and depressive symptoms versus savoring beliefs on such processes in real-life contexts. A sample of 164 nonclinical undergraduates provided baseline measures of anxiety and depressive symptom severity and savoring beliefs prior to completing 14 daily assessments of positive emotions and emotion regulatory responses to daily positive events. Results indicated that higher baseline anxiety and depressive symptom severity were associated with decreased positive emotion reactivity and increased down-regulation of positive emotions; higher baseline savoring beliefs were associated with increased positive emotion reactivity, decreased down-regulation and increased up-regulation of positive emotions. Potential clinical implications are discussed.
C1 [Carl, Jenna R.; Thompson-Hollands, Johanna; Barlow, David H.] Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA.
[Fairholme, Christopher P.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Gallagher, Matthew W.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Natl Ctr PTSD 116B 2, Boston, MA 02130 USA.
RP Carl, JR (reprint author), Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA.
EM jcarl@bu.edu
NR 58
TC 0
Z9 0
U1 9
U2 39
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0882-2689
EI 1573-3505
J9 J PSYCHOPATHOL BEHAV
JI J. Psychopathol. Behav. Assess.
PD JUN
PY 2014
VL 36
IS 2
BP 224
EP 236
DI 10.1007/s10862-013-9387-9
PG 13
WC Psychology, Clinical
SC Psychology
GA AG3KA
UT WOS:000335313600005
ER
PT J
AU Minzenberg, MJ
Gomes, GC
Yoon, JH
Watrous, AJ
Geng, J
Firl, AJ
Carter, CS
AF Minzenberg, Michael J.
Gomes, Glenn C.
Yoon, Jong H.
Watrous, Andrew J.
Geng, Joy
Firl, Alana J.
Carter, Cameron S.
TI Modafinil augments oscillatory power in middle frequencies during rule
selection
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Prefrontal cortex; Cognitive control; Oscillations; Theta; Modafinil;
Rule selection
ID INDEPENDENT COMPONENT ANALYSIS; INTERNEURON DIVERSITY SERIES; PREFRONTAL
CORTEX; LOCUS-COERULEUS; WORKING-MEMORY; THETA-OSCILLATIONS; COGNITIVE
CONTROL; 1ST-EPISODE SCHIZOPHRENIA; PHASE SYNCHRONIZATION; NETWORK
OSCILLATIONS
AB Control-related cognitive processes are associated with cortical oscillations and modulated by catecholamine neurotransmitters. It remains unclear how catecholamine systems modulate control-related oscillations. We tested modafinil effects on rule-related 4-30 Hz oscillations, with double-blind, placebo-controlled (within-subjects) testing of 22 healthy adults, using EEG during cognitive control task performance. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-30 Hz oscillations. Modafinil enhanced oscillatory power associated with high-control rule selection in theta, alpha, and beta ranges, with a frontotemporal topography and minimal effects during rule maintenance. Augmentation of catecholamine signaling enhances middle-frequency cortical oscillatory power associated with rule selection, which may subserve diverse subcomponent processes in proactive cognitive control.
C1 [Minzenberg, Michael J.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Minzenberg, Michael J.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Gomes, Glenn C.; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA.
[Yoon, Jong H.] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA.
[Yoon, Jong H.] Palo Alto Vet Affairs Med Ctr, Palo Alto, CA USA.
[Watrous, Andrew J.; Geng, Joy; Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA.
[Firl, Alana J.] Univ Calif Berkeley, Program Vis Neurosci, Berkeley, CA 94720 USA.
RP Minzenberg, MJ (reprint author), 116C San Francisco Vet Affairs Med Ctr, Outpatient Mental Hlth Serv, 4150 Clement St, San Francisco, CA 94121 USA.
EM Michael.minzenberg@ucsf.edu
FU Doris Duke Charitable Foundation; NARSAD (Brain and Behavior
Foundation); National Center for Research Resources (NCRR), a component
of the National Institutes of Health (NIH) [UL1 RR024146]; NIH Roadmap
for Medical Research
FX This work was supported by a Clinical Scientist Development Award from
the Doris Duke Charitable Foundation and a Young Investigator award from
NARSAD (Brain and Behavior Foundation) to MJM. This publication was also
made possible by Grant Number UL1 RR024146 from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research. Its contents are
solely the responsibility of the authors and do not necessarily
represent the official view of NCRR or NIH. The authors would like to
acknowledge the assistance of Janeth Nunez del Prado, Jenny Yen, and
Dennis Thompson in the conduct and analysis of the study.
NR 84
TC 4
Z9 4
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0048-5772
EI 1469-8986
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD JUN
PY 2014
VL 51
IS 6
BP 510
EP 519
DI 10.1111/psyp.12201
PG 10
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA AG1SL
UT WOS:000335196300002
PM 24611660
ER
PT J
AU Leung, CM
Stone, WS
Lee, EHM
Seidman, LJ
Chen, EYH
AF Leung, Chung-Ming
Stone, William S.
Lee, Edwin Ho-Ming
Seidman, Larry J.
Chen, Eric Yu-Hai
TI Impaired facilitation of self-control cognition by glucose in patients
with schizophrenia: A randomized controlled study
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Nutrition-based intervention; Cognition; Willpower; Impulse control
ID BLOOD-GLUCOSE; INSULIN-RESISTANCE; LIMITED RESOURCE; ALZHEIMER-TYPE;
MEMORY; DEPLETION; ENERGY; SCALE; IMPULSIVITY; PERFORMANCE
AB Objective: Studies in healthy individuals show that exerting self-control consumes cognitive resources, which reduces subsequent self-control performance. Restoring the availability of blood glucose eliminates this impairment. Patients with schizophrenia are found to have self-regulatory dysfunctions. This study aims to investigate whether patient's (a) glucose facilitation effects will be impaired, and (b) will have exaggerated depletion in a self-control task.
Method: 40 patients with schizophrenia-spectrum disorders and 40 normal controls were recruited. A two drinks (glucose vs. placebo) x two depleting phases (self-control depleted vs. non-depleted) between groups design was used. We examined the blood glucose levels before and after the selfcontrol depletion phase and the subsequent performances in two self-control tasks (handgrip and Stroop tests) after the drink condition.
Results: The four groups (depleting x glucose, depleting x placebo, non-depleting x glucose and nondepleting x placebo) of both patients and normal controls were comparable on a number of characteristics. The change in blood glucose level in the depleting group was significantly different from those in the non-depleting group. Two x two between-subjects ANOVAs were carried out to test the performances in the handgrip and Stroop tasks. Significant interactions were found in healthy controls regarding both tasks. However, a significant interaction was only found in patients regarding the handgrip task but not the Stroop task.
Conclusions: This study demonstrated an abnormal glucose facilitation effect in patients during a cognitive self-control task but not during a physical self-control task. The findings also suggested for the first time that a self-control depletion effect is intact in patients with schizophrenia. (C) 2014 Elsevier B. V. All rights reserved.
C1 [Leung, Chung-Ming; Lee, Edwin Ho-Ming; Chen, Eric Yu-Hai] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Stone, William S.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat,Div Publ Psychiat,Med Sch, Boston, MA 02115 USA.
[Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Chen, Eric Yu-Hai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China.
RP Chen, EYH (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Psychiat, 102 Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China.
EM eyhchen@hku.hk
FU Psychiatry Department, University of Hong Kong, Hong Kong
FX The project was funded by the internal funding of the Psychiatry
Department, University of Hong Kong, Hong Kong.
NR 62
TC 3
Z9 3
U1 2
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUN
PY 2014
VL 156
IS 1
BP 38
EP 45
DI 10.1016/j.schres.2014.03.010
PG 8
WC Psychiatry
SC Psychiatry
GA AG5IF
UT WOS:000335452000006
PM 24731620
ER
PT J
AU Yeo, RA
Gangestad, SW
Walton, E
Ehrlich, S
Pommy, J
Turner, JA
Liu, JY
Mayer, AR
Schulz, SC
Ho, BC
Bustillo, JR
Wassink, TH
Sponheim, SR
Morrow, EM
Calhoun, VD
AF Yeo, Ronald A.
Gangestad, Steven W.
Walton, Esther
Ehrlich, Stefan
Pommy, Jessica
Turner, Jessica A.
Liu, Jingyu
Mayer, Andrew R.
Schulz, S. Charles
Ho, Beng-Choon
Bustillo, Juan R.
Wassink, Thomas H.
Sponheim, Scott R.
Morrow, Eric M.
Calhoun, Vince D.
TI Genetic influences on cognitive endophenotypes in schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Genetics; Executive function; Mutation; Cognitive;
Endophenotype
ID COPY NUMBER VARIATION; INTELLIGENCE; EVOLUTION; DEFICIT; DISEASE; SIZE
AB Background: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.
Methods: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA).
Results: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes.
Limitations: Though adequately powered, our sample size is small for a genetic study.
Conclusions: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls. (C) 2014 Elsevier B. V. All rights reserved.
C1 [Yeo, Ronald A.; Gangestad, Steven W.; Pommy, Jessica] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Yeo, Ronald A.; Turner, Jessica A.; Liu, Jingyu; Mayer, Andrew R.; Bustillo, Juan R.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA.
[Walton, Esther; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Walton, Esther; Ehrlich, Stefan] Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany.
[Walton, Esther; Ehrlich, Stefan] Tech Univ Dresden, Dresden, Germany.
[Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA.
[Turner, Jessica A.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA.
[Liu, Jingyu; Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA.
[Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Ho, Beng-Choon; Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
[Bustillo, Juan R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
[Sponheim, Scott R.] Minneapolis Vet Adm Hlth Care Syst, Minneapolis, MN USA.
[Morrow, Eric M.] Brown Univ, Mol Med Lab, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
RP Yeo, RA (reprint author), Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
EM ryeo@unm.edu
RI Ho, Beng-Choon/D-6959-2011; Turner, Jessica/H-7282-2015;
OI Ho, Beng-Choon/0000-0003-3976-1555; Turner, Jessica/0000-0003-0076-8434;
Ehrlich, Stefan/0000-0003-2132-4445; Gangestad,
Steven/0000-0002-8879-4348; Walton, Esther/0000-0002-0935-2200; Liu,
Jingyu/0000-0002-1724-7523
FU U.S. Department of Energy [DE-FG02-08ER64581]; National Institutes of
Health [5P20RR 021938, 1RC1MH089257, R01EB005846]
FX This work was supported by grants from the U.S. Department of Energy
under Award Number DE-FG02-08ER64581, and the National Institutes of
Health (grants 5P20RR 021938, 1RC1MH089257 and R01EB005846).
NR 30
TC 6
Z9 6
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUN
PY 2014
VL 156
IS 1
BP 71
EP 75
DI 10.1016/j.schres.2014.03.022
PG 5
WC Psychiatry
SC Psychiatry
GA AG5IF
UT WOS:000335452000013
PM 24768440
ER
PT J
AU Terasaki, Y
Liu, Y
Hayakawa, K
Pham, LD
Lo, EH
Ji, X
Arai, K
AF Terasaki, Y.
Liu, Y.
Hayakawa, K.
Pham, L. D.
Lo, E. H.
Ji, X.
Arai, K.
TI Mechanisms of Neurovascular Dysfunction in Acute Ischemic Brain
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Cell-cell interaction; extracellular vesicles; neuronal cell death;
neuroprotection; neurovascular unit; stroke
ID NEURONAL CELL-DEATH; CIRCULATING ENDOTHELIAL MICROPARTICLES; FOCAL
CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; MATRIX METALLOPROTEINASES; NMDA
RECEPTOR; OLIGODENDROCYTE DIFFERENTIATION; NEUROTROPHIC FACTOR;
GLUTAMATE RELEASE; SECRETE EXOSOMES
AB The neurovascular unit is now well accepted as a conceptual framework for investigating the mechanisms of ischemic stroke. From a molecular and cellular perspective, three broad mechanisms may underlie stroke pathophysiology-excitotoxicity, oxidative stress and inflammation. To date, however, most investigations of these basic mechanisms have focused on neuronal responses. In this mini-review, we ask whether these mechanisms of excitotoxicity, oxidative stress and inflammation can also be examined in terms of non-neuronal interactions in the neurovascular unit, including the release of extracellular vesicles for cell-cell signaling.
C1 [Liu, Y.; Ji, X.] Capital Med Univ, Amer Massachusetts Gen Hosp, Joint Inst Neurosci, China Xuan Wu Hosp,Xuan Wu Hosp, Beijing, Peoples R China.
[Liu, Y.; Ji, X.] Geriatr Med Res Ctr, Beijing, Peoples R China.
[Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Ji, X (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
EM jixm@ccmu.edu.cn; karai@partners.org
FU National Institutes of Health; SUMITOMO Life Social Welfare Service
Foundation; National Natural Science Foundation of China [81200915];
Beijing Natural Science Foundation; China National Basic Research 973
Program
FX Supported in part by grants from the National Institutes of Health, the
SUMITOMO Life Social Welfare Service Foundation, the National Natural
Science Foundation of China (Grant No. 81200915), the Beijing Natural
Science Foundation, and the China National Basic Research 973 Program.
NR 123
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Z9 13
U1 1
U2 15
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD JUN
PY 2014
VL 21
IS 18
BP 2035
EP 2042
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AF6UM
UT WOS:000334850100003
PM 24372202
ER
PT J
AU Kim, JY
Kawabori, M
Yenari, MA
AF Kim, J. Y.
Kawabori, M.
Yenari, M. A.
TI Innate Inflammatory Responses in Stroke: Mechanisms and Potential
Therapeutic Targets
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Brain ischemia; inflammation; neuroprotection; stroke
ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; TUMOR-NECROSIS-FACTOR;
NITRIC-OXIDE SYNTHASE; INTERCELLULAR-ADHESION MOLECULE-1;
CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1;
INTERLEUKIN-1 RECEPTOR ANTAGONIST; NF-KAPPA-B; TRANSIENT FOREBRAIN
ISCHEMIA
AB Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke.
C1 [Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, Calif 4150 Clement St, San Francisco, CA 94121 USA.
EM Yenari@alum.mit.edu
FU National Institutes of Health [NS40516]; Veteran's Merit Award; American
Heart Association; Uehara Foundation; Veterans Affairs Medical Center,
San Francisco, California
FX This work was supported by grants from the National Institutes of Health
(NS40516, to MY), the Veteran's Merit Award (MY), the American Heart
Association (to JYK), and the Uehara Foundation (2013 Research
Fellowship, to MK). Grants to MY and JYK were administered by the
Northern California Institute for Research and Education, and supported
by resources of the Veterans Affairs Medical Center, San Francisco,
California.
NR 351
TC 30
Z9 33
U1 2
U2 23
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD JUN
PY 2014
VL 21
IS 18
BP 2076
EP 2097
PG 22
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AF6UM
UT WOS:000334850100006
PM 24372209
ER
PT J
AU Bobo, WV
Reilly-Harrington, NA
Ketter, TA
Brody, BD
Kinrys, G
Kemp, DE
Shelton, RC
McElroy, SL
Sylvia, LG
Kocsis, JH
McInnis, MG
Friedman, ES
Singh, V
Tohen, M
Bowden, CL
Deckersbach, T
Calabrese, JR
Thase, ME
Nierenberg, AA
Rabideau, DJ
Schoenfeld, DA
Faraone, SV
Kamali, M
AF Bobo, William V.
Reilly-Harrington, Noreen A.
Ketter, Terence A.
Brody, Benjamin D.
Kinrys, Gustavo
Kemp, David E.
Shelton, Richard C.
McElroy, Susan L.
Sylvia, Louisa G.
Kocsis, James H.
McInnis, Melvin G.
Friedman, Edward S.
Singh, Vivek
Tohen, Mauricio
Bowden, Charles L.
Deckersbach, Thilo
Calabrese, Joseph R.
Thase, Michael E.
Nierenberg, Andrew A.
Rabideau, Dustin J.
Schoenfeld, David A.
Faraone, Stephen V.
Kamali, Masoud
TI Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or
quetiapine-treated outpatients with bipolar I or II disorder: Results
from the Bipolar CHOICE trial
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Benzodiazepines; Bipolar disorder; Lithium; Quetiapine; Clinical outcome
ID SEVERE MENTAL-ILLNESS; PRESCRIPTION; SCALE; ABUSE
AB Background: Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders.
Methods: The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-basecl treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses.
Results: Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders.
Limitations: This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use
Conclusions: Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar l or II disorder over 6 months, after controlling for potential confounding factors. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Bobo, William V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA.
[Reilly-Harrington, Noreen A.; Kinrys, Gustavo; Sylvia, Louisa G.; Deckersbach, Thilo; Nierenberg, Andrew A.; Rabideau, Dustin J.; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ketter, Terence A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Brody, Benjamin D.; Kocsis, James H.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
[Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Shelton, Richard C.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[McElroy, Susan L.] Univ Cincinnati, Coll Med, Lindner Ctr HOPE, Cincinnati, OH USA.
[McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Friedman, Edward S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Singh, Vivek; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Tohen, Mauricio] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Faraone, Stephen V.] SUNY Syracuse, Upstate Med Univ, Syracuse, NY USA.
RP Bobo, WV (reprint author), 200 First St SW,Generose 2A, Rochester, MN 55904 USA.
EM bobo.william@mayo.edu
OI Faraone, Stephen/0000-0002-9217-3982
FU AHRQ [R01 HS019371-01]; NIMH [MH087747]
FX This study was funded by AHRQ Grant R01 HS019371-01. Dr Bobo was
supported, in part, by NIMH Grant MH087747.
NR 17
TC 5
Z9 5
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JUN 1
PY 2014
VL 161
BP 30
EP 35
DI 10.1016/j.jad.2014.02.046
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AF5GE
UT WOS:000334741200006
PM 24751304
ER
PT J
AU Sheets, ES
Duncan, LE
Bjornsson, AS
Craighead, LW
Craighead, WE
AF Sheets, Erin S.
Duncan, Laramie E.
Bjornsson, Andri S.
Craighead, Linda W.
Craighead, W. Edward
TI Personality Pathology Factors Predict Recurrent Major Depressive
Disorder in Emerging Adults
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE personality disorders; depression; factor structure; Axis II pathology;
emerging adulthood
ID EARLY ADOLESCENT BOYS; CONDUCT PROBLEMS; YOUNG-ADULTS; INTERPERSONAL
STRESS; NATURAL COURSE; MENTAL-HEALTH; EARLY-ONSET; FOLLOW-UP; SYMPTOMS;
COMORBIDITY
AB Objective
Prior investigations consistently indicate that personality pathology is a risk factor for recurrence of major depressive disorder (MDD). Lack of emipircal support, however, for the Diagnostic and Statistical Manual of Mental Disorders (DSM) Fourth Edition organization of Axis II disorders supports the investigation of empirically derived factors of personality pathology as predictors of recurrence.
Method
A sample of 130 previously depressed emerging adults (80% female; aged 18 to 21 years) were assessed for personality disorder symptoms at baseline. Participants were then followed for 18 months to identify MDD recurrence during the first 2 years of college.
Results
Based on a previous factor analysis of DSM personality disorder criteria, eight personality pathology factors were examined as predictors of MDD recurrence. Survival analysis indicated that factors of interpersonal hypersensitivity, antisocial conduct, and social anxiety were associated with increased risk of MDD recurrence.
Conclusions
These findings suggest that an empirically based approach to personality pathology organization may yield useful predictors of MDD recurrence during emerging adulthood.
C1 [Sheets, Erin S.] Colby Coll, Waterville, ME 04901 USA.
[Duncan, Laramie E.] Harvard Univ, Sch Publ Hlth, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Bjornsson, Andri S.] Univ Iceland, IS-101 Reykjavik, Iceland.
[Craighead, Linda W.; Craighead, W. Edward] Emory Univ, Atlanta, GA 30322 USA.
RP Sheets, ES (reprint author), Colby Coll, Dept Psychol, 5550 Mayflower Hill, Waterville, ME 04901 USA.
EM essheets@colby.edu
FU NIMH NIH HHS [R21-MH-59629]
NR 48
TC 5
Z9 5
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9762
EI 1097-4679
J9 J CLIN PSYCHOL
JI J. Clin. Psychol.
PD JUN
PY 2014
VL 70
IS 6
BP 536
EP 545
DI 10.1002/jclp.22028
PG 10
WC Psychology, Clinical
SC Psychology
GA AF6TB
UT WOS:000334846400005
PM 23852879
ER
PT J
AU Stanford, FC
Durkin, MW
Stallworth, JR
Powell, CK
Poston, MB
Blair, SN
AF Stanford, Fatima Cody
Durkin, Martin W.
Stallworth, James Rast
Powell, Caroline Keller
Poston, Mary Beth
Blair, Steven N.
TI Factors that Influence Physicians' and Medical Students' Confidence in
Counseling Patients About Physical Activity
SO JOURNAL OF PRIMARY PREVENTION
LA English
DT Article
DE Physicians; Exercise; Medical students; Physician's role; United States
Department of Health and Human Services; Healthy people programs
ID PRIMARY-CARE PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; EXERCISE; HEALTH;
WEIGHT; ADVICE; PRESCRIPTION; BEHAVIORS; DOCTORS; FITNESS
AB Less than half of US adults and two-thirds of US high school students do not meet current US guidelines for physical activity. We examined which factors promoted physicians' and medical students' confidence in counseling patients about physical activity. We established an online exercise survey targeting attending physicians, resident and fellow physicians, and medical students to determine their current level of physical activity and confidence in counseling patients about physical activity. We compared their personal level of physical activity with the 2008 Physical Activity Guidelines of the US Department of Health and Human Services (USDHHS). We administered a survey in 2009 and 2010 that used the short form of the International Physical Activity Questionnaire. A total of 1,949 individuals responded to the survey, of whom 1,751 (i.e., 566 attending physicians, 138 fellow physicians, 806 resident physicians, and 215 medical students) were included in this analysis. After adjusting for their BMI, the odds that physicians and medical students who met USDHHS guidelines for vigorous activity would express confidence in their ability to provide exercise counseling were more than twice that of physicians who did not meet these guidelines. Individuals who were overweight were less likely to be confident than those with normal BMI, after adjusting for whether they met the vigorous exercise guidelines. Physicians with obesity were even less likely to express confidence in regards to exercise counseling. We conclude that physicians and medical students who had a normal BMI and met vigorous USDHHS guidelines were more likely to feel confident about counseling their patients about physical activity. Our findings suggest that graduate medical school education should focus on health promotion in their students, as this will likely lead to improved health behaviors in their students' patient populations.
C1 [Stanford, Fatima Cody] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Durkin, Martin W.] Palmetto Hlth Richland Res Adm, Columbia, SC USA.
[Stallworth, James Rast; Powell, Caroline Keller; Poston, Mary Beth] Univ S Carolina, Sch Med, Palmetto Hlth Richland, Columbia, SC USA.
[Blair, Steven N.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
RP Stanford, FC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,4th Floor, Boston, MA 02114 USA.
EM fstanford@mgh.harvard.edu
OI Stanford, Fatima/0000-0003-4616-533X
NR 34
TC 5
Z9 5
U1 2
U2 23
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0278-095X
EI 1573-6547
J9 J PRIM PREV
JI J. Prim. Prev.
PD JUN
PY 2014
VL 35
IS 3
BP 193
EP 201
DI 10.1007/s10935-014-0345-4
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AF8AW
UT WOS:000334938400006
PM 24682887
ER
PT J
AU Sharma, J
Gray, KP
Harshman, LC
Evan, C
Nakabayashi, M
Fichorova, R
Rider, J
Mucci, L
Kantoff, PW
Sweeney, CJ
AF Sharma, Jaya
Gray, Kathryn P.
Harshman, Lauren C.
Evan, Carolyn
Nakabayashi, Mari
Fichorova, Raina
Rider, Jennifer
Mucci, Lorelei
Kantoff, Philip W.
Sweeney, Christopher J.
TI Elevated IL-8, TNF-alpha, and MCP-1 in men with metastatic prostate
cancer starting androgen-deprivation therapy (ADT) are associated with
shorter time to castration-resistance and overall survival
SO PROSTATE
LA English
DT Article
DE prostate cancer; TNF-alpha and MCP-1; inflammation; elevated IL-8
ID NF-KAPPA-B; INTRAEPITHELIAL NEOPLASIA; RANDOMIZED-TRIAL; INTERLEUKIN-6;
ACTIVATION; TARGET; GROWTH; CARCINOGENESIS; PARTHENOLIDE; SUPPRESSION
AB BACKGROUND
Chemokines and cytokines have been implicated in progression to castration-resistant prostate cancer (CRPC).
METHODS
Retrospective data were accessed from 122 men with serum samples drawn at a median of 0.5 months after starting ADT for metastatic prostate cancer. MCP-1, IL-1-beta, IL-2, IL-8, IL-6, and TNF-alpha levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to CRPC and overall survival by the protein levels and adjusted for clinical variables (age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and extent of metastases). Associations were reported as hazard ratio (HR) with 95% confidence interval (CI).
RESULTS
Median follow-up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (>= 1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1-7.0), P = 0.03], and PSA nadir < 0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2-0.5), P < 0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI: 0.9, 2.2, P = 0.13) for IL-8; 1.3 (95% CI: 0.8, 2, P = 0.18) for TNF-alpha; 1.0 (95% CI: 0.7, 1.6, P = 0.95) for MCP-1. The HR for median overall survival for protein levels above the median was: 1.9 (95% CI: 1.0, 3.5, P = 0.04) for IL-8; 2.0 (95% CI: 1.1, 3.5, P = 0.02) for TNF-alpha; 1.7 (95% CI: 1.7, 3.0, P = 0.08) for MCP-1. There was no association with IL-1-beta, IL-2, or IL-6.
CONCLUSION
Higher levels of inflammation-associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy. Prostate 74:820-828, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [Sharma, Jaya; Harshman, Lauren C.; Evan, Carolyn; Nakabayashi, Mari; Kantoff, Philip W.; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Gray, Kathryn P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Gray, Kathryn P.; Rider, Jennifer; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Harshman, Lauren C.; Fichorova, Raina; Kantoff, Philip W.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Fichorova, Raina; Rider, Jennifer] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Sweeney, Christopher J.] Hoosier Oncol Grp, Indianapolis, IN USA.
RP Sweeney, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02215 USA.
EM christopher_sweeney@dfci.harvard.edu
RI Fichorova, Raina/G-9969-2014
NR 39
TC 17
Z9 17
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD JUN
PY 2014
VL 74
IS 8
BP 820
EP 828
DI 10.1002/pros.22788
PG 9
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA AF7KK
UT WOS:000334893800003
PM 24668612
ER
PT J
AU Chang, CNY
Huang, AJ
Bredella, MA
Kattapuram, SV
Torriani, M
AF Chang, Connie Y.
Huang, Ambrose J.
Bredella, Miriam A.
Kattapuram, Susan V.
Torriani, Martin
TI Association between distal ulnar morphology and extensor carpi ulnaris
tendon pathology
SO SKELETAL RADIOLOGY
LA English
DT Article
DE Wrist; Extensor carpi ulnaris; Ulna; Ulnar variance
ID TRIANGULAR FIBROCARTILAGE COMPLEX; ULNOCARPAL IMPACTION SYNDROME;
VARIANCE; FOREARM; ARTHROGRAPHY
AB The purpose of this study was to evaluate the association between distal ulnar morphology and extensor carpi ulnaris (ECU) tendon pathology.
We retrospectively reviewed 71 adult wrist MRI studies with ECU tendon pathology (tenosynovitis, tendinopathy, or tear), and/or ECU subluxation. Subjects did not have a history of trauma, surgery, infection, or inflammatory arthritis. MRI studies from 46 subjects without ECU tendon pathology or subluxation were used as controls. The following morphological parameters of the distal ulna were measured independently by two readers: ulnar variance relative to radius, ulnar styloid process length, ECU groove depth and length. Subjects and controls were compared using Student's t test. Inter-observer agreement (ICC) was calculated.
There was a significant correlation between negative ulnar variance and ECU tendon pathology (reader 1 [R1], P = 0.01; reader 2 [R2], P < 0.0001; R1 and R2 averaged data, P < 0.0001) and ECU tendon subluxation (P = 0.001; P = 0.0001; P < 0.0001). In subjects with ECU tendon subluxation there was also a trend toward a shorter length (P = 0.3; P < 0.0001; P = 0.001) and a shallower ECU groove (P = 0.01; P = 0.03; P = 0.01; R1 and R2 averaged data with Bonferroni correction, P = 0.08). ECU groove depth (P = 0.6; P = 0.8; P = 0.9) and groove length (P = 0.1; P = 0.4; P = 0.7) showed no significant correlation with ECU tendon pathology, and length of the ulnar styloid process showed no significant correlation with ECU tendon pathology (P = 0.2; P = 0.3; P = 0.2) or subluxation (P = 0.4; P = 0.5; P = 0.5). Inter-observer agreement (ICC) was > 0.64 for all parameters.
Distal ulnar morphology may be associated with ECU tendon abnormalities.
C1 [Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Kattapuram, Susan V.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA.
[Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Kattapuram, Susan V.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA USA.
RP Chang, CNY (reprint author), 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
EM cychang@mgh.harvard.edu
NR 25
TC 4
Z9 4
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
EI 1432-2161
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD JUN
PY 2014
VL 43
IS 6
BP 793
EP 800
DI 10.1007/s00256-014-1845-2
PG 8
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA AF8AY
UT WOS:000334938600007
PM 24595441
ER
PT J
AU Baik, SH
Cha, MY
Hyun, YM
Cho, H
Hamza, B
Kim, DK
Han, SH
Choi, H
Kim, KH
Moon, M
Lee, J
Kim, M
Irimia, D
Mook-Jung, I
AF Baik, Sung Hoon
Cha, Moon-Yong
Hyun, Young-Min
Cho, Hansang
Hamza, Bashar
Kim, Dong Kyu
Han, Sun-Ho
Choi, Heesun
Kim, Kyung Ho
Moon, Minho
Lee, Jeewoo
Kim, Minsoo
Irimia, Daniel
Mook-Jung, Inhee
TI Migration of neutrophils targeting amyloid plaques in Alzheimer's
disease mouse model
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Neutrophils; Amyloid plaques; Immune cells
ID INNATE IMMUNE-RESPONSE; TRANSGENIC MICE; BETA; BRAIN; NEURODEGENERATION;
MICROGLIA; SYSTEM
AB Immune responses in the brain are thought to play a role in disorders of the central nervous system, but an understanding of the process underlying how immune cells get into the brain and their fate there remains unclear. In this study, we used a 2-photon microscopy to reveal that neutrophils infiltrate brain and migrate toward amyloid plaques in a mouse model of Alzheimer's disease. These findings suggest a new molecular process underlying the pathophysiology of Alzheimer's disease. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Baik, Sung Hoon; Cha, Moon-Yong; Kim, Dong Kyu; Han, Sun-Ho; Choi, Heesun; Kim, Kyung Ho; Moon, Minho; Kim, Minsoo; Mook-Jung, Inhee] Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, Seoul 110799, South Korea.
[Hyun, Young-Min; Kim, Minsoo] Univ Rochester, David H Smith Ctr Vaccine Biol & Immunol, Dept Microbiol & Immunol, Rochester, NY USA.
[Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Dept Pharmacol, Seoul, South Korea.
[Cho, Hansang; Hamza, Bashar; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA.
RP Mook-Jung, I (reprint author), Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, 103 Daehak Ro, Seoul 110799, South Korea.
EM inhee@snu.ac.kr
OI Irimia, Daniel/0000-0001-7347-2082
FU National Research Foundation of Korea [2012R1A2A1A01002881, MRC
[2011-0030738]]; Korea National Institute of Health ROAD R&D Program
Project [A092058]; Korea Institute of Science and Technology
Institutional Program [2E24242- 13e135]; Cooperative Research Program
for Agriculture Science & Technology Development [PJ009103]
FX This work was supported by grants from the National Research Foundation
of Korea (2012R1A2A1A01002881, MRC [2011-0030738]); the Korea National
Institute of Health ROAD R&D Program Project (A092058), Korea Institute
of Science and Technology Institutional Program (2E24242-13-135) for
Inhee Mook-Jung, and the Cooperative Research Program for Agriculture
Science & Technology Development (PJ009103) for Kyung Ho Kim.
NR 18
TC 22
Z9 22
U1 1
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
BP 1286
EP 1292
DI 10.1016/j.neurobiolaging.2014.01.003
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800008
PM 24485508
ER
PT J
AU Coutu, JP
Chen, JJ
Rosas, HD
Salat, DH
AF Coutu, Jean-Philippe
Chen, J. Jean
Rosas, H. Diana
Salat, David H.
TI Non-Gaussian water diffusion in aging white matter
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE MRI; Diffusional kurtosis imaging; Diffusion tensor imaging; Aging;
White matter integrity; Region-of-interest analysis; Tract-based spatial
statistics; K-means clustering; Multivariate analysis
ID SPATIAL STATISTICS; CLINICAL-APPLICATIONS; ALZHEIMERS-DISEASE; VOXELWISE
ANALYSIS; NERVOUS-SYSTEM; BRAIN; KURTOSIS; MRI; INTEGRITY; DECLINE
AB Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Coutu, Jean-Philippe; Chen, J. Jean; Rosas, H. Diana; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA.
[Coutu, Jean-Philippe] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA.
[Chen, J. Jean; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Rosas, H. Diana] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA.
RP Coutu, JP (reprint author), MIT, Div Hlth Sci & Technol, Bldg E25-518,77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM coutu@nmr.mgh.harvard.edu
OI /0000-0003-4895-5642
FU National Institutes of Health [R01NR010827, NS042861, NS058793]; Center
for Functional Neuroimaging Technologies [P41RR14075]; Biomedical
Technology Program of the National Center for Research Resources (NCRR);
National Institutes of Health; NCRR Shared Instrumentation Grant Program
and/or High-End Instrumentation Grant Program [S10RR021110, S10RR023401,
S10RR019307, S10RR019254, S10RR023043]; Advanced Multimodal Neuroimaging
Training Program at the MGH/HST Athinoula A. Martinos Center for
Biomedical Imaging [2T90DA022759]; Natural Sciences and Engineering
Research Council of Canada; Fonds Quebecois de la Recherche sur la
Nature et les Technologies
FX This study was funded by the National Institutes of Health grants
R01NR010827, NS042861, NS058793 and was carried out at the Athinoula A.
Martinos Center for Biomedical Imaging at the Massachusetts General
Hospital, using resources provided by the Center for Functional
Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported
by the Biomedical Technology Program of the National Center for Research
Resources (NCRR), National Institutes of Health. This work also involved
the use of instrumentation supported by the NCRR Shared Instrumentation
Grant Program and/or High-End Instrumentation Grant Program;
specifically, grant numbers S10RR021110, S10RR023401, S10RR019307,
S10RR019254, and S10RR023043. J.P.C. was funded by the Advanced
Multimodal Neuroimaging Training Program (2T90DA022759; P.I. Bruce
Rosen) at the MGH/HST Athinoula A. Martinos Center for Biomedical
Imaging, the Natural Sciences and Engineering Research Council of Canada
and the Fonds Quebecois de la Recherche sur la Nature et les
Technologies.
NR 55
TC 27
Z9 29
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
BP 1412
EP 1421
DI 10.1016/j.neurobiolaging.2013.12.001
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800022
PM 24378085
ER
PT J
AU Gin, JL
Stein, JA
Heslin, KC
Dobalian, A
AF Gin, June L.
Stein, Judith A.
Heslin, Kevin C.
Dobalian, Aram
TI Responding to risk: Awareness and action after the September 11, 2001
terrorist attacks
SO SAFETY SCIENCE
LA English
DT Article
DE Emergency preparedness; Terrorism; Social psychology; Pre-disposing
factors; Disaster planning; Cognitive awareness
ID INDIVIDUAL-RESPONSE; PREPAREDNESS; PERSPECTIVE; CANADA; HAZARD; STATES;
MODEL
AB Adoption of preparedness measures among the US public remains low after the expansion of the all-hazards approach to personal preparedness campaigns following the terrorist attacks of September 11, 2001 (9/11). This study sought to understand factors influencing preparedness behavior, particularly how demographics might influence preparedness behavior and whether preparedness actions are related to preparedness attitudes and related behaviors that may prime individuals to take these actions. Using data from the 2008 General Social Survey (n = 1338), we tested a conceptual path model of preparedness that includes demographic variables and three latent variables as mediators of the effects of demographics on preparedness: Cognitive Preparedness; Peer Group Behavior Awareness, and Perceived Effectiveness. The model explains 65% of the variance in preparedness behavior. It suggests that the effects of demographic factors on preparedness actually reflect indirect relationships mediated by predisposing attitudes, behaviors and experiences, specifically, Cognitive Preparedness, Peer Group Behavior Awareness, and Perceived Effectiveness that predispose individuals toward taking preparedness actions. Because these social and cognitive factors reflect behaviors that, unlike fixed demographics, can be shaped by public education programs, efforts to increase public preparedness should focus on improving public awareness, social networks, and more persuasive messaging as keys to increasing preparedness behavior among the US public. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Gin, June L.; Stein, Judith A.; Heslin, Kevin C.; Dobalian, Aram] US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, North Hills, CA 91343 USA.
[Heslin, Kevin C.; Dobalian, Aram] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
[Dobalian, Aram] UCLA Sch Nursing, Los Angeles, CA USA.
RP Gin, JL (reprint author), US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, 16111 Plummer St,MS-152, North Hills, CA 91343 USA.
EM june.gin@va.gov; jastein@ucla.edu; kevin.heslin@va.gov;
aram.dobalian@va.gov
FU US Department of Veterans Affairs, Veterans Health Administration,
Office of Public Health
FX This material is based on work supported by the US Department of
Veterans Affairs, Veterans Health Administration, Office of Public
Health. The views expressed in this article are those of the authors and
do not necessarily reflect the position or policy of the US Department
of Veterans Affairs or the US government. The authors thank Michael N.
Mitchell for statistical consulting assistance provided on the GSS data
set.
NR 35
TC 1
Z9 1
U1 4
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-7535
EI 1879-1042
J9 SAFETY SCI
JI Saf. Sci.
PD JUN
PY 2014
VL 65
BP 86
EP 92
DI 10.1016/j.ssci.2014.01.001
PG 7
WC Engineering, Industrial; Operations Research & Management Science
SC Engineering; Operations Research & Management Science
GA AD8JQ
UT WOS:000333512700011
ER
PT J
AU Prashanth, R
Roy, SD
Mandal, PK
Ghosh, S
AF Prashanth, R.
Roy, Sumantra Dutta
Mandal, Pravat K.
Ghosh, Shantanu
TI Automatic classification and prediction models for early Parkinson's
disease diagnosis from SPECT imaging
SO EXPERT SYSTEMS WITH APPLICATIONS
LA English
DT Article
DE Computer-aided early diagnosis; Parkinson's disease; Risk prediction;
Pattern analysis; Support vector machine; Logistic regression
ID ESSENTIAL TREMOR; LOGISTIC-REGRESSION; DOPAMINERGIC SYSTEM; FOLLOW-UP;
SWEDDS; IMAGES; SCANS
AB Early and accurate diagnosis of Parkinson's disease (PD) is important for early management, proper prognostication and for initiating neuroprotective therapies once they become available. Recent neuroimaging techniques such as dopaminergic imaging using single photon emission computed tomography (SPECT) with I-123-Ioflupane (DaTSCAN) have shown to detect even early stages of the disease. In this paper, we use the striatal binding ratio (SBR) values that are calculated from the I-123-loflupane SPECT scans (as obtained from the Parkinson's progression markers initiative (PPMI) database) for developing automatic classification and prediction/prognostic models for early PD. We used support vector machine (SVM) and logistic regression in the model building process. We observe that the SVM classifier with RBF kernel produced a high accuracy of more than 96% in classifying subjects into early PD and healthy normal; and the logistic model for estimating the risk of PD also produced high degree of fitting with statistical significance indicating its usefulness in PD risk estimation. Hence, we infer that such models have the potential to aid the clinicians in the PD diagnostic process. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Prashanth, R.; Roy, Sumantra Dutta] Indian Inst Technol Delhi, Dept Elect Engn, Delhi, India.
[Mandal, Pravat K.] Natl Brain Res Ctr, Neurospect & Neuroimaging Lab, Gurgaon, Haryana, India.
[Mandal, Pravat K.] Johns Hopkins Med, Dept Radiol, Baltimore, MD USA.
[Ghosh, Shantanu] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Ghosh, Shantanu] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Prashanth, R (reprint author), Indian Inst Technol Delhi, Dept Elect Engn, Delhi, India.
EM eez108051@ee.iitd.ac.in
RI MANDAL, PRAVAT/C-3705-2009
FU Michael J. Fox Foundation
FX PPMI - a public-private partnership - is funded by the Michael J. Fox
Foundation for Parkinson's Research and funding partners, including
[list of all of the PPMI funding partners found at
www.ppmi-info.org/fundingpartners].
NR 36
TC 19
Z9 19
U1 2
U2 42
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0957-4174
EI 1873-6793
J9 EXPERT SYST APPL
JI Expert Syst. Appl.
PD JUN 1
PY 2014
VL 41
IS 7
BP 3333
EP 3342
DI 10.1016/j.eswa.2013.11.031
PG 10
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic; Operations Research & Management Science
SC Computer Science; Engineering; Operations Research & Management Science
GA AA3UM
UT WOS:000331019800018
ER
PT J
AU Yoo, B
Ghosh, SK
Kumar, M
Moore, A
Yigit, MV
Medarova, Z
AF Yoo, Byunghee
Ghosh, Subrata K.
Kumar, Mohanraja
Moore, Anna
Yigit, Mehmet V.
Medarova, Zdravka
TI Design of Nanodrugs for miRNA Targeting in Tumor Cells
SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
LA English
DT Article
DE Gene Silencing; Microrna; Locked Nucleic Acids; Integrin Specific
Peptide; Iron Oxide Nanoparticles; Delivery Vehicle
ID MAGNETIC NANOPARTICLES; SIRNA DELIVERY; MICRORNAS; BIOGENESIS; CANCER
AB The delivery of oligonucleotide antagonists to cytosolic RNA targets such as microRNA represents an avenue for the post-transcriptional control of cellular phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked to processes that ultimately determine cancer initiation, progression, and response to therapy. Therefore, the capacity to redirect tumor cell fate towards therapeutically beneficial phenotypes holds promise in a future clinical scenario. Previously, we have designed "nanodrugs" for the specific inhibition of oncogenic microRNAs in tumor cells. The basic design of these nanodrugs includes dextran coated iron oxide nanoparticles, conjugated to a tumor-targeting peptide, and a locked nucleic acid (LNA)-modified antisense oligonucleotide that stably binds and inhibits the complementary mature miRNA. Here, we focus on elucidating an optimal nanodrug design for effective miRNA inhibition in tumor cells. Specifically, we investigate the choice of chemical linker for the conjugation of the oligonucleotide to the nanoparticles and evaluate the contribution of tumor-cell targeting to nanodrug uptake and functionality. We find that short labile linkers (SPDP; N-Succinimidyl 3-(2-pyridyldithio)-propionate) are superior to non-labile short linkers (GMBS; N-(gamma-Maleimidobutyryloxy)succinimide ester) or non-labile long linkers (PEG24; Succinimidyl-([N-maleimidopropionamido]-24ethyleneglycol)ester) in terms of their capacity to gain access to the cytosolic cellular compartment and to engage their cognate miRNA. Furthermore, using the nanodrug design that incorporates SPDP as a linker, we establish that the addition of tumor-cell targeting through functionalization of the nanodrug with the alpha v beta 3-specific cyclic RGDfK-PEG peptide does not confer an advantage in vitro at long incubation times required for inhibition.
C1 Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Yigit, MV (reprint author), SUNY Albany, Dept Chem, RNA Inst, 1400 Washington Ave, Albany, NY 12222 USA.
EM myigit@albany.edu; zmedarova@partners.org
FU NIH [NCIR00CA129070, NCI-1R01CA163461-01A1]; Breast Cancer Alliance
FX This work was supported by grants NCIR00CA129070 and
NCI-1R01CA163461-01A1 to ZM by the NIH and the Young Investigator Award
to ZM by the Breast Cancer Alliance.
NR 27
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U1 1
U2 108
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1550-7033
EI 1550-7041
J9 J BIOMED NANOTECHNOL
JI J. Biomed. Nanotechnol.
PD JUN
PY 2014
VL 10
IS 6
BP 1114
EP 1122
DI 10.1166/jbn.2014.1795
PG 9
WC Nanoscience & Nanotechnology; Materials Science, Biomaterials
SC Science & Technology - Other Topics; Materials Science
GA 276DX
UT WOS:000328729400020
PM 24749405
ER
PT J
AU Imamura, Y
Lochhead, P
Yamauchi, M
Kuchiba, A
Qian, ZR
Liao, XY
Nishihara, R
Jung, SY
Wu, KN
Nosho, K
Wang, YE
Peng, SY
Bass, AJ
Haigis, KM
Meyerhardt, JA
Chan, AT
Fuchs, CS
Ogino, S
AF Imamura, Yu
Lochhead, Paul
Yamauchi, Mai
Kuchiba, Aya
Qian, Zhi Rong
Liao, Xiaoyun
Nishihara, Reiko
Jung, Seungyoun
Wu, Kana
Nosho, Katsuhiko
Wang, Yaoyu E.
Peng, Shouyong
Bass, Adam J.
Haigis, Kevin M.
Meyerhardt, Jeffrey A.
Chan, Andrew T.
Fuchs, Charles S.
Ogino, Shuji
TI Analyses of clinicopathological, molecular, and prognostic associations
of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort
study and literature review
SO MOLECULAR CANCER
LA English
DT Review
DE Clinical outcome; Colon cancer; Genetic change; RAF; RAS
ID ISLAND METHYLATOR PHENOTYPE; RAS GENE-MUTATIONS; CETUXIMAB PLUS
IRINOTECAN; ADVANCED RECTAL-CANCER; K-RAS; COLON-CANCER; MICROSATELLITE
INSTABILITY; 1ST-LINE TREATMENT; BRAF MUTATIONS; WILD-TYPE
AB Background: KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear.
Methods: We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse's Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI.
Results: KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation].
Conclusions: Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion (approximately 5%) of colorectal cancers, and their clinicopathological and molecular features appear generally similar to KRAS codon 12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and 146 testing, large-scale trials are warranted.
C1 [Imamura, Yu; Lochhead, Paul; Yamauchi, Mai; Kuchiba, Aya; Qian, Zhi Rong; Liao, Xiaoyun; Nishihara, Reiko; Peng, Shouyong; Bass, Adam J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Imamura, Yu; Lochhead, Paul; Yamauchi, Mai; Kuchiba, Aya; Qian, Zhi Rong; Liao, Xiaoyun; Nishihara, Reiko; Peng, Shouyong; Bass, Adam J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Aberdeen, Scotland.
[Kuchiba, Aya; Nishihara, Reiko; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Jung, Seungyoun; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Nosho, Katsuhiko] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan.
[Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA.
[Bass, Adam J.] Broad Inst & Harvard, Canc Program, Cambridge, MA USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA.
EM shuji_ogino@dfci.harvard.edu
FU U.S. National Institute of Health (NIH) [P01 CA87969, P01 CA55075, UM1
CA167552, P50 CA127003, R01 CA137178, R01 CA151993]; Bennett Family
Fund; Entertainment Industry Foundation through National Colorectal
Cancer Research Alliance; Harvard University Frank Knox Memorial
Fellowship
FX We deeply thank hospitals and pathology departments throughout the U.S.
for generously providing us with tissue specimens. In addition, we would
like to thank the participants and staff of the Nurses' Health Study and
the Health Professionals Follow-Up Study, for their valuable
contributions as well as the following state cancer registries for their
help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME,
MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA,
WA, WY. This work was supported by U.S. National Institute of Health
(NIH) grants [P01 CA87969 to S. E. Hankinson; P01 CA55075 to W. C.
Willett; UM1 CA167552 to W. C. Willett; P50 CA127003 to CSF; R01
CA137178 to ATC; and R01 CA151993 to SO]; and by grants from the Bennett
Family Fund and the Entertainment Industry Foundation through National
Colorectal Cancer Research Alliance. ATC is a Damon Runyon Clinical
Investigator. PL is a Scottish Government Clinical Academic Fellow and
was supported by a Harvard University Frank Knox Memorial Fellowship.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of NIH. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 94
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U1 3
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD MAY 31
PY 2014
VL 13
AR 135
DI 10.1186/1476-4598-13-135
PG 15
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA AK2OC
UT WOS:000338257900004
PM 24885062
ER
PT J
AU Vergallo, R
Jia, HB
Soeda, T
Tian, JW
Jang, IK
AF Vergallo, Rocco
Jia, Haibo
Soeda, Tsunenari
Tian, Jinwei
Jang, Ik-Kyung
TI Interpretation of optical coherence tomography images
SO LANCET
LA English
DT Letter
ID PLAQUE
C1 [Vergallo, Rocco; Jia, Haibo; Soeda, Tsunenari; Tian, Jinwei; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
[Jia, Haibo; Tian, Jinwei] Harbin Med Univ, Key Lab Myocardial Ischemia, Affiliated Hosp 2, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China.
RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
EM ijang@partners.org
NR 3
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAY 31
PY 2014
VL 383
IS 9932
BP 1887
EP 1887
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4PR
UT WOS:000336847800025
PM 24881991
ER
PT J
AU Colicino, E
Power, MC
Cox, DG
Weisskopf, MG
Hou, LF
Alexeeff, SE
Sanchez-Guerra, M
Vokonas, P
Spiro, A
Schwartz, J
Baccarelli, AA
AF Colicino, Elena
Power, Melinda C.
Cox, David G.
Weisskopf, Marc G.
Hou, Lifang
Alexeeff, Stacy E.
Sanchez-Guerra, Marco
Vokonas, Pantel
Spiro, Avron, III
Schwartz, Joel
Baccarelli, Andrea A.
TI Mitochondrial haplogroups modify the effect of black carbon on
age-related cognitive impairment
SO ENVIRONMENTAL HEALTH
LA English
DT Article
DE mtDNA haplogroups; Air pollution; Black carbon; Cognitive decline;
Mini-mental state examination
ID AIR-POLLUTION; ULTRAFINE PARTICLES; DNA HAPLOGROUPS; HUMAN MTDNA;
EXPOSURE; DISEASE; TREE; MEN
AB Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution.
Methods: We investigated 582 older men (72 +/- 7 years) in the VA Normative Aging Study cohort with = 4 visits per participant (1.8 in average) between 1995-2007. Low (<= 25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant's address.
Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups.
Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects.
C1 [Colicino, Elena; Power, Melinda C.; Weisskopf, Marc G.; Alexeeff, Stacy E.; Sanchez-Guerra, Marco; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Power, Melinda C.; Weisskopf, Marc G.; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Cox, David G.] Ctr Rech Canc Lyon, INSERM, U1052, F-69008 Lyon, France.
[Cox, David G.] Pole Rech Translat Lyon, Ctr Lyon Berard, F-69008 Lyon, France.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02118 USA.
[Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA.
RP Colicino, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM ecolicin@hsph.harvard.edu
RI Cox, David/A-2023-2009; Colicino, Elena/Q-4973-2016;
OI Cox, David/0000-0002-2152-9259; Colicino, Elena/0000-0002-1875-8448;
Baccarelli, Andrea/0000-0002-3436-0640
FU National Institute of Environmental Health Sciences (NIEHS)
[R01ES021733]; NIEHS [ES015172, ES014663, ES020010, T32 ES007069];
Environmental Protection Agency (EPA) [RD832416]; Cooperative Studies
Program/ERIC, US Department of Veterans Affairs; VA Merit Review; CSR&D
Research Career Scientist award; US Department of Agriculture,
Agricultural Research Service [53-K06-510]; National Institute of Aging
(NIA) [F31 AG038233]
FX EC is supported by a grant from the National Institute of Environmental
Health Sciences (NIEHS) (R01ES021733). Other support comes from NIEHS
grants ES015172, ES014663 and ES020010, and Environmental Protection
Agency (EPA) grant RD832416. The US Department of Veterans Affairs (VA)
Normative Aging Study (NAS) is supported by the Cooperative Studies
Program/ERIC, US Department of Veterans Affairs, and is a research
component of the Massachusetts Veterans Epidemiology Research and
Information Center (MAVERIC). Cognitive data collection at the VA NAS
was supported by a VA Merit Review and a CSR&D Research Career Scientist
award to AS. The views expressed in this paper are those of the authors
and do not necessarily represent the views of the US Department of
Veterans Affairs. Additional support was provided by the US Department
of Agriculture, Agricultural Research Service (contract 53-K06-510). MCP
was supported by grants from the NIEHS (T32 ES007069) and National
Institute of Aging (NIA) (F31 AG038233).
NR 28
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U1 3
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD MAY 30
PY 2014
VL 13
AR 42
DI 10.1186/1476-069X-13-42
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA AJ0CU
UT WOS:000337317700001
PM 24884505
ER
PT J
AU Ichinose, F
AF Ichinose, Fumito
TI H2S in sepsis and shock - A story of mice and men
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Meeting Abstract
CT 3rd International Conference on H2S Biology and Medicine
CY JUN 04-06, 2014
CL Kyoto, JAPAN
SP Antibe Therapeut Inc, Sulfagenix, Inc, Fondazione Int Menarini, Asahi Kasei Pharma Corp, Kobayashi Pharmaceut Co, Ltd, Noevir Holdings Co, Ltd
C1 [Ichinose, Fumito] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
EI 1089-8611
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD MAY 30
PY 2014
VL 39
SU 1
BP S4
EP S4
DI 10.1016/j.niox.2014.03.014
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH7UL
UT WOS:000336340700012
ER
PT J
AU Kakinohana, M
Kida, K
Ichinose, F
AF Kakinohana, Manabu
Kida, Kotaro
Ichinose, Fumito
TI Inhaled hydrogen sulfide can prevent delayed neuronal death after spinal
cord ischemia in mice
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Meeting Abstract
CT 3rd International Conference on H2S Biology and Medicine
CY JUN 04-06, 2014
CL Kyoto, JAPAN
SP Antibe Therapeut Inc, Sulfagenix, Inc, Fondazione Int Menarini, Asahi Kasei Pharma Corp, Kobayashi Pharmaceut Co, Ltd, Noevir Holdings Co, Ltd
C1 [Kakinohana, Manabu] Univ Ryukyus, Dept Anesthesiol, Nishihara, Okinawa 90301, Japan.
[Kida, Kotaro; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
EI 1089-8611
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD MAY 30
PY 2014
VL 39
SU 1
BP S28
EP S28
DI 10.1016/j.niox.2014.03.089
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH7UL
UT WOS:000336340700086
ER
PT J
AU Finkelstein, DM
Schoenfeld, DA
AF Finkelstein, Dianne M.
Schoenfeld, David A.
TI A joint test for progression and survival with interval-censored data
from a cancer clinical trial
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Conditional Expected Score Test (CEST); progression-free survival (PFS);
PRO logistic model; interval-censored failure time data
ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME DATA; EM ALGORITHM;
RANDOMIZED-TRIAL; BREAST-CANCER; TAMOXIFEN; LETROZOLE; THERAPY; EVENT
AB Clinical trials often assess efficacy by comparing treatments on the basis of two or more event-time outcomes. In the case of cancer clinical trials, progression-free survival (PFS), which is the minimum of the time from randomization to progression or to death, summarizes the comparison of treatments on the hazards for disease progression and mortality. However, the analysis of PFS does not utilize all the information we have on patients in the trial. First, if both progression and death times are recorded, then information on death time is ignored in the PFS analysis. Second, disease progression is monitored at regular clinic visits, and progression time is recorded as the first visit at which evidence of progression is detected. However, many patients miss or have irregular visits (resulting in interval-censored data) and sometimes die of the cancer before progression was recorded. In this case, the previous progression-free time could provide additional information on the treatment efficacy. The aim of this paper is to propose a method for comparing treatments that could more fully utilize the data on progression and death. We develop a test for treatment effect based on of the joint distribution of progression and survival. The issue of interval censoring is handled using the very simple and intuitive approach of the Conditional Expected Score Test (CEST). We focus on the application of these methods in cancer research. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Finkelstein, Dianne M.] Harvard Univ, Biostat Unit, Boston, MA 02114 USA.
RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA.
EM dfinkelstein@mgh.harvard.edu
FU Avon Foundation; NIH [CA167570, UL1RR025758, CA160233]
FX We wish to thank Dr. Paul Goss for allowing us to use the MA 17 data.
This work was partially funded by grants from the Avon Foundation and
from the NIH: CA167570, UL1RR025758, and CA160233.
NR 18
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 30
PY 2014
VL 33
IS 12
BP 1981
EP 1989
DI 10.1002/sim.6096
PG 9
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AG8PO
UT WOS:000335680900001
PM 24500790
ER
PT J
AU Brown, JR
Byrd, JC
Coutre, SE
Benson, DM
Flinn, IW
Wagner-Johnston, ND
Spurgeon, SE
Kahl, BS
Bello, C
Webb, HK
Johnson, DM
Peterman, S
Li, D
Jahn, TM
Lannutti, BJ
Ulrich, RG
Yu, AS
Miller, LL
Furman, RR
AF Brown, Jennifer R.
Byrd, John C.
Coutre, Steven E.
Benson, Don M.
Flinn, Ian W.
Wagner-Johnston, Nina D.
Spurgeon, Stephen E.
Kahl, Brad S.
Bello, Celeste
Webb, Heather K.
Johnson, Dave M.
Peterman, Sissy
Li, Daniel
Jahn, Thomas M.
Lannutti, Brian J.
Ulrich, Roger G.
Yu, Albert S.
Miller, Langdon L.
Furman, Richard R.
TI Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110 delta,
for relapsed/refractory chronic lymphocytic leukemia
SO BLOOD
LA English
DT Article
ID B-CELL MALIGNANCIES; CLINICAL ACTIVITY; FLUDARABINE; RITUXIMAB;
LYMPHOMA; LENALIDOMIDE; ACTIVATION; CAL-101; PATHWAY; PI3K
AB In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3K delta, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3K delta led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade >= 3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kd pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.
C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Byrd, John C.; Benson, Don M.] Ohio State Univ, Columbus, OH 43210 USA.
[Coutre, Steven E.] Stanford Univ, Stanford, CA 94305 USA.
[Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA.
[Wagner-Johnston, Nina D.] Washington Univ, St Louis, MO USA.
[Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Kahl, Brad S.] Univ Wisconsin, Madison, WI USA.
[Bello, Celeste] H Lee Moffitt Canc Ctr & Res Inst, Seattle, WA USA.
[Webb, Heather K.; Johnson, Dave M.; Peterman, Sissy; Li, Daniel; Jahn, Thomas M.; Lannutti, Brian J.; Ulrich, Roger G.; Yu, Albert S.; Miller, Langdon L.] Gilead Sci Inc, Seattle, WA USA.
[Furman, Richard R.] Weill Cornell Med Coll, New York, NY USA.
RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Jennifer_brown@dfci.harvard.edu
FU Gilead Sciences, Inc (Foster City, CA); Gilead Sciences, Inc (Seattle,
WA); Calistoga Pharmaceuticals, Inc (Seattle, WA)
FX This study was sponsored and funded by Gilead Sciences, Inc (Foster
City, CA and Seattle, WA), and by Calistoga Pharmaceuticals, Inc
(Seattle, WA) (now a wholly owned subsidiary of Gilead Sciences, Inc).
NR 35
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U1 3
U2 22
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 29
PY 2014
VL 123
IS 22
BP 3390
EP 3397
DI 10.1182/blood-2013-11-535047
PG 8
WC Hematology
SC Hematology
GA AQ2LD
UT WOS:000342616600013
PM 24615777
ER
PT J
AU Kahl, BS
Spurgeon, SE
Furman, RR
Flinn, IW
Coutre, SE
Brown, JR
Benson, DM
Byrd, JC
Peterman, S
Cho, Y
Yu, A
Godfrey, WR
Wagner-Johnston, ND
AF Kahl, Brad S.
Spurgeon, Stephen E.
Furman, Richard R.
Flinn, Ian W.
Coutre, Steven E.
Brown, Jennifer R.
Benson, Don M.
Byrd, John C.
Peterman, Sissy
Cho, Yoonjin
Yu, Albert
Godfrey, Wayne R.
Wagner-Johnston, Nina D.
TI A phase 1 study of the PI3K delta inhibitor idelalisib in patients with
relapsed/refractory mantle cell lymphoma (MCL)
SO BLOOD
LA English
DT Article
ID PHOSPHOINOSITIDE 3-KINASE P110-DELTA; MTOR CONSTITUTIVE ACTIVATION;
CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; B-CELL; MARGINAL
ZONE; CYCLIN D1; PI3K; CYCLOPHOSPHAMIDE; COMBINATION
AB Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase delta (PI3K delta), was evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 40 patients with relapsed or refractory mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (range, 52-83) and receivedmedian of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Commongrade >= 3 adverse events (AEs) included (total%/grade >= 3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3K delta is a viable strategy and worthy of additional study in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528.
C1 [Kahl, Brad S.] Univ Wisconsin, Dept Med, Carbone Canc Ctr, Madison, WI USA.
[Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Furman, Richard R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA.
[Coutre, Steven E.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Benson, Don M.; Byrd, John C.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Peterman, Sissy; Cho, Yoonjin; Yu, Albert; Godfrey, Wayne R.] Gilead Sci Inc, Seattle, WA USA.
[Wagner-Johnston, Nina D.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
RP Kahl, BS (reprint author), 4059 Wisconsin Inst Med Res, 1111 Highland Ave, Madison, WI 53705 USA.
EM bsk@medicine.wisc.edu
FU Gilead Sciences, Inc. (Foster City, CA); Gilead Sciences, Inc. (Seattle,
WA); Calistoga Pharmaceuticals, Inc. of Seattle, WA
FX This clinical study was sponsored and funded by Gilead Sciences, Inc.
(Foster City, CA, and Seattle, WA) and Calistoga Pharmaceuticals, Inc.
of Seattle, WA (acquired by Gilead Sciences, Inc.).
NR 38
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U1 3
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 29
PY 2014
VL 123
IS 22
BP 3398
EP 3405
DI 10.1182/blood-2013-11-537555
PG 8
WC Hematology
SC Hematology
GA AQ2LD
UT WOS:000342616600014
PM 24615778
ER
PT J
AU Flinn, IW
Kahl, BS
Leonard, JP
Furman, RR
Brown, JR
Byrd, JC
Wagner-Johnston, ND
Coutre, SE
Benson, DM
Peterman, S
Cho, Y
Webb, HK
Johnson, DM
Yu, AS
Ulrich, RG
Godfrey, WR
Miller, LL
Spurgeon, SE
AF Flinn, Ian W.
Kahl, Brad S.
Leonard, John P.
Furman, Richard R.
Brown, Jennifer R.
Byrd, John C.
Wagner-Johnston, Nina D.
Coutre, Steve E.
Benson, Don M.
Peterman, Sissy
Cho, Yoonjin
Webb, Heather K.
Johnson, David M.
Yu, Albert S.
Ulrich, Roger G.
Godfrey, Wayne R.
Miller, Langdon L.
Spurgeon, Stephen E.
TI Idelalisib, a selective inhibitor of phosphatidylinositol
3-kinase-delta, as therapy for previously treated indolent non-Hodgkin
lymphoma
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL MALIGNANCIES; REFRACTORY INDOLENT;
RITUXIMAB; PI3K; BENDAMUSTINE; MULTICENTER; CAL-101
AB Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-delta, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (>= 1 lymph nodes >= 5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade >= 3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414.
C1 [Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN 37203 USA.
[Kahl, Brad S.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Leonard, John P.; Furman, Richard R.] Weill Cornell Med Coll, New York, NY USA.
[Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Byrd, John C.; Benson, Don M.] Ohio State Univ, Columbus, OH 43210 USA.
[Wagner-Johnston, Nina D.] Washington Univ, Sch Med, St Louis, MO USA.
[Coutre, Steve E.] Stanford Univ, Ctr Canc, Stanford, CA 94305 USA.
[Peterman, Sissy; Cho, Yoonjin; Webb, Heather K.; Johnson, David M.; Yu, Albert S.; Ulrich, Roger G.; Godfrey, Wayne R.; Miller, Langdon L.] Gilead Sci Inc, Seattle, WA USA.
[Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Flinn, IW (reprint author), Sarah Cannon Res Inst, 250 25th Ave North, Nashville, TN 37203 USA.
EM iflinn@tnonc.com
FU Gilead Sciences, Inc (Foster City, CA); Gilead Sciences, Inc (Seattle,
WA); Calistoga Pharmaceuticals, Inc (Seattle, WA)
FX This clinical study was sponsored and funded by Gilead Sciences, Inc
(Foster City, CA and Seattle, WA) and by Calistoga Pharmaceuticals, Inc
(Seattle, WA) (acquired by Gilead Sciences, Inc.).
NR 34
TC 82
Z9 82
U1 3
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 29
PY 2014
VL 123
IS 22
BP 3406
EP 3413
DI 10.1182/blood-2013-11-538546
PG 8
WC Hematology
SC Hematology
GA AQ2LD
UT WOS:000342616600015
PM 24615776
ER
PT J
AU Aplenc, R
Zhang, MJ
Sung, LL
Zhu, XC
Ho, VT
Cooke, K
Dvorak, C
Hale, G
Isola, LM
Lazarus, HM
McCarthy, PL
Olsson, R
Pulsipher, M
Pasquini, MC
Bunin, N
AF Aplenc, Richard
Zhang, Mei-Jie
Sung, Lillian
Zhu, Xiaochun
Ho, Vincent T.
Cooke, Kenneth
Dvorak, Christopher
Hale, Gregory
Isola, Luis M.
Lazarus, Hillard M.
McCarthy, Philip L.
Olsson, Richard
Pulsipher, Michael
Pasquini, Marcelo C.
Bunin, Nancy
CA Ctr Int Blood Marrow Transplant
TI Effect of body mass in children with hematologic malignancies undergoing
allogeneic bone marrow transplantation
SO BLOOD
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; OBESITY; LEUKEMIA;
OVERWEIGHT; ADOLESCENTS; OUTCOMES; MORTALITY; DISEASES; IMPACT
AB The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median ageandrace were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM.
C1 [Aplenc, Richard; Bunin, Nancy] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Zhang, Mei-Jie; Zhu, Xiaochun; Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Sung, Lillian] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cooke, Kenneth; Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Dvorak, Christopher] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hale, Gregory] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
[Isola, Luis M.] Mt Sinai Hosp, New York, NY 10029 USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Olsson, Richard] Karolinska Inst, Stockholm, Sweden.
[Pulsipher, Michael] Univ Utah, Sch Med, Salt Lake City, UT USA.
RP Pasquini, MC (reprint author), 9200 West Wisconsin Ave,CCC5500, Milwaukee, WI 53226 USA.
EM mpasquini@mcw.edu
OI Olsson, Richard/0000-0001-5970-2128
FU Public Health Service from the National Institutes of Health National
Cancer Institute [U24-CA076518]; National Heart, Lung and Blood
Institute; National Institute of Allergy and Infectious Diseases;
National Heart, Lung and Blood Institute [5U10HL069294]; National Cancer
Institute; Health Resources and Services Administration
[HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142,
N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.;
Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield
Association; Celgene Corporation; Fred Hutchinson Cancer Research
Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint
Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation;
GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute;
HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's
Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH;
Medical College of Wisconsin, Merck Co, Inc.; Millennium: The Takeda
Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; NMDP; Onyx
Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics,
Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy
Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals;
Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; A Global Cord
Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.;
THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint,
Inc.
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA076518 from the National Institutes of Health National
Cancer Institute, the National Heart, Lung and Blood Institute, and the
National Institute of Allergy and Infectious Diseases; Grant/Cooperative
Agreement 5U10HL069294 from National Heart, Lung and Blood Institute and
National Cancer Institute; a contract HHSH250201200016C with Health
Resources and Services Administration; 2 grants (N00014-12-1-0142 and
N00014-13-1-0039) from the Office of Naval Research; and grants from
Actinium Pharmaceuticals, Allos Therapeutics, Inc., Amgen, Inc.,
nnonymous donation to the Medical College of Wisconsin, Ariad, Be the
Match Foundation, Blue Cross and Blue Shield Association, Celgene
Corporation, Fred Hutchinson Cancer Research Center, Fresenius-Biotech
North America, Inc., Gamida Cell Teva Joint Venture Ltd., Genentech,
Inc., Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health
Research, Inc. Roswell Park Cancer Institute, HistoGenetics, Inc.,
Incyte Corporation, Jeff Gordon Children's Foundation, Kiadis Pharma,
The Leukemia & Lymphoma Society, Medac GmbH, The Medical College of
Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co.,
Milliman USA, Inc., Miltenyi Biotec, Inc., NMDP, Onyx Pharmaceuticals,
Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc., Otsuka
America Pharmaceutical, Inc., Perkin Elmer, Inc., Remedy Informatics,
Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Inc.,
St. Baldrick's Foundation, StemCyte, A Global Cord Blood Therapeutics
Co., Stemsoft Software, Inc., Swedish Orphan Biovitrum, Tarix
Pharmaceuticals, TerumoBCT, Teva Neuroscience, Inc., THERAKOS, Inc.,
University of Minnesota, University of Utah, and Wellpoint, Inc. The
views expressed in this article do not reflect the official policy or
position of the National Institutes of Health, the Department of the
Navy, the Department of Defense, Health Resources and Services
Administration, or any other agency of the U.S. Government.
NR 32
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U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 29
PY 2014
VL 123
IS 22
BP 3504
EP 3511
DI 10.1182/blood-2013-03-490334
PG 8
WC Hematology
SC Hematology
GA AQ2LD
UT WOS:000342616600026
PM 24711663
ER
PT J
AU Rampal, R
Al-Shahrour, F
Abdel-Wahab, O
Patel, JP
Brunel, JP
Mermel, CH
Bass, AJ
Pretz, J
Ahn, J
Hricik, T
Kilpivaara, O
Wadleigh, M
Busque, L
Gilliland, DG
Golub, TR
Ebert, BL
Levine, RL
AF Rampal, Raajit
Al-Shahrour, Fatima
Abdel-Wahab, Omar
Patel, Jay P.
Brunel, Jean-Philippe
Mermel, Craig H.
Bass, Adam J.
Pretz, Jennifer
Ahn, Jihae
Hricik, Todd
Kilpivaara, Outi
Wadleigh, Martha
Busque, Lambert
Gilliland, D. Gary
Golub, Todd R.
Ebert, Benjamin L.
Levine, Ross L.
TI Integrated genomic analysis illustrates the central role of JAK-STAT
pathway activation in myeloproliferative neoplasm pathogenesis
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA;
GENE-EXPRESSION; MYELOID MALIGNANCIES; ESSENTIAL THROMBOCYTHEMIA;
LEUKEMIC TRANSFORMATION; V617F MUTATION; TET2; MYELOFIBROSIS
AB Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in allMPN patients regardless of clinical phenotype ormutational status. In addition, the activated JAK2 signature was present in patients with somaticCALRmutations. Conversely, weidentified a gene expression signature ofCALRmutations; this signaturewas significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK2 mutational status, are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis.
C1 [Rampal, Raajit; Abdel-Wahab, Omar; Patel, Jay P.; Ahn, Jihae; Hricik, Todd; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Rampal, Raajit; Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA.
[Rampal, Raajit; Abdel-Wahab, Omar; Levine, Ross L.] Weill Cornell Med Coll, New York, NY USA.
[Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr, Translat Bioinformat Unit, Clin Res Programme, Madrid, Spain.
[Brunel, Jean-Philippe; Mermel, Craig H.; Bass, Adam J.; Pretz, Jennifer; Golub, Todd R.; Ebert, Benjamin L.] Broad Inst Harvard Univ, Cambridge, MA USA.
[Brunel, Jean-Philippe; Mermel, Craig H.; Bass, Adam J.; Pretz, Jennifer; Golub, Todd R.; Ebert, Benjamin L.] MIT, Cambridge, MA 02139 USA.
[Mermel, Craig H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Mermel, Craig H.] Dept Pathol, Boston, MA USA.
[Bass, Adam J.; Pretz, Jennifer; Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kilpivaara, Outi] Univ Helsinki, Dept Med Genet, Genome Scale Biol Res Program, Helsinki, Finland.
[Busque, Lambert] Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada.
[Busque, Lambert] Maisonneuve Rosemont Hosp, Dept Hematol, Montreal, PQ, Canada.
[Busque, Lambert] Univ Montreal, Montreal, PQ, Canada.
[Gilliland, D. Gary] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Golub, Todd R.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA.
RP Ebert, BL (reprint author), Brigham & Womens Hosp, 1 Blackfan Circle, Boston, MA 02115 USA.
EM bebert@partners.org; leviner@mskcc.org
OI Abdel-Wahab, Omar/0000-0002-3907-6171
FU Myeloproliferative Neoplasm Foundation; Starr Cancer Consortium;
National Institutes of Health, National Cancer Institute
[1R01CA151949-01]
FX This work was supported by grants from the Myeloproliferative Neoplasm
Foundation (R. L. L., B. L. E.), the Starr Cancer Consortium (D. G. G.,
T. R. G., B. L. E., R. L. L.), and the National Institutes of Health,
National Cancer Institute (grant 1R01CA151949-01) (R. L. L.). R. L. L.
and B. L. E. are Leukemia and Lymphoma Society Scholars, and O.A.-W. and
R. R. are American Society of Hematology Scholars.
NR 66
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U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 29
PY 2014
VL 123
IS 22
BP E123
EP E133
DI 10.1182/blood-2014-02-554634
PG 11
WC Hematology
SC Hematology
GA AQ2LD
UT WOS:000342616600001
PM 24740812
ER
PT J
AU Yasmeen, A
Ringe, R
Derking, R
Cupo, A
Julien, JP
Burton, DR
Ward, AB
Wilson, IA
Sanders, RW
Moore, JP
Klasse, PJ
AF Yasmeen, Anila
Ringe, Rajesh
Derking, Ronald
Cupo, Albert
Julien, Jean-Philippe
Burton, Dennis R.
Ward, Andrew B.
Wilson, Ian A.
Sanders, Rogier W.
Moore, John P.
Klasse, Per Johan
TI Differential binding of neutralizing and non-neutralizing antibodies to
native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and
monomeric subunits
SO RETROVIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN
MONOCLONAL-ANTIBODIES; INTERMOLECULAR DISULFIDE BOND; VACCINE
DEVELOPMENT; POTENT NEUTRALIZATION; IMMUNOGEN DESIGN; VARIABLE LOOPS;
GP41 SUBUNITS; CD4 BINDING
AB Background: The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically.
Results: We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP. 664 trimers, cleaved gp120-gp41(ECTO) protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41(ECTO) protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41(ECTO), and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T332N pseudovirus.
Conclusions: The antigenicity and structural integrity of cleaved BG505 SOSIP. 664 trimers render these proteins good mimics of functional Env spikes on virions. In contrast, uncleaved gp140s antigenically resemble individual gp120-gp41(ECTO) protomers and gp120 monomers, but not native trimers. Although NAb binding to functional trimers may thus be both necessary and sufficient for neutralization, the kinetics and stoichiometry of the interaction influence the neutralizing efficacy of individual NAbs.
C1 [Yasmeen, Anila; Ringe, Rajesh; Cupo, Albert; Sanders, Rogier W.; Moore, John P.; Klasse, Per Johan] Cornell Univ, Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
[Derking, Ronald; Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands.
[Julien, Jean-Philippe; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Julien, Jean-Philippe; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Burton, Dennis R.] Harvard Univ, Boston, MA 02115 USA.
[Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
RP Klasse, PJ (reprint author), Cornell Univ, Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
EM pek2003@med.cornell.edu
RI Ward, Andrew/F-9203-2014
OI Ward, Andrew/0000-0001-7153-3769
FU NIH [P01 AI82362, R37 AI36082]; IAVI Neutralizing Antibody Consortium;
Aids fonds Netherlands [2011032]; Canadian Institutes of Health Research
(CIHR) Fellowship; Netherlands Organization for Scientific Research
(NWO) [91711314]; European Research Council [ERC-StG-2011-280829-SHEV]
FX This work was supported by NIH grants P01 AI82362, R37 AI36082, by the
IAVI Neutralizing Antibody Consortium, and by the Aids fonds
Netherlands, grant 2011032. JPJ is a recipient of a Canadian Institutes
of Health Research (CIHR) Fellowship. RWS is a recipient of a Vidi grant
from the Netherlands Organization for Scientific Research (NWO;
91711314) and a Starting Investigator Grant from the European Research
Council (ERC-StG-2011-280829-SHEV). We are grateful to John Mascola and
James Robinson for reagents and to Kevin de Los Reyes, Michael Golabek,
and Jacob Korzun for excellent technical assistance.
NR 93
TC 53
Z9 53
U1 2
U2 26
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD MAY 29
PY 2014
VL 11
AR 41
DI 10.1186/1742-4690-11-41
PG 17
WC Virology
SC Virology
GA AK2KB
UT WOS:000338247000001
PM 24884783
ER
PT J
AU Meng, C
Kuster, B
Culhane, AC
Gholami, AM
AF Meng, Chen
Kuster, Bernhard
Culhane, Aedin C.
Gholami, Amin Moghaddas
TI A multivariate approach to the integration of multi-omics datasets
SO BMC BIOINFORMATICS
LA English
DT Article
DE Multivariate analysis; Multiple co-inertia; Data integration; Omic data;
Visualization
ID GENE-EXPRESSION DATA; CO-INERTIA ANALYSIS; PRINCIPAL COMPONENT ANALYSIS;
CANCER-CELL LINE; RNA-SEQ; OVARIAN-CARCINOMA; CROSS-PLATFORM;
MESSENGER-RNA; PANEL; MICROARRAY
AB Background: To leverage the potential of multi-omics studies, exploratory data analysis methods that provide systematic integration and comparison of multiple layers of omics information are required. We describe multiple co-inertia analysis (MCIA), an exploratory data analysis method that identifies co-relationships between multiple high dimensional datasets. Based on a covariance optimization criterion, MCIA simultaneously projects several datasets into the same dimensional space, transforming diverse sets of features onto the same scale, to extract the most variant from each dataset and facilitate biological interpretation and pathway analysis.
Results: We demonstrate integration of multiple layers of information using MCIA, applied to two typical "omics" research scenarios. The integration of transcriptome and proteome profiles of cells in the NCI-60 cancer cell line panel revealed distinct, complementary features, which together increased the coverage and power of pathway analysis. Our analysis highlighted the importance of the leukemia extravasation signaling pathway in leukemia that was not highly ranked in the analysis of any individual dataset. Secondly, we compared transcriptome profiles of high grade serous ovarian tumors that were obtained, on two different microarray platforms and next generation RNA-sequencing, to identify the most informative platform and extract robust biomarkers of molecular subtypes. We discovered that the variance of RNA-sequencing data processed using RPKM had greater variance than that with MapSplice and RSEM. We provided novel markers highly associated to tumor molecular subtype combined from four data platforms. MCIA is implemented and available in the R/Bioconductor "omicade4" package.
Conclusion: We believe MCIA is an attractive method for data integration and visualization of several datasets of multi-omics features observed on the same set of individuals. The method is not dependent on feature annotation, and thus it can extract important features even when there are not present across all datasets. MCIA provides simple graphical representations for the identification of relationships between large datasets.
C1 [Meng, Chen; Kuster, Bernhard; Gholami, Amin Moghaddas] Tech Univ Munich, Chair Prote & Bioanalyt, Freising Weihenstephan, Germany.
[Kuster, Bernhard] Ctr Integrated Prot Sci Munich, Freising Weihenstephan, Germany.
[Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
RP Culhane, AC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
EM aedin@jimmy.harvard.edu; amin@tum.de
RI Kuster, Bernhard/Q-6031-2016
OI Kuster, Bernhard/0000-0002-9094-1677
FU Dana-Farber Cancer Institute Women's Cancers Program, Claudia Adams Barr
foundation; National Cancer Institute at the National Institutes of
Health [1RC4CA156551-01, 1U19CA148065]
FX The authors gratefully acknowledge Hannes Hahne and Mathias Wilhelm of
TUM and Curtis Huttenhower of Harvard School of Public Health for
critical reading of the manuscript. Funding for this work was provided
by Dana-Farber Cancer Institute Women's Cancers Program, the Claudia
Adams Barr foundation and the National Cancer Institute at the National
Institutes of Health [grant numbers 1RC4CA156551-01, 1U19CA148065].
NR 60
TC 27
Z9 28
U1 2
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAY 29
PY 2014
VL 15
AR 162
DI 10.1186/1471-2105-15-162
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AJ0CR
UT WOS:000337317300001
PM 24884486
ER
PT J
AU Quackenbush, J
AF Quackenbush, John
TI PERSPECTIVE Learning to share
SO NATURE
LA English
DT Editorial Material
C1 Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA.
RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA.
EM johnq@jimmy.harvard.edu
FU NHLBI NIH HHS [R01 HL111759]
NR 0
TC 0
Z9 0
U1 0
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 MAY 29
PY 2014
VL 509
IS 7502
BP S68
EP S68
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100010
PM 24870827
ER
PT J
AU Kradin, RL
Fidias, P
Digumarthy, S
Mark, EJ
AF Kradin, Richard L.
Fidias, Panos
Digumarthy, Subba
Mark, Eugene J.
TI Case 17-2014: A 64-Year-Old Man with Chest Pain and a Pleural Effusion
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LUNG-CANCER; MALIGNANT MESOTHELIOMA; ASBESTOS EXPOSURE; PHASE-III;
EPIDEMIOLOGY; CISPLATIN; SURVEILLANCE; POPULATION; PROGRAM
C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kradin, Richard L.; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Fidias, Panos] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA.
[Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kradin, Richard L.; Fidias, Panos] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kradin, Richard L.; Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Digumarthy, Subba] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
FU Genentech
FX Drs. Kradin and Mark report receiving payments for providing expert
testimony in litigation regarding asbestos on behalf of patients. Dr.
Fidias reports receiving fees from Genentech for serving on an advisory
board. No other potential conflict of interest relevant to this article
was reported.
NR 24
TC 2
Z9 2
U1 0
U2 1
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 MAY 29
PY 2014
VL 370
IS 22
BP 2132
EP 2140
DI 10.1056/NEJMcpc1400835
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH9BM
UT WOS:000336434000012
PM 24869724
ER
PT J
AU Narasimha, AM
Kaulich, M
Shapiro, GS
Choi, YJ
Sicinski, P
Dowdy, SF
AF Narasimha, Anil M.
Kaulich, Manuel
Shapiro, Gary S.
Choi, Yoon J.
Sicinski, Piotr
Dowdy, Steven F.
TI Cyclin D activates the Rb tumor suppressor by mono-phosphorylation
SO ELIFE
LA English
DT Article
ID RETINOBLASTOMA SUSCEPTIBILITY GENE; CELL-CYCLE; DNA-DAMAGE; MYOGENIC
DIFFERENTIATION; ECTOPIC EXPRESSION; SKELETAL-MUSCLE; CDK COMPLEXES;
PROTEIN; KINASE; INHIBITION
AB The widely accepted model of G(1) cell cycle progression proposes that cyclin D: Cdk4/6 inactivates the Rb tumor suppressor during early G(1) phase by progressive multi-phosphorylation, termed hypo-phosphorylation, to release E2F transcription factors. However, this model remains unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is exclusively mono-phosphorylated in early G(1) phase by cyclin D:Cdk4/6. Mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but show preferential E2F binding patterns. At the late G(1) Restriction Point, cyclin E: Cdk2 inactivates Rb by quantum hyper-phosphorylation. Cells undergoing a DNA damage response activate cyclin D: Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription, whereas cells undergoing differentiation utilize un-phosphorylated Rb. These observations fundamentally change our understanding of G(1) cell cycle progression and show that mono-phosphorylated Rb, generated by cyclin D:Cdk4/6, is the only Rb isoform in early G(1) phase.
C1 [Narasimha, Anil M.; Kaulich, Manuel; Shapiro, Gary S.; Dowdy, Steven F.] UCSD Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Choi, Yoon J.; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA.
[Choi, Yoon J.; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
RP Dowdy, SF (reprint author), UCSD Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM sdowdy@ucsd.edu
NR 53
TC 35
Z9 35
U1 2
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAY 29
PY 2014
VL 3
AR e02872
DI 10.7554/eLife.02872
PG 45
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AI2DA
UT WOS:000336666200003
ER
PT J
AU Baffy, G
Loscalzo, J
AF Baffy, Gyoergy
Loscalzo, Joseph
TI Complexity and network dynamics in physiological adaptation: An
integrated view
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Homeostasis; Allostasis; Complex adaptive systems; Chaotic exploration;
Phase space; Attractor networks
ID UNCOUPLING PROTEINS; ATTRACTOR LANDSCAPE; INSULIN-RESISTANCE; METABOLIC
SYNDROME; SELF-ORGANIZATION; ALLOSTATIC LOAD; FEEDBACK LOOPS;
GENE-THERAPY; OBESITY; DISEASE
AB Living organisms constantly interact with their surroundings and sustain internal stability against perturbations. This dynamic process follows three fundamental strategies (restore, explore, and abandon) articulated in historical concepts of physiological adaptation such as homeostasis, allostasis, and the general adaptation syndrome. These strategies correspond to elementary forms of behavior (ordered, chaotic, and static) in complex adaptive systems and invite a network-based analysis of the operational characteristics, allowing us to propose an integrated framework of physiological adaptation from a complex network perspective. Applicability of this concept is illustrated by analyzing molecular and cellular mechanisms of adaptation in response to the pervasive challenge of obesity, a chronic condition resulting from sustained nutrient excess that prompts chaotic exploration for system stability associated with tradeoffs and a risk of adverse outcomes such as diabetes, cardiovascular disease, and cancer. Deconstruction of this complexity holds the promise of gaining novel insights into physiological adaptation in health and disease. Published by Elsevier Inc.
C1 [Baffy, Gyoergy] VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA.
[Baffy, Gyoergy; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA.
RP Baffy, G (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA.
EM gbaffy@partners.org
FU NHLBI NIH HHS [R37 HL061795, U01 HL108630]
NR 104
TC 6
Z9 6
U1 6
U2 24
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD MAY 28
PY 2014
VL 131
BP 49
EP 56
DI 10.1016/j.physbeh.2014.04.018
PG 8
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA AJ7HA
UT WOS:000337866600007
PM 24751342
ER
PT J
AU Ferlemi, AV
Avgoustatos, D
Kokkosis, AG
Protonotarios, V
Constantinou, C
Margarity, M
AF Ferlemi, Anastasia-Varvara
Avgoustatos, Dionisis
Kokkosis, Alexandros G.
Protonotarios, Vasilis
Constantinou, Caterina
Margarity, Marigoula
TI Lead-induced effects on learning/memory and fear/anxiety are correlated
with disturbances in specific cholinesterase isoform activity and redox
imbalance in adult brain
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Lead; Learning/memory; Anxiety-like behavior; Acetylcholinesterase;
Redox balance; Correlation analysis
ID LIPID-PEROXIDATION PRODUCTS; ELEVATED PLUS-MAZE; OXIDATIVE STRESS;
RAT-BRAIN; MEMORY CONSOLIDATION; IN-VIVO; ANTIOXIDANT ENZYMES;
GENE-EXPRESSION; MOUSE-BRAIN; ACETYLCHOLINESTERASE
AB The aim of the present study was to investigate whether the underlying mechanism of lead (Pb)-induced effects on learning/memory and fear/anxiety behavior involves changes either on AChE G4 (most abundant in brain) or on G1 isoform activity, and/or to a putative local disruption of oxidant/antioxidant balance. Adult male mice were randomly divided into two groups (18 animals/group): a vehicle group [500 ppm (mg/L) CH3COONa/day for 4 weeks in their drinking water] and a Pb-treated group [500 ppm Pb(CH3COO)(2)/day for 4 weeks in their drinking water]. At the end of the treatment period, mice were subjected to the behavioral tasks. Learning/memory was tested by step-through passive avoidance test, whereas fear/anxiety was studied using the elevated plus-maze and thigmotaxis tests. Pb levels in mice brain were determined using atomic absorption spectrometry. AChE activity was determined colorimetrically, and GSH and MDA levels fluorometrically in whole brain minus cerebellum, cerebral cortex, midbrain, hippocampus, striatum and cerebellum. The possible correlations between learning/memory or fear/anxiety behavior with the AChE activity and/or the lipid peroxidation levels and GSH content were also examined. Pb consumption caused significant deficits on mice learning/memory ability and increased anxiety. The consumption of the Pb solution inhibited the activity of the two AChE isoforms in all brain regions tested. Moreover, Pb exposure increased lipid peroxidation and decreased GSH levels in all brain regions examined. Spearman correlation analysis revealed that the coefficients between the particular behaviors, AChE activity and redox balance were brain region- and AChE isoform-specific. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ferlemi, Anastasia-Varvara; Avgoustatos, Dionisis; Kokkosis, Alexandros G.; Margarity, Marigoula] Univ Patras, Dept Biol, Lab Human & Anim Physiol, Patras 26500, Greece.
[Protonotarios, Vasilis] Lavrion Technol & Cultural Pk, Lavrion 19500, Greece.
[Constantinou, Caterina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, Boston, MA 02114 USA.
[Constantinou, Caterina] Harvard Univ, Sch Med, Shrines Burns Inst, Boston, MA 02114 USA.
RP Constantinou, C (reprint author), Univ Patras, Pharmacol Lab, Dept Med, Patras 26500, Greece.
EM cconst12@yahoo.com; margar@upatras.gr
OI Constantinou, Caterina/0000-0003-3589-0739
NR 67
TC 12
Z9 12
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD MAY 28
PY 2014
VL 131
BP 115
EP 122
DI 10.1016/j.physbeh.2014.04.033
PG 8
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA AJ7HA
UT WOS:000337866600018
PM 24768645
ER
PT J
AU Ahmed, OJ
Vijayan, S
AF Ahmed, Omar J.
Vijayan, Sujith
TI The Roles of Sleep-Wake States and Brain Rhythms in Epileptic Seizure
Onset
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID TETANUS TOXIN MODEL; THETA-OSCILLATIONS
C1 [Ahmed, Omar J.; Vijayan, Sujith] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Ahmed, Omar J.; Vijayan, Sujith] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vijayan, Sujith] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Ahmed, OJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Thier 423, Boston, MA 02114 USA.
EM omar.j.ahmed@gmail.com
FU NINDS NIH HHS [F32 NS083208]
NR 12
TC 2
Z9 2
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 28
PY 2014
VL 34
IS 22
BP 7395
EP 7397
DI 10.1523/JNEUROSCI.1168-14.2014
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA AI8CE
UT WOS:000337131800001
PM 24872545
ER
PT J
AU Zhang, QX
Ren, H
Baker, GL
AF Zhang, Quanxuan
Ren, Hong
Baker, Gregory L.
TI A practical and scalable process to selectively monofunctionalize
water-soluble alpha,omega-diols
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Monofunctionalization; Water-soluble alpha,omega-diols; THP ether
protection and deprotection; Scalable
ID SYMMETRICAL DIOLS; ALCOHOLS; MONOPROTECTION; ACID
AB A practical protocol for rapid and scalable synthesis of monofunctionalized alpha,omega-diols using a simple and inexpensive THP ether protection/deprotection strategy was described. Use of inexpensive DHP source and ease to remove excess water-soluble alpha,omega-diols and THP ether after deprotection render the process scale-friendly without need of column chromatographic separation. The application of present method was also illustrated in the preparation of heterobifunctional diols and well-defined extended oligo (ethylene glycol). (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Zhang, Quanxuan; Baker, Gregory L.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.
[Ren, Hong] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Ren, Hong] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol, Charlestown, MA 02129 USA.
RP Zhang, QX (reprint author), Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.
EM zhangqua@msu.edu
RI Ren, Hong/J-5191-2015
OI Ren, Hong/0000-0003-0375-0360
NR 23
TC 3
Z9 3
U1 2
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD MAY 28
PY 2014
VL 55
IS 22
BP 3384
EP 3386
DI 10.1016/j.tetlet.2014.04.066
PG 3
WC Chemistry, Organic
SC Chemistry
GA AI8XG
UT WOS:000337209700026
ER
PT J
AU Rogers, T
Milkman, KL
Volpp, KG
AF Rogers, Todd
Milkman, Katherine L.
Volpp, Kevin G.
TI Commitment Devices Using Initiatives to Change Behavior
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID SMOKING-CESSATION
C1 [Rogers, Todd] Harvard Univ, Kennedy Sch, Boston, MA 02115 USA.
[Milkman, Katherine L.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Volpp, Kevin G.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
RP Volpp, KG (reprint author), Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, 423 Guardian Dr,1120 Blockley Hall, Philadelphia, PA 19104 USA.
EM volpp70@exchange.upenn.edu
NR 7
TC 11
Z9 11
U1 2
U2 14
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 28
PY 2014
VL 311
IS 20
BP 2065
EP 2066
DI 10.1001/jama.2014.3485
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH8MQ
UT WOS:000336392400018
PM 24777472
ER
PT J
AU Cotton, PB
Durkalski, V
Romagnuolo, J
Pauls, Q
Fogel, E
Tarnasky, P
Aliperti, G
Freeman, M
Kozarek, R
Jamidar, P
Wilcox, M
Serrano, J
Brawman-Mintzer, O
Elta, G
Mauldin, P
Thornhill, A
Hawes, R
Wood-Williams, A
Orrell, K
Drossman, D
Robuck, P
AF Cotton, Peter B.
Durkalski, Valerie
Romagnuolo, Joseph
Pauls, Qi
Fogel, Evan
Tarnasky, Paul
Aliperti, Giuseppe
Freeman, Martin
Kozarek, Richard
Jamidar, Priya
Wilcox, Mel
Serrano, Jose
Brawman-Mintzer, Olga
Elta, Grace
Mauldin, Patrick
Thornhill, Andre
Hawes, Robert
Wood-Williams, April
Orrell, Kyle
Drossman, Douglas
Robuck, Patricia
TI Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi
Dysfunction on Pain-Related Disability Following Cholecystectomy The
EPISOD Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; FUNCTIONAL GASTROINTESTINAL
DISORDERS; FINDINGS TYPE-I; HEALTH-STATUS; RISK-FACTORS; DSM-IV; ERCP;
GALLBLADDER; SYMPTOMS; DISEASE
AB IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy.
OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief.
DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013.
INTERVENTIONS After ERCP, patients were randomized 2: 1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1: 1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny.
MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention.
RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P =.01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI, 19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P =.22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment.
CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients.
C1 [Cotton, Peter B.; Durkalski, Valerie; Romagnuolo, Joseph; Pauls, Qi; Mauldin, Patrick; Thornhill, Andre; Hawes, Robert; Wood-Williams, April; Orrell, Kyle] Med Univ S Carolina, Charleston, SC 29425 USA.
[Fogel, Evan] Indiana Univ, Indianapolis, IN 46204 USA.
[Tarnasky, Paul] Dallas Med Ctr, Dallas, TX USA.
[Aliperti, Giuseppe] Midwest Therapeut Endoscopy Consultants, St Louis, MO USA.
[Freeman, Martin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Kozarek, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Jamidar, Priya] Yale Univ, New Haven, CT USA.
[Wilcox, Mel] Univ Alabama Birmingham, Birmingham, AL USA.
[Serrano, Jose; Robuck, Patricia] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Elta, Grace] Univ Michigan, Ann Arbor, MI 48109 USA.
[Hawes, Robert] Florida Hosp, Orlando, FL USA.
[Drossman, Douglas] Univ N Carolina, Chapel Hill, NC USA.
[Drossman, Douglas] Drossman Gastroenterol PLLC, Chapel Hill, NC USA.
RP Cotton, PB (reprint author), Med Univ S Carolina, Ctr Digest Dis, ART 7094,MSC 290,25 Courtenay Dr, Charleston, SC 29425 USA.
EM cottonp@musc.edu
FU National Institutes of Diabetes and Digestive and Kidney Diseases [U01
DK074739]
FX This study was funded by grant U01 DK074739 from the National Institutes
of Diabetes and Digestive and Kidney Diseases.
NR 40
TC 38
Z9 39
U1 12
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 28
PY 2014
VL 311
IS 20
BP 2101
EP 2109
DI 10.1001/jama.2014.5220
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH8MQ
UT WOS:000336392400026
PM 24867013
ER
PT J
AU Arany, PR
Cho, A
Hunt, TD
Sidhu, G
Shin, K
Hahm, E
Huang, GX
Weaver, J
Chen, ACH
Padwa, BL
Hamblin, MR
Barcellos-Hoff, MH
Kulkarni, AB
Mooney, DJ
AF Arany, Praveen R.
Cho, Andrew
Hunt, Tristan D.
Sidhu, Gursimran
Shin, Kyungsup
Hahm, Eason
Huang, George X.
Weaver, James
Chen, Aaron Chih-Hao
Padwa, Bonnie L.
Hamblin, Michael R.
Barcellos-Hoff, Mary Helen
Kulkarni, Ashok B.
Mooney, David J.
TI Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1
Directs Dental Stem Cell Differentiation for Regeneration
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR-BETA; LEVEL LASER IRRADIATION; IN-VITRO; PULP COMPLEX;
BONE-MARROW; ACTIVATION; TGF-BETA-1; AMELOBLASTS; PROTEINS; MATRIX
AB Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor-beta 1 (TGF-beta 1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-beta 1 (LTGF-beta 1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-beta 1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-LPL-induced receptor II (TGF-beta RII) conditional knockout (DSPP(Cre)TGF-beta RIIfl/fl) mice or when wild-type mice were given a TGF-beta RI inhibitor. These findings indicate a pivotal role for TGF-beta in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications.
C1 [Arany, Praveen R.; Hunt, Tristan D.; Sidhu, Gursimran; Shin, Kyungsup; Hahm, Eason; Huang, George X.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Arany, Praveen R.; Weaver, James; Mooney, David J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Arany, Praveen R.; Shin, Kyungsup] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Arany, Praveen R.] Leder Human Biol & Translat Med, Boston, MA 02115 USA.
[Arany, Praveen R.; Cho, Andrew; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA.
[Chen, Aaron Chih-Hao; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Padwa, Bonnie L.] Childrens Hosp, Boston, MA 02115 USA.
[Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Barcellos-Hoff, Mary Helen] NYU, Sch Med, New York, NY 10016 USA.
RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM mooneyd@seas.harvard.edu
OI Barcellos-Hoff, Mary Helen/0000-0002-5994-9558
FU Harvard Presidential Scholarship; Wyss institute, Harvard Catalyst;
Harvard Clinical and Translational Science Center [National Center for
Research Resources (NCRR)]; National Center for Advancing Translational
Sciences (NCATS); NIH [1UL1 TR001102-01]; Harvard University;
[R37-DE-013349]; [R01-DE019023-01]; [R01-AI-050875]; [ZIA-DE-000698]
FX R37-DE-013349 (D.J.M.), R01-DE019023-01, R01-AI-050875 (M.R.H.),
ZIA-DE-000698 (A.B.K.), Harvard Presidential Scholarship (P.R.A.), Wyss
institute, Harvard Catalyst, Harvard Clinical and Translational Science
Center [National Center for Research Resources (NCRR) and National
Center for Advancing Translational Sciences (NCATS), NIH, 1UL1
TR001102-01, and financial contributions from Harvard University and its
affiliated academic health care centers], and the intramural research
program, NIDCR, NIH (A.B.K. and P.R.A.). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University and its
affiliated academic health care centers, or the NIH.
NR 45
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Z9 22
U1 0
U2 33
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAY 28
PY 2014
VL 6
IS 238
AR 238ra69
DI 10.1126/scitranslmed.3008234
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AI2DZ
UT WOS:000336668900002
PM 24871130
ER
PT J
AU Hochberg, LR
Cudkowicz, ME
AF Hochberg, Leigh R.
Cudkowicz, Merit E.
TI Locked in, but not out?
SO NEUROLOGY
LA English
DT Editorial Material
ID BRAIN-COMPUTER INTERFACE; IN SYNDROME; CONSCIOUSNESS; DISORDERS;
TETRAPLEGIA
C1 [Hochberg, Leigh R.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurotechnol Trials Unit,Dept Neurol, Boston, MA 02163 USA.
[Hochberg, Leigh R.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Inst,Dept Neurol, Boston, MA USA.
[Hochberg, Leigh R.] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Rehabil Res & Dev Serv, Off Res & Dev, Providence, RI USA.
Brown Univ, Sch Engn, Providence, RI 02912 USA.
Brown Univ, Inst Brain Sci, Providence, RI 02912 USA.
RP Hochberg, LR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurotechnol Trials Unit,Dept Neurol, Boston, MA 02163 USA.
EM lhochberg@partners.org
FU NIDCD NIH HHS [R01DC009899, R01 DC009899]
NR 14
TC 4
Z9 4
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 27
PY 2014
VL 82
IS 21
BP 1852
EP 1853
DI 10.1212/WNL.0000000000000460
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AQ5BM
UT WOS:000342817600007
PM 24789868
ER
PT J
AU Ryu, SY
Coutu, JP
Rosas, HD
Salat, DH
AF Ryu, Seon Young
Coutu, Jean-Philippe
Rosas, H. Diana
Salat, David H.
TI Effects of insulin resistance on white matter microstructure in
middle-aged and older adults
SO NEUROLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; PLASMA-INSULIN; HUMAN BRAIN; RISK; ABNORMALITIES;
DEGENERATION; METABOLISM; GENOTYPE; GLUCOSE
AB Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults.
Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41-86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: "high HOMA-IR" (>= 2.5, n= 27) and "low HOMA-IR" (<2.5, n=100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis.
Results: The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity.
Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults.
C1 [Ryu, Seon Young] Catholic Univ Korea, Coll Med, Daejeon St Marys Hosp, Dept Neurol, Seoul, South Korea.
[Ryu, Seon Young; Coutu, Jean-Philippe; Rosas, H. Diana; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA.
[Rosas, H. Diana] Harvard Univ, Sch Med, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA.
[Coutu, Jean-Philippe] MIT, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Salat, David H.] VA Boston Healthcare Syst, Boston, MA USA.
RP Ryu, SY (reprint author), Catholic Univ Korea, Coll Med, Daejeon St Marys Hosp, Dept Neurol, Seoul, South Korea.
EM streamline@catholic.ac.kr
OI /0000-0003-4895-5642
FU NIH/NINR [R01NR10827, R01NS42861]; Biomedical Technology Program of the
National Center for Research Resources (NCRR), NIH; NCRR [S10RR021110,
S10RR023401, S10RR019307, S10RR019254, S10RR023043]; Advanced Multimodal
Neuroimaging Training Program at MGH/HST Athinoula A. Martinos Center
for Biomedical Imaging [2T90DA022759]; Fonds de Recherche du
Quebec-Sante
FX Supported by NIH/NINR: R01NR10827, R01NS42861. The authors thank the
Athinoula A. Martinos Center for Biomedical Imaging, MGH, where this
study was performed, and acknowledge the use of resources provided by
the Center for Functional Neuroimaging Technologies, P41RR14075, a P41
Regional Resource supported by the Biomedical Technology Program of the
National Center for Research Resources (NCRR), NIH, as well as
instrumentation obtained through the support of NCRR Shared
Instrumentation Grant Program and/or High-End Instrumentation Grant
Program; specifically, grants S10RR021110, S10RR023401, S10RR019307,
S10RR019254, and S10RR023043. The authors also thank the Advanced
Multimodal Neuroimaging Training Program (2T90DA022759; principal
investigator Bruce Rosen) at the MGH/HST Athinoula A. Martinos Center
for Biomedical Imaging and the Fonds de Recherche du Quebec-Sante, which
supported J.-P.C.
NR 38
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Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 27
PY 2014
VL 82
IS 21
BP 1862
EP 1870
DI 10.1212/WNL.0000000000000452
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA AQ5BM
UT WOS:000342817600010
PM 24771537
ER
PT J
AU Zhao, X
Chen, F
Feng, ZJ
Li, XS
Zhou, XH
AF Zhao, Xing
Chen, Fei
Feng, Zijian
Li, Xiaosong
Zhou, Xiao-Hua
TI Characterizing the effect of temperature fluctuation on the incidence of
malaria: an epidemiological study in south-west China using the varying
coefficient distributed lag non-linear model
SO MALARIA JOURNAL
LA English
DT Article
ID DENGUE VIRUS TRANSMISSION; EAST-AFRICAN HIGHLANDS; METEOROLOGICAL
FACTORS; YUNNAN PROVINCE; SPATIOTEMPORAL DISTRIBUTION;
PLASMODIUM-FALCIPARUM; CLIMATE-CHANGE; AEDES-AEGYPTI; ASSOCIATION; RISK
AB Background: Malaria transmission is strongly determined by the environmental temperature and the environment is rarely constant. Therefore, mosquitoes and parasites are not only exposed to the mean temperature, but also to daily temperature variation. Recently, both theoretical and laboratory work has shown, in addition to mean temperatures, daily fluctuations in temperature can affect essential mosquito and parasite traits that determine malaria transmission intensity. However, so far there is no epidemiological evidence at the population level to this problem.
Methods: Thirty counties in southwest China were selected, and corresponding weekly malaria cases and weekly meteorological variables were collected from 2004 to 2009. Particularly, maximum, mean and minimum temperatures were collected. The daily temperature fluctuation was measured by the diurnal temperature range (DTR), the difference between the maximum and minimum temperature. The distributed lag non-linear model (MDLNM) was used to study the correlation between weekly malaria incidences and weekly mean temperatures, and the correlation pattern was allowed to vary over different levels of daily temperature fluctuations.
Results: The overall non-linear patterns for mean temperatures are distinct across different levels of DTR. When under cooler temperature conditions, the larger mean temperature effect on malaria incidences is found in the groups of higher DTR, suggesting that large daily temperature fluctuations act to speed up the malaria incidence in cooler environmental conditions. In contrast, high daily fluctuations under warmer conditions will lead to slow down the mean temperature effect. Furthermore, in the group of highest DTR, 24-25 degrees C or 21-23 degrees C are detected as the optimal temperature for the malaria transmission.
Conclusion: The environment is rarely constant, and the result highlights the need to consider temperature fluctuations as well as mean temperatures, when trying to understand or predict malaria transmission. This work may be the first epidemiological study confirming that the effect of the mean temperature depends on temperature fluctuations, resulting in relevant evidence at the population level.
C1 [Zhao, Xing; Chen, Fei; Li, Xiaosong] Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Peoples R China.
[Zhao, Xing; Zhou, Xiao-Hua] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Feng, Zijian] Chinese Ctr Dis Control & Prevent, Off Dis Control & Emergency Response, Beijing 102206, Peoples R China.
[Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA.
RP Li, XS (reprint author), Sichuan Univ, West China Sch Publ Hlth, 17 Sect 3,South Renmin Rd, Chengdu 610041, Peoples R China.
EM lixiaosong1101@126.com; azhou@u.washington.edu
FU Natural Science Foundation of China, China Scholarship Council
[30571618]
FX The three reviewers' comments have greatly improved the content and
readability of the manuscript. The Figure in the Additional file 1 was
reproduced from a previous article written by same authors [35], and the
Figure was included for the purpose of completeness. In addition, Table
1, with some new data, was partly reproduced from that previous article.
This study was supported by the Natural Science Foundation of China (No.
30571618), China Scholarship Council (http://en.csc.edu.cn/).
NR 45
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U1 2
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD MAY 27
PY 2014
VL 13
AR 192
DI 10.1186/1475-2875-13-192
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AL2JC
UT WOS:000338950900003
PM 24886630
ER
PT J
AU Carreras, ET
Mega, JL
AF Carreras, Edward T.
Mega, Jessica L.
TI Dual Antiplatelet Therapy for Heart Disease
SO CIRCULATION
LA English
DT Editorial Material
C1 [Carreras, Edward T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA.
[Mega, Jessica L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA.
RP Mega, JL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM jmega@partners.org
NR 2
TC 3
Z9 4
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAY 27
PY 2014
VL 129
IS 21
BP E506
EP E508
DI 10.1161/CIRCULATIONAHA.113.004305
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AI9SR
UT WOS:000337277000002
PM 24868000
ER
PT J
AU Kleijn, A
Kloezeman, J
Treffers-Westerlaken, E
Fulci, G
Leenstra, S
Dirven, C
Debets, R
Lamfers, M
AF Kleijn, Anne
Kloezeman, Jenneke
Treffers-Westerlaken, Elike
Fulci, Giulia
Leenstra, Sieger
Dirven, Clemens
Debets, Reno
Lamfers, Martine
TI The In Vivo Therapeutic Efficacy of the Oncolytic Adenovirus Delta24-RGD
Is Mediated by Tumor-Specific Immunity
SO PLOS ONE
LA English
DT Article
ID CONDITIONALLY REPLICATIVE ADENOVIRUS; VESICULAR STOMATITIS-VIRUS; PHASE
I/II TRIAL; INFLAMMATORY RESPONSE; ANTITUMOR IMMUNITY; MALIGNANT
GLIOMAS; CANCER-PATIENTS; CELL-DEATH; GLIOBLASTOMA; VECTORS
AB The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.
C1 [Kleijn, Anne; Kloezeman, Jenneke; Leenstra, Sieger; Dirven, Clemens; Lamfers, Martine] ErasmusMC, Dept Neurosurg, Brain Tumor Ctr, Rotterdam, Netherlands.
[Treffers-Westerlaken, Elike; Debets, Reno] ErasmusMC, Dept Med Oncol, Lab Expt Tumor Immunol, Rotterdam, Netherlands.
[Fulci, Giulia] Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Brain Tumor Res Ctr, Boston, MA 02114 USA.
RP Lamfers, M (reprint author), ErasmusMC, Dept Neurosurg, Brain Tumor Ctr, Rotterdam, Netherlands.
EM m.lamfers@erasmusmc.nl
RI Lamfers, Martine/C-6246-2016;
OI Lamfers, Martine/0000-0001-7745-9029
NR 54
TC 9
Z9 9
U1 1
U2 9
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 MAY 27
PY 2014
VL 9
IS 5
AR e97495
DI 10.1371/journal.pone.0097495
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI5NG
UT WOS:000336914100014
PM 24866126
ER
PT J
AU McCormick, AW
Abuelezam, NN
Rhode, ER
Hou, TG
Walensky, RP
Pei, PP
Becker, JE
DiLorenzo, MA
Losina, E
Freedberg, KA
Lipsitch, M
Seage, GR
AF McCormick, Alethea W.
Abuelezam, Nadia N.
Rhode, Erin R.
Hou, Taige
Walensky, Rochelle P.
Pei, Pamela P.
Becker, Jessica E.
DiLorenzo, Madeline A.
Losina, Elena
Freedberg, Kenneth A.
Lipsitch, Marc
Seage, George R., III
TI Development, Calibration and Performance of an HIV Transmission Model
Incorporating Natural History and Behavioral Patterns: Application in
South Africa
SO PLOS ONE
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; ACTIVE ANTIRETROVIRAL THERAPY;
RANDOMIZED-CONTROLLED-TRIAL; SEXUAL RISK BEHAVIOR; DRUG-RESISTANT HIV;
COST-EFFECTIVENESS; POTENTIAL IMPACT; UNITED-STATES; COTE-DIVOIRE;
MATHEMATICAL-MODELS
AB Understanding HIV transmission dynamics is critical to estimating the potential population-wide impact of HIV prevention and treatment interventions. We developed an individual-based simulation model of the heterosexual HIV epidemic in South Africa and linked it to the previously published Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Model, which simulates the natural history and treatment of HIV. In this new model, the CEPAC Dynamic Model (CDM), the probability of HIV transmission per sexual encounter between short-term, long-term and commercial sex worker partners depends upon the HIV RNA and disease stage of the infected partner, condom use, and the circumcision status of the uninfected male partner. We included behavioral, demographic and biological values in the CDM and calibrated to HIV prevalence in South Africa pre-antiretroviral therapy. Using a multi-step fitting procedure based on Bayesian melding methodology, we performed 264,225 simulations of the HIV epidemic in South Africa and identified 3,750 parameter sets that created an epidemic and had behavioral characteristics representative of a South African population pre-ART. Of these parameter sets, 564 contributed 90% of the likelihood weight to the fit, and closely reproduced the UNAIDS HIV prevalence curve in South Africa from 1990-2002. The calibration was sensitive to changes in the rate of formation of short-duration partnerships and to the partnership acquisition rate among high-risk individuals, both of which impacted concurrency. Runs that closely fit to historical HIV prevalence reflect diverse ranges for individual parameter values and predict a wide range of possible steady-state prevalence in the absence of interventions, illustrating the value of the calibration procedure and utility of the model for evaluating interventions. This model, which includes detailed behavioral patterns and HIV natural history, closely fits HIV prevalence estimates.
C1 [McCormick, Alethea W.; Abuelezam, Nadia N.; Lipsitch, Marc; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP McCormick, AW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM amccormi@hsph.harvard.edu
RI Barley, Kamal/F-9579-2011
OI Barley, Kamal/0000-0003-1874-9813
FU [RO1-AI-058736]; [RO1-MH-087326]; [T32-AI-007535]; [T32-AI-007433]
FX This work was funded by the following grants: RO1-AI-058736,
RO1-MH-087326, T32-AI-007535 and T32-AI-007433. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 102
TC 3
Z9 3
U1 3
U2 8
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 MAY 27
PY 2014
VL 9
IS 5
AR e98272
DI 10.1371/journal.pone.0098272
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI5NG
UT WOS:000336914100044
PM 24867402
ER
PT J
AU Nandi, B
Pai, C
Huang, Q
Prabhala, RH
Munshi, NC
Gold, JS
AF Nandi, Bisweswar
Pai, Christine
Huang, Qin
Prabhala, Rao H.
Munshi, Nikhil C.
Gold, Jason S.
TI CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous
Intestinal Tumorigenesis
SO PLOS ONE
LA English
DT Article
ID INFLAMMATORY PROTEIN 3-ALPHA; COLORECTAL-CANCER; APC(MIN/+) MICE;
EXPRESSION LEVEL; TUMOR-GROWTH; CELLS; MACROPHAGES; METASTASIS; TH17;
PROLIFERATION
AB Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APC(MIN/+) mice) to generate APC(MIN/+) mice with CCR6 knocked out (CCR6KO-APC(MIN/+) mice). CCR6KO-APC(MIN/+) mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APC(MIN/+) also had normal sized spleens as compared to the enlarged spleens found in APC(MIN/+) mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APC(MIN/+) as compared to APC(MIN/+) mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy.
C1 [Nandi, Bisweswar; Pai, Christine; Prabhala, Rao H.] VA Boston Healthcare Syst, Res Serv, West Roxbury, MA USA.
[Nandi, Bisweswar; Huang, Qin; Prabhala, Rao H.; Munshi, Nikhil C.; Gold, Jason S.] Harvard Univ, Sch Med, Boston, MA 02138 USA.
[Huang, Qin] VA Boston Healthcare Syst, Serv, Pathol, West Roxbury, MA USA.
[Prabhala, Rao H.; Munshi, Nikhil C.] Dana Farber Canc Ctr, Boston, MA USA.
[Munshi, Nikhil C.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA.
[Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA.
[Gold, Jason S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Gold, JS (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA.
EM jgold4@partners.org
RI Gold, Jason/O-5112-2014
OI Gold, Jason/0000-0002-2925-4755
FU Department of Veterans Affairs Office of Research and Development
FX This work is supported by the Department of Veterans Affairs Office of
Research and Development through a Career Development Award-2 to JSG.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 41
TC 14
Z9 14
U1 0
U2 2
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 MAY 27
PY 2014
VL 9
IS 5
AR e97566
DI 10.1371/journal.pone.0097566
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI5NG
UT WOS:000336914100017
PM 24866282
ER
PT J
AU Wan, LX
Tan, MJ
Yang, J
Inuzuka, H
Dai, XP
Wu, T
Liu, J
Shaik, S
Chen, GA
Deng, J
Malumbres, M
Letai, A
Kirschner, MW
Sun, Y
Wei, WY
AF Wan, Lixin
Tan, Mingjia
Yang, Jie
Inuzuka, Hiroyuki
Dai, Xiangpeng
Wu, Tao
Liu, Jia
Shaik, Shavali
Chen, Guoan
Deng, Jing
Malumbres, Marcos
Letai, Anthony
Kirschner, Marc W.
Sun, Yi
Wei, Wenyi
TI APC(Cdc20) Suppresses Apoptosis through Targeting Bim for Ubiquitination
and Destruction
SO DEVELOPMENTAL CELL
LA English
DT Article
ID ANAPHASE-PROMOTING COMPLEX; CANCER THERAPEUTIC TARGET; BCL-2
FAMILY-MEMBERS; SPINDLE CHECKPOINT; CELL-DEATH; MITOTIC EXIT; BH3
DOMAINS; BETA-TRCP; CDC20; DEGRADATION
AB Anaphase-promoting complex Cdc20 (APC(Cdc20)) plays pivotal roles in governing mitotic progression. By suppressing APC(Cdc20), antimitotic agents activate the spindle-assembly checkpoint and induce apoptosis after prolonged treatment, whereas depleting endogenous Cdc20 suppresses tumorigenesis in part by triggering mitotic arrest and subsequent apoptosis. However, the molecular mechanism(s) underlying apoptosis induced by Cdc20 abrogation remains poorly understood. Here, we report the BH3-only proapoptotic protein Bim as an APC(Cdc20) target, such that depletion of Cdc20 sensitizes cells to apoptotic stimuli. Strikingly, Cdc20 and multiple APC-core components were identified in a small interfering RNA screen that, upon knockdown, sensitizes otherwise resistant cancer cells to chemoradiation in a Bim-dependent manner. Consistently, human adult T cell leukemia cells that acquire elevated APC(Cdc20) activity via expressing the Tax viral oncoprotein exhibit reduced Bim levels and resistance to anticancer agents. These results reveal an important role for APC(Cdc20) in governing apoptosis, strengthening the rationale for developing specific Cdc20 inhibitors as effective anticancer agents.
C1 [Wan, Lixin; Inuzuka, Hiroyuki; Dai, Xiangpeng; Liu, Jia; Shaik, Shavali; Wei, Wenyi] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tan, Mingjia; Yang, Jie; Sun, Yi] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
[Yang, Jie] Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China.
[Wu, Tao; Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Liu, Jia] Xi An Jiao Tong Univ, Inst Mitochondrial Biol & Med, Sch Life Sci & Technol, Xian 710049, Shaanxi, Peoples R China.
[Chen, Guoan] Univ Michigan, Ann Arbor, MI 48109 USA.
[Deng, Jing; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Malumbres, Marcos] Spanish Natl Canc Res Ctr CNIO, Cell Div, Madrid 28029, Spain.
[Malumbres, Marcos] Spanish Natl Canc Res Ctr CNIO, Canc Grp, Madrid 28029, Spain.
RP Wei, WY (reprint author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
EM wwei2@bidmc.harvard.edu
FU NIH [GM089763, GM094777, CA118762, CA156744, GM39023]; Lady Tata
Memorial Trust International Award for Research in Leukemia; University
of Michigan Comprehensive Cancer Center
FX We thank members of the Wei laboratory for critical reading of the
manuscript; Roya Khosravi-Far, Gutian Xiao, Christophe P. Nicot, Peter
Jackson, Matthew Meyerson, William Hahn, Frederic D. Sigoillot, and
Randall W. King for providing reagents; and Timothy J. Mitchison,
Randall W. King, and Susan E. Morgan-Lappe for helpful suggestions. W.
W. is a Leukemia and Lymphoma Society Scholar and ACS Research Scholar.
This work was supported in part by NIH grants GM089763 and GM094777 to
W. W., CA118762 and CA156744 to Y.S., and GM39023 to M. W. K. L. W. was
supported by the Lady Tata Memorial Trust International Award for
Research in Leukemia. This work was also partially supported by a
research grant from University of Michigan Comprehensive Cancer Center
to Y.S.
NR 45
TC 30
Z9 32
U1 4
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD MAY 27
PY 2014
VL 29
IS 4
BP 377
EP 391
DI 10.1016/j.devcel.2014.04.022
PG 15
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA AI1KA
UT WOS:000336608600003
PM 24871945
ER
PT J
AU Carroll, KJ
Esain, V
Garnaas, MK
Cortes, M
Dovey, MC
Nissim, S
Frechette, GM
Liu, SY
Kwan, W
Cutting, CC
Harris, JM
Gorelick, DA
Halpern, ME
Lawson, ND
Goessling, W
North, TE
AF Carroll, Kelli J.
Esain, Virginie
Garnaas, Maija K.
Cortes, Mauricio
Dovey, Michael C.
Nissim, Sahar
Frechette, Gregory M.
Liu, Sarah Y.
Kwan, Wanda
Cutting, Claire C.
Harris, James M.
Gorelick, Daniel A.
Halpern, Marnie E.
Lawson, Nathan D.
Goessling, Wolfram
North, Trista E.
TI Estrogen Defines the Dorsal-Ventral Limit of VEGF Regulation to Specify
the Location of the Hemogenic Endothelial Niche
SO DEVELOPMENTAL CELL
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; RECEPTOR-BETA; GROWTH-FACTOR; VENOUS
PROGENITORS; AORTIC ENDOTHELIUM; NORMAL-PREGNANCY; IN-VIVO; ZEBRAFISH;
NOTCH; PATHWAY
AB Genetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17 beta-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects. Conversely, repression of endogenous E2 activity increased somitic VEGF expression and vascular target regulation, shifting assignment of arterial/venous fate and HE localization; blocking E2 signaling allowed venous production of scl+/runx1+ cells, independent of arterial identity acquisition. Together, these data suggest that yolk-derived E2 sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral regulatory limits of VEGF.
C1 [Carroll, Kelli J.; Esain, Virginie; Cortes, Mauricio; Dovey, Michael C.; Frechette, Gregory M.; Liu, Sarah Y.; Kwan, Wanda; Harris, James M.; North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Garnaas, Maija K.; Nissim, Sahar; Cutting, Claire C.; Goessling, Wolfram] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gorelick, Daniel A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Halpern, Marnie E.] Carnegie Inst Sci, Baltimore, MD 21218 USA.
[Lawson, Nathan D.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Goessling, Wolfram; North, Trista E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Goessling, W (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM wgoessling@partners.org; tnorth@bidmc.harvard.edu
OI Goessling, Wolfram/0000-0001-9972-1569
FU American Society of Hematology Scholar Award; National Institute of
Environmental Health Sciences [R21]; National Science Foundation
Graduate Research Fellowship; Harvard University Vranos Family Graduate
Research Fellowship
FX We thank P. Crosier and K. Crosier for the runx1P1:eGFP line, S. W. Jin
for the hs:VEGFAa line, and B. Paw, I. Drummond, C. Burns, and M. Lin
for suggestions and reagents. This investigation was supported by an
American Society of Hematology Scholar Award and a National Institute of
Environmental Health Sciences R21 (to T.E.N.). K.J.C. is supported by a
National Science Foundation Graduate Research Fellowship and a Harvard
University Vranos Family Graduate Research Fellowship.
NR 64
TC 4
Z9 4
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD MAY 27
PY 2014
VL 29
IS 4
BP 437
EP 453
DI 10.1016/j.devcel.2014.04.012
PG 17
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA AI1KA
UT WOS:000336608600007
PM 24871948
ER
PT J
AU Muller, E
White, S
Delmonico, F
AF Muller, Elmi
White, Sarah
Delmonico, Francis
TI Regional Perspective: Developing Organ Transplantation in Sub-Saharan
Africa
SO TRANSPLANTATION
LA English
DT Editorial Material
DE Developing countries/Africa
C1 [Muller, Elmi] Univ Cape Town, Groote Schuur Hosp, Dept Surg, ZA-7925 Cape Town, South Africa.
[White, Sarah] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Delmonico, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Muller, E (reprint author), Groote Schuur Hosp, Dept Surg, Main Rd, ZA-7925 Cape Town, South Africa.
EM elmi.muller@uct.ac.za
RI Muller, Elmi/I-3258-2014
OI Muller, Elmi/0000-0003-4891-5296
NR 1
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD MAY 27
PY 2014
VL 97
IS 10
BP 975
EP 976
DI 10.1097/TP.0000000000000144
PG 2
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA AI3FL
UT WOS:000336745900006
PM 24770622
ER
PT J
AU Lassen, KG
Kuballa, P
Conway, KL
Patel, KK
Becker, CE
Peloquin, JM
Villablanca, EJ
Norman, JM
Liu, TC
Heath, RJ
Becker, ML
Fagbami, L
Horn, H
Mercer, J
Yilmaz, OH
Jaffe, JD
Shamji, AF
Bhan, AK
Carr, SA
Daly, MJ
Virgin, HW
Schreiber, SL
Stappenbeck, TS
Xavier, RJ
AF Lassen, Kara G.
Kuballa, Petric
Conway, Kara L.
Patel, Khushbu K.
Becker, Christine E.
Peloquin, Joanna M.
Villablanca, Eduardo J.
Norman, Jason M.
Liu, Ta-Chiang
Heath, Robert J.
Becker, Morgan L.
Fagbami, Lola
Horn, Heiko
Mercer, Johnathan
Yilmaz, Omer H.
Jaffe, Jacob D.
Shamji, Alykhan F.
Bhan, Atul K.
Carr, Steven A.
Daly, Mark J.
Virgin, Herbert W.
Schreiber, Stuart L.
Stappenbeck, Thaddeus S.
Xavier, Ramnik J.
TI Atg16L1 T300A variant decreases selective autophagy resulting in altered
cytokine signaling and decreased antibacterial defense
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; PANETH CELLS; SUSCEPTIBILITY
LOCI; GENE ATG16L1; PATHOGENESIS; PHENOTYPES; REVEALS; NOD2
AB A coding polymorphism (Thr300Ala) in the essential autophagy gene, autophagy related 16-like 1 (ATG16L1), confers increased risk for the development of Crohn disease, although the mechanisms by which single disease-associated polymorphisms contribute to pathogenesis have been difficult to dissect given that environmental factors likely influence disease initiation in these patients. Here we introduce a knock-in mouse model expressing the Atg16L1 T300A variant. Consistent with the human polymorphism, T300A knock-in mice do not develop spontaneous intestinal inflammation, but exhibit morphological defects in Paneth and goblet cells. Selective autophagy is reduced in multiple cell types from T300A knock-in mice compared with WT mice. The T300A polymorphism significantly increases caspase 3- and caspase 7-mediated cleavage of Atg16L1, resulting in lower levels of full-length Atg16Ll T300A protein. Moreover, Atg16L1 T300A is associated with decreased antibacterial autophagy and increased IL-1 beta production in primary cells and in vivo. Quantitative proteomics for protein interactors of ATG16L1 identified previously unknown nonoverlapping sets of proteins involved in ATG16L1-dependent antibacterial autophagy or IL-1 beta production. These findings demonstrate how the T300A polymorphism leads to cell type- and pathway-specific disruptions of selective autophagy and suggest a mechanism by which this polymorphism contributes to disease.
C1 [Lassen, Kara G.; Kuballa, Petric; Conway, Kara L.; Villablanca, Eduardo J.; Heath, Robert J.; Fagbami, Lola; Horn, Heiko; Mercer, Johnathan; Jaffe, Jacob D.; Carr, Steven A.; Daly, Mark J.; Xavier, Ramnik J.] Broad Inst, Cambridge, MA 02142 USA.
[Lassen, Kara G.; Kuballa, Petric; Conway, Kara L.; Becker, Christine E.; Peloquin, Joanna M.; Villablanca, Eduardo J.; Heath, Robert J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Conway, Kara L.; Peloquin, Joanna M.; Villablanca, Eduardo J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Patel, Khushbu K.; Norman, Jason M.; Liu, Ta-Chiang; Becker, Morgan L.; Virgin, Herbert W.; Stappenbeck, Thaddeus S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Horn, Heiko] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Yilmaz, Omer H.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Yilmaz, Omer H.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Yilmaz, Omer H.; Bhan, Atul K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shamji, Alykhan F.; Schreiber, Stuart L.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.
[Bhan, Atul K.; Daly, Mark J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
RP Schreiber, SL (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.
EM stuart_schreiber@harvard.edu; xavier@molbio.mgh.harvard.edu
OI Horn, Heiko/0000-0003-4898-0557; Villablanca,
Eduardo/0000-0001-9522-9729
FU Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis
Foundation of America Genetics Initiative; National Institutes of Health
[DK097485, DK043351, AI084887]; Deutsche Forschungsgemeinschaft
[KU2511/1-1]
FX We thank Natalia Nedelsky for editorial assistance and Brian Seed and
Naifang Liu for help with the knock-in model design. This work was
supported by the Leona M. and Harry B. Helmsley Charitable Trust, the
Crohn's and Colitis Foundation of America Genetics Initiative, National
Institutes of Health Grants DK097485 and DK043351 (to R.J.X.) and
AI084887 (to T.S.S. and H.W.V.), and Deutsche Forschungsgemeinschaft
Fellowship Award KU2511/1-1 (to P.K.).
NR 37
TC 72
Z9 73
U1 1
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7741
EP 7746
DI 10.1073/pnas.1407001111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300057
PM 24821797
ER
PT J
AU Yi, TF
Zhai, B
Yu, YH
Kiyotsugu, Y
Raschle, T
Etzkorn, M
Seo, HC
Nagiec, M
Luna, RE
Reinherz, EL
Blenis, J
Gygi, SP
Wagner, G
AF Yi, Tingfang
Zhai, Bo
Yu, Yonghao
Kiyotsugu, Yoshikawa
Raschle, Thomas
Etzkorn, Manuel
Seo, Hee-Chan
Nagiec, Michal
Luna, Rafael E.
Reinherz, Ellis L.
Blenis, John
Gygi, Steven P.
Wagner, Gerhard
TI Quantitative phosphoproteomic analysis reveals system-wide signaling
pathways downstream of SDF-1/CXCR4 in breast cancer stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chemokine receptor; GPCR; MAPK
ID PROTEIN-KINASE-A; MAP KINASE; IN-VIVO; PHOSPHORYLATION; IDENTIFICATION;
ACTIVATION; NETWORKS; ISOFORMS; FAMILY
AB Breast cancer is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.7 million new cases and 522,000 deaths around the world in 2012 alone. Cancer stem cells (CSCs) are essential for tumor reoccurrence and metastasis which is the major source of cancer lethality. G protein-coupled receptor chemokine (C-X-C motif) receptor 4 (CXCR4) is critical for tumor metastasis. However, stromal cell-derived factor 1 (SDF-1)/CXCR4-mediated signaling pathways in breast CSCs are largely unknown. Using isotope reductive dimethylation and large-scale MS-based quantitative phosphoproteome analysis, we examined protein phosphorylation induced by SDF-1/CXCR4 signaling in breast CSCs. We quantified more than 11,000 phosphorylation sites in 2,500 phosphoproteins. Of these phosphosites, 87% were statistically unchanged in abundance in response to SDF-1/CXCR4 stimulation. In contrast, 545 phosphosites in 266 phosphoproteins were significantly increased, whereas 113 phosphosites in 74 phosphoproteins were significantly decreased. SDF-1/CXCR4 increases phosphorylation in 60 cell migration-and invasion-related proteins, of them 43 (>70%) phosphoproteins are unrecognized. In addition, SDF-1/CXCR4 upregulates the phosphorylation of 44 previously uncharacterized kinases, 8 phosphatases, and 1 endogenous phosphatase inhibitor. Using computational approaches, we performed system-based analyses examining SDF-1/CXCR4-mediated phosphoproteome, including construction of kinase-substrate network and feedback regulation loops downstream of SDF-1/CXCR4 signaling in breast CSCs. We identified a previously unidentified SDF-1/CXCR4-PKA-MAP2K2-ERK signaling pathway and demonstrated the feedback regulation on MEK, ERK1/2, delta-catenin, and PPP1C alpha in SDF-1/CXCR4 signaling in breast CSCs. This study gives a system-wide view of phosphorylation events downstream of SDF-1/CXCR4 signaling in breast CSCs, providing a resource for the study of CSC-targeted cancer therapy.
C1 [Yi, Tingfang; Raschle, Thomas; Etzkorn, Manuel; Seo, Hee-Chan; Luna, Rafael E.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Zhai, Bo; Yu, Yonghao; Nagiec, Michal; Blenis, John; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kiyotsugu, Yoshikawa; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Gygi, SP (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM steven_gygi@hms.harvard.edu; gerhard_wagner@hms.harvard.edu
RI Etzkorn, Manuel/H-5042-2013
OI Etzkorn, Manuel/0000-0002-9796-3246
FU National Institutes of Health [CA068262]
FX We thank Robert Weinberg of Whitehead Institute for Biomedical Research
of Massachusetts Institute of Technology for the HMLER cell lines. This
work was supported by funding from National Institutes of Health Grant
CA068262 (to G.W.).
NR 32
TC 31
Z9 34
U1 2
U2 25
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP E2182
EP E2190
DI 10.1073/pnas.1404943111
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300007
PM 24782546
ER
PT J
AU Han, SH
Cho, FH
Song, YK
Paulsen, J
Song, YQ
Kim, YR
Kim, JK
Cho, G
Cho, H
AF Han, S. H.
Cho, F. H.
Song, Y. K.
Paulsen, J.
Song, Y. Q.
Kim, Y. R.
Kim, J. K.
Cho, G.
Cho, H.
TI Ultrafast 3D spin-echo acquisition improves Gadolinium-enhanced MRI
signal contrast enhancement
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MAGNETIC-RESONANCE; IMAGING TECHNIQUE; TRACER KINETICS; GRADIENT-ECHO;
DYNAMIC MRI; DCE-MRI; K-SPACE; SEQUENCE; AGENTS; FLASH
AB Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T-2* effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (X32) and compressed sensing (CS) sampling (X8) allowed highly-accelerated 3D Multiple-Modulation-Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (X7) over that of corresponding FLASH acquisitions (X2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.
C1 [Han, S. H.; Cho, F. H.; Song, Y. K.; Cho, H.] UNIST, Dept Biomed Engn, Ulsan, South Korea.
[Paulsen, J.; Song, Y. Q.] Schlumberger Doll Res Ctr, Cambridge, MA USA.
[Kim, Y. R.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Kim, J. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol,Dept Radiol, Seoul, South Korea.
[Cho, G.] Korea Basic Sci Inst, Ochang, South Korea.
RP Cho, G (reprint author), Korea Basic Sci Inst, Ochang, South Korea.
EM gyunggoo@kbsi.re.kr; hjcho@unist.ac.kr
FU National Research Foundation of Korea (NRF) - Korean government
[2010-0028684]; Future Challenge Research Fund of UNIST (Ulsan National
Institute of Science and Technology) [1.130030.01]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korean government (No.2010-0028684). This work
was also supported by the 2013 Future Challenge Research Fund (Project
No. 1.130030.01) of UNIST (Ulsan National Institute of Science and
Technology).
NR 49
TC 1
Z9 1
U1 0
U2 11
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 MAY 27
PY 2014
VL 4
AR 5061
DI 10.1038/srep05061
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8DO
UT WOS:000336364500003
PM 24863102
ER
PT J
AU Khan, S
Lefevre, J
Baillet, S
Michmizos, KP
Ganesan, S
Kitzbichler, MG
Zetino, M
Haemaelaeinen, M
Papadelis, C
Kenet, T
AF Khan, Sheraz
Lefevre, Julien
Baillet, Sylvain
Michmizos, Konstantinos P.
Ganesan, Santosh
Kitzbichler, Manfred G.
Zetino, Manuel
Haemaelaeinen, MattiS.
Papadelis, Christos
Kenet, Tal
TI Encoding cortical dynamics in sparse features
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE motion field; optical flow; MEG source imaging; Helmholtz-Hodge
decomposition; epilepsy
ID TUBEROUS SCLEROSIS; OPTICAL-FLOW; FIELD DECOMPOSITION; LOCALIZATION;
PROPAGATION; BRAIN; MEG; MAGNETOENCEPHALOGRAPHY; EPILEPSY; EEG
AB Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz-Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical MEG/EEG source imaging data.
C1 [Khan, Sheraz; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Haemaelaeinen, MattiS.; Kenet, Tal] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Khan, Sheraz; Michmizos, Konstantinos P.] MIT, McGovern Inst, Cambridge, MA 02139 USA.
[Khan, Sheraz; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Kenet, Tal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Lefevre, Julien] Univ Toulon & Var, Aix Marseille Univ, CNRS, ENSAM LSIS UMR 7296, Marseille, France.
[Baillet, Sylvain] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Kitzbichler, Manfred G.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England.
[Papadelis, Christos] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci,BabyMEG Fac, Boston, MA USA.
[Papadelis, Christos] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med, Boston, MA USA.
RP Khan, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, 1115-Q,149 13th St, Charlestown, MA 02129 USA.
EM sheraz@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013;
OI Khan, Sheraz/0000-0002-6792-3577
FU Nancy Lurie Marks Family Foundation; Simons Foundation; NIBIB
[5R01EB009048]; Quebec Fund for Health Research; Natural Sciences and
Engineering Research Council of Canada; [P41RR014075]; [NIH
2R01EB009048-05]
FX This work was supported by the Nancy Lurie Marks Family Foundation
(Sheraz Khan, Manfred G. Kitzbichler, Tal Kenet), Simons Foundation (Tal
Kenet), NIBIB:5R01EB009048 (Matti S. Hamalainen), P41RR014075 (Matti S.
Hamalainen), Senior-Scientist Salary Award from the Quebec Fund for
Health Research (Sylvain Baillet), NIH 2R01EB009048-05 (Sylvain Baillet)
and a Discovery Grant from the Natural Sciences and Engineering Research
Council of Canada (Sylvain Baillet).
NR 37
TC 2
Z9 2
U1 0
U2 7
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD MAY 23
PY 2014
VL 8
AR 338
DI 10.3389/fnhum.2014.00338
PG 9
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA AL9XX
UT WOS:000339498000001
PM 24904377
ER
PT J
AU Liu, RJ
Dai, ZY
Yeager, M
Irizarry, RA
Ritchie, ME
AF Liu, Ruijie
Dai, Zhiyin
Yeager, Meredith
Irizarry, Rafael A.
Ritchie, Matthew E.
TI KRLMM: an adaptive genotype calling method for common and low frequency
variants
SO BMC BIOINFORMATICS
LA English
DT Article
DE Genotyping; Clustering; Microarray data analysis
ID GENOME-WIDE ASSOCIATION; ALGORITHM; POPULATION; BEADCHIPS; RARE; MAP
AB Background: SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the underlying models rely on each genotype having a reasonable number of observations to ensure accurate clustering.
Results: Here we develop KRLMM, a new method for converting raw intensities into genotype calls that aims to overcome this issue. Our method is unique in that it applies careful between sample normalization and allows a variable number of clusters k (1, 2 or 3) for each SNP, where k is predicted using the available data. We compare our method to four genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several Illumina data sets that include samples from the HapMap project where the true genotypes are known in advance. All methods were found to have high overall accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be consistently more accurate than GenCall and Illuminus on our test data.
Conclusions: Methods that tailor their approach to calling low frequency variants by either varying the number of clusters (KRLMM) or using information from other SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source crlmm package distributed via the Bioconductor project (http://www.bioconductor.org).
C1 [Liu, Ruijie; Dai, Zhiyin; Ritchie, Matthew E.] Walter & Eliza Hall Inst Med Res, Mol Med Div, Parkville, Vic 3052, Australia.
[Yeager, Meredith] NCI Frederick, Canc Genom Res Lab, SAIC Frederick Inc, Frederick, MD 20877 USA.
[Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Ritchie, Matthew E.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia.
[Ritchie, Matthew E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
RP Irizarry, RA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, CLSB 11007,450 Brookline Ave, Boston, MA 02215 USA.
EM rafa@jimmy.harvard.edu; mritchie@wehi.edu.au
OI Ritchie, Matthew/0000-0002-7383-0609
FU NHMRC [1050661]; Victorian State Government; Australian Government NHMRC
IRIISS; NIH [R01GM083084]
FX We thank Gordon Smyth for advice on regression analysis. This research
was supported by NHMRC Project grant 1050661 (RL, MR), Victorian State
Government Operational Infrastructure Support, Australian Government
NHMRC IRIISS and NIH grant R01GM083084 (RI).
NR 26
TC 0
Z9 0
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAY 23
PY 2014
VL 15
AR 158
DI 10.1186/1471-2105-15-158
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AK2IS
UT WOS:000338243300001
PM 24886250
ER
PT J
AU Kunchithapautham, K
Atkinson, C
Rohrer, B
AF Kunchithapautham, Kannan
Atkinson, Carl
Rohrer, Baerbel
TI Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid
Accumulation in Retinal Pigment Epithelium through Oxidative Stress and
Complement Activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
CIGARETTE-SMOKE; BRUCHS MEMBRANE; CHOROIDAL NEOVASCULARIZATION;
REGULATORY PROTEINS; ALTERNATIVE PATHWAY; GEOGRAPHIC ATROPHY;
APOLIPOPROTEIN-E
AB Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD.
C1 [Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
[Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Rohrer, Baerbel] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA.
RP Rohrer, B (reprint author), 167 Ashley Ave, Charleston, SC 29425 USA.
EM rohrer@musc.edu
FU National Institutes of Health [C06RR015455]
FX Animal studies were conducted in a facility constructed with support
from the National Institutes of Health Grant C06RR015455.
NR 78
TC 26
Z9 26
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 23
PY 2014
VL 289
IS 21
BP 14534
EP 14546
DI 10.1074/jbc.M114.564674
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI9JE
UT WOS:000337248100012
PM 24711457
ER
PT J
AU Wang, J
Lin, XQ
Wang, S
Wang, CF
Wang, QX
Duan, XK
Lu, P
Wang, Q
Wang, CY
Liu, XS
Huang, JY
AF Wang, Juan
Lin, Xueqiu
Wang, Su
Wang, Chenfei
Wang, Qixuan
Duan, Xikun
Lu, Peng
Wang, Qian
Wang, Chengyang
Liu, X. Shirley
Huang, Jinyan
TI PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene
expression
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LINKED MENTAL-RETARDATION; CLEFT LIP/CLEFT PALATE; HISTONE METHYLATION;
LOCATION ANALYSIS; DEMETHYLASE PHF8; H3K4 DEMETHYLASE; NEURONAL GENES;
TRANSCRIPTION; MUTATIONS; GENOME
AB Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associate with another regulator, REST/NRSF, predominately at promoter regions via studying several published PHF8 chromatin immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that PHF8 not only activates but may also repress gene expression.
C1 [Wang, Juan; Lin, Xueqiu; Wang, Su; Wang, Chenfei; Wang, Qixuan; Duan, Xikun; Wang, Qian; Wang, Chengyang; Huang, Jinyan] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China.
[Lu, Peng] Fudan Univ, ShanghaiMed Sch, Dept Environm Hlth, Yangpu, Peoples R China.
[Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
[Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
RP Huang, JY (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China.
EM jyhuang@tongji.edu.cn
FU National Basic Reaserch Program of China (973 Programs) [2010CB944904];
National Natural Science Foundation of China [31329003]
FX We thank group members for constructive comments. This project was
supported by the National Basic Reaserch Program of China (973 Programs:
2010CB944904), the National Natural Science Foundation of China
(31329003).
NR 28
TC 1
Z9 1
U1 4
U2 8
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 MAY 23
PY 2014
VL 4
AR 5008
DI 10.1038/srep05008
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH6TN
UT WOS:000336263700001
PM 24852203
ER
PT J
AU Schwerdtfeger, K
Wand, S
Schmid, O
Roessler, M
Quintel, M
Leissner, KB
Russo, SG
AF Schwerdtfeger, Katrin
Wand, Saskia
Schmid, Oliver
Roessler, Markus
Quintel, Michael
Leissner, Kay B.
Russo, Sebastian G.
TI A prospective, blinded evaluation of a video-assisted '4-stage approach'
during undergraduate student practical skills training
SO BMC MEDICAL EDUCATION
LA English
DT Article
DE Teaching methods; Medical students; Trauma care
ID TEACHING TECHNIQUE; MEDICAL-EDUCATION; EMERGENCY
AB Background: The 4-stage approach (4-SA) is used as a didactic method for teaching practical skills in international courses on resuscitation and the structured care of trauma patients. The aim of this study was to evaluate objective and subjective learning success of a video-assisted 4-SA in teaching undergraduate medical students.
Methods: The participants were medical students learning the principles of the acute treatment of trauma patients in their multidiscipline course on emergency and intensive care medicine. The participants were quasi-randomly divided into two groups. The 4-SA was used in both groups. In the control group, all four steps were presented by an instructor. In the study group, the first two steps were presented as a video. At the end of the course a 5-minute objective, structured clinical examination (OSCE) of a simulated trauma patient was conducted. The test results were divided into objective results obtained through a checklist with 9 dichotomous items and the assessment of the global performance rated subjectively by the examiner on a Likert scale from 1 to 6.
Results: 313 students were recruited; the results of 256 were suitable for analysis. The OSCE results were excellent in both groups and did not differ significantly (control group: median 9, interquantil range (IQR) 8-9, study group: median 9, IQR 8-9; p = 0.29). The global performance was rated significantly better for the study group (median 1, IQR 1-2 vs. median 2, IQR 1-3; p < 0.01). The relative knowledge increase, stated by the students in their evaluation after the course, was greater in the study group (85% vs. 80%).
Conclusion: It is possible to employ video assistance in the classical 4-SA with comparable objective test results in an OSCE. The global performance was significantly improved with use of video assistance.
C1 [Schwerdtfeger, Katrin; Wand, Saskia; Schmid, Oliver; Roessler, Markus; Quintel, Michael; Russo, Sebastian G.] Univ Hosp Gottingen, Dept Anaesthesiol, D-37075 Gottingen, Germany.
[Leissner, Kay B.] VA Boston Healthcare Syst, Boston, MA USA.
RP Russo, SG (reprint author), Univ Hosp Gottingen, Dept Anaesthesiol, D-37075 Gottingen, Germany.
EM s.russo@medizin.uni-goettingen.de
NR 14
TC 1
Z9 1
U1 2
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6920
J9 BMC MED EDUC
JI BMC Med. Educ.
PD MAY 22
PY 2014
VL 14
AR 104
DI 10.1186/1472-6920-14-104
PG 6
WC Education & Educational Research; Education, Scientific Disciplines
SC Education & Educational Research
GA AJ0AZ
UT WOS:000337312600002
PM 24885140
ER
PT J
AU Sun, T
Wang, X
He, HH
Sweeney, CJ
Liu, SX
Brown, M
Balk, S
Lee, GSM
Kantoff, PW
AF Sun, T.
Wang, X.
He, H. H.
Sweeney, C. J.
Liu, S. X.
Brown, M.
Balk, S.
Lee, G-S M.
Kantoff, P. W.
TI MiR-221 promotes the development of androgen independence in prostate
cancer cells via downregulation of HECTD2 and RAB1A
SO ONCOGENE
LA English
DT Article
DE microRNA; miR-221; castration resistant prostate cancer; androgen
receptor signaling
ID BREAST-CANCER; MESENCHYMAL TRANSITION; TAMOXIFEN RESISTANCE; RECEPTOR;
EXPRESSION; GENES; PROGRESSION; CASTRATION; MICRORNAS; PROTEINS
AB Hormone-sensitive prostate cancer typically progresses to castration resistant prostate cancer (CRPC) after the androgen deprivation therapy. We investigated the impact of microRNAs (miRs) in the transition of prostate cancer to CRPC. MiR-221/-222 was highly expressed in bone metastatic CRPC tumor specimens. We previously demonstrated that transient overexpression of miR-221/-222 in LNCaP promoted the development of the CRPC phenotype. In current study, we show that stably overexpressing miR-221 confers androgen independent (AI) cell growth in LNCaP by rescuing LNCaP cells from growth arrest at G1 phase due to the lack of androgen. Overexpressing of miR-221 in LNCaP reduced the transcription of a subgroup of androgen-responsive genes without affecting the androgen receptor (AR) or AR-androgen integrity. By performing systematic biochemical and bioinformatical analyses, we identified two miR-221 targets, HECTD2 and RAB1A, which could mediate the development of CRPC phenotype in multiple prostate cancer cell lines. Downregulation of HECTD2 significantly affected the androgen-induced and AR-mediated transcription, and downregulation of HECTD2 or RAB1A enhances AI cell growth. As a result of the elevated expression of miR-221, expression of many cell cycle genes was altered and pathways promoting epithelial to mesenchymal transition/tumor metastasis were activated. We hypothesize that a major biological consequence of upregulation of miR-221 is reprogramming of AR signaling, which in turn may mediate the transition to the CRPC phenotype.
C1 [Sun, T.; Wang, X.; He, H. H.; Sweeney, C. J.; Brown, M.; Lee, G-S M.; Kantoff, P. W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[He, H. H.; Liu, S. X.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Balk, S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Biol Program,Dept Med, Boston, MA 02215 USA.
RP Lee, GSM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Gwo-shu_lee@dfci.harvard.edu; philip_kantoff@dfci.harvard.edu
OI Brown, Myles/0000-0002-8213-1658
FU SPORE in Prostate Cancer [2 P50 CA090381-06]; Department of Defense
(DoD) Prostate Cancer Training [W81XWH-09-1-0372]
FX This work was supported by a SPORE in Prostate Cancer 2 P50 CA090381-06
and TS was supported by a Department of Defense (DoD) Prostate Cancer
Training Award W81XWH-09-1-0372. We thank Dr Peter T Nelson at
University of Kentucky and Dr Zissimos Mourelatos at University of
Pennsylvania for kindly providing us the anti-AGO antibody. We also
thank Dr Wang-xia Wang for technical suggestions on AGO-RIP-Chip
experiments.
NR 50
TC 42
Z9 44
U1 1
U2 8
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 MAY 22
PY 2014
VL 33
IS 21
BP 2790
EP 2800
DI 10.1038/onc.2013.230
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AI9EH
UT WOS:000337231700012
PM 23770851
ER
PT J
AU Birnbaum, ME
Mendoza, JL
Sethi, DK
Dong, S
Glanville, J
Dobbins, J
Ozkan, E
Davis, MM
Wucherpfennig, KW
Garcia, KC
AF Birnbaum, Michael E.
Mendoza, Juan L.
Sethi, Dhruv K.
Dong, Shen
Glanville, Jacob
Dobbins, Jessica
Oezkan, Engin
Davis, Mark M.
Wucherpfennig, Kai W.
Garcia, K. Christopher
TI Deconstructing the Peptide-MHC Specificity of T Cell Recognition
SO CELL
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; CLASS-II MHC;
RECEPTOR CROSS-REACTIVITY; YEAST SURFACE DISPLAY; MULTIPLE-SCLEROSIS;
MOLECULAR MIMICRY; DIRECTED EVOLUTION; ANTIGEN; LIGANDS
AB In order to survey a universe of major histocompatibility complex (MHC)-presented peptide antigens whose numbers greatly exceed the diversity of the T cell repertoire, T cell receptors (TCRs) are thought to be cross- reactive. However, the nature and extent of TCR cross- reactivity has not been conclusively measured experimentally. We developed a system to identify MHC-presented peptide ligands by combining TCR selection of highly diverse yeast-displayed peptide-MHC libraries with deep sequencing. Although we identified hundreds of peptides reactive with each of five different mouse and human TCRs, the selected peptides possessed TCR recognition motifs that bore a close resemblance to their known antigens. This structural conservation of the TCR interaction surface allowed us to exploit deep-sequencing information to computationally identify activating microbial and self-ligands for human autoimmune TCRs. The mechanistic basis of TCR cross- reactivity described here enables effective surveillance of diverse self and foreign antigens without necessitating degenerate recognition of nonhomologous peptides.
C1 [Birnbaum, Michael E.; Mendoza, Juan L.; Dong, Shen; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Birnbaum, Michael E.; Mendoza, Juan L.; Dong, Shen; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA.
[Glanville, Jacob; Davis, Mark M.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
[Birnbaum, Michael E.; Glanville, Jacob; Davis, Mark M.; Garcia, K. Christopher] Stanford Univ, Sch Med, Program Immunol, Stanford, CA 94305 USA.
[Oezkan, Engin; Davis, Mark M.; Garcia, K. Christopher] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Sethi, Dhruv K.; Dobbins, Jessica; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Dobbins, Jessica; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA.
RP Garcia, KC (reprint author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM kcgarcia@stanford.edu
OI Birnbaum, Michael/0000-0002-2281-3518; Dobbins,
Jessica/0000-0002-6074-5595
FU Regina Casper Stanford Graduate Fellowship; Gerald J. Lieberman
Fellowship; National Science Foundation; Helen Hay Whitney Foundation;
NIH [PO1 AI045757, R01 AI03867, R01 AI022511, U19 4100041120,
P41GM103393]; HHMI; U.S. Department of Energy [DE-AC02-76SF00515]; DOE
Office of Biological and Environmental Research; NCI-K01CA175127
FX We thank Suzanne Fischer, Gary Mantalas, and Nelida Prado for technical
assistance and Jarrett Adams, Lauren Ely, and Evan Newell for helpful
discussions. M.E.B. was supported by a Regina Casper Stanford Graduate
Fellowship, a Gerald J. Lieberman Fellowship, and a National Science
Foundation Graduate Fellowship. J.L.M. was supported by NCI-K01CA175127
and a Helen Hay Whitney Foundation postdoctoral fellowship. This work
was supported by the NIH (PO1 AI045757 to K.W.W., R01 AI03867 to K. C.
G., R01 AI022511 to M. M. D., and U19 4100041120 to M. M. D. and K. C.
G.) and HHMI (to M. M. D. and K. C. G.). Use of the Stanford Synchrotron
Radiation Lightsource, SLAC National Accelerator Laboratory, is
supported by the U.S. Department of Energy under Contract No.
DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is
supported by the DOE Office of Biological and Environmental Research and
by the National Institutes of Health (including P41GM103393).
NR 68
TC 101
Z9 103
U1 7
U2 54
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 MAY 22
PY 2014
VL 157
IS 5
BP 1073
EP 1087
DI 10.1016/j.cell.2014.03.047
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH9CG
UT WOS:000336437200011
PM 24855945
ER
PT J
AU Rai, G
Joshi, N
Jung, JE
Liu, Y
Schultz, L
Yasgar, A
Perry, S
Diaz, G
Zhang, QL
Kenyon, V
Jadhav, A
Simeonov, A
Lo, EH
van Leyen, K
Maloney, DJ
Holman, TR
AF Rai, Ganesha
Joshi, Netra
Jung, Joo Eun
Liu, Yu
Schultz, Lena
Yasgar, Adam
Perry, Steve
Diaz, Giovanni
Zhang, Qiangli
Kenyon, Victor
Jadhav, Ajit
Simeonov, Anton
Lo, Eng H.
van Leyen, Klaus
Maloney, David J.
Holman, Theodore R.
TI Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase
as Anti-Stroke Therapies
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLATELET-TYPE 12-LIPOXYGENASE; SPONGE-DERIVED TERPENOIDS; TRANSIENT
FOCAL ISCHEMIA; PANCREATIC-CANCER CELLS; OXIDATIVE STRESS; HUMAN
15-LIPOXYGENASE; 5-LIPOXYGENASE INHIBITION; MAMMALIAN 15-LIPOXYGENASE;
GLUTATHIONE DEPLETION; RHEUMATOID-ARTHRITIS
AB A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.
C1 [Jung, Joo Eun; Liu, Yu; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA.
[Rai, Ganesha; Schultz, Lena; Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Joshi, Netra; Perry, Steve; Diaz, Giovanni; Zhang, Qiangli; Kenyon, Victor; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
RP van Leyen, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA.
EM klaus_vanleyen@hms.harvard.edu; maloneyd@mail.nih.gov;
tholman@chemistry.ucsc.edu
FU National Institute of Health [R01 GM56062, R01 NS049430, R01 NS069939];
Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [R03 MH081283, U54MH084681]; National
Center for Advancing Translational Sciences; NIH [S10-RR20939];
California Institute for Quantitative Biosciences
FX We thank Sam Michael and Richard Jones for automation support; Paul
Shinn and Danielle van Leer for assistance with compound management;
William Leister, Heather Baker, James Bougie, Elizabeth Fernandez, and
Christopher Leclair for analytical chemistry and purification support;
Kimloan Nguyen for in vitro ADME data; and Eric Hoobler for helping with
the COX assays. Financial support was from the National Institute of
Health (grants R01 GM56062 (T.R.H.), R01 NS049430 (K.v.L.), and R01
NS069939) and the Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research (R03 MH081283
(T.R.H.)). G.R., L.S., A.Y., A.J., A.S., and D.J.M. were supported by
the intramural research program of the National Center for Advancing
Translational Sciences and the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research
(U54MH084681). Additional financial support was from NIH (S10-RR20939
(T.R.H.)) and the California Institute for Quantitative Biosciences for
the UCSC MS Facility (T.R.H.).
NR 79
TC 21
Z9 21
U1 4
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 22
PY 2014
VL 57
IS 10
BP 4035
EP 4048
DI 10.1021/jm401915r
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AI0BB
UT WOS:000336510100010
PM 24684213
ER
PT J
AU Ramogola-Masire, D
Russell, AH
Dryden-Peterson, S
Efstathiou, JA
Kayembe, MKA
Wilbur, DC
AF Ramogola-Masire, Doreen
Russell, Anthony H.
Dryden-Peterson, Scott
Efstathiou, Jason A.
Kayembe, Mukendi K. A.
Wilbur, David C.
TI Case 16-2014: A 46-Year-Old Woman in Botswana with Postcoital Bleeding
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; SUB-SAHARAN AFRICA; ANTIRETROVIRAL
THERAPY; PARTICLE VACCINE; CERVICAL-CANCER; VAGINAL-CANCER; YOUNG-WOMEN;
HIV; HPV; PREVENTION
C1 [Ramogola-Masire, Doreen] Botswana UPenn Partnership, Philadelphia, PA 19104 USA.
[Ramogola-Masire, Doreen] Botswana UPenn Partnership, Gaborone, Botswana.
[Ramogola-Masire, Doreen] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Russell, Anthony H.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Dryden-Peterson, Scott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Russell, Anthony H.; Efstathiou, Jason A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Dryden-Peterson, Scott] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Kayembe, Mukendi K. A.] Univ Botswana, Dept Anat Pathol, Natl Hlth Lab, Gaborone, Botswana.
[Kayembe, Mukendi K. A.] Univ Botswana, Dept Pathol, Gaborone, Botswana.
RP Ramogola-Masire, D (reprint author), Botswana UPenn Partnership, Philadelphia, PA 19104 USA.
FU Harvard University Center for AIDS Research [NIH 2P30 AI060354-06];
McCord Hospital (Durban); University of KwaZulu-Natal; South African HIV
Clinicians Society; Department of Health, KwaZulu-Natal
FX Sponsored by the Harvard University Center for AIDS Research (NIH 2P30
AI060354-06), McCord Hospital (Durban), the University of KwaZulu-Natal,
the South African HIV Clinicians Society, and the Department of Health,
KwaZulu-Natal.
NR 34
TC 1
Z9 1
U1 1
U2 5
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 MAY 22
PY 2014
VL 370
IS 21
BP 2032
EP 2041
DI 10.1056/NEJMcpc1400839
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH4UZ
UT WOS:000336125500012
PM 24849087
ER
PT J
AU Turbett, SE
Baggett, MV
AF Turbett, Sarah E.
Baggett, Meridale V.
TI Case 5-2014: A Man with Fever, Thrombocytopenia, and Renal Failure REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Turbett, Sarah E.; Baggett, Meridale V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Turbett, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 1
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 MAY 22
PY 2014
VL 370
IS 21
BP 2054
EP 2054
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH4UZ
UT WOS:000336125500027
PM 24849099
ER
PT J
AU Lin, L
Savoia, E
Agboola, F
Viswanath, K
AF Lin, Leesa
Savoia, Elena
Agboola, Foluso
Viswanath, Kasisomayajula
TI What have we learned about communication inequalities during the H1N1
pandemic: a systematic review of the literature
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Communication; Communication inequalities; Risk communication H1N1;
Pandemic; Public health emergency preparedness
ID INFLUENZA-A H1N1; HONG-KONG; VACCINE UPTAKE; UNITED-STATES;
BEHAVIORAL-RESPONSES; SEASONAL INFLUENZA; GENERAL-POPULATION; A/H1N1
VACCINATION; MEDIA COVERAGE; HAND HYGIENE
AB Background: During public health emergencies, public officials are busy in developing communication strategies to protect the population from existing or potential threats. However, a population's social and individual determinants (i.e. education, income, race/ethnicity) may lead to inequalities in individual or group-specific exposure to public health communication messages, and in the capacity to access, process, and act upon the information received by specific sub-groups-a concept defined as communication inequalities.
The aims of this literature review are to: 1) characterize the scientific literature that examined issues related to communication to the public during the H1N1 pandemic, and 2) summarize the knowledge gained in our understanding of social determinants and their association with communication inequalities in the preparedness and response to an influenza pandemic.
Methods: Articles were searched in eight major communication, social sciences, and health and medical databases of scientific literature and reviewed by two independent reviewers by following the PRISMA guidelines. The selected articles were classified and analyzed in accordance with the Structural Influence Model of Public Health Emergency Preparedness Communications.
Results: A total of 118 empirical studies were included for final review. Among them, 78% were population-based studies and 22% were articles that employed information environment analyses techniques. Consistent results were reported on the association between social determinants of communication inequalities and emergency preparedness outcomes. Trust in public officials and source of information, worry and levels of knowledge about the disease, and routine media exposure as well as information-seeking behaviors, were related to greater likelihood of adoption of recommended infection prevention practices. When addressed in communication interventions, these factors can increase the effectiveness of the response to pandemics.
Conclusions: Consistently across studies, a number of potential predictors of behavioral compliance to preventive recommendations during a pandemic were identified. Our findings show the need to include such evidence found in the development of future communication campaigns to ensure the highest rates of compliance with recommended protection measures and reduce communication inequalities during future emergencies.
C1 [Lin, Leesa; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Ctr, Boston, MA 02115 USA.
[Lin, Leesa; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Savoia, Elena] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lin, Leesa; Savoia, Elena; Agboola, Foluso] Harvard Univ, Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA.
RP Lin, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Ctr, 677 Huntington Ave,3rd Floor East, Boston, MA 02115 USA.
EM llin@hsph.harvard.edu
FU U.S. Centers for Disease Control and Prevention (CDC) [5PO1TP000307-05]
FX We acknowledge funding support from the U.S. Centers for Disease Control
and Prevention (CDC) grant number 5PO1TP000307-05 Supplement. The
content of this publication as well as the views and discussions
expressed in this paper are solely those of the authors and do not
necessarily represent the views of any partner organizations, the CDC or
the U.S. Department of Health and Human Services nor does mention of
trade names, commercial practices, or organizations imply endorsement by
the U.S. Government. We thank John Mazza for his editing and for
critically reviewing the final manuscript.
NR 74
TC 4
Z9 5
U1 1
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD MAY 21
PY 2014
VL 14
AR 484
DI 10.1186/1471-2458-14-484
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI5PS
UT WOS:000336922100001
PM 24884634
ER
PT J
AU Ma, QL
Zuo, XH
Yang, FS
Ubeda, OJ
Gant, DJ
Alaverdyan, M
Kiosea, NC
Nazari, S
Chen, PP
Nothias, F
Chan, P
Teng, E
Frautschy, SA
Cole, GM
AF Ma, Qiu-Lan
Zuo, Xiaohong
Yang, Fusheng
Ubeda, Oliver J.
Gant, Dana J.
Alaverdyan, Mher
Kiosea, Nicolae C.
Nazari, Sean
Chen, Ping Ping
Nothias, Fatiha
Chan, Piu
Teng, Edmond
Frautschy, Sally A.
Cole, Greg M.
TI Loss of MAP Function Leads to Hippocampal Synapse Loss and Deficits in
the Morris Water Maze with Aging
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease; knock-out; MAPs; Morris Water Maze; synaptic
markers; tau
ID MICROTUBULE-ASSOCIATED PROTEIN; GLYCOGEN-SYNTHASE KINASE-3-BETA;
ALPHA-LIPOIC ACID; ALZHEIMERS-DISEASE PATIENTS; MILD COGNITIVE
IMPAIRMENT; N-TERMINAL KINASE; MOUSE MODEL; NEUROFIBRILLARY TANGLES;
PHOSPHORYLATION SITES; NEURONAL CYTOSKELETON
AB Hyperphosphorylation and accumulation of tau aggregates are prominent features in tauopathies, including Alzheimer's disease, but the impact of loss of tau function on synaptic and cognitive deficits remains poorly understood. We report that old (19 - 20 months; OKO) but not middle-aged (8 - 9 months; MKO) tau knock-out mice develop Morris Water Maze(MWM) deficits and loss of hippocampal acetylated alpha-tubulin and excitatory synaptic proteins. Mild motor deficits and reduction in tyrosine hydroxylase (TH) in the substantia nigra were present by middle age, but did not affect MWM performance, whereas OKO mice showed MWM deficits paralleling hippocampal deficits. Deletion of tau, a microtubule-associated protein (MAP), resulted in increased levels of MAP1A, MAP1B, and MAP2 in MKO, followed by loss of MAP2 and MAP1B in OKO. Hippocampal synaptic deficits in OKO mice were partially corrected with dietary supplementation with docosahexaenoic acid (DHA) and both MWM and synaptic deficits were fully corrected by combining DHA with alpha-lipoic acid (ALA), which also prevented TH loss. DHA or DHA/ALA restored phosphorylated and total GSK3 beta and attenuated hyperactivation of the tau C-Jun N-terminal kinases (JNKs) while increasing MAP1B, dephosphorylated (active) MAP2, and acetylated alpha-tubulin, suggesting improved microtubule stability and maintenance of active compensatory MAPs. Our results implicate the loss of MAP function in age-associated hippocampal deficits and identify a safe dietary intervention, rescuing both MAP function and TH in OKO mice. Therefore, in addition to microtubule-stabilizing therapeutic drugs, preserving or restoring compensatory MAP function may be a useful new prevention strategy.
C1 [Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Kiosea, Nicolae C.; Nazari, Sean; Chen, Ping Ping; Teng, Edmond; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
[Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Kiosea, Nicolae C.; Nazari, Sean; Chen, Ping Ping; Teng, Edmond; Frautschy, Sally A.; Cole, Greg M.] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA.
[Nothias, Fatiha] Univ Paris 06, CNRS, INSERM U952, Unite Mixte Rech 7224, F-75005 Paris, France.
[Chan, Piu] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Neurobiol & Neurol, Beijing 10053, Peoples R China.
RP Cole, GM (reprint author), Vet Greater Los Angeles Healthcare, Mary S Easton Translat Ctr, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA.
EM frautsch@ucla.edu; gmcole@ucla.edu
RI Zuo, Xiaohong/H-6254-2016
FU National Institutes of Health [AT003008]; Alzheimer's Disease Research
Center [P01AG16570, RC1AG035878, AG13471, U01 28583, R01AG021975];
Alzheimer's Association [NIRG-07-59659]; UCLA Alzheimer's Disease
Research Center Mary S. Easton Drug Discovery Program; UCLA Mary S.
Easton Translational Center; Beijing High Standard Health Human Resource
Cultural Program [e1e12]
FX This work was supported by the National Institutes of Health (Grant
AT003008 to G. M. C.; Grant P01AG16570 from the Alzheimer's Disease
Research Center to G. M. C.; Grant RC1AG035878 to G. M. C. and S. A. F.;
Grant AG13471 to G. M. C.; Grant U01 28583 to S. A. F.; and Grant
R01AG021975 to S. A. F.), the Alzheimer's Association (Grant
NIRG-07-59659 to Q. L. M.), the UCLA Alzheimer's Disease Research Center
Mary S. Easton Drug Discovery Program (G. M. C.), the UCLA Mary S.
Easton Translational Center (G. M. C., S. A. F.), and David and Dr.
Sharon Comden (S. A. F., G. M. C.). X.Z. was supported by the Beijing
High Standard Health Human Resource Cultural Program (Grant e1e12 to P.
P. C.). The polyclonal antibody to dephosphorylated, active MAP2 "MAP2
972" was provided by Jesus Avila, PhD (Professor, Universidad Autonoma
de Madrid, Spain).
NR 80
TC 27
Z9 28
U1 0
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 21
PY 2014
VL 34
IS 21
BP 7124
EP 7136
DI 10.1523/JNEUROSCI.3439-13.2014
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AI5HB
UT WOS:000336895200010
PM 24849348
ER
PT J
AU Liao, F
Hori, Y
Hudry, E
Bauer, AQ
Jiang, H
Mahan, TE
Lefton, KB
Zhang, TJ
Dearborn, JT
Kim, J
Culver, JP
Betensky, R
Wozniak, DF
Hyman, BT
Holtzman, DM
AF Liao, Fan
Hori, Yukiko
Hudry, Eloise
Bauer, Adam Q.
Jiang, Hong
Mahan, Thomas E.
Lefton, Katheryn B.
Zhang, Tony J.
Dearborn, Joshua T.
Kim, Jungsu
Culver, Joseph P.
Betensky, Rebecca
Wozniak, David F.
Hyman, Bradley T.
Holtzman, David M.
TI Anti-ApoE Antibody Given after Plaque Onset Decreases A beta
Accumulation and Improves Brain Function in a Mouse Model of A beta
Amyloidosis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Alzheimer's; amyloid; antibody; apolipoprotein E
ID PROTEIN TRANSGENIC MICE; HUMAN APOLIPOPROTEIN-E; DENSITY-LIPOPROTEIN
RECEPTOR; ALZHEIMERS-DISEASE; PASSIVE IMMUNOTHERAPY; TYPE-4 ALLELE;
GENE-TRANSFER; IN-VIVO; DEPOSITION; PATHOLOGY
AB Apolipoprotein E (apoE) is the strongest known genetic risk factor for late onset Alzheimer's disease (AD). It influences amyloid-beta(A beta) clearance and aggregation, which likely contributes in large part to its role in AD pathogenesis. We recently found that HJ6.3, a monoclonal antibody against apoE, significantly reduced A beta plaque load when given to APPswe/PS1 Delta E9 (APP/PS1) mice starting before the onset of plaque deposition. To determine whether the anti-apoE antibody HJ6.3 affects A beta plaques, neuronal network function, and behavior in APP/PS1 mice after plaque onset, we administered HJ6.3 (10 mg/kg/week) or PBS intraperitoneally to 7-month-old APP/PS1 mice for 21 weeks. HJ6.3 mildly improved spatial learning performance in the water maze, restored resting-state functional connectivity, and modestly reduced brain A beta plaque load. There was no effect of HJ6.3 on total plasma cholesterol or cerebral amyloid angiopathy. To investigate the underlying mechanisms of anti-apoE immunotherapy, HJ6.3 was applied to the brain cortical surface and amyloid deposition was followed over 2 weeks using in vivo imaging. Acute exposure to HJ6.3 affected the course of amyloid deposition in that it prevented the formation of new amyloid deposits, limited their growth, and was associated with occasional clearance of plaques, a process likely associated with direct binding to amyloid aggregates. Topical application of HJ6.3 for only 14 d also decreased the density of amyloid plaques assessed postmortem. Collectively, these studies suggest that anti-apoE antibodies have therapeutic potential when given before or after the onset of A beta pathology.
C1 [Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Holtzman, David M.] Washington Univ, Dept Neurol, Sch Med, St Louis, MO 63110 USA.
[Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Wozniak, David F.; Holtzman, David M.] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA.
[Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Holtzman, David M.] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA.
[Bauer, Adam Q.; Culver, Joseph P.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Dearborn, Joshua T.; Wozniak, David F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Hori, Yukiko; Hudry, Eloise; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Hori, Yukiko; Hudry, Eloise; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Wozniak, David F.] Washington Univ, Sch Med, Taylor Family Inst Innovat Psychiat Res, St Louis, MO 63110 USA.
[Kim, Jungsu] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Betensky, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Holtzman, DM (reprint author), Washington Univ, Dept Neurol, Sch Med, 660 S Euclid Ave,Box 8111, St Louis, MO 63110 USA.
EM holtzman@neuro.wustl.edu
OI Mahan, Thomas/0000-0001-9811-7490; Liao, Fan/0000-0003-4874-460X
FU BrightFocus Foundation [A2013037F]; AstraZeneca; Cure Alzheimer's Fund;
Dreyfoos Program; Uehara Memorial Foundation; National Institutes of
Health [R37 AG13956]; Eli Lilly
FX This work was supported by the BrightFocus Foundation (Grant A2013037F
to F. L.), AstraZeneca (D. M. H.), the Cure Alzheimer's Fund (D. M. H.),
the Dreyfoos Program (B. T. H. and E. H.), the Uehara Memorial
Foundation (post-doctoral fellowship to Y.H.), and the National
Institutes of Health (Grant R37 AG13956 to D.M.H.).; D.M.H. and
Washington University have ownership interests in C2N Diagnostics. D. M.
H. is on the scientific advisory board of C2N Diagnostics, consults for
AstraZeneca, Genentech, and Eli Lilly, and his laboratory receives
research grants from AstraZeneca and Eli Lilly. The remaining authors
declare no competing financial interests.
NR 54
TC 19
Z9 20
U1 0
U2 17
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 21
PY 2014
VL 34
IS 21
BP 7281
EP 7292
DI 10.1523/JNEUROSCI.0646-14.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AI5HB
UT WOS:000336895200022
PM 24849360
ER
PT J
AU Harrison, WJ
Bex, PJ
AF Harrison, William J.
Bex, Peter J.
TI Integrating Retinotopic Features in Spatiotopic Coordinates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE crowding; feature integration; remapping; spatiotopy; trans-saccade;
visual stability
ID SACCADIC EYE-MOVEMENTS; HUMAN OCCIPITAL CORTEX; OBJECT RECOGNITION;
VISUAL-MOTION; PSYCHOPHYSICS TOOLBOX; RECEPTIVE-FIELDS; PARIETAL CORTEX;
REFERENCE FRAME; ATTENTION; SPACE
AB The receptive fields of early visual neurons are anchored in retinotopic coordinates (Hubel and Wiesel, 1962). Eye movements shift these receptive fields and therefore require that different populations of neurons encode an object's constituent features across saccades. Whether feature groupings are preserved across successive fixations or processing starts anew with each fixation has been hotly debated (Melcher and Morrone, 2003; Melcher, 2005, 2010; Knapen et al., 2009; Cavanagh et al., 2010a, b; Morris et al., 2010). Here we show that feature integration initially occurs within retinotopic coordinates, but is then conserved within a spatiotopic coordinate frame independent of where the features fall on the retinas. With human observers, we first found that the relative timing of visual features plays a critical role in determining the spatial area over which features are grouped. We exploited this temporal dependence of feature integration to show that features co-occurring within 45 ms remain grouped across eye movements. Our results thus challenge purely feedforward models of feature integration (Pelli, 2008; Freeman and Simoncelli, 2011) that begin de novo after every eye movement, and implicate the involvement of brain areas beyond early visual cortex. The strong temporal dependence we quantify and its link with trans-saccadic object perception instead suggest that feature integration depends, at least in part, on feedback from higher brain areas (Mumford, 1992; Rao and Ballard, 1999; Di Lollo et al., 2000; Moore and Armstrong, 2003; Stanford et al., 2010).
C1 [Harrison, William J.; Bex, Peter J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA.
RP Harrison, WJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA.
EM willjharri@gmail.com
OI Harrison, William/0000-0002-6408-0359
FU National Institutes of Health [R01 EY19281, R01 EY018664]
FX This work was supported by National Institutes of Health Grants R01
EY19281 and R01 EY018664. We thank MiYoung Kwon for her help with
preparing the manuscript.
NR 70
TC 9
Z9 9
U1 0
U2 18
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 21
PY 2014
VL 34
IS 21
BP 7351
EP 7360
DI 10.1523/JNEUROSCI.5252-13.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AI5HB
UT WOS:000336895200029
PM 24849367
ER
PT J
AU Shapiro, IM
Kolev, VN
Vidal, CM
Kadariya, Y
Ring, JE
Wright, Q
Weaver, DT
Menges, C
Padval, M
McClatchey, AI
Xu, QL
Testa, JR
Pachter, JA
AF Shapiro, Irina M.
Kolev, Vihren N.
Vidal, Christian M.
Kadariya, Yuwaraj
Ring, Jennifer E.
Wright, Quentin
Weaver, David T.
Menges, Craig
Padval, Mahesh
McClatchey, Andrea I.
Xu, Qunli
Testa, Joseph R.
Pachter, Jonathan A.
TI Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal
Relationship
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID FOCAL-ADHESION KINASE; MALIGNANT MESOTHELIOMA CELLS; TUMOR-SUPPRESSOR;
ADHERENS JUNCTIONS; BREAST-CANCER; STEM-CELLS; NF2; GENE; TUMORIGENESIS;
MUTATIONS
AB The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlinnegative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment.
C1 [Shapiro, Irina M.; Kolev, Vihren N.; Vidal, Christian M.; Ring, Jennifer E.; Wright, Quentin; Weaver, David T.; Padval, Mahesh; Xu, Qunli; Pachter, Jonathan A.] Verastem Inc, Cambridge, MA 02142 USA.
[Kadariya, Yuwaraj; Menges, Craig; Testa, Joseph R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[McClatchey, Andrea I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA.
RP Pachter, JA (reprint author), Verastem Inc, Cambridge, MA 02142 USA.
EM jpachter@verastem.com
FU Verastem Inc; NIH [R01CA113733]; MGH Research Scholars Award; National
Cancer Institute [CA148805]
FX This work was funded by Verastem Inc. A.I.M. was also funded by the NIH
(R01CA113733) and an MGH Research Scholars Award. J.R.T., C.M.V., and
Y.K. were also supported by National Cancer Institute grant CA148805.
NR 34
TC 33
Z9 33
U1 0
U2 10
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAY 21
PY 2014
VL 6
IS 237
AR 237ra68
DI 10.1126/scitranslmed.3008639
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AI2DY
UT WOS:000336668800009
PM 24848258
ER
EF