FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Kozin, ED
Remenschneider, AK
Cheng, S
Nakajima, HH
Lee, DJ
AF Kozin, Elliott D.
Remenschneider, Aaron K.
Cheng, Song
Nakajima, Hideko Heidi
Lee, Daniel J.
TI Three-Dimensional Printed Prosthesis for Repair of Superior Canal
Dehiscence
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE superior semicircular canal dehiscence; superior semicircular canal
dehiscence syndrome; 3-dimensional printing
ID SURGICAL-MANAGEMENT; POROUS TITANIUM
AB Outcomes following repair of superior canal dehiscence (SCD) are variable, and surgery carries a risk of persistent or recurrent SCD symptoms, as well as a risk of hearing loss and vestibulopathy. Poor outcomes may occur from inadequate repair of the SCD or mechanical insult to the membranous labyrinth. Repair of SCD using a customized, fixed-length prosthesis may address current operative limitations and improve surgical outcomes. We aim to 3-dimensionally print customized prostheses to resurface or occlude bony SCD defects. Dehiscences were created along the arcuate eminence of superior semicircular canals in cadaveric temporal bones. Prostheses were designed and created using computed tomography and a 3-dimensional printer. The prostheses occupied the superior semicircular canal defect, reflected in postrepair computed tomography scans. This novel approach to SCD repair could have advantages over current techniques. Refinement of prosthesis design and materials will be important if this approach is translated into clinical use.
C1 [Kozin, Elliott D.; Remenschneider, Aaron K.; Cheng, Song; Nakajima, Hideko Heidi; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Kozin, Elliott D.; Remenschneider, Aaron K.; Cheng, Song; Nakajima, Hideko Heidi; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
RP Remenschneider, AK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Aaron_Remenschneider@meei.harvard.edu
NR 15
TC 0
Z9 0
U1 3
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
EI 1097-6817
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD OCT
PY 2015
VL 153
IS 4
BP 616
EP 619
DI 10.1177/0194599815592602
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA CS9XD
UT WOS:000362445800025
PM 26150379
ER
PT J
AU Singal, G
Upadhyay, GA
Borgquist, R
Friedman, DJ
Chatterjee, NA
Kandala, J
Park, MY
Orencole, M
Dec, GW
Picard, MH
Singh, JP
Mela, T
AF Singal, Gaurav
Upadhyay, Gaurav A.
Borgquist, Rasmus
Friedman, Daniel J.
Chatterjee, Neal A.
Kandala, Jagdesh
Park, Mi Young
Orencole, Mary
Dec, George W.
Picard, Michael H.
Singh, Jagmeet P.
Mela, Theofanie
TI Renal Response in Patients with Chronic Kidney Disease Predicts Outcome
Following Cardiac Resynchronization Therapy
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Article
DE heart failure; cardiorenal syndrome; chronic kidney disease; cardiac
resynchronization therapy; pacemakers
ID GLOMERULAR-FILTRATION-RATE; CHRONIC HEART-FAILURE; CARDIORENAL SYNDROME;
INSUFFICIENCY; DYSFUNCTION; MORTALITY; TRIAL; ASSOCIATIONS; COHORT;
DEATH
AB BackgroundChronic kidney disease (CKD) severity is associated with increased morbidity and mortality in congestive heart failure. There is a paucity of data regarding renal improvement after cardiac resynchronization therapy (CRT) and its potential impact on clinical outcomes, especially in patients with severe CKD.
MethodThis was a retrospective analysis of a prospectively collected cohort of 260 patients with CKD undergoing CRT at a single center. Renal function was compared before and after CRT. The primary end point was a composite of death, heart transplant, and left ventricular assist device (LVAD), assessed at 5 years.
ResultsPatients with more severe CKD demonstrated increased risk of death, transplant, or LVAD following CRT (P = 0.015). Renal response (estimated glomerular filtration rate improvement 10 mL/min/1.73 m(2)) was observed in 14% of all patients and 28% of patients with stage IV CKD. Independent predictors of renal response included left ventricular ejection fraction improvement (odds ratio [OR] 1.06, confidence interval [CI] 1.01-1.10), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (OR 4.31, CI 1.08-17.23), and advanced CKD stage (OR 2.19, CI 1.14-4.23). Renal response independently decreased hazard of the primary outcome (HR 0.24, CI 0.08-0.73, P = 0.01). Renal responders with stage IV CKD had 80% 5-year event-free survival, compared to 0% for nonrenal responders in stage IV (P = 0.03).
ConclusionAlthough severity of CKD is associated with poorer outcome after CRT, improvement in renal function can occur in patients across all CKD stages. Renal responders, including those with stage IV CKD, demonstrate favorable 5-year outcomes. Assessment of renal response may help better prognostic outcomes following CRT.
C1 [Singal, Gaurav; Friedman, Daniel J.; Chatterjee, Neal A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Upadhyay, Gaurav A.; Borgquist, Rasmus; Kandala, Jagdesh; Orencole, Mary; Singh, Jagmeet P.; Mela, Theofanie] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Upadhyay, Gaurav A.; Kandala, Jagdesh; Park, Mi Young; Orencole, Mary; Dec, George W.; Picard, Michael H.; Singh, Jagmeet P.; Mela, Theofanie] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Borgquist, Rasmus] Lund Univ, Skane Univ Hosp, Arrhythmia Clin, Lund, Sweden.
RP Mela, T (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Gray 109,75 Fruit St, Boston, MA 02114 USA.
EM tmela@partners.org
OI Picard, Michael/0000-0002-9264-3243; Friedman, Daniel
/0000-0001-5791-1954
FU Swedish Heart and Lung Foundation; Swedish National Health Service
FX Dr. Borgquist was supported by grants from the Swedish Heart and Lung
Foundation and by governmental funding of clinical research within the
Swedish National Health Service.
NR 31
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0147-8389
EI 1540-8159
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD OCT
PY 2015
VL 38
IS 10
BP 1192
EP 1200
DI 10.1111/pace.12685
PG 9
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA CT1MZ
UT WOS:000362563900008
PM 26179289
ER
PT J
AU Huber, RJ
O'Day, DH
AF Huber, Robert J.
O'Day, Danton H.
TI Proteomic profiling of the extracellular matrix (slime sheath) of
Dictyostelium discoideum
SO PROTEOMICS
LA English
DT Article
DE Cell biology; Development; Dictyostelium discoideum; Extracellular
matrix; Model system
ID EGF-LIKE PEPTIDE; CELL-MIGRATION; MATRICELLULAR PROTEIN; MEDIATED
CHEMOTAXIS; MASS-SPECTROMETRY; STATISTICAL-MODEL; MOTILITY; DATABASE;
SLUG; CHEMOATTRACTANT
AB Dictyostelium discoideum has historically served as a model system for cell and developmental biology, but recently it has gained increasing attention as a model for the study of human diseases. The extracellular matrix (ECM) of this eukaryotic microbe serves multiple essential functions during development. It not only provides structural integrity to the moving multicellular pseudoplasmodium, or slug, it also provides components that regulate cell motility and differentiation. An LC/MS/MS analysis of slug ECM revealed the presence of a large number of proteins in two wild-type strains, NC4 and WS380B. GO annotation identified a large number of proteins involved in some form of binding (e.g. protein, polysaccharide, cellulose, carbohydrate, ATP, cAMP, ion, lipid, vitamin), as well as proteins that modulate metabolic processes, cell movement, and multicellular development. In addition, this proteomic analysis identified numerous expected (e.g. EcmA, EcmD, discoidin I, discoidin II), as well as unexpected (e.g. ribosomal and nuclear proteins) components. These topics are discussed in terms of the structure and function of the ECM during the development of this model amoebozoan and their relevance to ongoing biomedical research.
C1 [Huber, Robert J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Ctr Human Genet Res, Boston, MA USA.
[O'Day, Danton H.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada.
[O'Day, Danton H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
RP Huber, RJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA.
EM rhuber@mgh.harvard.edu
FU CIHR [MFE127336]; NSERC DG [A6807]
FX CIHR Fellowship (MFE127336 to R.J.H.); NSERC DG (A6807 to D.H.O'D.).
NR 38
TC 3
Z9 3
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD OCT
PY 2015
VL 15
IS 19
BP 3315
EP 3319
DI 10.1002/pmic.201500143
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT0RP
UT WOS:000362504300005
PM 26152465
ER
PT J
AU Kasckow, J
Gao, SS
Hanusa, B
Rotondi, A
Chinman, M
Zickmund, S
Gurklis, J
Fox, L
Cornelius, J
Richmond, I
Haas, GL
AF Kasckow, John
Gao, Shasha
Hanusa, Barbara
Rotondi, Armando
Chinman, Matthew
Zickmund, Susan
Gurklis, John
Fox, Lauren
Cornelius, Jack
Richmond, Ira
Haas, Gretchen L.
TI Telehealth Monitoring of Patients with Schizophrenia and Suicidal
Ideation
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID DEPRESSION RATING-SCALE; VETERANS; RISK; SYMPTOMS; MORTALITY; DISORDER;
OUTCOMES; MINI
AB A telehealth system was developed to monitor risk following hospitalization for suicidal ideation. We hypothesized that 3months of telehealth monitoring will result in a greater reduction in suicidal ideation. Veterans with schizophrenia admitted with recent suicidal ideation and/or a suicidal attempt were recruited into a discharge program of VA Usual Care with daily Health Buddy (c) monitoring (HB) or Usual Care (UC) alone. Fifteen of 25 were randomized to HB and 10 received UC. Daily adherence in the use of the HB system during months 1-3 was, respectively, 86.9%, 86.3%, and 84.1%. There were significant improvements in Beck Scale for Suicide Ideation scores in HB participants. There were no changes in depressive symptoms. Telehealth monitoring for this population of patients appears to be feasible.
C1 [Kasckow, John] VA Pittsburgh MIRECC, CHERP & Behav Hlth, Pittsburgh, PA USA.
[Kasckow, John; Cornelius, Jack; Haas, Gretchen L.] UPMC Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Gao, Shasha; Zickmund, Susan] VA Pittsburgh CHERP, Pittsburgh, PA USA.
[Hanusa, Barbara; Rotondi, Armando; Chinman, Matthew; Fox, Lauren; Cornelius, Jack] VA Pittsburgh MIRECC, Pittsburgh, PA USA.
[Rotondi, Armando] UPMC Crit Care, Pittsburgh, PA USA.
[Chinman, Matthew] CHERP, Pittsburgh, PA USA.
[Zickmund, Susan] UPMC Dept Med, Pittsburgh, PA USA.
[Gurklis, John] VA Pittsburgh Behav Hlth, Pittsburgh, PA USA.
[Richmond, Ira] VA Pittsburgh Patient Care Serv, Pittsburgh, PA USA.
[Haas, Gretchen L.] VA Pittsburgh MIRECC & Behav Hlth, Pittsburgh, PA USA.
RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, Behav Hlth 116A, Univ Dr C, Pittsburgh, PA 15240 USA.
EM kasckowjw@upmc.edu
FU VISN 4 MIRECC; HSRD PPO [10-249-2]
FX Funded by the VISN 4 MIRECC and HSRD PPO 10-249-2 (JWK). The views do
not represent the views of the U.S. Department of veterans Affairs or
that of the U.S. government.
NR 33
TC 2
Z9 2
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0363-0234
EI 1943-278X
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD OCT
PY 2015
VL 45
IS 5
BP 600
EP 611
DI 10.1111/sltb.12154
PG 12
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA CT3FR
UT WOS:000362693100007
ER
PT J
AU Venne, VL
Scheuner, MT
AF Venne, Vickie L.
Scheuner, Maren T.
TI Securing and Documenting Cancer Family History in the Age of the
Electronic Medical Record
SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Family health history; Pedigree; Genetic risk assessment; Electronic
medical records
ID GENETIC RISK-ASSESSMENT; PRIMARY-CARE; BREAST-CANCER; DECISION-SUPPORT;
HEREDITARY BREAST; OVARIAN-CANCER; TOOL; TELEPHONE; IMPACT; WOMEN
AB Family health history is one of the least expensive, most useful, and most underused methods available to conduct assessments of the genetic aspect of a condition or to target the need for a genetic evaluation. This article introduces to the surgical oncologist the reason and process of collecting family history information. As medical records shift from paper to electronic formats, pedigree drawings are not readily available within the electronic health records. International efforts are underway to develop searchable, updatable, and interoperable formats that can collect family history information to inform clinical decision support for genetic risk assessment.
C1 [Venne, Vickie L.] SLC VA Med Ctr, Genom Med Serv, Salt Lake City, UT 84148 USA.
[Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Scheuner, Maren T.] VA Greater Los Angeles Healthcare Syst, Med Genet, Los Angeles, CA 90073 USA.
RP Venne, VL (reprint author), SLC VA Med Ctr, Genom Med Serv, 500 Foothill Dr, Salt Lake City, UT 84148 USA.
EM vickie.venne@va.gov
NR 44
TC 1
Z9 1
U1 2
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1055-3207
EI 1558-5042
J9 SURG ONCOL CLIN N AM
JI Surg. Oncol. Clin. N. Am.
PD OCT
PY 2015
VL 24
IS 4
BP 639
EP +
DI 10.1016/j.soc.2015.06.001
PG 15
WC Oncology; Surgery
SC Oncology; Surgery
GA CT3GA
UT WOS:000362694000004
PM 26363534
ER
PT J
AU Yeh, DD
Ghoshhajra, B
Inglessis-Azuaje, I
MacGillivray, T
Liberthson, R
Bhatt, AB
AF Yeh, Doreen DeFaria
Ghoshhajra, Brian
Inglessis-Azuaje, Ignacio
MacGillivray, Thomas
Liberthson, Richard
Bhatt, Ami B.
TI Massive Pulmonary Artery Aneurysm Causing Left Main Coronary Artery
Compression in the Absence of Pulmonary Hypertension
SO TEXAS HEART INSTITUTE JOURNAL
LA English
DT Article
DE Angina pectoris/etiology; coronary vessel anomalies/complications; heart
defects; congenital/complications/diagnosis/radiography; heart
valves/abnormalities; pulmonary artery/abnormalities/pathology/surgery;
treatment outcome
ID TETRALOGY; FALLOT
AB We report the case of a 62-year-old woman who presented with classic symptoms of stable angina. Cardiac images and catheterization results revealed absent pulmonary valve syndrome and compression of the left main coronary artery by a massively dilated pulmonary artery aneurysm. The patient's anginal symptoms were relieved after pulmonary arterioplasty.
Others have described proximal left main coronary artery compression in the presence of a dilated and hypertensive pulmonary artery To our knowledge, this is the first case in which a pulmonary artery aneurysm caused left main coronary insufficiency in the absence of pulmonary hypertension a clinically important complication of congenital pulmonary valve-related pulmonary arteriopathy.
C1 [Yeh, Doreen DeFaria; Inglessis-Azuaje, Ignacio; Bhatt, Ami B.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
[Ghoshhajra, Brian] Massachusetts Gen Hosp, Dept Radiol, Cardiac Radiol Sect, Boston, MA 02114 USA.
[MacGillivray, Thomas] Massachusetts Gen Hosp, Cardiothorac Surg Sect, Dept Surg, Boston, MA 02114 USA.
[Liberthson, Richard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Liberthson, Richard] Massachusetts Gen Hosp, Dept Pediat, Div Cardiol, Boston, MA 02114 USA.
RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA.
EM ddefariayeh@partners.org
NR 8
TC 0
Z9 0
U1 0
U2 1
PU TEXAS HEART INST
PI HOUSTON
PA PO BOX 20345, HOUSTON, TX 77225-0345 USA
SN 0730-2347
EI 1526-6702
J9 TEX HEART I J
JI Tex. Heart Inst. J.
PD OCT
PY 2015
VL 42
IS 5
BP 465
EP 467
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CS9SD
UT WOS:000362430900013
PM 26504443
ER
PT J
AU Al-Alusi, MA
Du, L
Li, N
Yeh, MW
He, XM
Braverman, LE
Leung, AM
AF Al-Alusi, Mostafa A.
Du, Lin
Li, Ning
Yeh, Michael W.
He, Xuemei
Braverman, Lewis E.
Leung, Angela M.
TI Metformin Does Not Suppress Serum Thyrotropin by Increasing
Levothyroxine Absorption
SO THYROID
LA English
DT Article
ID DIABETIC-PATIENTS; RESPIRATORY-CHAIN; HYPOTHYROIDISM; WOMEN; TSH;
EXPRESSION; THERAPY; KINASE; OBESE; CREB
AB Background: Levothyroxine (LT4) absorption is affected by concomitant ingestion of certain minerals, medications, and foods. It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis. This study examined the effect of metformin ingestion on LT4 absorption, as assessed by serum total thyroxine (TT4) concentrations. Methods: A modified Food and Drug Administration LT4 bioequivalence protocol was applied to healthy, metformin-naive, euthyroid adult volunteers. Following an overnight fast, 600g LT4 was administered orally. Serum TT4 concentrations were measured at baseline and at 0.5, 1, 1.5, 2, 4, and 6h following LT4 administration. Measurements were performed before and after one week of metformin ingestion (850mg three times daily). Peak serum TT4 concentrations, time to peak TT4 concentrations, and area under the concentration-time curve (AUC) were calculated. Results: Twenty-six subjects (54% men, 27% white, age 3310 years) were studied. There were no significant differences in peak serum TT4 concentrations (p=0.13) and time to peak TT4 concentrations (p=0.19) before and after one week of metformin use. A trend toward reduced TT4 AUC was observed after metformin ingestion (pre-metformin 3893 +/- 568g/dL-min, post-metformin 3765 +/- 588g/dL-min, p=0.09). Conclusions: LT4 absorption is unchanged by concomitant metformin ingestion. Mechanisms other than increased LT4 absorption may be responsible for the suppressed TSH concentrations observed in patients ingesting both drugs.
C1 [Al-Alusi, Mostafa A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Du, Lin] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90073 USA.
[Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90073 USA.
[Yeh, Michael W.] Univ Calif Los Angeles, David Geffen Sch Med, Sect Endocrine Surg, Los Angeles, CA 90073 USA.
[Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Los Angeles, CA 90073 USA.
[He, Xuemei; Braverman, Lewis E.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Leung, Angela M.] VA Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA USA.
RP Leung, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM amleung@mednet.ucla.edu
FU NIH [K23HD068552]; NIH/National Center for Advancing Translational
Science (NCATS) UCLA CTSI [UL1TR000124]
FX This work was funded by NIH K23HD068552 (A.M.L.) and NIH/National Center
for Advancing Translational Science (NCATS) UCLA CTSI UL1TR000124. This
work was presented as an abstract at the 2015 Annual Meeting of the
Endocrine Society under the title "The Effect of Metformin on
Levothyroxine Absorption."
NR 30
TC 1
Z9 1
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD OCT 1
PY 2015
VL 25
IS 10
BP 1080
EP 1084
DI 10.1089/thy.2015.0211
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS7LY
UT WOS:000362266300002
PM 26191653
ER
PT J
AU McLeod, DSA
Jonklaas, J
Brierley, JD
Ain, KB
Cooper, DS
Fein, HG
Haugen, BR
Ladenson, PW
Magner, J
Ross, DS
Skarulis, MC
Steward, DL
Xing, MZ
Litofsky, DR
Maxon, HR
Sherman, SI
AF McLeod, Donald S. A.
Jonklaas, Jacqueline
Brierley, James D.
Ain, Kenneth B.
Cooper, David S.
Fein, Henry G.
Haugen, Bryan R.
Ladenson, Paul W.
Magner, James
Ross, Douglas S.
Skarulis, Monica C.
Steward, David L.
Xing, Mingzhao
Litofsky, Danielle R.
Maxon, Harry R.
Sherman, Steven I.
TI Reassessing the NTCTCS Staging Systems for Differentiated Thyroid
Cancer, Including Age at Diagnosis
SO THYROID
LA English
DT Article
ID TALL-CELL VARIANT; CARCINOMA; PAPILLARY; PROGNOSIS; SURVIVAL; THERAPY;
THYROTROPIN; REGISTRY; RISK
AB Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R-2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45-50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p=0.200). The best five alternate follicular cancer systems had age cut-points of 50-55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p=0.003-0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p=0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation.
C1 [McLeod, Donald S. A.] Royal Brisbane & Womens Hosp, Dept Endocrinol & Diabet, Herston, Qld, Australia.
[McLeod, Donald S. A.] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Herston, Qld, Australia.
[McLeod, Donald S. A.] Univ Queensland, Sch Med, Herston, Qld, Australia.
[Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20007 USA.
[Brierley, James D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada.
[Ain, Kenneth B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY USA.
[Ain, Kenneth B.] Univ Kentucky, Lexington, KY USA.
[Cooper, David S.; Ladenson, Paul W.; Xing, Mingzhao] Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD USA.
[Fein, Henry G.] Sinai Hosp, Div Endocrinol & Metab, Baltimore, MD 21215 USA.
[Haugen, Bryan R.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA.
[Magner, James] Genzyme, Cambridge, MA USA.
[Ross, Douglas S.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
[Skarulis, Monica C.] NIH, Diabet, Endocrinol, Obes Branch, Bethesda, MD 20892 USA.
[Steward, David L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45267 USA.
[Maxon, Harry R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA.
[Litofsky, Danielle R.; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
RP Sherman, SI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, 1400 Pressler,Unit 1461, Houston, TX 77030 USA.
EM sisherma@mdanderson.org
RI McLeod, Donald/C-4242-2014;
OI McLeod, Donald/0000-0003-1131-020X; Sherman, Steven/0000-0002-3079-5153
FU Genzyme; Sanofi Company; Pfizer; University of Texas M.D. Anderson
Cancer Center Support Grant (NCI) [P30 CA016672]; Cancer Council
Queensland; National Health and Medical Research Council of Australia
[APP1092153]
FX The NTCTCS has been supported in part by research grants from Genzyme, a
Sanofi Company, and Pfizer, and by the University of Texas M.D. Anderson
Cancer Center Support Grant (NCI Grant P30 CA016672). The Cancer Council
Queensland (PhD Scholarship) and the National Health and Medical
Research Council of Australia (APP1092153) supported D.M.
NR 35
TC 4
Z9 4
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD OCT 1
PY 2015
VL 25
IS 10
BP 1097
EP 1105
DI 10.1089/thy.2015.0148
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS7LY
UT WOS:000362266300005
PM 26203804
ER
PT J
AU Lee, RA
Ray, M
Kasuga, DT
Kumar, V
Witherspoon, CD
Baddley, JW
AF Lee, R. A.
Ray, M.
Kasuga, D. T.
Kumar, V.
Witherspoon, C. D.
Baddley, J. W.
TI Ocular bartonellosis in transplant recipients: two case reports and
review of the literature
SO TRANSPLANT INFECTIOUS DISEASE
LA English
DT Article
DE Bartonella henselae; cat scratch disease; transplant; bartonellosis;
chorioretinitis
ID CAT-SCRATCH DISEASE; SOLID-ORGAN; COMPLICATIONS
AB Cat scratch disease is caused by Bartonella henselae and usually manifests as localized lymphadenopathy and fever in immunocompetent patients. Immunocompromised patients are at risk for developing disseminated disease affecting the liver, spleen, eyes, central nervous system, and other organs. Bartonellosis is infrequently reported in solid organ transplant recipients, and published case reports usually discuss disseminated infection. Localized ocular disease with B.henselae, while well documented in immunocompetent hosts, is uncommon in immunocompromised patients. Herein, we present 2 cases of ocular bartonellosis in renal transplant patients, 1 with disseminated infection, and 1 without.
C1 [Lee, R. A.; Ray, M.; Baddley, J. W.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA.
[Kasuga, D. T.; Witherspoon, C. D.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA.
[Kumar, V.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA.
[Baddley, J. W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Lee, RA (reprint author), Univ Alabama Birmingham, Infect Dis, 1900 Univ Blvd,THT 229, Birmingham, AL 35294 USA.
EM ralee@uabmc.edu
OI Witherspoon, Clark/0000-0003-4456-9437
NR 15
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-2273
EI 1399-3062
J9 TRANSPL INFECT DIS
JI Transpl. Infect. Dis.
PD OCT
PY 2015
VL 17
IS 5
BP 723
EP 727
DI 10.1111/tid.12418
PG 5
WC Immunology; Infectious Diseases; Transplantation
SC Immunology; Infectious Diseases; Transplantation
GA CT1YB
UT WOS:000362597900014
PM 26146758
ER
PT J
AU Ahmad, S
Hur, S
AF Ahmad, Sadeem
Hur, Sun
TI Helicases in Antiviral Immunity: Dual Properties as Sensors and
Effectors
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID DOUBLE-STRANDED-RNA; RECEPTOR RIG-I; INNATE IMMUNITY; C-ELEGANS;
CAENORHABDITIS-ELEGANS; STRUCTURAL BASIS; PATTERN-RECOGNITION;
SIGNAL-TRANSDUCTION; DSRNA RECOGNITION; MAMMALIAN-CELLS
AB Many helicases have a unique ability to couple cognate RNA binding to ATP hydrolysis, which can induce a large conformational change that affects its interaction with RNA, position along RNA, or oligomeric state. A growing number of these helicases contribute to the innate immune system, either as sensors that detect foreign nucleic acids and/or as effectors that directly participate in the clearance of such foreign species. In this review, we discuss a few examples, including retinoic acid-inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and Dicer, focusing on their dual functions as both sensors and effectors. We will also discuss the closely related, but less understood, helicases, laboratory of genetics and physiology 2 (LGP2) and Dicerrelated helicase-1 and -3 (DRH-1 and -3).
C1 [Ahmad, Sadeem; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Ahmad, Sadeem; Hur, Sun] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM Sun.Hur@childrens.harvard.edu
FU [AI106912]; [AI111784]
FX We apologize in advance to those whose work was not discussed owing to
space limitations. This work was supported by R01 grants AI106912 (S.H.)
and AI111784 (S.H.).
NR 91
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD OCT
PY 2015
VL 40
IS 10
BP 576
EP 585
DI 10.1016/j.tibs.2015.08.001
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT2DJ
UT WOS:000362611900006
PM 26410598
ER
PT J
AU Grazioli, S
Matute-Bello, G
AF Grazioli, Serge
Matute-Bello, Gustavo
TI Ccn1, a molecular switch that imposes a self-limiting control on
inflammation and wound healing in a multitude of organs? Reply
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Letter
ID MYOFIBROBLASTS
C1 [Grazioli, Serge] Univ Hosp Geneva, Pediat Crit Care Unit, Geneva, Switzerland.
[Grazioli, Serge; Matute-Bello, Gustavo] Univ Washington, Div Pulm & Crit Med, Dept Med, Ctr Lung Biol, Seattle, WA 98109 USA.
[Matute-Bello, Gustavo] VA Puget Sound Healthcare Syst, Seattle, WA USA.
RP Matute-Bello, G (reprint author), Univ Washington, 850 Republican St, Seattle, WA 98109 USA.
EM matuteb@u.washington.edu
RI Grazioli, Serge/A-1457-2016
NR 5
TC 0
Z9 0
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD OCT 1
PY 2015
VL 309
IS 7
BP L749
EP L749
DI 10.1152/ajplung.00265.2015
PG 1
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA CS7BN
UT WOS:000362238600012
PM 26429904
ER
PT J
AU Perlis, RH
AF Perlis, Roy H.
TI Getting Past Proof of Concept For New Treatments
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA.
[Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA.
NR 3
TC 0
Z9 0
U1 1
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD OCT
PY 2015
VL 172
IS 10
BP 937
EP 938
DI 10.1176/appi.ajp.2015.15070906
PG 2
WC Psychiatry
SC Psychiatry
GA CS5XH
UT WOS:000362151100004
PM 26423476
ER
PT J
AU Keraliya, AR
Rosenthal, MH
Krajewski, KM
Jagannathan, JP
Shinagare, AB
Tirumani, SH
Ramaiya, NH
AF Keraliya, Abhishek R.
Rosenthal, Michael H.
Krajewski, Katherine M.
Jagannathan, Jyothi P.
Shinagare, Atul B.
Tirumani, Sree Harsha
Ramaiya, Nikhil H.
TI Imaging of Fluid in Cancer Patients Treated With Systemic Therapy:
Chemotherapy, Molecular Targeted Therapy, and Hematopoietic Stem Cell
Transplantation
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE fluid; hematopoietic stem cell transplantation; molecular targeted
therapy
ID HEPATIC VENOOCCLUSIVE DISEASE; CHRONIC MYELOID-LEUKEMIA; BREAST-CANCER;
LIVER METASTASES; CARDIOTOXICITY; MANAGEMENT; CHILDREN; CT;
COMPLICATIONS; TRASTUZUMAB
AB OBJECTIVE. The purpose of this article is to provide a comprehensive review of the imaging features of various systemic treatment-related causes of fluid accumulation in cancer patients.
CONCLUSION. Systemic treatment-related fluid accumulation can occur with chemotherapy, molecular targeted therapy, or hematopoietic stem cell transplantation. Imaging findings such as new ascites, pleural and pericardial effusions, and subcutaneous edema should be interpreted with caution on restaging studies.
C1 [Keraliya, Abhishek R.; Rosenthal, Michael H.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA.
[Keraliya, Abhishek R.; Rosenthal, Michael H.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA.
RP Keraliya, AR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA.
EM akeraliya@partners.org
FU Radiological Society of North America
FX A. B. Shinagare received a research grant from the Radiological Society
of North America (start date: July 2014).
NR 65
TC 0
Z9 1
U1 1
U2 3
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 709
EP 719
DI 10.2214/AJR.15.14459
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300019
PM 26397319
ER
PT J
AU Zurkiya, O
Walker, TG
AF Zurkiya, Omar
Walker, T. Gregory
TI Angiographic Evaluation and Management of Nonvariceal Gastrointestinal
Hemorrhage
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE angiography; gastrointestinal hemorrhage; provocative angiography;
therapeutic embolization
ID METHYLENE-BLUE INJECTION; ARTERIOVENOUS-MALFORMATION; BOWEL; CT
AB OBJECTIVE. The purpose of this article is to review the roles of angiography, embolization, and various ancillary techniques in evaluating and managing gastrointestinal hemorrhage.
CONCLUSION. Nonvariceal gastrointestinal hemorrhage typically resolves spontaneously or responds to medical or endoscopic management. Refractory hemorrhage may require angiography and transcatheter intervention. Noninvasive imaging evaluation may be useful for characterizing the bleeding source and confirming the presence of active hemorrhage before angiography. If a bleeding source is angiographically identified, superselective catheterization with embolization is typically effective in controlling hemorrhage while minimizing complications.
C1 [Zurkiya, Omar; Walker, T. Gregory] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA.
RP Walker, TG (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St,GRB 298, Boston, MA 02114 USA.
EM Tgwalker@mgh.harvard.edu
NR 19
TC 1
Z9 1
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 753
EP 763
DI 10.2214/AJR.15.14803
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300024
PM 26397323
ER
PT J
AU Petranovic, M
Gilman, MD
Muniappan, A
Hasserjian, RP
Digumarthy, SR
Muse, VV
Sharma, A
Shepard, JAO
Wu, CC
AF Petranovic, Milena
Gilman, Matthew D.
Muniappan, Ashok
Hasserjian, Robert P.
Digumarthy, Subba R.
Muse, Victorine V.
Sharma, Amita
Shepard, Jo-Anne O.
Wu, Carol C.
TI Diagnostic Yield of CT-Guided Percutaneous Transthoracic Needle Biopsy
for Diagnosis of Anterior Mediastinal Masses
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE anterior mediastinal masses; CT-guided biopsy
ID ON-SITE EVALUATION; FINE-NEEDLE; ASPIRATION BIOPSY; ACCURACY; LYMPHOMA;
TUMORS
AB OBJECTIVE. The purpose of this study was to evaluate the diagnostic yield and accuracy of CT-guided percutaneous biopsy of anterior mediastinal masses and assess prebiopsy characteristics that may help to select patients with the highest diagnostic yield.
MATERIALS AND METHODS. Retrospective review of all CT-guided percutaneous biopsies of the anterior mediastinum conducted at our institution from January 2003 through December 2012 was performed to collect data regarding patient demographics, imaging characteristics of biopsied masses, presence of complications, and subsequent surgical intervention or medical treatment (or both). Cytology, core biopsy pathology, and surgical pathology results were recorded. A per-patient analysis was performed using two-tailed t test, Fisher's exact test, and Pearson chi-square test.
RESULTS. The study cohort included 52 patients (32 men, 20 women; mean age, 49 years) with mean diameter of mediastinal mass of 6.9 cm. Diagnostic yield of CT-guided percutaneous biopsy was 77% (40/52), highest for thymic neoplasms (100% [11/11]). Non-diagnostic results were seen in 12 of 52 patients (23%), primarily in patients with lymphoma (75% [9/12]). Fine-needle aspiration yielded the correct diagnosis in 31 of 52 patients (60%), and core biopsy had a diagnostic rate of 77% (36/47). None of the core biopsies were discordant with surgical pathology. There was no statistically significant difference between the diagnostic and the nondiagnostic groups in patient age, lesion size, and presence of necrosis. The complication rate was 3.8% (2/52), all small self-resolving pneumothoraces.
CONCLUSION. CT-guided percutaneous biopsy is a safe diagnostic procedure with high diagnostic yield (77%) for anterior mediastinal lesions, highest for thymic neoplasms (100%), and can potentially obviate more invasive procedures.
C1 [Petranovic, Milena; Gilman, Matthew D.; Digumarthy, Subba R.; Muse, Victorine V.; Sharma, Amita; Shepard, Jo-Anne O.; Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Muniappan, Ashok] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Petranovic, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM mpetranovic@mgh.harvard.edu
NR 22
TC 4
Z9 5
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 774
EP 779
DI 10.2214/AJR.15.14442
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300026
PM 26397325
ER
PT J
AU Zucker, EJ
Newman, B
Larson, DB
Rubesova, E
Barth, RA
AF Zucker, Evan J.
Newman, Beverley
Larson, David B.
Rubesova, Erika
Barth, Richard A.
TI Added Value of Radiologist Consultation for Pediatric Ultrasound:
Implementation and Survey Assessment
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE anxiety; pediatric; radiologist consultation; satisfaction; survey;
ultrasound
ID PATIENT COMMUNICATION; PATIENTS PREFERENCES; IMAGING FINDINGS; DOCTOR;
DISCLOSURE; ATTITUDES; TIME
AB OBJECTIVE. The purpose of this study was to determine whether radiologist-parent (guardian) consultation sessions for pediatric ultrasound with immediate disclosure of examination results if desired increases visit satisfaction, decreases anxiety, and increases understanding of the radiologist's role.
SUBJECTS AND METHODS. Parents chaperoning any outpatient pediatric ultrasound were eligible and completed surveys before and after ultrasound examinations. Before the second survey, parents met with a pediatric radiologist on a randomized basis but could opt out and request or decline the consultation. Differences in anxiety and understanding of the radiologist's role before and after the examination were compared, and overall visit satisfaction measures were tabulated.
RESULTS. Seventy-seven subjects participated, 71 (92%) of whom spoke to a radiologist, mostly on request. In the consultation group, the mean score (1, lowest; 4, highest) for overall experience was 3.8 +/- 0.4 (SD), consultation benefit was 3.7 +/- 0.6, and radiologist interaction was 3.7 +/- 0.6. Demographics were not predictive of satisfaction with statistical significance in a multivariate model. Forty-six of 68 (68%) respondents correctly described the radiologist's role before consultation. The number increased to 60 (88%) after consultation, and the difference was statistically significant (p < 0.001). There was also a statistically significant decrease in mean anxiety score from 2.0 +/- 1.0 to 1.5 +/- 0.8 after consultation (p < 0.001). Sixty-four of 70 (91%) respondents indicated that they would prefer to speak with a radiologist during every visit.
CONCLUSION. Radiologist consultation is well received among parents and associated with decreased anxiety and increased understanding of the radiologist's role. The results of this study support the value of routine radiologist-parent interaction for pediatric ultrasound.
C1 [Zucker, Evan J.; Newman, Beverley; Larson, David B.; Rubesova, Erika; Barth, Richard A.] Stanford Univ, Sch Med, Lucile Packard Childrens Hosp, Dept Radiol, Stanford, CA 94305 USA.
RP Zucker, EJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM zucker@post.harvard.edu
NR 27
TC 1
Z9 1
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 822
EP 826
DI 10.2214/AJR.15.14542
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300033
PM 26397331
ER
PT J
AU Zhu, QL
Faquin, WC
Samir, AE
AF Zhu, Qing-Li
Faquin, William C.
Samir, Anthony E.
TI Relationship Between Sonographic Characteristics and Afirma Gene
Expression Classifier Results in Thyroid Nodules With Indeterminate
Fine-Needle Aspiration Cytopathology
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE Afirma; fine-needle aspiration; indeterminate; thyroid nodules;
ultrasound
ID UNDETERMINED SIGNIFICANCE; FOLLICULAR LESION; BETHESDA SYSTEM; SCIENCE
CONFERENCE; MALIGNANCY RATE; ATYPIA; MANAGEMENT; CYTOLOGY;
RECOMMENDATIONS; DIAGNOSIS
AB OBJECTIVE. The purpose of this article is to investigate whether specific clinical and sonographic characteristics are predictive of a benign Afirma test result.
MATERIALS AND METHODS. We conducted a retrospective study of Afirma gene expression classifier analysis performed in 44 patients with 45 indeterminate thyroid fine-needle aspiration (FNA) cytologic results between March 2013 and April 2014. Of these, 33 of 45 nodules (73.3%) were repeat atypia of undetermined significance (AUS) and follicular lesions of undetermined significance (FLUS), or follicular neoplasm (FN) and suspicious for a follicular neoplasm (SFN) before Afirma testing.
RESULTS. Of the 45 nodules, 21 (46.7%) were cytologically diagnosed as FLUS, 16 (35.6%) were diagnosed as AUS, and eight (17.8%) were diagnosed as FN or SFN. By Afirma testing, 23 of the 45 nodules (51.1%) were benign, 21 (46.7%) were suspicious, and one (2.2%) had nondiagnostic results. The mean (+/- SD) nodule size was smaller in the Afirma-benign group than in the Afirma-suspicious group (1.8 +/- 0.8 cm [95% CI, 1.4-2.1] vs 2.2 +/- 0.8 cm [ 95% CI, 1.8-2.6]; p < 0.035). No sonographic feature was statistically significantly different between the Afirma-benign and -suspicious groups, including nodule solidity (p = 0.225), echogenicity (p = 0.543), calcification (p = 0.542), and hypervascularity (p = 0.976). All nodules were ovoid shaped and had circumscribed margins in both Afirma groups.
CONCLUSION. Smaller nodule size was the only characteristic associated with a benign diagnosis on Afirma testing. Sonographic characteristics are not helpful in cases that had a repeat indeterminate FNA finding before Afirma testing.
C1 [Zhu, Qing-Li] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Ultrasound, Beijing 100730, Peoples R China.
[Zhu, Qing-Li; Samir, Anthony E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Faquin, William C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Samir, AE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA.
EM asamir@mgh.harvard.edu
NR 22
TC 2
Z9 2
U1 1
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 861
EP 865
DI 10.2214/AJR.14.13984
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300039
PM 26397337
ER
PT J
AU Drubach, LA
Jenkins, KJ
Stamoulis, C
Palmer, EL
Lee, EY
AF Drubach, Laura A.
Jenkins, Kathy J.
Stamoulis, Catherine
Palmer, Edwin L., III
Lee, Edward Y.
TI Evaluation of Primary Pulmonary Vein Stenosis in Children: Comparison of
Radionuclide Perfusion Lung Scan and Angiography
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE angiography; pediatric; primary pulmonary vein stenosis; radionuclide
perfusion lung scan
ID PEDIATRIC-PATIENTS; CHEST; SCINTIGRAPHY; FLOW
AB OBJECTIVE. The purpose of this study was to evaluate the utility of radionuclide perfusion lung scanning in the evaluation of primary pulmonary vein stenosis (PVS) in pediatric patients by comparing it with angiography.
MATERIALS AND METHODS. We retrospectively identified pediatric patients with primary PVS who underwent both lung scanning and angiography. A cohort of 34 patients was evaluated. The presence of PVS in the right upper, right lower, left upper, and left lower pulmonary veins on angiograms was recorded. Two nuclear medicine physicians evaluated the lung scans for perfusion defects. Agreement between lung scan and angiographic findings was assessed with contingency tables. Sensitivity and specificity of lung scanning for accurate detection of PVS with angiographic findings as the reference standard were assessed by ROC analysis.
RESULTS. Angiography depicted PVS in 90 of the total 136 pulmonary veins (66%). Lung scans correctly depicted 65 (72%) of the cases of PVS diagnosed with angiography. The sensitivity and specificity of lung scans were 76.0% and 88.9% for the right upper pulmonary vein, 70.6% and 94.1% for the right lower pulmonary vein, 77.3% and 58.3% for the left upper pulmonary vein, and 65.4% and 87.5% for the left lower pulmonary vein.
CONCLUSION. Lung scan findings correlate with angiographic findings in the detection of primary PVS in pediatric patients. Perfusion lung scanning may have a role in angiographically diagnosed PVS by noninvasively showing relative perfusion at the tissue level.
C1 [Drubach, Laura A.; Stamoulis, Catherine; Lee, Edward Y.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02466 USA.
[Drubach, Laura A.; Jenkins, Kathy J.; Stamoulis, Catherine; Palmer, Edwin L., III; Lee, Edward Y.] Harvard Univ, Sch Med, Boston, MA 02466 USA.
[Jenkins, Kathy J.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02466 USA.
[Palmer, Edwin L., III] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Drubach, LA (reprint author), Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02466 USA.
EM Laura.drubach@childrens.harvard.edu
NR 20
TC 1
Z9 1
U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP 873
EP 877
DI 10.2214/AJR.14.13581
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300041
PM 26397339
ER
PT J
AU Shriki, JE
Seyal, AR
Dighe, MK
Yeh, MM
Jalikis, FG
Andeen, NK
Lall, C
Bhargava, P
AF Shriki, Jabi E.
Seyal, Adeel R.
Dighe, Manjiri K.
Yeh, Matthew M.
Jalikis, Florencia G.
Andeen, Nicole K.
Lall, Chandana
Bhargava, Puneet
TI CT of Atypical and Uncommon Presentations of Hepatocellular Carcinoma
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE CT; hepatocellular carcinoma; imaging
ID TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; MR-IMAGING DIAGNOSIS;
OF-THE-LITERATURE; HEPATITIS-C; LIVER-TRANSPLANTATION; UNITED-STATES; US
POPULATION; RISK-FACTORS; CIRRHOSIS; DISEASE
AB OBJECTIVE. The purpose of this article is to familiarize radiologists with uncommon presentations of hepatocellular carcinoma (HCC) with an emphasis on the CT spectrum of atypical appearances.
CONCLUSION. HCC is the fifth most common neoplasm worldwide and the second most common cause of cancer-related death. In many cases, HCC can be confidently diagnosed with noninvasive imaging. However, there are numerous unusual appearances of HCC with which the radiologist must be familiar.
C1 [Shriki, Jabi E.; Dighe, Manjiri K.; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
[Shriki, Jabi E.; Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA.
[Seyal, Adeel R.] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA.
[Yeh, Matthew M.; Jalikis, Florencia G.; Andeen, Nicole K.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
[Lall, Chandana] Univ Calif Irvine, Dept Radiol, Orange, CA 92668 USA.
RP Bhargava, P (reprint author), Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
EM bhargp@uw.edu
NR 82
TC 0
Z9 0
U1 1
U2 5
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2015
VL 205
IS 4
BP W411
EP W423
DI 10.2214/AJR.14.14000
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS1SF
UT WOS:000361847300004
PM 26397348
ER
PT J
AU Howitt, BE
Emori, MM
Drapkin, R
Gaspar, C
Barletta, JA
Nucci, MR
McCluggage, WG
Oliva, E
Hirsch, MS
AF Howitt, Brooke E.
Emori, Megan M.
Drapkin, Ronny
Gaspar, Cynthia
Barletta, Justine A.
Nucci, Marisa R.
McCluggage, W. Glenn
Oliva, Esther
Hirsch, Michelle S.
TI GATA3 Is a Sensitive and Specific Marker of Benign and Malignant
Mesonephric Lesions in the Lower Female Genital Tract
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE mesonephric; cervix; GATA3; endocervical; endometrial; FATWO;
immunohistochemistry; Mullerian; Wolffian
ID PLACENTAL S100 S100P; BINDING-PROTEIN 3; OF-THE-LITERATURE; UTERINE
CERVIX; UROTHELIAL CARCINOMA; HUMAN-PAPILLOMAVIRUS; GLANDULAR LESIONS;
PAX8 EXPRESSION; IMMUNOHISTOCHEMICAL EVALUATION; ENDOCERVICAL
ADENOCARCINOMAS
AB GATA3 is a transcription factor critical for embryogenesis, development, and cell differentiation. Recent studies have suggested that GATA3 is a sensitive and relatively specific biomarker for urothelial and breast carcinomas, with most Mullerian carcinomas being negative. We investigated GATA3 expression in mesonephric/Wolffian remnants and tumors in the female genital tract. A western blot was performed to assess specificity for the GATA3 antibody. GATA3 immunohistochemistry was performed on 59 formalin-fixed paraffin-embedded mesonephric samples, including 17 mesonephric remnants (MR; 11 cervical and 6 fallopian tube), 15 mesonephric hyperplasias, 21 mesonephric carcinomas, and 6 female adnexal tumors of probable Wolffian origin. Thirty conventional endocervical adenocarcinomas (ENDO-CA), 9 gastric-type cervical adenocarcinomas, and 165 endometrial adenocarcinomas (EM-CA) were also evaluated. GATA3 nuclear intensity and extent of staining was evaluated. The western blot revealed GATA3 expression in seminal vesicle and cell lines derived from breast and urothelial carcinomas, but not in other cell lines including ovarian, cervical, and endometrial cancers. All cervical MRs and mesonephric hyperplasias, 5/6 (83%) fallopian tube MRs, and 20/21 (95%) mesonephric carcinomas were GATA3 positive, although with great variability in both intensity (weak to strong) and extent (1+ to 3+) of staining. Only 1/6 (17%) female adnexal tumors of probable Wolffian origin showed weak multifocal staining. One of 30 (3%) usual-type ENDO-CAs and 3/165 EM-CAs exhibited weak-moderate GATA3 immunoreactivity; all gastric-type cervical adenocarcinomas were negative. GATA3 is a highly sensitive and specific marker for mesonephric lesions in the lower genital tract; however, its utility in the upper genital tract may be more limited. In addition, GATA3 can aid in distinguishing lower genital mesonephric lesions from usual-type and gastric-type ENDO-CAs and uterine EM-CAs.
C1 [Howitt, Brooke E.; Drapkin, Ronny; Gaspar, Cynthia; Barletta, Justine A.; Nucci, Marisa R.; Hirsch, Michelle S.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA.
[Howitt, Brooke E.; Drapkin, Ronny; Barletta, Justine A.; Nucci, Marisa R.; Oliva, Esther; Hirsch, Michelle S.] Harvard Univ, Sch Med, Boston, MA USA.
[Emori, Megan M.; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[McCluggage, W. Glenn] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland.
RP Hirsch, MS (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA.
EM mhirsch1@partners.org
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
FU Debra and Robert First Fund; Honorable Tina Brozman Foundation
FX The authors wish to acknowledge administrative and laboratory assistance
from the Brigham and Women's Hospital histology and IHC laboratories,
especially Marc Buchanan, Mei Zheng, Tatiana Zolotarev, Derek Bernay,
and Wanjiang Wei, and the Dana Farber/Harvard Cancer Center tissue
microarray core facility. Research support was provided by the Debra and
Robert First Fund (R.D.) and the Honorable Tina Brozman Foundation
(R.D.).
NR 70
TC 7
Z9 8
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD OCT
PY 2015
VL 39
IS 10
BP 1411
EP 1419
DI 10.1097/PAS.0000000000000471
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA CS5IU
UT WOS:000362112400015
PM 26135559
ER
PT J
AU Irving, JA
Lee, CH
Yip, S
Oliva, E
McCluggage, WG
Young, RH
AF Irving, Julie A.
Lee, Cheng-Han
Yip, Stephen
Oliva, Esther
McCluggage, W. Glenn
Young, Robert H.
TI Microcystic Stromal Tumor A Distinctive Ovarian Sex Cord-Stromal
Neoplasm Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and beta-catenin
Nuclear Expression and CTNNB1 Mutations
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE microcystic stromal tumor; ovary; immunohistochemistry; -catenin; FOXL2
ID SOLID PSEUDOPAPILLARY NEOPLASM; GRANULOSA-CELL TUMORS;
OF-THE-LITERATURE; BETA-CATENIN; E-CADHERIN; NUCLEAR-LOCALIZATION;
OVARIAN NEOPLASM; PANCREAS; FOXL2; EXPRESSION
AB Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10(+)/vimentin(+)/inhibin(-)/calretinin(-) immunophenotype, 3 examples with -catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and -catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons 32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT-1/cyclin D1/nuclear -catenin-positive immunohistochemical profile, which may be useful in diagnosis and in the exclusion of histologic mimics. The presence of diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most supports the classification of MST within the sex cord-stromal category. Aberrant nuclear -catenin expression, detected in all MSTs, appears to be the result of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of MST and may involve activation of -catenin with upregulation of cyclin D1.
C1 [Irving, Julie A.] Royal Jubilee Hosp, Dept Lab Med Pathol & Med Genet, Victoria, BC V8R 1J8, Canada.
[Irving, Julie A.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada.
[Yip, Stephen] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada.
[Lee, Cheng-Han] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada.
[Lee, Cheng-Han] Royal Alexandra Hosp, Edmonton, AB, Canada.
[Oliva, Esther; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Oliva, Esther; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[McCluggage, W. Glenn] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland.
RP Irving, JA (reprint author), Royal Jubilee Hosp, Dept Lab Med Pathol & Med Genet, 1952 Bay St, Victoria, BC V8R 1J8, Canada.
EM julie.irving@viha.ca
NR 30
TC 10
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD OCT
PY 2015
VL 39
IS 10
BP 1420
EP 1426
DI 10.1097/PAS.0000000000000482
PG 7
WC Pathology; Surgery
SC Pathology; Surgery
GA CS5IU
UT WOS:000362112400016
PM 26200099
ER
PT J
AU Rivera, CM
Copeland, LA
McNeal, CJ
Mortensen, EM
Pugh, MJ
MacCarthy, DJ
AF Rivera, Cathleen M.
Copeland, Laurel A.
McNeal, Catherine J.
Mortensen, Eric M.
Pugh, Mary J.
MacCarthy, Daniel J.
TI Use of Health Care System-Supplied Aspirin by Veterans With
Postoperative Heart Attack or Unstable Angina
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Aspirin; Epidemiology; Preventive Medicine; Primary Care; Veterans
ID SECONDARY PREVENTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION;
STATIN THERAPY; NUTRITION EXAMINATION; ATHEROSCLEROSIS RISK; MEDICATION
ADHERENCE; NATIONAL-HEALTH; METAANALYSIS; CORONARY
AB Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention.
C1 [Rivera, Cathleen M.; Copeland, Laurel A.; McNeal, Catherine J.] Baylor Scott & White Hlth, Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Dept Med, Temple, TX 76502 USA.
[Mortensen, Eric M.] Univ Texas Southwestern Med Ctr, Dept Internal Med, Dallas, TX 75390 USA.
[Mortensen, Eric M.] Univ Texas Southwestern Med Ctr, Dept Clin Sci, Dallas, TX 75390 USA.
[Pugh, Mary J.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA.
[MacCarthy, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX USA.
RP Copeland, LA (reprint author), Baylor Scott & White Hlth, Cent Texas Vet Hlth Care Syst, Temple, TX 76502 USA.
EM laurelacopeland@gmail.com
OI Mortensen, Eric/0000-0002-3880-5563; Copeland,
Laurel/0000-0002-9478-0209
NR 34
TC 0
Z9 0
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD OCT
PY 2015
VL 350
IS 4
BP 263
EP 267
DI 10.1097/MAJ.0000000000000560
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS6UM
UT WOS:000362218400005
PM 26351774
ER
PT J
AU Makris, UE
Pugh, MJ
Alvarez, CA
Berlowitz, DR
Turner, BJ
Aung, K
Mortensen, EM
AF Makris, Una E.
Pugh, Mary Jo
Alvarez, Carlos A.
Berlowitz, Dan R.
Turner, Barbara J.
Aung, KoKo
Mortensen, Eric M.
TI Exposure to High-Risk Medications is Associated With Worse Outcomes in
Older Veterans With Chronic Pain
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Pharmacoepidemiology; Adverse drug outcomes; Chronic pain; Aging
ID LOW-BACK-PAIN; RECEIVING PRIMARY-CARE; ADVERSE DRUG EVENTS; PERSISTENT
PAIN; PREVALENCE; HEALTH; ADULTS; MANAGEMENT; TRENDS; METAANALYSIS
AB Background:Chronic pain is common, costly and leads to significant morbidity in older adults, yet there are limited data on medication safety. The authors sought to evaluate the association of incident high-risk medication in the elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain.Methods:A retrospective Veterans Health Administration cohort study was conducted examining older veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines and psychotropics). Outcomes evaluated included all-cause mortality, ED visits or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders.Results:Among 1,807,404 veterans who received Department of Veterans Affairs care in 2005 to 2006, 584,066 (32.3%) had chronic pain; 45,945 veterans with chronic pain (7.9%) had incident HRME exposure. The strongest significant associations of incident HRME were for high-risk opioids with all-cause hospitalizations (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.95-2.23), skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95% CI 2.52-2.73) and mortality (OR 0.80, 95% CI 0.74-0.86), antihistamines with all-cause ED visits (OR 2.82 95% CI 2.72-2.95) and psychotropics with all-cause hospitalizations (OR 2.15, 95% CI 1.96-2.35).Conclusions:Our data indicate that incident HRME is associated with clinically important adverse outcomes in older veterans with chronic pain and highlight the importance of being judicious with prescribing certain classes of drugs in this vulnerable population.
C1 [Makris, Una E.; Alvarez, Carlos A.; Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA.
[Makris, Una E.; Alvarez, Carlos A.; Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Alvarez, Carlos A.] Texas Tech Univ, Hlth Sci Ctr, Dallas, TX USA.
[Pugh, Mary Jo; Turner, Barbara J.; Aung, KoKo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Berlowitz, Dan R.] Ctr Healthcare Org & Implementat Res, Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA.
RP Mortensen, EM (reprint author), Dallas VA Med Ctr, Gen Internal Med 111E,4500 South Lancaster, Dallas, TX 75216 USA.
EM Eric.Mortensen@UTSouthwestern.edu
OI Mortensen, Eric/0000-0002-3880-5563
FU Rheumatology Research Foundation/ASP Junior Career Development Award in
Geriatric Medicine; NIA GEMSSTAR [R03AG040653]; Center for Translational
Medicine, NIH/NCATS [KL2TR001103, UL1TR001105]
FX U.E.M. was supported by the Rheumatology Research Foundation/ASP Junior
Career Development Award in Geriatric Medicine, an NIA GEMSSTAR
(R03AG040653) and the Center for Translational Medicine, NIH/NCATS
Grants (KL2TR001103 and UL1TR001105). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the Center for Translational Medicine, UT Southwestern
Medical Center and its affiliated academic and health care centers, the
National Center for Advancing Translational Sciences, or the National
Institutes of Health.
NR 37
TC 2
Z9 2
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD OCT
PY 2015
VL 350
IS 4
BP 279
EP 285
DI 10.1097/MAJ.0000000000000552
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS6UM
UT WOS:000362218400008
PM 26418380
ER
PT J
AU Kamen, DL
Oates, JC
AF Kamen, Diane L.
Oates, Jim C.
TI A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial
Function in Lupus Patients
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Systemic lupus erythematosus; Endothelial function; Nitric oxide;
Vitamin D; Flow-mediated dilation
ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; 25-HYDROXYVITAMIN
D; D DEFICIENCY; ARTERIAL STIFFNESS; DISEASE-ACTIVITY; CONTROLLED-TRIAL;
S-NITROSYLATION; BRACHIAL-ARTERY
AB Background:The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency.Methods:SLE patients with 25(OH) vitamin D (25(OH)D) levels <20 ng/mL were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to 32 ng/mL. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation.Results:Half of those who achieved 25(OH)D levels of 32 ng/mL experienced increases in FMD, whereas none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D-deficient SLE patients will require 35 patients in each group.Conclusions:These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive, multi-arm, treat-to-target, serum-level trial design may increase the efficiency and likelihood of success of such a study.
C1 [Kamen, Diane L.; Oates, Jim C.] Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA.
[Oates, Jim C.] Ralph H Johnson VA Med Ctr, Med Serv, Rheumatol Sect, Charleston, SC USA.
RP Oates, JC (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA.
EM oatesjc@musc.edu
FU Arthritis Foundation; NIH/NCRR MUSC-SCTR [UL1 RR029882]; NIH/NIAMS [K23
AR052364]; MUSC General and Clinical Research Center [M01RR001070]
FX Supported by a grant from the Arthritis Foundation. This material is the
result of work supported with resources and the use of facilities at the
Ralph H. Johnson VA Medical Center, NIH/NCRR MUSC-SCTR Grant number UL1
RR029882, NIH/NIAMS Grant number K23 AR052364 and the MUSC General and
Clinical Research Center (M01RR001070).
NR 49
TC 4
Z9 4
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD OCT
PY 2015
VL 350
IS 4
BP 302
EP 307
DI 10.1097/MAJ.0000000000000556
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS6UM
UT WOS:000362218400012
PM 26351776
ER
PT J
AU Mathison, DJ
AF Mathison, Douglas J.
TI Introducing Policy Perspectives
SO ANNALS OF THORACIC SURGERY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Mathison, DJ (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA.
EM dmathisen@partners.org
NR 1
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 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2015
VL 100
IS 4
BP 1142
EP 1142
DI 10.1016/j.athoracsur.2015.08.026
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CS7TE
UT WOS:000362288000010
PM 26434422
ER
PT J
AU Kobrin, DM
McCarthy, FH
Herrmann, HC
Anwaruddin, S
Kobrin, S
Szeto, WY
Bavaria, JE
Groeneveld, PW
Desai, ND
AF Kobrin, Dale M.
McCarthy, Fenton H.
Herrmann, Howard C.
Anwaruddin, Saif
Kobrin, Sidney
Szeto, Wilson Y.
Bavaria, Joseph E.
Groeneveld, Peter W.
Desai, Nimesh D.
TI Transcatheter and Surgical Aortic Valve Replacement in Dialysis
Patients: A Propensity-Matched Comparison
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; LONG-TERM SURVIVAL; HIGH-RISK PATIENTS;
CLINICAL-OUTCOMES; CARDIAC-SURGERY; STENOSIS; IMPLANTATION; MORTALITY;
HEMODIALYSIS; IMPACT
AB Background. Transcatheter aortic valve replacement (TAVR) clinical trials in North America excluded patients on dialysis and, consequently, the outcomes of TAVR in dialysis-dependent patients remain unknown.
Methods. All Medicare fee-for-service patients undergoing TAVR (n=5,005) or surgical aortic valve replacement (SAVR) (n=32,634) between January 1, 2011, and November 30, 2012, were identified using procedural codes collected by the Centers for Medicare & Medicaid Services. Dialysis status and comorbidities were identified using diagnosis codes present on arrival for TAVR hospitalization. Patients supported on dialysis who underwent TAVR (n=224) were compared with non-dialysis patients who underwent TAVR as well as a propensity-matched group of contemporaneous dialysis patients who underwent SAVR (n=194 pairs).
Results. The TAVR patients on dialysis were younger than non-dialysis TAVR patients (79.2 years vs 84.1 years; p < 0.01) but had higher prevalence of comorbidities. Dialysis TAVR patients had increased mortality at 30 days (13% vs 6%, p < 0.01) and significantly worse survival by Kaplan-Meier analysis. Multivariable regression found dialysis to be independently associated with worse survival (hazard ratio, 1.73; 95% confidence interval, 1.33% to 2.25%, p < 0.01) in TAVR patients. Propensity-matched dialysis SAVR and dialysis TAVR patients had no significant differences in demographic or risk factors. Matched dialysis TAVR patients had shorter length of stay (6 interquartile range, 4 to 10] vs 10 [IQR 7 to 18] days; p < 0.01) and comparable survival.
Conclusions. TAVR in dialysis patients is associated with decreased survival compared with non-dialysis patients; however, it is comparable with SAVR in high risk dialysis patients based on a propensity-matched comparison. (C) 2015 by The Society of Thoracic Surgeons
C1 [Desai, Nimesh D.] Univ Penn, Perelman Sch Med, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
Univ Penn, Perelman Sch Med, Renal Elect & Hypertens Div, Philadelphia, PA 19104 USA.
Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
Leonard Davis Inst Hlth Econ, Philadelphia, PA USA.
Philadephia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Desai, ND (reprint author), Univ Penn, Perelman Sch Med, Div Cardiovasc Surg, 3400 Spruce St,6 Silverstein, Philadelphia, PA 19104 USA.
EM nimesh.desai@uphd.upenn.edu
NR 26
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 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2015
VL 100
IS 4
BP 1230
EP 1237
DI 10.1016/j.athoracsur.2015.05.039
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CS7TE
UT WOS:000362288000027
PM 26271581
ER
PT J
AU Stephens, EH
Odell, D
Stein, W
La Par, DJ
DeNino, WF
Aftab, M
Berfield, K
Eilers, AL
Groth, S
Lazar, JF
Robich, MP
Shah, AA
Smith, DA
Stock, C
Tchantchaleishvili, V
Mery, CM
Turek, JW
Salazar, J
Nguyen, TC
AF Stephens, Elizabeth H.
Odell, David
Stein, William
La Par, Damien J.
DeNino, Walter F.
Aftab, Muhammad
Berfield, Kathleen
Eilers, Amanda L.
Groth, Shawn
Lazar, John F.
Robich, Michael P.
Shah, Asad A.
Smith, Danielle A.
Stock, Cameron
Tchantchaleishvili, Vakhtang
Mery, Carlos M.
Turek, Joseph W.
Salazar, Jorge
Nguyen, Tom C.
TI A Decade of Change: Training and Career Paths of Cardiothoracic Surgery
Residents 2003 to 2014
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID THORACIC SURGICAL EDUCATION; FUTURE; APPLICANTS; BRIGHTEST; PROGRAM
AB Background. During the past decade, cardiothoracic surgery (CTS) education has undergone tremendous change with the advent of new technologies and the implementation of integrated programs, to name a few. The goal of this study was to assess how residents' career paths, training, and perceptions changed during this period.
Methods. The 2006 to 2014 surveys accompanying the Thoracic Surgery Residents Association/Thoracic Surgery Directors' Association in-training examination taken by CTS residents were analyzed, along with a 2003 survey of graduating CTS residents. Of 2,563 residents surveyed, 2,434 (95%) responded.
Results. During the decade, fewer residents were interested in mixed adult cardiac/thoracic practice (20% in 2014 vs 52% in 2003, p=0.004), more planned on additional training (10% in 2003 vs 41% to 47% from 2011 to 2014), and the frequent use of simulation increased from 1% in 2009 to 24% in 2012 (p < 0.001). More residents recommended CTS to potential trainees (79% in 2014 vs 65% in 2010, p=0.007). Job offers increased from a low of 12% in 2008 with three or more offers to 34% in 2014. Debt increased from 0% with more than $ 200,000 in 2003 to 40% in 2013 (p < 0.001). Compared with residents in traditional programs, more integrated residents in 2014 were interested in adult cardiac surgery (53% vs 31%) and congenital surgery (22% vs 7%), fewer were interested in general thoracic surgery (5% vs 31%, p < 0.001), and more planned on additional training (66% vs 36%, p < 0.001).
Conclusions. With the evolution in CTS over the last decade, residents' training and career paths have changed substantially, with increased specialization and simulation accompanied by increased resident satisfaction and an improved job market. (C) 2015 by The Society of Thoracic Surgeons
C1 Columbia Univ, Dept Cardiac Thorac & Vasc Surg, New York, NY USA.
Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA.
Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30322 USA.
Univ Virginia, Div Thorac & Cardiovasc Surg, Charlottesville, VA USA.
Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA.
Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA.
Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA.
Univ Texas Hlth Sci Ctr San Antonio, Dept Cardiothorac Surg, San Antonio, TX 78229 USA.
Baylor Coll Med, Div Gen Thorac Surg, Houston, TX 77030 USA.
Pinnacle Hlth CardioVasc Inst, Harrisburg, PA USA.
Duke Univ, Dept Surg, Durham, NC USA.
Northwestern Univ, Div Cardiac Surg, Chicago, IL 60611 USA.
Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
Univ Rochester, Med Ctr, Div Cardiothorac Surg, Rochester, NY 14642 USA.
Texas Childrens Hosp, Congenital Heart Surg, Dept Surg, Houston, TX 77030 USA.
Univ Iowa, Dept Cardiothorac Surg, Iowa City, IA USA.
Univ Mississippi, Div Cardiothorac Surg, Oxford, MS USA.
Univ Texas Mem Hermann Texas Med Ctr, Dept Cardiothorac & Vasc Surg, Houston, TX USA.
RP Nguyen, TC (reprint author), 6400 Fannin St,Ste 2850, Houston, TX 77030 USA.
EM tom.c.nguyen@gmail.com
NR 17
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2015
VL 100
IS 4
BP 1305
EP 1314
DI 10.1016/j.athoracsur.2015.04.026
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CS7TE
UT WOS:000362288000037
PM 26169046
ER
PT J
AU Shahian, DM
He, X
Jacobs, JP
Kurlansky, PA
Badhwar, V
Cleveland, JC
Fazzalari, FL
Filardo, G
Normand, SLT
Furnary, AP
Magee, MJ
Rankin, JS
Welke, KF
Han, J
O'Brien, SM
AF Shahian, David M.
He, Xia
Jacobs, Jeffrey P.
Kurlansky, Paul A.
Badhwar, Vinay
Cleveland, Joseph C., Jr.
Fazzalari, Frank L.
Filardo, Giovanni
Normand, Sharon-Lise T.
Furnary, Anthony P.
Magee, Mitchell J.
Rankin, J. Scott
Welke, Karl F.
Han, Jane
O'Brien, Sean M.
TI The Society of Thoracic Surgeons Composite Measure of Individual Surgeon
Performance for Adult Cardiac Surgery: A Report of The Society of
Thoracic Surgeons Quality Measurement Task Force
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID BYPASS-GRAFTING SURGERY; NEW-YORK-STATE; MORTALITY-RATES; HOSPITAL
OUTCOMES; SURGICAL QUALITY; LIMITATIONS; CARE; CLUSTER; ISSUES; VOLUME
AB Background. Previous composite performance measures of The Society of Thoracic Surgeons (STS) were estimated at the STS participant level, typically a hospital or group practice. The STS Quality Measurement Task Force has now developed a multiprocedural, multidimensional composite measure suitable for estimating the performance of individual surgeons.
Methods. The development sample from the STS National Database included 621,489 isolated coronary artery bypass grafting procedures, isolated aortic valve replacement, aortic valve replacement plus coronary artery bypass grafting, mitral, or mitral plus coronary artery bypass grafting procedures performed by 2,286 surgeons between July 1, 2011, and June 30, 2014. Each surgeon's composite score combined their aggregate risk-adjusted mortality and major morbidity rates (each weighted inversely by their standard deviations) and reflected the proportion of case types they performed. Model parameters were estimated in a Bayesian framework. Composite star ratings were examined using 90%, 95%, or 98% Bayesian credible intervals. Measure reliability was estimated using various 3-year case thresholds.
Results. The final composite measure was defined as 0.81 x (1 minus risk-standardized mortality rate) + 0.19 x (1 minus risk-standardized complication rate). Riskadjusted mortality (median, 2.3%; interquartile range, 1.7% to 3.0%), morbidity (median, 13.7%; interquartile range, 10.8% to 17.1%), and composite scores (median, 95.4%; interquartile range, 94.4% to 96.3%) varied substantially across surgeons. Using 98% Bayesian credible intervals, there were 207 1-star (lower performance) surgeons (9.1%), 1,701 2-star (as-expected performance) surgeons (74.4%), and 378 3-star (higher performance) surgeons (16.5%). With an eligibility threshold of 100 cases over 3 years, measure reliability was 0.81.
Conclusions. The STS has developed a multiprocedural composite measure suitable for evaluating performance at the individual surgeon level. (C) 2015 by The Society of Thoracic Surgeons
C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA.
[Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA.
[He, Xia; O'Brien, Sean M.] Clin Res Inst, Durham, NC USA.
[Jacobs, Jeffrey P.] Johns Hopkins All Childrens Heart Inst, St Petersburg, FL USA.
[Kurlansky, Paul A.] Columbia Univ Coll Phys & Surg, Columbia HeartSource, New York, NY 10032 USA.
[Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA.
[Cleveland, Joseph C., Jr.] Univ Colorado, Sch Med, Div Cardiothorac Surg, Aurora, CO USA.
[Fazzalari, Frank L.] Univ Michigan Hlth Syst, Dept Cardiac Surg, Ann Arbor, MI USA.
[Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Furnary, Anthony P.] Starr Wood Cardiac Grp, Portland, OR USA.
[Magee, Mitchell J.] HCA North Texas Div, Dallas, TX USA.
[Rankin, J. Scott] Cardiothorac Surg Associates, Nashville, TN USA.
[Welke, Karl F.] Childrens Hosp Illinois, Peoria, IL USA.
[Welke, Karl F.] Univ Illinois, Coll Med, Peoria, IL 61656 USA.
[Han, Jane] Soc Thorac Surg, Chicago, IL USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 284, Boston, MA 02114 USA.
EM dshahian@partners.org
NR 37
TC 11
Z9 11
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2015
VL 100
IS 4
BP 1315
EP 1325
DI 10.1016/j.athoracsur.2015.06.122
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CS7TE
UT WOS:000362288000038
PM 26330012
ER
PT J
AU Velasquez, JF
Ramirez, MF
Ai, D
Lewis, V
Cata, JP
AF Velasquez, Jose F.
Ramirez, Maria F.
Ai, Di
Lewis, Valerae
Cata, Juan P.
TI Impaired Immune Function in Patients Undergoing Surgery for Bone Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Bone cancer; surgery; immune function; inflammatory response
ID NATURAL-KILLER-CELLS; PROGNOSTIC-FACTOR; COLORECTAL-CANCER; SURGICAL
STRESS; MURINE MODEL; LUNG-CANCER; TUMOR-CELLS; NK CELLS; CARCINOMA;
INTERLEUKIN-6
AB Background: Natural killer (NK) cells undergo quantitative and functional changes after oncological surgery. Patients and Methods: After Institutional Review Board approval, the count and function of NK cells from patients with malignant bone tumors were assessed only days 1, 3, 5 and during first postoperative visit, and compared with preoperative values. The serum concentrations of interleukins (IL)-2, -4 and -6 were also measured before and after surgery. Results: Complete clinical and laboratory data were analyzed from 17 patients with different bone malignancies. The number of NK cells significantly decreased postoperatively as well as their function. The maximum deterioration in their function occurred 5 days postoperatively. The serum concentrations of IL-2 and IL-4 did not change perioperatively. In contrast, a significant increase in the concentrations of IL-6 was observed on day 1, 3 and 5 postoperatively. Conclusion: A significant inflammatory response and innate immune suppression occurred after surgery for malignant bone tumors.
C1 [Velasquez, Jose F.; Cata, Juan P.] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Houston, TX 77030 USA.
[Lewis, Valerae] Univ Texas MD Anderson Canc Ctr, Dept Orthoped Oncol, Houston, TX 77030 USA.
[Ramirez, Maria F.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA.
[Cata, Juan P.] Anesthesia & Surg Oncol Res Grp, Houston, TX USA.
[Ai, Di] Baylor Scott & White Mem Hosp, Texas A&M Canc Ctr, Dept Pathol, Temple, TX USA.
RP Cata, JP (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 409,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM jcata@mdanderson.org
FU Triumph Over Kid Cancer foundation
FX This work was funded by a grant award to JPC from the Triumph Over Kid
Cancer foundation.
NR 32
TC 0
Z9 0
U1 0
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD OCT
PY 2015
VL 35
IS 10
BP 5461
EP 5466
PG 6
WC Oncology
SC Oncology
GA CS1KM
UT WOS:000361823200037
PM 26408709
ER
PT J
AU Kohan, R
Mole, SE
Cotman, SL
AF Kohan, Romina
Mole, Sara E.
Cotman, Susan L.
TI Special issue: Molecular basis of NCL Preface
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Editorial Material
C1 [Kohan, Romina] Univ Nacl Cordoba, Fac Odontol, Fac Ciencias Med, Ctr Estudio Metabolopatias Congenitas CEMECO, RA-5000 Cordoba, Argentina.
[Mole, Sara E.] UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England.
[Mole, Sara E.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Mole, Sara E.] UCL Inst Child Hlth, Genet & Genom Med Programme, Genet & Epigenet Hlth & Dis, London WC1N 1EH, England.
[Cotman, Susan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cotman, Susan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
RP Mole, SE (reprint author), UCL, MRC Lab Mol Cell Biol, Gower St, London WC1E 6BT, England.
EM kohanromina@gmail.com; s.mole@ucl.ac.uk; cotman@helix.mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 OCT
PY 2015
VL 1852
IS 10
SI SI
BP 2235
EP 2236
DI 10.1016/j.bbadis.2015.06.023
PN B
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CS2TM
UT WOS:000361924900001
PM 26122823
ER
PT J
AU Mole, SE
Connan, SL
AF Mole, Sara E.
Connan, Susan L.
TI Genetics of the neuronal ceroid lipofuscinoses (Batten disease)
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Batten; CLN; Neuronal ceroid lipofuscinosis; NCL, genetics, mutation
ID CATHEPSIN-D DEFICIENCY; TRANSMEMBRANE PROTEIN; MISSENSE MUTATION;
KUFS-DISEASE; MUTANT MICE; ONSET; VARIANT; KCTD7; CLN8; PROGRANULIN
AB The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders that affect children and adults and are grouped together by similar clinical features and the accumulation of autofluorescent storage material. More than a dozen genes containing over 430 mutations underlying human NCLs have been identified. These genes encode lysosomal enzymes (CLN1, CLN2, CLN10, CLN13), a soluble lysosomai protein (CLN5), a protein in the secretory pathway (CLN11), two cytoplasmic proteins that also peripherally associate with membranes (CLN4, CLN14), and many transmembrane proteins with different subcellular locations (CLN3, CLN6, CLN7, CLN8, CLN12). For most NCLs, the function of the causative gene has not been fully defined. Most of the mutations in these genes are associated with a typical disease phenotype, but some result in variable disease onset, severity, and progression, including distinct clinical phenotypes. There remain disease subgroups with unknown molecular genetic backgrounds. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofiiscinoses (Batten Disease)." (C) 2015 Elsevier B.V. All rights reserved.
C1 [Mole, Sara E.] UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England.
[Mole, Sara E.] UCL, UCL Inst Child Hlth, London WC1E 6BT, England.
[Mole, Sara E.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Connan, Susan L.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Mole, SE (reprint author), UCL, MRC Lab Mol Cell Biol, Gower St, London WC1E 6BT, England.
EM s.mole@ucl.ac.uk
OI Mole, Sara/0000-0003-4385-4957
FU UK Batten Disease Family Association; USA Batten Disease Support and
Research Association in the maintenance of this database; National
Institutes of Health: National Institute of Neurological Disorders
Stroke [R01NS073813]
FX The authors thank clinicians, scientists, and families who continue to
report or directly submit new changes in NCL genes and more recently
cases to the NCL Mutation Database. We acknowledge financial support
from the UK Batten Disease Family Association and the USA Batten Disease
Support and Research Association in the maintenance of this database.
SLC receives research support from by the National Institutes of Health:
National Institute of Neurological Disorders & Stroke (R01NS073813).
NR 39
TC 19
Z9 19
U1 1
U2 17
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 OCT
PY 2015
VL 1852
IS 10
SI SI
BP 2237
EP 2241
DI 10.1016/j.bbadis.2015.05.011
PN B
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CS2TM
UT WOS:000361924900002
PM 26026925
ER
PT J
AU Kohan, R
Pesaola, F
Guelbert, N
Pons, P
Oller-Ramirez, AM
Rautenberg, G
Becerra, A
Sims, K
Xin, WN
Cismondi, IA
de Halac, IN
AF Kohan, Romina
Pesaola, Favio
Guelbert, Norberto
Pons, Patricia
Maria Oller-Ramirez, Ana
Rautenberg, Gisela
Becerra, Adriana
Sims, Katherine
Xin, Winnie
Adriana Cismondi, Ines
Noher de Halac, Ines
TI The neuronal ceroid lipofuscinoses program: A translational research
experience in Argentina
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Neuronal ceroid lipofuscinoses; Algorithm; Morphology; Enzymes; DNA
variants
ID PALMITOYL-PROTEIN THIOESTERASE; TRIPEPTIDYL-PEPTIDASE-I; GRANULAR
OSMIOPHILIC DEPOSITS; CATHEPSIN-D DEFICIENCY; B KUFS-DISEASE;
BATTEN-DISEASE; MUTATIONS; GENE; DIAGNOSIS; ONSET
AB Background: The Argentinean program was initiated more than a decade ago as the first experience of systematic translational research focused on NCL in Latin America. The aim was to overcome misdiagnoses and underdiagnoses in the region.
Subjects: 216 NCL suspected individuals from 8 different countries and their direct family members. Methods: Clinical assessment, enzyme testing, electron microscopy, and DNA screening.
Results and discussion: 1) The study confirmed NCL disease in 122 subjects. Phenotypic studies comprised epileptic seizures and movement disorders, ophthalmology, neurophysiology, image analysis, rating scales, enzyme testing, and electron microscopy, carried out under a consensus algorithm; 2) DNA screening and validation of mutations in genes PPT1 (CLN1), TPP1 (CLN2), CLN3, CLN5, CLN6, MFSD8 (CLN7), and CLN8: characterization of variant types, novel/known mutations and polymorphisms; 3) Progress of the epidemiological picture in Latin America; and 4) NCL-like pathology studies in progress. The Translational Research Program was highly efficient in addressing the misdiagnosis/underdiagnosis in the NCL disorders. The study of "orphan diseases" in a public administrated hospital should be adopted by the health systems, as it positively impacts upon the family's quality of life, the collection of epidemiological data, and triggers research advances. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". (C) 2015 Elsevier B.V. All rights reserved.
C1 [Kohan, Romina; Pesaola, Favio; Guelbert, Norberto; Maria Oller-Ramirez, Ana; Rautenberg, Gisela; Becerra, Adriana; Adriana Cismondi, Ines; Noher de Halac, Ines] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Estudio Metabolopatias Congenitas CEMECO, RA-5014 Cordoba, Argentina.
[Kohan, Romina; Adriana Cismondi, Ines; Noher de Halac, Ines] Univ Nacl Cordoba, Fac Odontol, RA-5000 Cordoba, Argentina.
[Pesaola, Favio; Noher de Halac, Ines] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina.
[Pons, Patricia] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Microscopia Elect, RA-5000 Cordoba, Argentina.
[Sims, Katherine; Xin, Winnie] Massachusetts Gen Hosp, Dept Neurol, Ctr Genet Res CHGR, Boston, MA 02114 USA.
RP de Halac, IN (reprint author), Univ Nacl Cordoba, Fac Ciencias Med, CEMECO, Ferroviarios 1250, RA-5014 Cordoba, Argentina.
EM kohanromina@gmail.com; favio.pesaola@gmail.com; nguelbert@arnet.com.ar;
ppons@cmefcm.uncor.edu; ramirezoller@gmail.com;
giselarautenberg@hotmail.com; dra.adrianabecerra@hotmail.com;
sims@helix.mgh.harvard.edu; xin@helix.mgh.harvard.edu;
ines.adriana.cismondi@unc.edu.ar; nclcemeco1789@gmail.com
FU Argentinean National Research Council (CONICET-RA) [PIP 6185-2005, PIP
112-2011]; Secretary of Science and Technology of the National
University Cordoba (SECyT-UNC) [05/J155, 05/H295, 05/J079]; Ministry of
Science and Technology from the Province of Cordoba (MINCYT: PID); NIH
(Fogarty Program "Brain Disorders in the Developing World")
[1R21TW008433-01]; Batten Disease Support and Research Association
(BDSRA-US)
FX We kindly acknowledge the NCL families from Latin America, the personnel
of the Centro de Estudio de las Metabolopatias Congenitas (CEMECO) at
the Children's Hospital, Cordoba Argentina, and the National University
Cordoba. We thank the Science and Technology Organizations that provided
grant support to our research: Argentinean National Research Council
(CONICET-RA: PIP 6185-2005, PIP 112-2011), Secretary of Science and
Technology of the National University Cordoba (SECyT-UNC: 05/J155,
05/H295, 05/J079), Ministry of Science and Technology from the Province
of Cordoba (MINCYT: PID 2009), NIH (Fogarty Program "Brain Disorders in
the Developing World": 1R21TW008433-01), and Batten Disease Support and
Research Association (BDSRA-US: years 2001-2002-2003-2005-2006). We
thank Michael Fietz from Australia for the comments on his SCAR7
patient, Ana Lia Taratuto from Argentina for her contribution with EM
photographs, and all the colleagues that derived patients and samples
for study, from Chile (Monica Troncoso, Sacarlett Witting, Gloria
Duran), Brazil (Roberto Giugliani, Marta Regina Clivati), Mexico (Sandra
Nieto-Martinez, Matilde Ruiz-Garcia), Uruguay (Roberto Quadrelli),
Colombia (Lisseth Cabarcas Castro), Argentina (Raquel Dodelson de
Kremer, Maria del Rosario Aldao, Liliana Czornyj, Alejandra Visich, Ana
Maria Guercio, Mercedes Villanueva, Santiago Sfaello, Hugo Arroyo,
Rosana Ocampo, Gabriel Vazquez, Soledad Monges, Ines Denzler, Laura
Cassar, Silvia Tenembaun, Marcela Pereyra, Griselda Ray, Femanda Garro,
Ricardo Fauze, and other neuropediatricians and clinical geneticians,
residents and fellows of our country).
NR 94
TC 2
Z9 2
U1 1
U2 5
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 OCT
PY 2015
VL 1852
IS 10
SI SI
BP 2301
EP 2311
DI 10.1016/j.bbadis.2015.05.003
PN B
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CS2TM
UT WOS:000361924900010
PM 25976102
ER
PT J
AU Cotman, SL
Mole, SE
Kohan, R
AF Cotman, Susan L.
Mole, Sara E.
Kohan, Romina
TI Future perspectives: Moving towards NCL treatments
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Neuronal Ceroid Lipofuscinosis (NCL); Batten disease
ID NEURONAL CEROID-LIPOFUSCINOSIS; ENZYME REPLACEMENT; BATTEN-DISEASE;
METABOLOMICS; MUTATION; BRAIN; PATHOLOGY; MODEL; TPP1; CLN3
AB Clinicians, basic researchers, representatives from pharma and families from around the world met in Cordoba, Argentina in October, 2014 to discuss recent research progress at the 14th International Congress on Neuronal Ceroid Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal, inherited lysosomal disorders with primarily neurodegenerative symptoms. This brief review article will provide perspectives on the anticipated future directions of NCL basic and clinical research as we move towards improved diagnosis, care and treatment of NCL patients.
This article is part of a Special Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease). (C) 2015 Elsevier B.V. All rights reserved.
C1 [Cotman, Susan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cotman, Susan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Mole, Sara E.] UCL, UCL Inst Child Hlth, Dept Genet Evolut & Environm, MRC Lab Cell Biol, London WC1E 6BT, England.
[Kohan, Romina] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Estudio Metabolopatias Congenitas CEMECO, RA-5014 Cordoba, Argentina.
RP Cotman, SL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA.
EM cotman@helix.mgh.harvard.edu
OI Mole, Sara/0000-0003-4385-4957
FU NINDS NIH HHS [R01 NS073813]
NR 20
TC 0
Z9 0
U1 0
U2 5
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 OCT
PY 2015
VL 1852
IS 10
SI SI
BP 2336
EP 2338
DI 10.1016/j.bbadis.2015.04.001
PN B
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CS2TM
UT WOS:000361924900015
PM 25857620
ER
PT J
AU Kressin, NR
Lin, MY
AF Kressin, Nancy R.
Lin, Meng-Yun
TI Race/ethnicity, and Americans' perceptions and experiences of over- and
under-use of care: a cross-sectional study
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Patient preferences; Disparities; Survey research
ID HEALTH; PHYSICIANS; LITERACY
AB Background: Despite widespread documentation of racial/ethnic disparities in care (predominantly under-use of needed care), differences in population-wide attitudes or experiences about under-or overuse (care where harms may outweigh potential benefits) of care are not well understood. We examined whether race/ethnicity is associated with perceptions or experiences of overuse or underuse.
Methods: We conducted secondary analysis of a cross-sectional national telephone survey of nationally representative sample of 1238 American adults; 57.9 % female, 75.4 % Non-Hispanic White, 11.8 % Non-Hispanic Black, 10.1 % Hispanic. The main outcome measures are general perceptions and personal experiences of overuse and underuse, including cost-related dimensions of each.
Results: Bivariate results indicated that respondents of minority race/ethnicity generally viewed both overuse and underuse as bigger problems than did Whites, and reported more personal experiences of each. After adjustment, Hispanics were less likely than Whites to report personal experiences of overuse (odds ratio [OR] [95 % CI], 0.44 [0.23 to 0.86]), while Blacks and Others were more likely to report cost-related overuse (ORs [95 % CIs], 4.16 [2.30 to 7.51]; 3.55 [1.52 to 8.28], respectively). Non-Hispanic Others more often reported doctors' protection from overuse (OR [95 % CI], 3.69 [1.75 to 7.78]). General concerns with underuse were more frequent among Blacks and Hispanics (ORs [95 % CIs], 3.07 [1.72 to 5.54]; 2.12 [1.24 to 3.61] respectively), while Others reported significantly fewer concerns (OR [95 % CI], 0.43 [0.23 to 0.80]).
Conclusions: Over-and underuse of medical care are important problems for many Americans, and experiences vary by race/ethnicity. Clinician communication and educational campaigns about appropriateness of care may need tailoring for varying population groups.
C1 [Kressin, Nancy R.; Lin, Meng-Yun] Boston Univ, Sch Med, Sect Gen Internal Med, Crosstown Ctr, Boston, MA 02118 USA.
[Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Lin, Meng-Yun] Boston Univ, Sch Publ Hlth, Hlth Policy & Management Dept, Boston, MA 02118 USA.
RP Kressin, NR (reprint author), Boston Univ, Sch Med, Sect Gen Internal Med, Crosstown Ctr, 801 Massachusetts Ave, Boston, MA 02118 USA.
EM nkressin@bu.edu
FU Department of Veterans Affairs, Health Services Research & Development
Service [RCS 02-066-1]
FX Dr. Kressin is supported in part by a Research Career Scientist award
from the Department of Veterans Affairs, Health Services Research &
Development Service (RCS 02-066-1).
NR 22
TC 0
Z9 0
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD OCT 1
PY 2015
VL 15
AR 443
DI 10.1186/s12913-015-1106-7
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CS6DY
UT WOS:000362169000001
PM 26428620
ER
PT J
AU Peppercorn, J
Houck, K
Beri, N
Villagra, V
Wogu, AF
Lyman, GH
Wheeler, SB
AF Peppercorn, Jeffrey
Houck, Kevin
Beri, Nina
Villagra, Victor
Wogu, Adane F.
Lyman, Gary H.
Wheeler, Stephanie B.
TI Breast cancer screening utilization and understanding of current
guidelines among rural US women with private insurance
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer screening; Rural; Health disparities; Survey; Guidelines
ID SERVICES TASK-FORCE; CARCINOMA MORTALITY; MAMMOGRAPHY; IMPACT;
DIAGNOSIS; THERAPY; TRIAL; RECOMMENDATIONS; POPULATION; PROGRAM
AB Women living in rural areas of the U.S. face disparities in screening mammography and breast cancer outcomes. We sought to evaluate utilization of mammography, awareness of screening guidelines, and attitudes towards screening among rural insured U.S. women. We conducted a cross-sectional self-administered anonymous survey among 2000 women aged 40-64 insured by the National Rural Electric Cooperative Association, a non-profit insurer for electrical utility workers in predominantly rural areas across the U.S. Outcomes included mammographic screening in the past year, screening interval, awareness of guidelines, and perceived barriers to screening. 1588 women responded to the survey (response rate 79.4 %). 74 % of respondents lived in a rural area. Among women aged 40-49, 66.5 % reported mammographic screening in the past year. 46 % received annual screening, 32 % biennial screening, and 22 % rare/no screening. Among women aged 50-64, 77.1 % reported screening in the past year. 63 % received annual screening, 25 % biennial screening, and 12 % rare/no screening. The majority of women (98 %) believed that the mammography can find breast cancer early and save lives. Less than 1 % of younger women, and only 14 % of women over age 50 identified the recommendations of the U.S. Preventative Services Screening Task Force as the current expert recommendations for screening. Screening practices tended to follow perceived guideline recommendations. When rural U.S. women over age 40 have insurance, most receive breast cancer screening. The screening guidelines of cancer advocacy groups and specialty societies appear more influential and widely recognized than those of the U.S. preventative services taskforce.
C1 [Peppercorn, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Houck, Kevin; Beri, Nina] Duke Univ, Med Ctr, Durham, NC USA.
[Villagra, Victor] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Wogu, Adane F.; Wheeler, Stephanie B.] Univ N Carolina, Sch Global Publ Hlth, Chapel Hill, NC USA.
[Lyman, Gary H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Peppercorn, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA.
EM jpeppercorn@mgh.harvard.edu
FU American Cancer Society
FX This study was supported by a Research Scholar grant from the American
Cancer Society (JP).
NR 30
TC 2
Z9 2
U1 1
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 OCT
PY 2015
VL 153
IS 3
BP 659
EP 667
DI 10.1007/s10549-015-3566-1
PG 9
WC Oncology
SC Oncology
GA CS3PS
UT WOS:000361987300019
PM 26386956
ER
PT J
AU Chan, CHF
Coopey, SB
Freer, PE
Hughes, KS
AF Chan, Carlos H. F.
Coopey, Suzanne B.
Freer, Phoebe E.
Hughes, Kevin S.
TI False-negative rate of combined mammography and ultrasound for women
with palpable breast masses
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast ultrasound; Mammography; Palpable breast mass
ID FINE-NEEDLE ASPIRATION; COMBINED PHYSICAL-EXAMINATION; TRIPLE-TEST;
SYMPTOMATIC POPULATION; CLINICAL EXAMINATION; CANCER; DIAGNOSIS; BENIGN;
BIOPSY; ACCURACY
AB Mammography and ultrasound are often used concurrently for patients with palpable breast masses. While mammography has a false-negative rate of approximately 15 %, the addition of breast ultrasound decreases this rate among patients with palpable breast masses. There are no recent outcome data regarding the use of combined reporting of ultrasound and mammography (CRUM) for palpable breast masses. In this study, female patients presenting with a palpable breast mass were retrospectively reviewed in a prospectively entered database at a single institution from June 2010 to July 2013. All cancer cases and false-negative cases using CRUM were identified. Cancer rates, false-negative rates, and negative predictive values were calculated based on CRUM breast imaging-reporting and data system (BI-RADS) categories. One thousand two hundreds and twelve female patients presenting with a palpable breast mass were identified; 77 % of patients had CRUM and 73 % (682/932) were BI-RADS 1-2. Despite negative or benign BI-RADS, 9.5 % of patients with BI-RADS 1-2 (65/682) underwent biopsy, compared to 96 % of patients with a BI-RADS 4-5 designation. Eighty-one patients were found to have cancers; 2 had BI-RADS 1-2 imaging. The false-negative rate of CRUM was 2.4 % (2/81). Since 69 % (428/617) of BI-RADS 1-2 patients without tissue diagnosis had follow-up imaging and/or clinical exam (median: 27 months, range: 2-62 months) and none developed cancers, the cancer rate and negative predictive value of a palpable breast mass of BI-RADS 1-2 were estimated to be 0.3 % (2/682) and 99.7 %, respectively. In the modern era of combined imaging for breast masses, a patient with a low suspicion exam can be reassured with a negative CRUM report.
C1 [Chan, Carlos H. F.; Coopey, Suzanne B.; Hughes, Kevin S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA.
[Freer, Phoebe E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM carloshfchan@gmail.com; kshughes@partners.org
OI Freer, Phoebe/0000-0001-6886-7100
NR 21
TC 1
Z9 1
U1 1
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 OCT
PY 2015
VL 153
IS 3
BP 699
EP 702
DI 10.1007/s10549-015-3557-2
PG 4
WC Oncology
SC Oncology
GA CS3PS
UT WOS:000361987300023
PM 26341750
ER
PT J
AU Frazer, JK
Li, KJ
Galardy, P
Perkins, SL
Auperin, A
Anderson, JR
Pinkerton, R
Buxton, A
Gross, TG
Weinstein, H
Harrison, L
Shiramizu, B
Barth, M
Goldman, S
Patte, C
Cairo, MS
AF Frazer, J. Kimble
Li, Kevin J.
Galardy, Paul
Perkins, Sherrie L.
Auperin, Anne
Anderson, James R.
Pinkerton, Ross
Buxton, Allen
Gross, Thomas G.
Weinstein, Howard
Harrison, Lauren
Shiramizu, Bruce
Barth, Matthew
Goldman, Stanton
Patte, Catherine
Cairo, Mitchell S.
TI Excellent outcomes in children and adolescents with central nervous
system-positive (CNS+) Burkitt lymphoma/leukemia (BL) or other mature
B-NHL using intrathecal and systemic chemotherapy without CNS
irradiation: results from FAB/LMB96 and ANHL01P1 studies
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Meeting Abstract
CT 5th International Symposium on Childhood, Adolescent and Young Adult
Non-Hodgkin Lymphoma
CY OCT 22, 2015
CL Varese, ITALY
C1 [Frazer, J. Kimble; Li, Kevin J.] Univ Oklahoma, Hlth Sci Ctr, Pediat Hematol Oncol, Oklahoma City, OK USA.
[Galardy, Paul] Mayo Clin, Pediat Hematol Oncol, Rochester, MN USA.
[Perkins, Sherrie L.] Univ Utah, Pathol Labs, Salt Lake City, UT USA.
[Perkins, Sherrie L.] Univ Utah, ARUP Labs, Salt Lake City, UT USA.
[Auperin, Anne; Patte, Catherine] CLCC Inst Cancerol Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France.
[Anderson, James R.] Frontier Sci & Technol Res Fdn Inc, Madison, WI USA.
[Pinkerton, Ross] Univ Queensland, Brisbane, Qld, Australia.
[Buxton, Allen] Childrens Oncol Grp, Monrovia, CA USA.
[Gross, Thomas G.] NCI, Ctr Global Hlth, NIH, Rockville, MD USA.
[Weinstein, Howard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Hematol Oncol, Boston, MA USA.
[Harrison, Lauren; Cairo, Mitchell S.] New York Med Coll, Pediat, Valhalla, NY 10595 USA.
[Shiramizu, Bruce] Univ Hawaii, Pediat Hematol Oncol, Honolulu, HI 96822 USA.
[Barth, Matthew] Roswell Pk Canc Inst, Pediat, Buffalo, NY 14263 USA.
[Goldman, Stanton] Med City Childrens Hosp, Pediat Hematol Oncol, Dallas, TX USA.
[Cairo, Mitchell S.] New York Med Coll, Med Pathol Microbiol & Immunol, Valhalla, NY 10595 USA.
[Cairo, Mitchell S.] New York Med Coll, Cell Biol & Anat, Valhalla, NY 10595 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 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2015
VL 171
SU 1
SI SI
MA 10
BP 6
EP 7
PG 2
WC Hematology
SC Hematology
GA CS9QG
UT WOS:000362425300009
ER
PT J
AU Chen, HY
Liu, X
Clayman, ES
Shao, FY
Xiao, MS
Tian, XY
Fu, WY
Zhang, CY
Ruan, BB
Zhou, PJ
Liu, Z
Wang, YF
Rui, W
AF Chen, Hongyuan
Liu, Xiao
Clayman, Eric S.
Shao, Fangyuan
Xiao, Manshan
Tian, Xuyan
Fu, Wuyu
Zhang, Caiyun
Ruan, Bibo
Zhou, Pengjun
Liu, Zhong
Wang, Yifei
Rui, Wen
TI Synthesis and Evaluation of a CBZ-AAN-Dox Prodrug and its in vitro
Effects on SiHa Cervical Cancer Cells Under Hypoxic Conditions
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Article
DE asparagine endopeptidase; doxorubicin; hypoxia; legumain;
N-benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin; prodrug; SiHa cells
ID BREAST-CANCER; LEGUMAIN EXPRESSION; TUMOR MICROENVIRONMENT; DOXORUBICIN
UPTAKE; PROGNOSTIC-FACTOR; TARGET; ASSOCIATION; THERAPY; GROWTH; GENE
AB Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors, it causes many side-effects such as heart and kidney damage, bone marrow suppression, and drug resistance. Legumain is a lysosomal protease that is elevated and associated with an invasive and metastatic phenotype in a number of solid tumors. In this study, we designed and synthesized a Dox prodrug, N-benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin (CBZ-AAN-Dox), with 94% purity. Single substrate kinetic assays demonstrated hLegumain-specific enzymatic cleavage and activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug substrate was more sensitive in acidic conditions, releasing more than 70% of Dox after 24h. Treatment of tumor cells with our prodrug demonstrated a much higher IC50 value, significantly enhanced uptake of the prodrug, and considerably less cellular toxicity compared to Dox treatment alone. Our study presents a novel prodrug, CBZ-AAN-Dox, to potentially increase both the safety and efficacy of clinical treatment of tumors by exploiting the tumor's innate expression of legumain.
C1 [Chen, Hongyuan; Liu, Xiao; Shao, Fangyuan; Xiao, Manshan; Tian, Xuyan; Fu, Wuyu; Zhang, Caiyun; Ruan, Bibo; Zhou, Pengjun] Guangdong Pharmaceut Univ, Sch Basic Course, Dept Pathogen Biol & Immunol, Guangzhou 510060, Guangdong, Peoples R China.
[Chen, Hongyuan] Guangdong Pharmaceut Univ, Guangdong Key Lab Pharmaceut Bioact Subst, Guangzhou 510006, Guangdong, Peoples R China.
[Clayman, Eric S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Clayman, Eric S.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Liu, Zhong; Wang, Yifei] Jinan Univ, Natl Engn Res Ctr Genet Med, Guangdong Prov Key Lab Bioengn Med, Biomed Res & Dev Ctr, Guangzhou 510632, Guangdong, Peoples R China.
[Rui, Wen] Guangdong Pharmaceut Univ, Ctr Lab, Guangzhou 510006, Guangdong, Peoples R China.
RP Rui, W (reprint author), Guangdong Pharmaceut Univ, Ctr Lab, Guangzhou 510006, Guangdong, Peoples R China.
EM r_wing@163.com
RI Liu, Zhong/B-6323-2016
OI Liu, Zhong/0000-0002-5132-7463
FU China Postdoctoral Science Foundation [2013M542234]; Science and
Technology Planning Project of Guangdong Province [2013B021800085];
Science and Technology Project Guangzhou City Grant [2014J4100058]
FX This research were supported by China Postdoctoral Science Foundation
(No. 2013M542234), 2013 Science and Technology Planning Project of
Guangdong Province (No. 2013B021800085), and Science and Technology
Project Guangzhou City Grant (No. 2014J4100058).
NR 32
TC 3
Z9 3
U1 2
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-0277
EI 1747-0285
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD OCT
PY 2015
VL 86
IS 4
BP 589
EP 598
DI 10.1111/cbdd.12525
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA CS6BZ
UT WOS:000362163500021
PM 25619622
ER
PT J
AU Asplund, KM
Kair, LR
Arain, YH
Cervantes, M
Oreskovic, NM
Zuckerman, KE
AF Asplund, Karin M.
Kair, Laura R.
Arain, Yassar H.
Cervantes, Marlene
Oreskovic, Nicolas M.
Zuckerman, Katharine E.
TI Early Childhood Screen Time and Parental Attitudes Toward Child
Television Viewing in a Low-Income Latino Population Attending the
Special Supplemental Nutrition Program for Women, Infants, and Children
SO CHILDHOOD OBESITY
LA English
DT Article
ID YOUNG-CHILDREN; MEDIA USE; ADOLESCENTS; OVERWEIGHT; ENVIRONMENT;
OBESITY; RISK
AB Background: Early childhood media exposure is associated with obesity and multiple adverse health conditions. The aims of this study were to assess parental attitudes toward childhood television (TV) viewing in a low-income population and examine the extent to which child BMI, child/parent demographics, and household media environment are associated with adherence to American Academy of Pediatrics (AAP) guidelines for screen time. Methods: This was a cross-sectional survey study of 314 parents of children ages 0-5 years surveyed in English or Spanish by self-administered questionnaire at a Special Supplemental Nutrition Program for Women, Infants and Children (WIC) clinic in Oregon. Results: In this majority Latino sample (73%), half (53%) of the children met AAP guidelines on screen time limits, 56% met AAP guidelines for no TV in the child's bedroom, and 29% met both. Children were more likely to meet AAP guidelines when there were <2 TVs in the home, there was no TV during dinner, or their parents spent less time viewing electronic media. Parents who spent less time viewing electronic media were more likely to report believing that TV provides little value or usefulness. Conclusions: In this low-income, predominantly Latino population attending WIC, parent media-viewing and household media environment are strongly associated with child screen time. Programs aimed at reducing child screen time may benefit from interventions that address parental viewing habits.
C1 [Asplund, Karin M.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA.
[Kair, Laura R.] Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, Iowa City, IA USA.
[Arain, Yassar H.] Lucile Packard Childrens Hosp Stanford, Dept Pediat, Stanford, CA USA.
[Cervantes, Marlene; Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Doernbecher Childrens Hosp, Portland, OR 97239 USA.
[Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
[Oreskovic, Nicolas M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Asplund, KM (reprint author), Oregon Hlth & Sci Univ, Sch Med, Mail Code L102,3181 Southwest Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM asplund@ohsu.edu
FU National Institute of Mental Health [1K23MH095828]; National Heart,
Lung, and Blood Institute [K23HL103841]
FX Dr. Zuckerman's effort was funded by grant 1K23MH095828 from the
National Institute of Mental Health. Dr. Oreskovic's effort was funded
by grant K23HL103841 from the National Heart, Lung, and Blood Institute.
The funding sources had no role in the design and conduct of the study;
collection, management, analysis, and interpretation of the data;
preparation, review, or approval of the manuscript; and decision to
submit the manuscript for publication.
NR 38
TC 0
Z9 0
U1 3
U2 16
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-2168
EI 2153-2176
J9 CHILD OBES
JI Child Obes.
PD OCT 1
PY 2015
VL 11
IS 5
BP 590
EP 599
DI 10.1089/chi.2015.0001
PG 10
WC Pediatrics
SC Pediatrics
GA CS7NE
UT WOS:000362269500014
PM 26390321
ER
PT J
AU Tsai, TY
Li, JS
Dimitriou, D
Kwon, YM
AF Tsai, Tsung-Yuan
Li, Jing-Sheng
Dimitriou, Dimitris
Kwon, Young-Min
TI Does component alignment affect gait symmetry in unilateral total hip
arthroplasty patients?
SO CLINICAL BIOMECHANICS
LA English
DT Article
DE Total hip arthroplasty; Gait; Component alignment; Kinematics;
Fluoroscope
ID REPLACEMENT PATIENTS; SURGICAL APPROACH; IN-VITRO; MOTION; RANGE;
KINEMATICS; WALKING; IMPINGEMENT; ORIENTATION; OFFSET
AB Background: Component malposition in total hip arthroplasty patients has been associated with adverse clinical outcomes. However, whether the component alignment influences hip dynamic performance following total hip arthroplasty remains unclear. The purpose of this study was to investigate the relationship between the component alignment and in vivo hip kinematics during gait.
Methods: Nineteen unilateral total hip arthroplasty patients received CT scan for creation of 3D hip models. The component alignment between the non-implanted and implanted hips were measured and compared. Three-dimensional hip kinematics for both hips of the total hip arthroplasty patients during gait was quantified using a dual fluoroscopic imaging technique. The differences between the implanted and non-implanted hip kinematics during gait were calculated. A forward stepwise multiple linear regression was performed to evaluate the relationships between the changes in implanted hip kinematics and the differences in component alignment with respect to the non-implanted hips.
Findings: An average 5.1 degrees (SD 6.5 degrees; range -11.1 degrees to 18.3 degrees) increase in internal rotation was observed in the implanted hip than the contralateral non-implanted hip and significantly correlated with a linear combination of the increase of cup anteversion, cup medial translation and leg lengthening (R = 0.81).
Interpretation: Results suggested that the total hip arthroplasty patients compensated the changes in hip geometry by altering the dynamic movement during gait. Restoration of the native hip geometry, including acetabular cup anteversion, position and leg length could be one of the factors that influence the hip kinematics symmetry in total hip arthroplasty patients during gait. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Tsai, Tsung-Yuan; Li, Jing-Sheng; Dimitriou, Dimitris; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA.
EM ymkwon@mgh.harvard.edu
OI Tsai, Tsung-Yuan/0000-0003-1522-2987; Dimitriou,
Dimitris/0000-0002-9558-7080
FU MAKO Surgical Corp./Stryker Medical [2011P000444]
FX Technical guidance of Dr. Guoan Li and Dr. Harry E. Rubash is greatly
appreciated. Thanks for financial support from MAKO Surgical
Corp./Stryker Medical (2011P000444).
NR 42
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0268-0033
EI 1879-1271
J9 CLIN BIOMECH
JI Clin. Biomech.
PD OCT
PY 2015
VL 30
IS 8
BP 802
EP 807
DI 10.1016/j.clinbiomech.2015.06.010
PG 6
WC Engineering, Biomedical; Orthopedics; Sport Sciences
SC Engineering; Orthopedics; Sport Sciences
GA CS5VH
UT WOS:000362145900006
PM 26117163
ER
PT J
AU Pianta, A
Drouin, EE
Crowley, JT
Arvikar, S
Strle, K
Costello, CE
Steere, AC
AF Pianta, Annalisa
Drouin, Elise E.
Crowley, Jameson T.
Arvikar, Sheila
Strle, Klemen
Costello, Catherine E.
Steere, Allen C.
TI Annexin A2 is a target of autoimmune T and B cell responses associated
with synovial fibroblast proliferation in patients with
antibiotic-refractory Lyme arthritis
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Annexin A2; Autoantigen; Lyme arthritis; Lyme disease; Borrelia
burgdorferi
ID RHEUMATOID-ARTHRITIS; ANTIPHOSPHOLIPID-SYNDROME; BORRELIA-BURGDORFERI;
GROWTH-FACTOR; DISEASE; AUTOANTIBODIES; AUTOANTIGEN; RECEPTOR;
PLASMINOGEN; ANTIBODIES
AB In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (IA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pianta, Annalisa; Drouin, Elise E.; Crowley, Jameson T.; Arvikar, Sheila; Strle, Klemen; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Costello, Catherine E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA.
RP Pianta, A (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, CNY 149-8301,55 Fruit St, Boston, MA 02114 USA.
EM apianta@mgh.harvard.edu
FU NIH [RO1 AI-101175, AR-007258, K01-AR-062098]; English, Bonter, Mitchell
Foundation; Ounsworth-Fitzgerald Foundation; Eshe Fund; Lyme Disease and
Arthritis Research Fund at Massachusetts General Hospital
FX This work was supported by a NIH grant (RO1 AI-101175), the English,
Bonter, Mitchell Foundation, the Ounsworth-Fitzgerald Foundation, the
Eshe Fund, and the Lyme Disease and Arthritis Research Fund at
Massachusetts General Hospital. Dr. Arvikar was supported by the NIH
(training grant AR-007258), and Dr. Strle was supported by the NIH
(grant K01-AR-062098).
NR 38
TC 7
Z9 8
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 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD OCT
PY 2015
VL 160
IS 2
BP 336
EP 341
DI 10.1016/j.clim.2015.07.005
PG 6
WC Immunology
SC Immunology
GA CS5XL
UT WOS:000362151500024
PM 26187145
ER
PT J
AU Rinaldi, L
Vecchi, T
Fantino, M
Merabet, LB
Cattaneo, Z
AF Rinaldi, Luca
Vecchi, Tomas
Fantino, Micaela
Merabet, Lotfi B.
Cattaneo, Zaira
TI The effect of hand movements on numerical bisection judgments in early
blind and sighted individuals
SO CORTEX
LA English
DT Article
DE Number bisection; Blindness; Pseudoneglect; Number line; Hand movements;
Lateralization
ID MENTAL NUMBER LINE; VISUAL EXPERIENCE; SPATIAL REPRESENTATION; MINDS
EYE; SPACE; NEGLECT; BIASES; ACTIVATION; ATTENTION; MAGNITUDE
AB Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemispace in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants' previous visual experience. In particular, both sighted and early blind individuals representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e., from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in noncanonical direction. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Rinaldi, Luca; Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, Milan, Italy.
[Vecchi, Tomas; Cattaneo, Zaira] C Mondino Natl Neurol Inst, Brain Connect Ctr, Pavia, Italy.
[Vecchi, Tomas; Fantino, Micaela] Univ Pavia, Dept Brain & Behav Sci, I-27100 Pavia, Italy.
[Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Visual Neuroplast,Dept Ophthalmol, Boston, MA USA.
RP Cattaneo, Z (reprint author), Univ Milano Bicocca, Dept Psychol, Milan, Italy.
EM zaira.cattaneo@unimib.it
NR 57
TC 2
Z9 2
U1 2
U2 7
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD OCT
PY 2015
VL 71
BP 76
EP 84
DI 10.1016/j.cortex.2015.06.005
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CS5PV
UT WOS:000362131300008
PM 26184675
ER
PT J
AU Ohtani, T
Bouix, S
Lyall, AE
Hosokawa, T
Saito, Y
Melonakos, E
Westin, CF
Seidman, LJ
Goldstein, J
Mesholam-Gately, R
Petryshen, T
Wojcik, J
Kubicki, M
AF Ohtani, Toshiyuki
Bouix, Sylvain
Lyall, Amanda E.
Hosokawa, Taiga
Saito, Yukiko
Melonakos, Eric
Westin, Carl-Fredrik
Seidman, Larry J.
Goldstein, Jill
Mesholam-Gately, Raquelle
Petryshen, Tracey
Wojcik, Joanne
Kubicki, Marek
TI Abnormal white matter connections between medial frontal regions predict
symptoms in patients with first episode schizophrenia
SO CORTEX
LA English
DT Article
DE White matter; Fractional anisotropy; Orbitofrontal cortex; Anterior
cingulate cortex; First episode schizophrenia
ID ANTERIOR CINGULATE CORTEX; RECENT-ONSET SCHIZOPHRENIA; DIFFUSION TENSOR;
1ST-EPISODE SCHIZOPHRENIA; ORBITOFRONTAL CORTEX; CORPUS-CALLOSUM;
AUDITORY HALLUCINATIONS; FUNCTIONAL NEUROANATOMY; NONVERBAL TASK;
PSYCHOSIS
AB Introduction: The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ).
Methods: After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions.
Results: Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ.
Conclusions: The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Ohtani, Toshiyuki; Bouix, Sylvain; Lyall, Amanda E.; Hosokawa, Taiga; Saito, Yukiko; Melonakos, Eric; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA.
[Ohtani, Toshiyuki; Hosokawa, Taiga; Kubicki, Marek] VA Boston Healthcare Syst, Boston, MA USA.
[Seidman, Larry J.; Mesholam-Gately, Raquelle] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Dept Psychiat,Sch Med, Boston, MA 02215 USA.
[Seidman, Larry J.; Goldstein, Jill; Wojcik, Joanne] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Petryshen, Tracey] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA.
[Petryshen, Tracey] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Sch Med, Surg Planning Lab,MRI Div,Dept Radiol, Boston, MA 02115 USA.
[Ohtani, Toshiyuki] Chiba Univ, Safety & Hlth Org, Chiba, Chiba, Japan.
[Hosokawa, Taiga] Tsuchida Hosp, Tokyo, Japan.
[Saito, Yukiko] Kansai Med Univ, Dept Neuropsychiat, Moriguchi, Osaka 570, Japan.
RP Kubicki, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA.
EM kubicld@bwh.harvard.edu
OI Melonakos, Eric D./0000-0002-3643-9838
FU National Institute of Health [K05 MH070047, R01AG042512, R01MH102377,
R01 MH 50740, R01 MH 40799, R01 MH 082918, R01MH 074794, P50MH 080272,
1P50MH080272-01]; VA Schizophrenia Center Grant; National Alliance for
Medical Image Computing (NAMIC); National Institutes of Health through
the NIH Roadmap for Medical Research [U54 EB005149]; NIH [P41 RR013218];
Center for Integration of Medicine and Innovative Technology Soldier in
Medicine Award
FX We gratefully acknowledge the support of the National Institute of
Health (K05 MH070047, R01AG042512, R01MH102377, R01 MH 50740, R01 MH
40799, R01 MH 082918, R01MH 074794, P50MH 080272, 1P50MH080272-01, the
VA Schizophrenia Center Grant. This work is also part of the National
Alliance for Medical Image Computing (NAMIC), funded by the National
Institutes of Health through the NIH Roadmap for Medical Research, Grant
U54 EB005149, and is also supported by NIH Grant P41 RR013218 to the
Neuroimage Analysis Center. In addition, the work has been supported by
the Center for Integration of Medicine and Innovative Technology Soldier
in Medicine Award.
NR 82
TC 4
Z9 5
U1 2
U2 12
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD OCT
PY 2015
VL 71
BP 264
EP 276
DI 10.1016/j.cortex.2015.05.028
PG 13
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CS5PV
UT WOS:000362131300024
PM 26277547
ER
PT J
AU Mannel, C
Meyer, L
Wilcke, A
Boltze, J
Kirsten, H
Friederici, AD
AF Maennel, Claudia
Meyer, Lars
Wilcke, Arndt
Boltze, Johannes
Kirsten, Holger
Friederici, Angela D.
TI Working-memory endophenotype and dyslexia-associated genetic variant
predict dyslexia phenotype
SO CORTEX
LA English
DT Article
DE Developmental dyslexia; Genetic risk; Gray matter; Posterior temporal
cortex; Working memory
ID VOXEL-BASED MORPHOMETRY; TUMOR-NECROSIS-FACTOR; VISUAL WORD RECOGNITION;
SHORT-TERM-MEMORY; WHITE-MATTER STRUCTURE; PREDATE READING ONSET;
DEVELOPMENTAL DYSLEXIA; FUNCTIONAL NEUROANATOMY; SPEECH-PERCEPTION;
CONNECTIONIST MODELS
AB Developmental dyslexia, a severe impairment of literacy acquisition, is known to have a neurological basis and a strong genetic background. However, effects of individual genetic variations on dyslexia-associated deficits are only moderate and call for the assessment of the genotype's impact on mediating neuro-endophenotypes by the imaging genetics approach. Using voxel-based morphometry (VBM) in German participants with and without dyslexia, we investigated gray matter changes and their association with impaired phonological processing, such as reduced verbal working memory. These endophenotypical alterations were, together with dyslexia-associated genetic variations, examined on their suitability as potential predictors of dyslexia. We identified two gray matter clusters in the left posterior temporal cortex related to verbal working memory capacity. Regional cluster differences correlated with genetic risk variants in TNFRSF1B. High-genetic-risk participants exhibit a structural predominance of auditory-association areas relative to auditory-sensory areas, which may partly compensate for deficient early auditory-sensory processing stages of verbal working memory. The reverse regional predominance observed in low-genetic-risk participants may in turn reflect reliance on these early auditorysensory processing stages. Logistic regression analysis further supported that regional gray matter differences and genetic risk interact in the prediction of individuals' diagnostic status: With increasing genetic risk, the working-memory related structural predominance of auditory-association areas relative to auditory-sensory areas classifies participants with dyslexia versus control participants. Focusing on phonological deficits in dyslexia, our findings suggest endophenotypical changes in the left posterior temporal cortex could comprise novel pathomechanisms for verbal working memory-related processes translating TNFRSF1B genotype into the dyslexia phenotype. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Maennel, Claudia; Meyer, Lars; Friederici, Angela D.] Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, D-04103 Leipzig, Germany.
[Wilcke, Arndt; Boltze, Johannes; Kirsten, Holger] Fraunhofer Inst Cell Therapy & Immunol, Leipzig, Germany.
[Wilcke, Arndt; Boltze, Johannes; Kirsten, Holger] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany.
[Boltze, Johannes] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Boltze, Johannes] Harvard Univ, Sch Med, Boston, MA USA.
[Kirsten, Holger] Univ Leipzig, IMISE, D-04109 Leipzig, Germany.
RP Mannel, C (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, Stephanstr 1a, D-04103 Leipzig, Germany.
EM maennel@cbs.mpg.de
OI Mannel, Claudia/0000-0003-0678-4697; Meyer, Lars/0000-0002-7487-5518
FU Max Planck Society; German Federal Ministry of Education and Research
[PtJ-Bio 0315883]
FX We thank Anke Kummer, Mandy Jochemko, and Domenica Wilfing for imaging
data acquisition, and Elfi Quente for technical assistance. This work
was supported by the Max Planck Society (C. M., L. M., and A. F.) and
the German Federal Ministry of Education and Research (H. K. and A. W.,
grant number PtJ-Bio 0315883).
NR 172
TC 3
Z9 3
U1 4
U2 22
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD OCT
PY 2015
VL 71
BP 291
EP 305
DI 10.1016/j.cortex.2015.06.029
PG 15
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CS5PV
UT WOS:000362131300026
PM 26283516
ER
PT J
AU Izamis, ML
Perk, S
Calhoun, C
Uygun, K
Yarmush, ML
Berthiaume, F
AF Izamis, Maria-Louisa
Perk, Sinem
Calhoun, Candice
Uygun, Korkut
Yarmush, Martin L.
Berthiaume, Francois
TI Machine perfusion enhances hepatocyte isolation yields from ischemic
livers
SO CRYOBIOLOGY
LA English
DT Article
DE Perfusion; UW; Williams E; Vasosol; Lifor; Hepatocytes; Viscosity;
Temperature; Isolation
ID MONITORING BATCH PROCESSES; NORMOTHERMIC EXTRACORPOREAL PERFUSION;
SATURATED LIFOR SOLUTION; PIG ISOLATED HEARTS; CELL TRANSPLANTATION;
ORGAN PRESERVATION; DONOR LIVER; LOW-FLOW; VIVO; 26-DEGREES-C
AB Background: High-quality human hepatocytes form the basis of drug safety and efficacy tests, cell-based therapies, and bridge-to-transplantation devices. Presently the only supply of cells derives from an inadequate pool of suboptimal disqualified donor livers. Here we evaluated whether machine perfusion could ameliorate ischemic injury that many of these livers experience prior to hepatocyte isolation.
Methods: Non-heparinized female Lewis rat livers were exposed to an hour of warm ischemia (34 degrees C) and then perfused for 3 h. Five different perfusion conditions that utilized the cell isolation apparatus were investigated, namely: (1) modified Williams Medium E and (2) Lifor, both with active oxygenation (95%O-2/5%CO2), as well as (3) Lifor passively oxygenated with ambient air (21%O-2/0.04%CO2), all at ambient temperatures (20 +/- 2 degrees C). At hypothermic temperatures, (5 +/- 1 degrees C) and under passive oxygenation were (4) University of Wisconsin solution (MN) and (5) Vasosol. Negative and positive control groups comprised livers that had ischemia (WI) and livers that did not (Fresh) prior to cell isolation, respectively.
Results: Fresh livers yielded 32 +/- 9 million cells/g liver while an hour of ischemia reduced the cell yield to 1.6 +/- 0.6 million cells/g liver. Oxygenated Williams Medium E and Lifor recovered yields of 39 +/- 11 and 31 +/- 2.3 million cells/g liver, respectively. The passively oxygenated groups produced 15 +/- 7 (Lifor), 13 +/- 7 (Vasosol), and 10 +/- 6 (UW) million cells/g liver. Oxygenated Williams Medium E was most effective at sustaining pH values, avoiding the accumulation of lactate, minimizing edematous weight gain and producing bile during perfusion.
Conclusions: Machine perfusion results in a dramatic increase in cell yields from livers that have had up to an hour of warm ischemia, but perfusate choice significantly impacts the extent of recovery. Oxygenated Williams Medium E at room temperature is superior to Lifor, UW and Vasosol, largely facilitated by its high oxygen content and low viscosity. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Izamis, Maria-Louisa; Perk, Sinem; Calhoun, Candice; Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02114 USA.
[Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA.
EM mizamis@mgh.harvard.edu; perksin@gmail.com; Calhoun.ck@gmail.com;
uygun.korkut@mgh.harvard.edu; ireis@sbi.org; fberthia@rci.rutgers.edu
FU US National Institutes of Health [R01DK59766, R01 DK096075, R00DK08896];
Shriners Hospitals for Children; Lifeblood Medical Inc.
FX Funding from the US National Institutes of Health (R01DK59766, R01
DK096075, R00DK088962), the Shriners Hospitals for Children, and
Lifeblood Medical Inc. is gratefully acknowledged.
NR 55
TC 0
Z9 1
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 0011-2240
EI 1090-2392
J9 CRYOBIOLOGY
JI Cryobiology
PD OCT
PY 2015
VL 71
IS 2
BP 244
EP 255
DI 10.1016/j.cryobiol.2015.07.006
PG 12
WC Biology; Physiology
SC Life Sciences & Biomedicine - Other Topics; Physiology
GA CS8BU
UT WOS:000362311500007
PM 26188080
ER
PT J
AU Cheung, EJ
Chuang, GS
Grassi, AM
AF Cheung, Evelyn J.
Chuang, Gary S.
Grassi, Anita M.
TI Cutaneous and Mucosal Manifestations of Hereditary Hemorrhagic
Telangiectasia Treated With Pulsed Dye Laser
SO DERMATOLOGIC SURGERY
LA English
DT Letter
C1 [Cheung, Evelyn J.; Chuang, Gary S.; Grassi, Anita M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr, Boston, MA 02138 USA.
[Chuang, Gary S.] Tufts Med Ctr, Dept Dermatol, Boston, MA USA.
RP Cheung, EJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr, Boston, MA 02138 USA.
NR 5
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1076-0512
EI 1524-4725
J9 DERMATOL SURG
JI Dermatol. Surg.
PD OCT
PY 2015
VL 41
IS 10
BP 1186
EP 1188
DI 10.1097/DSS.0000000000000445
PG 3
WC Dermatology; Surgery
SC Dermatology; Surgery
GA CS5LS
UT WOS:000362120200016
PM 26336056
ER
PT J
AU Fisichella, PM
Ramirez, M
Patti, MG
AF Fisichella, P. Marco
Ramirez, Mauricio
Patti, Marco G.
TI An underappreciated cause of intermittent chest pain, asthma, and iron
deficiency anaemia
SO DIGESTIVE AND LIVER DISEASE
LA English
DT Editorial Material
C1 [Fisichella, P. Marco] Brigham & Womens Hosp, Dept Surg, Boston VA Hlth Care Syst, Boston, MA 02115 USA.
[Ramirez, Mauricio; Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA.
[Ramirez, Mauricio; Patti, Marco G.] Univ Chicago, Pritzker Sch Med, Ctr Esophageal Dis, Chicago, IL 60637 USA.
RP Fisichella, PM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Boston VA Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM piero.fisichella@va.gov
OI Fisichella, P. Marco/0000-0002-7697-7884
NR 1
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 1590-8658
EI 1878-3562
J9 DIGEST LIVER DIS
JI Dig. Liver Dis.
PD OCT
PY 2015
VL 47
IS 10
BP 897
EP 897
DI 10.1016/j.dld.2015.05.015
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS1RZ
UT WOS:000361846700015
PM 26089035
ER
PT J
AU Nomoto, H
Kondo, T
Miyoshi, H
Nakamura, A
Hida, Y
Yamashita, K
Sharma, AJ
Atsumi, T
AF Nomoto, Hiroshi
Kondo, Takuma
Miyoshi, Hideaki
Nakamura, Akinobu
Hida, Yoko
Yamashita, Ken-ichiro
Sharma, Arun J.
Atsumi, Tatsuya
TI Inhibition of Small Maf Function in Pancreatic beta-Cells Improves
Glucose Tolerance Through the Enhancement of Insulin Gene Transcription
and Insulin Secretion
SO ENDOCRINOLOGY
LA English
DT Article
ID MOLECULE GLUCOKINASE ACTIVATOR; CHRONIC EXPOSURE; TRANSGENIC MICE;
EXPRESSION; PROTEINS; RIPE3B1; BINDING; DIFFERENTIATION; PROLIFERATION;
HETERODIMER
AB The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic beta-cell function and maturation. However, insights about the effects of small Maf factors on beta-cells are limited. Our goal was to elucidate the function of small-Maf factors on beta-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with beta-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of beta-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates beta-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve beta-cell function.
C1 [Nomoto, Hiroshi; Kondo, Takuma; Miyoshi, Hideaki; Nakamura, Akinobu; Hida, Yoko; Atsumi, Tatsuya] Hokkaido Univ, Grad Sch Med, Div Rheumatol Endocrinol & Nephrol, Sapporo, Hokkaido 0608638, Japan.
[Yamashita, Ken-ichiro] Hokkaido Univ, Grad Sch Med, Dept Transplant Surg, Sapporo, Hokkaido 0608638, Japan.
[Sharma, Arun J.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA.
[Sharma, Arun J.] MedImmune LLC, Gaithersburg, MD 20878 USA.
RP Kondo, T (reprint author), Hokkaido Univ, Grad Sch Med, Div Rheumatol Endocrinol & Nephrol, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM takkondo@med.hokudai.ac.jp
FU Japanese Ministry of Education, Culture, Sports, Science, Technology
Foundation; Suzuken Memorial Foundation; National Institutes of Health
[RO1 DK60127]
FX This work was supported by grants from the Japanese Ministry of
Education, Culture, Sports, Science, Technology Foundation and the
Suzuken Memorial Foundation (H.M.) and by the National Institutes of
Health Grant RO1 DK60127 (to A.J.S.).
NR 33
TC 2
Z9 2
U1 0
U2 3
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD OCT
PY 2015
VL 156
IS 10
BP 3570
EP 3580
DI 10.1210/en.2014-1906
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS7AG
UT WOS:000362235300025
PM 25763640
ER
PT J
AU Ni, JQ
Wood, K
Wang, X
Li, GA
AF Ni, Jianqiang
Wood, Kirkham B.
Wang, Xin
Li, Guoan
TI Letter to the Editor concerning "ALIF and total disc replacement versus
2-level circumferential fusion with TLIF: a prospective, randomized,
clinical and radiological trial" by Hoff EK, Strube P, Pumberger M et
al. (2015). Eur Spine J. Mar 7. [Epub ahead of print]
SO EUROPEAN SPINE JOURNAL
LA English
DT Letter
ID GUIDELINE
C1 [Ni, Jianqiang; Wang, Xin] Qingdao Univ, Yuhungding Hosp, Dept Orthoped, Qingdao, Shandong, Peoples R China.
[Ni, Jianqiang; Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA.
[Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA.
RP Ni, JQ (reprint author), Qingdao Univ, Yuhungding Hosp, Dept Orthoped, Qingdao, Shandong, Peoples R China.
EM njqspine@163.com
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0940-6719
EI 1432-0932
J9 EUR SPINE J
JI Eur. Spine J.
PD OCT
PY 2015
VL 24
IS 10
BP 2345
EP 2346
DI 10.1007/s00586-015-3967-1
PG 2
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA CS8FC
UT WOS:000362320200038
PM 25900298
ER
PT J
AU Li, YR
van Setten, J
Verma, SS
Lu, YT
Holmes, MV
Gao, H
Lek, M
Nair, N
Chandrupatla, H
Chang, BL
Karczewski, KJ
Wong, C
Mohebnasab, M
Mukhtar, E
Phillips, R
Tragante, V
Hou, CP
Steel, L
Lee, T
Garifallou, J
Guettouche, T
Cao, HZ
Guan, WH
Himes, A
van Houten, J
Pasquier, A
Yu, RN
Carrigan, E
Miller, MB
Schladt, D
Akdere, A
Gonzalez, A
Llyod, KM
McGinn, D
Gangasani, A
Michaud, Z
Colasacco, A
Snyder, J
Thomas, K
Wang, TC
Wu, BL
Alzahrani, AJ
Al-Ali, AK
Al-Muhanna, FA
Al-Rubaish, AM
Al-Mueilo, S
Monos, DS
Murphy, B
Olthoff, KM
Wijmenga, C
Webster, T
Kamoun, M
Balasubramanian, S
Lanktree, MB
Oetting, WS
Garcia-Pavia, P
MacArthur, DG
de Bakker, PIW
Hakonarson, H
Birdwell, KA
Jacobson, PA
Ritchie, MD
Asselbergs, FW
Israni, AK
Shaked, A
Keating, BJ
AF Li, Yun R.
van Setten, Jessica
Verma, Shefali S.
Lu, Yontao
Holmes, Michael V.
Gao, Hui
Lek, Monkol
Nair, Nikhil
Chandrupatla, Hareesh
Chang, Baoli
Karczewski, Konrad J.
Wong, Chanel
Mohebnasab, Maede
Mukhtar, Eyas
Phillips, Randy
Tragante, Vinicius
Hou, Cuiping
Steel, Laura
Lee, Takesha
Garifallou, James
Guettouche, Toumy
Cao, Hongzhi
Guan, Weihua
Himes, Aubree
van Houten, Jacob
Pasquier, Andrew
Yu, Reina
Carrigan, Elena
Miller, Michael B.
Schladt, David
Akdere, Abdullah
Gonzalez, Ana
Llyod, Kelsey M.
McGinn, Daniel
Gangasani, Abhinav
Michaud, Zach
Colasacco, Abigail
Snyder, James
Thomas, Kelly
Wang, Tiancheng
Wu, Baolin
Alzahrani, Alhusain J.
Al-Ali, Amein K.
Al-Muhanna, Fahad A.
Al-Rubaish, Abdullah M.
Al-Mueilo, Samir
Monos, Dimitri S.
Murphy, Barbara
Olthoff, Kim M.
Wijmenga, Cisca
Webster, Teresa
Kamoun, Malek
Balasubramanian, Suganthi
Lanktree, Matthew B.
Oetting, William S.
Garcia-Pavia, Pablo
MacArthur, Daniel G.
de Bakker, Paul I. W.
Hakonarson, Hakon
Birdwell, Kelly A.
Jacobson, Pamala A.
Ritchie, Marylyn D.
Asselbergs, Folkert W.
Israni, Ajay K.
Shaked, Abraham
Keating, Brendan J.
TI Concept and design of a genome-wide association genotyping array
tailored for transplantation-specific studies
SO GENOME MEDICINE
LA English
DT Article
ID KIDNEY-TRANSPLANTATION; SNP ARRAY; GENE; POLYMORPHISMS; RECIPIENTS;
POPULATION; MISMATCH; MANAGEMENT; IMPUTATION; REJECTION
AB Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation.
Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios.
Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms.
Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.
C1 [Li, Yun R.; Akdere, Abdullah; Gonzalez, Ana; Llyod, Kelsey M.; McGinn, Daniel; Gangasani, Abhinav; Michaud, Zach; Colasacco, Abigail] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA.
[Li, Yun R.; Gao, Hui; Nair, Nikhil; Chandrupatla, Hareesh; Chang, Baoli; Wong, Chanel; Mohebnasab, Maede; Mukhtar, Eyas; Phillips, Randy; Hou, Cuiping; Steel, Laura; Lee, Takesha; Garifallou, James; Guettouche, Toumy; Himes, Aubree; van Houten, Jacob; Pasquier, Andrew; Yu, Reina; Carrigan, Elena; Snyder, James; Thomas, Kelly; Wang, Tiancheng; Monos, Dimitri S.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[van Setten, Jessica; Tragante, Vinicius; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
[Lu, Yontao; Webster, Teresa] Affymetrix Inc, Santa Clara, CA USA.
[Holmes, Michael V.; Gao, Hui; Nair, Nikhil; Chandrupatla, Hareesh; Chang, Baoli; Wong, Chanel; Mukhtar, Eyas; Phillips, Randy; Steel, Laura; Lee, Takesha; Himes, Aubree; Olthoff, Kim M.; Lanktree, Matthew B.; Shaked, Abraham; Keating, Brendan J.] Hosp Univ Penn, Penn Transplant Inst, Philadelphia, PA 19104 USA.
[Verma, Shefali S.; Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA.
[Lek, Monkol; Karczewski, Konrad J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Lek, Monkol; Karczewski, Konrad J.; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
[Cao, Hongzhi] BGI Shenzhen, Shenzhen, Peoples R China.
[Cao, Hongzhi] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
[Guan, Weihua; Wu, Baolin] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[Miller, Michael B.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Al-Ali, Amein K.; Al-Muhanna, Fahad A.; Al-Rubaish, Abdullah M.; Al-Mueilo, Samir] Univ Dammam, Coll Med, Dammam, Saudi Arabia.
[Monos, Dimitri S.; Kamoun, Malek] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Monos, Dimitri S.; Kamoun, Malek] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Murphy, Barbara] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY 10029 USA.
[Murphy, Barbara] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
[Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Balasubramanian, Suganthi] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA.
[Balasubramanian, Suganthi] Yale Univ, Dept Biochem & Mol Biophys, New Haven, CT USA.
[Oetting, William S.] Univ Minnesota, Expt & Clin Pharmacol, Minneapolis, MN USA.
[Garcia-Pavia, Pablo] Hosp Univ Puerta de Hierro Majadahonda, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Madrid, Spain.
[Birdwell, Kelly A.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Jacobson, Pamala A.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
[Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
[Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England.
[Alzahrani, Alhusain J.] King Saud Univ, Coll Appl Med Sci, Dept Clin Labs Sci, Riyadh, Saudi Arabia.
[Schladt, David] Hennepin Cty Med Ctr, Minneapolis Med Res Fd, Minneapolis, MN 55415 USA.
[Israni, Ajay K.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Keating, Brendan J.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Keating, Brendan J.] Hosp Univ Penn, Div Transplantat, Philadelphia, PA 19104 USA.
RP Keating, BJ (reprint author), Hosp Univ Penn, Penn Transplant Inst, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM bkeating@mail.med.upenn.edu
RI Wijmenga, Cisca/D-2173-2009;
OI Birdwell, Kelly/0000-0002-7996-3947; Karczewski,
Konrad/0000-0003-2878-4671
FU Fundacion Mutua Madrilena, Spain - Dutch PLN Foundation; UCL Hospitals
NIHR Biomedical Research Centre; Dekker scholarship - Netherlands Heart
Foundation [2014T001]; Deanship of Scientific Research at King Saud
University, Riyadh; NIH [U01 HG006830, U01-DK062494, UM1AI109565,
U01-AI63589, U19-AI070119]
FX We would like to thank the patients and their families for their
participation in the genotyping studies. We are also very thankful for
the contributions of the all of the study coordinators and clinicians
from the respective studies that made collection of these DNA samples
and phenotyping possible. This project was funded in part by Fundacion
Mutua Madrilena, Spain. Part of this work is also supported by the Dutch
PLN Foundation (www.stichtingpln.nl). Folkert W. Asselbergs is supported
by UCL Hospitals NIHR Biomedical Research Centre and by a Dekker
scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation.
Partial funding was also provided by the Deanship of Scientific Research
at King Saud University, Riyadh. We also acknowledge funding from the
following NIH grants: U01 HG006830; U01-DK062494; UM1AI109565;
U01-AI63589 and U19-AI070119.
NR 50
TC 3
Z9 3
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD OCT 1
PY 2015
VL 7
AR 90
DI 10.1186/s13073-015-0211-x
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA CS4VW
UT WOS:000362075200001
PM 26423053
ER
PT J
AU Hoybye, C
Cohen, P
Hoffman, AR
Ross, R
Biller, BMK
Christiansen, JS
AF Hoybye, Charlotte
Cohen, Pinchas
Hoffman, Andrew R.
Ross, Richard
Biller, Beverly M. K.
Christiansen, Jens Sandahl
CA Growth Hormone Res Soc
TI Status of long-acting-growth hormone preparations-2015
SO GROWTH HORMONE & IGF RESEARCH
LA English
DT Review
DE Growth hormone; Growth hormone deficiency; Growth hormone treatment;
Long-acting growth hormone preparations
ID GH-DEFICIENT ADULTS; PREPARATION NUTROPIN DEPOT; WEEKLY TREATMENT
PROFILE; PHARMACODYNAMIC CHARACTERISTICS; DOUBLE-BLIND; HALF-LIFE;
WEEKLY IM; CHILDREN; RELEASE; INJECTIONS
AB Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Hoybye, Charlotte] Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, S-17176 Stockholm, Sweden.
[Hoybye, Charlotte] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Cohen, Pinchas] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Hoffman, Andrew R.] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA.
[Hoffman, Andrew R.] Stanford Univ, Palo Alto, CA 94304 USA.
[Ross, Richard] Univ Sheffield, Dept Human Metab, Sheffield S10 2TN, S Yorkshire, England.
[Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Christiansen, Jens Sandahl] Aarhus Univ Hosp, Dept Endocrinol, MEA, NBG, DK-8000 Aarhus, Denmark.
RP Hoybye, C (reprint author), Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, S-17176 Stockholm, Sweden.
EM charlotte.hoybye@karolinska.se
OI Cohen, Pinchas/0000-0002-0035-8366
FU OPKO; Novartis; Novo Nordisk
FX Beverly MK Biller is an investigator on research grants to Massachusetts
General Hospital from OPKO, Novartis and Novo Nordisk and has received
occasional consulting honoraria from Novartis, Novo Nordisk, Pfizer and
Versartis.
NR 56
TC 10
Z9 10
U1 3
U2 9
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1096-6374
EI 1532-2238
J9 GROWTH HORM IGF RES
JI Growth Horm. IGF Res.
PD OCT
PY 2015
VL 25
IS 5
BP 201
EP 206
DI 10.1016/j.ghir.2015.07.004
PG 6
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA CS5SS
UT WOS:000362139000001
PM 26187188
ER
PT J
AU Ravicz, ME
Chien, WW
Rosowski, JJ
AF Ravicz, Michael E.
Chien, Wade W.
Rosowski, John J.
TI Restoration of middle-ear input in fluid-filled middle ears by
controlled introduction of air or a novel air-filled implant
SO HEARING RESEARCH
LA English
DT Article
DE Middle ear; Otitis media; Effusion; Implant; Aeration
ID ACUTE OTITIS-MEDIA; GERBIL MERIONES-UNGUICULATUS; SOUND-POWER
COLLECTION; HEXA FLUORIDE SF6; TYMPANIC MEMBRANE; HEARING-LOSS; AUDITORY
PERIPHERY; GUINEA-PIGS; MODEL; MECHANICS
AB The effect of small amounts of air on sound-induced umbo velocity in an otherwise saline-filled middle ear (ME) was investigated to examine the efficacy of a novel balloon-like air-filled ME implant suitable for patients with chronically non-aerated MEs. In this study, air bubbles or air-filled implants were introduced into saline-filled human cadaveric MEs. Umbo velocity, a convenient measure of ME response, served as an indicator of hearing sensitivity. Filling the ME with saline reduced umbo velocity by 25-30 dB at low frequencies and more at high frequencies, consistent with earlier work (Ravicz et al., Hear. Res. 195: 103-130 (2004)). Small amounts of air (similar to 30 mu l) in the otherwise saline-filled ME increased umbo velocity substantially, to levels only 10-15 dB lower than in the dry ME, in a frequency- and location-dependent manner: air in contact with the tympanic membrane (TM) increased umbo velocity at all frequencies, while air located away from the TM increased umbo velocity only below about 500 Hz. The air-filled implant also affected umbo velocity in a manner Similar to an air bubble of equivalent compliance. Inserting additional implants into the ME had the same effect as increasing air volume. These results suggest these middle-ear implants would significantly reduce conductive hearing loss in patients with chronically fluid-filled MEs. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Ravicz, Michael E.; Chien, Wade W.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Ravicz, Michael E.; Chien, Wade W.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM Mike_Ravicz@meei.harvard.edu
FU NIDCD [R01 DC004798]; MEEI Foundation
FX We dedicate this manuscript to our late and beloved colleague Saumil
Merchant, who was the driving force behind this project and who was
taken from us suddenly and much too soon. We thank Diane Jones of the
Otopathology Laboratory, Heidi Nakajima, and the staff of the
Eaton-Peabody Laboratory for technical support. Supported by NIDCD R01
DC004798 and the MEEI Foundation.
NR 65
TC 1
Z9 1
U1 2
U2 2
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 OCT
PY 2015
VL 328
BP 8
EP 23
DI 10.1016/j.heares.2015.06.012
PG 16
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA CS5XQ
UT WOS:000362152000002
PM 26121946
ER
PT J
AU Fowler, CG
Chiasson, KB
Colman, RJ
Kemnitz, JW
Beasley, TM
Weindruch, RH
AF Fowler, Cynthia G.
Chiasson, Kirstin Beach
Colman, Ricki J.
Kemnitz, Joseph W.
Beasley, T. Mark
Weindruch, Richard H.
TI Hyperinsulinemia/diabetes, hearing, and aging in the University of
Wisconsin calorie restriction monkeys
SO HEARING RESEARCH
LA English
DT Article
DE Age-related hearing loss; Auditory evoked potentials; Caloric
restriction; Distortion product otoacoustic emissions; Hearing; Rhesus
macaque; Hyperinsulinemia; Type 2 diabetes
ID PRODUCT OTOACOUSTIC EMISSIONS; DEPENDENT DIABETES-MELLITUS;
RHESUS-MONKEYS; AUDITORY FUNCTION; DIETARY RESTRICTION; MACACA-MULATTA;
AGE; HUMANS; ASSOCIATION; POPULATION
AB The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with 12 frequencies from 2211 to 8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8-17 dB larger in the NL group than in the HI-D and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5-8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, inter-wave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with K-G (glucose tolerance), S-I (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at risk with HI-T2DM. Loss of auditory function begins in the hyperinsulinemia, pre-diabetic state. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Fowler, Cynthia G.] Univ Wisconsin, Dept Commun Sci & Disorders, Madison, WI 53706 USA.
[Chiasson, Kirstin Beach] Cascade Ear Nose Throat & Facial Plast Surg, Klamath Falls, OR USA.
[Colman, Ricki J.; Kemnitz, Joseph W.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Kemnitz, Joseph W.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53715 USA.
[Beasley, T. Mark] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Weindruch, Richard H.] Univ Wisconsin, Dept Med, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA.
RP Fowler, CG (reprint author), Univ Wisconsin, Dept Commun Sci & Disorders, 1975 Willow Dr Madison, Madison, WI 53706 USA.
EM cgfowler@wisc.edu; rcolman@primate.wisc.edu; kemnitz@primate.wisc.edu;
mbeasley@ms.soph.uab.edu; rhweindr@wisc.edu
OI Kemnitz, Joseph/0000-0001-6511-404X
FU National Institutes of Health (NIH) [P01 AG 11915, P51 RR000167,
RO1AG040178]; Research Facilities Improvement Program [RR15459-01,
RR020141-01]
FX This publication was made possible by grants P01 AG 11915, P51 RR000167,
and RO1AG040178 from the National Institutes of Health (NIH). This
research was conducted at a facility constructed with support from
Research Facilities Improvement Program grant numbers RR15459-01 and
RR020141-01.
NR 37
TC 1
Z9 1
U1 2
U2 8
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 OCT
PY 2015
VL 328
BP 78
EP 86
DI 10.1016/j.heares.2015.07.001
PG 9
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA CS5XQ
UT WOS:000362152000008
PM 26163094
ER
PT J
AU Verrier, RL
AF Verrier, Richard L.
TI What can mechanics teach electricians about arrhythmias in heart
failure?
SO HEART RHYTHM
LA English
DT Editorial Material
C1 [Verrier, Richard L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Verrier, RL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Med,Div Cardiovasc Med,Harvard Thorndike Electrop, 99 Brookline Ave,RN-301, Boston, MA 02215 USA.
EM rverrier@bidmc.harvard.edu
NR 8
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 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD OCT
PY 2015
VL 12
IS 10
BP 2184
EP 2185
DI 10.1016/j.hrthm.2015.06.006
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CS1RK
UT WOS:000361845200022
PM 26051532
ER
PT J
AU Cornejo, KM
Dong, F
Zhou, AG
Wu, CL
Young, RH
Braaten, K
Sadow, PM
Nielsen, GP
Oliva, E
AF Cornejo, Kristine M.
Dong, Fei
Zhou, Amy G.
Wu, Chin-Lee
Young, Robert H.
Braaten, Kristina
Sadow, Peter M.
Nielsen, G. P.
Oliva, Esther
TI Papillary renal cell carcinoma: correlation of tumor grade and
histologic characteristics with clinical outcome
SO HUMAN PATHOLOGY
LA English
DT Article
DE Papillary renal cell carcinoma; Fuhnnan grade; International Society of
Urological Pathology nucleolar grade; Prognosis; PRCC; ISUP
ID PATHOLOGICAL PROGNOSTIC PARAMETERS; HISTOMORPHOLOGIC CHARACTERISTICS;
MULTIVARIATE-ANALYSIS; ONCOCYTIC CELLS; SURVIVAL; FEATURES;
CLASSIFICATION; UTILITY; SYSTEM; SERIES
AB Histologic prognostic parameters in papillary renal cell carcinoma (PRCC) are unclear. The aims were to review the clinicopathological features of PRCC, including Fuhrman grade and International Society of Urological Pathology (ISUP) nucleolar grade, and to identify parameters that may be independent prognostic indicators. PRCCs in patients treated by nephrectomy were retrieved from the pathology files from 1984 to 2010. Parameters studied included tumor multifocality, size, PRCC type (1 or 2), Fuhrman grade, ISUP nucleolar grade, presence of necrosis, lymphovascular invasion, and stage at presentation. Cancer-specific survival (CSS) and overall survival (OS) were used as prognostic measures. Of 154 PRCCs, 112 (73%) were type 1, and 42 (27%), type 2. A total of 125 patients were male, and 29, female, with ages from 26 to 86 (mean, 62.7) years Fuhnnan grade was 1 in 8 (5%), 2 in 95 (62%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. ISUP nucleolar grade was 1 in 47 (31%), 2 in 56 (36%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. Mean follow-up interval was 73.9 months (0.13-222 months). ISUP nucleolar grade was a significant predictor of both CSS and OS in univariate (CSS, P = .001; OS, P = .004) and multivariate (CSS, P = .04; OS, P = .008) analyses, whereas Fuhrman grade was only predictive of CSS in univariate (P = .001) and multivariate (P = .04) analyses. Only ISUP nucleolar grade and lymphovascular invasion were independently prognostic for CSS and OS in univariate and multivariate analyses. Therefore, the ISUP nucleolar grade appears to be superior in predicting survival in patients with PRCC. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Cornejo, Kristine M.; Dong, Fei; Wu, Chin-Lee; Young, Robert H.; Braaten, Kristina; Sadow, Peter M.; Nielsen, G. P.; Oliva, Esther] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Cornejo, Kristine M.; Dong, Fei; Wu, Chin-Lee; Young, Robert H.; Braaten, Kristina; Sadow, Peter M.; Nielsen, G. P.; Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Zhou, Amy G.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA.
RP Cornejo, KM (reprint author), UMass Mem Healthcare, Dept Pathol, One Innovat Dr,Biotech 3, Worcester, MA 01605 USA.
EM Kristine.Cornejo@umassmemorial.org
NR 35
TC 2
Z9 2
U1 2
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD OCT
PY 2015
VL 46
IS 10
BP 1411
EP 1417
DI 10.1016/j.humpath.2015.07.001
PG 7
WC Pathology
SC Pathology
GA CS4QQ
UT WOS:000362061400001
PM 26297250
ER
PT J
AU Komatsu, Y
Doi, T
Sawaki, A
Kanda, T
Yamada, Y
Kuss, I
Demetri, GD
Nishida, T
AF Komatsu, Yoshito
Doi, Toshihiko
Sawaki, Akira
Kanda, Tatsuo
Yamada, Yasuhide
Kuss, Iris
Demetri, George D.
Nishida, Toshirou
TI Regorafenib for advanced gastrointestinal stromal tumors following
imatinib and sunitinib treatment: a subgroup analysis evaluating
Japanese patients in the phase III GRID trial
SO INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
DE Regorafenib; Japanese; Gastrointestinal stromal tumor; Hand-foot
syndrome; Hypertension
ID RENAL-CELL CARCINOMA; EFFICACY; SAFETY; GIST; THERAPY
AB The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19-0.39; p < 0.0001].
A subgroup analysis of Japanese patients in the GRID study was performed to compare the efficacy and safety of oral regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs).
Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02-0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand-foot skin reaction (HFSR) (92 % versus 20 %, respectively).
Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.
C1 [Komatsu, Yoshito] Hokkaido Univ Hosp, Ctr Canc, Kita Ku, Sapporo, Hokkaido 0608648, Japan.
[Doi, Toshihiko] Natl Canc Ctr, Hosp East, Kashiwa, Chiba, Japan.
[Sawaki, Akira] Nagoya Second Red Cross Hosp, Dept Oncol & Gastroenterol, Nagoya, Aichi, Japan.
[Kanda, Tatsuo] Niigata Univ, Div Digest & Gen Surg, Sch Med & Dent Sci, Niigata, Japan.
[Yamada, Yasuhide] Natl Canc Ctr, Gastrointestinal Oncol Div, Tokyo, Japan.
[Kuss, Iris] Bayer Pharma AG, Global Clin Dev Oncol Ophthalmol & Neurol, Berlin, Germany.
[Demetri, George D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ludwig Canc Ctr, Boston, MA 02115 USA.
[Nishida, Toshirou] Natl Canc Ctr, Hosp East, Dept Surg, Kashiwa, Chiba, Japan.
RP Komatsu, Y (reprint author), Hokkaido Univ Hosp, Ctr Canc, Kita Ku, Kita 14 Nishi 5, Sapporo, Hokkaido 0608648, Japan.
EM ykomatsu@ac.cyberhome.ne.jp
FU Bayer Health Care Pharmaceuticals
FX We thank the participating patients and staff at each of the study
centers. Editorial assistance in the preparation of this manuscript was
provided by Succinct Medical Communications, with financial support from
Bayer Health Care Pharmaceuticals; the authors retained editorial
control over the content.
NR 19
TC 4
Z9 5
U1 0
U2 2
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 1341-9625
EI 1437-7772
J9 INT J CLIN ONCOL
JI Int. J. Clin. Oncol.
PD OCT
PY 2015
VL 20
IS 5
BP 905
EP 912
DI 10.1007/s10147-015-0790-y
PG 8
WC Oncology
SC Oncology
GA CS3VC
UT WOS:000362002200009
PM 25655899
ER
PT J
AU Rosenbaum, BL
Bui, E
Marin, MF
Holt, DJ
Lasko, NB
Pitman, RK
Orr, SP
Milad, MR
AF Rosenbaum, Blake L.
Bui, Eric
Marin, Marie-France
Holt, Daphne J.
Lasko, Natasha B.
Pitman, Roger K.
Orr, Scott P.
Milad, Mohammed R.
TI Demographic factors predict magnitude of conditioned fear
SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
LA English
DT Article
DE Fear conditioning; Demographics; Classical conditioning; Education;
Extinction; Skin conductance
ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; EXTINCTION
RETENTION; SEX-DIFFERENCES; HUMANS; PTSD; NEUROSCIENCE; AWARENESS;
RESPONSES; VETERANS
AB There is substantial variability across individuals in the magnitudes of their skin conductance (SC) responses during the acquisition and extinction of conditioned fear. To manage this variability, subjects may be matched for demographic variables, such as age, gender and education. However, limited data exist addressing how much variability in conditioned SC responses is actually explained by these variables. The present study assessed the influence of age, gender and education on the SC responses of 222 subjects who underwent the same differential conditioning paradigm. The demographic variables were found to predict a small but significant amount of variability in conditioned responding during fear acquisition, but not fear extinction learning or extinction recall. A larger differential change in SC during acquisition was associated with more education. Older participants and women showed smaller differential SC during acquisition. Our findings support the need to consider age, gender and education when studying fear acquisition but not necessarily when examining fear extinction learning and recall. Variability in demographic factors across studies may partially explain the difficulty in reproducing some SC findings. (C) 2015 Published by Elsevier B.V.
C1 [Rosenbaum, Blake L.; Bui, Eric; Marin, Marie-France; Holt, Daphne J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Bui, Eric; Marin, Marie-France; Holt, Daphne J.; Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.; Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA USA.
[Holt, Daphne J.; Milad, Mohammed R.] HST MIT Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY 2614, Charlestown, MA 02129 USA.
EM milad@nmr.mgh.harvard.edu
RI Bui, Eric/J-8347-2015
OI Bui, Eric/0000-0002-1413-6473
FU National Institute of Mental Health [1R01MH097964]; Department of
Psychiatry at MGH
FX This work was supported by the National Institute of Mental Health grant
1R01MH097964 and institutional funds from the Department of Psychiatry
at MGH to MRM. The authors would like to thank the Translation
Neuroscience team for their help preparing this manuscript.
NR 42
TC 0
Z9 0
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-8760
EI 1872-7697
J9 INT J PSYCHOPHYSIOL
JI Int. J. Psychophysiol.
PD OCT
PY 2015
VL 98
IS 1
BP 59
EP 64
DI 10.1016/j.ijpsycho.2015.06.010
PG 6
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA CS5QT
UT WOS:000362133700008
PM 26151498
ER
PT J
AU Wagner, C
Abramson, LY
Alloy, LB
AF Wagner, Clara
Abramson, Lyn Y.
Alloy, Lauren B.
TI Brief report: Executive functions in adolescent offspring of mothers
with a history of depression
SO JOURNAL OF ADOLESCENCE
LA English
DT Article
DE Executive functions; Depression; Adolescents; Maternal depression
ID EVERYDAY-ATTENTION; CHILDREN; RISK; PSYCHOPATHOLOGY; PERFORMANCE;
DISORDERS
AB Deficits in executive functions (EFs) have been documented among individuals with unipolar depression, but controversy exists as to whether such deficits are state-dependent or are trait markers that precede disorder onset. The present study examined whether maternal history of unipolar depression was associated with deficits in EFs in early adolescent offspring, a finding that would support a trait marker conceptualization of EF deficits.
Participants were a diverse sample (N = 493) of adolescents and their mothers recruited through local schools. Measures included semi-structured diagnostic interviews of mother and adolescent, mother-report forms assessing demographic information, and tests of executive function. Hierarchical linear regression analyses were conducted to examine the association between maternal depression diagnosis and adolescent offspring performance on tests of EF. Maternal lifetime history of depression was not associated with offspring EF task performance. Findings are not consistent with the conceptualization of impaired executive functions as trait markers of unipolar depression. Published by Elsevier Ltd on behalf of The Foundation for Professionals in Services for Adolescents.
C1 [Wagner, Clara] Philadelphia VA Med Ctr, VA Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA.
[Abramson, Lyn Y.] Univ Wisconsin, Dept Psychol, Philadelphia, PA 19104 USA.
[Alloy, Lauren B.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA.
RP Wagner, C (reprint author), Philadelphia VA Med Ctr, VA Ctr Hlth Equity Res & Promot, 3900 Woodland Ave,Bldg 4100 Annex, Philadelphia, PA 19104 USA.
EM Clara.Wagner@va.gov
FU National Institute of Mental Health [MH79369, MH101168]
FX This research was supported by National Institute of Mental Health
grants MH79369 and MH101168 to Lauren B. Alloy. 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 the United
States government.
NR 19
TC 1
Z9 1
U1 5
U2 12
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0140-1971
EI 1095-9254
J9 J ADOLESCENCE
JI J. Adolesc.
PD OCT
PY 2015
VL 44
BP 32
EP 36
DI 10.1016/j.adolescence.2015.06.005
PG 5
WC Psychology, Developmental
SC Psychology
GA CS5PP
UT WOS:000362130600004
PM 26208078
ER
PT J
AU Rusanescu, G
Mao, JR
AF Rusanescu, Gabriel
Mao, Jianren
TI Immature spinal cord neurons are dynamic regulators of adult nociceptive
sensitivity
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE neuronal differentiation; chronic pain; neurotrophins; peripheral nerve
injury; adult neurogenesis; nociception; BDNF; 7; 8-dihydroxyflavone
ID PERIPHERAL-NERVE INJURY; NEURAL STEM-CELL; NEUROPATHIC PAIN;
DORSAL-HORN; PROGENITOR CELLS; RECEPTOR DESENSITIZATION; GABAERGIC
INHIBITION; OLFACTORY-BULB; MESSENGER-RNA; DNA-SYNTHESIS
AB Chronic pain is a debilitating condition with unknown mechanism. Nociceptive sensitivity may be regulated by genetic factors, some of which have been separately linked to neuronal progenitor cells and neuronal differentiation. This suggests that genetic factors that interfere with neuronal differentiation may contribute to a chronic increase in nociceptive sensitivity, by extending the immature, hyperexcitable stage of spinal cord neurons. Although adult rodent spinal cord neurogenesis was previously demonstrated, the fate of these progenitor cells is unknown. Here, we show that peripheral nerve injury in adult rats induces extensive spinal cord neurogenesis and a long-term increase in the number of spinal cord laminae I-II neurons ipsilateral to injury. The production and maturation of these new neurons correlates with the time course and modulation of nociceptive behaviour, and transiently mimics the cellular and behavioural conditions present in genetically modified animal models of chronic pain. This suggests that the number of immature neurons present at any time in the spinal cord dorsal horns contributes to the regulation of nociceptive sensitivity. The continuous turnover of these neurons, which can fluctuate between normal and injured states, is a dynamic regulator of nociceptive sensitivity. In support of this hypothesis, we find that promoters of neuronal differentiation inhibit, while promoters of neurogenesis increase long-term nociception. TrkB agonists, well-known promoters of nociception in the short-term, significantly inhibit long-term nociception by promoting the differentiation of newly produced immature neurons. These findings suggest that promoters of neuronal differentiation may be used to alleviate chronic pain.
C1 [Rusanescu, Gabriel; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med,Sch Med, Boston, MA 02115 USA.
RP Rusanescu, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med,Sch Med, Boston, MA 02115 USA.
EM grusanes@gmail.com
OI Rusanescu, Gabriel/0000-0002-2811-905X
FU NIDCR NIH HHS [R01 DE022901]
NR 79
TC 1
Z9 1
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD OCT
PY 2015
VL 19
IS 10
BP 2352
EP 2364
DI 10.1111/jcmm.12648
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CS6WB
UT WOS:000362222800005
PM 26223362
ER
PT J
AU Srinivasan, VJ
Yu, E
Radhakrishnan, H
Can, A
Climov, M
Leahy, C
Ayata, C
Eikermann-Haerter, K
AF Srinivasan, Vivek J.
Yu, Esther
Radhakrishnan, Harsha
Can, Anil
Climov, Mihail
Leahy, Conor
Ayata, Cenk
Eikermann-Haerter, Katharina
TI Micro-heterogeneity of flow in a mouse model of chronic cerebral
hypoperfusion revealed by longitudinal Doppler optical coherence
tomography and angiography
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE angiography; capillary recruitment; Doppler optical coherence
tomography; hypoperfusion; vascular dementia
ID BLOOD-FLOW; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CORTEX; BRAIN;
MICROSCOPY; PERFUSION; ISCHEMIA; RAT; DYSFUNCTION
AB Although microvascular dysfunction accompanies cognitive decline in aging, vascular dementia, and Alzheimer's disease, tools to study microvasculature longitudinally in vivo are lacking. Here, we use Doppler optical coherence tomography (OCT) and angiography for noninvasive, longitudinal imaging of mice with chronic cerebral hypoperfusion for up to 1 month. In particular, we optimized the OCT angiography method to selectively image red blood cell (RBC)-perfused capillaries, leading to a novel way of assessing capillary supply heterogeneity in vivo. After bilateral common carotid artery stenosis (BCAS), cortical blood flow measured by Doppler OCT dropped to half of baseline throughout the imaged tissue acutely. Microscopic imaging of the capillary bed with OCT angiography further revealed local heterogeneities in cortical flow supply during hypoperfusion. The number of RBC-perfused capillaries decreased, leading to increased oxygen diffusion distances in the days immediately after BCAS. Linear regression showed that RBC-perfused capillary density declined by 0.3% for a drop in flow of 1 mL/100 g per minute, and decreases in RBC-perfused capillary density as high as 25% were observed. Taken together, these results demonstrate the existence of local supply heterogeneity at the capillary level even at nonischemic global flow levels, and demonstrate a novel imaging method to assess this heterogeneity.
C1 [Srinivasan, Vivek J.; Radhakrishnan, Harsha; Leahy, Conor] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Yu, Esther; Can, Anil; Climov, Mihail; Ayata, Cenk; Eikermann-Haerter, Katharina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA.
[Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA.
[Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Boston, MA USA.
RP Srinivasan, VJ (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 E Hlth Sci Dr,GBSF 2521, Davis, CA 95616 USA.
EM vjsriniv@ucdavis.edu
OI Climov, Mihail/0000-0001-9150-8608
FU National Institutes of Health [NS067050, NS061505, NS055104]; American
Heart Association [IRG5440002, 10SDG2610275]; Glaucoma Research
Foundation Catalyst for a Cure; Massachusetts General Hospital Claflin
Distinguished Award; Fondation Leducq; Heitman Foundation; Ellison
Foundation
FX We thank Maria Angela Franceschini, Michael Moskowitz, and Bruce Rosen
for general support. We thank Yahya Atalay and Andrea Negro for
assistance with data analysis. We acknowledge support from the National
Institutes of Health (VJS: NS067050; CA: NS061505, NS055104), the
American Heart Association (VJS: IRG5440002; KE-H: 10SDG2610275), the
Glaucoma Research Foundation Catalyst for a Cure (VJS), The
Massachusetts General Hospital Claflin Distinguished Award, and
Fondation Leducq (CA), The Heitman Foundation (CA), and The Ellison
Foundation (CA).
NR 34
TC 3
Z9 3
U1 1
U2 4
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 OCT
PY 2015
VL 35
IS 10
BP 1552
EP 1560
DI 10.1038/jcbfm.2015.175
PG 9
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA CS4KS
UT WOS:000362045300002
PM 26243708
ER
PT J
AU Kim, JI
Turka, LA
AF Kim, James I.
Turka, Laurence A.
TI Transplant tolerance: a new role for IL-34
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID REGULATORY T-CELLS; LANGERHANS CELLS; MACROPHAGES; DIFFERENTIATION;
MECHANISMS; FREQUENCY; INDUCTION; CYTOKINE; RECEPTOR
AB Immune-suppressive cell populations, including Tregs and suppressor monocytes, have been implicated in long-term survival of allografts in both human transplant recipients and animal models. The factors that drive differentiation and function of these cell populations are not completely understood. In this issue, Bezie and colleagues identify IL-34 as an important mediator of allograft tolerance in a rat model of heart transplantation. Their data support a model in which IL-34 production by Tregs promotes a population of suppressive macrophages that in turn promote Treg differentiation. The results of this study support further exploration of the immunosuppressive properties of IL-34.
C1 Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02129 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Turka, LA (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, MGH East, Bldg 149-9019,13th St, Boston, MA 02129 USA.
EM lturka@partners.org
FU NIAID NIH HHS [R01 AI037691]
NR 19
TC 0
Z9 1
U1 0
U2 5
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 OCT
PY 2015
VL 125
IS 10
BP 3751
EP 3753
DI 10.1172/JCI84010
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CS8BW
UT WOS:000362311700007
PM 26389671
ER
PT J
AU Koh, SH
Lo, EH
AF Koh, Seong-Ho
Lo, Eng H.
TI The Role of the PI3K Pathway in the Regeneration of the Damaged Brain by
Neural Stem Cells after Cerebral Infarction
SO JOURNAL OF CLINICAL NEUROLOGY
LA English
DT Review
DE neural stem cells; stroke; phosphatidylinositol-3-kinases; regeneration
ID EXTRACELLULAR-REGULATED KINASES; EPIDERMAL-GROWTH-FACTOR; ADULT-RAT
BRAIN; PROGENITOR CELLS; SIGNALING PATHWAY; PHOSPHATIDYLINOSITOL
3-KINASE; NEUROTROPHIC FACTOR; DIFFERENTIAL REGULATION;
HIPPOCAMPAL-NEURONS; ISCHEMIC-STROKE
AB Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction.
C1 [Koh, Seong-Ho; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA USA.
[Koh, Seong-Ho] Hanyang Univ, Coll Med, Dept Neurol, Seoul, South Korea.
RP Koh, SH (reprint author), Hanyang Univ, Coll Med, Dept Neurol, 153 Gyeongchun Ro, Guri 11923, South Korea.
EM ksh213@hanyang.ac.kr
FU Korea Research Foundation [2012R1A1B3000473]; NanoBio R&D Program of the
Korea Science and Engineering Foundation - Ministry of Education,
Science and Technology [2007-04717]
FX This work was supported by a grant from the Korea Research Foundation
(no. 2012R1A1B3000473), and a grant from the NanoBio R&D Program of the
Korea Science and Engineering Foundation, funded by the Ministry of
Education, Science and Technology (no. 2007-04717).
NR 71
TC 7
Z9 10
U1 2
U2 8
PU KOREAN NEUROLOGICAL ASSOC
PI SEOUL
PA 1111 DAEIL BLD, 43 INSA-DONG, JONGNO-GU, SEOUL, 110-741, SOUTH KOREA
SN 1738-6586
EI 2005-5013
J9 J CLIN NEUROL
JI J. Clin. Neurol.
PD OCT
PY 2015
VL 11
IS 4
BP 297
EP 304
DI 10.3988/jcn.2015.11.4.297
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CS2UE
UT WOS:000361926700001
PM 26320845
ER
PT J
AU Blakeley, JO
Grossman, SA
Mikkelsen, T
Rosenfeld, MR
Peereboom, D
Nabors, LB
Chi, AS
Emmons, G
Ribas, IG
Supko, JG
Desideri, S
Ye, XB
AF Blakeley, Jaishri O.
Grossman, Stuart A.
Mikkelsen, Tom
Rosenfeld, Myrna R.
Peereboom, David
Nabors, L. Burt
Chi, Andrew S.
Emmons, Gary
Ribas, Ignacio Garcia
Supko, Jeffrey G.
Desideri, Serena
Ye, Xiaobu
TI Phase I study of iniparib concurrent with monthly or continuous
temozolomide dosing schedules in patients with newly diagnosed malignant
gliomas
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Malignant glioma; Newly diagnosed; Dose finding; Cytotoxic; Combination
therapy
ID GLIOBLASTOMA-MULTIFORME; TUMOR-CELLS; RELAPSE; TRIAL
AB Iniparib is a prodrug that converts to highly reactive cytotoxic metabolites intracellularly with activity in preclinical glioma models. We investigated the maximum tolerated dose (MTD) of iniparib with monthly (m) and continuous (c) temozolomide (TMZ) dosing schedules in patients with malignant gliomas (MG). Adults with newly diagnosed MG who had successfully completed a parts per thousand yen80 % of radiation (RT) and TMZ without toxicity received mTMZ dosing (150-200 mg/m(2) days 1-5/28 days) or cTMZ dosing (75 mg/m(2)/days x 6 weeks) in conjunction with iniparib (i.v. 2 days/week) in the adjuvant setting. Iniparib was dose escalated using a modified continual reassessment method (mCRM). 43 patients (32 male; 34 GBM, 8 AA, 1 gliosarcoma; median age 54 years; median KPS 90) were enrolled across 4 dose levels. In the mTMZ group, 2/4 patients had dose limiting toxicities (DLT) at 19 mg/kg/week (rash/hypersensitivity). At 17.2 mg/kg/week, 1/9 patients had a DLT (grade 3 fatigue). Additional grade 3 toxicities were neutropenia, lymphopenia, and nausea. In the cTMZ group, one DLT (thromboembolic event) occurred at 10.2 mg/kg/week. Dose escalation stopped at 16 mg/kg/week based on mCRM. The mean maximum plasma concentration of iniparib increased with dose. Concentration of the two major circulating metabolites, 4-iodo-3-aminobenzamide and 4-iodo-3-aminobenzoic acid, was a parts per thousand currency sign5 % of the corresponding iniparib concentration. Iniparib is well tolerated, at doses higher than previously investigated, in combination with TMZ after completion of RT + TMZ in patients with MG. Recommended phase 2 dosing of iniparib based on mCRM is 17.2 mg/kg/week with mTMZ and 16 mg/kg/week with cTMZ. An efficacy study of TMZ/RT + iniparib followed by TMZ + iniparib in newly diagnosed GBM using these doses has completed enrollment. Survival assessment is ongoing.
C1 [Blakeley, Jaishri O.; Grossman, Stuart A.; Desideri, Serena; Ye, Xiaobu] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA.
[Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA.
[Rosenfeld, Myrna R.] Univ Penn, Philadelphia, PA 19104 USA.
[Peereboom, David] Cleveland Clin, Cleveland, OH 44106 USA.
[Chi, Andrew S.; Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA.
[Emmons, Gary; Ribas, Ignacio Garcia] Sanofi, Cambridge, MA USA.
RP Blakeley, JO (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1550 Orleans St,Suite 1 M-16, Baltimore, MD 21287 USA.
EM jblakel3@jhmi.edu
OI Rosenfeld, Myrna/0000-0001-5095-2534
FU National Institutes of Health [U01 CA-62475, U01 CA-137443]; Sanofi
Pharmaceuticals, Inc.
FX National Institutes of Health (U01 CA-62475 to S.G., U01 CA-137443 to
S.G.); Sanofi Pharmaceuticals, Inc.
NR 22
TC 1
Z9 1
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 OCT
PY 2015
VL 125
IS 1
BP 123
EP 131
DI 10.1007/s11060-015-1876-0
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CS8JY
UT WOS:000362334800013
PM 26285766
ER
PT J
AU Balboni, MJ
Bandini, J
Mitchell, C
Epstein-Peterson, ZD
Amobi, A
Cahill, J
Enzinger, AC
Peteet, J
Balboni, T
AF Balboni, Michael J.
Bandini, Julia
Mitchell, Christine
Epstein-Peterson, Zachary D.
Amobi, Ada
Cahill, Jonathan
Enzinger, Andrea C.
Peteet, John
Balboni, Tracy
TI Religion, Spirituality, and the Hidden Curriculum: Medical Student and
Faculty Reflections
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Professionalism; hidden curriculum; religion; spirituality; medical
education
ID PHYSICIAN BURNOUT; SUICIDAL IDEATION; NATIONAL-SURVEY; PROFESSIONALISM;
EDUCATION; SCHOOL; HEALTH; US; MULTICENTER; DEPRESSION
AB Context. Religion and spirituality play an important role in physicians' medical practice, but little research has examined their influence within the socialization of medical trainees and the hidden curriculum.
Objectives. The objective is to explore the role of religion and spirituality as they intersect with aspects of medicine's hidden curriculum.
Methods. Semiscripted, one-on-one interviews and focus groups (n = 33 respondents) were conducted to assess Harvard Medical School student and faculty experiences of religion/spirituality and the professionalization process during medical training. Using grounded theory, theme extraction was performed with interdisciplinary input (medicine, sociology, and theology), yielding a high inter-rater reliability score (kappa = 0.75).
Results. Three domains emerged where religion and spirituality appear as a factor in medical training. First, religion/spirituality may present unique challenges and benefits in relation to the hidden curriculum. Religious/spiritual respondents more often reported to struggle with issues of personal identity, increased self-doubt, and perceived medical knowledge inadequacy. However, religious/spiritual participants less often described relationship conflicts within the medical team, work-life imbalance, and emotional stress arising from patient suffering. Second, religion/spirituality may influence coping strategies during encounters with patient suffering. Religious/spiritual trainees described using prayer, faith, and compassion as means for coping whereas nonreligious/nonspiritual trainees discussed compartmentalization and emotional repression. Third, levels of religion/spirituality appear to fluctuate in relation to medical training, with many trainees experiencing an increase in religiousness/spirituality during training.
Conclusion. Religion/spirituality has a largely unstudied but possibly influential role in medical student socialization. Future study is needed to characterize its function within the hidden curriculum. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
C1 [Balboni, Michael J.; Peteet, John] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Enzinger, Andrea C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Balboni, Tracy] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Balboni, Michael J.; Amobi, Ada; Enzinger, Andrea C.; Peteet, John; Balboni, Tracy] Harvard Univ, Sch Med, Boston, MA USA.
[Bandini, Julia] Brandeis Univ, Dept Sociol, Waltham, MA USA.
[Mitchell, Christine] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Epstein-Peterson, Zachary D.] Univ Washington, Dept Med, Seattle, WA USA.
[Cahill, Jonathan] Boston Coll, Dept Theol, Chestnut Hill, MA 02167 USA.
RP Balboni, MJ (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Dana 1101,450 Brookline Ave, Boston, MA 02115 USA.
EM Michael_Balboni@dfci.harvard.edu
FU Templeton Foundation Award; University of Chicago Program in Religion
and Medicine Faculty Scholars Award
FX This research was supported in part by a Templeton Foundation Award and
a University of Chicago Program in Religion and Medicine Faculty
Scholars Award. None of the authors have relationships with any entities
having a financial interest in this topic.
NR 42
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD OCT
PY 2015
VL 50
IS 4
BP 507
EP 515
DI 10.1016/j.jpainsymman.2015.04.020
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA CS5CN
UT WOS:000362093800012
PM 26025271
ER
PT J
AU Ahluwalia, SC
Tisnado, DM
Walling, AM
Dy, SM
Asch, SM
Ettner, SL
Kim, B
Pantoja, P
Schreibeis-Baum, HC
Lorenz, KA
AF Ahluwalia, Sangeeta C.
Tisnado, Diana M.
Walling, Anne M.
Dy, Sydney M.
Asch, Steven M.
Ettner, Susan L.
Kim, Benjamin
Pantoja, Philip
Schreibeis-Baum, Hannah C.
Lorenz, Karl A.
TI Association of Early Patient-Physician Care Planning Discussions and
End-of-Life Care Intensity in Advanced Cancer
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID EARLY PALLIATIVE CARE; RANDOMIZED CONTROLLED-TRIAL; VETERANS-AFFAIRS;
PRIVATE-SECTOR; OLDER PATIENTS; NEAR-DEATH; QUALITY; HEALTH;
AGGRESSIVENESS; INDICATORS
AB Background: Early patient-physician care planning discussions may influence the intensity of end-of-life (EOL) care received by veterans with advanced cancer. Objective: The study objective was to evaluate the association between medical record documentation of patient-physician care planning discussions and intensity of EOL care among veterans with advanced cancer. Methods: This was a retrospective cohort study. Subjects were 665 veteran decedents diagnosed with stage IV colorectal, lung, or pancreatic cancer in 2008, and followed till death or the end of the study period in 2011. We estimated the effect of patient-physician care planning discussions documented within one month of metastatic diagnosis on the intensity of EOL care measured by receipt of acute care, intensive interventions, chemotherapy, and hospice care, using multivariate logistic regression models. Results: Veterans in our study were predominantly male (97.1%), white (74.7%), with an average age at diagnosis of 66.4 years. Approximately 31% received some acute care, 9.3% received some intensive intervention, and 6.5% had a new chemotherapy regimen initiated in the last month of life. Approximately 41% of decedents received no hospice or were admitted within three days of death. Almost half (46.8%) had documentation of a care planning discussion within the first month after diagnosis and those who did were significantly less likely to receive acute care at EOL (OR: 0.67; p=0.025). Documented discussions were not significantly associated with intensive interventions, chemotherapy, or hospice care. Conclusion: Early care planning discussions are associated with lower rates of acute care use at the EOL in a system with already low rates of intensive EOL care.
C1 [Ahluwalia, Sangeeta C.] RAND Corp, Santa Monica, CA 90401 USA.
[Walling, Anne M.; Pantoja, Philip; Schreibeis-Baum, Hannah C.; Lorenz, Karl A.] VA Greater Los Angeles Med Ctr, Los Angeles, CA USA.
[Walling, Anne M.; Lorenz, Karl A.] UCLA Sch Med, Los Angeles, CA USA.
[Dy, Sydney M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Asch, Steven M.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA.
[Asch, Steven M.] Stanford Univ Sch Med, Palo Alto, CA USA.
[Ettner, Susan L.] UCLA Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Kim, Benjamin] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Tisnado, Diana M.] Calif State Univ Fullerton, Dept Hlth Sci, Fullerton, CA 92634 USA.
RP Ahluwalia, SC (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
EM sahluwal@rand.org
FU U.S. Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Health Services Research &
Development Service [IIR 09-097]; National Palliative Care Research
Center Career Development Award; VA/NIMH Implementation Research
Fellowship [R25 MH080916-01A2]; UCLA CTSI [UL1TR000124]; NIH Loan
Repayment Program
FX This work was supported by the U.S. Department of Veterans Affairs,
Veterans Health Administration, Office of Research and Development,
Health Services Research & Development Service (IIR 09-097). 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 the U.S. government. Dr. Ahluwalia was supported by a
National Palliative Care Research Center Career Development Award and a
VA/NIMH Implementation Research Fellowship (R25 MH080916-01A2). Dr.
Walling was supported by UCLA CTSI grant number UL1TR000124 and the NIH
Loan Repayment Program.
NR 25
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U2 1
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 OCT 1
PY 2015
VL 18
IS 10
BP 834
EP 841
DI 10.1089/jpm.2014.0431
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CS7MY
UT WOS:000362268900009
PM 26186553
ER
PT J
AU Higgins, PC
Garrido, MM
Prigerson, HG
AF Higgins, Philip C.
Garrido, Melissa M.
Prigerson, Holly G.
TI Factors Predicting Bereaved Caregiver Perception of Quality of Care in
the Final Week of Life: Implications for Health Care Providers
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID FAMILY-MEMBERS; CANCER-PATIENTS; MENTAL-HEALTH; MEDICAL-CARE; PALLIATIVE
CARE; PSYCHIATRIC-DISORDERS; POSTTRAUMATIC STRESS; HOSPICE ENROLLMENT;
INITIAL VALIDATION; TERMINAL ILLNESS
AB Background: Cancer caregivers are key stakeholders in the final weeks of life and in bereavement. Research has highlighted end-of-life (EOL) factors important to caregivers, as well as factors contributing to caregiver mental health and bereavement outcomes. There has been limited data on factors predicting caregiver perceptions of quality of EOL care. Objective: This study's purpose was to identify modifiable predictors of caregivers' Caregiver Evaluation of Quality of End of Life Care (CEQUEL) scores, with the broader aim of informing clinical interventions to improve caregiver impressions of care and subsequent bereavement adjustment. Methods: Study data came from Coping with Cancer I (CwC1). CwC1 investigators interviewed advanced cancer patients and caregivers prior to the patient's death (Wave 1) and reinterviewed caregivers following the death (Wave 2) (N=275 dyads). The authors identified potential Wave 1 predictors of CEQUEL scores and performed a series of linear regression analyses to identify a parsimonious predictive model using corrected Akaike's Information Criterion (AICc) values. Results: In adjusted analyses, caregivers rated quality of care as poorer when patients died in a hospital (B=-1.40, SE=0.40, p=0.001) (B, unstandardized regression coefficient; SE, standard error) or had less than one week of inpatient hospice care (B=-1.98, SE=-0.70, p=0.006). Whole-person physician care and caregiver religiosity were associated with perceived higher quality of care in unadjusted, but not adjusted, analyses. Conclusions: Findings suggest that place of death and hospice length of stay best predict bereaved caregiver evaluations of quality of EOL care. These findings equip health care providers with modifiable targets to improve caregivers' experience of EOL care and subsequent bereavement.
C1 [Higgins, Philip C.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Higgins, Philip C.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Garrido, Melissa M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Garrido, Melissa M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Prigerson, Holly G.] Weill Cornell Med Coll, Ctr Res End Of Life Care, New York, NY 10065 USA.
RP Prigerson, HG (reprint author), Weill Cornell Med Coll, Ctr Res End Of Life Care, 525 East 68th St,Box 39,1404 Baker Pavil, New York, NY 10065 USA.
EM hgp2001@med.cornell.edu
FU American Cancer Society [DSW1009403SW]; Department of Veterans Affairs,
Veterans Health Administration, Office of Research and Development,
Health Services Research and Development Service [CDA 11-201/CDP
12-255]; National Institute of Mental Health [MH63892]; National Cancer
Institute [CA106370, CA156732]
FX This research was supported in part by the following grants and other
funding sources: Dr. Higgins is supported by DSW1009403SW from the
American Cancer Society. Dr. Garrido is supported by CDA 11-201/CDP
12-255 from the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Health Services
Research and Development Service. Dr. Prigerson was supported by MH63892
from the National Institute of Mental Health and CA106370 and CA156732
from the National Cancer Institute. These grants paid for the Coping
with Cancer study on which these analyses are based.
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U2 12
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 OCT 1
PY 2015
VL 18
IS 10
BP 849
EP 857
DI 10.1089/jpm.2015.29001.hp
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CS7MY
UT WOS:000362268900011
PM 26186021
ER
PT J
AU Smith, D
Kuzla, N
Thorpe, J
Scott, L
Ersek, M
AF Smith, Dawn
Kuzla, Natalie
Thorpe, Joshua
Scott, Laura
Ersek, Mary
TI Exploring Nonresponse Bias in the Department of Veterans Affairs'
Bereaved Family Survey
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID PATIENT SATISFACTION SURVEYS; LIFE CARE; QUALITY MEASURE; HOSPITAL
SURVEY; RESPONSE BIAS; END; HEALTH; NATIONWIDE; IMPACT; MODEL
AB Background: Patients' and families' evaluations of health care, including palliative care, are widely used as performance measures. Survey scores may be affected by nonresponse bias, resulting in inaccurate performance evaluation. Objectives: Our aim was to examine nonresponse bias for the mailed version of the Department of Veterans Affairs (VA) Bereaved Family Survey Performance Measure (BFS-PM) and evaluate the effect of nonresponse bias on facilities' BFS-PM scores. Methods: A cross-sectional analysis of a national sample was conducted. The sample consisted of 20,540 veterans who died in one of 146 VA Medical Centers (VAMCs) between October 2012 and September 2013. Next of kin (NOK) were asked to complete and return the survey. The BFS-PM is defined as the proportion of NOK who rated overall care for the veteran during the last month of life as excellent. After creating a model to predict the likelihood of response based on patient and clinical characteristics, we applied inverse probability weights to examine their effect on facilities' scores. We also evaluated facility performance before and after weighting for nonresponse vis-a-vis varying benchmarks. Results: We received 8912 surveys (45% response rate). The mean change in facility BFS-PM scores after weighting was -2%, (range: -10% to+11%). The scores of 31% of facilities changed more than2%. The number of facilities meeting hypothetical benchmarks of 60%, 70%, and 80% also changed as a result of weighting for nonresponse. Conclusion: Our results underscore the importance of appropriately addressing nonresponse in the use of quality-of-care metrics based on Bereaved Family Survey (BFS) data.
C1 [Smith, Dawn; Kuzla, Natalie; Thorpe, Joshua; Scott, Laura; Ersek, Mary] Philadelphia Vet Affairs Med Ctr, PROMISE Ctr, Philadelphia, PA 19104 USA.
[Thorpe, Joshua] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Thorpe, Joshua] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Smith, Dawn; Kuzla, Natalie; Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
RP Ersek, M (reprint author), Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave,Annex Suite 203, Philadelphia, PA 19104 USA.
EM Mary.ersek@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development
FX This material is based upon work supported by the Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, which had no role in the design, methods, participant
recruitment, data collection, analysis, or preparation of manuscript or
in the decision to submit the manuscript for publication. All authors
had full access to all of the data in the study and take responsibility
for the integrity of the data and the accuracy of the data analysis. 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 the U.S. Government.
NR 35
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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 OCT 1
PY 2015
VL 18
IS 10
BP 858
EP 864
DI 10.1089/jpm.2015.0050
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CS7MY
UT WOS:000362268900012
PM 26172910
ER
PT J
AU Steffens, JP
Wang, XS
Starr, JR
Spolidorio, LC
Van Dyke, TE
Kantarci, A
AF Steffens, Joao Paulo
Wang, Xiaoshan
Starr, Jacqueline R.
Spolidorio, Luis Carlos
Van Dyke, Thomas E.
Kantarci, Alpdogan
TI Associations Between Sex Hormone Levels and Periodontitis in Men:
Results From NHANES III
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE Androgens; cross-sectional studies; gonadal steroid hormones;
inflammation; periodontitis; testosterone
ID MIDDLE-AGED MEN; BODY-MASS INDEX; 3RD NATIONAL-HEALTH; WAIST-HIP RATIO;
CIGARETTE-SMOKING; TESTOSTERONE LEVELS; HYPERGONADOTROPIC HYPOGONADISM;
MULTIPLE-IMPUTATION; SERUM TESTOSTERONE; BINDING GLOBULIN
AB Background: Sex hormones are linked to inflammation and bone turnover. The goal of this study is to explore the association between sex hormone levels and periodontitis in men using data from the third National Health and Nutrition Examination Survey (NHANES III).
Methods: Data from 755 men (aged >= 30 years), including serum levels of testosterone, estradiol, sex hormone binding globulin, and androstenediol glucuronide, were analyzed. Calculated bioavailable testosterone (CBT) and estradiol-to-testosterone ratio were calculated. Periodontitis was defined using the latest classification of extent and severity of periodontitis for NHANES data (>= 2 interproximal sites with >= 3 mm attachment loss, >= 2 interproximal sites with probing depth [PD] >= 4 mm not on the same tooth, or one site with PD >= 5 mm). Sex hormones were evaluated as categorized and continuous variables. Correlations between the presence and severity of periodontitis and levels of sex hormones were determined and expressed as odds ratios (ORs).
Results: When adjusted for confounding factors, high total testosterone (TT) and CBT levels correlated with both the prevalence (OR [95% confidence interval (CI)], 2.1 [1 to 4.5] and 3.9 [1 to 14.8], respectively) and severity (OR [95% CI], 2.1 [1 to 4.3] and 3.4 [1.2 to 9.8]) of periodontitis. When continuous variables were used, the ORs (95% CIs) for presence and severity of periodontitis were 1.4 (0.6 to 3.3) and 1.5 (0.6 to 3.6) for TT and 1.3 (0.9 to 1.9) and 1.3 (0.9 to 1.8) for CBT, respectively.
Conclusions: These findings are consistent with the existence of an association of periodontitis with sex hormone levels, especially testosterone, in men.
C1 [Steffens, Joao Paulo; Wang, Xiaoshan; Starr, Jacqueline R.; Van Dyke, Thomas E.; Kantarci, Alpdogan] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA.
[Steffens, Joao Paulo; Spolidorio, Luis Carlos] Univ Estadual Paulista, Sch Dent Araraquara, Dept Physiol & Pathol, Araraquara, SP, Brazil.
[Starr, Jacqueline R.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA.
[Starr, Jacqueline R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Kantarci, A (reprint author), 245 First St, Cambridge, MA 02142 USA.
EM akantarci@forsyth.org
FU Sao Paulo State Research Foundation (FAPESP), Sao Paulo, SP, Brazil
[2010/09658-0, 2010/12021-4]; Coordination for the Improvement of Higher
Education Personnel (CAPES), Brasilia, DF, Brazil [5258-11-1]; National
Council for Scientific and Technological Development (CNPq), Brasilia,
DF, Brazil [470870/2011-7]; National Institutes of Health/National
Institute of Dental and Craniofacial Research [DE015566, DE020906]
FX JPS is a Post-Doctoral Fellow at UNESP, Araraquara, SP, Brazil, and was
the recipient of a scholarship from the Sao Paulo State Research
Foundation (FAPESP), Sao Paulo, SP, Brazil (#2010/09658-0) and from the
Coordination for the Improvement of Higher Education Personnel (CAPES),
Brasilia, DF, Brazil (#5258-11-1). JPS and LCS held research support
grants from FAPESP (#2010/12021-4) and from the National Council for
Scientific and Technological Development (CNPq), Brasilia, DF, Brazil
(#470870/2011-7). LCS holds a Productivity Scholarship from CNPq.
Supported by National Institutes of Health/National Institute of Dental
and Craniofacial Research grants DE015566 and DE020906 to AK and TVD.
The authors report no conflicts of interest related to this study.
NR 54
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U2 3
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD OCT
PY 2015
VL 86
IS 10
BP 1116
EP 1125
DI 10.1902/jop.2015.140530
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CS4KR
UT WOS:000362045200003
PM 26062840
ER
PT J
AU Grubbs, V
Vittinghoff, E
Beck, JD
Kshirsagar, AV
Wang, W
Griswold, ME
Powe, NR
Correa, A
Young, B
AF Grubbs, Vanessa
Vittinghoff, Eric
Beck, James D.
Kshirsagar, Abhijit V.
Wang, Wei
Griswold, Michael E.
Powe, Neil R.
Correa, Adolfo
Young, Bessie
TI Association Between Periodontal Disease and Kidney Function Decline in
African Americans: The Jackson Heart Study
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE African Americans; disease progression; health status disparities;
periodontal disease; renal insufficiency; chronic; risk factors
ID STAGE RENAL-DISEASE; ATHEROSCLEROSIS RISK; SERUM CREATININE;
COMMUNITIES; POPULATION; PREVALENCE; ADULTS; CKD
AB Background: Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. The authors seek to examine to what extent periodontal disease is associated with kidney function decline.
Methods: This retrospective cohort study examines 699 African American participants with preserved kidney function (defined by estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73m(2) at baseline) who underwent complete dental examinations as part of the Dental-Atherosclerosis Risk in Communities study (1996 to 1998) and subsequently enrolled in the Jackson Heart Study (2000 to 2004). Using multivariable Poisson regression, the authors examined the association of periodontal disease (severe versus non-severe) with incident CKD, defined as incident eGFR <60 mL/minute/1.73m(2) and rapid (5% annualized) eGFR decline at follow-up among those with preserved eGFR at baseline.
Results: Mean (+/- SD) age at baseline was 65.4 (+/- 5.2) years, and 16.3% (n = 114) had severe periodontal disease. There were 21 cases (3.0%) of incident CKD after a mean follow-up of 4.8 (+/- 0.6) years. Compared with participants with non-severe periodontal disease, those with severe periodontal disease had a four-fold greater rate of incident CKD (adjusted incidence rate ratio 4.18 [95% confidence interval 1.68 to 10.39], P = 0.002).
Conclusions: Severe periodontal disease is prevalent among a population at high risk for CKD and is associated with clinically significant kidney function decline. Further research is needed to determine if periodontal disease treatment alters the trajectory of renal deterioration.
C1 [Grubbs, Vanessa] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Grubbs, Vanessa] San Francisco Gen Hosp, Div Nephrol, San Francisco, CA 94110 USA.
[Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Beck, James D.] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Kshirsagar, Abhijit V.] Univ N Carolina, Div Nephrol & Hypertens, Chapel Hill, NC USA.
[Wang, Wei; Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[Powe, Neil R.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA.
[Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Young, Bessie] Univ Washington, Kidney Res Inst, Div Nephrol, Vet Affairs Puget Sound, Seattle, WA 98195 USA.
RP Grubbs, V (reprint author), 1001 Potrero Ave,Bldg 100,Room 342, San Francisco, CA 94110 USA.
EM vanessa.grubbs@ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Disease (NIDDK),
Bethesda, Maryland [1K23DK093710-01A1, 1R01DK102134-01]; Harold Amos
Medical Faculty Development Program of Robert Wood Johnson Foundation,
Princeton, New Jersey; National Heart, Lung, and Blood Institute
[HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]; National Institute on Minority
Health and Health Disparities, Bethesda, Maryland; Valeant
Pharmaceuticals, Bridgewater, New Jersey; Amgen (Thousand Oaks,
California)
FX The authors thank the participants and staff of the
Dental-Atherosclerosis Risk in Communities and Jackson Heart Studies. VG
was supported by grant 1K23DK093710-01A1 from the National Institute of
Diabetes and Digestive and Kidney Disease (NIDDK), Bethesda, Maryland,
and by the Harold Amos Medical Faculty Development Program of the Robert
Wood Johnson Foundation, Princeton, New Jersey. BY was supported by
grant 1R01DK102134-01 from the NIDDK. The Jackson Heart Study is
supported by contracts HHSN268201300046C, HHSN268201300047C,
HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the
National Heart, Lung, and Blood Institute and the National Institute on
Minority Health and Health Disparities, Bethesda, Maryland. VG received
investigator-initiated research funding from Valeant Pharmaceuticals,
Bridgewater, New Jersey. AVK received investigator-initiated research
funding from Amgen (Thousand Oaks, California) and has served on an
advisory board for Fresenius (Waltham, Massachusetts). No other
co-authors have any potential conflicts of interests to disclose.
NR 23
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PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD OCT
PY 2015
VL 86
IS 10
BP 1126
EP 1132
DI 10.1902/jop.2015.150195
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CS4KR
UT WOS:000362045200004
PM 26110451
ER
PT J
AU Pinheiro, LR
Scarfe, WC
Sales, MAD
Gaia, BF
Cortes, ARG
Cavalcanti, MG
AF Pinheiro, Lucas Rodrigues
Scarfe, William C.
de Oliveira Sales, Marcelo Augusto
Gaia, Bruno Felipe
Gonzalez Cortes, Arthur Rodriguez
Cavalcanti, Marcelo Gusmao
TI Effect of Cone-Beam Computed Tomography Field of View and Acquisition
Frame on the Detection of Chemically Simulated Peri-Implant Bone Loss In
Vitro
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE Animal; bone and bones; cone-beam computed tomography; dental implants;
diagnosis; peri-implantitis
ID INDUCED PERIAPICAL LESIONS; HORIZONTAL ROOT FRACTURE; ANGULAR
MEASUREMENTS; CONVENTIONAL FILM; DENTAL IMPLANTS; DEFECTS; RADIOGRAPHY;
ACCURACY; MULTISLICE; IMPACT
AB Background: The aim of this study is to determine the influence of field of view (FOV) and number of acquisition projection images (frames) on the detection of chemically simulated peri-implant defects by cone-beam computed tomography (CBCT) using an in vitro bovine rib bone model.
Methods: Eighty implants were placed in bovine ribs in which small and large bone defects were created using 70% perchloric acid. CBCT images were acquired at three acquisition protocols: protocol 1 (FOV 4 x 4 cm, 0.08-mm voxel size, 1,009 frames [high fidelity]; protocol 2 (same as protocol 1 except 512 frames [standard]); and protocol 3 (FOV 14 x 5 cm, 0.25-mm voxel size; high fidelity). Two oral and maxillofacial radiologists (OMRs) and two oral and maxillofacial surgeons (OMSs) rated the presence or absence of bone defects on a five-point scale. k and area under the curve (AUC) were calculated and compared using analysis of variance with post hoc Tukey test at P <= 0.05.
Results: Intra- and interobserver agreement for OMRs ranged from moderate to good and from slight to moderate for OMSs. For the detection of small lesions, protocol 1 (AUC 0.813 +/- 0.045) provided higher detection rates than protocol 2 (AUC 0.703 +/- 0.02) and protocol 3 (AUC 0.773 +/- 0.55) [F(2,9) = 1.6377]. For larger defects, the trends were similar, with protocol 1 (AUC 0.852 +/- 0.108) providing higher detection rates than protocol 2 (AUC 0.730 +/- 0.045) and protocol 3 (AUC 0.783 +/- 0.058) [F(2,9) = 1.9576].
Conclusion: Within the limits of this study, optimal detection of chemically simulated pericircumferential implant crestal bone defects is achieved at the least radiation detriment using the smallest FOV, the highest number of acquisition frames, and the smallest voxel.
C1 [Pinheiro, Lucas Rodrigues; Scarfe, William C.] Univ Louisville, Sch Dent, Dept Surg & Hosp Dent, Louisville, KY 40292 USA.
[de Oliveira Sales, Marcelo Augusto; Gaia, Bruno Felipe; Cavalcanti, Marcelo Gusmao] Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, Brazil.
[Gonzalez Cortes, Arthur Rodriguez] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Pinheiro, LR (reprint author), Ave Prof Lineu Prestes 2227, BR-05508000 Sao Paulo, Brazil.
EM lrp@usp.br
RI Cortes, Arthur/C-8738-2013
OI Cortes, Arthur/0000-0001-6591-7256
FU National Council for Research (CNPq), Brasilia, Brazil; Universal
Research Project [472895/2009-5]; Research Productivity Scholarship
[303847/2009-3]; FAPESP (Foundation of Research of Sao Paulo State, Sao
Paulo, Brazil) [2011/20179-0]; Coordination of Advancement of Higher
Education (CAPES), Brasilia; [2011/20304-9]
FX This study was funded by National Council for Research (CNPq), Brasilia,
Brazil, Universal Research Project (grant 472895/2009-5), Research
Productivity Scholarship (grant 303847/2009-3), and FAPESP (Foundation
of Research of Sao Paulo State, Sao Paulo, Brazil; grant 2011/20179-0)
to MC. The authors thank Coordination of the Advancement of Higher
Education (CAPES), Brasilia, for its financial support provided through
grants to BG and FAPESP for its grant to LP (2011/20304-9). The authors
also thank Implancil De Bortoli, Sao Paulo, for providing the implants.
The authors report no conflicts of interest related to this study.
NR 28
TC 0
Z9 0
U1 0
U2 2
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD OCT
PY 2015
VL 86
IS 10
BP 1159
EP 1165
DI 10.1902/jop.2015.150223
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CS4KR
UT WOS:000362045200008
PM 26156676
ER
PT J
AU Rubinsky, AD
Chen, C
Batki, SL
Williams, EC
Harris, AHS
AF Rubinsky, Anna D.
Chen, Cheng
Batki, Steven L.
Williams, Emily C.
Harris, Alex H. S.
TI Comparative utilization of pharmacotherapy for alcohol use disorder and
other psychiatric disorders among US Veterans Health Administration
patients with dual diagnoses
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Alcohol use disorder; Pharmacotherapy; Medication; Dual diagnosis;
Psychiatric disorders
ID NATIONAL EPIDEMIOLOGIC SURVEY; DSM-IV ALCOHOL; SUBSTANCE USE;
MENTAL-DISORDERS; UNITED-STATES; SMOKING-CESSATION; TOBACCO USE;
DEPENDENCE; CARE; METAANALYSIS
AB Patients with alcohol use disorder (AUD) and another co-occurring psychiatric disorder are a vulnerable population with high symptom severity. Such patients may benefit from a full arsenal of treatment options including pharmacotherapy. Receipt of AUD pharmacotherapy is generally very low despite recommendations that it be made available to every patient with AUD, including those with co-occurring disorders. Little is known about pharmacotherapy rates for AUD compared to other psychiatric disorders among patients with dual diagnoses. This study compared rates of pharmacotherapy for AUD to those for non-substance use psychiatric disorders and tobacco use disorder among patients with dual diagnoses in the U.S. Veterans Affairs (VA) healthcare system. VA data were used to identify patients with AUD and another psychiatric disorder in fiscal year 2012, and to estimate the proportion receiving pharmacotherapy for AUD and for each comorbid condition. Among subsets of patients with AUD and co-occurring schizophrenic, bipolar, posttraumatic stress or major depressive disorder, receipt of medications for AUD ranged from 7% to 11%, whereas receipt of medications for the comorbid disorder ranged from 69% to 82%. Among patients with AUD and co-occurring tobacco use disorder, 6% received medication for their AUD and 34% for their tobacco use disorder. Among patients with dual diagnoses, rates of pharmacotherapy for AUD were far lower than those for the comorbid disorders and contrary to evidence that medications for AUD are effective. Additional system-wide implementation efforts to identify and address patient- and provider-level barriers are needed to increase AUD pharmacotherapy in this highneed population. Published by Elsevier Ltd.
C1 [Rubinsky, Anna D.; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Vet Affairs VA Substance Use Disorder Qual Enhanc, Menlo Pk, CA 94025 USA.
[Rubinsky, Anna D.; Chen, Cheng; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, Hlth Serv Res & Dev, Menlo Pk, CA 94025 USA.
[Batki, Steven L.] San Francisco VA Med Ctr, Addict Psychiat Res Program, San Francisco, CA 94121 USA.
[Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Williams, Emily C.] VA Puget Sound Hlth Care Syst, Seattle Ctr Innovat Veteran Ctr & Value Driven Ca, Hlth Serv Res & Dev S152, Seattle, WA 98108 USA.
[Williams, Emily C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Rubinsky, AD (reprint author), VA Palo Alto Hlth Care Syst, Vet Affairs VA Substance Use Disorder Qual Enhanc, 795 Willow Rd MPD 152, Menlo Pk, CA 94025 USA.
EM Anna.Rubinsky@va.gov
FU United States Department of Veterans Affairs (VA) Health Services
Research & Development (HSRD) Program; VA HSR&D Substance Use Disorders
Quality Enhancement Research Initiative (SUD QUERI); VA HSRD [CDA
12-276]; National Institute of Mental Health [R25 MH080916-01A2]; VA
HSRD QUERI
FX This work was supported by the United States Department of Veterans
Affairs (VA) Health Services Research & Development (HSR&D) Program and
VA HSR&D Substance Use Disorders Quality Enhancement Research Initiative
(SUD QUERI). Dr. Williams is supported by a Career Development Award
from VA HSR&D (CDA 12-276) and is an investigator with the
Implementation Research Institute (IRI) at the George Warren Brown
School of Social Work at Washington University in St. Louis. IRI is
supported through an award from the National Institute of Mental Health
(R25 MH080916-01A2) and the VA HSR&D QUERI.
NR 73
TC 5
Z9 5
U1 3
U2 6
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 OCT
PY 2015
VL 69
BP 150
EP 157
DI 10.1016/j.jpsychires.2015.07.016
PG 8
WC Psychiatry
SC Psychiatry
GA CS2UP
UT WOS:000361927800022
PM 26343607
ER
PT J
AU Isakova, T
Ix, JH
Sprague, SM
Raphael, KL
Fried, L
Gassman, JJ
Raj, D
Cheung, AK
Kusek, JW
Flessner, MF
Wolf, M
Block, GA
AF Isakova, Tamara
Ix, Joachim H.
Sprague, Stuart M.
Raphael, Kalani L.
Fried, Linda
Gassman, Jennifer J.
Raj, Dominic
Cheung, Alfred K.
Kusek, John W.
Flessner, Michael F.
Wolf, Myles
Block, Geoffrey A.
TI Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23
Reduction in CKD
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Review
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; DIETARY PHOSPHORUS
RESTRICTION; RANDOMIZED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL;
LEFT-VENTRICULAR MASS; VITAMIN-D METABOLISM; HEMODIALYSIS-PATIENTS;
PARATHYROID-HORMONE; CARDIOVASCULAR EVENTS
AB Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With Binders and NicotinannidE study.
C1 [Isakova, Tamara; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Div Nephrol & Hypertens, Dept Med, Chicago, IL 60611 USA.
[Isakova, Tamara; Wolf, Myles] Northwestern Univ, Feinberg Sch Med, Ctr Translat Metab & Hlth, Inst Publ Hlth & Med, Chicago, IL 60611 USA.
[Ix, Joachim H.] Univ Calif San Diego, Nephrol Sect, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Prevent Med, San Diego, CA 92103 USA.
[Sprague, Stuart M.] Univ Chicago, Pritzker Sch Med, NprthShore Univ Hlth Syst, Evanston, IL USA.
[Raphael, Kalani L.; Cheung, Alfred K.] Univ Utah, Salt Lake City Vet Affairs Healthcare Syst, Salt Lake City, UT USA.
[Raphael, Kalani L.; Cheung, Alfred K.] Univ Utah, Div Nephrol & Hypertens, Salt Lake City, UT USA.
[Fried, Linda] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Gassman, Jennifer J.] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA.
[Raj, Dominic] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC USA.
[Kusek, John W.; Flessner, Michael F.] NIDDK, Bethesda, MD USA.
[Block, Geoffrey A.] Denver Nephrol, Denver, CO USA.
RP Isakova, T (reprint author), 633 N St Clair St,Suite 18-083, Chicago, IL 60611 USA.
EM tamara.isakova@northwestern.edu
OI Raphael, Kalani/0000-0002-1378-2609
FU National Institute of Diabetes and Digestive and Kidney Diseases
[K23-DK081673, R01-DK102438, U01-DK099877, U01-DK097093, U01-DK099930,
U01-DK099933, U01-DK099924]; Carl W. Gottschalk Research Scholar Grant
from the American Society of Nephrology Foundation for Kidney Research;
VA Career Development Award [IK2CX000537]; Harold Amos Medical Faculty
Development Award from the Robert Wood Johnson Foundation
FX T.I. is supported by grants K23-DK081673 and R01-DK102438 from the
National Institute of Diabetes and Digestive and Kidney Diseases and by
the Carl W. Gottschalk Research Scholar Grant from the American Society
of Nephrology Foundation for Kidney Research.; K.L.R. is supported by
the VA Career Development Award (IK2CX000537) and the Harold Amos
Medical Faculty Development Award from the Robert Wood Johnson
Foundation.; The COMBINE study is supported by grants U01-DK099877,
U01-DK097093, U01-DK099930, U01-DK099933, U01-DK099924, and R01-DK102438
from the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 102
TC 20
Z9 22
U1 0
U2 11
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 OCT
PY 2015
VL 26
IS 10
BP 2328
EP 2339
DI 10.1681/ASN.2015020117
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA CS5ZL
UT WOS:000362156700007
PM 25967123
ER
PT J
AU Safa, K
Ohori, S
Borges, TJ
Uehara, M
Batal, I
Shimizu, T
Magee, CN
Belizaire, R
Abdi, R
Wu, C
Chandraker, A
Riella, LV
AF Safa, Kassem
Ohori, Shunsuke
Borges, Thiago J.
Uehara, Mayuko
Batal, Ibrahim
Shimizu, Tetsunosuke
Magee, Ciara N.
Belizaire, Roger
Abdi, Reza
Wu, Chuan
Chandraker, Anil
Riella, Leonardo V.
TI Salt Accelerates Allograft Rejection through Serum- and
Glucocorticoid-Regulated Kinase-1-Dependent Inhibition of Regulatory T
Cells
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID RENAL-TRANSPLANT RECIPIENTS; PATHOGENIC T(H)17 CELLS; BLOOD-PRESSURE;
PROTEIN-KINASE; FOXP3 EXPRESSION; SGK; DIFFERENTIATION; INDUCTION;
FOXO3A; MODEL
AB A high-salt diet (HSD) in humans is linked to a number of complications, including hypertension and cardiovascular events. Whether a HSD affects the immune response in transplantation is unknown. Using a murine transplantation model, we investigated the effect of NaCl on the alloimmune response in vitro and in vivo. Incremental NaCl concentrations in vitro augmented T cell proliferation in the settings of both polyclonal and allospecific stimulation. Feeding a HSD to C57BL/6 wild-type recipients of bm12 allografts led to accelerated cardiac allograft rejection, despite similar mean BP and serum sodium levels in HSD and normal salt diet (NSD) groups. The accelerated rejection was associated with a reduction in the proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) and a significant decrease in Treg proliferation, leading to an increased ratio of antigen-experienced CDC+ T cells to Tregs in mice recipients of a HSD compared with mice recipients of a NSD. Because serum- and glucocorticoid-regulated kinase-1 (SGK1) has been proposed as a potential target of salt in immune cells, we fed a HSD to CD4(Cre)SGK1(fl/fl) B6-transplanted recipients and observed abrogation of the deleterious effect of a HSD in the absence of SGK1 on CD4(+) cells. In summary, we show that NaCl negatively affects the regulatory balance of T cells in transplantation and precipitates rejection in an SGK1-dependent manner.
C1 [Safa, Kassem; Ohori, Shunsuke; Borges, Thiago J.; Uehara, Mayuko; Shimizu, Tetsunosuke; Magee, Ciara N.; Abdi, Reza; Chandraker, Anil; Riella, Leonardo V.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Schuster Family Transplantat Res Ctr,Div Renal, Boston, MA USA.
[Safa, Kassem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA.
[Safa, Kassem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA.
[Borges, Thiago J.] Pontificia Univ Catolica Rio Grande do Sul, Sch Biosci, Porto Alegre, RS, Brazil.
[Borges, Thiago J.] Pontificia Univ Catolica Rio Grande do Sul, Biomed Res Inst, Porto Alegre, RS, Brazil.
[Batal, Ibrahim; Belizaire, Roger] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Magee, Ciara N.] Natl Hlth Serv Fdn Trust, Royal Free London, Dept Renal Med & Transplantat, London, England.
[Wu, Chuan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA USA.
RP Riella, LV (reprint author), 221 Longwood Ave, Boston, MA 02115 USA.
EM lriella@rics.bwh.harvard.edu
OI Borges, Thiago J/0000-0002-6554-0169
FU NIAID NIH HHS [K99 AI110649]
NR 27
TC 8
Z9 8
U1 0
U2 8
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 OCT
PY 2015
VL 26
IS 10
BP 2341
EP 2347
DI 10.1681/ASN.2014090914
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA CS5ZL
UT WOS:000362156700008
PM 25833841
ER
PT J
AU Ix, JH
Biggs, ML
Mukamal, K
Djousse, L
Siscovick, D
Tracy, R
Katz, R
Delaney, JA
Chaves, P
Rifkin, DE
Hughes-Austin, JM
Garimella, PS
Sarnak, MJ
Shlipak, MG
Kizer, JR
AF Ix, Joachim H.
Biggs, Mary L.
Mukamal, Kenneth
Djousse, Luc
Siscovick, David
Tracy, Russell
Katz, Ronit
Delaney, Joseph A.
Chaves, Paulo
Rifkin, Dena E.
Hughes-Austin, Jan M.
Garimella, Pranav S.
Sarnak, Mark J.
Shlipak, Michael G.
Kizer, Jorge R.
TI Urine Collagen Fragments and CKD Progression-The Cardiovascular Health
Study
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID AMINO-TERMINAL PROPEPTIDE; CREATININE EXCRETION RATE; INJURY MOLECULE-1
KIM-1; KIDNEY-FUNCTION DECLINE; CASE-COHORT DESIGNS; CYSTATIN-C; SERUM
BICARBONATE; III PROCOLLAGEN; ATHEROSCLEROSIS MESA; LIPOCALIN NGAL
AB Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged >= 65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (+/- SD) was 78 +/- 5 years, mean eGFR was 63 +/- 18 ml/min per 1.73 m(2), and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) mu g/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.
C1 [Ix, Joachim H.; Rifkin, Dena E.] Univ Calif San Diego & Vet Affairs San Diego Heal, Div Nephrol Hypertens, San Diego, CA USA.
[Biggs, Mary L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Djousse, Luc] Brigham & Womens Hosp & Boston Vet Affairs Hlth S, Div Aging, Boston, MA USA.
[Siscovick, David] New York Acad Med, New York, NY USA.
[Tracy, Russell] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Katz, Ronit] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Delaney, Joseph A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Chaves, Paulo] Florida Int Univ, Dept Med, Miami, FL 33199 USA.
[Hughes-Austin, Jan M.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Garimella, Pranav S.; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol Hypertens, 3350 La Jolla Village Dr,Mail Code 9111-H, San Diego, CA 92161 USA.
EM joeix@ucsd.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Institute of Diabetes Digestive and Kidney Diseases
[R01-DK098234]; National Heart, Lung, and Blood Institute [R01-HL094555,
U01-HL080295]; American Heart Association Established Investigator Award
[14EIA18560026]; National Institute on Aging [R01-AG027002,
R01-AG023629]; [HHSN268201200036C]; [HHSN268200800007C];
[N01-HC55222]; [N01-HC85079]; [N01-HC85080]; [N01-HC85081];
[N01-HC85082]; [N01-HC85083]; [N01-HC85086]
FX Supported by grants from the National Institute of Diabetes Digestive
and Kidney Diseases (grant no. R01-DK098234) (to Drs. Ix and Shlipak);
National Heart, Lung, and Blood Institute (grant no. R01-HL094555) (to
Drs. Ix, Mukamal, Djousse, and Kizer); American Heart Association
Established Investigator Award (award no. 14EIA18560026) (to Dr. Ix);
and National Institute on Aging (grant nos. R01-AG027002) (Dr Sarnak).
The CHS was supported by contracts HHSN268201200036C, HHSN268200800007C,
N01-HC55222, N01-HC85079, N01-HC85080, N01-HC85081, N01-HC85082,
N01-HC85083, N01-HC85086, and grant U01-HL080295 from the National
Heart, Lung, and Blood Institute, with additional contribution from the
National Institute of Neurological Disorders and Stroke and from grant
R01-AG023629 from the National Institute on Aging. This material is the
result of work supported with resources of the VA San Diego Healthcare
System.
NR 38
TC 7
Z9 7
U1 1
U2 1
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 OCT
PY 2015
VL 26
IS 10
BP 2494
EP 2503
DI 10.1681/ASN.2014070696
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA CS5ZL
UT WOS:000362156700021
PM 25655067
ER
PT J
AU King, DR
Butler, F
Kragh, JF
AF King, David R.
Butler, Frank
Kragh, John F.
TI Re: Tourniquet use at the Boston Marathon bombing
SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
LA English
DT Letter
C1 [King, David R.] Harvard Univ, Sch Med, Knight Surg Res Lab, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02115 USA.
[King, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Butler, Frank] Dept Def Comm Tact Combat Casualty Care, Prehosp Care Branch, Dept Def Joint Trauma Syst, Def Hlth Board,Trauma & Injury Subcomm, Washington, DC USA.
[Kragh, John F.] USUHS Sch Med, US Army Inst Surg Res, Damage Control Resuscitat, San Antonio, TX USA.
RP King, DR (reprint author), Harvard Univ, Sch Med, Knight Surg Res Lab, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02115 USA.
OI King, David/0000-0003-1028-1478
NR 5
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2163-0755
EI 2163-0763
J9 J TRAUMA ACUTE CARE
JI J. Trauma Acute Care Surg.
PD OCT
PY 2015
VL 79
IS 4
BP 702
EP 703
DI 10.1097/TA.0000000000000803
PG 2
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA CS5IZ
UT WOS:000362112900028
PM 26402551
ER
PT J
AU Grob, JJ
Amonkar, MM
Karaszewska, B
Schachter, J
Dummer, R
Mackiewicz, A
Stroyakovskiy, D
Drucis, K
Grange, F
Chiarion-Sileni, V
Rutkowski, P
Lichinitser, M
Levchenko, E
Wolter, P
Hauschild, A
Long, GV
Nathan, P
Ribas, A
Flaherty, K
Sun, P
Legos, JJ
McDowell, DO
Mookerjee, B
Schadendorf, D
Robert, C
AF Grob, Jean Jacques
Amonkar, Mayur M.
Karaszewska, Boguslawa
Schachter, Jacob
Dummer, Reinhard
Mackiewicz, Andrzej
Stroyakovskiy, Daniil
Drucis, Kamil
Grange, Florent
Chiarion-Sileni, Vanna
Rutkowski, Piotr
Lichinitser, Mikhail
Levchenko, Evgeny
Wolter, Pascal
Hauschild, Axel
Long, Georgina V.
Nathan, Paul
Ribas, Antoni
Flaherty, Keith
Sun, Peng
Legos, Jeffrey J.
McDowell, Diane Opatt
Mookerjee, Bijoyesh
Schadendorf, Dirk
Robert, Caroline
TI Comparison of dabrafenib and trametinib combination therapy with
vemurafenib monotherapy on health-related quality of life in patients
with unresectable or metastatic cutaneous BRAF Val600-mutation-positive
melanoma (COMBI-v): results of a phase 3, open-label, randomised trial
SO LANCET ONCOLOGY
LA English
DT Article
ID QUESTIONNAIRE QLQ-C30; EUROPEAN-ORGANIZATION; CANCER; RELIABILITY;
VALIDITY; SURVIVAL; SCORES; EQ-5D
AB Background In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study.
Methods COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1: 1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients.
Findings From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were signifi cant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7.92, 7.62, 6.86, 7.47, 5.16, 7.56, and 7.57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0.001 for all assessments except p=0.005 at week 40), EORTC QLQ-C30 pain (-13.20, -8.05, -8.82, -12.69, -12.46, -11.41, and -10.57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p< 0.001), EQ-5D thermometer scores (7.96, 8.05, 6.83, 11.53, 7.41, 9.08, and 10.51 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p< 0.001 for all assessments except p=0.006 at week 32), and FACT-M Melanoma Subscale score (3.62, 2.93, 2.45, 3.39, 2.85, 3.00, and 3.68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p< 0.001).
Interpretation From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population.
C1 [Grob, Jean Jacques] Aix Marseille Univ, Serv Dermatol, Marseille, France.
[Grob, Jean Jacques] Univ Hosp Timone, APHM, Marseille, France.
[Amonkar, Mayur M.; Sun, Peng; Legos, Jeffrey J.; McDowell, Diane Opatt; Mookerjee, Bijoyesh] GlaxoSmithKline Oncol Res & Dev, Collegeville, PA USA.
[Karaszewska, Boguslawa] Przychodnia Lekarska Komed, Konin, Poland.
[Schachter, Jacob] Chaim Sheba Med Ctr, Ramat Gan, Ramat, Israel.
[Dummer, Reinhard] Univ Zurich, Dept Dermatol, Zurich, Switzerland.
[Mackiewicz, Andrzej] Poznan Univ Med Sci, Med Polonia, Div Oncol, Poznan, Poland.
[Stroyakovskiy, Daniil] Moscow City Oncol Hosp 62, Moscow, Russia.
[Drucis, Kamil] Swissmed Ctr Zdrowia, Gdansk, Poland.
[Drucis, Kamil] Gdansk Med Univ, Gdansk, Poland.
[Grange, Florent] Hop Robert Debre, Ctr Hosp Univ Reims, Reims, France.
[Chiarion-Sileni, Vanna] Ist Ricovero & Cura Carattere Sci, Ist Oncol Veneto, Padua, Italy.
[Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Rutkowski, Piotr] Inst Oncol, Warsaw, Poland.
[Lichinitser, Mikhail] NN Blokhin Russian Canc Res Ctr, Moscow, Russia.
[Levchenko, Evgeny] NN Petrov Oncol Res Inst, St Petersburg, Russia.
[Wolter, Pascal] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium.
[Hauschild, Axel] UKSH, Dept Dermatol, Kiel, Germany.
[Long, Georgina V.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia.
[Long, Georgina V.] Mater Hosp, Sydney, NSW, Australia.
[Nathan, Paul] Mt Vernon Canc Ctr, Northwood, Middx, England.
[Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, Essen, Germany.
[Robert, Caroline] Gustave Roussy, Dept Med Oncol, Serv Dermatol, Villejuif, France.
[Robert, Caroline] Univ Paris 11, Fac Med, Villejuif, France.
RP Grob, JJ (reprint author), Aix Marseille Univ, Serv Dermatol, 264 Rue St Pierre, Marseille, France.
EM jean-jacques.grob@ap-hm.fr
FU GlaxoSmithKline
FX Medical writing assistance in the form of collating author comments,
copyediting, and editorial assistance was provided by Beverley Swain
(SciMentum, UK), and funded by GlaxoSmithKline.
NR 25
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U1 3
U2 10
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 OCT
PY 2015
VL 16
IS 13
BP 1389
EP 1398
PG 10
WC Oncology
SC Oncology
GA CS3BO
UT WOS:000361946300045
PM 26433819
ER
PT J
AU Grob, JJ
Long, GV
Schadendorf, D
Flaherty, K
AF Grob, Jean Jacques
Long, Georgina V.
Schadendorf, Dirk
Flaherty, Keith
TI Disease kinetics for decision-making in advanced melanoma: a call for
scenario-driven strategy trials
SO LANCET ONCOLOGY
LA English
DT Article
ID METASTATIC MELANOMA; CUTANEOUS MELANOMA; BRAF; SURVIVAL; IPILIMUMAB;
VEMURAFENIB; DABRAFENIB; NIVOLUMAB
AB In the past 5 years, the treatment of metastatic melanoma has changed from almost no effective treatment to the use of targeted and immune therapies with proven improvements in survival. The time has now come to define the optimal drug combinations, sequence of treatment, and drug regimens (intermittent vs continuous dosing) in the treatment of patients with metastatic melanoma. In view of the prevalence of advanced melanoma, finite resources, and the heterogeneity of disease characteristics, not all possibilities can be tested in therapeutic trials starting from an unselected population of patients with metastatic melanoma. In practice, clinicians rely on a few clinically derived signals, especially dynamic signals, to categorise patients into scenarios, from fast disease kinetics to slow disease kinetics, which drive clinicians' therapeutic decision making. The realistic goals of therapy are different in each scenario. We recommend that these scenarios are incorporated into clinical trials as either patient inclusion criteria or stratification factors. This approach is not only feasible but is also the only way to generate evidence for more effective and individualised treatment strategies for patients with metastatic melanoma.
C1 [Grob, Jean Jacques] Aix Marseille Univ, F-13885 Marseille, France.
[Grob, Jean Jacques] APHM Hosp CHU Timone, F-13885 Marseille, France.
[Long, Georgina V.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia.
[Long, Georgina V.] Mater Hosp, Sydney, NSW, Australia.
[Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany.
[Schadendorf, Dirk] German Canc Consortium, Essen, Germany.
[Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Grob, JJ (reprint author), Aix Marseille Univ, F-13885 Marseille, France.
EM jean-jacques.grob@ap-hm.fr
FU Roche; GlaxoSmithKline; Bristol-Myers Squibb; Merck; Novartis; Amgen;
Electra
FX JJG has received research grants to his institution from Roche, personal
fees for lectures from Roche and GlaxoSmithKline, and personal fees for
advisory boards from Roche, GlaxoSmithKline, Bristol-Myers Squibb,
Merck, Novartis, Amgen, and Electra. GVL has acted as a consultant
advisor for Amgen, Bristol-Myers Squibb, Merck, Novartis, Provectus
Biopharmaceuticals, and Roche. DS has received honoraria for
consultancy, speaker's bureau, and advisory boards from Bristol-Myers
Squibb, Merck, Novartis, Roche, Boehringer Ingelheim, Pfizer, Merck
Serono, and GlaxoSmithKline. KF has acted as a consultant advisor for
GSK, Novartis, Roche, and Merck.
NR 19
TC 5
Z9 5
U1 0
U2 3
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 OCT
PY 2015
VL 16
IS 13
BP E522
EP E526
PG 5
WC Oncology
SC Oncology
GA CS3BO
UT WOS:000361946300020
PM 26433825
ER
PT J
AU Saxon, AJ
AF Saxon, Andrew J.
TI Comparative safety of methadone and buprenorphine
SO LANCET PSYCHIATRY
LA English
DT Editorial Material
ID PHARMACOKINETICS; DEPENDENCE; INDUCTION; HUMANS
C1 Univ Washington, Dept Psychiat & Behav Sci, CESATE, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Saxon, AJ (reprint author), Univ Washington, Dept Psychiat & Behav Sci, CESATE, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
EM asaxon@uw.edu
FU Alkermes
FX I have received an honoraria for lectures from ReckittBenckiser,
scientific advisory board fees from Alkermes, and royalties from
UpToDate.
NR 11
TC 0
Z9 0
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD OCT
PY 2015
VL 2
IS 10
BP 855
EP 856
DI 10.1016/S2215-0366(15)00413-7
PG 2
WC Psychiatry
SC Psychiatry
GA CS5GU
UT WOS:000362106500005
PM 26384620
ER
PT J
AU Bril, F
Cusi, K
AF Bril, Fernando
Cusi, Kenneth
TI Response to do ultrasonographic semiquantitative indices predict
histological changes in NASH irrespective of steatosis extent?
SO LIVER INTERNATIONAL
LA English
DT Letter
ID FATTY LIVER
C1 [Bril, Fernando; Cusi, Kenneth] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA.
[Bril, Fernando; Cusi, Kenneth] Malcom Randall Vet Adm Med Ctr, Gainesville, FL USA.
[Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA.
[Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA.
RP Bril, F (reprint author), Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA.
NR 5
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1478-3223
EI 1478-3231
J9 LIVER INT
JI Liver Int.
PD OCT
PY 2015
VL 35
IS 10
BP 2341
EP 2342
DI 10.1111/liv.12869
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS6PC
UT WOS:000362201800021
PM 25964992
ER
PT J
AU Molina, Y
Silva, A
Rauscher, GH
AF Molina, Yamile
Silva, Abigail
Rauscher, Garth H.
TI Racial/Ethnic Disparities in Time to a Breast Cancer Diagnosis The
Mediating Effects of Health Care Facility Factors
SO MEDICAL CARE
LA English
DT Article
DE breast cancer; disparities; between-facility effects; accreditation;
multisite care
ID FOLLOW-UP; WOMEN; MAMMOGRAPHY; PREDICTORS; SURVIVAL; DELAY; STAGE;
RACE/ETHNICITY; INSURANCE; HOSPITALS
AB Background:Racial/ethnic disparities exist along the breast cancer continuum, including time to a diagnosis. Previous research has largely focused on patient-level factors, and less is known about the role that health care facilities may play in delayed breast cancer care.Objectives:We examined racial/ethnic disparities in delayed diagnosis for breast cancer in the Breast Cancer Care in Chicago Study and estimated the potential mediating effects of facility factors.Research Design and Subjects:Breast cancer patients (N=606) contributed interview and medical record data as part of a population-based study.Measures:Race/ethnicity was self-reported at interview. Diagnostic delay was defined as an excess of 60 days between medical presentation and a definitive diagnosis. Facility factors included the facility of medical presentation with respect to: (1) accreditation through the National Consortium of Breast Centers; (2) certification as a Breast Imaging Center of Excellence through the American College of Radiology; and (3) status as a disproportionate share hospital through the state of Illinois as well as the number of facilities used between presentation and diagnosis.Results:Relative to non-Hispanic whites, minorities were more likely to experience a diagnostic delay, present at a nonaccredited facility and at a disproportionate share hospital, and involve multiple facilities in their diagnosis. Together, facility factors accounted for 43% of the disparity in diagnostic delay (P<0.0001).Conclusions:Initial presentation of breast cancer at higher resourced facilities can reduce diagnostic delays. Disparities in delay are partly due to a disproportionate presentation at lower resourced facilities by minorities.
C1 [Molina, Yamile; Rauscher, Garth H.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA.
[Molina, Yamile] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Silva, Abigail] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA.
RP Molina, Y (reprint author), 1603 West Taylor,6th Floor, Chicago, IL 60612 USA.
EM ymolin2@uic.edu
OI Silva, Abigail/0000-0002-1112-1209; Rauscher, Garth/0000-0003-0374-944X
FU National Institutes of Health [P50CA106743, P50CA148143, R25CA92408];
University of Illinois-Chicago Center for Research on Women and Gender;
University of Illinois Cancer Center; Office of Academic Affiliations,
Department of Veterans Affairs [TPP 42-013]
FX Supported by multiple National Institutes of Health grants (P50CA106743,
P50CA148143, R25CA92408). Dr Molina was supported by the University of
Illinois-Chicago Center for Research on Women and Gender and the
University of Illinois Cancer Center. Dr Silva's work was supported by
the Office of Academic Affiliations (TPP 42-013), Department of Veterans
Affairs. The conclusions, opinions, and recommendations expressed in
this article are not necessarily that of the Department of Veterans
Affairs nor National Institutes of Health.
NR 46
TC 2
Z9 2
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD OCT
PY 2015
VL 53
IS 10
BP 872
EP 878
DI 10.1097/MLR.0000000000000417
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CS5IL
UT WOS:000362111500006
PM 26366519
ER
PT J
AU Urech, TH
Woodard, LD
Virani, SS
Dudley, RA
Lutschg, MZ
Petersen, LA
AF Urech, Tracy H.
Woodard, LeChauncy D.
Virani, Salim S.
Dudley, R. Adams
Lutschg, Meghan Z.
Petersen, Laura A.
TI Calculations of Financial Incentives for Providers in a
Pay-for-Performance Program Manual Review Versus Data From Structured
Fields in Electronic Health Records
SO MEDICAL CARE
LA English
DT Article
DE payment system design; performance measurement; incentives
ID QUALITY MEASURES; MEASURING-AGREEMENT; HYPERTENSION CARE; KAPPA; TRIAL
AB Background:Hospital report cards and financial incentives linked to performance require clinical data that are reliable, appropriate, timely, and cost-effective to process. Pay-for-performance plans are transitioning to automated electronic health record (EHR) data as an efficient method to generate data needed for these programs.Objective:To determine how well data from automated processing of structured fields in the electronic health record (AP-EHR) reflect data from manual chart review and the impact of these data on performance rewards.Research Design:Cross-sectional analysis of performance measures used in a cluster randomized trial assessing the impact of financial incentives on guideline-recommended care for hypertension.Subjects:A total of 2840 patients with hypertension assigned to participating physicians at 12 Veterans Affairs hospital-based outpatient clinics. Fifty-two physicians and 33 primary care personnel received incentive payments.Measures:Overall, positive and negative agreement indices and Cohen's kappa were calculated for assessments of guideline-recommended antihypertensive medication use, blood pressure (BP) control, and appropriate response to uncontrolled BP. Pearson's correlation coefficient was used to assess how similar participants' calculated earnings were between the data sources.Results:By manual chart review data, 72.3% of patients were considered to have received guideline-recommended antihypertensive medications compared with 65.0% by AP-EHR review (=0.51). Manual review indicated 69.5% of patients had controlled BP compared with 66.8% by AP-EHR review (=0.87). Compared with 52.2% of patients per the manual review, 39.8% received an appropriate response by AP-EHR review (=0.28). Participants' incentive payments calculated using the 2 methods were highly correlated (r0.98). Using the AP-EHR data to calculate earnings, participants' payment changes ranged from a decrease of $91.00 (-30.3%) to an increase of $18.20 (+7.4%) for medication use (interquartile range, -14.4% to 0%) and a decrease of $100.10 (-31.4%) to an increase of $36.40 (+15.4%) for BP control or appropriate response to uncontrolled BP (interquartile range, -11.9% to -6.1%).Conclusions:Pay-for-performance plans that use only EHR data should carefully consider the measures and the structure of the EHR before data collection and financial incentive disbursement. For this study, we feel that a 10% difference in the total amount of incentive earnings disbursed based on AP-EHR data compared with manual review is acceptable given the time and resources required to abstract data from medical records.
C1 [Urech, Tracy H.; Woodard, LeChauncy D.; Virani, Salim S.; Lutschg, Meghan Z.; Petersen, Laura A.] Baylor Coll Med, Hlth Policy Qual & Informat Program, Michael E DeBakey VA HSR&D Ctr Innovat Qual Effec, Houston, TX 77030 USA.
[Urech, Tracy H.; Woodard, LeChauncy D.; Virani, Salim S.; Lutschg, Meghan Z.; Petersen, Laura A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Dudley, R. Adams] Univ Calif San Francisco, Dept Med, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA.
[Dudley, R. Adams] Univ Calif San Francisco, Hlth Serv Informat, San Francisco, CA USA.
RP Petersen, LA (reprint author), Michael E De Bakey Vet Affairs Med Ctr, HSR&D 152,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM laura.petersen@va.gov
OI Virani, Salim/0000-0001-9541-6954
FU US Department of Veterans Affairs, Veterans Health Administration,
Health Services Research & Development (HSR&D) Investigator-Initiated
Research (IIR) [04-349]; National Institutes of Health (NIH) [RO1
HL079173-01]; American Heart Association Established Investigator Award
[0540043N]
FX Supported in part by the US Department of Veterans Affairs, Veterans
Health Administration, Health Services Research & Development (HSR&D)
Investigator-Initiated Research (IIR) 04-349 (L.A.P.) and the National
Institutes of Health (NIH) RO1 HL079173-01 (L.A.P.).; L.A.P. is the
Director at the Center for Innovations in Quality, Effectiveness and
Safety (CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, TX.
L.A.P. was a recipient of the American Heart Association Established
Investigator Award (Grant number 0540043N). R.A.D. is a Robert Wood
Johnson Investigator Awardee in Health Policy. The remaining authors
declare no conflict of interest.
NR 26
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U1 4
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD OCT
PY 2015
VL 53
IS 10
BP 901
EP 907
DI 10.1097/MLR.0000000000000418
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CS5IL
UT WOS:000362111500010
PM 26340661
ER
PT J
AU Haley, L
Tseng, LH
Zheng, G
Dudley, J
Anderson, DA
Azad, NS
Gocke, CD
Eshleman, JR
Lin, MT
AF Haley, Lisa
Tseng, Li-Hui
Zheng, Gang
Dudley, Jonathan
Anderson, Derek A.
Azad, Nilofer S.
Gocke, Christopher D.
Eshleman, James R.
Lin, Ming-Tseh
TI Performance characteristics of next-generation sequencing in clinical
mutation detection of colorectal cancers
SO MODERN PATHOLOGY
LA English
DT Article
ID RAS MUTATIONS; ACQUIRED-RESISTANCE; MOLECULAR-FEATURES; KRAS MUTATIONS;
BRAF MUTATIONS; PHASE-III; CHALLENGES; CETUXIMAB; MELANOMA; TRIAL
AB Activating mutations in downstream genes of the epidermal growth factor receptor (EGFR) pathway may cause anti-EGFR resistance in patients with colorectal cancers. We present performance characteristics of a next-generation sequencing assay designed to detect such mutations. In this retrospective quality assessment study, we analyzed mutation detected in the KRAS, NRAS, BRAF, and PIK3CA genes by a clinically validated next-generation sequencing assay in 310 colorectal cancer specimens. Tumor cellularity and mutant allele frequency were analyzed to identify tumor heterogeneity and mutant allele-specific imbalance. Next-generation sequencing showed precise measurement of mutant allele frequencies and detected 23% of mutations with 2-20% mutant allele frequencies. Of the KRAS mutations detected, 17% were outside of codons 12 and 13. Among PIK3CA mutations, 48% were outside of codons 542, 545, and 1047. The percentage of tumors with predicted resistance to anti-EGFR therapy increased from 40% when testing for only mutations in KRAS exon 2 to 47% when testing for KRAS exons 2-4, 48% when testing for KRAS and NRAS exons 2-4, 58% when including BRAF codon 600 mutations, and 59% when adding PIK3CA exon 20 mutations. Right-sided colorectal cancers carried a higher risk of predicted anti-EGFR resistance. A concomitant KRAS mutation was detected in 51% of PIK3CA, 23% of NRAS, and 33% of kinase-impaired BRAF-mutated tumors. Lower than expected mutant allele frequency indicated tumor heterogeneity, while higher than expected mutant allele frequency indicated mutant allele-specific imbalance. Two paired neuroendocrine carcinomas and adjacent adenomas showed identical KRAS mutations, but only PIK3CA mutations in neuroendocrine carcinomas. Next-generation sequencing is a robust tool for mutation detection in clinical laboratories. It demonstrates high analytic sensitivity and broad reportable range, and it provides simultaneous detection of concomitant mutations and a quantitative measurement of mutant allele frequencies to predict tumor heterogeneity and mutant allele-specific imbalance.
C1 [Haley, Lisa; Tseng, Li-Hui; Zheng, Gang; Dudley, Jonathan; Anderson, Derek A.; Gocke, Christopher D.; Eshleman, James R.; Lin, Ming-Tseh] Johns Hopkins Univ, Sch Med, Dept Pathol, Johns Hopkins Hosp, Baltimore, MD 21287 USA.
[Tseng, Li-Hui] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei, Taiwan.
[Dudley, Jonathan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Azad, Nilofer S.; Gocke, Christopher D.; Eshleman, James R.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Oncol, Baltimore, MD 21287 USA.
RP Lin, MT (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Pk SB202,600 North Wolfe St, Baltimore, MD 21287 USA.
EM mlin36@jhmi.edu
FU National Cancer Institute of USA [1UM1CA186691-01]
FX Supported by 1UM1CA186691-01 from the National Cancer Institute of USA.
NR 41
TC 11
Z9 11
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD OCT
PY 2015
VL 28
IS 10
BP 1390
EP 1399
DI 10.1038/modpathol.2015.86
PG 10
WC Pathology
SC Pathology
GA CS6NH
UT WOS:000362195900010
PM 26226847
ER
PT J
AU Westin, SN
Ju, ZL
Broaddus, RR
Krakstad, C
Li, J
Pal, N
Lu, KH
Coleman, RL
Hennessy, BT
Klempner, SJ
Werner, HMJ
Salvesen, HB
Cantley, LC
Mills, GB
Myers, AP
AF Westin, Shannon N.
Ju, Zhenlin
Broaddus, Russell R.
Krakstad, Camilla
Li, Jane
Pal, Navdeep
Lu, Karen H.
Coleman, Robert L.
Hennessy, Bryan T.
Klempner, Samuel J.
Werner, Henrica M. J.
Salvesen, Helga B.
Cantley, Lewis C.
Mills, Gordon B.
Myers, Andrea P.
TI PTEN loss is a context-dependent outcome determinant in obese and
non-obese endometrioid endometrial cancer patients
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE Endometrial cancer; PTEN loss; Obesity; Survival; PI3K/AKT pathway
ID BODY-MASS INDEX; CLINICAL-TRIALS GROUP; PROTEIN EXPRESSION;
GYNECOLOGICAL MALIGNANCIES; PROMOTER METHYLATION; AKT PHOSPHORYLATION;
PIK3CA MUTATIONS; PROGNOSTIC VALUE; HIGH-FREQUENCY; BETA-CATENIN
AB Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3-kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathway alterations on progression free survival in a cohort of endometrioid endometrial cancers. Prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss by immunohistochemistry, was explored in the context of patient body mass index. Reverse-phase protein arrays were utilized to assess protein expression based on PTEN status. Among 187 endometrioid endometrial cancers, there were no statistically significant associations between PFS and PIK3CA, PIK3R1, PTEN mutation or loss. When stratified by body mass index, PTEN loss was associated with improved progression free survival (P < 0.006) in obese (body mass index >= 30) patients. PTEN loss resulted in distinct protein changes: Canonical PI3K pathway activation was observed only in the non-obese population while decreased expression of beta-CATENIN and phosphorylated FOXO3A was observed in obese patients. These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of body mass index, and provide a potential explanation for discrepant reports on the effect of PTEN status and obesity on prognosis in endometrial cancer. This reveals a clinically important interaction between metabolic state and tumor genetics that may unveil the biologic underpinning of obesity-related cancers and impact ongoing clinical trials with PI3K pathway inhibitors. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Westin, Shannon N.; Pal, Navdeep; Lu, Karen H.; Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA.
[Ju, Zhenlin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Broaddus, Russell R.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Krakstad, Camilla; Werner, Henrica M. J.; Salvesen, Helga B.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
[Krakstad, Camilla; Werner, Henrica M. J.; Salvesen, Helga B.] Univ Bergen, Dept Clin Sci, Bergen, Norway.
[Li, Jane; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Hennessy, Bryan T.] Beaumont Hosp, Dublin 9, Ireland.
[Hennessy, Bryan T.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Klempner, Samuel J.; Cantley, Lewis C.; Myers, Andrea P.] Beth Israel Deaconess Med Ctr, Hematol Oncol, Boston, MA 02215 USA.
[Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Myers, Andrea P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Westin, SN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Unit 1362, 1155 Herman Pressler Blvd, Houston, TX 77030 USA.
EM swestin@mdanderson.org
RI Cantley, Lewis/D-1800-2014; salvesen, Helga/C-1187-2017;
OI Cantley, Lewis/0000-0002-1298-7653; salvesen, Helga/0000-0002-4438-8831;
Krakstad, Camilla/0000-0002-0174-8139
FU NIH [K12 CA088084]; NCI SPORE in Uterine Cancer [2P50 CA098258-06]; NCI
Cancer Center [P30 CA016672]; Program of the Entertainment Industry
Foundation [SU2C-AACR-DT0209]; Helse Vest; Research Council of Norway;
Norwegian Cancer Society
FX NIH K12 Calabresi Scholar Award (K12 CA088084) to SNW, NCI SPORE in
Uterine Cancer (2P50 CA098258-06) to SNW, RRB, KHL, GBM. NCI Cancer
Center Support Grant (P30 CA016672) to MD Anderson Cancer Center Stand
Up to Cancer Dream Team Translational Research Grant, a Program of the
Entertainment Industry Foundation (SU2C-AACR-DT0209) to SNW, RRB, RLC,
KHL, LCC, GBM, APM, Helse Vest, Research Council of Norway and The
Norwegian Cancer Society, Harald Andersens legat to HBS.
NR 52
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
EI 1878-0261
J9 MOL ONCOL
JI Mol. Oncol.
PD OCT
PY 2015
VL 9
IS 8
BP 1694
EP 1703
DI 10.1016/j.molonc.2015.04.014
PG 10
WC Oncology
SC Oncology
GA CS8AQ
UT WOS:000362308500015
PM 26045339
ER
PT J
AU Govindan, JA
Jayamani, E
Zhang, XR
Breen, P
Larkins-Ford, J
Mylonakis, E
Ruvkun, G
AF Govindan, J. Amaranath
Jayamani, Elamparithi
Zhang, Xinrui
Breen, Peter
Larkins-Ford, Jonah
Mylonakis, Eleftherios
Ruvkun, Gary
TI Lipid signalling couples translational surveillance to systemic
detoxification in Caenorhabditis elegans
SO NATURE CELL BIOLOGY
LA English
DT Article
ID C. ELEGANS; MAPK PHOSPHATASE; BACTERIA; PROLIFERATION; ASSOCIATION;
INFECTIONS; RESISTANCE; INHIBITION; IMMUNITY; PATHWAYS
AB Translation in eukaryotes is followed to detect toxins and virulence factors and coupled to the induction of defence pathways. Caenorhabditis elegans germline-specific mutations in translation components are detected by this system to induce detoxification and immune responses in distinct somatic cells. An RNA interference screen revealed gene inactivations that act at multiple steps in lipid biosynthetic and kinase pathways upstream of MAP kinase to mediate the systemic communication of translation defects to induce detoxification genes. Mammalian bile acids can rescue the defect in detoxification gene induction caused by C. elegans lipid biosynthetic gene inactivations. Extracts prepared from C. elegans with translation deficits but not from the wild type can also rescue detoxification gene induction in lipid-biosynthesis-defective strains. These eukaryotic antibacterial countermeasures are not ignored by bacteria: particular bacterial species suppress normal C. elegans detoxification responses to mutations in translation factors.
C1 [Govindan, J. Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Breen, Peter; Larkins-Ford, Jonah; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Govindan, J. Amaranath; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Jayamani, Elamparithi; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Infect Dis, Providence, RI 02903 USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU NIH Office at Research Infrastructure Programs [P40 OD010440]; Japanese
National Bioresources Project; National Institutes it Health
[AG043184-16A]
FX Strains were provided by the Caenorhabditis Genetics Center (CGC), which
is funded by the NIH Office at Research Infrastructure Programs (P40
OD010440), and S. Mitani of the Japanese National Bioresources Project.
This work was supported in part by the National Institutes it Health
Grant AG043184-16A (to G.R). Thanks to D. Coil and J. Eisen tor
providing Kocuria species.
NR 37
TC 5
Z9 5
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2015
VL 17
IS 10
BP 1294
EP +
DI 10.1038/ncb3229
PG 24
WC Cell Biology
SC Cell Biology
GA CS6SZ
UT WOS:000362213500009
PM 26322678
ER
PT J
AU Kottakis, F
Bardeesy, N
AF Kottakis, Filippos
Bardeesy, Nabeel
TI Gene signatures from pancreatic cancer tumor and stromal cells predict
disease outcome
SO NATURE GENETICS
LA English
DT Editorial Material
ID DUCTAL ADENOCARCINOMA
AB Pancreatic cancers consist of a heterogeneous amalgam of assorted cell types, making it challenging to develop a classification system that groups these tumors according to common molecular features. A new study tackles this important issue using bioinformatics approaches to decipher gene expression signatures derived specifically from either tumor cells or nonmalignant stromal cells that predict patient outcome and may inform personalized treatments.
C1 [Kottakis, Filippos; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Kottakis, Filippos; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Kottakis, Filippos; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Kottakis, F (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
EM bardeesy.nabeel@mgh.harvard.edu
NR 15
TC 1
Z9 1
U1 1
U2 7
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 OCT
PY 2015
VL 47
IS 10
BP 1102
EP 1103
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA CS3JR
UT WOS:000361969900002
PM 26417858
ER
PT J
AU Nikpay, M
Goel, A
Won, HH
Hall, LM
Willenborg, C
Kanoni, S
Saleheen, D
Kyriakou, T
Nelson, CP
Hopewell, JC
Webb, TR
Zeng, L
Dehghan, A
Alver, M
Armasu, SM
Auro, K
Bjonnes, A
Chasman, DI
Chen, SF
Ford, I
Franceschini, N
Gieger, C
Grace, C
Gustafsson, S
Huang, J
Hwang, SJ
Kim, YK
Kleber, ME
Lau, KW
Lu, XF
Lu, YC
Lyytikainen, LP
Mihailov, E
Morrison, AC
Pervjakova, N
Qu, LM
Rose, LM
Salfati, E
Saxena, R
Scholz, M
Smith, AV
Tikkanen, E
Uitterlinden, A
Yang, XL
Zhang, WH
Zhao, W
de Andrade, M
de Vries, PS
van Zuydam, NR
Anand, SS
Bertram, L
Beutner, F
Dedoussis, G
Frossard, P
Gauguier, D
Goodall, AH
Gottesman, O
Haber, M
Han, BG
Huang, J
Jalilzadeh, S
Kessler, T
Konig, IR
Lannfelt, L
Lieb, W
Lind, L
Lindgren, CM
Lokki, ML
Magnusson, PK
Mallick, NH
Mehra, N
Meitinger, T
Memon, FUR
Morris, AP
Nieminen, MS
Pedersen, NL
Peters, A
Rallidis, LS
Rasheed, A
Samuel, M
Shah, SH
Sinisalo, J
Stirrups, KE
Trompet, S
Wang, LY
Zaman, KS
Ardissino, D
Boerwinkle, E
Borecki, IB
Bottinger, EP
Buring, JE
Chambers, JC
Collins, R
Cupples, LA
Danesh, J
Demuth, I
Elosua, R
Epstein, SE
Esko, T
Feitosa, MF
Franco, OH
Franzosi, MG
Granger, CB
Gu, DF
Gudnason, V
Hall, AS
Hamsten, A
Harris, TB
Hazen, SL
Hengstenberg, C
Hofman, A
Ingelsson, E
Iribarren, C
Jukema, JW
Karhunen, PJ
Kim, BJ
Kooner, JS
Kullo, IJ
Lehtimaki, T
Loos, RJF
Melander, O
Metspalu, A
Marz, W
Palmer, CN
Perola, M
Quertermous, T
Rader, DJ
Ridker, PM
Ripatti, S
Roberts, R
Salomaa, V
Sanghera, DK
Schwartz, SM
Seedorf, U
Stewart, AF
Stott, DJ
Thiery, J
Zalloua, PA
O'Donnell, CJ
Reilly, MP
Assimes, TL
Thompson, JR
Erdmann, J
Clarke, R
Watkins, H
Kathiresan, S
McPherson, R
Deloukas, P
Schunkert, H
Samani, NJ
Farrall, M
AF Nikpay, Majid
Goel, Anuj
Won, Hong-Hee
Hall, Leanne M.
Willenborg, Christina
Kanoni, Stavroula
Saleheen, Danish
Kyriakou, Theodosios
Nelson, Christopher P.
Hopewell, Jemma C.
Webb, Thomas R.
Zeng, Lingyao
Dehghan, Abbas
Alver, Maris
Armasu, Sebastian M.
Auro, Kirsi
Bjonnes, Andrew
Chasman, Daniel I.
Chen, Shufeng
Ford, Ian
Franceschini, Nora
Gieger, Christian
Grace, Christopher
Gustafsson, Stefan
Huang, Jie
Hwang, Shih-Jen
Kim, Yun Kyoung
Kleber, Marcus E.
Lau, King Wai
Lu, Xiangfeng
Lu, Yingchang
Lyytikainen, Leo-Pekka
Mihailov, Evelin
Morrison, Alanna C.
Pervjakova, Natalia
Qu, Liming
Rose, Lynda M.
Salfati, Elias
Saxena, Richa
Scholz, Markus
Smith, Albert V.
Tikkanen, Emmi
Uitterlinden, Andre
Yang, Xueli
Zhang, Weihua
Zhao, Wei
de Andrade, Mariza
de Vries, Paul S.
van Zuydam, Natalie R.
Anand, Sonia S.
Bertram, Lars
Beutner, Frank
Dedoussis, George
Frossard, Philippe
Gauguier, Dominique
Goodall, Alison H.
Gottesman, Omri
Haber, Marc
Han, Bok-Ghee
Huang, Jianfeng
Jalilzadeh, Shapour
Kessler, Thorsten
Koenig, Inke R.
Lannfelt, Lars
Lieb, Wolfgang
Lind, Lars
Lindgren, Cecilia M.
Lokki, Marja-Liisa
Magnusson, Patrik K.
Mallick, Nadeem H.
Mehra, Narinder
Meitinger, Thomas
Memon, Fazal-ur-Rehman
Morris, Andrew P.
Nieminen, Markku S.
Pedersen, Nancy L.
Peters, Annette
Rallidis, Loukianos S.
Rasheed, Asif
Samuel, Maria
Shah, Svati H.
Sinisalo, Juha
Stirrups, Kathleen E.
Trompet, Stella
Wang, Laiyuan
Zaman, Khan S.
Ardissino, Diego
Boerwinkle, Eric
Borecki, Ingrid B.
Bottinger, Erwin P.
Buring, Julie E.
Chambers, John C.
Collins, Rory
Cupples, L. Adrienne
Danesh, John
Demuth, Ilja
Elosua, Roberto
Epstein, Stephen E.
Esko, Tonu
Feitosa, Mary F.
Franco, Oscar H.
Franzosi, Maria Grazia
Granger, Christopher B.
Gu, Dongfeng
Gudnason, Vilmundur
Hall, Alistair S.
Hamsten, Anders
Harris, Tamara B.
Hazen, Stanley L.
Hengstenberg, Christian
Hofman, Albert
Ingelsson, Erik
Iribarren, Carlos
Jukema, J. Wouter
Karhunen, Pekka J.
Kim, Bong-Jo
Kooner, Jaspal S.
Kullo, Iftikhar J.
Lehtimaki, Terho
Loos, Ruth J. F.
Melander, Olle
Metspalu, Andres
Maerz, Winfried
Palmer, Colin N.
Perola, Markus
Quertermous, Thomas
Rader, Daniel J.
Ridker, Paul M.
Ripatti, Samuli
Roberts, Robert
Salomaa, Veikko
Sanghera, Dharambir K.
Schwartz, Stephen M.
Seedorf, Udo
Stewart, Alexandre F.
Stott, David J.
Thiery, Joachim
Zalloua, Pierre A.
O'Donnell, Christopher J.
Reilly, Muredach P.
Assimes, Themistocles L.
Thompson, John R.
Erdmann, Jeanette
Clarke, Robert
Watkins, Hugh
Kathiresan, Sekar
McPherson, Ruth
Deloukas, Panos
Schunkert, Heribert
Samani, Nilesh J.
Farrall, Martin
CA CARDIoGRAMplusC4D Consortium
TI A comprehensive 1000 Genomes-based genome-wide association meta-analysis
of coronary artery disease
SO NATURE GENETICS
LA English
DT Article
ID HEART-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION;
SUSCEPTIBILITY LOCUS; GENETIC-VARIANTS; CELL-MIGRATION; IDENTIFIES 13;
MICE LACKING; EXPRESSION; RISK
AB Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
C1 [Nikpay, Majid; Stewart, Alexandre F.; McPherson, Ruth] Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada.
[Goel, Anuj; Kyriakou, Theodosios; Grace, Christopher; Jalilzadeh, Shapour; Watkins, Hugh; Farrall, Martin] Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.
[Goel, Anuj; Kyriakou, Theodosios; Grace, Christopher; van Zuydam, Natalie R.; Jalilzadeh, Shapour; Lindgren, Cecilia M.; Morris, Andrew P.; Ingelsson, Erik; Watkins, Hugh; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Won, Hong-Hee; Bjonnes, Andrew; Saxena, Richa; Lindgren, Cecilia M.; Esko, Tonu; Kathiresan, Sekar] Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
[Won, Hong-Hee; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Won, Hong-Hee; Bjonnes, Andrew; Saxena, Richa; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Won, Hong-Hee; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hall, Leanne M.; Nelson, Christopher P.; Webb, Thomas R.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Willenborg, Christina; Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.
[Willenborg, Christina; Koenig, Inke R.; Erdmann, Jeanette] DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany.
[Kanoni, Stavroula; Stirrups, Kathleen E.; Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
[Saleheen, Danish; Zhao, Wei] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Saleheen, Danish; Frossard, Philippe; Rasheed, Asif; Samuel, Maria] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Nelson, Christopher P.; Webb, Thomas R.; Goodall, Alison H.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.
[Hopewell, Jemma C.; Lau, King Wai; Collins, Rory; Clarke, Robert] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Hopewell, Jemma C.; Lau, King Wai; Collins, Rory; Clarke, Robert] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England.
[Zeng, Lingyao; Kessler, Thorsten; Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.
[Zeng, Lingyao; Gieger, Christian; Meitinger, Thomas; Peters, Annette; Hengstenberg, Christian; Schunkert, Heribert] DZHK German Ctr Cardiovasc Res, Munich, Germany.
[Dehghan, Abbas; Uitterlinden, Andre; de Vries, Paul S.; Franco, Oscar H.; Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Alver, Maris; Mihailov, Evelin; Pervjakova, Natalia; Esko, Tonu; Metspalu, Andres; Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Alver, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Armasu, Sebastian M.; de Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Auro, Kirsi; Pervjakova, Natalia; Perola, Markus] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
[Auro, Kirsi; Pervjakova, Natalia; Tikkanen, Emmi; Perola, Markus; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Auro, Kirsi; Pervjakova, Natalia; Perola, Markus] Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland.
[Chasman, Daniel I.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Shufeng; Lu, Xiangfeng; Yang, Xueli; Wang, Laiyuan; Gu, Dongfeng] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.
[Chen, Shufeng; Lu, Xiangfeng; Yang, Xueli; Huang, Jianfeng; Wang, Laiyuan; Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Gieger, Christian; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol, Uppsala, Sweden.
[Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, Uppsala, Sweden.
[Huang, Jie; Danesh, John; Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England.
[Hwang, Shih-Jen; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hwang, Shih-Jen; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Kim, Yun Kyoung; Han, Bok-Ghee; Kim, Bong-Jo] Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany.
[Lu, Yingchang; Gottesman, Omri; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Lyytikainen, Leo-Pekka; Karhunen, Pekka J.; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.
[Qu, Liming] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Salfati, Elias; Ingelsson, Erik; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
[Saxena, Richa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Scholz, Markus] Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
[Scholz, Markus; Beutner, Frank; Thiery, Joachim] LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Tikkanen, Emmi; Ripatti, Samuli] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.
[Zhang, Weihua; Chambers, John C.; Kooner, Jaspal S.] Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.
[van Zuydam, Natalie R.; Palmer, Colin N.] Univ Dundee, Med Res Inst, Dundee, Scotland.
[Anand, Sonia S.] McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada.
[Bertram, Lars] Univ Lubeck, Inst Neurogenet & Integrat, Platform Genome Analyt, Lubeck, Germany.
[Bertram, Lars] Univ Lubeck, Inst Expt Gen, Platform Genome Analyt, Lubeck, Germany.
[Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Neuroepidemiol & Ageing Res Unit, London, England.
[Beutner, Frank] Univ Leipzig, Heart Ctr Leipzig, Cardiol, D-04109 Leipzig, Germany.
[Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Gauguier, Dominique] INSERM, Ctr Rech Cordeliers, UMRS 1138, Paris, France.
[Goodall, Alison H.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Haber, Marc; Zalloua, Pierre A.] Lebanese Amer Univ, Sch Med, Beirut, Lebanon.
[Huang, Jianfeng] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Hypertens Div, Beijing 100730, Peoples R China.
[Kessler, Thorsten] Klinikum Rechts Der Isar, Munich, Germany.
[Koenig, Inke R.] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany.
[Lannfelt, Lars] Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Uppsala, Sweden.
[Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden.
[Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland.
[Magnusson, Patrik K.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Mallick, Nadeem H.] Punjab Inst Cardiol, Lahore, Pakistan.
[Mehra, Narinder] All India Inst Med Sci, New Delhi, India.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Humangenet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany.
[Memon, Fazal-ur-Rehman; Rasheed, Asif] Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland.
[Rallidis, Loukianos S.] Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece.
[Shah, Svati H.; Granger, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Stirrups, Kathleen E.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Wang, Laiyuan] Natl Human Genome Ctr Beijing, Beijing, Peoples R China.
[Zaman, Khan S.] Natl Inst Cardiovasc Dis, Karachi, Pakistan.
[Ardissino, Diego] Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy.
[Ardissino, Diego] Assoc Studio Trombosi Cardiol, Pavia, Italy.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Borecki, Ingrid B.; Feitosa, Mary F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London, England.
[Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Demuth, Ilja] Berlin Aging Study 2, Berlin, Germany.
[Demuth, Ilja] Charite, Res Grp Geriatr, D-13353 Berlin, Germany.
[Demuth, Ilja] Charite, Inst Med & Human Genet, D-13353 Berlin, Germany.
[Elosua, Roberto] Inst Hosp Mar Invest Med IMIM, Grp Epidemiol & Genet Cardiovasc, Barcelona, Spain.
[Epstein, Stephen E.] MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC USA.
[Esko, Tonu] Boston Childrens Hosp, Div Endocrinol & Basic & Translat Obes Res, Boston, MA USA.
[Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Franzosi, Maria Grazia] IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England.
[Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Hazen, Stanley L.] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Iribarren, Carlos] Kaiser Permanente Div Res, Oakland, CA USA.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands.
[Karhunen, Pekka J.] Univ Tampere, Sch Med, Dept Forens Med, FIN-33101 Tampere, Finland.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.
[Kullo, Iftikhar J.] Mayo Clin, Dept Med, Cardiovasc Dis, Rochester, MN USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Melander, Olle] Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
[Maerz, Winfried] Synlab Acad, Synlab Serv, Mannheim, Germany.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
[Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Rader, Daniel J.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Roberts, Robert] Univ Ottawa, Inst Heart, Ottawa, ON, Canada.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Coll Med, Oklahoma City, OK 73190 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.
[Sanghera, Dharambir K.] Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
[Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.
[Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Seedorf, Udo] Univ Med Ctr Hamburg Eppendorf, Ctr Dent & Oral Med, Dept Prosthet Dent, Hamburg, Germany.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Thiery, Joachim] Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
[Zalloua, Pierre A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia.
RP Watkins, H (reprint author), Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.
EM hugh.watkins@rdm.ox.ac.uk; sekar@broadinstitute.org;
rmcpherson@ottawaheart.ca; martin.farrall@well.ox.ac.uk
RI Konig, Inke/A-4544-2009; Magnusson, Patrik/C-4458-2017; Lieb,
Wolfgang/C-1990-2012; Feitosa, Mary/K-8044-2012; Meitinger,
Thomas/O-1318-2015; Kessler, Thorsten/O-7426-2015; Webb,
Tom/C-6237-2011; Peters, Annette/A-6117-2011; Lyytikainen,
Leo-Pekka/C-8544-2016; Bertram, Lars/K-3889-2015; Smith,
Albert/K-5150-2015; Deloukas, Panos/B-2922-2013; Study,
GoDARTS/K-9448-2016; Gudnason, Vilmundur/K-6885-2015; Erdmann,
Jeanette/P-7513-2014;
OI Feitosa, Mary/0000-0002-0933-2410; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Bertram, Lars/0000-0002-0108-124X; Smith,
Albert/0000-0003-1942-5845; Deloukas, Panos/0000-0001-9251-070X; Won,
Hong-Hee/0000-0001-5719-0552; Gudnason, Vilmundur/0000-0001-5696-0084;
ELOSUA, ROBERTO/0000-0001-8235-0095; Palmer, Colin/0000-0002-6415-6560;
Stewart, Alexandre/0000-0003-2673-9164; Gieger,
Christian/0000-0001-6986-9554; Erdmann, Jeanette/0000-0002-4486-6231;
Zhao, Wei/0000-0002-8301-9297; zalloua, pierre/0000-0002-8494-5081;
Watkins, Hugh/0000-0002-5287-9016; Assimes,
Themistocles/0000-0003-2349-0009; Sinisalo, Juha/0000-0002-0169-5137;
Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X;
Peters, Annette/0000-0001-6645-0985
FU British Heart Foundation [RG/08/014/24067, FS/14/55/30806,
RE/13/1/30181, RG/14/5/30893]; Medical Research Council [MR/L003120/1,
MR/L01629X/1]; NCI NIH HHS [UM1 CA182913]; NHLBI NIH HHS [R01 HL117078,
R01 HL127564, R33 HL120757]; NIDDK NIH HHS [R01 DK089256]
NR 83
TC 110
Z9 111
U1 11
U2 38
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 OCT
PY 2015
VL 47
IS 10
BP 1121
EP +
DI 10.1038/ng.3396
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA CS3JR
UT WOS:000361969900007
PM 26343387
ER
PT J
AU Dina, C
Bouatia-Naji, N
Tucker, N
Delling, FN
Toomer, K
Durst, R
Perrocheau, M
Fernandez-Friera, L
Solis, J
Le Tourneau, T
Chen, MH
Probst, V
Bosse, Y
Pibarot, P
Zelenika, D
Lathrop, M
Hercberg, S
Roussel, R
Benjamin, EJ
Bonnet, F
Lo, SH
Dolmatova, E
Simonet, F
Lecointe, S
Kyndt, F
Redon, R
Le Marec, H
Froguel, P
Ellinor, PT
Vasan, RS
Bruneval, P
Markwald, RR
Norris, RA
Milan, DJ
Slaugenhaupt, SA
Levine, RA
Schott, JJ
Hagege, AA
Jeunemaitre, X
AF Dina, Christian
Bouatia-Naji, Nabila
Tucker, Nathan
Delling, Francesca N.
Toomer, Katelynn
Durst, Ronen
Perrocheau, Maelle
Fernandez-Friera, Leticia
Solis, Jorge
Le Tourneau, Thierry
Chen, Ming-Huei
Probst, Vincent
Bosse, Yohan
Pibarot, Philippe
Zelenika, Diana
Lathrop, Mark
Hercberg, Serge
Roussel, Ronan
Benjamin, Emelia J.
Bonnet, Fabrice
Lo, Su Hao
Dolmatova, Elena
Simonet, Floriane
Lecointe, Simon
Kyndt, Florence
Redon, Richard
Le Marec, Herve
Froguel, Philippe
Ellinor, Patrick T.
Vasan, Ramachandran S.
Bruneval, Patrick
Markwald, Roger R.
Norris, Russell A.
Milan, David J.
Slaugenhaupt, Susan A.
Levine, Robert A.
Schott, Jean-Jacques
Hagege, Albert A.
Jeunemaitre, Xavier
CA PROMESA Investigators
MVP-France
Leducq Transatlantic MITRAL Networ
TI Genetic association analyses highlight biological pathways underlying
mitral valve prolapse
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CARDIAC VALVULAR DYSTROPHY; FILAMIN-A;
NATURAL-HISTORY; MARFAN-SYNDROME; CELL-MIGRATION; EXPRESSION; LOCUS;
PATHOGENESIS; METAANALYSIS
AB Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death(1). Previous family and pathophysiological studies suggest a complex pattern of inheritance(2-5). We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor(6) and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns(1-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair(7).
C1 [Dina, Christian; Le Tourneau, Thierry; Probst, Vincent; Simonet, Floriane; Lecointe, Simon; Kyndt, Florence; Redon, Richard; Le Marec, Herve; Schott, Jean-Jacques] CNRS, INSERM, Inst Thorax, UMR 1087,UMR 6291, Nantes, France.
[Dina, Christian; Le Tourneau, Thierry; Probst, Vincent; Lecointe, Simon; Kyndt, Florence; Redon, Richard; Le Marec, Herve; Schott, Jean-Jacques] Univ Nantes, CHU Nantes, Nantes, France.
[Bouatia-Naji, Nabila; Perrocheau, Maelle; Bruneval, Patrick; Hagege, Albert A.; Jeunemaitre, Xavier] Paris Cardiovasc Res Ctr, INSERM, UMR 970, Paris, France.
[Bouatia-Naji, Nabila; Perrocheau, Maelle; Hercberg, Serge; Bruneval, Patrick; Jeunemaitre, Xavier] Paris Descartes Univ, Paris Sorbonne Cite, Paris, France.
[Tucker, Nathan; Dolmatova, Elena; Ellinor, Patrick T.; Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Delling, Francesca N.; Chen, Ming-Huei; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Populat Sci Branch, Div Intramural Res,US Natl Inst Hlth, Framingham, MA USA.
[Delling, Francesca N.; Benjamin, Emelia J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02215 USA.
[Toomer, Katelynn; Markwald, Roger R.; Norris, Russell A.] Med Univ S Carolina, Childrens Res Inst, Cardiovasc Dev Biol Ctr, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[Durst, Ronen] Hadassah Hebrew Univ Med Ctr, Dept Cardiol, Jerusalem, Israel.
[Fernandez-Friera, Leticia; Solis, Jorge] Univ Ctr Estudios Univ CEU, Hosp Univ Monteprincipe, Madrid, Spain.
[Fernandez-Friera, Leticia; Solis, Jorge; Leducq Transatlantic MITRAL Networ] Carlos III CNIC, Ctr Nacl Invest Cardiovasc, Madrid, Spain.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Bosse, Yohan; Pibarot, Philippe] Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
[Zelenika, Diana; Lathrop, Mark] Ctr Natl Genotypage, Evry, France.
[Lathrop, Mark] Genome Quebec, Montreal, PQ, Canada.
[Hercberg, Serge] Univ Paris 13, Sorbonne Paris Cite, Bobigny, France.
[Hercberg, Serge] INRA, INSERM, U1153, U1125,Nutr Epidemiol Res Unit,Epidemiol & Biostat, Bobigny, France.
[Hercberg, Serge] Avicenne Hosp, AP HP, Dept Publ Hlth, Bobigny, France.
[Hercberg, Serge; Roussel, Ronan] Paris Diderot Univ, Paris, France.
[Roussel, Ronan] Ctr Rech Cordeliers, INSERM, UMRS 1138, Paris, France.
[Roussel, Ronan] Hop Xavier Bichat, AP HP, Fibrosis Inflammat Remodeling Cardiovasc Resp & R, Dept Endocrinol Diabet & Nutr, Paris, France.
[Bonnet, Fabrice] Univ Hosp Pontchaillou, INSERM, CIC 0203, Rennes, France.
[Bonnet, Fabrice] Univ Hosp, Dept Endocrinol, Rennes, France.
[Lo, Su Hao] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA.
[Froguel, Philippe] Univ Lille 2, CNRS, Lille Pasteur Inst, UMR 8199,EGID, Lille, France.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Ellinor, Patrick T.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Bruneval, Patrick] Hop Europeen Georges Pompidou, AP HP, Dept Pathol, Paris, France.
[Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Slaugenhaupt, Susan A.; Levine, Robert A.] Harvard Univ, Sch Med, Boston, MA USA.
[Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
[Hagege, Albert A.] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France.
[Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France.
RP Dina, C (reprint author), CNRS, INSERM, Inst Thorax, UMR 1087,UMR 6291, Nantes, France.
EM christian.dina@univ-nantes.fr; nabila.bouatia-naji@inserm.fr;
xavier.jeunemaitre@inserm.fr
RI probst, vincent/D-4996-2015; BOUATIA-NAJI, NABILA/D-5863-2013; Redon,
Richard/F-3303-2014;
OI Benjamin, Emelia/0000-0003-4076-2336; Redon,
Richard/0000-0001-7751-2280; Bouatia-Naji, Nabila/0000-0001-5424-2134
FU Nantes Hospital (CHU Nantes); US National Institutes of Health (NIH)
[K24 HL67434, R01 HL72265, HL109506]; French young investigator fund
[ANR-13-ISV1-0006-0]; Hassenfeld Scholar Program; NIH [HL092577,
HL104156, K24HL105780, HL065962]; American Heart Association
[13EIA14220013, 15GRNT25080052]; Fondation Leducq [14CVD01]; Canadian
Institutes of Health Research (CIHR) [MOP-102737, MOP-114997,
MOP-126072]; Fonds de recherche Quebec-Sante (FRQS); CIHR [MOP-102481,
MOP-137058]; Spanish Society of Cardiology; fund for medical discovery
of the Massachusetts General Hospital; European Commission; US National
Institutes of Health [C06 RR018823]; Extramural Research Facilities
Program of the Heart, Lung, and Blood Institute [R01-HL33756, COBRE 1P30
GM103342, 8P20 GM103444-07, R01-HL127692]; INSERM; French Society of
Cardiology
FX We acknowledge the major contribution of the Leducq Foundation, Paris
for supporting a transatlantic consortium investigating the
physiopathology of mitral valve disease, for which this genome-wide
association study was a major project (coordinators: R.A.L. and A.A.H.).
We thank J. Leyton-Mange, X.-X. Nguyen and M. McLellan for help with the
zebrafish experiments and P. Mathieu as one of the main investigators of
the PROGRAM (Determinants of the Progression and Outcomes of Organic
Mitral Regurgitation) study, from which was ascertained the Canadian MVP
case control study. C.D., T.L.T. and J.-J.S. acknowledge a translational
research grant on genetics of mitral valve funded by the Nantes Hospital
(CHU Nantes). R.A.L. acknowledges grant support from the US National
Institutes of Health (NIH; grants K24 HL67434, R01 HL72265 and
HL109506). N.B.-N. is recipient of a French young investigator fund
(ANR-13-ISV1-0006-0). D.J.M. acknowledges the support of the Hassenfeld
Scholar Program and a gift from Michael Zak. P.T.E. is supported by
grants from the NIH (HL092577, HL104156, K24HL105780, HL065962), an
Established Investigator Award from the American Heart Association
(13EIA14220013) and support from the Fondation Leducq (14CVD01). P.P.
holds the Canada Research Chair in Valvular Heart Diseases and is
supported by grants from the Canadian Institutes of Health Research
(CIHR; grants MOP-102737, MOP-114997 and MOP-126072). Y.B. is the
recipient of a Junior 2 Research Scholar award from the Fonds de
recherche Quebec-Sante (FRQS) and is supported by the CIHR (MOP-102481
and MOP-137058). L.F.-F. and J.S. received financial support from the
Spanish Society of Cardiology. R.D. was supported by fellowships from
the fund for medical discovery of the Massachusetts General Hospital and
by a Marie Curie reintegration award from the European Commission R.R.M.
and R.A.N. performed their work in a facility constructed with support
from the US National Institutes of Health, grant C06 RR018823, from the
Extramural Research Facilities Program of the Heart, Lung, and Blood
Institute: R01-HL33756 (R.R.M.), COBRE 1P30 GM103342 (R.R.M. and
R.A.N.), 8P20 GM103444-07 (R.R.M. and R.A.N.), R01-HL127692 (D.J.M.,
S.A.S. and R.A.N.) and American Heart Association 15GRNT25080052
(R.A.N.). A.A.H., N.B.-N. and X.J. acknowledge funds from INSERM and the
French Society of Cardiology.
NR 38
TC 11
Z9 11
U1 4
U2 23
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 OCT
PY 2015
VL 47
IS 10
BP 1206
EP +
DI 10.1038/ng.3383
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA CS3JR
UT WOS:000361969900017
PM 26301497
ER
PT J
AU Janiszewska, M
Liu, L
Almendro, V
Kuang, Y
Paweletz, C
Sakr, RA
Weigelt, B
Hanker, AB
Chandarlapaty, S
King, TA
Reis, JS
Arteaga, CL
Park, SY
Michor, F
Polyak, K
AF Janiszewska, Michalina
Liu, Lin
Almendro, Vanessa
Kuang, Yanan
Paweletz, Cloud
Sakr, Rita A.
Weigelt, Britta
Hanker, Ariella B.
Chandarlapaty, Sarat
King, Tari A.
Reis-Filho, Jorge S.
Arteaga, Carlos L.
Park, So Yeon
Michor, Franziska
Polyak, Kornelia
TI In situ single-cell analysis identifies heterogeneity for PIK3CA
mutation and HER2 amplification in HER2-positive breast cancer
SO NATURE GENETICS
LA English
DT Article
ID PRACTICE GUIDELINE UPDATE; PI3K PATHWAY ACTIVATION; INTRATUMORAL
HETEROGENEITY; CLINICAL ONCOLOGY/COLLEGE; GENE AMPLIFICATION; AMERICAN
SOCIETY; TRASTUZUMAB RESISTANCE; PCR-AMPLIFICATION; TUMOR EVOLUTION;
DIGITAL PCR
AB Detection of minor, genetically distinct subpopulations within tumors is a key challenge in cancer genomics. Here we report STAR-FISH (specific-to-allele PCR-FISH), a novel method for the combined detection of single-nucleotide and copy number alterations in single cells in intact archived tissues. Using this method, we assessed the clinical impact of changes in the frequency and topology of PIK3CA mutation and HER2 (ERBB2) amplification within HER2-positive breast cancer during neoadjuvant therapy. We found that these two genetic events are not always present in the same cells. Chemotherapy selects for PIK3CA-mutant cells, a minor subpopulation in nearly all treatment-naive samples, and modulates genetic diversity within tumors. Treatment-associated changes in the spatial distribution of cellular genetic diversity correlated with poor long-term outcome following adjuvant therapy with trastuzumab. Our findings support the use of in situ single cell-based methods in cancer genomics and imply that chemotherapy before HER2-targeted therapy may promote treatment resistance.
C1 [Janiszewska, Michalina; Almendro, Vanessa; Kuang, Yanan; Paweletz, Cloud; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Janiszewska, Michalina; Almendro, Vanessa; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Janiszewska, Michalina; Almendro, Vanessa; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Liu, Lin; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Liu, Lin; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kuang, Yanan; Paweletz, Cloud] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA.
[Sakr, Rita A.; King, Tari A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10021 USA.
[Weigelt, Britta; Reis-Filho, Jorge S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Hanker, Ariella B.; Arteaga, Carlos L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Canc Biol, Nashville, TN 37235 USA.
[Chandarlapaty, Sarat; Reis-Filho, Jorge S.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Arteaga, Carlos L.] Vanderbilt Univ, Dept Med, Breast Canc Res Program, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Park, So Yeon] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
[Polyak, Kornelia] Broad Inst, Cambridge, MA USA.
[Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM michor@jimmy.harvard.edu; kornelia_polyak@dfci.harvard.edu
OI Hanker, Ariella/0000-0002-8655-8341
FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center
[U54CA143798]; European Molecular Biology Organization (EMBO); Swiss
National Science Foundation; American Cancer Society
[CRP-07-234-06-COUN]; Breast Cancer Research Foundation
FX We thank E. Winer, I. Krop, B. Vogelstein and members of the Polyak and
Michor laboratories for their critical reading of the manuscript and
useful discussions. We thank A. Marusyk and D. Tabassum for their help
with the xenograft assays, R. Witwicki for help with data processing, L.
Cameron in the Dana-Farber Cancer Institute Confocal Microscopy center
for her technical support, A. Richardson (Dana-Farber Cancer Institute)
for providing slides from a human breast tumor with known status for the
PIK3CA mutation encoding p.His1047Arg, and H. Russness and I. Rye (Oslo
University Hospital) for providing the BAC probe for HER2. This work was
supported by the Dana-Farber Cancer Institute Physical Sciences-Oncology
Center (U54CA143798 to F.M.), the European Molecular Biology
Organization (EMBO; M.J.), the Swiss National Science Foundation (M.J.),
the American Cancer Society (CRP-07-234-06-COUN to C.L.A.) and the
Breast Cancer Research Foundation (K.P.).
NR 55
TC 27
Z9 27
U1 3
U2 16
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 OCT
PY 2015
VL 47
IS 10
BP 1212
EP +
DI 10.1038/ng.3391
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA CS3JR
UT WOS:000361969900018
PM 26301495
ER
PT J
AU Hernandez, SF
Vahidi, NA
Park, S
Weitzel, RP
Tisdale, J
Rueda, BR
Wolff, EF
AF Hernandez, Silvia F.
Vahidi, Nima A.
Park, Solji
Weitzel, R. Patrick
Tisdale, John
Rueda, Bo R.
Wolff, Erin F.
TI Characterization of extracellular DDX4-or Ddx4-positive ovarian cells
SO NATURE MEDICINE
LA English
DT Letter
ID ACTIVE GERM-CELLS; LINE; MOUSE
C1 [Hernandez, Silvia F.; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Hernandez, Silvia F.; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA USA.
[Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA.
[Vahidi, Nima A.; Park, Solji; Wolff, Erin F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Weitzel, R. Patrick; Tisdale, John; Wolff, Erin F.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Wolff, EF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
EM erin.wolff@nih.gov
FU Intramural NIH HHS
NR 6
TC 8
Z9 8
U1 2
U2 6
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 OCT
PY 2015
VL 21
IS 10
BP 1114
EP 1116
DI 10.1038/nm.3966
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CS8RG
UT WOS:000362355400006
PM 26444630
ER
PT J
AU Gilja, V
Pandarinath, C
Blabe, CH
Nuyujukian, P
Simeral, JD
Sarma, AA
Sorice, BL
Perge, JA
Jarosiewicz, B
Hochberg, LR
Shenoy, KV
Henderson, JM
AF Gilja, Vikash
Pandarinath, Chethan
Blabe, Christine H.
Nuyujukian, Paul
Simeral, John D.
Sarma, Anish A.
Sorice, Brittany L.
Perge, Janos A.
Jarosiewicz, Beata
Hochberg, Leigh R.
Shenoy, Krishna V.
Henderson, Jaimie M.
TI Clinical translation of a high-performance neural prosthesis
SO NATURE MEDICINE
LA English
DT Article
ID POSTERIOR PARIETAL CORTEX; CORTICAL CONTROL; MOVEMENT SIGNAL;
TETRAPLEGIA; INTERFACE; HUMANS; FEEDBACK; DEVICES; ARM
AB Neural prostheses have the potential to improve the quality of life of individuals with paralysis by directly mapping neural activity to limb- and computer-control signals. We translated a neural prosthetic system previously developed in animal model studies for use by two individuals with amyotrophic lateral sclerosis who had intracortical microelectrode arrays placed in motor cortex. Measured more than 1 year after implant, the neural cursor-control system showed the highest published performance achieved by a person to date, more than double that of previous pilot clinical trial participants.
C1 [Gilja, Vikash; Pandarinath, Chethan; Blabe, Christine H.; Nuyujukian, Paul; Henderson, Jaimie M.] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA.
[Gilja, Vikash; Pandarinath, Chethan; Nuyujukian, Paul; Shenoy, Krishna V.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
[Gilja, Vikash; Simeral, John D.; Sarma, Anish A.; Perge, Janos A.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA.
[Gilja, Vikash] Univ Calif San Diego, Dept Elect & Comp Engn, La Jolla, CA 92093 USA.
[Pandarinath, Chethan; Nuyujukian, Paul; Shenoy, Krishna V.; Henderson, Jaimie M.] Stanford Univ, Stanford Neurosci Inst, Stanford, CA 94305 USA.
[Simeral, John D.; Sarma, Anish A.; Perge, Janos A.; Jarosiewicz, Beata; Hochberg, Leigh R.] Dept Vet Affairs Med Ctr, Rehabil R&D Serv, Ctr Neurorestorat & Neurotechnol, Providence, RI USA.
[Simeral, John D.; Sarma, Anish A.; Perge, Janos A.; Jarosiewicz, Beata; Hochberg, Leigh R.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA.
[Simeral, John D.; Sarma, Anish A.; Sorice, Brittany L.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Jarosiewicz, Beata] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Hochberg, Leigh R.] Harvard Univ, Sch Med, Neurol, Boston, MA USA.
[Shenoy, Krishna V.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
[Shenoy, Krishna V.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Shenoy, Krishna V.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
RP Henderson, JM (reprint author), Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA.
EM henderj@stanford.edu
OI Pandarinath, Chethan/0000-0003-1241-1432; Blabe,
Christine/0000-0003-4623-4251
FU Stanford Institute for Neuro-Innovation and Translational Neuroscience;
Stanford BioX-NeuroVentures; Stanford Office of Postdoctoral Affairs;
Garlick Foundation; Craig H. Neilsen Foundation; US National Institutes
of Health: the National Institute on Deafness and Other Communication
Disorders (NIDCD) [R01DC009899, R01DC014034]; US National Institutes of
Health: National Institute of Neurological Disorders and Stroke (NINDS)
[RO1NS066311-S1]; US National Institutes of Health: Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD)-National Center for Medical Rehabilitation Research (NCMRR)
[N01HD53403, N01HD10018]; Rehabilitation Research and Development
Service, Department of Veterans Affairs [B6453R, B6310N]; Massachusetts
General Hospital (MGH)-Deane Institute for Integrated Research on Atrial
Fibrillation and Stroke
FX The authors would like to thank participants T6, T7, S3 and their
families; E.N. Eskandar for participant T7's implantation surgery; B.
Davis, B. Pedrick, M. Coburn, B. Travers and D. Rosler for
administrative support; S.I. Ryu for surgical assistance; L. Barefoot,
P. Gigante, A. Sachs, S. Cash, J. Menon and S. Mernoff for clinical
assistance; K. Newell for data collection assistance; J. Saab and N.
Schmansky for technical assistance; and J.P. Donoghue for helpful
scientific discussions. This work was supported by the Stanford
Institute for Neuro-Innovation and Translational Neuroscience; Stanford
BioX-NeuroVentures; the Stanford Office of Postdoctoral Affairs; the
Garlick Foundation; the Craig H. Neilsen Foundation; The US National
Institutes of Health: the National Institute on Deafness and Other
Communication Disorders (NIDCD) (R01DC009899, principal investigator
(PI): L.R.H.; R01DC014034, PI: J.M.H.), the National Institute of
Neurological Disorders and Stroke (NINDS) (RO1NS066311-S1, PI: K.V.S.),
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD)-National Center for Medical Rehabilitation Research
(NCMRR) (N01HD53403 and N01HD10018, Sub-award PI: L.R.H.); the
Rehabilitation Research and Development Service, Department of Veterans
Affairs (B6453R and B6310N, PI: L.R.H.); and the Massachusetts General
Hospital (MGH)-Deane Institute for Integrated Research on Atrial
Fibrillation and Stroke. The content of this paper is solely the
responsibility of the authors and does not necessarily represent the
official views of the US National Institutes of Health, the Department
of Veterans Affairs or the United States Government.
NR 31
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U1 3
U2 18
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 OCT
PY 2015
VL 21
IS 10
BP 1142
EP +
DI 10.1038/nm.3953
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CS8RG
UT WOS:000362355400015
PM 26413781
ER
PT J
AU Mazur, PK
Herner, A
Mello, SS
Wirth, M
Hausmann, S
Sanchez-Rivera, FJ
Lofgren, SM
Kuschma, T
Hahn, SA
Vangala, D
Trajkovic-Arsic, M
Gupta, A
Heid, I
Noel, PB
Braren, R
Erkan, M
Kleeff, J
Sipos, B
Sayles, LC
Heikenwalder, M
Hessmann, E
Ellenrieder, V
Esposito, I
Jacks, T
Bradner, JE
Khatri, P
Sweet-Cordero, EA
Attardi, LD
Schmid, RM
Schneider, G
Sage, J
Siveke, JT
AF Mazur, Pawel K.
Herner, Alexander
Mello, Stephano S.
Wirth, Matthias
Hausmann, Simone
Sanchez-Rivera, Francisco J.
Lofgren, Shane M.
Kuschma, Timo
Hahn, Stephan A.
Vangala, Deepak
Trajkovic-Arsic, Marija
Gupta, Aayush
Heid, Irina
Noel, Peter B.
Braren, Rickmer
Erkan, Mert
Kleeff, Joerg
Sipos, Bence
Sayles, Leanne C.
Heikenwalder, Mathias
Hessmann, Elisabeth
Ellenrieder, Volker
Esposito, Irene
Jacks, Tyler
Bradner, James E.
Khatri, Purvesh
Sweet-Cordero, E. Alejandro
Attardi, Laura D.
Schmid, Roland M.
Schneider, Guenter
Sage, Julien
Siveke, Jens T.
TI Combined inhibition of BET family proteins and histone deacetylases as a
potential epigenetics-based therapy for pancreatic ductal adenocarcinoma
SO NATURE MEDICINE
LA English
DT Article
ID ENGINEERED MOUSE MODELS; LUNG-CANCER; C-MYC; INTRAEPITHELIAL NEOPLASIA;
BROMODOMAIN INHIBITION; SELECTIVE-INHIBITION; DRUG-COMBINATION; IN-VIVO;
PROGRESSION; KRAS
AB Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9-based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy-induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors.
C1 [Mazur, Pawel K.; Kuschma, Timo; Sayles, Leanne C.; Sweet-Cordero, E. Alejandro; Sage, Julien] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
[Mazur, Pawel K.; Mello, Stephano S.; Kuschma, Timo; Attardi, Laura D.; Sage, Julien] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Herner, Alexander; Wirth, Matthias; Trajkovic-Arsic, Marija; Gupta, Aayush; Schmid, Roland M.; Schneider, Guenter; Siveke, Jens T.] Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 2, D-80290 Munich, Germany.
[Mello, Stephano S.; Attardi, Laura D.] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA.
[Hausmann, Simone; Erkan, Mert; Kleeff, Joerg] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-80290 Munich, Germany.
[Sanchez-Rivera, Francisco J.; Jacks, Tyler] MIT, Dept Biol, David H Koch Inst Integrat Canc Res, Cambridge, MA USA.
[Sanchez-Rivera, Francisco J.; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA USA.
[Lofgren, Shane M.; Khatri, Purvesh] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Lofgren, Shane M.; Khatri, Purvesh] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
[Hahn, Stephan A.] Ruhr Univ Bochum, Dept Mol Gastrointestinal Oncol, Bochum, Germany.
[Vangala, Deepak] Ruhr Univ Bochum, Med Clin, Knappschaftskrankenhaus, Bochum, Germany.
[Heid, Irina; Noel, Peter B.; Braren, Rickmer] Tech Univ Munich, Klinikum Rechts Isar, Inst Radiol, D-80290 Munich, Germany.
[Sipos, Bence] Univ Tubingen, Inst Pathol, Tubingen, Germany.
[Heikenwalder, Mathias] Tech Univ Munich, Klinikum Rechts Isar, Inst Virol, D-80290 Munich, Germany.
[Heikenwalder, Mathias] German Canc Res Ctr, Div Chron Inflammat & Canc, Heidelberg, Germany.
[Hessmann, Elisabeth; Ellenrieder, Volker] Univ Med Ctr Gottingen, Dept Gastroenterol & Gastrointestinal Oncol, Gottingen, Germany.
[Esposito, Irene] Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-80290 Munich, Germany.
[Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Schmid, Roland M.; Siveke, Jens T.] German Canc Consortium DKTK, Heidelberg, Germany.
[Schmid, Roland M.; Siveke, Jens T.] German Canc Res Ctr, Heidelberg, Germany.
RP Mazur, PK (reprint author), Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
EM pmazur@stanford.edu; julsage@stanford.edu; j.siveke@dkfz.de
RI Hahn, Stephan/E-3880-2010; Kleeff, Jorg/B-2124-2009;
OI Kleeff, Jorg/0000-0003-3432-6669; Mazur, Pawel/0000-0002-5820-8344;
Noel, Peter/0000-0002-9671-6171
FU German Research Foundation [SFB824/C4]; European Union [602783]; German
Cancer Consortium (DKTK); Lustgarten Foundation; Tobacco-Related Disease
Research Program; Stanford University; Child Health Research Institute;
Lucile Packard Foundation for Children's Health at Stanford; Boehringer
Ingelheim Fonds MD Fellowship
FX P.K.M. and A.H. significantly contributed to the work and are listed as
co-first authors based on a previous agreement. We thank C. Vakoc (Cold
Spring Harbor Laboratory) for sharing shRNA plasmids, M. Winslow
(Stanford University) for the R26CAG-tdTomato reporter mice
and I. Moreno de Alboran (Spanish National Biotechnology Centre) for
MycloxP mice. This work was supported by the German Research
Foundation (SFB824/C4 to J.T.S.), the European Union's Seventh Framework
Program for research, technological development and demonstration
(FP7/CAM-PaC) under grant agreement 602783, the German Cancer Consortium
(DKTK) (to R.M.S. and J.T.S.), and the Lustgarten Foundation (J.S.).
P.K.M. was supported by the Tobacco-Related Disease Research Program, a
Dean's Fellowship from Stanford University, and the Child Health
Research Institute and Lucile Packard Foundation for Children's Health
at Stanford. J.S. is the Harriet and Mary Zelencik Scientist in
Children's Cancer and Blood Diseases. T.K. was supported by a Boehringer
Ingelheim Fonds MD Fellowship.
NR 79
TC 42
Z9 42
U1 5
U2 36
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 OCT
PY 2015
VL 21
IS 10
BP 1163
EP +
DI 10.1038/nm.3952
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CS8RG
UT WOS:000362355400018
PM 26390243
ER
PT J
AU Sinatra, R
Deville, P
Szell, M
Wang, DS
Barabsi, AL
AF Sinatra, Roberta
Deville, Pierre
Szell, Michael
Wang, Dashun
Barabsi, Albert-Laszlo
TI A century of physics
SO NATURE PHYSICS
LA English
DT Article
ID SCIENTIFIC IMPACT; EVOLUTION
C1 [Sinatra, Roberta; Deville, Pierre; Szell, Michael; Barabsi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
[Sinatra, Roberta; Deville, Pierre; Szell, Michael; Barabsi, Albert-Laszlo] Northwestern Univ, Dept Phys, Boston, MA 02115 USA.
[Wang, Dashun] Penn State Univ, Coll Informat Sci & Technol, University Pk, PA 16801 USA.
[Wang, Dashun] Catholic Univ Louvain, Dept Appl Math, B-1348 Louvain La Neuve, Belgium.
[Barabsi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Barabsi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Barabsi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary.
RP Sinatra, R (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
EM r.sinatra@neu.edu; alb@neu.edu
OI Sinatra, Roberta/0000-0002-7558-1028
FU AFOSR [FA9550-15-1-0077, FA9550-15-1-0162]; National Foundation for
Scientific Research (FNRS); Research Department of the Communaute
Francaise de Belgique (Large Graph Concerted Research Action); James S.
McDonnell Foundation; Future and Emerging Technologies Project -
European Commission [317 532]
FX R.S., M.S. and A.L.B. are supported by the AFOSR grant FA9550-15-1-0077.
P.D. is supported by the National Foundation for Scientific Research
(FNRS) and by the Research Department of the Communaute Francaise de
Belgique (Large Graph Concerted Research Action). D.W. is supported by
the AFOSR, grant FA9550-15-1-0162. R.S. is also supported by the James
S. McDonnell Foundation. A.L.B. is also supported by the Future and
Emerging Technologies Project 317 532 'Multiplex' financed by the
European Commission. We wish to thank I. Georgescu for many fruitful
discussions and ideas throughout this project and J. De Nicolo for
support with handling the WoS data.
NR 24
TC 17
Z9 17
U1 7
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1745-2473
EI 1745-2481
J9 NAT PHYS
JI Nat. Phys.
PD OCT
PY 2015
VL 11
IS 10
BP 791
EP 796
PG 6
WC Physics, Multidisciplinary
SC Physics
GA CS6KX
UT WOS:000362188600003
ER
PT J
AU Angulo, MT
Liu, YY
Slotine, JJ
AF Angulo, Marco Tulio
Liu, Yang-Yu
Slotine, Jean-Jacques
TI Network motifs emerge from interconnections that favour stability
SO NATURE PHYSICS
LA English
DT Article
ID PARADOXICAL COMPONENTS; SYSTEMS; ORGANIZATION; MODULARITY; EVOLUTION;
CIRCUITS; DESIGN
AB The microscopic principles organizing dynamic units in complex networks-from proteins to power generators-can be understood in terms of network 'motifs': small interconnection patterns that appear much more frequently in real networks than expected in random networks(1,2). When considered as small subgraphs isolated from a large network, these motifs are more robust to parameter variations, easier to synchronize than other possible subgraphs, and can provide specific functionalities(3-15). But one can isolate these subgraphs only by assuming, for example, a significant separation of timescales, and the origin of network motifs and their functionalities when embedded in larger networks remain unclear. Here we show that most motifs emerge from interconnection patterns that best exploit the intrinsic stability characteristics at different scales of interconnection, from simple nodes to whole modules. This functionality suggests an efficient mechanism to stably build complex systems by recursively interconnecting nodes and modules as motifs. We present direct evidence of this mechanism in several biological networks.
C1 [Angulo, Marco Tulio] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA.
[Angulo, Marco Tulio; Liu, Yang-Yu] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Angulo, Marco Tulio; Liu, Yang-Yu] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02139 USA.
[Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Liu, YY (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM yyl@channing.harvard.edu; jjs@mit.edu
RI Liu, Yang-Yu/G-8885-2011
OI Liu, Yang-Yu/0000-0003-2728-4907
FU CONACyT postdoctoral grant [207609]; ARL NS-CTA grant
[W911NF-09-2-0053]; DARPA grant [W911NF-12-C-002]; John Templeton
Foundation [51977]
FX We thank A.-L. Barabasi for valuable discussions. M.T.A. was supported
by the CONACyT postdoctoral grant 207609, the ARL NS-CTA grant
(W911NF-09-2-0053), and the DARPA grant (W911NF-12-C-002). Y.-Y.L. was
supported in part by the John Templeton Foundation (award number 51977).
NR 30
TC 1
Z9 1
U1 3
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1745-2473
EI 1745-2481
J9 NAT PHYS
JI Nat. Phys.
PD OCT
PY 2015
VL 11
IS 10
BP 848
EP 852
DI 10.1038/NPHYS3402
PG 5
WC Physics, Multidisciplinary
SC Physics
GA CS6KX
UT WOS:000362188600021
ER
PT J
AU MacRae, CA
Peterson, RT
AF MacRae, Calum A.
Peterson, Randall T.
TI Zebrafish as tools for drug discovery
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID CHEMICAL GENETIC SCREEN; WNT/BETA-CATENIN PATHWAY; BLOOD-BRAIN-BARRIER;
SMALL MOLECULES; ANTIANGIOGENIC COMPOUNDS; TRANSGENIC ZEBRAFISH; NEURAL
CREST; STEM-CELLS; INHIBITION; SYSTEM
AB The zebrafish has become a prominent vertebrate model for disease and has already contributed to several examples of successful phenotype-based drug discovery. For the zebrafish to become useful in drug development more broadly, key hurdles must be overcome, including a more comprehensive elucidation of the similarities and differences between human and zebrafish biology. Recent studies have begun to establish the capabilities and limitations of zebrafish for disease modelling, drug screening, target identification, pharmacology, and toxicology. As our understanding increases and as the technologies for manipulating zebrafish improve, it is hoped that the zebrafish will have a key role in accelerating the emergence of precision medicine.
C1 [MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[MacRae, Calum A.] Brigham & Womens Hosp, Network Med Div, Boston, MA 02115 USA.
[MacRae, Calum A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[MacRae, Calum A.; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[MacRae, Calum A.; Peterson, Randall T.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Peterson, Randall T.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA.
RP MacRae, CA (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
EM camacrae@bics.bwh.harvard.edu; peterson@cvrc.mgh.harvard.edu
FU Innovation in Regulatory Science Award from the Burroughs Wellcome Fund
FX The authors thank A. Rennekamp for his help compiling Table 1. R.T.P
acknowledges support from The toxicology work of C.A.M. has been funded
by an Innovation in Regulatory Science Award from the Burroughs Wellcome
Fund.
NR 106
TC 44
Z9 45
U1 13
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD OCT
PY 2015
VL 14
IS 10
BP 721
EP 731
DI 10.1038/nrd4627
PG 11
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA CS6LT
UT WOS:000362191100015
PM 26361349
ER
PT J
AU Braga, RM
Leech, R
AF Braga, Rodrigo M.
Leech, Robert
TI Echoes of the Brain: Local-Scale Representation of Whole-Brain
Functional Networks within Transmodal Cortex
SO NEUROSCIENTIST
LA English
DT Review
DE transmodal cortex; multimodal; association; integration; networks; hubs;
intrinsic connectivity networks; neural dynamics
ID POSTERIOR CINGULATE CORTEX; DEFAULT MODE NETWORK; RICH-CLUB
ORGANIZATION; HUMAN CEREBRAL-CORTEX; RESTING HUMAN BRAIN; CONNECTIVITY
NETWORKS; COGNITIVE CONTROL; ARCHITECTURE; TASK; FMRI
AB Transmodal (nonsensory-specific) regions sit at the confluence of different information streams, and play an important role in cognition. These regions are thought to receive and integrate information from multiple functional networks. However, little is known about (1) how transmodal cortices are functionally organized and (2) how this organization might facilitate information processing. In this article, we discuss recent findings that transmodal cortices contain a detailed local functional architecture of adjacent and partially overlapping subregions. These subregions show relative specializations, and contain traces or echoes of the activity of different large-scale intrinsic connectivity networks. We propose that this finer-grained organization can (1) explain how the same transmodal region can play a role in multiple tasks and cognitive disorders, (2) provide a mechanism by which different types of signals can be simultaneously segregated and integrated within transmodal regions, and (3) enhance current network- and node-level models of brain function, by showing that non-stationary functional connectivity patterns may be a result of dynamic shifts in subnodal signals. Finally, we propose that LFA may have an important role in regulating neural dynamics and facilitating balanced activity across the cortex to enable efficient and flexible high-level cognition.
C1 [Braga, Rodrigo M.; Leech, Robert] Univ London Imperial Coll Sci Technol & Med, Computat Cognit & Clin Neuroimaging Lab, Div Brain Sci, London W12 0NN, England.
[Braga, Rodrigo M.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Braga, Rodrigo M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Braga, Rodrigo M.] Harvard Univ, Sch Med, Charlestown, MA USA.
RP Leech, R (reprint author), Univ London Imperial Coll Sci Technol & Med, Imaging Neurosci Computat Cognit & Clin Neuroimag, Div Brain Sci, Hammersmith Hosp Campus,Du Cane Rd, London W12 0NN, England.
EM r.leech@imperial.ac.uk
FU Wellcome Trust
FX RMB is supported by the Wellcome Trust.
NR 92
TC 3
Z9 3
U1 1
U2 7
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 OCT
PY 2015
VL 21
IS 5
BP 540
EP 551
DI 10.1177/1073858415585730
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CS7TU
UT WOS:000362290000013
ER
PT J
AU Takahashi, H
Jin, C
Rajabi, H
Pitroda, S
Alam, M
Ahmad, R
Raina, D
Hasegawa, M
Suzuki, Y
Tagde, A
Bronson, RT
Weichselbaum, R
Kufe, D
AF Takahashi, H.
Jin, C.
Rajabi, H.
Pitroda, S.
Alam, M.
Ahmad, R.
Raina, D.
Hasegawa, M.
Suzuki, Y.
Tagde, A.
Bronson, R. T.
Weichselbaum, R.
Kufe, D.
TI MUC1-C activates the TAK1 inflammatory pathway in colon cancer
SO ONCOGENE
LA English
DT Article
ID COLITIS-ASSOCIATED CANCER; COLORECTAL-CANCER; BOWEL-DISEASE;
LUNG-CANCER; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODY; MOUSE MODEL;
ONCOPROTEIN; KINASE; CELLS
AB The mucin 1 (MUC1) oncoprotein has been linked to the inflammatory response by promoting cytokine-mediated activation of the NF-kappa B pathway. The TGF-beta-activated kinase 1 (TAK1) is an essential effector of proinflammatory NF-kappa B signaling that also regulates cancer cell survival. The present studies demonstrate that the MUC1-C transmembrane subunit induces TAK1 expression in colon cancer cells. MUC1 also induces TAK1 in a MUC1(+/-)/IL-10(-/-) mouse model of colitis and colon tumorigenesis. We show that MUC1C promotes NF-kappa B-mediated activation of TAK1 transcription and, in a positive regulatory loop, MUC1-C contributes to TAK1-induced NF-kappa B signaling. In this way, MUC1-C binds directly to TAK1 and confers the association of TAK1 with TRAF6, which is necessary for TAK1-mediated activation of NF-kappa B. Targeting MUC1-C thus suppresses the TAK1 -> NF-kappa B pathway, downregulates BCL-XL and in turn sensitizes colon cancer cells to MEK inhibition. Analysis of colon cancer databases further indicates that MUC1, TAK1 and TRAF6 are upregulated in tumors associated with decreased survival and that MUC1-C-induced gene expression patterns predict poor outcomes in patients. These results support a model in which MUC1-C-induced TAK1 -> NF-kappa B signaling contributes to intestinal inflammation and colon cancer progression.
C1 [Takahashi, H.; Rajabi, H.; Alam, M.; Ahmad, R.; Hasegawa, M.; Suzuki, Y.; Tagde, A.; Kufe, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Jin, C.; Raina, D.] Genus Oncol, Boston, MA USA.
[Pitroda, S.; Weichselbaum, R.] Univ Chicago, Dept Radiat & Cellular Oncol, Ludwig Ctr Metastasis Res, Chicago, IL 60637 USA.
[Bronson, R. T.] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA.
EM donald_kufe@dfci.harvard.edu
RI Tagde, Ashujit/M-9497-2014
OI Tagde, Ashujit/0000-0002-0770-097X
FU Department of Defense; National Cancer Institute of the National
Institutes of Health [CA97098, CA166480]; CDMRP [CA110495]
FX Research reported in this publication was supported by Grant CDMRP
CA110495 awarded by the Department of Defense and by the National Cancer
Institute of the National Institutes of Health under award numbers
CA97098 and CA166480.
NR 50
TC 15
Z9 16
U1 0
U2 5
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 OCT 1
PY 2015
VL 34
IS 40
BP 5187
EP 5197
DI 10.1038/onc.2014.442
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA CS6ZP
UT WOS:000362233400008
PM 25659581
ER
PT J
AU Jampel, JD
Safren, SA
Blashill, AJ
AF Jampel, Jonathan D.
Safren, Steven A.
Blashill, Aaron J.
TI Muscularity Disturbance and Methamphetamine Use Among HIV-Infected Men
Who Have Sex With Men
SO PSYCHOLOGY OF MEN & MASCULINITY
LA English
DT Article
DE HIV/AIDS; gay and bisexual men; body image; methamphetamine use;
muscularity concerns
ID ANABOLIC-ANDROGENIC STEROIDS; QUALITY-OF-LIFE; BODY-IMAGE; ADOLESCENT
BOYS; BISEXUAL MEN; ADULT MEN; DRUG-USE; HEALTH; RISK; BEHAVIORS
AB Previous research has established a link between methamphetamine use and body dissatisfaction among HIV-infected men who have sex with men (MSM). However, to date, no study has examined the specific role that muscularity disturbance, a key component of body dissatisfaction among men, has in this relationship. Thus, the current study aimed to examine links between muscularity disturbance and methamphetamine use among HIV-infected MSM. Participants were 97 HIV-infected MSM, who completed a number of self-report measures of muscularity disturbance, depressive symptoms, and substance use. Results indicated that after controlling for depression and polysubstance use, elevated muscularity disturbance was associated with increased methamphetamine use. Future interventions may benefit from integrating body image dissatisfaction and methamphetamine use in an approach that encompasses the intertwined psychosocial stressors that HIV-infected MSM face.
C1 [Jampel, Jonathan D.; Safren, Steven A.; Blashill, Aaron J.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Safren, Steven A.; Blashill, Aaron J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA.
RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM ablashill@mgh.harvard.edu
FU National Institute of Mental Health of the National Institutes of Health
[K23MH096647]; Harvard University Center for AIDS Research/National
Institutes of Health [5P30 AI060354-08, K24MH094214]
FX Research reported in this publication was supported by the National
Institute of Mental Health of the National Institutes of Health
(K23MH096647) and awards from the Harvard University Center for AIDS
Research/National Institutes of Health to Aaron J. Blashill (5P30
AI060354-08) and Steven A. Safren (K24MH094214). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 51
TC 2
Z9 2
U1 5
U2 7
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1524-9220
EI 1939-151X
J9 PSYCHOL MEN MASCULIN
JI Psychol. Men Masculinity
PD OCT
PY 2015
VL 16
IS 4
BP 474
EP 479
DI 10.1037/a0038461
PG 6
WC Psychology, Social
SC Psychology
GA CS2NB
UT WOS:000361906800016
ER
PT J
AU Dueck, AC
Mitchell, SA
Rogak, LJ
Ginos, B
Sargent, DJ
Shi, Q
Farma, JM
Eng, C
Crane, C
Kennecke, H
O'Mara, AM
Minasian, LM
Schrag, D
Basch, E
AF Dueck, Amylou C.
Mitchell, Sandra A.
Rogak, Lauren J.
Ginos, Brenda
Sargent, Daniel J.
Shi, Qian
Farma, Jeffrey M.
Eng, Cathy
Crane, Christopher
Kennecke, Hagen
O'Mara, Ann M.
Minasian, Lori M.
Schrag, Deborah
Basch, Ethan
TI A cluster-randomized study of clinician-patient shared vs standard
reporting of symptomatic adverse events using PRO-CTCAE nested in a
multicenter trial of multimodal therapy for rectal cancer (Alliance
N1048 PROSPECT)
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Dueck, Amylou C.; Ginos, Brenda] Mayo Clin, Scottsdale, AZ USA.
[Mitchell, Sandra A.; O'Mara, Ann M.; Minasian, Lori M.] NCI, Rockville, MD USA.
[Rogak, Lauren J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Sargent, Daniel J.; Shi, Qian] Mayo Clin, Rochester, MN USA.
[Farma, Jeffrey M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Eng, Cathy; Crane, Christopher] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kennecke, Hagen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Basch, Ethan] Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 1
Z9 1
U1 1
U2 3
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 OCT
PY 2015
VL 24
SU 1
MA 2
BP 1
EP 2
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CS3RA
UT WOS:000361991100003
ER
PT J
AU Basch, E
Deal, A
Dueck, A
Bennett, A
Atkinson, TM
Rogak, LJ
Sloan, JA
Schrag, D
AF Basch, Ethan
Deal, Allison
Dueck, Amylou
Bennett, Antonia
Atkinson, Thomas M.
Rogak, Lauren J.
Sloan, Jeff A.
Schrag, Deborah
TI Effect of electronic patient reporting of symptoms during cancer
treatment: a randomized controlled trial
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Basch, Ethan; Deal, Allison; Bennett, Antonia] Univ N Carolina, Chapel Hill, NC USA.
[Dueck, Amylou] Mato Clin, Scottsdale, AZ USA.
[Atkinson, Thomas M.; Rogak, Lauren J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Sloan, Jeff A.] Mayo Clin, Rochester, MN USA.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 OCT
PY 2015
VL 24
SU 1
MA 104.1
BP 19
EP 19
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CS3RA
UT WOS:000361991100050
ER
PT J
AU Reeve, BB
McFatrich, M
Baker, JN
Freyer, DR
Gagne, J
Gattuso, JS
Gibson, D
Kohler, RE
Levine, A
Lollar, S
Lukshis, J
Mack, JW
Martens, C
Mowbray, C
Palma, D
Pinheiro, LC
Sung, LL
Taddei, SC
Tomlinson, D
Waldron, M
Weaver, M
Wind, J
Withycombe, J
Hinds, PS
AF Reeve, Bryce B.
McFatrich, Molly
Baker, Justin N.
Freyer, David R.
Gagne, Joshua
Gattuso, Jami S.
Gibson, Deborah
Kohler, Racquel E.
Levine, Alyssa
Lollar, Selena
Lukshis, Jane
Mack, Jennifer W.
Martens, Christa
Mowbray, Catriona
Palma, Diana
Pinheiro, Laura C.
Sung, Lillian
Taddei, Sarah C.
Tomlinson, Deborah
Waldron, Mia
Weaver, Meaghann
Wind, Jennifer
Withycombe, Janice
Hinds, Pamela S.
TI Integrating the child's voice in adverse event reporting in oncology
trials: cognitive interview findings from the multisite pediatric
PRO-CTCAE initiative
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Reeve, Bryce B.; McFatrich, Molly; Kohler, Racquel E.; Martens, Christa; Pinheiro, Laura C.] Univ N Carolina, Chapel Hill, NC USA.
[Baker, Justin N.; Gattuso, Jami S.; Gibson, Deborah] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Freyer, David R.; Palma, Diana] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Gagne, Joshua; Levine, Alyssa; Mack, Jennifer W.; Taddei, Sarah C.; Wind, Jennifer] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
[Lollar, Selena; Lukshis, Jane; Withycombe, Janice] Palmetto Hlth Childrens Hosp, Columbia, SC USA.
[Mowbray, Catriona; Waldron, Mia; Hinds, Pamela S.] Childrens Natl Hlth Syst, Washington, DC USA.
[Sung, Lillian; Tomlinson, Deborah] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Weaver, Meaghann] St Jude Childrens Res Hosp, Childrens Natl Hlth Syst, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
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 OCT
PY 2015
VL 24
SU 1
MA 3033
BP 161
EP 162
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CS3RA
UT WOS:000361991100360
ER
PT J
AU Rahimy, E
Kuehlewein, L
Sadda, SR
Sarraf, D
AF Rahimy, Ehsan
Kuehlewein, Laura
Sadda, Srinivas R.
Sarraf, David
TI Paracentral Acute Middle Maculopathy What We Knew Then and What We Know
Now
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Editorial Material
ID ACUTE MACULAR NEURORETINOPATHY; DEEP CAPILLARY ISCHEMIA; COHERENCE
TOMOGRAPHY ANGIOGRAPHY; RETINAL ARTERY-OCCLUSION; FLUORESCEIN
ANGIOGRAPHY; OXYGEN DISTRIBUTION; VASCULATURE; SPECTRUM; OCT
C1 [Rahimy, Ehsan] Wills Eye Hosp & Res Inst, Retina Serv, Philadelphia, PA USA.
[Kuehlewein, Laura; Sadda, Srinivas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
[Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
NR 31
TC 7
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD OCT
PY 2015
VL 35
IS 10
BP 1921
EP 1930
DI 10.1097/IAE.0000000000000785
PG 10
WC Ophthalmology
SC Ophthalmology
GA CS6US
UT WOS:000362219000001
PM 26360227
ER
PT J
AU Manschreck, TC
Chun, J
Merrill, AM
Maher, BA
Boshes, RA
Glatt, SJ
Faraone, SV
Tsuang, MT
Seidman, LJ
AF Manschreck, T. C.
Chun, J.
Merrill, A. M.
Maher, B. A.
Boshes, R. A.
Glatt, S. J.
Faraone, S. V.
Tsuang, M. T.
Seidman, L. J.
TI Impaired motor performance in adolescents at familial high-risk for
schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Familial high-risk; Motor performance; Genetics;
Lateralization
ID NEUROLEPTIC-NAIVE; WORKING-MEMORY; GENETIC RISK; YOUNG-ADULTS; CHILDREN;
PSYCHOSIS; SYMPTOMS; METAANALYSIS; INDIVIDUALS; IMPAIRMENTS
AB Background: The Harvard Adolescent Family High Risk (FHR) Study examined multiple domains of function in young relatives of individuals diagnosed with schizophrenia to identify precursors of the illness. One such area is motor performance, which is deviant in people with schizophrenia and in children at risk for schizophrenia, usually offspring. The present study assessed accuracy of motor performance and degree of lateralization in FHR adolescents and young adults.
Methods: Subjects were 33 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 30 non-psychotic comparison subjects (NpC), ranging in age from 13 to 25 who were compared using a line-drawing task.
Results: FHR individuals exhibited less precise and coordinated line drawing but greater degree of lateralization than controls. Performance on the linedrawing task was correlated with degree of genetic loading, a possible predictor of higher risk for schizophrenia in the pedigree.
Conclusions: The observation of increased motor deviance and increased lateralization in FHR can be utilized in identification and initiation of the treatment in those at high risk in order to prevent or delay the full manifestation of this devastating condition. The use of a rigorously quantified measure is likely to add to the sensitivity of measuring motor performance, especially when impairments may be subtle. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Manschreck, T. C.; Chun, J.; Merrill, A. M.; Boshes, R. A.; Seidman, L. J.] Harvard Univ, Commonwealth Res Ctr, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA.
[Manschreck, T. C.; Chun, J.; Merrill, A. M.; Maher, B. A.; Boshes, R. A.] Harvard Univ, Lab Clin & Expt Psychopathol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA.
[Manschreck, T. C.; Chun, J.; Merrill, A. M.; Maher, B. A.; Boshes, R. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Glatt, S. J.] Med Genet Res Ctr, Psychiat Genet Epidemiol & Neurobiol Lab PsychGEN, Syracuse, NY USA.
[Glatt, S. J.; Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Glatt, S. J.; Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
[Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Genom, Dept Psychiat, Inst Genom Med, San Diego, CA 92103 USA.
[Seidman, L. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Dept Psychiat,Sch Med, Boston, MA 02115 USA.
[Seidman, L. J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Manschreck, TC (reprint author), Lab Clin & Expt Psychopathol, 49 Hillside St, Fall River, MA USA.
EM theo.manschreck@state.ma.us
OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982
FU Stanley Medical Research Institute; National Association for Research on
Schizophrenia and Depression (NARSAD); Mental Illness and Neuroscience
Discovery (MIND) Institute [MH-43518, MH-46318]; Commonwealth Research
Center of the Massachusetts Department of Mental Health
[SCDMH82101008006]
FX This study was funded by the following: Stanley Medical Research
Institute (LJS); National Association for Research on Schizophrenia and
Depression (NARSAD; LJS, MTT); Mental Illness and Neuroscience Discovery
(MIND) Institute (LJS); MH-43518 (MTT, LJS); MH-46318 (MTT); and The
Commonwealth Research Center of the Massachusetts Department of Mental
Health, SCDMH82101008006 (LJS, TCM). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the funding agencies.
NR 58
TC 3
Z9 3
U1 1
U2 2
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 OCT
PY 2015
VL 168
IS 1-2
BP 44
EP 49
DI 10.1016/j.schres.2015.06.013
PG 6
WC Psychiatry
SC Psychiatry
GA CS1LK
UT WOS:000361826400007
PM 26165939
ER
PT J
AU Kranz, TM
Goetz, RR
Walsh-Messinger, J
Goetz, D
Antonius, D
Dolgalev, I
Heguy, A
Seandel, M
Malaspina, D
Chao, MV
AF Kranz, Thorsten M.
Goetz, Ray R.
Walsh-Messinger, Julie
Goetz, Deborah
Antonius, Daniel
Dolgalev, Igor
Heguy, Adriana
Seandel, Marco
Malaspina, Dolores
Chao, Moses V.
TI Rare variants in the neurotrophin signaling pathway implicated in
schizophrenia risk
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Sporadic; De novo; ARMS; Kidins220; Rare variant;
Neurotrophin; Exome sequencing
ID DENDRITIC SPINE PATHOLOGY; MEMBRANE-SPANNING PROTEIN; NEGATIVE SYNDROME
SCALE; NERVE GROWTH-FACTOR; DE-NOVO MUTATIONS; ALZHEIMERS-DISEASE;
DEVELOPMENTAL DELAY; BIPOLAR DISORDER; MOOD DISORDERS; MESSENGER-RNA
AB Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Kranz, Thorsten M.; Chao, Moses V.] NYU, Skirball Inst Biomol Med, Dept Cell Biol, New York, NY 10016 USA.
[Kranz, Thorsten M.; Chao, Moses V.] NYU, Skirball Inst Biomol Med, Dept Physiol & Neurosci, New York, NY 10016 USA.
[Kranz, Thorsten M.; Chao, Moses V.] NYU, Skirball Inst Biomol Med, Dept Psychiat, New York, NY 10016 USA.
[Goetz, Ray R.] New York State Psychiat Inst & Hosp, Div Clin Phenomenol, New York, NY 10032 USA.
[Goetz, Ray R.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Walsh-Messinger, Julie] James J Peters VA Med Ctr, MIRECC, Bronx, NY 10468 USA.
[Walsh-Messinger, Julie] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Goetz, Deborah; Antonius, Daniel; Malaspina, Dolores] NYU, Dept Psychiat Social & Psychiat Initiat, New York, NY 10016 USA.
[Antonius, Daniel] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14215 USA.
[Dolgalev, Igor; Heguy, Adriana] NYU, Genome Technol Ctr, Langone Med Ctr, New York, NY 10016 USA.
[Seandel, Marco] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
RP Kranz, TM (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, 540 First Ave,Rm 5-15, New York, NY 10016 USA.
EM Thorsten.Kranz@nyumc.org
OI Dolgalev, Igor/0000-0003-4451-126X; Chao, Moses/0000-0002-6969-3744
FU National Institutes of Health [NS21072, MH086651, RC1-MH088843,
5K24MH001699]; NYU CTSI [UL1TR000038]
FX This work was supported in part by the National Institutes of Health
Grants NS21072 (MVC), MH086651 (MVC), RC1-MH088843 (DM), 5K24MH001699
(DM) and NYU CTSI UL1TR000038 (DM).
NR 67
TC 6
Z9 6
U1 2
U2 6
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 OCT
PY 2015
VL 168
IS 1-2
BP 421
EP 428
DI 10.1016/j.schres.2015.07.002
PG 8
WC Psychiatry
SC Psychiatry
GA CS1LK
UT WOS:000361826400060
PM 26215504
ER
PT J
AU Tabak, NT
Horan, WP
Green, MF
AF Tabak, Naomi T.
Horan, William P.
Green, Michael F.
TI Mindfulness in schizophrenia: Associations with self-reported
motivation, emotion regulation, dysfunctional attitudes, and negative
symptoms
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Mindfulness; Motivation; Emotion regulation; Cognitive reappraisal;
Dysfunctional attitudes; Defeatist beliefs
ID RANDOMIZED CONTROLLED-TRIAL; COMMITMENT THERAPY; BEHAVIORAL ACTIVATION;
INHIBITION SYSTEMS; COGNITIVE THERAPY; MEDITATION; ACCEPTANCE;
PSYCHOSIS; ASYMMETRY; DYSREGULATION
AB Mindfulness-based interventions are gaining empirical support as alternative or adjunctive treatments for a variety of mental health conditions, including anxiety, depression, and substance use disorders. Emerging evidence now suggests that mindfulness-based treatments may also improve clinical features of schizophrenia, including negative symptoms. However, no research has examined the construct of mindfulness and its correlates in schizophrenia. In this study, we examined self-reported mindfulness in patients (n = 35) and controls (n = 25) using the Five-Facet Mindfulness Questionnaire. We examined correlations among mindfulness, negative symptoms, and psychological constructs associated with negative symptoms and adaptive functioning, including motivation, emotion regulation, and dysfunctional attitudes. As hypothesized, patients endorsed lower levels of mindfulness than controls. In patients, mindfulness was unrelated to negative symptoms, but it was associated with more adaptive emotion regulation (greater reappraisal) and beliefs (lower dysfunctional attitudes). Some facets of mindfulness were also associated with self-reported motivation (behavioral activation and inhibition). These patterns of correlations were similar in patients and controls. Findings from this initial study suggest that schizophrenia patients may benefit from mindfulness-based interventions because they (a) have lower self-reported mindfulness than controls and (b) demonstrate strong relationships between mindfulness and psychological constructs related to adaptive functioning. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Tabak, Naomi T.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Tabak, Naomi T.; Horan, William P.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
RP Tabak, NT (reprint author), Univ Calif Los Angeles, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM ntabak@ucla.edu
FU Veterans Affairs Merit grant; NIMH [MH095878]; NIMH training grant in
Cognitive and Affective Dysfunctions in the Psychoses at the University
of California, Los Angeles [T32MH09668]
FX Funding for the current study was provided by a Veterans Affairs Merit
grant (Dr. Horan) and NIMH grant MH095878 (Dr. Green). A postdoctoral
fellowship for Dr. Tabak was supported by an NIMH training grant in
Cognitive and Affective Dysfunctions in the Psychoses at the University
of California, Los Angeles (T32MH09668).
NR 48
TC 3
Z9 3
U1 5
U2 37
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 OCT
PY 2015
VL 168
IS 1-2
BP 537
EP 542
DI 10.1016/j.schres.2015.07.030
PG 6
WC Psychiatry
SC Psychiatry
GA CS1LK
UT WOS:000361826400076
PM 26232242
ER
PT J
AU Becker, MA
Fitz-Patrick, D
Choi, HK
Dalbeth, N
Storgard, C
Cravets, M
Baumgartner, S
AF Becker, Michael A.
Fitz-Patrick, David
Choi, Hyon K.
Dalbeth, Nicola
Storgard, Chris
Cravets, Matt
Baumgartner, Scott
TI An open-label, 6-month study of allopurinol safety in gout: The LASSO
study
SO SEMINARS IN ARTHRITIS AND RHEUMATISM
LA English
DT Review
DE Allopurinol; Dose titration; Gout; Hyperuricemia; Open-label study;
Serum uric acid
ID URATE-LOWERING THERAPIES; SERUM URATE; RENAL-FUNCTION; DOSE ASPIRIN;
HYPERURICEMIA; FEBUXOSTAT; MANAGEMENT; ADHERENCE; ARTHRITIS;
EPIDEMIOLOGY
AB Objectives: Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses >300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses.
Methods: Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and >= 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0 mg/dl.. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency.
Results: Of 1735 patients enrolled, 1732 received >= 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the <300-, 300-, and >300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0 mg/cIL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 483% in dosing categories <300, 300, and >300 mg, respectively.
Conclusions: This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA. 0 2015 The Authors. Published by Elsevier HS Journals, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgflicenses/by-nc-nd/4.0/).
C1 [Becker, Michael A.] Univ Chicago Med, Dept Med, Chicago, IL 60637 USA.
[Fitz-Patrick, David] East West Med Res Inst, Honolulu, HI USA.
[Choi, Hyon K.] Harvard Univ, Sch Med, Boston, MA USA.
[Choi, Hyon K.] Massachusetts Gen Hosp, Gout & Crystal Arthropathy Ctr, Boston, MA 02114 USA.
[Dalbeth, Nicola] Univ Auckland, Dept Med, Auckland, New Zealand.
[Storgard, Chris] Ardea Biosci Inc, Clin Res & Dev, San Diego, CA USA.
[Cravets, Matt] Ardea Biosci Inc, Biostat, San Diego, CA USA.
[Baumgartner, Scott] Ardea Biosci Inc, Med Affairs, San Diego, CA USA.
RP Becker, MA (reprint author), Univ Chicago Med, Dept Med, MC0930,5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mbecker@medicine.bsd.uchicago.edu
FU Ardea Biosciences, Inc., a member of the AstraZeneca Group; AstraZeneca
FX This clinical study was funded by Ardea Biosciences, Inc., a member of
the AstraZeneca Group. The study sponsor had a role in the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; and review and approval of the article.
Editorial support for this article was provided by Bill Wolvey of
PAREXEL, which was funded by AstraZeneca.
NR 31
TC 8
Z9 8
U1 2
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0049-0172
EI 1532-866X
J9 SEMIN ARTHRITIS RHEU
JI Semin. Arthritis Rheum.
PD OCT
PY 2015
VL 45
IS 2
BP 174
EP 183
DI 10.1016/j.semarthrit.2015.05.005
PG 10
WC Rheumatology
SC Rheumatology
GA CS5ZA
UT WOS:000362155600008
PM 26190562
ER
PT J
AU Avina-Zubieta, JA
Vostretsova, K
De Vera, MA
Sayre, EC
Choi, HK
AF Avina-Zubieta, J. Antonio
Vostretsova, Kateryna
De Vera, Mary A.
Sayre, Eric C.
Choi, Hyon K.
TI The risk of pulmonary embolism and deep venous thrombosis in systemic
lupus erythematosus: A general population-based study
SO SEMINARS IN ARTHRITIS AND RHEUMATISM
LA English
DT Review
DE Cardiovascular disease; Systemic lupus erythematosus; Deep venous
thrombosis; Pulmonary embolism; Risk
ID ACUTE MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; ANTIPHOSPHOLIPID
ANTIBODIES; ADMINISTRATIVE DATA; VEIN THROMBOSIS; THROMBOEMBOLISM;
COHORT; DISEASE; GLUCOCORTICOIDS; SENSITIVITY
AB Objective: To estimate the future risk and time trends of newly diagnosed venous thromboembolism (VTE) in individuals with incident systemic lupus erythematosus (SLE) in the general population.
Methods: Using a population-based database that includes all residents of British Columbia, Canada we conducted a study cohort of all patients with incident SLE and up to 10 age-, sex-, and entry-time-matched individuals from the general population. We compared incidence rates of pulmonary embolism (PE), deep venous thrombosis (DVT), and VTE between the two groups according to SLE disease duration. We calculated hazards ratios (FIR), adjusting for confounders.
Results: Among 4863 individuals with SLE (86% female; mean age, 48.9 years), the incidence rates (IRS) of PE, DVT, and VTE were 2.58, 3.33, and 5.32 per 1000 person-years, respectively, whereas the corresponding rates in the comparison cohort were 0.67, 0.57, and 1.11 per 1000 person-years. Compared with non-SLE individuals, the multivariable HRs among SLE patients were 3.04 (95% CI: 2.08-4.45), 4.46 (95% Cl: 3.11-6.41), and 3.55 (95% CI: 2.69-4.69), respectively. The age-, sex-, and entry-time-matched HRs for PE, DVT, and VTE were highest during the first year after SLE diagnosis [13.57 (95% CI: 7.66-24.02), 11.13 (95% CI: 6.55-18.90), and 12.89 (95% Cl: 8.56-19.41), respectively].
Conclusion: These findings provide population-based evidence that patients with SLE have a substantially increased risk of VTE, especially in the first year after SLE diagnosis. Awareness and increased vigilance of this potentially fatal, but preventable, complication is recommended. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Avina-Zubieta, J. Antonio; De Vera, Mary A.; Sayre, Eric C.; Choi, Hyon K.] Univ British Columbia, Arthrit Res Canada, Dept Med, Div Rheumatol, Richmond, BC, Canada.
[Avina-Zubieta, J. Antonio] Univ British Columbia, Dept Med, Div Rheumatol, Vancouver, BC, Canada.
[Vostretsova, Kateryna] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
[De Vera, Mary A.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada.
[Choi, Hyon K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA.
RP Avina-Zubieta, JA (reprint author), Arthrit Res Canada, 5591 3 Rd, Richmond, BC V6X 2C7, Canada.
EM azubieta@arthritisresearch.ca
FU Canadian Arthritis Network, Toronto, ON, Canada [10-SRP-IJD-01]; British
Columbia Lupus Society, Vancouver, BC, Canada [10-SRP-IJD-01]; Canadian
Institutes for Health Research, Ottawa, ON, Canada [MOP 125960, THC
135235]
FX This study was funded by the Canadian Arthritis Network (Grant
10-SRP-IJD-01, Toronto, ON, Canada) and the British Columbia Lupus
Society (Grant: 10-SRP-IJD-01, Vancouver, BC, Canada) and the Canadian
Institutes for Health Research (Grants: MOP 125960 and THC 135235,
Ottawa, ON, Canada), Dr. Avina-Zubieta is the British Columbia Lupus
Society Research Scholar and a Michael Smith Foundation for Health
Research Scholar.
NR 47
TC 4
Z9 4
U1 0
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0049-0172
EI 1532-866X
J9 SEMIN ARTHRITIS RHEU
JI Semin. Arthritis Rheum.
PD OCT
PY 2015
VL 45
IS 2
BP 195
EP 201
DI 10.1016/j.semarthrit.2015.05.008
PG 7
WC Rheumatology
SC Rheumatology
GA CS5ZA
UT WOS:000362155600011
PM 26364556
ER
PT J
AU Aritake, S
Blackwell, T
Peters, KW
Rueschman, M
Mobley, D
Morrical, MG
Platt, SF
Dam, TTL
Redline, S
Winkelman, JW
AF Aritake, Sayaka
Blackwell, Terri
Peters, Katherine W.
Rueschman, Michael
Mobley, Daniel
Morrical, Michael G.
Platt, Samuel F.
Dam, Thuy-Tien L.
Redline, Susan
Winkelman, John W.
CA Osteoporotic Fractures Men MrOS
TI Prevalence and associations of respiratory-related leg movements: the
MrOS sleep study
SO SLEEP MEDICINE
LA English
DT Article
DE Leg movement; Obstructive sleep apnea; Respiratory-related events;
Cardiovascular disease; Hypertension
ID PERIODIC LIMB MOVEMENTS; TO-NIGHT VARIABILITY; OSTEOPOROTIC FRACTURES;
BLOOD-PRESSURE; OLDER MEN; APNEA; SCALE; HYPERTENSION; HYPOXEMIA;
AROUSALS
AB Objectives: Obstructive respiratory events often terminate with an associated respiratory-related leg movement (RRLM). Such leg movements are not scored as periodic leg movements (periodic limb movements during sleep, PLMS), although the criteria for distinguishing RRLM from PLMS differ between the American Academy of Sleep Medicine (AASM) and the World Association of Sleep Medicine (WASM)/International Restless Legs Syndrome Study Group (IRLSSG) scoring manuals. Such LMs may be clinically significant in patients with obstructive sleep apnea (OSA). The prevalence and correlation of RRLM in men with OSA were examined.
Methods: A case-control sample of 575 men was selected from all men with an apnea-hypopnea index (AHI, >= 3% desaturation criteria) >= 10 and good data from piezoelectric leg movement sensors at the first in-home sleep study in the MrOS cohort (mean age = 76.8 years). Sleep studies were rescored for RRLMs using five different RRLM definitions varying in both latency of leg movement onset from respiratory event termination and duration of the leg movement. The quartile of RRLM% (the number of RRLM/the number of hypopneas + apneas) was derived.
Results: The nonparametric densities of RRLM% were most influenced by alterations in the latency rather than the duration of the LM. The most liberal RRLM definition (latency 0-5 s, duration 0.5-10 s) led to a median RRLM% of 23.4 (interquartile range 12.41, 37.12) in this sample. The average AHI and arousal index increased as the quartile of RRLM% increased, as well as the prevalence of chronic obstructive pulmonary disease (COPD). The prevalence of those with a history of hypertension decreased as RRLM% increased. The non-Caucasian race was associated with lower RRLM%.
Conclusion: Within an elderly sample with moderate to severe OSA, piezoelectric-defined RRLM% is associated with a number of sleep-related and demographic factors. Further study of the optimal definition, predictors, and consequences of RRLM is warranted. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Aritake, Sayaka; Winkelman, John W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med,Dept Med, Boston, MA 02115 USA.
[Aritake, Sayaka] Japan Soc Promot Sci, Tokyo, Japan.
[Blackwell, Terri; Peters, Katherine W.] San Francisco Coordinating Ctr, Calif Pacific Med Ctr Res Inst, San Francisco, CA USA.
[Rueschman, Michael; Mobley, Daniel; Morrical, Michael G.; Platt, Samuel F.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
[Dam, Thuy-Tien L.] Columbia Univ, Dept Med, Div Geriatr Med & Aging, New York, NY USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA.
[Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM jwwinkelman@partners.org
FU National Institutes of Health; National Institute on Aging (NIA);
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS); National Center for Advancing Translational Sciences (NCATS);
NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01
AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01
AR066160, UL1 TR000128]; National Heart, Lung, and Blood Institute
(NHLBI) [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01
HL070841, R01 HL070837, R01 HL070838, R01 HL070839]
FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National
Institutes of Health funding. The following institutes provide support:
the National Institute on Aging (NIA), the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National
Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for
Medical Research under the following grant numbers: U01 AG027810, U01
AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01
AG042168, U01 AR066160, and UL1 TR000128. The National Heart, Lung, and
Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary
study "Outcomes of Sleep Disorders in Older Men" under the following
grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842,
R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.
NR 43
TC 3
Z9 3
U1 3
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD OCT
PY 2015
VL 16
IS 10
BP 1236
EP 1244
DI 10.1016/j.sleep.2015.06.012
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA CS5BQ
UT WOS:000362091100011
PM 26429752
ER
PT J
AU Gelaye, B
Kajeepeta, S
Zhong, QY
Borba, CPC
Rondon, MB
Sanchez, SE
Henderson, DC
Williams, MA
AF Gelaye, Bizu
Kajeepeta, Sandhya
Zhong, Qiu-Yue
Borba, Christina P. C.
Rondon, Marta B.
Sanchez, Sixto E.
Henderson, David C.
Williams, Michelle A.
TI Childhood abuse is associated with stress-related sleep disturbance and
poor sleep quality in pregnancy
SO SLEEP MEDICINE
LA English
DT Article
DE Childhood abuse; Sleep disturbance; Pregnancy; Stress; Life course
ID PATIENT HEALTH QUESTIONNAIRE; INTIMATE PARTNER VIOLENCE; SEXUAL-ABUSE;
PRIMARY INSOMNIA; PERUVIAN WOMEN; EXPERIENCES; DEPRESSION; SEVERITY;
VALIDITY; ADULTS
AB Objectives: Childhood abuse is associated with increased risks of adult psychiatric disorders and physical health conditions. Mounting evidence documents associations of childhood abuse with sleep disturbances in adulthood. However, to date, no study has evaluated associations of childhood abuse and sleep disturbances among pregnant women.
Methods: This cross-sectional study included 634 pregnant Peruvian women. To collect information regarding socio-demographic characteristics, history of childhood abuse, and complaints of sleep disturbances, face-to-face interviews were conducted with women in early pregnancy. Ford Insomnia Response to Stress Test (FIRST-S) and the Pittsburgh Sleep Quality Index (PSQI-S), translated from English to Spanish, were used to assess stress-related sleep disturbance and sleep quality, respectively. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CIs).
Results: Women who experienced any childhood abuse had a 1.65-fold increased odds of stress-related sleep disturbance (aOR = 1.65; 95% CI: 1.15-2.38) and 2.11-fold increased odds of poor sleep quality during early pregnancy (aOR = 2.11; 95% CI: 1.35-3.30) as compared with women who reported no abuse. Women who reported both physical and sexual abuse during childhood were more than twice as likely to suffer from stress-related sleep disturbance (aOR = 2.26; 95% CI: 1.44-3.53) and poor sleep quality (aOR = 2.43; 95% CI: 1.45-4.09) in comparison to women who reported no childhood abuse.
Conclusions: A history of childhood abuse is associated with increased odds of stress-related sleep disturbance and poor sleep quality during pregnancy. These findings, if replicated, should be used to inform the development of trauma-informed care for such sleep disturbances induced by childhood trauma. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Gelaye, Bizu; Kajeepeta, Sandhya; Zhong, Qiu-Yue; Henderson, David C.; Williams, Michelle A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Borba, Christina P. C.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Borba, Christina P. C.; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rondon, Marta B.] Cayetano Heredia Peruvian Univ, Dept Med, Lima, Peru.
[Sanchez, Sixto E.] Univ Peruana Ciencias Aplicadas, Lima, Peru.
[Sanchez, Sixto E.] Asociac Civil PROESA, Lima, Peru.
RP Gelaye, B (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,K505F, Boston, MA 02115 USA.
EM bgelaye@hsph.harvard.edu
OI Gelaye, Bizu/0000-0001-7934-548X
FU National Institutes of Health (NIH) [R01-HD-059835, T37-MD000149,
K01MH100428]
FX This study was supported by awards from the National Institutes of
Health (NIH; R01-HD-059835, T37-MD000149 and K01MH100428). The NIH had
no further role in study design; in the collection, analysis, and
interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication. The authors wish to thank
the dedicated staff members of Asociacion Civil Proyectos en Salud
(PROESA), Peru, and Instituto Materno Perinatal, Peru, for their expert
technical assistance with this study.
NR 50
TC 3
Z9 3
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD OCT
PY 2015
VL 16
IS 10
BP 1274
EP 1280
DI 10.1016/j.sleep.2015.07.004
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CS5BQ
UT WOS:000362091100016
PM 26429757
ER
PT J
AU Tsai, AC
Venkataramani, AS
AF Tsai, Alexander C.
Venkataramani, Atheendar S.
TI The causal effect of education on HIV stigma in Uganda: Evidence from a
natural experiment
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE AIDS/HIV; Behavioral interventions; Developing countries; International
health; Social determinants
ID UNIVERSAL PRIMARY-EDUCATION; SUB-SAHARAN AFRICA; ANTIDEPRESSANT
MEDICATION TREATMENT; REGRESSION DISCONTINUITY DESIGNS; AIDS-RELATED
STIGMA; SOUTH-AFRICA; RURAL UGANDA; CAPE-TOWN; ANTIRETROVIRAL THERAPY;
RANDOMIZED EXPERIMENTS
AB Rationale: HIV is highly stigmatized in sub-Saharan Africa. This is an important public health problem because HIV stigma has many adverse effects that threaten to undermine efforts to control the HIV epidemic.
Objective: The implementation of a universal primary education policy in Uganda in 1997 provided us with a natural experiment to test the hypothesis that education is causally related to HIV stigma.
Methods: For this analysis, we pooled publicly available, population-based data from the 2011 Uganda Demographic and Health Survey and the 2011 Uganda AIDS Indicator Survey. The primary outcomes of interest were negative attitudes toward persons with HIV, elicited using four questions about anticipated stigma and social distance.
Results: Standard least squares estimates suggested a statistically significant, negative association between years of schooling and HIV stigma (each P < 0.001, with t-statistics ranging from 4.9 to 14.7). We then used a natural experiment design, exploiting differences in birth cohort exposure to universal primary education as an instrumental variable. Participants who were <13 years old at the time of the policy change had 1.36 additional years of schooling compared to those who were >13 years old. Adjusting for linear age trends before and after the discontinuity, two-stage least squares estimates suggested no statistically significant causal effect of education on HIV stigma (P-values ranged from 0.21 to 0.69). Three of the four estimated regression coefficients were positive, and in all cases the lower confidence limits convincingly excluded the possibility of large negative effect sizes. These instrumental variables estimates have a causal interpretation and were not overturned by several robustness checks.
Conclusion: We conclude that, for young adults in Uganda, additional years of education in the formal schooling system driven by a universal primary school intervention have not had a causal effect on reducing negative attitudes toward persons with HIV. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Tsai, Alexander C.; Venkataramani, Atheendar S.] Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA.
[Tsai, Alexander C.; Venkataramani, Atheendar S.] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA.
[Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA.
RP Tsai, AC (reprint author), Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Suite 722, Boston, MA 02114 USA.
EM actsai@partners.org
OI Tsai, Alexander/0000-0001-6397-7917
FU U.S. National Institutes of Health [K23 MH096620]; Robert Wood Johnson
Health and Society Scholars Program
FX No specific funding was received for this study. ACT acknowledges salary
support from U.S. National Institutes of Health K23 MH096620 and the
Robert Wood Johnson Health and Society Scholars Program. No funders had
any role in the collection, analysis, or interpretation of data; in the
writing of the article; or in the decision to submit it for publication.
NR 106
TC 4
Z9 4
U1 3
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD OCT
PY 2015
VL 142
BP 37
EP 46
DI 10.1016/j.socscimed.2015.08.009
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CS4QL
UT WOS:000362060900005
PM 26282707
ER
PT J
AU Hoerster, KD
Millstein, RA
Hall, KS
Gray, KE
Reiber, GE
Nelson, KM
Saelens, BE
AF Hoerster, Katherine D.
Millstein, Rachel A.
Hall, Katherine S.
Gray, Kristen E.
Reiber, Gayle E.
Nelson, Karin M.
Saelens, Brian E.
TI Individual and contextual correlates of physical activity among a
clinical sample of United States Veterans
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Veterans; Physical activity; Neighborhood; Social support
ID OLDER-ADULTS; MULTIPLE IMPUTATION; NATIONAL SAMPLE; HEALTH-CARE; ODDS
RATIO; EXERCISE; OBESITY; ASSOCIATIONS; DISABILITY; LIFE
AB Rationale: Veterans, especially those using U.S. Department of Veterans Affairs (VA) healthcare, have poorer health than the general population. In addition, Veterans using VA services are more likely than non-VA users to be physically inactive. Little is known about physical activity correlates among Veterans. To identify targets for health promotion interventions, understanding barriers to and facilitators of physical activity in this population is critical.
Methods: This study examined individual-, social-, and perceived neighborhood-level associations of meeting weekly physical activity recommendations (150 min/week of combined leisure and transportation activity) based on the International Physical Activity Questionnaire (IPAQ) among N = 717 patients from VA Puget Sound, Seattle Division using a mailed survey sent 2012-2013 (response rate = 40%). Independent associations were identified with direct estimation of relative risks using generalized linear models (dichotomous outcome), and linear regression (continuous outcome), including variables associated in bivariate tests (p < .05).
Results: Most participants were male, Caucasian, and unemployed, and had an annual income <=$40,000. Over two-thirds (69.9%) reported meeting physical activity recommendations. Fewer days of limitations due to physical or mental health (Relative Risk (RR) = 0.99 per day; 95% Confidence Interval (CI) = 0.98, 0.99; p = .01), others doing physical activity with the Veteran (RR = 1.18; 95% Cl = 1.04, 133; p = .01), receiving ideas from others regarding physical activity (RR = 1.14; 95% Cl = 1.01, 1.29; p = .03) and better perceived neighborhood aesthetics (RR = 1.14; 95% Cl = 1.06, 1.24; p = .001) were associated with meeting physical activity recommendations. Findings were comparable for total weekly physical activity, but lower depression symptom severity was also associated with increased physical activity.
Conclusion: This study identified individual and contextual correlates of physical activity among VA-using Veterans. Targeting these factors will be important in promoting physical activity in order to address the disproportionate disease burden facing U.S. Veterans. Existing VA interventions targeting physical activity may need to be adapted to account for the influence of contextual factors. Published by Elsevier Ltd.
C1 [Hoerster, Katherine D.; Millstein, Rachel A.] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, Seattle, WA 98108 USA.
[Hoerster, Katherine D.; Saelens, Brian E.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Millstein, Rachel A.] San Diego State Univ, Univ Calif San Diego, Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA.
[Hall, Katherine S.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA.
[Hall, Katherine S.] Duke Univ, Dept Med, Durham, NC 27706 USA.
[Gray, Kristen E.; Reiber, Gayle E.; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Seattle Div, Hlth Serv Res & Dev, Seattle, WA 98108 USA.
[Gray, Kristen E.; Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Nelson, Karin M.] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA 98108 USA.
[Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Saelens, Brian E.] Seattle Childrens Res Inst, Seattle, WA USA.
RP Hoerster, KD (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, 1660 S Columbian Way S-116, Seattle, WA 98108 USA.
EM Katherine.Hoerster@va.gov
FU VA Puget Sound, Seattle Division Mental Illness Research Education and
Clinical Center; VA Puget Sound, Seattle Division Health Services
Research and Development Center of Excellence; VA Career Development
Awards [RRD 1IK2RX001316, HSRD CDA 12-263]; VA HSR&D Senior Research
Career Scientist Award [RCS 98-353]
FX We would like to thank Linda Guerrero, David Tice, and Marie Lutton for
their work on managing the survey mailing, Carol Malte for extracting VA
administrative data, and Jeff Rodenbaugh for his assistance with running
analyses. This material is the result of work supported by resources
from VA Puget Sound Healthcare System. Funding for the study was
provided by the VA Puget Sound, Seattle Division Mental Illness Research
Education and Clinical Center and the VA Puget Sound, Seattle Division
Health Services Research and Development Center of Excellence. Drs. Hall
and Hoerster are supported by VA Career Development Awards (RRD
1IK2RX001316 and HSR&D CDA 12-263, respectively). Dr. Reiber is funded
through a VA HSR&D Senior Research Career Scientist Award (RCS 98-353).
The funding sources had no involvement in study design; in the
collection, analysis and interpretation of data; in the writing of the
article; and in the decision to submit it for publication. The abstract
for this paper was presented at the 2015 Society of Behavioral Medicine
Annual Meeting. 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 the United States government.
NR 66
TC 3
Z9 3
U1 3
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD OCT
PY 2015
VL 142
BP 100
EP 108
DI 10.1016/j.socscimed.2015.07.034
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CS4QL
UT WOS:000362060900011
PM 26298646
ER
PT J
AU Gupta, MK
Teo, AKK
Rao, TN
Bhatt, S
Kleinridders, A
Shirakawa, J
Takatani, T
Hu, J
De Jesus, DF
Windmueller, R
Wagers, AJ
Kulkarni, RN
AF Gupta, Manoj K.
Teo, Adrian Kee Keong
Rao, Tata Nageswara
Bhatt, Shweta
Kleinridders, Andre
Shirakawa, Jun
Takatani, Tomozumi
Hu, Jiang
De Jesus, Dario F.
Windmueller, Rebecca
Wagers, Amy J.
Kulkarni, Rohit N.
TI Excessive Cellular Proliferation Negatively Impacts Reprogramming
Efficiency of Human Fibroblasts
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Reprogramming; Insulin signaling; Cell proliferation; Human pluripotency
ID PLURIPOTENT STEM-CELLS; SMALL-MOLECULE COMPOUNDS; SOMATIC-CELLS; DEFINED
FACTORS; INDUCTION; INHIBITORS; OCT4; PKM2
AB The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1101-1108
C1 [Gupta, Manoj K.; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F.; Windmueller, Rebecca; Wagers, Amy J.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA.
[Kleinridders, Andre] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
[Gupta, Manoj K.; Teo, Adrian Kee Keong; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F.; Windmueller, Rebecca; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
[Rao, Tata Nageswara; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA.
EM rohit.kulkarni@joslin.harvard.edu
RI Teo, Adrian/A-4009-2013;
OI Teo, Adrian/0000-0001-5901-7075; Shirakawa, Jun/0000-0002-0822-8750
FU NIH [5 P30 DK036836-27, R01 DK67536]; Juvenile Diabetes Research
Foundation Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft
[KL2399/1-1, KL2399/3-1]; AstraZeneca
FX We thank Dr. G. Mostoslavsky (Boston University) for the kind gift of
lentiviral plasmids and R. Martinez for technical assistance. We thank
Dr. C.R. Kahn (Joslin Diabetes Center) for allowing access to the
Seahorse instrument. The Joslin DRC iPS Core is supported by NIH Grant 5
P30 DK036836-27. A.K.K.T. is supported by a Juvenile Diabetes Research
Foundation Postdoctoral Fellowship. A.K. was supported by Deutsche
Forschungsgemeinschaft projects KL2399/1-1 and KL2399/3-1. R.N.K. is
supported by NIH Grant R01 DK67536 and a grant from AstraZeneca.
NR 31
TC 2
Z9 2
U1 1
U2 4
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 OCT
PY 2015
VL 4
IS 10
BP 1101
EP 1108
DI 10.5966/sctm.2014-0217
PG 8
WC Cell & Tissue Engineering
SC Cell Biology
GA CS5XO
UT WOS:000362151800005
PM 26253715
ER
PT J
AU Zhang, WT
Liu, J
Hu, XM
Li, PY
Leak, RK
Gao, YQ
Chen, J
AF Zhang, Wenting
Liu, Jia
Hu, Xiaoming
Li, Peiying
Leak, Rehana K.
Gao, Yanqin
Chen, Jun
TI n-3 Polyunsaturated Fatty Acids Reduce Neonatal Hypoxic/Ischemic Brain
Injury by Promoting Phosphatidylserine Formation and Akt Signaling
SO STROKE
LA English
DT Article
DE docosahexaenoic acids; eicosapentaenoic acid; neurons; omega-3 fatty
acids; phosphatidylserine synthase
ID FOCAL CEREBRAL-ISCHEMIA; DOCOSAHEXAENOIC ACID; NEURONAL APOPTOSIS;
CELL-SURVIVAL; ACTIVATION; OMEGA-3-FATTY-ACIDS; NEUROPROTECTION; STROKE;
DEATH; PHOSPHORYLATION
AB Background and Purpose Omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate neonatal hypoxic/ischemic (H/I) brain damage, but the underlying mechanisms are not fully understood. This study tested the hypothesis that n-3 PUFAs enhance Akt-dependent prosurvival signaling by promoting the biosynthesis of phosphatidylserine in neuronal cell membranes.
Methods Dietary n-3 PUFA supplementation was initiated on the second day of pregnancy in dams. H/I was induced in 7-day-old rat pups by ipsilateral common carotid artery occlusion followed by hypoxia (8% oxygen for 2.5 hours). Neurological outcomes, brain tissue loss, cell death, and the activation of signaling events were assessed after H/I. The effects of n-3 PUFAs (docosahexaenoic acid and eicosapentaenoic acid) on oxygen-glucose deprivation-induced cell death and the underlying mechanism of protection were also examined in primary cortical neuron cultures.
Resultsn-3 PUFAs reduced brain tissue loss at 7 days after H/I and improved neurological outcomes, whereas inhibition of PI3K/Akt signaling by LY294002 partially abrogated this neuroprotective effect. Docosahexaenoic acid/eicosapentaenoic acid also prevented ischemic neuronal death through the Akt prosurvival pathway in vitro. Furthermore, docosahexaenoic acid/eicosapentaenoic acid increased the production of phosphatidylserine, the major membrane-bound phospholipids, after ischemia both in vitro and in vivo. A reduction in membrane phosphatidylserine by shRNA-mediated knockdown of phosphatidylserine synthetase-1 attenuated Akt activation and neuronal survival after docosahexaenoic acid/eicosapentaenoic acid treatment in the oxygen-glucose deprivation model.
Conclusionsn-3 PUFAs robustly protect against H/I-induced brain damage in neonates by activating Akt prosurvival pathway in compromised neurons. In addition, n-3 PUFAs promote the formation of membrane phosphatidylserine, thereby promoting Akt activity and improving cellular survival.
C1 [Zhang, Wenting; Liu, Jia; Hu, Xiaoming; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China.
[Zhang, Wenting; Liu, Jia; Hu, Xiaoming; Li, Peiying; Gao, Yanqin; Chen, Jun] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200433, Peoples R China.
[Hu, Xiaoming; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA.
[Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA.
[Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA.
EM wtzhang@fudan.edu.cn; chenj2@upmc.edu
RI Gao, Yanqin/I-6790-2016
OI Gao, Yanqin/0000-0002-4915-9819
FU US National Institutes of Health [NS095671, NS36736, NS089534, NS45048,
NS092618]; US Department of Veterans Affairs [I01RX000420]; Chinese
Natural Science Foundation [81020108021, 81171149, 81371306, 81571285,
81228008, 81529002]; Shanghai Committee of Science and Technology
Support Program [14431907002]; American Heart Association
[13SDG14570025]; China Postdoctoral Science Foundation [20110490665];
Shanghai Postdoctoral Sustentation Fund [11R21410500]; Fudan University
[20520131150]; National Natural Science Foundation [81100978, 81471332,
81400956]; Science and Technology Commission of Shanghai Municipality
[13ZR1452200]
FX This project was supported by the US National Institutes of Health
grants NS095671, NS36736, NS089534, and NS45048 (to Dr Chen) and
NS092618 (to Dr Hu); the US Department of Veterans Affairs Research
Career Scientist Award and RR & D Merit Review I01RX000420 (to Dr Chen);
the Chinese Natural Science Foundation grants 81020108021, 81171149,
81371306, 81571285 (to Dr Gao), and 81228008, 81529002 (to Dr Chen); the
Shanghai Committee of Science and Technology Support Program 14431907002
(to Dr Gao); and the American Heart Association Scientist Development
grant 13SDG14570025 (to Dr Hu). Dr Zhang was supported by the China
Postdoctoral Science Foundation grants (No. 20110490665), the Shanghai
Postdoctoral Sustentation Fund (No. 11R21410500), the Young Teacher
Program of Fudan University (No. 20520131150), and National Natural
Science Foundation grants (No. 81100978 and No. 81471332). Dr Li is
supported by the Science and Technology Commission of Shanghai
Municipality (13ZR1452200) and National Natural Science Foundation grant
(No. 81400956).
NR 42
TC 3
Z9 4
U1 1
U2 10
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 OCT
PY 2015
VL 46
IS 10
BP 2943
EP 2950
DI 10.1161/STROKEAHA.115.010815
PG 8
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CS3TT
UT WOS:000361998600034
PM 26374481
ER
PT J
AU Fagenholz, PJ
Fuentes, E
Kaafarani, H
Cropano, C
King, D
de Moya, M
Butler, K
Velmahos, G
Chang, YC
Yeh, DD
AF Fagenholz, Peter J.
Fuentes, Eva
Kaafarani, Haytham
Cropano, Catrina
King, David
de Moya, Marc
Butler, Kathryn
Velmahos, George
Chang, Yuchiao
Yeh, D. Dante
TI Computed Tomography Is More Sensitive than Ultrasound for the Diagnosis
of Acute Cholecystitis
SO SURGICAL INFECTIONS
LA English
DT Article
ID CT EVALUATION; ACCURACY; DISEASE; PAIN
AB Background: Ultrasound (US) is the first-line diagnostic study for evaluating gallstone disease and is considered the test of choice for diagnosing acute cholecystitis (AC). However, computed tomography (CT) is used widely for the evaluation of abdominal pain and is often obtained as a first abdominal imaging test, particularly in cases in which typical clinical signs of AC are absent or other possible diagnoses are being considered. We hypothesized that CT is more sensitive than US for diagnosing AC. Methods: A prospective registry of all urgent cholecystectomies performed by our acute care surgery service between June 2008 and January 2014 was searched for cases of AC. The final diagnosis was based on operative findings and pathology. Patients were classified into two groups according to pre-operative radiographic work-up: US only or CT and US. The US group was compared with the CT and US group with respect to clinical and demographic characteristics. For patients undergoing both tests the sensitivity of the two tests was compared. Results: One hundred one patients with AC underwent both US and CT. Computed tomography was more sensitive than US for the diagnosis of AC (92% versus 79%, p=0.015). Ultrasound was more sensitive than CT for identification of cholelithiasis (87% versus 60%, p<0.01). Patients undergoing both tests prior to surgery were more likely to be older, male, have medical comorbidities, and lack typical clinical signs of AC. Conclusions: Computed tomography is more sensitive than US for the diagnosis of AC and is most often used in patients without typical clinical signs of AC.
C1 [Fagenholz, Peter J.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Crit Care, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Crit Care, Dept Surg, 165 Cambridge St,St 810, Boston, MA 02114 USA.
EM pfagenholz@mgh.harvard.edu
OI King, David/0000-0003-1028-1478
NR 12
TC 2
Z9 2
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-2964
EI 1557-8674
J9 SURG INFECT
JI Surg. Infect.
PD OCT 1
PY 2015
VL 16
IS 5
BP 509
EP 512
DI 10.1089/sur.2015.102
PG 4
WC Infectious Diseases; Surgery
SC Infectious Diseases; Surgery
GA CS6VT
UT WOS:000362221800005
PM 26375322
ER
PT J
AU Landow, SM
Oh, DH
Weinstock, MA
AF Landow, Shoshana M.
Oh, Dennis H.
Weinstock, Martin A.
TI Teledermatology Within the Veterans Health Administration, 2002-2014
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE telehealth; telemedicine; teledermatology; teleconsultation
AB Background:In order to increase veterans' access to dermatologic care, the Veterans Health Administration (VHA) has developed one of the largest teledermatology programs in the United States. This article describes the recent expansion of the VHA's teledermatology program after local and national initiatives and resource allocation.Materials and Methods:This report describes routinely collected VHA data.Results:For the first half of fiscal year 2014, the VHA recorded 31,926 teledermatology encounters, which represents 14% of all recorded teledermatology visits. Although every region in the VHA used teledermatology in the past year, four regions created 51% of the encounters. The use of store-and-forward telehealth (SFT), in which physicians view patient images after the patients were photographed, is increasing, whereas live video use is decreasing. Starting in 2012, encounters for patients in urban areas exceeded those in rural areas. The majority of patients were male veterans 60-79 years of age. Seventy-one percent of SFT consultations for the first half of 2014 were completed within 1 week.Conclusions:Although errors in and the evolution of coding encounters may distort results, the data show rapid growth of a telemedicine system that increases access to dermatology services for veterans. Most likely this growth reflects institutional commitment to telehealth via policy and resources.
C1 [Landow, Shoshana M.; Weinstock, Martin A.] Providence VA Med Ctr, Providence, RI 02908 USA.
[Landow, Shoshana M.; Weinstock, Martin A.] Brown Univ, Providence, RI 02912 USA.
[Oh, Dennis H.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Oh, Dennis H.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Landow, SM (reprint author), Providence VA Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA.
EM Shoshana.Landow@va.gov
NR 6
TC 6
Z9 6
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD OCT 1
PY 2015
VL 21
IS 10
BP 769
EP 773
DI 10.1089/tmj.2014.0225
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CS6LZ
UT WOS:000362191800002
PM 26083585
ER
PT J
AU Pang, YG
Tsigkou, O
Spencer, JA
Lin, CP
Neville, C
Grottkau, B
AF Pang, Yonggang
Tsigkou, Olga
Spencer, Joel A.
Lin, Charles P.
Neville, Craig
Grottkau, Brian
TI Analyzing Structure and Function of Vascularization in Engineered Bone
Tissue by Video-Rate Intravital Microscopy and 3D Image Processing
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; IN-VIVO; OPTICAL MICROSCOPY; ANGIOGENESIS;
SCAFFOLDS; TRACKING; DELIVERY; MARROW
AB Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (d,l-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad applicability for evaluating vascularization in other engineered tissues as well.
C1 [Pang, Yonggang; Neville, Craig; Grottkau, Brian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Tsigkou, Olga] Univ Manchester, Sch Mat, Manchester, Lancs, England.
[Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Grottkau, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA.
EM bgrottkau@partners.org
OI Tsigkou, Olga/0000-0002-5250-8610
NR 30
TC 1
Z9 1
U1 3
U2 10
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 OCT 1
PY 2015
VL 21
IS 10
BP 1025
EP 1031
DI 10.1089/ten.tec.2015.0091
PG 7
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA CS5AI
UT WOS:000362087300004
PM 25962617
ER
PT J
AU Desai, NR
Sabatine, MS
AF Desai, Nihar R.
Sabatine, Marc S.
TI PCSK9 inhibition in patients with hypercholesterolemia
SO TRENDS IN CARDIOVASCULAR MEDICINE
LA English
DT Article
ID SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN CHOLESTEROL; HETEROZYGOUS
FAMILIAL HYPERCHOLESTEROLEMIA; PLACEBO-CONTROLLED TRIAL; EVOLOCUMAB AMG
145; MONOCLONAL-ANTIBODY; LDL CHOLESTEROL; DOUBLE-BLIND;
RANDOMIZED-TRIAL; HEALTHY-VOLUNTEERS
AB Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in clinically challenging populations such as patients intolerant to statin therapy and those with familial hypercholesterolemia. To date, the clinical trials have not raised any significant safety concerns, with no appreciable excess of myalgias, elevation in aminotransferases, or other adverse events. Large, cardiovascular outcomes trials are underway to assess definitively the efficacy and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab), while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in the early-phase development. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Desai, Nihar R.] Yale Univ, Yale New Haven Hosp, Ctr Outcomes Res & Evaluat, Sect Cardiovasc Med,Sch Med, New Haven, CT USA.
[Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,TIMI Study Grp, Boston, MA 02115 USA.
RP Sabatine, MS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,TIMI Study Grp, Boston, MA 02115 USA.
EM msabatine@partners.org
NR 55
TC 12
Z9 12
U1 0
U2 14
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1050-1738
J9 TRENDS CARDIOVAS MED
JI Trends Cardiovasc. Med.
PD OCT
PY 2015
VL 25
IS 7
BP 567
EP 574
DI 10.1016/j.tcm.2015.01.009
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CS4NY
UT WOS:000362053700001
PM 25771732
ER
PT J
AU Huffman, JC
Celano, CM
AF Huffman, Jeff C.
Celano, Christopher M.
TI Depression in cardiovascular disease: From awareness to action
SO TRENDS IN CARDIOVASCULAR MEDICINE
LA English
DT Editorial Material
ID AMERICAN-HEART-ASSOCIATION; COLLABORATIVE CARE; TREATING DEPRESSION;
CARDIOLOGY; RECOMMENDATIONS; OUTCOMES; TRIAL
C1 [Huffman, Jeff C.; Celano, Christopher M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Huffman, Jeff C.; Celano, Christopher M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Blake 11, Boston, MA 02114 USA.
EM jhuffman@partners.org
FU NHLBI NIH HHS [R01HL113272, R01 HL113272]
NR 17
TC 1
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U1 0
U2 0
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1050-1738
J9 TRENDS CARDIOVAS MED
JI Trends Cardiovasc. Med.
PD OCT
PY 2015
VL 25
IS 7
BP 623
EP 624
DI 10.1016/j.tcm.2015.02.007
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CS4NY
UT WOS:000362053700010
PM 25910599
ER
PT J
AU Weinberg, I
Gu, XK
Giri, J
Kim, SE
Bacharach, MJ
Gray, BH
Katzen, BT
Matsumoto, AH
Chi, YW
Rogers, KR
Froehlich, J
Olin, JW
Gornik, HL
Jaff, MR
AF Weinberg, Ido
Gu, Xiaokui
Giri, Jay
Kim, Soo E.
Bacharach, Michael J.
Gray, Bruce H.
Katzen, Barry T.
Matsumoto, Alan H.
Chi, Yung-Wei
Rogers, Kevin R.
Froehlich, James
Olin, Jeffrey W.
Gornik, Heather L.
Jaff, Michael R.
TI Anti-platelet and anti-hypertension medication use in patients with
fibromuscular dysplasia: Results from the United States Registry for
Fibromuscular Dysplasia
SO VASCULAR MEDICINE
LA English
DT Article
DE anti-platelet; fibromuscular dysplasia; FMD; hypertension; medication
ID CLINICAL-PRACTICE GUIDELINES; ED AMERICAN-COLLEGE; ANTITHROMBOTIC
THERAPY; PREVENTION; THROMBOSIS
AB Fibromuscular dysplasia (FMD), a non-inflammatory arterial disease, may lead to renovascular hypertension (HTN) and cerebrovascular disease. Little is known about medication use in FMD. Clinical features and medication use were reviewed in a national FMD registry (12 US sites). Medication usage was assessed in raw and adjusted analyses. Covariates included demographic characteristics, co-morbid conditions and vascular bed involvement. A total of 874 subjects (93.6% female) were included in the analysis. Mean age was 55.6 +/- 13.1 years, 74.5% had HTN, 25.4% had a history of transient ischemic attack or stroke, and 7.5% had a history of coronary artery disease (CAD). Renal and cerebrovascular arteries were affected in 70.4% and 74.7%, respectively. Anti-platelet agents were administered to 72.9% of patients. In multivariate analyses, factors associated with a greater likelihood of anti-platelet agent use were older age (OR=1.02 per year, p=0.005), CAD (OR=3.76, p=0.015), cerebrovascular artery FMD involvement in isolation (OR=2.31, p<0.0001) or a history of previous intervention for FMD (OR=1.52, p=0.036). A greater number of anti-HTN medications was evident in isolated renal versus isolated cerebrovascular FMD patients. Factors associated with a greater number of anti-HTN medications were older age (OR=1.03 per year, p<0.0001), history of HTN (OR=24.04, p<0.0001), history of CAD (OR=2.71, p=0.0008) and a history of a previous therapeutic procedure (OR=1.72, p=0.001). In conclusion, in FMD, medication use varies based on vascular bed involvement. Isolated renal FMD patients receive more anti-HTN agents and there is greater anti-platelet agent use among patients with cerebrovascular FMD. Further studies correlating medication use in FMD with clinically meaningful patient outcomes are necessary.
C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Fireman Vasc Ctr, Boston, MA 02114 USA.
[Gu, Xiaokui] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA.
[Giri, Jay] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Kim, Soo E.; Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA.
[Kim, Soo E.; Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Bacharach, Michael J.] North Cent Heart Inst, Soux Falls, SD USA.
[Gray, Bruce H.] Sch Med, Sch Medicine, Greenville, SC USA.
[Katzen, Barry T.] Baptist Cardiac & Vasc Inst, Miami, FL USA.
[Matsumoto, Alan H.] Univ Virginia Hlth Syst, Div Vasc Intervent Radiol, Dept Radiol, Charlottesville, VA USA.
[Chi, Yung-Wei] Univ Calif Davis, Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA.
[Rogers, Kevin R.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA.
[Froehlich, James] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA.
[Olin, Jeffrey W.] Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA.
[Olin, Jeffrey W.] Mt Sinai Sch Med, Marie Jose & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA.
RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Fireman Vasc Ctr, 55 Fruit St,GB 800, Boston, MA 02114 USA.
EM iweinberg@partners.org
FU FMD Society of America
FX The United States Registry for FMD is funded by the FMD Society of
America.
NR 16
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Z9 2
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD OCT
PY 2015
VL 20
IS 5
BP 447
EP 453
DI 10.1177/1358863X15584982
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CS8PT
UT WOS:000362351000007
PM 25964292
ER
PT J
AU Jaff, MR
White, CJ
Hiatt, WR
Fowkes, GR
Dormandy, J
Razavi, M
Reekers, J
Norgren, L
AF Jaff, Michael R.
White, Christopher J.
Hiatt, William R.
Fowkes, Gerry R.
Dormandy, John
Razavi, Mahmood
Reekers, Jim
Norgren, Lars
CA TASC Steering Comm
TI An Update on Methods for Revascularization and Expansion of the TASC
Lesion Classification to Include Below-the-Knee Arteries: A Supplement
to the Inter-Society Consensus for the Management of Peripheral Arterial
Disease (TASC II)
SO VASCULAR MEDICINE
LA English
DT Article
DE angioplasty; arteries; claudication; critical limb ischemia; occlusion;
peripheral artery disease; revascularization; stenosis; stents; surgery
ID CRITICAL LIMB ISCHEMIA; AORTOILIAC OCCLUSIVE DISEASE; SUPERFICIAL
FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED
CONTROLLED-TRIAL; NITINOL STENT IMPLANTATION; DRUG-ELUTING STENTS;
BARE-METAL STENTS; EXTREMITY BYPASS-SURGERY; VEIN GRAFT FAILURE
AB The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.
C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[White, Christopher J.] Univ Queensland, Ochsner Clin Sch, Ochsner Clin Fdn, New Orleans, LA USA.
[Hiatt, William R.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA.
[Hiatt, William R.] CPC Clin Res, Aurora, CO USA.
[Fowkes, Gerry R.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Dormandy, John] St George Hosp, London, England.
[Razavi, Mahmood] St Joseph Hosp, Orange, CA USA.
[Reekers, Jim] Univ Hosp Amsterdam, Acad Med Ctr, Amsterdam, Netherlands.
[Norgren, Lars] Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden.
RP Norgren, L (reprint author), Orebro Univ Hosp, Dept Surg, Surg, SE-70185 Orebro, Sweden.
EM lars.norgren@regionorebrolan.se
FU VIVA Physicians; Aastrom Biosciences; Abbott Vascular; AnGes MG Inc;
Bayer Schering Pharma; Biomedix; Cook; ev3; Medtronic; Mitsubishi
Tanabe; Otsuka Pharmaceutical Co; Sanofi-Aventis; Toray Industries
FX The author(s) report receiving the following financial support for the
research, authorship, and/or publication of this article: VIVA
Physicians [a 501(c)(3) education and research multispecialty
organization] provided an unrestricted grant to the TASC organization.
The development of this TASC II Supplement was supported by unrestricted
educational grants awarded to Discovery London from (in alphabetical
order): Aastrom Biosciences, Abbott Vascular, AnGes MG Inc, Bayer
Schering Pharma, Biomedix, Cook, ev3, Medtronic, Mitsubishi Tanabe,
Otsuka Pharmaceutical Co, Sanofi-Aventis, and Toray Industries. The
companies did not participate in the discussions or in the preparation,
review, or approval of the document.
NR 91
TC 2
Z9 2
U1 3
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD OCT
PY 2015
VL 20
IS 5
BP 465
EP 478
DI 10.1177/1358863X15597877
PG 14
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CS8PT
UT WOS:000362351000010
ER
PT J
AU Prabhakar, HB
Kraeft, JJ
Schorge, JO
Scott, JA
Lee, SI
AF Prabhakar, Hima B.
Kraeft, Jessica J.
Schorge, John O.
Scott, James A.
Lee, Susanna I.
TI FDG PET-CT of gynecologic cancers: pearls and pitfalls
SO ABDOMINAL IMAGING
LA English
DT Article
DE PET-CT; PET image quality; Gynecologic cancer; Female pelvic imaging
ID POSITRON-EMISSION-TOMOGRAPHY; STAGE CERVICAL-CANCER; CORPUS LUTEAL CYST;
ENDOMETRIAL CANCER; F-18-FDG PET/CT; OVARIAN-CANCER; RADICAL
HYSTERECTOMY; RADIATION-THERAPY; NODE METASTASES; CONTRAST AGENTS
AB FDG PET-CT plays an important role in treatment planning and in prognosis assessment of gynecologic cancer patients. Detection of hypermetabolic tissue with FDG PET, when combined with the high spatial resolution of CT, results in improved cancer detection and localization not afforded by either modality independently. This article is a primer for a radiologist performing PET-CT on gynecologic cancer patients and includes the imaging protocol, normal pattern of FDG distribution in the female pelvis and the lymph node drainage pathways from the gynecologic organs. Clinically relevant imaging findings that should be included in the report are discussed. Case examples illustrate how potential errors in exam interpretation can be avoided by concurrently performing a high-quality diagnostic CT with the FDG PET scan and by analyzing both the stand-alone and the fusion images.
C1 [Prabhakar, Hima B.] Univ Penn, Univ Penn Hlth Syst, Penn Hosp, Dept Radiol, Philadelphia, PA 19104 USA.
[Kraeft, Jessica J.; Scott, James A.; Lee, Susanna I.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Scott, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Gynecol Oncol, Boston, MA USA.
[Kraeft, Jessica J.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Radiol, Boston, MA 02111 USA.
RP Prabhakar, HB (reprint author), Univ Penn, Univ Penn Hlth Syst, Penn Hosp, Dept Radiol, 800 Spruce St, Philadelphia, PA 19104 USA.
EM himaprab@gmail.com
NR 50
TC 2
Z9 2
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-8925
EI 1432-0509
J9 ABDOM IMAGING
JI Abdom. Imaging
PD OCT
PY 2015
VL 40
IS 7
BP 2472
EP 2485
DI 10.1007/s00261-015-0362-7
PG 14
WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
GA CS1OJ
UT WOS:000361835700042
PM 25680500
ER
PT J
AU Pedrelli, P
Nyer, M
Yeung, A
Zulauf, C
Wilens, T
AF Pedrelli, Paola
Nyer, Maren
Yeung, Albert
Zulauf, Courtney
Wilens, Timothy
TI College Students: Mental Health Problems and Treatment Considerations
SO ACADEMIC PSYCHIATRY
LA English
DT Article
DE College; Mental health; Treatment considerations
ID AGE-OF-ONSET; COMORBIDITY SURVEY REPLICATION; OBSESSIVE-COMPULSIVE
DISORDER; MAJOR DEPRESSIVE DISORDER; ADOLESCENT MARIJUANA USE; SUBSTANCE
USE DISORDERS; BIPOLAR-I DISORDER; BINGE-DRINKING;
PSYCHIATRIC-DISORDERS; SUICIDAL-BEHAVIOR
AB Attending college can be a stressful time for many students. In addition to coping with academic pressure, some students have to deal with the stressful tasks of separation and individuation from their family of origin while some may have to attend to numerous work and family responsibilities. In this context, many college students experience the first onset of mental health and substance use problems or an exacerbation of their symptoms. Given the uniqueness of college students, there is a need to outline critical issues to consider when working with this population. In this commentary, first, the prevalence of psychiatric and substance use problems in college students and the significance of assessing age of onset of current psychopathology are described. Then, the concerning persistent nature of mental health problems among college students and its implications are summarized. Finally, important aspects of treatment to consider when treating college students with mental health problems are outlined, such as the importance of including parents in the treatment, communicating with other providers, and employing of technology to increase adherence. It is concluded that, by becoming familiar with the unique problems characteristic of the developmental stage and environment college students are in, practitioners will be able to better serve them.
C1 [Pedrelli, Paola; Nyer, Maren; Yeung, Albert; Zulauf, Courtney; Wilens, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Pedrelli, P (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM ppedrelli@partners.org
FU NIH [K24 DA016264]; NIAAA [K23AA020064-012]; National Institute on Drug
Abuse (NIDA); Euthymics; Shire; Theravance; TRIS
FX This research was supported by NIH K24 DA016264 to Timothy Wilens and in
part by NIAAA K23AA020064-012 to Paola Pedrelli. Timothy Wilens
receives/d research support from or is/has been on the advisory board
for the following Pharmaceutical Companies: National Institute on Drug
Abuse (NIDA), Euthymics, Shire, Theravance, and TRIS. Dr. Timothy Wilens
is or has been a consultant for Euthymics, Major League Baseball, Minor
League Baseball, the National Football League, and Shire. Dr. Timothy
Wilens has a published book with Guilford Press: Straight Talk About
Psychiatric Medications for Kids. Drs. Pedrelli, Nyer, and Yeung as well
as Ms. Zulauf have no conflicts of interest to report.
NR 114
TC 3
Z9 3
U1 7
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1042-9670
EI 1545-7230
J9 ACAD PSYCHIATR
JI Acad. Psych.
PD OCT
PY 2015
VL 39
IS 5
BP 503
EP 511
DI 10.1007/s40596-014-0205-9
PG 9
WC Education & Educational Research; Psychiatry
SC Education & Educational Research; Psychiatry
GA CR8JA
UT WOS:000361596100003
PM 25142250
ER
PT J
AU Geller, BJ
Giugliano, RP
Braunwald, E
Murphy, SA
Hanyok, JJ
Jin, JQ
Mercuri, M
Antman, EM
Ruff, CT
AF Geller, Bram J.
Giugliano, Robert P.
Braunwald, Eugene
Murphy, Sabina A.
Hanyok, James J.
Jin, Jianqing
Mercuri, Michele
Antman, Elliott M.
Ruff, Christian T.
TI Systemic, noncerebral, arterial embolism in 21,105 patients with atrial
fibrillation randomized to edoxaban or warfarin: Results from the
Effective Anticoagulation With Factor Xa Next Generation in Atrial
Fibrillation-Thrombolysis in Myocardial Infarction Study 48 trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID STROKE PREVENTION; RISK-FACTORS; METAANALYSIS; THROMBOEMBOLISM;
XIMELAGATRAN; PREVALENCE; MANAGEMENT; EVENTS
AB Background Atrial fibrillation (AF) is a major risk factor for stroke and systemic embolism. Trials comparing warfarin with non-vitamin K oral anticoagulants (NOACs) have demonstrated that, when compared with warfarin, the NOACs are at least as effective in preventing stroke, although detailed analyses characterizing systemic embolic events (SEEs) are lacking.
Methods and results We performed a prespecified analysis in 21,105 patients with AF enrolled in the ENGAGE AF-TIMI 48 trial, which compared 2 once-daily regimens of edoxaban with warfarin for the prevention of stroke and SEE. Of 1,016 patients who met the primary end point, 67 (6.6%) experienced an SEE of which 13% were fatal. Of 73 total SEEs (including recurrent events), 85% involved the extremities, and 41% required a surgical or percutaneous intervention. There were 23 (0.12%/year) SEEs with warfarin versus 15 with higher dose edoxaban (0.08%/year; hazard ratio vs warfarin 0.65; 95% CI 0.34-1.24; P = .19) and 29 with lower dose edoxaban (0.15%/year; hazard ratio vs warfarin 1.24; 95% CI 0.72-2.15; P = .43). In a meta-analysis of 4 warfarin-controlled phase 3 AF trials, NOACs significantly reduced the risk of SEE by 37% (relative risk 0.63; 95% CI 0.43-0.91; P = .01).
Conclusion Although considerably less frequent than stroke, systemic embolism is associated with significant morbidity and mortality in patients with AF. Although the overall number of events was too small to show a significant difference in the risk of SEE between edoxaban and warfarin, a meta-analysis of all the NOAC trials demonstrates that NOACs significantly reduce the risk of SEE compared with warfarin.
C1 [Geller, Bram J.] Univ Penn Hlth Syst, Philadelphia, PA USA.
[Giugliano, Robert P.; Braunwald, Eugene; Murphy, Sabina A.; Antman, Elliott M.; Ruff, Christian T.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Giugliano, Robert P.; Braunwald, Eugene; Murphy, Sabina A.; Antman, Elliott M.; Ruff, Christian T.] Harvard Univ, Sch Med, Boston, MA USA.
[Hanyok, James J.; Jin, Jianqing; Mercuri, Michele] Daiichi Sankyo Pharma Dev, Edison, NJ USA.
RP Ruff, CT (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,First Floor, Boston, MA 02115 USA.
EM cruff@partners.org
FU Abbott; Amgen; AstraZeneca; Bayer Healthcare; Beckman Coulter; BG
Medicine; BRAHMS; Bristol-Myers Squibb; Buhlmann; Critical Diagnostics;
CV Therapeutics; Eli Lilly and Co; GlaxoSmithKline; Johnson Johnson;
Merck and Co; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical
Diagnostics; Pfizer; Randox; Roche Diagnostics; Sanofi-Aventis; Siemens;
Singulex; Janssen; Daiichi Sankyo; Merck; Portola; Sanofi; Medicines
Company; Menarini; Medscape; Bayer; Boehringer Ingelheim; Eisai;
Intarcia
FX In addition to study support provided by Daiichi Sankyo Pharma Division
for conducting the ENGAGE AF-TIMI 48 trial, the TIMI Study Group has
received research grant support from Abbott, Amgen, AstraZeneca, Bayer
Healthcare, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb,
Buhlmann, Critical Diagnostics, CV Therapeutics, Eli Lilly and Co,
GlaxoSmithKline, Johnson & Johnson, Merck and Co, Nanosphere, Novartis
Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche
Diagnostics, Sanofi-Aventis, Siemens, and Singulex. Dr Geller, none to
report. Dr Giugliano, reports receiving consulting fees from
Bristol-Myers Squibb, Janssen, Daiichi Sankyo, Merck, Pfizer, Portola,
and Sanofi; and grant support to his institution from Daiichi Sankyo,
Merck, Johnson & Johnson, Sanofi, and AstraZeneca. Dr Braunwald, reports
receiving consulting fees from The Medicines Company; lecture fees from
Menarini and Medscape; and grant support through his institution from
Daiichi Sankyo, AstraZeneca, Merck & Co, and GlaxoSmithKline. He also
reports serving as an unpaid consultant for Merck and Novartis and
providing uncompensated lectures for Merck & Co. Ms Murphy, reports
receiving grant support through her institution from Daiichi Sankyo. Dr
Hanyok, employed at Daiichi Sankyo. Dr Jin, employed at Daiichi Sankyo.
Dr Mercuri, employed at Daiichi Sankyo. Dr Antman, reports receiving
grant support through his institution from Daiichi Sankyo. Dr Ruff,
reports receiving consulting fees from Bayer, Daiichi Sankyo, Portola,
and Boehringer Ingelheim and grant support through his institution from
Daiichi Sankyo, Astra Zeneca, Eisai, and Intarcia. Submitted April 3,
2015; accepted June 21, 2015.
NR 25
TC 5
Z9 5
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 669
EP 674
DI 10.1016/j.ahj.2015.06.020
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200008
PM 26386790
ER
PT J
AU Bansilal, S
Bloomgarden, Z
Halperin, JL
Hellkamp, AS
Lokhnygina, Y
Patel, MR
Becker, RC
Breithardt, G
Hacke, W
Hankey, GJ
Nessel, CC
Singer, DE
Berkowitz, SD
Piccini, JP
Mahaffey, KW
Fox, KAA
AF Bansilal, Sameer
Bloomgarden, Zachary
Halperin, Jonathan L.
Hellkamp, Anne S.
Lokhnygina, Yuliya
Patel, Manesh R.
Becker, Richard C.
Breithardt, Guenter
Hacke, Werner
Hankey, Graeme J.
Nessel, Christopher C.
Singer, Daniel E.
Berkowitz, Scott D.
Piccini, Jonathan P.
Mahaffey, Kenneth W.
Fox, Keith A. A.
CA ROCKET AF Steering Committee
TI Efficacy and safety of rivaroxaban in patients with diabetes and
nonvalvular atrial fibrillation: The Rivaroxaban Once-daily, Oral,
Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for
Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET
AF Trial)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID RISK-FACTORS; MELLITUS; THERAPY; PREDICTORS; WARFARIN
AB Background The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial.
Methods We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding.
Results The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS(2) score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients.
Conclusions and Relevance The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.
C1 [Bansilal, Sameer; Bloomgarden, Zachary; Halperin, Jonathan L.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Breithardt, Guenter] Univ Hosp Munster, Div Electrophysiol, Dept Cardiovasc Med, Munster, Germany.
[Hacke, Werner] Heidelberg Univ, Heidelberg, Germany.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia.
[Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, 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.
RP Halperin, JL (reprint author), Mt Sinai Med Ctr, Icahn Sch Med Mt Sinai, Cardiovasc Inst, Box 1030,Fifth Ave & 100th St, New York, NY 10029 USA.
EM jonathan.halperin@mssm.edu
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
FU AstraZeneca; Astra Zeneca; Janssen; NovoNordisk; Merck; Amgen; Novartis;
Bayer AG HealthCare; Biotronik; Boehringer Ingelheim; Boston Scientific;
Daiichi Sankyo; Johnson Johnson; Medtronic; Ortho-McNeil-Janssen
Pharmaceuticals; Pfizer; Sanofi Aventis; Portola; Bayer; Medscape; ARCA
Biopharma; GE Healthcare; Janssen Scientific; ResMed; Sanofi-Aventis;
Johnson Johnson/Bayer; Eli Lilly
FX Bansilal: consulting fees from AstraZeneca; institutional research
grants from AstraZeneca. Bloomgarden: consulting fees from Astra Zeneca,
Janssen, NovoNordisk, Merck, Amgen, and Novartis; speaker's bureau for
Astra Zeneca, Janssen, NovoNordisk, and Merck; and ownership interest in
Baxter International, CVS Caremark, Roche Holdings, St Jude Medical, and
Novartis. Halperin: consulting fees from AstraZeneca, Bayer AG
HealthCare, Biotronik, Boehringer Ingelheim, Boston Scientific, Daiichi
Sankyo, Janssen, Johnson & Johnson, Medtronic, Ortho-McNeil-Janssen
Pharmaceuticals, Pfizer, and Sanofi Aventis. Hellkamp and Lokhnygina:
nothing to report. Patel: consultant/advisory board for Bayer, Janssen,
AstraZeneca, and Genzyme; institutional research grant for Johnson &
Johnson and AstraZeneca. Becker: consulting fees/honoraria from Portola,
Daiichi-Sankyo, Bristol-Myers Squibb, and Boehringer Ingelheim; research
grants from AstraZeneca and Johnson & Johnson. Breithardt: honoraria
from Bayer HealthCare and BMS/Pfizer; consultant/advisory board for
Bayer HealthCare, BMS/Pfizer, and Sanofi Aventis. Hacke: consulting fees
from Boehringer Ingelheim, Bayer HealthCare, and Daiichi Sankyo;
research grants from Boehringer Ingelheim. Hankey: honoraria/consulting
fees from Bayer and Medscape (theheart.org). Nessel: employee of Janssen
Research & Development. Singer: consulting/advisory board for Bayer
HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo,
Johnson & Johnson, Merck, and Pfizer; research grants from Bristol-Myers
Squibb and Johnson & Johnson. Berkowitz: employee of Bayer HealthCare
Pharmaceuticals. Piccini: research grants from ARCA Biopharma, Boston
Scientific, GE Healthcare, Janssen Scientific, Johnson & Johnson, and
ResMed; consultant/advisory boards for ChanRx, Johnson & Johnson, and
Spectranetics. Mahaffey: full disclosures prior to August 1, 2013,
available at www.dcri.org;disclosures after August 1, 2013, available at
http://med.stanford.edu/profiles/kenneth_mahaffey. Fox: consulting
fees/honoraria from Boehringer Ingelheim, Sanofi-Aventis, Astra Zeneca,
Johnson & Johnson/Bayer, and Janssen; research grants from Eli Lilly.
NR 16
TC 5
Z9 6
U1 2
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 675
EP +
DI 10.1016/j.ahj.2015.07.006
PG 16
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200009
PM 26386791
ER
PT J
AU Wang, TY
Henry, TD
Mccoy, LA
Berger, PB
Cohen, DJ
Effron, MB
Zettler, M
Baker, BA
Messenger, JC
Peterson, ED
AF Wang, Tracy Y.
Henry, Timothy D.
Mccoy, Lisa A.
Berger, Peter B.
Cohen, David J.
Effron, Mark B.
Zettler, Marjorie
Baker, Brian A.
Messenger, John C.
Peterson, Eric D.
TI Contemporary use of platelet function and pharmacogenomic
testingamongpatients with acute myocardial infarction undergoing
percutaneous coronary intervention in the United States
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ASSOCIATION TASK-FORCE; RANDOMIZED-TRIAL; CARDIOVASCULAR-ANGIOGRAPHY;
PRACTICE GUIDELINES; CLOPIDOGREL; REACTIVITY; MANAGEMENT; PRASUGREL;
THERAPY; SOCIETY
AB Background Although platelet function and pharmacogenomic testing have been studied in clinical trials, their adoption into contemporary practice is unknown.
Methods We studied patterns of platelet function and pharmacogenomic testing among 10,048 patients with acute myocardial infarction treated with percutaneous coronary intervention at 226 US hospitals in the TRANSLATE-ACS observational study between April 2010 and October 2012, excluding those receiving research protocol-mandated testing. Inverse probability-weighted propensity adjustment was used to compare 1-year bleeding and major adverse cardiac event risks between patients with and without testing.
Results Overall, 337 (3.4%) patients underwent predischarge platelet function testing, whereas 85 (0.9%) underwent pharmacogenomic testing; 82% and 93% of hospitals never performed any platelet function or pharmacogenomic testing, respectively. Patients undergoing testing were more likely to be on an adenosine diphosphate receptor inhibitor preadmission or to have percutaneous coronary intervention of a previously treated lesion. Tested patients were more likely than nontested patients to be switched from clopidogrel to prasugrel/ticagrelor (25.7% vs 9.7%, P < .001) and were more likely to be on prasugrel/ticagrelor 6 months postdischarge (33.8% vs 25.1%, P < .001). No significant differences in 1-year bleeding and major adverse cardiac event risks were observed between tested and nontested patients (adjusted hazard ratios 1.06 [95% CI 0.68-1.65] and 1.21 [95% CI 0.94-1.54], respectively).
Conclusions Platelet function and pharmacogenomic testing are rarely performed in contemporary myocardial infarction patients in the United States. When tested, patients were more likely to be treated with higher-potency adenosine diphosphate receptor inhibitors, yet no significant differences in longitudinal outcomes were observed.
C1 [Wang, Tracy Y.; Mccoy, Lisa A.; Berger, Peter B.; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Henry, Timothy D.] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA.
[Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA.
[Effron, Mark B.; Zettler, Marjorie] Lilly USA LLC, Indianapolis, IN USA.
[Baker, Brian A.] Daiichi Sankyo Inc, Parsippany, NJ USA.
[Messenger, John C.] Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Wang, TY (reprint author), Duke Clin Res Inst, Durham, NC 27705 USA.
EM tracy.wang@duke.edu
RI Effron, Mark/P-9300-2015
FU Daiichi Sankyo, Inc; Lilly USA
FX The TRANSLATE-ACS study (NCT01088503) is sponsored by Daiichi Sankyo,
Inc, and Lilly USA. The Duke Clinical Research Institute is the
coordinating center for this study, which represents a collaborative
effort with the American College of Cardiology.
NR 18
TC 2
Z9 2
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 706
EP 714
DI 10.1016/j.ahj.2015.06.021
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200012
PM 26386794
ER
PT J
AU Lee, YH
Armstrong, EJ
Kim, G
Oh, J
Kang, SM
Lee, BW
Ahn, CW
Cha, BS
Lee, HC
Mantzoros, CS
Kang, ES
AF Lee, Yong-ho
Armstrong, Ehrin J.
Kim, Gyuri
Oh, Jaewon
Kang, Seok-Min
Lee, Byung-Wan
Ahn, Chul Woo
Cha, Bong Soo
Lee, Hyun Chul
Mantzoros, Christos S.
Kang, Eun Seok
TI Undiagnosed diabetes is prevalent in younger adults and associated with
a higher risk cardiometabolic profile compared to diagnosed diabetes
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; FASTING
GLUCOSE; UNITED-STATES; US ADULTS; CARDIOVASCULAR-DISEASE;
NATIONAL-HEALTH; POST-CHALLENGE; ARTERY-DISEASE; MELLITUS
AB Background A substantial percentage of patients have undiagnosed diabetes. We investigated the demographic characteristics and cardiometabolic profiles of subjects with undiagnosed diabetes.
Methods A cross-sectional study with nationally representative samples of 25490 subjects aged >= 20 years from the KHNANES 2008 to 2011, which applied a complex, multistage, probability proportional to size sampling design. Subjects were categorized as having normal glucose (n = 16880), impaired fasting glucose (n = 5771), undiagnosed diabetes (n = 713), or diagnosed diabetes (n = 2126). Hyper low-density lipoprotein cholesterolemia was individually evaluated by the 2004 Adult Treatment Panel III guidelines and predicted risk of cardiovascular disease was estimated from the Framingham model.
Results Among overall subjects with diabetes, the prevalence of undiagnosed diabetes was markedly increased in younger adults compared to older adults (49% in diabetic subjects <50 years vs 23% in diabetic subjects >= 50 years, P < .001), suggesting significant discrepancies in age-based screening. Patients with undiagnosed diabetes were also more likely to have undiagnosed or uncontrolled hypertension and hyper-low-density lipoprotein cholesterolemia. Individuals with undiagnosed diabetes had a significantly higher predicted 10-year Framingham cardiovascular disease risk than those with diagnosed diabetes (11% vs 8% in <50 years, 33% vs 30% in >= 50 years; both P < .001). Patients with undiagnosed diabetes were also more likely to have multiple cardiovascular risk factors including obesity, smoking and uncontrolled hypertension.
Conclusions People with undiagnosed diabetes have a higher predicted risk for cardiovascular disease compared to those with diagnosed diabetes. Intensive screening for diabetes in younger adults should be stressed in public healthcare to reduce the burden of modifiable cardiometabolic risk among individuals with undiagnosed diabetes.
C1 [Lee, Yong-ho; Kim, Gyuri; Lee, Byung-Wan; Ahn, Chul Woo; Cha, Bong Soo; Lee, Hyun Chul; Kang, Eun Seok] Yonsei Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Seoul 120752, South Korea.
[Armstrong, Ehrin J.] Univ Colorado, Sch Med, Div Cardiol, Denver, CO USA.
[Oh, Jaewon; Kang, Seok-Min] Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Div Cardiol, Seoul 120752, South Korea.
[Oh, Jaewon; Kang, Seok-Min] Yonsei Univ, Coll Med, Cardiovasc Res Inst, Seoul 120752, South Korea.
[Lee, Byung-Wan; Ahn, Chul Woo; Cha, Bong Soo; Lee, Hyun Chul; Kang, Eun Seok] Yonsei Univ, Coll Med, Inst Endocrine Res, Seoul 120752, South Korea.
[Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA USA.
RP Kang, ES (reprint author), Yonsei Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab, 50-1 Yonsei Ro, Seoul 120752, South Korea.
EM edgo@yuhs.ac
NR 39
TC 2
Z9 2
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 760
EP +
DI 10.1016/j.ahj.2015.07.024
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200018
PM 26386800
ER
PT J
AU Alonso, A
Bahnson, JL
Gaussoin, SA
Bertoni, AG
Johnson, KC
Lewis, CE
Vetter, M
Mantzoros, CS
Jeffery, RW
Soliman, EZ
AF Alonso, Alvaro
Bahnson, Judy L.
Gaussoin, Sarah A.
Bertoni, Alain G.
Johnson, Karen C.
Lewis, Cora E.
Vetter, Marion
Mantzoros, Christos S.
Jeffery, Robert W.
Soliman, Elsayed Z.
CA Look AHEAD Res Grp
TI Effect of an intensive lifestyle intervention on atrial fibrillation
risk in individuals with type 2 diabetes: The Look AHEAD randomized
trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID BODY-MASS INDEX; ATHEROSCLEROSIS RISK; CARDIORESPIRATORY FITNESS;
PHYSICAL-ACTIVITY; CLINICAL-TRIAL; FOLLOW-UP; COMMUNITIES; OBESITY;
HEALTH; EPIDEMIOLOGY
AB Background Obesity is associated with higher risk of atrial fibrillation (AF), but the impact of behavioral weight loss interventions on atrial fibrillation (AF) risk in persons with diabetes is unknown. We addressed this question in the Look AHEAD randomized trial.
Methods and results A total of 5,067 overweight or obese individuals 45 to 76 years old with type 2 diabetes without prevalent AF were randomized to either an intensive lifestyle intervention (ILI) designed to achieve and maintain weight loss through caloric reduction and increased physical activity or a diabetes support and education usual care group. Atrial fibrillation was ascertained from electrocardiograms at study examinations and hospitalization discharge summaries. Multivariable Cox models were used to estimate the intention-to-treat effect of the intervention adjusting for baseline covariates. During a mean follow-up of 9.0 years, 294 incident AF cases were identified. Rates of AF were comparable in the ILI and diabetes support and education groups (6.1 and 6.7 cases per 1,000 person-years, respectively, P = .42). The intervention did not affect AF incidence (multivariable hazard ratio [HR] 0.99, 95% CI 0.77-1.28). Similarly, neither weight loss nor improvement in physical fitness during the first year of the intervention was significantly associated with AF incidence: multivariable hazard ratio (95% CI) comparing top versus bottom quartile was 0.70 (0.41-1.18) for weight loss and 0.88 (0.55-1.43) for physical fitness improvement.
Conclusion In a large randomized trial of overweight and obese individuals with type 2 diabetes, an ILI that induced modest weight loss did not reduce the risk of developing AF.
C1 [Alonso, Alvaro; Jeffery, Robert W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Bahnson, Judy L.; Gaussoin, Sarah A.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Bertoni, Alain G.; Soliman, Elsayed Z.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
[Vetter, Marion] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA.
[Vetter, Marion] Bristol Myers Squib Inc, Philadelphia, PA USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA USA.
RP Alonso, A (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA.
EM alonso@umn.edu
RI Alonso, Alvaro/A-4917-2010
OI Alonso, Alvaro/0000-0002-2225-8323
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX The primary sponsor, the National Institute of Diabetes and Digestive
and Kidney Diseases, was represented on the Steering Committee and
played a part in design and management of the Look AHEAD trial. The
statistician (S.G.) had access to the raw data. Alvaro Alonso had full
access to all results. All authors shared the final responsibility to
submit for publication.
NR 33
TC 7
Z9 7
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 770
EP +
DI 10.1016/j.ahj.2015.07.026
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200019
PM 26386801
ER
PT J
AU Kini, V
McCarthy, FH
Rajaei, S
Epstein, AJ
Heidenreich, PA
Groeneveld, PW
AF Kini, Vinay
McCarthy, Fenton H.
Rajaei, Sheeva
Epstein, Andrew J.
Heidenreich, Paul A.
Groeneveld, Peter W.
TI Variation in use of echocardiography among veterans who use the Veterans
Health Administration vs Medicare
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID LIFE TREATMENT INTENSITY; APPROPRIATE USE CRITERIA; QUALITY-OF-CARE;
GEOGRAPHIC-VARIATION; UNITED-STATES; MYOCARDIAL-INFARCTION;
REGIONAL-VARIATIONS; HEART-FAILURE; RISK; BENEFICIARIES
AB Background Rapid growth in the provision of cardiac imaging tests has led to concerns about overuse. Little is known about the degree to which health care delivery system characteristics influence use and variation in echocardiography.
Methods We analyzed administrative claims of veterans with heart failure older than 65 years from 2007 to 2010 across 34 metropolitan service areas (MSAs). We compared overall rates and geographic variation in use of transthoracic echocardiography (TTE) between veterans who used the Veterans Health Administration (VA) and propensity-matched veterans who used Medicare. "Dual users" were excluded.
Results There were no significant differences in clinical characteristics ormortality between the propensity-matched cohorts (overall n = 30,404 veterans, mean age 76 years, mortality rate 52%). The Medicare cohort had a significantly higher overall rate of TTE use compared with the VA cohort (1.25 vs 0.38 TTEs per person-year, incidence rate ratio 2.89 [95% CI 2.80-3.00], both P < .001), but a similar coefficient of variation across MSAs (0.36 [95% CI 0.27-0.45] vs 0.48 [95% CI 0.37-0.59]). There was a moderate to strong correlation in variation at the MSA level between cohorts (Spearman r = 0.58, P < .001).
Conclusion Overall rates of TTE use were significantly higher in a Medicare cohort compared with a propensity scorematched VA cohort of veterans with heart failure living in urban areas, with similar relative degrees of geographic variation and moderate to strong regional correlation. Rates of TTE use may be strongly influenced by health care system characteristics, but local practice styles influence echocardiography rates irrespective of health system.
C1 [Kini, Vinay] Hosp Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Kini, Vinay; McCarthy, Fenton H.; Epstein, Andrew J.; Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[McCarthy, Fenton H.] Hosp Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
[Rajaei, Sheeva; Heidenreich, Paul A.] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
[Epstein, Andrew J.; Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ & Res Promot, Dept Vet Affairs, Philadelphia, PA USA.
[Epstein, Andrew J.; Groeneveld, Peter W.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
RP Kini, V (reprint author), Hosp Univ Penn, Cardiovasc Med, 3400 Spruce St,9021 Gates, Philadelphia, PA 19104 USA.
EM vinay.kini@uphs.upenn.edu
FU NHLBI NIH HHS [T32 HL007843]
NR 40
TC 1
Z9 1
U1 2
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 805
EP 811
DI 10.1016/j.ahj.2015.07.016
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200023
PM 26386805
ER
PT J
AU Patorno, E
Wang, SV
Schneeweiss, S
Liu, J
Bateman, BT
AF Patorno, Elisabetta
Wang, Shirley V.
Schneeweiss, Sebastian
Liu, Jun
Bateman, Brian T.
TI Patterns of beta-blocker initiation in patients undergoing intermediate
to high-risk noncardiac surgery
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; ASSOCIATION TASK-FORCE; PERIOPERATIVE
CARDIOVASCULAR EVALUATION; PRACTICE GUIDELINES; AMERICAN-COLLEGE;
MYOCARDIAL-INFARCTION; MULTICENTER TRIAL; VASCULAR-SURGERY;
ARTERY-DISEASE; CARDIAC RISK
AB Background Based on 2 small randomized controlled trials (RCTs) from the 1990s, beta-blockers were promoted to prevent perioperative cardiac events in patients undergoing noncardiac surgery. In 2008, a large RCT (POISE trial) showed an increased mortality risk associated with perioperative beta-blockade, raising concerns about an extensive beta-Blocker use.
Objectives The objective of the study is to examine patterns of beta-Blocker initiation among patients undergoing noncardiac elective surgery in the US.
Methods From a large, nationwide US health care insurer, we identified patients >= 18 years old who underwent moderate-to high-risk noncardiac elective surgery between 2003 and 2012 and initiated a beta-Blocker within 30 days before surgery. We evaluated temporal trends and assessed the impact of the POISE trial on perioperative beta-Blocker initiation. We also evaluated patient characteristics and examined the effect of temporal proximity to surgery on the likelihood of beta-Blocker initiation.
Results Of 499,752 patients undergoing surgery, 9,014 (18 per 1,000 patients) initiated a beta-Blocker. beta-Blocker initiation increased from 12 per 1,000 patients in 2003 to 23 before POISE, after which it decreased to 14 by December 2012 (P = .0001). beta-Blocker initiation remained relatively high among patients undergoing vascular surgery or with Revised Cardiac Risk Index score >= 2. Proximity to surgery was highly predictive of beta-Blocker initiation (odds ratio 3.34, 95% CI 3.17-3.51).
Conclusions After a period of a rapidly increasing trend, perioperative beta-Blocker initiation decreased sharply in the second half of 2008 and continued to decrease afterwards. beta-Blocker initiation remained relatively high in patients with Revised Cardiac Risk Index score >= 2 and in those undergoing major vascular surgery.
C1 [Patorno, Elisabetta; Wang, Shirley V.; Schneeweiss, Sebastian; Liu, Jun; Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02120 USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Patorno, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
EM epatorno@partners.org
RI Schneeweiss, Sebastian/C-2125-2013
FU Division of Pharmacoepidemiology and Pharmacoeconomics, Department of
Medicine, Brigham; Women's Hospital, Harvard Medical School, Boston, MA
FX This study was funded by the Division of Pharmacoepidemiology and
Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA.
NR 32
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 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2015
VL 170
IS 4
BP 812
EP +
DI 10.1016/j.ahj.2015.06.028
PG 15
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8BD
UT WOS:000361575200024
PM 26386806
ER
PT J
AU Carter, J
Tseng, LH
Zheng, G
Dudley, J
Illei, P
Gocke, CD
Eshleman, JR
Lin, MT
AF Carter, Jamal
Tseng, Li-Hui
Zheng, Gang
Dudley, Jonathan
Illei, Peter
Gocke, Christopher D.
Eshleman, James R.
Lin, Ming-Tseh
TI Non-p.V600E BRAF Mutations Are Common Using a More Sensitive and Broad
Detection Tool
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE BRAF; Lung cancer; Colorectal cancer; Melanoma; Next-generation
sequencing
ID CELL LUNG-CANCER; METASTATIC MELANOMA; COLORECTAL-CANCER; V600E
MUTATION; INHIBITOR VEMURAFENIB; CLINICAL VALIDATION;
MALIGNANT-MELANOMA; TUMOR CELLULARITY; IMPROVED SURVIVAL; OPEN-LABEL
AB Objectives: To assess the performance of a next-generation sequencing (NGS) platform for the clinical detection of BRAF mutations.
Methods: In this retrospective quality assessment of an NGS assay, we analyzed BRAF mutations within parts of exons 11 and 15 in 835 neoplastic tissues submitted to our molecular diagnostics laboratory.
Results: The NGS assays detected a BRAF mutation in 5.9% of lung adenocarcinomas, 13% of colorectal cancers, and 44% of melanomas. Mutant allele frequencies were less than 20% in 28% of 88 BRAF-mutated specimens. Two lymph node specimens with subcapsular or infiltrative metastasis showed 1% to 2% mutant alleles. There were 26 unique BRAF mutations in exons 11 and 15, including three novel mutations. Mutations were located outside codon 600 in 39% of BRAF-mutated tumors. Lung adenocarcinomas showed significantly higher non-p. V600E mutations (86%) than did colorectal cancers (23%) and melanomas (34%). The three most common BRAF mutations in lung cancers accounted for only 41% of the observed BRAF mutations (p.D594G [18%], p.V600E [14%], and p.G469A [9%]).
Conclusions: The NGS assay demonstrated a high analytic sensitivity and a broad reportable range for clinical detection of BRAF mutations. Elucidating the spectrum of non-p. V600E BRAF mutations in different malignancies is a first step toward understanding their clinical significance.
C1 [Carter, Jamal; Tseng, Li-Hui; Zheng, Gang; Dudley, Jonathan; Illei, Peter; Gocke, Christopher D.; Eshleman, James R.; Lin, Ming-Tseh] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Gocke, Christopher D.; Eshleman, James R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA.
[Tseng, Li-Hui] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei, Taiwan.
[Dudley, Jonathan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Lin, MT (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Pk SB202,600 North Wolfe St, Baltimore, MD 21287 USA.
EM mlin36@jhmi.edu
NR 54
TC 9
Z9 9
U1 0
U2 4
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 OCT
PY 2015
VL 144
IS 4
BP 620
EP 628
DI 10.1309/AJCP85ATMJOZOUDJ
PG 9
WC Pathology
SC Pathology
GA CR7XJ
UT WOS:000361565000011
PM 26386083
ER
PT J
AU Hagiwara, Y
Watase, H
Okamoto, H
Goto, T
Hasegawa, K
AF Hagiwara, Yusuke
Watase, Hiroko
Okamoto, Hiroshi
Goto, Tadahiro
Hasegawa, Kohei
CA Japanese Emergency Med Network
TI Prospective validation of the modified LEMON criteria to predict
difficult intubation in the ED
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID TRACHEAL INTUBATION; ENDOTRACHEAL INTUBATION; AIRWAY MANAGEMENT; SCORE;
GUIDELINES; OUTCOMES
AB Background: Evidence to predict difficult intubation remains scarce in the emergency department (ED) setting. A previously defined clinical decision rule, the modified LEMON criteria, may provide a reliable and reproducible means of identifying difficult intubations. We aimed to prospectively evaluate the external validity of the modified LEMON criteria in the EDs.
Methods: We conducted a 13-center prospective observational study, the second Japanese Emergency Airway Network study. We prospectively collected data on all patients undergoing intubations in the ED from February 2012 through September 2014. The primary outcomes were sensitivity, specificity, and predictive values of the modified LEMON criteria for predicting difficult intubation (>= 2 attempts by emergency attending physicians or anesthesiologists).
Results: The database recorded a total of 4034 encounters (capture rate, 96%) in the EDs. Of these, 3313 patients (84%) underwent the intubation attempt with a direct laryngoscope and 610 patients (16%) with a video laryngoscope. The proportion of difficult intubation was 5.4% (95% confidence interval [CI], 4.7%-6.2%) in the direct laryngoscope group and 7.4% (95% CI, 5.6%-9.7%) in the video laryngoscope group. The sensitivity was 85.7% (95% CI, 79.3%-90.4%) with direct laryngoscope and 94.9% (95% CI, 83.5%-98.6%) with video laryngoscope. The specificity was 47.6% (95% CI, 47.2%-47.9%) and 40.3% (95% CI, 39.4%-40.6%), respectively. The negative predictive value was 98.2% (95% CI, 97.5%-98.8%) and 99.0% (95% CI, 96.6%-99.7%), respectively.
Conclusions: In this multicenter prospective study, we found a high sensitivity and a negative predictive value of the modified LEMON criteria for predicting difficult intubation. The modified LEMON might assist ED providers in better identifying difficult intubations. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Emergency & Crit Care Med, Fuchu, Tokyo 1838561, Japan.
[Watase, Hiroko] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Okamoto, Hiroshi] Kurashiki Cent Hosp, Dept Emergency Med, Kurashiki, Okayama, Japan.
[Goto, Tadahiro; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Hagiwara, Y (reprint author), Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Emergency & Crit Care Med, 2-8-29 Musashidai, Fuchu, Tokyo 1838561, Japan.
EM yusukehagiwara-tky@umin.ac.jp; hiroko7@uw.edu;
hiroshi.okamota.1121@gmail.com; tadahirogoto@gmail.com;
khasegawa@partners.org
FU St Luke's Life Science Institute
FX This study was supported by a grant from St Luke's Life Science
Institute. The study sponsors have no involvement in the study design;
in the collection, analysis, and interpretation of data; in the writing
of the manuscript; and in the decision to submit the manuscript for
publication.
NR 21
TC 2
Z9 3
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0735-6757
EI 1532-8171
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD OCT
PY 2015
VL 33
IS 10
BP 1492
EP 1496
DI 10.1016/j.ajem.2015.06.038
PG 5
WC Emergency Medicine
SC Emergency Medicine
GA CS1PM
UT WOS:000361839300032
PM 26166379
ER
PT J
AU Fourman, LT
Fogelman, AG
AF Fourman, Lindsay T.
Fogelman, Amy G.
TI Lost in the Woods: Granulomatosis with Polyangiitis
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID WEGENERS-GRANULOMATOSIS; DIAGNOSIS
C1 [Fourman, Lindsay T.; Fogelman, Amy G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Fourman, LT (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
EM LindsayFourman@gmail.com
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 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD OCT
PY 2015
VL 128
IS 10
BP 1080
EP 1082
DI 10.1016/j.amjmed.2015.06.019
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR9DE
UT WOS:000361652600042
PM 26164563
ER
PT J
AU Melton, BL
Zillich, AJ
Russell, SA
Weiner, M
McManus, MS
Spina, JR
Russ, AL
AF Melton, Brittany L.
Zillich, Alan J.
Russell, Scott A.
Weiner, Michael
McManus, M. Sue
Spina, Jeffrey R.
Russ, Alissa L.
TI Reducing Prescribing Errors Through Creatinine Clearance Alert Redesign
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Electronic health records; Evaluation; Health information technology;
Patient safety; Renal disease
ID CLINICAL DECISION-SUPPORT; HUMAN-FACTORS PRINCIPLES; DRUG INTERACTION
ALERTS; PHYSICIAN ORDER ENTRY; RENAL-INSUFFICIENCY; SAFETY ALERTS;
SYSTEMS; DESIGN; EFFICIENCY; USABILITY
AB BACKGROUND: Literature has shown that computerized creatinine clearance alerts reduce errors during prescribing, and applying human factors principles may further reduce errors. Our objective was to apply human factors principles to creatinine clearance alert design and assess whether the redesigned alerts increase usability and reduce prescribing errors compared with the original alerts.
METHODS: Twenty Veterans Affairs (VA) outpatient providers (14 physicians, 2 nurse practitioners, and 4 clinical pharmacists) completed 2 usability sessions in a counterbalanced study to evaluate original and redesigned alerts. Each session consisted of fictional patient scenarios with 3 medications that warranted prescribing changes because of renal impairment, each associated with creatinine clearance alerts. Quantitative and qualitative data were collected to assess alert usability and the occurrence of prescribing errors.
RESULTS: There were 43% fewer prescribing errors with the redesigned alerts compared with the original alerts (P = .001). Compared with the original alerts, redesigned alerts significantly reduced prescribing errors for allopurinol and ibuprofen (85% vs 40% and 65% vs 25%, P = .012 and P = .008, respectively), but not for spironolactone (85% vs 65%). Nine providers (45%) voiced confusion about why the alert was appearing when they encountered the original alert design. When laboratory links were presented on the redesigned alert, laboratory information was accessed 3.5 times more frequently.
CONCLUSIONS: Although prescribing errors were high with both alert designs, the redesigned alerts significantly improved prescribing outcomes. This investigation provides some of the first evidence on how alerts may be designed to support safer prescribing for patients with renal impairment. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Melton, Brittany L.] Univ Kansas, Sch Pharm, Lawrence, KS 66045 USA.
[Zillich, Alan J.; Russell, Scott A.; Weiner, Michael; Russ, Alissa L.] Hlth Serv Res & Dev Serv CIN 13 416, Ctr Hlth Informat & Commun, Dept Vet Affairs, Vet Hlth Adm, Indianapolis, IN USA.
[Zillich, Alan J.; Weiner, Michael; Russ, Alissa L.] Regenstrief Inst Inc, Indianapolis, IN USA.
[Zillich, Alan J.; Weiner, Michael; Russ, Alissa L.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA.
[Zillich, Alan J.; Russ, Alissa L.] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA.
[McManus, M. Sue] Nephrol Serv Cent Texas, Dept Vet Affairs, Temple, TX USA.
[Spina, Jeffrey R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Spina, Jeffrey R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Melton, BL (reprint author), 3901 Rainbow Blvd,Wescoe 6012,Mailstop 4047, Kansas City, KS 66160 USA.
EM bmelton2@kumc.edu
FU VA Health Services Research & Development Grant [PPO 09-298]; VA Health
Services Research & Development Research Career Development Awards [CDA
11-214, RCD 06-304-1]
FX This work was supported by VA Health Services Research & Development
Grant PPO 09-298 (Principal Investigator, ALR). AJZ and ALR were
supported by VA Health Services Research & Development Research Career
Development Awards (CDA 11-214, and RCD 06-304-1, respectively). The
views expressed in this article are those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs or
the US government.
NR 42
TC 3
Z9 3
U1 1
U2 2
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 OCT
PY 2015
VL 128
IS 10
BP 1117
EP 1125
DI 10.1016/j.amjmed.2015.05.033
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR9DE
UT WOS:000361652600048
PM 26087048
ER
PT J
AU Brondfield, S
Reid, M
Patel, K
Ten, R
Dhaliwal, G
AF Brondfield, Sam
Reid, Michael
Patel, Kiran
Ten, Rosa
Dhaliwal, Gurpreet
TI Disseminated Mycobacterial Infection and Scabies Infestation
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Brondfield, Sam] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Reid, Michael] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA.
[Patel, Kiran] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Ten, Rosa] Univ Calif San Francisco, Dept Med, Div Pulm Allergy & Immunol, San Francisco, CA 94143 USA.
[Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
RP Brondfield, S (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Rm 987, San Francisco, CA 94143 USA.
EM sam.brondfield@ucsf.edu
NR 5
TC 0
Z9 0
U1 1
U2 2
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 OCT
PY 2015
VL 128
IS 10
BP E41
EP E42
DI 10.1016/j.amjmed.2015.06.008
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR9DE
UT WOS:000361652600015
PM 26149672
ER
PT J
AU O'Malley, DP
Louissaint, A
Vasef, MA
Auerbach, A
Miranda, R
Brynes, RK
Fedoriw, Y
Hudnall, SD
AF O'Malley, Dennis P.
Louissaint, Abner, Jr.
Vasef, Mohammad A.
Auerbach, Aaron
Miranda, Roberto
Brynes, Russell K.
Fedoriw, Yuri
Hudnall, S. David
CA Int Spleen Consortium
TI Recommendations for gross examination and sampling of surgical specimens
of the spleen
SO ANNALS OF DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE spleen; gross examination; sampling histology; pathology
ID T-CELL LYMPHOMA; SPLENIC-GONADAL FUSION; INFLAMMATORY PSEUDOTUMOR;
SPONTANEOUS RUPTURE; GAMMA-DELTA; INFECTIOUS-MONONUCLEOSIS; DIAGNOSIS;
SPLENOSIS; LEUKEMIA; FEATURES
AB This review examines handling and processing of spleen biopsies and splenectomy specimens with the aim of providing the pathologist with guidance in optimizing examination and diagnosis of splenic disorders. It also offers recommendations as to relevant reporting factors in gross examination, which may guide diagnostic workup. The role of splenic needle biopsies is discussed. The International Spleen Consortium is a group dedicated to promoting education and research on the anatomy, physiology, and pathology of the spleen. In keeping with these goals, we have undertaken to provide guidelines for gross examination, sectioning, and sampling of spleen tissue to optimize diagnosis (Burke Ill). The pathology of the spleen may be complicated in routine practice due to a number of factors. Among these are lack of familiarity with lesions, complex histopathology, mimicry within several types of lesions, and overall rarity. To optimize diagnosis, appropriate handling and processing of splenic tissue are crucial. The importance of complete and accurate clinical history cannot be overstated. In many cases, significant clinical history such as previous lymphoproliferative disorders, hematologic disorders, trauma, etc, can provide important information to guide the evaluation of spleen specimens. Clinical information helps plan for appropriate processing of the spleen specimen. The pathologist should encourage surgical colleagues, who typically provide the specimens, to include as much clinical information as possible. (C) 2015 Elsevier Inc. All rights reserved.
C1 [O'Malley, Dennis P.] Clarient Diagnost Serv, Aliso Viejo, CA 92656 USA.
[Louissaint, Abner, Jr.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Vasef, Mohammad A.] TriCore Reference Labs, Albuquerque, NM 87102 USA.
[Auerbach, Aaron] Joint Pathol Ctr, Silver Spring, MD 20910 USA.
[Miranda, Roberto] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Brynes, Russell K.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Fedoriw, Yuri] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Hudnall, S. David] Yale Univ, Dept Pathol, New Haven, CT 06520 USA.
RP O'Malley, DP (reprint author), Clarient Diagnost Serv, 31 Columbia, Aliso Viejo, CA 92656 USA.
EM domalley@clarientinc.com; alouissaint@partners.org;
mvasef@salud.unm.edu; aaron.auerbach.civ@mail.mil;
Roberto.miranda@mdanderson.org; brynes@usc.edu; Gfedoriw@unch.unc.edu;
david.hudnall@yale.edu
OI Bhagat, Govind/0000-0001-6250-048X
NR 61
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 1092-9134
EI 1532-8198
J9 ANN DIAGN PATHOL
JI Ann. Diagn. Pathol.
PD OCT
PY 2015
VL 19
IS 5
BP 288
EP 295
DI 10.1016/j.anndiagpath.2015.06.004
PG 8
WC Pathology
SC Pathology
GA CR8ZI
UT WOS:000361642600003
PM 26143481
ER
PT J
AU Blasi, F
Oliveira, BL
Rietz, TA
Rotile, NJ
Naha, PC
Cormode, DP
Izquierdo-Garcia, D
Catana, C
Caravan, P
AF Blasi, Francesco
Oliveira, Bruno L.
Rietz, Tyson A.
Rotile, Nicholas J.
Naha, Pratap C.
Cormode, David P.
Izquierdo-Garcia, David
Catana, Ciprian
Caravan, Peter
TI Multisite Thrombus Imaging and Fibrin Content Estimation With a Single
Whole-Body PET Scan in Rats
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE diagnostic techniques; cardiovascular; fibrin; magnetic resonance
imaging; molecular imaging; positron-emission tomography; thrombosis;
whole body imaging
ID DEEP-VEIN THROMBOSIS; CONTRAST AGENT; PULMONARY-EMBOLISM; CORONARY
THROMBUS; THROMBOLYSIS; MODEL; STROKE; SUSCEPTIBILITY; FEASIBILITY;
VALIDATION
AB Objective Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but a thrombus-specific whole-body imaging approach is still missing. Moreover, imaging techniques to assess thrombus composition are underdeveloped, although therapeutic strategies may benefit from such technology. Therefore, our goal was to test whether positron emission tomography (PET) with the fibrin-binding probe Cu-64-FBP8 allows multisite thrombus detection and fibrin content estimation.
Approach and Results Thrombosis was induced in Sprague-Dawley rats (n=32) by ferric chloride application on both carotid artery and femoral vein. Cu-64-FBP8-PET/CT imaging was performed 1, 3, or 7 days after thrombosis to detect thrombus location and to evaluate age-dependent changes in target uptake. Ex vivo biodistribution, autoradiography, and histopathology were performed to validate imaging results. Arterial and venous thrombi were localized on fused PET/CT images with high accuracy (97.6%; 95% confidence interval, 92-100). A single whole-body PET/MR imaging session was sufficient to reveal the location of both arterial and venous thrombi after Cu-64-FBP8 administration. PET imaging showed that probe uptake was greater in younger clots than in older ones for both arterial and venous thrombosis (P<0.0001). Quantitative histopathology revealed an age-dependent reduction of thrombus fibrin content (P<0.001), consistent with PET results. Biodistribution and autoradiography further confirmed the imaging findings.
Conclusions We demonstrated that Cu-64-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin can provide, noninvasively, insight into clot composition.
C1 [Blasi, Francesco; Oliveira, Bruno L.; Rietz, Tyson A.; Rotile, Nicholas J.; Izquierdo-Garcia, David; Catana, Ciprian; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA USA.
[Naha, Pratap C.; Cormode, David P.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Caravan, Peter] Massachusetts Gen Hosp, Inst Innovat Imaging, Boston, MA 02114 USA.
RP Caravan, P (reprint author), Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
RI Blasi, Francesco/G-1055-2015;
OI Blasi, Francesco/0000-0002-6616-8418; Cormode,
David/0000-0002-8391-9500; Oliveira, Bruno/0000-0002-7687-4746
FU National Heart, Lung, and Blood Institute [HL109448]; National Center
for Research Resources [RR029495]; Office of the Director at NIH
[OD010650]
FX This work was supported by HL109448 from the National Heart, Lung, and
Blood Institute. The National Center for Research Resources (RR029495)
and the Office of the Director (OD010650) at NIH are acknowledged for
funding instrumentation used.
NR 37
TC 6
Z9 6
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2015
VL 35
IS 10
BP 2114
EP 2121
DI 10.1161/ATVBAHA.115.306055
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA CR8NL
UT WOS:000361610700008
PM 26272938
ER
PT J
AU Cavusoglu, E
Marmur, JD
Yanamadala, S
Chopra, V
Hegde, S
Nazli, A
Singh, KP
Zhang, M
Eng, C
AF Cavusoglu, Erdal
Marmur, Jonathan D.
Yanamadala, Sunitha
Chopra, Vineet
Hegde, Sudhanva
Nazli, Anila
Singh, Kamal Preet
Zhang, Ming
Eng, Calvin
TI Elevated baseline plasma IL-8 levels are an independent predictor of
long-term all-cause mortality in patients with acute coronary syndrome
SO ATHEROSCLEROSIS
LA English
DT Article
DE IL-8; Biomarkers; Acute coronary syndrome; Prognosis; Mortality
ID HUMAN-ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; NATRIURETIC PEPTIDE;
INTERLEUKIN-8; MACROPHAGES; EXPRESSION; PROTEIN; TISSUE;
CHEMOATTRACTANT; POPULATION
AB Objectives: To investigate the long-term prognostic significance of baseline plasma IL-8 levels in a group of well-characterized male patients presenting with acute coronary syndrome.
Background: IL-8 is a cytokine that has been implicated in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated plasma levels have been reported in patients with acute coronary syndrome.
Methods: Baseline plasma IL-8 levels were measured in 180 male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years.
Results: In a multivariate model that included a wide variety of baseline clinical, laboratory and angiographic parameters in the selection process, baseline plasma IL-8 levels (analyzed as a continuous variable) emerged as a significant predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p = 0.0123). Furthermore, in 3 additional multivariate models that also included in the selection process a number of contemporary biomarkers with established prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8 remained an independent predictor of all-cause mortality at 5 years.
Conclusion: Elevated baseline plasma levels of IL-8 are associated with an increased risk of long-term all-cause mortality in patients with acute coronary syndrome. Furthermore, this association is independent of a variety of clinical, laboratory and angiographic variables, including contemporary biomarkers with established prognostic efficacy in acute coronary syndrome. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Div Cardiol, Dept Med, Bronx, NY USA.
[Cavusoglu, Erdal; Marmur, Jonathan D.; Yanamadala, Sunitha; Hegde, Sudhanva; Nazli, Anila; Singh, Kamal Preet] Suny Downstate Med Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA.
[Zhang, Ming] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
[Zhang, Ming] Suny Downstate Med Ctr, Dept Anesthesiol, Brooklyn, NY 11203 USA.
RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, 450 Clarkson Ave,Box 1199, Brooklyn, NY 11203 USA.
EM ECavusoglu@aol.com
NR 27
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD OCT
PY 2015
VL 242
IS 2
BP 589
EP 594
DI 10.1016/j.atherosclerosis.2015.08.022
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR7DV
UT WOS:000361509000030
PM 26318109
ER
PT J
AU Nicolaidis, C
Raymaker, DM
Ashkenazy, E
McDonald, KE
Dern, S
Baggs, AEV
Kapp, SK
Weiner, M
Boisclair, WC
AF Nicolaidis, Christina
Raymaker, Dora M.
Ashkenazy, Elesia
McDonald, Katherine E.
Dern, Sebastian
Baggs, Amelia E. V.
Kapp, Steven K.
Weiner, Michael
Boisclair, W. Cody
TI "Respect the way I need to communicate with you": Healthcare experiences
of adults on the autism spectrum
SO AUTISM
LA English
DT Article
DE adults; autism spectrum disorders; community-based participatory
research; health services; qualitative research
ID DISORDER; PARTNERSHIP; DISPARITIES; SERVICES; AQ
AB Our objective was to obtain an in-depth understanding of autistic adults' experiences with healthcare and their recommendations for improving care. Our academic-community partnership used a community-based participatory research approach to conduct semi-structured, open-ended interviews with 39 autistic adults and 16 people who had experience supporting autistic adults in healthcare settings. Participants identified patient-level, autism-related factors that impact healthcare interactions, including verbal communication skills, sensory sensitivities, challenges with body awareness, slow processing speed, atypical non-verbal communication, and challenges with organization. However, the success of healthcare interactions largely depended on the interplay between patient- and provider-level factors, as well as the larger context in which patients were receiving care. Provider-level factors included providers' knowledge about autism in adults, incorrect assumptions about individual patients, willingness to allow written communication, use of accessible language, openness to providing other accommodations, and skill in appropriately incorporating supporters. System-level factors included the availability of supporters, complexity of the healthcare system, accessibility of healthcare facilities, and stigma about autism. Further efforts are needed to empower patients, adequately train providers, increase the accessibility of the healthcare system, and decrease discrimination.
C1 [Nicolaidis, Christina; Raymaker, Dora M.] Portland State Univ, Portland, OR 97201 USA.
[Nicolaidis, Christina] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Nicolaidis, Christina; Raymaker, Dora M.; Ashkenazy, Elesia; McDonald, Katherine E.; Dern, Sebastian; Baggs, Amelia E. V.; Kapp, Steven K.; Weiner, Michael; Boisclair, W. Cody] Acad Autist Spectrum Partnership Res & Educ, Washington, DC USA.
[McDonald, Katherine E.] Syracuse Univ, Syracuse, NY 13244 USA.
[Weiner, Michael] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Bloomington, IN 47405 USA.
[Weiner, Michael] Regenstrief Inst Inc, Indianapolis, IN USA.
[Weiner, Michael] US Dept Vet Affairs, Washington, DC USA.
RP Nicolaidis, C (reprint author), Portland State Univ, Reg Res Inst, Sch Social Work, 1600 SW 4th Ave,Suite 900, Portland, OR 97201 USA.
EM Nicol22@pdx.edu
FU National Institute of Mental Health [R34MH092503]; Oregon Clinical and
Translational Research Institute (OCTRI) from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research
FX This study was funded by the National Institute of Mental Health
[R34MH092503] and the Oregon Clinical and Translational Research
Institute (OCTRI), grant number UL1 RR024140 from the National Center
for Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research.
NR 20
TC 6
Z9 6
U1 3
U2 22
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1362-3613
EI 1461-7005
J9 AUTISM
JI Autism
PD OCT
PY 2015
VL 19
IS 7
SI SI
BP 824
EP 831
DI 10.1177/1362361315576221
PG 8
WC Psychology, Developmental
SC Psychology
GA CS0RK
UT WOS:000361769700007
PM 25882392
ER
PT J
AU Williams, DL
Minshew, NJ
Goldstein, G
AF Williams, Diane L.
Minshew, Nancy J.
Goldstein, Gerald
TI Further understanding of complex information processing in verbal
adolescents and adults with autism spectrum disorders
SO AUTISM
LA English
DT Article
DE adults; autism spectrum disorders; conceptual reasoning; information
processing; language
ID HIGH-FUNCTIONING AUTISM; DIAGNOSTIC OBSERVATION SCHEDULE;
UNDERCONNECTIVITY; INDIVIDUALS; CHILDREN; SYNCHRONIZATION;
COMPREHENSION; ACTIVATION; INTERVIEW; LANGUAGE
AB More than 20years ago, Minshew and colleagues proposed the Complex Information Processing model of autism in which the impairment is characterized as a generalized deficit involving multiple modalities and cognitive domains that depend on distributed cortical systems responsible for higher order abilities. Subsequent behavioral work revealed a related dissociation between concept formation and concept identification in autism suggesting the lack of an underlying organizational structure to manage increases in processing loads. The results of a recent study supported the impact of this relative weakness in conceptual reasoning on adaptive functioning in children and adults with autism. In this study, we provide further evidence of the difficulty relatively able older adolescents and adults with autism have with conceptual reasoning and provide evidence that this characterizes their difference from age- and ability-matched controls with typical development better than their differences in language. For verbal adults with autism, language may serve as a bootstrap or compensatory mechanism for learning but cannot overcome an inherent weakness in concept formation that makes information processing challenging as task demands increase.
C1 [Williams, Diane L.] Duquesne Univ, Pittsburgh, PA USA.
[Minshew, Nancy J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr 151R, Pittsburgh, PA 15240 USA.
EM ggold@nb.net
RI Williams, Diane/B-4128-2017
FU National Institute of Neurological Disorders and Stroke (NINDS)
[NS3335]; National Institute of Child Health and Human Development
(NICHD) Collaborative Program of Excellence in Autism (CPEA) [HD35469];
Medical Research Service, Department of Veterans Affairs
FX This work was supported by the National Institute of Neurological
Disorders and Stroke (NINDS) [grant NS3335]; by the National Institute
of Child Health and Human Development (NICHD) Collaborative Program of
Excellence in Autism (CPEA) [grant HD35469]; and the Medical Research
Service, Department of Veterans Affairs.
NR 49
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PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1362-3613
EI 1461-7005
J9 AUTISM
JI Autism
PD OCT
PY 2015
VL 19
IS 7
SI SI
BP 859
EP 867
DI 10.1177/1362361315586171
PG 9
WC Psychology, Developmental
SC Psychology
GA CS0RK
UT WOS:000361769700011
PM 26019307
ER
PT J
AU Matar, AJ
Patil, AR
Al-Musa, A
Hanekamp, I
Sachs, DH
Huang, CA
Duran-Struuck, R
AF Matar, Abraham J.
Patil, Aarti R.
Al-Musa, Ahmad
Hanekamp, Isabel
Sachs, David H.
Huang, Christene A.
Duran-Struuck, Raimon
TI Effect of Irradiation on Incidence of Post-Transplant
Lymphoproliferative Disorder after Hematopoietic Cell Transplantation in
Miniature Swine
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Hematopoietic cell transplantation; Post-transplant lymphoproliferative
disease
ID EPSTEIN-BARR-VIRUS; LARGE-ANIMAL-MODEL; PREPARATIVE REGIMEN; MIXED
CHIMERISM; CD3 IMMUNOTOXIN; BONE-MARROW; SCID MICE; IN-VIVO; DISEASE
AB Post-transplant lymphoproliferative disease (PTLD) is a major complication of clinical organ and cell transplantation. Conditioning and immunosuppressive regimens that significantly impair T cell immunity, including depleting antibodies and calcineurin inhibitors, increase the risk of PTLD after transplantation. Swine PTLD has been shown to closely resemble human PTLD in morphology, histology, and viral-driven reactivation of B cells. Previously, we reported high incidences of PTLD after hematopoietic cell transplantation (HCT) in miniature swine recipients conditioned with thymic irradiation (TI) in addition to T cell depletion and cyclosporine A monotherapy after transplantation. Replacement of TI with 100 cGy of total body irradiation resulted in similar numbers of B cells early post-transplantation, greater numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting that a threshold number of T cells may be necessary to prevent subsequent B cell proliferation and development of overt PTLD. Results from this large cohort of animals provide insight into the important effect of irradiation and T cell immunity on the incidence of PTLD after HCT and reinforce the pig model as a valuable tool for the study of PTLD and HCT. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Matar, Abraham J.; Patil, Aarti R.; Al-Musa, Ahmad; Hanekamp, Isabel; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
[Matar, Abraham J.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA.
[Duran-Struuck, Raimon] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA.
RP Duran-Struuck, R (reprint author), Univ Penn, Dept Pathobiol, 3800 Spruce St, Philadelphia, PA 19104 USA.
EM rduranst@gmail.com
OI Al-musa, Ahmad/0000-0002-4192-0140; Hanekamp, Isabel/0000-0002-6218-3979
FU National Cancer Institute [P01CA111519]; National Institute of Allergy
and Infectious Disease of the National Institutes of Health
[R01A184657]; NCRR [1K01RR024466]
FX Financial disclosure: Supported in part by grants from the National
Cancer Institute (P01CA111519; D.H.S.) and the National Institute of
Allergy and Infectious Disease (R01A184657; C.A.H.) of the National
Institutes of Health. Also supported by NCRR (1K01RR024466; R.D.-S.). We
acknowledge C06RR020135-01 for construction of the facility used for
production and maintenance of miniature swine and Novartis for the
generous gift of cyclosporine A.
NR 20
TC 1
Z9 1
U1 0
U2 2
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 OCT
PY 2015
VL 21
IS 10
BP 1732
EP 1738
DI 10.1016/j.bbmt.2015.07.017
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100007
PM 26210443
ER
PT J
AU Urbano-Ispizua, A
Pavletic, SZ
Flowers, ME
Klein, JP
Zhang, MJ
Carreras, J
Montoto, S
Perales, MA
Aljurf, MD
Akpek, G
Bredeson, CN
Costa, LJ
Dandoy, C
Freytes, CO
Fung, HC
Gale, RP
Gibson, J
Hamadani, M
Hayashi, RJ
Inamoto, Y
Inwards, DJ
Lazarus, HM
Maloney, DG
Martino, R
Munker, R
Nishihori, T
Olsson, RF
Rizzieri, DA
Reshef, R
Saad, A
Savani, BN
Schouten, HC
Smith, SM
Socie, G
Wirk, B
Yu, LC
Saber, W
AF Urbano-Ispizua, Alvaro
Pavletic, Steven Z.
Flowers, Mary E.
Klein, John P.
Zhang, Mei-Jie
Carreras, Jeanette
Montoto, Silvia
Perales, Miguel-Angel
Aljurf, Mahmoud D.
Akpek, Goerguen
Bredeson, Christopher N.
Costa, Luciano J.
Dandoy, Christopher
Freytes, Cesar O.
Fung, Henry C.
Gale, Robert Peter
Gibson, John
Hamadani, Mehdi
Hayashi, Robert J.
Inamoto, Yoshihiro
Inwards, David J.
Lazarus, Hillard M.
Maloney, David G.
Martino, Rodrigo
Munker, Reinhold
Nishihori, Taiga
Olsson, Richard F.
Rizzieri, David A.
Reshef, Ran
Saad, Ayman
Savani, Bipin N.
Schouten, Harry C.
Smith, Sonali M.
Socie, Gerard
Wirk, Baldeep
Yu, Lolie C.
Saber, Wael
TI The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients
with Lymphoma Depends on the Histological Subtype and the Intensity of
the Conditioning Regimen
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Graft-versus-host disease; Lymphoma
ID STEM-CELL TRANSPLANTATION; BONE-MARROW TRANSPLANT; NON-HODGKIN-LYMPHOMA;
ALLOGENEIC TRANSPLANTATION; FOLLICULAR LYMPHOMA; AUTOLOGOUS
TRANSPLANTATION; EUROPEAN GROUP; BLOOD; INFUSIONS; REMISSIONS
AB The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR],.51; P = 3.049) and in MCL (RR,.41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR,.14; P = .007; and RR,.15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Urbano-Ispizua, Alvaro] Univ Barcelona, Hosp Clin, IDIBAPS, Dept Hematol, Barcelona, Spain.
[Urbano-Ispizua, Alvaro] Inst Res Josep Carreras, Barcelona, Spain.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Flowers, Mary E.; Inamoto, Yoshihiro; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Klein, John P.; Zhang, Mei-Jie; Carreras, Jeanette; Hamadani, Mehdi; Saber, Wael] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Klein, John P.; Zhang, Mei-Jie] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
[Montoto, Silvia] Barts Hlth NHS Trust, St Bartholomews Hosp, Dept Haematooncol, London, England.
[Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Bone Marrow Transplant Serv, New York, NY 10021 USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia.
[Akpek, Goerguen] Banner MD Anderson Canc Ctr, Hematol Oncol Sect, Gilbert, AZ USA.
[Bredeson, Christopher N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada.
[Bredeson, Christopher N.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Costa, Luciano J.; Saad, Ayman] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA.
[Dandoy, Christopher] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Fung, Henry C.] Temple Hlth, Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England.
[Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia.
[Hayashi, Robert J.] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA.
[Inwards, David J.] Mayo Clin, Div Hematol, Rochester, MN USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA.
[Martino, Rodrigo] Hosp Santa Creu & Sant Pau, Div Hematol, Barcelona, Spain.
[Munker, Reinhold] Louisiana State Univ Hlth, Dept Internal Med, Div Hematol Oncol, Shreveport, LA USA.
[Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Med Oncol, Tampa, FL 33612 USA.
[Olsson, Richard F.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
[Olsson, Richard F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden.
[Rizzieri, David A.] Duke Univ, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA.
[Reshef, Ran] Univ Penn, Dept Med, Abramson Canc Ctr, Med Ctr, Philadelphia, PA 19104 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
[Schouten, Harry C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands.
[Smith, Sonali M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Socie, Gerard] Hop St Louis, Dept Hematol, Paris, France.
[Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Dept Internal Med, Stony Brook, NY 11794 USA.
[Yu, Lolie C.] Louisiana State Univ, Med Ctr, Childrens Hosp, Div Hematol Oncol,Ctr Canc & Blood Disorders, New Orleans, LA USA.
RP Urbano-Ispizua, A (reprint author), Hosp Clin Barcelona, Dept Hematol, Villarroel 170, E-08036 Barcelona, Spain.
EM aurbano@clinic.ub.es
OI Saad, Ayman /0000-0003-0003-0130
FU National Cancer Institute [U24-CA076518]; National Heart, Lung, and
Blood Institute [5U10HL069294]; National Institute of Allergy and
Infectious Diseases; Health Resources and Services Administration
[HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142,
N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.;
Amgen
FX The CIBMTR is supported by Public Health Service grant/cooperative
agreement U24-CA076518 from the National Cancer Institute, the National
Heart, Lung, and Blood Institute, and the National Institute of Allergy
and Infectious Diseases; grant/cooperative agreement 5U10HL069294 from
the National Heart, Lung, and Blood Institute and National Cancer
Institute; contract HHSH250201200016C with Health Resources and Services
Administration; 2 grants from the Office of Naval Research
(N00014-12-1-0142 and N00014-13-1-0039); and grants from *Actinium
Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen; an anonymous donation
to the Medical College of Wisconsin; Ariad; Be The Match Foundation;
*Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix,
Inc.; 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; Histo-Genetics; 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; National Marrow Donor Program; Onyx Pharmaceuticals;
Optum Healthcare Solutions, Inc.; Osiris Therapeutics; 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; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos;
University of Minnesota; University of Utah; and *WellPoint. The views
expressed in this article do not reflect the official policy or position
of the National Institute of Health, the Department of the Navy, the
Department of Defense, Health Resources and Services Administration, or
any other agency of the US Government.
NR 27
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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 OCT
PY 2015
VL 21
IS 10
BP 1746
EP 1753
DI 10.1016/j.bbmt.2015.05.010
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100009
PM 25981509
ER
PT J
AU Inamoto, Y
Flowers, MED
Wang, T
Urbano-Ispizua, A
Hemmer, MT
Cutler, CS
Couriel, DR
Alousi, AM
Antin, JH
Gale, RP
Gupta, V
Hamilton, BK
Kharfan-Dabaja, MA
Marks, DI
Ringden, OTH
Socie, G
Solh, MM
Akpek, G
Cairo, MS
Chao, NJ
Hayashi, RJ
Nishihori, T
Reshef, R
Saad, A
Shah, A
Teshima, T
Tallman, MS
Wirk, B
Spellman, SR
Arora, M
Martin, PJ
AF Inamoto, Yoshihiro
Flowers, Mary E. D.
Wang, Tao
Urbano-Ispizua, Alvaro
Hemmer, Michael T.
Cutler, Corey S.
Couriel, Daniel R.
Alousi, Amin M.
Antin, Joseph H.
Gale, Robert Peter
Gupta, Vikas
Hamilton, Betty K.
Kharfan-Dabaja, Mohamed A.
Marks, David I.
Ringden, Olle T. H.
Socie, Gerard
Solh, Melhem M.
Akpek, Goerguen
Cairo, Mitchell S.
Chao, Nelson J.
Hayashi, Robert J.
Nishihori, Taiga
Reshef, Ran
Saad, Ayman
Shah, Ami
Teshima, Takanori
Tallman, Martin S.
Wirk, Baldeep
Spellman, Stephen R.
Arora, Mukta
Martin, Paul J.
TI Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation
for Acquired Aplastic Anemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Aplastic anemia; Hematopoietic cell transplantation; Graft-versus-host
disease; Immunosuppression; Cyclosporine; Tacrolimus
ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; UNRELATED DONOR
TRANSPLANTATION; PERIPHERAL-BLOOD; COMPARING METHOTREXATE; SIBLING
DONORS; ACUTE GVHD; PHASE-III; GRAFT; PROPHYLAXIS
AB Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia, Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo 1040045, Japan.
[Flowers, Mary E. D.; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Wang, Tao; Hemmer, Michael T.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Wang, Tao] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA.
[Urbano-Ispizua, Alvaro] Univ Barcelona, Dept Hematol, Hosp Clin, IDIBAPS, Barcelona, Spain.
[Urbano-Ispizua, Alvaro] Inst Res Josep Carreras, Barcelona, Spain.
[Cutler, Corey S.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA.
[Couriel, Daniel R.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX 77030 USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Dept Med, Div Expt Med, London, England.
[Gupta, Vikas] Univ Hlth Network, Princess Margaret Canc Ctr, Blood & Marrow Transplant Program, Toronto, ON, Canada.
[Hamilton, Betty K.] Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA.
[Kharfan-Dabaja, Mohamed A.; Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA.
[Marks, David I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England.
[Ringden, Olle T. H.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
[Ringden, Olle T. H.] Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Socie, Gerard] Hosp St Louis, Dept Hematol, Paris, France.
[Solh, Melhem M.] Florida Hosp, Med Grp, Blood & Marrow Transplant Ctr, Orlando, FL USA.
[Akpek, Goerguen] Banner MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy Program, Gilbert, AZ USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA.
[Chao, Nelson J.] Duke Univ, Med Ctr, Dept Med, Div Cell Therapy & Hematol, Durham, NC 27710 USA.
[Hayashi, Robert J.] Washington Univ, Dept Pediat, Sch Med St Louis, Div Pediat Hematol Oncol, St Louis, MO 63130 USA.
[Reshef, Ran] Univ Penn, Med Ctr, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA.
[Saad, Ayman] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA.
[Shah, Ami] Univ Calif Los Angeles, Dept Pediat, Mattel Childrens Hosp, Div Hematol Oncol, Los Angeles, CA 90024 USA.
[Teshima, Takanori] Hokkaido Univ, Grad Sch Med, Dept Hematol, Sapporo, Hokkaido, Japan.
[Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Wirk, Baldeep] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA.
[Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Be Match, Minneapolis, MN USA.
[Arora, Mukta] Univ Minnesota, Med Ctr, Dept Med, Div Hematol,Oncol,Transplantat, Minneapolis, MN 55455 USA.
RP Inamoto, Y (reprint author), Natl Canc Ctr, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan.
EM yinamoto@ncc.go.jp
OI Saad, Ayman /0000-0003-0003-0130
FU 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]; Health
Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C];
Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium
Pharmaceuticals; Allos Therapeutics, Inc.; Amgen
FX The CIBMTR is supported by Public Health Service grant/cooperative
agreement U24-CA076518 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 5U10HL069294 from
National Heart, Lung, and Blood Institute and National Cancer Institute;
a contract HHSH250201200016C with Health Resources and Services
Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and
N00014-14-1-0028 from the Office of Naval Research; and grants from
*Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen; an
anonymous donation to the Medical College of Wisconsin; Ariad; Be The
Match Foundation; *Blue Cross and Blue Shield Association; *Celgene
Corporation; Chimerix, Inc.; 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; 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; National Marrow Donor
Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris
Therapeutics; 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; *Terumo BCT; *Teva
Neuroscience, Inc.; *Therakos; University of Minnesota; University of
Utah; and *WellPoint The views expressed in this article do not reflect
the official policy or position of the National Institute of Health, the
Department of the Navy, the Department of Defense, Health Resources and
Services Administration or any other agency of the US Government.
NR 25
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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 OCT
PY 2015
VL 21
IS 10
BP 1776
EP 1782
DI 10.1016/j.bbmt.2015.05.023
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100013
PM 26033280
ER
PT J
AU Verneris, MR
Lee, SJ
Ahn, KW
Wang, HL
Battiwalla, M
Inamoto, Y
Fernandez-Vina, MA
Gajewski, J
Pidala, J
Munker, R
Aljurf, M
Saber, W
Spellman, S
Koreth, J
AF Verneris, Michael R.
Lee, Stephanie J.
Ahn, Kwang Woo
Wang, Hai-Lin
Battiwalla, Minoo
Inamoto, Yoshihiro
Fernandez-Vina, Marcelo A.
Gajewski, James
Pidala, Joseph
Munker, Reinhold
Aljurf, Mahmoud
Saber, Wael
Spellman, Stephen
Koreth, John
TI HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor
Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An
Analysis from the Center for International Blood and Marrow Transplant
Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Bone marrow transplantation; Leukemia; Hematologic malignancies;
Pediatric oncology
ID CLASS-I; CLINICAL-SIGNIFICANCE; HLA-DPB1; GRAFT; SURVIVAL; RECIPIENTS;
LEUKEMIA; REGISTRY; IMPACT
AB Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DPI (based on T cell epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Verneris, Michael R.] Univ Minnesota, Dept Pediat BMT, Minneapolis, MN 55455 USA.
[Lee, Stephanie J.; Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Ahn, Kwang Woo] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Wang, Hai-Lin; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Fernandez-Vina, Marcelo A.] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA.
[Gajewski, James] Oregon Hlth & Sci Univ, Dept Hematol, Portland, OR 97201 USA.
[Pidala, Joseph] Univ S Florida, Dept Blood & Marrow Transplantat, Tampa, FL USA.
[Munker, Reinhold] Louisiana State Univ, Hlth Sci Ctr, Dept Hematol Oncol, Shreveport, LA 71105 USA.
[Aljurf, Mahmoud] King Faisal Specialist Hosp & Res Ctr, Pediat HSCT, Adult HSCT, Riyadh 11211, Saudi Arabia.
[Spellman, Stephen] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Koreth, John] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA.
RP Verneris, MR (reprint author), Univ Minnesota, Dept Pediat BMT, 425 E River Rd,CCRB 654, Minneapolis, MN 55455 USA.
EM verneris@umn.edu
OI Verneris, Michael/0000-0002-7097-5917
FU NCI NIH HHS [U24 CA076518]; NHLBI NIH HHS [U01 HL069294]
NR 26
TC 10
Z9 11
U1 4
U2 5
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 OCT
PY 2015
VL 21
IS 10
BP 1783
EP 1789
DI 10.1016/j.bbmt.2015.05.028
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100014
PM 26055300
ER
PT J
AU Khera, N
Majhail, NS
Brazauskas, R
Wang, ZW
He, NY
Aljurf, MD
Akpek, G
Atsuta, Y
Beattie, S
Bredeson, CN
Burns, LJ
Dalal, JD
Freytes, CO
Gupta, V
Inamoto, Y
Lazarus, HM
LeMaistre, CF
Steinberg, A
Szwajcer, D
Wingard, JR
Wirk, B
Wood, WA
Joffe, S
Hahn, TE
Loberiza, FR
Anasetti, C
Horowitz, MM
Lee, SJ
AF Khera, Nandita
Majhail, Navneet S.
Brazauskas, Ruta
Wang, Zhiwei
He, Naya
Aljurf, Mahmoud D.
Akpek, Goerguen
Atsuta, Yoshiko
Beattie, Sara
Bredeson, Christopher N.
Burns, Linda J.
Dalal, Jignesh D.
Freytes, Cesar O.
Gupta, Vikas
Inamoto, Yoshihiro
Lazarus, Hillard M.
LeMaistre, Charles F.
Steinberg, Amir
Szwajcer, David
Wingard, John R.
Wirk, Baldeep
Wood, William A.
Joffe, Steven
Hahn, Theresa E.
Loberiza, Fausto R.
Anasetti, Claudio
Horowitz, Mary M.
Lee, Stephanie J.
TI Comparison of Characteristics and Outcomes of Trial Participants and
Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials
Network 0201 Trial
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Trial participation; Hematopoietic cell transplantation
ID VERSUS-HOST-DISEASE; UNRELATED DONORS; MYOCARDIAL-INFARCTION; EXTERNAL
VALIDITY; IMPROVED SURVIVAL; CANCER; POPULATION; GENERALIZABILITY;
LEUKEMIA; REGISTRY
AB Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and non-participants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Khera, Nandita] Mayo Clin, Dept Hematol Oncol, Phoenix, AZ 85054 USA.
[Majhail, Navneet S.] Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA.
[Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Horowitz, Mary M.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia.
[Akpek, Goerguen] Banner MD Anderson Canc Ctr, Hematol Oncol Sect, Gilbert, AZ USA.
[Atsuta, Yoshiko] Japanese Data Ctr Hematopoiet Cell Transplantat, Nagoya, Aichi, Japan.
[Atsuta, Yoshiko] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan.
[Beattie, Sara] Univ Ottawa, Sch Psychol, Ottawa, ON K1N 6N5, Canada.
[Bredeson, Christopher N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada.
[Bredeson, Christopher N.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Burns, Linda J.] Be Match, Natl Marrow Donor Program, Hlth Serv Res, Minneapolis, MN USA.
[Dalal, Jignesh D.] Childrens Mercy Hosp & Clin, Bone Marrow Transplantat, Pediat Hematol Oncol, Kansas City, MO USA.
[Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Gupta, Vikas] Univ Hlth Network, Blood & Marrow Transplant Program, Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan.
[Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH 44106 USA.
[LeMaistre, Charles F.] Sarah Cannon, Hematol & Bone Marrow Transplant, Nashville, TN USA.
[Steinberg, Amir] Mt Sinai Hosp, Dept Hematol Oncol, New York, NY 10029 USA.
[Szwajcer, David] Univ Manitoba, Dept Hematol, CancerCare Manitoba, Winnipeg, MB, Canada.
[Wingard, John R.] Univ Florida, Div Hematol & Oncol, Dept Med, Gainesville, FL USA.
[Wirk, Baldeep] SUNY Stony Brook, Dept Internal Med, Stony Brook, NY 11794 USA.
[Wood, William A.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA.
[Joffe, Steven] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
[Hahn, Theresa E.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Loberiza, Fausto R.] Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Anasetti, Claudio] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Bone Marrow Transplant Program, Tampa, FL 33612 USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Clin Transplant Res, Seattle, WA 98104 USA.
RP Khera, N (reprint author), Mayo Clin, Coll Med, Med, 5777 E Mayo Blvd, Phoenix, AZ 85054 USA.
EM khera.nandita@mayo.edu
OI Joffe, Steven/0000-0002-0667-7384
FU NCI [U24-CA076518]; NHLBI; National Institute of Allergy and Infectious
Diseases; NHLBI [5U10HL069294]; NCI; Health Resources and Services
Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research
[N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos
Therapeutics, Inc.; Amgen
FX The CIBMTR is supported by Public Health Service grant/cooperative
agreement U24-CA076518 from the NCI, the NHLBI, and the National
Institute of Allergy and Infectious Diseases; a grant/cooperative
agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C
with Health Resources and Services Administration (HRSA/DHHS); 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; anonymous donation to the Medical College of Wisconsin; Ariad;
Be The Match Foundation; *Blue Cross and Blue Shield Association;
*Celgene Corporation; Chimerix, Inc.; 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; 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; National Marrow Donor
Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris
Therapeutics; 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; *Terumo BCT; *Teva
Neuroscience, Inc.; *Therakos; University of Minnesota; University of
Utah; and *WellPoint. The views expressed in this article do not reflect
the official policy or position of the National Institute of Health, the
Department of the Navy, the Department of Defense, Health Resources and
Services Administration or any other agency of the US Government.
NR 24
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U2 7
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 OCT
PY 2015
VL 21
IS 10
BP 1815
EP 1822
DI 10.1016/j.bbmt.2015.06.004
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100019
PM 26071866
ER
PT J
AU Ustun, C
Stone, R
Weisdorf, D
AF Ustun, Celalettin
Stone, Richard
Weisdorf, Daniel
TI New Models of Therapy: When Acute Leukemia Becomes Chronic
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Letter
ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; ACUTE
LYMPHOBLASTIC-LEUKEMIA; INTERNAL TANDEM DUPLICATION; MOLECULAR
REMISSION; SORAFENIB; CHEMOTHERAPY; IMATINIB; DASATINIB; TRIAL
C1 [Ustun, Celalettin] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA.
[Stone, Richard; Weisdorf, Daniel] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Ustun, C (reprint author), Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, 14-142 PWB,516 Delaware St SE, Minneapolis, MN 55455 USA.
EM custun@umn.edu
NR 16
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U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD OCT
PY 2015
VL 21
IS 10
BP 1856
EP 1857
DI 10.1016/j.bbmt.2015.07.011
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CS0VU
UT WOS:000361781100024
PM 26183079
ER
PT J
AU Hofer, AM
AF Hofer, Aldebaran M.
TI Ca2+ signaling at membrane contact sites
SO CELL CALCIUM
LA English
DT Editorial Material
C1 [Hofer, Aldebaran M.] Harvard Univ, Sch Med, Boston, MA 02132 USA.
[Hofer, Aldebaran M.] VA Boston Healthcare Syst, Boston, MA 02132 USA.
RP Hofer, AM (reprint author), Harvard Univ, Sch Med, Boston, MA 02132 USA.
EM Aldebaran_Hofer@hms.harvard.edu
NR 10
TC 0
Z9 0
U1 3
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 0143-4160
EI 1532-1991
J9 CELL CALCIUM
JI Cell Calcium
PD OCT
PY 2015
VL 58
IS 4
SI SI
BP 331
EP 332
DI 10.1016/j.ceca.2015.07.002
PG 2
WC Cell Biology
SC Cell Biology
GA CS1TD
UT WOS:000361849700001
PM 26248790
ER
PT J
AU Chhatwal, J
Chen, QS
Kanwal, F
AF Chhatwal, Jagpreet
Chen, Qiushi
Kanwal, Fasiha
TI Why We Should Be Willing to Pay for Hepatitis C Treatment
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Editorial Material
ID GENOTYPE 1 INFECTION; COST-EFFECTIVENESS; UNITED-STATES; VIRUS;
REGIMENS; BOCEPREVIR; SOFOSBUVIR; THERAPY; BURDEN
C1 [Chhatwal, Jagpreet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA.
[Chen, Qiushi] Georgia Inst Technol, H Milton Stewart Sch Ind & Syst Engn, Atlanta, GA 30332 USA.
[Kanwal, Fasiha] Michael E DeBakey VA Med Ctr, Ctr Excellence, Hlth Serv Res & Dev, Houston Vet Affairs, Houston, TX USA.
[Kanwal, Fasiha] Baylor Coll Med, Dept Med Gastroenterol & Hepatol, Houston, TX 77030 USA.
RP Chhatwal, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA.
FU NCATS NIH HHS [KL2 TR000146]
NR 21
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Z9 3
U1 0
U2 3
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 OCT
PY 2015
VL 13
IS 10
BP 1711
EP 1713
DI 10.1016/j.cgh.2015.06.005
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR8AW
UT WOS:000361574500006
PM 26091736
ER
PT J
AU Sahora, K
Ferrone, CR
Brugge, WR
Morales-Oyarvide, V
Warshaw, AL
Lillemoe, KD
Fernandez-del Castillo, C
AF Sahora, Klaus
Ferrone, Cristina R.
Brugge, William R.
Morales-Oyarvide, Vicente
Warshaw, Andrew L.
Lillemoe, Keith D.
Fernandez-del Castillo, Carlos
TI Effects of Comorbidities on Outcomes of Patients With Intraductal
Papillary Mucinous Neoplasms
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Pancreas; Management; Treatment; Cancer Risk
ID PANCREATIC-CANCER; NONOPERATIVE MANAGEMENT; SURGERY; VALIDATION;
MORTALITY; INDEX; RISK
AB BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas occur mostly in older individuals. Individual life expectancy and risk of death from other factors must be carefully considered in analyzing the risks that IPMNs pose. We investigated whether there is a subset of patients with IPMNs and a high risk of dying from other causes who would not benefit from pancreatic surgery.
METHODS: We collected data from 725 patients at Massachusetts General Hospital who underwent resection or have been under observation for IPMNs from 1992 through 2012. Comorbidities were classified according to the age-adjusted Charlson comorbidity index (CACI). Causes of death were recorded, and survival data were analyzed by the Kaplan-Meier method.
RESULTS: The patients' median CACI score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55% underwent resection, and the remaining 45% have been under observation. After a median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within 5 years of diagnosis); 78% of deaths were not related to IPMNs. The median survival time for all patients with CACI score of 7 or more was 43 months. Multivariate regression analysis revealed that the chance of non-IPMN-related death within 3 years of diagnosis is 11-fold higher for patients with CACI score of 7 or more than for patients with lower scores.
CONCLUSIONS: The CACI can be used to identify patients with a high risk of death from factors other than IPMNs within a few years after diagnosis. These patients are therefore not likely to benefit from further IPMN observation or pancreatic resection.
C1 [Sahora, Klaus; Ferrone, Cristina R.; Morales-Oyarvide, Vicente; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Brugge, William R.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA.
EM CFERNANDEZ@mgh.harvard.edu
NR 22
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Z9 7
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 OCT
PY 2015
VL 13
IS 10
BP 1816
EP 1823
DI 10.1016/j.cgh.2015.04.177
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR8AW
UT WOS:000361574500023
PM 25956837
ER
PT J
AU Westover, MB
Ching, SN
Kumaraswamy, VM
Akeju, O
Pierce, E
Cash, SS
Kilbride, R
Brown, EN
Purdon, PL
AF Westover, M. Brandon
Ching, ShiNung
Kumaraswamy, Vishakhadatta M.
Akeju, Oluwaseun
Pierce, Eric
Cash, Sydney S.
Kilbride, Ronan
Brown, Emery N.
Purdon, Patrick L.
TI The human burst suppression electroencephalogram of deep hypothermia
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Burst suppression; Electroencephalogram; Hypothermia
ID CIRCULATORY ARREST; MODERATE HYPOTHERMIA; CEREBRAL METABOLISM;
EVOKED-POTENTIALS; CARDIAC-ARREST; BRAIN-INJURY; EEG; ANESTHESIA; COMA;
NEUROPHYSIOLOGY
AB Objective: Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity.
Methods: We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis.
Results: Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant.
Conclusions: These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures.
Significance: These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Westover, M. Brandon; Kumaraswamy, Vishakhadatta M.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02113 USA.
[Westover, M. Brandon; Cash, Sydney S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Ching, ShiNung] Washington Univ, Elect & Syst Engn, St Louis, MO 63130 USA.
[Akeju, Oluwaseun; Pierce, Eric; Brown, Emery N.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02113 USA.
[Pierce, Eric; Brown, Emery N.; Purdon, Patrick L.] Harvard Univ, Sch Med, Dept Anaesthesiol, Boston, MA USA.
[Kilbride, Ronan] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
[Brown, Emery N.; Purdon, Patrick L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 735, Boston, MA 02113 USA.
EM mwestover@mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu
FU National Institutes of Health, Bethesda, Maryland [DP2-OD006454,
DP1-OD003646, TR01-GM104948, T32GM007592]; FAER; MGH MAO/ECOR Faculty
Development award; Department of Anesthesia, Critical Care and Pain
Medicine, Massachusetts General Hospital, Boston, Massachusetts;
Burroughs-Wellcome Fund
FX American Brain Foundation (MBW); DP2-OD006454 (to PLP), DP1-OD003646 and
TR01-GM104948 (to ENB), and T32GM007592 (to OA) from the National
Institutes of Health, Bethesda, Maryland; FAER and MGH MAO/ECOR Faculty
Development award to (OA); Funds from the Department of Anesthesia,
Critical Care and Pain Medicine, Massachusetts General Hospital, Boston,
Massachusetts. SC Holds a Career Award at the Scientific Interface from
the Burroughs-Wellcome Fund.
NR 49
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U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD OCT
PY 2015
VL 126
IS 10
BP 1901
EP 1914
DI 10.1016/j.clinph.2014.12.022
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CS0HR
UT WOS:000361739500008
ER
PT J
AU Grob, SR
Jakobiec, FA
Stagner, AM
Colby, KA
AF Grob, Seanna R.
Jakobiec, Frederick A.
Stagner, Anna M.
Colby, Kathryn A.
TI Diffuse Epibulbar Complex Lacrimal-Cartilaginous Choristoma: Diagnostic
Clues and Management
SO CORNEA
LA English
DT Article
DE complex choristoma; lacrimal; ocular surface reconstruction; pediatric
ocular surface neoplasms
ID AMNIOTIC MEMBRANE TRANSPLANTATION; RECONSTRUCTION
AB Purpose:To describe the clinical and histopathologic features distinguishing an extensive complex choristoma of the epibulbar surface and to address the management of such lesions.Methods:Clinical history, diagnostic imaging studies, and histopathologic sections stained with hematoxylin and eosin were reviewed from a 2-year-old girl with a congenital conjunctival lesion of the right eye that was surgically excised.Results:The patient clinically displayed an extensive, vascularized amelanotic conjunctival lesion located superotemporally with extension onto the cornea. Her visual acuity was reduced to 20/670. The clinical diagnosis was a large lacrimal gland choristoma with corneal involvement and resulting deprivation amblyopia. The patient underwent an excision of the lesion including the corneal portion, and the ocular surface was reconstructed with amniotic membrane. Histopathologic evaluation disclosed lobules of lacrimal tissue and cartilage plaques, smooth muscle, and nerves consistent with a complex choristoma. Six weeks postoperatively, the visual acuity had improved to 20/180. The patient returned to her local ophthalmologist for amblyopia management.Conclusions:We emphasize the importance of recognizing lesion-induced amblyopia and the timely performance of appropriate surgery for complex epibulbar choristomas. A differential diagnosis of other congenital epibulbar lesions is provided.
C1 [Grob, Seanna R.; Jakobiec, Frederick A.; Stagner, Anna M.; Colby, Kathryn A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA.
[Colby, Kathryn A.] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg, Boston, MA 02114 USA.
[Colby, Kathryn A.] Boston Childrens Hosp, Pediat Cornea Serv, Boston, MA USA.
RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Suite 328,243 Charles St, Boston, MA 02114 USA.
EM fred_jakobiec@meei.harvard.edu
NR 13
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD OCT
PY 2015
VL 34
IS 10
BP 1321
EP 1323
DI 10.1097/ICO.0000000000000517
PG 3
WC Ophthalmology
SC Ophthalmology
GA CR7MF
UT WOS:000361533500024
PM 26147834
ER
PT J
AU Ozieh, MN
Bishu, KG
Dismuke, CE
Egede, LE
AF Ozieh, Mukoso N.
Bishu, Kinfe G.
Dismuke, Clara E.
Egede, Leonard E.
TI Trends in Health Care Expenditure in US Adults With Diabetes: 2002-2011
SO DIABETES CARE
LA English
DT Article
ID MEDICARE PART D; UNITED-STATES; DRUG COVERAGE; COSTS; HYPERTENSION;
PROJECTIONS; DIAGNOSIS; MELLITUS; RECEIPT; BURDEN
AB OBJECTIVEDirect medical cost of diabetes in the U.S. has been estimated to be 2.3 times higher relative to individuals without diabetes. This study examines trends in health care expenditures by expenditure category in U.S. adults with diabetes between 2002 and 2011.RESEARCH DESIGN AND METHODSWe analyzed 10 years of data representing a weighted population of 189,013,514 U.S. adults aged 18 years from the Medical Expenditure Panel Survey. We used a novel two-part model to estimate adjusted mean and incremental medical expenditures by diabetes status, while adjusting for demographics, comorbidities, and time.RESULTSRelative to individuals without diabetes ($5,058 [95% CI 4,949-5,166]), individuals with diabetes ($12,180 [11,775-12,586]) had more than double the unadjusted mean direct expenditures over the 10-year period. After adjustment for confounders, individuals with diabetes had $2,558 (2,266-2,849) significantly higher direct incremental expenditures compared with those without diabetes. For individuals with diabetes, inpatient expenditures rose initially from $4,014 in 2002/2003 to $4,183 in 2004/2005 and then decreased continuously to $3,443 in 2010/2011, while rising steadily for individuals without diabetes. The estimated unadjusted total direct expenditures for individuals with diabetes were $218.6 billion/year and adjusted total incremental expenditures were approximately $46 billion/year.CONCLUSIONSOur findings show that compared with individuals without diabetes, individuals with diabetes had significantly higher health expenditures from 2002 to 2011 and the bulk of the expenditures came from hospital inpatient and prescription expenditures.
C1 [Ozieh, Mukoso N.; Bishu, Kinfe G.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Ozieh, Mukoso N.; Bishu, Kinfe G.; Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[K24DK093699]
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (grant K24DK093699, principal investigator
L.E.E.).
NR 36
TC 7
Z9 7
U1 2
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2015
VL 38
IS 10
BP 1844
EP 1851
DI 10.2337/dc15-0369
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS1PW
UT WOS:000361840500019
PM 26203060
ER
PT J
AU Jacobson, AM
Braffett, BH
Cleary, PA
Dunn, RL
Larkin, ME
Wessells, H
Sarma, AV
AF Jacobson, Alan M.
Braffett, Barbara H.
Cleary, Patricia A.
Dunn, Rodney L.
Larkin, Mary E.
Wessells, Hunter
Sarma, Aruna V.
CA DCCT-EDIC Res Grp
TI Relationship of Urologic Complications With Health-Related Quality of
Life and Perceived Value of Health in Men and Women With Type 1
Diabetes: The Diabetes Control and Complications Trial/Epidemiology of
Interventions and Complications (DCCT/EDIC) Cohort
SO DIABETES CARE
LA English
DT Article
ID URINARY-TRACT SYMPTOMS; SEXUAL DYSFUNCTION; ERECTILE DYSFUNCTION; SURVEY
SF-36; FOLLOW-UP; INDEX; IMPACT; TESTS; TRIAL; ADULTS
AB OBJECTIVELimited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSWe studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 6.6 and 50.6 7.2 years and duration of diabetes was 29.5 +/- 4.8 and 29.8 +/- 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R).RESULTSIn both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (25th percentile) were 3.01 (1.90-4.75) times greater with erectile dysfunction and 2.65 (1.68-4.18) times greater with LUTS and in women, 2.04 (1.25-3.35) times greater with sexual dysfunction and 2.71 (1.72-4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures.CONCLUSIONSSexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.
C1 [Jacobson, Alan M.] Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA.
[Braffett, Barbara H.; Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Dunn, Rodney L.; Sarma, Aruna V.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Larkin, Mary E.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA.
[Wessells, Hunter] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
RP Jacobson, AM (reprint author), Winthrop Univ Hosp, Res Inst, Mineola, NY 11501 USA.
EM amjacobson@winthrop.org
FU Division of Diabetes Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK094176, U01 DK094157, R01 DK083927]; National Eye Institute, the
National Institute of Neurological Disorders and Stroke, the General
Clinical Research Center Program; Clinical and Translational Science
Center Program, Bethesda, MD
FX The DCCT/EDIC has been supported by cooperative agreement grants
(1982-1993, 2012-2017) and contracts (1982-2012) with the Division of
Diabetes Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (current grant numbers U01
DK094176 and U01 DK094157 and additional support by grant R01 DK083927)
and by the National Eye Institute, the National Institute of
Neurological Disorders and Stroke, the General Clinical Research Center
Program (1993-2007), and the Clinical and Translational Science Center
Program (2000-present), Bethesda, MD.
NR 31
TC 3
Z9 3
U1 1
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2015
VL 38
IS 10
BP 1904
EP 1912
DI 10.2337/dc15-0286
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS1PW
UT WOS:000361840500027
PM 26203062
ER
PT J
AU Lo, CS
Shi, YX
Chang, SY
Abdo, S
Chenier, I
Filep, JG
Ingelfinger, JR
Zhang, SL
Chan, JSD
AF Lo, Chao-Sheng
Shi, Yixuan
Chang, Shiao-Ying
Abdo, Shaaban
Chenier, Isabelle
Filep, Janos G.
Ingelfinger, Julie R.
Zhang, Shao-Ling
Chan, John S. D.
TI Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates
renal Ace-2 gene expression and prevents TGF-beta 1-induced kidney
injury in a mouse model of diabetes
SO DIABETOLOGIA
LA English
DT Article
DE ACE-2; Akita mice; Angiotensinogen; Diabetes; Heterogeneous nuclear
ribonucleoprotein F; Hypertension; Renal fibrosis; TGF-beta 1
ID PROXIMAL TUBULAR CELLS; GROWTH-FACTOR-BETA; ANGIOTENSIN-CONVERTING
ENZYME-2; TRANSGENIC MICE; TUBULOINTERSTITIAL FIBROSIS; BINDING PROTEIN;
TGF-BETA; RAT; NEPHROPATHY; HYPERTENSION
AB Aims/hypothesis We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-beta 1 signalling, TGF-beta 1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
Methods Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied.
Results Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-beta 1, TGF-beta receptor II [Tgf-beta rII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1-7 receptor [MasR]) expression, and normalised urinary Ang 1-7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-beta 1 and Tgf-beta rII gene expression. Furthermore, hnRNP F overexpression prevented TGF-beta 1 signalling and TGF-beta 1 inhibition of Ace-2 gene expression.
Conclusions/interpretation These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-beta 1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.
C1 [Lo, Chao-Sheng; Shi, Yixuan; Chang, Shiao-Ying; Abdo, Shaaban; Chenier, Isabelle; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal CRCHUM, Montreal, PQ H2X 0A9, Canada.
[Filep, Janos G.] Univ Montreal, Res Ctr, Maisonneuve Rosemont Hosp, Montreal, PQ H2X 0A9, Canada.
[Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA.
RP Zhang, SL (reprint author), Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal CRCHUM, Tour Viger Pavillon R,900 St Denis St, Montreal, PQ H2X 0A9, Canada.
EM shao.ling.zhang@umontreal.ca; john.chan@umontreal.ca
FU Canadian Institutes of Health Research [MOP 84363, MOP 106688,
MOP-86450, MOP-97742]; Kidney Foundation of Canada [KFOC120008];
Canadian Diabetes Association [NOD_OG-3-14-4472-JC]; National Institutes
of Health (NIH) of USA [HL-48455]; Montreal Diabetes Research Centre of
the CRCHUM
FX This work was supported by grants from the Canadian Institutes of Health
Research (MOP 84363 and MOP 106688 to JSDC, MOP-86450 to SLZ and
MOP-97742 to JGF), the Kidney Foundation of Canada (KFOC120008 to JSDC),
the Canadian Diabetes Association (NOD_OG-3-14-4472-JC to JSDC), and the
National Institutes of Health (NIH) of USA (HL-48455 to JRI). CSL is the
recipient of a fellowship from the Montreal Diabetes Research Centre of
the CRCHUM. Editorial assistance was provided by the CRCHUM Research
Support Office.
NR 51
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD OCT
PY 2015
VL 58
IS 10
BP 2443
EP 2454
DI 10.1007/s00125-015-3700-y
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CR7NY
UT WOS:000361538600028
PM 26232095
ER
PT J
AU Markland, AD
Burgio, KL
Whitehead, WE
Richter, HE
Wilcox, CM
Redden, DT
Beasley, TM
Goode, PS
AF Markland, Alayne D.
Burgio, Kathryn L.
Whitehead, William E.
Richter, Holly E.
Wilcox, C. Mel
Redden, David T.
Beasley, Timothy M.
Goode, Patricia S.
TI Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence:
The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized
Clinical Trial
SO DISEASES OF THE COLON & RECTUM
LA English
DT Article
DE Accidental bowel leakage; Comparative effectiveness; Crossover design;
Fecal incontinence; Functional bowel disorders; Quality of life;
Randomized controlled trial
ID QUALITY-OF-LIFE; RISK-FACTORS; CROSSOVER TRIALS; ANORECTAL DISORDERS;
NICE GUIDANCE; ADULTS; PREVALENCE; HEALTH; OLDER; SUPPLEMENTATION
AB BACKGROUND: Fecal incontinence is a devastating condition with few US Food and Drug Administration-approved pharmacologic treatment options. Loperamide and psyllium, both first-line treatments, have different mechanisms of action without any comparative data.
OBJECTIVE: The purpose of this study was to examine the effectiveness and tolerability of loperamide compared with psyllium for reducing fecal incontinence. We hypothesized that psyllium fiber supplementation would be more effective than loperamide for reducing fecal incontinence episodes and have fewer adverse effects.
DESIGN: We conducted a randomized, double-blind, placebo-controlled crossover trial comparing loperamide (followed by psyllium) with psyllium (followed by loperamide).
SETTINGS: Our sites included outpatient clinics within a Veterans Affairs medical center and university affiliate.
PATIENTS: Participants included community-dwelling adults (n = 80) with at least 1 fecal incontinent episode on a 7-day bowel diary.
INTERVENTION: Participants received either daily loperamide (plus placebo psyllium powder) or psyllium powder (plus loperamide placebo) for 4 weeks. After a 2-week washout, participants crossed over to 4 weeks of alternate treatment.
MAIN OUTCOME MEASURES: The primary outcome was the number of fecal incontinence episodes from 7-day bowel diaries. Secondary outcomes included symptom severity, quality of life, and tolerability.
RESULTS: Mean age was 60.7 10.1 years; 68% were men. After determining nonsignificant carryover effects, combined analyses showed no differences between the loperamide and psyllium groups for reducing fecal incontinent episodes, symptom severity, or quality of life. Within each group, both loperamide and psyllium reduced fecal incontinent episodes and improved symptom severity and quality of life. Constipation occurred in 29% of participants for loperamide vs 10% for psyllium.
LIMITATIONS: Limitations include the washout period length and dropout rate after crossing over to the second intervention.
CONCLUSIONS: Both loperamide and psyllium improve fecal incontinence. Loperamide was associated with more adverse effects, especially constipation.
C1 [Markland, Alayne D.; Burgio, Kathryn L.; Goode, Patricia S.] Birmingham Dept Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA.
[Markland, Alayne D.; Burgio, Kathryn L.; Goode, Patricia S.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35233 USA.
[Whitehead, William E.] Univ N Carolina, Dept Med, Div Gastroenterol, Chapel Hill, NC USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Urogynecol & Pelv Reconstruct Surg, Birmingham, AL 35233 USA.
[Wilcox, C. Mel] Univ Alabama Birmingham, Dept Med, Div Gastroenterol, Birmingham, AL 35233 USA.
[Redden, David T.; Beasley, Timothy M.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35233 USA.
RP Markland, AD (reprint author), Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham Vet Affairs Med Ctr, GRECC 11-G,900 South 18th St, Birmingham, AL 35233 USA.
EM markland@uab.edu
OI Markland, Alayne/0000-0002-6567-6744
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Rehabilitation Research and Development
Service Career Development Awards [CDA-2, B6126W]; John A. Hartford
Foundation through the Southeast Center of Excellence in Geriatric
Medicine
FX This study was supported by the Department of Veterans Affairs, Veterans
Health Administration, Office of Research and Development,
Rehabilitation Research and Development Service Career Development
Awards (CDA-2) to Dr Markland (B6126W) and a grant from the John A.
Hartford Foundation through the Southeast Center of Excellence in
Geriatric Medicine.
NR 36
TC 5
Z9 5
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0012-3706
EI 1530-0358
J9 DIS COLON RECTUM
JI Dis. Colon Rectum
PD OCT
PY 2015
VL 58
IS 10
BP 983
EP 993
DI 10.1097/DCR.0000000000000442
PG 11
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA CR6JJ
UT WOS:000361452300010
PM 26347971
ER
PT J
AU Goto, T
Watase, H
Morita, H
Nagai, H
Brown, CA
Brown, DFM
Hasegawa, K
AF Goto, Tadahiro
Watase, Hiroko
Morita, Hiroshi
Nagai, Hideya
Brown, Calvin A., III
Brown, David F. M.
Hasegawa, Kohei
CA Japanese Emergency Med Network Inv
TI Repeated attempts at tracheal intubation by a single intubator
associated with decreased success rates in emergency departments: an
analysis of a multicentre prospective observational study
SO EMERGENCY MEDICINE JOURNAL
LA English
DT Article
ID AIRWAY MANAGEMENT; ENDOTRACHEAL INTUBATION; LARYNGOSCOPY
AB Objective To determine whether the success rate of repeated attempts at tracheal intubation by a single intubator was lower than those by alternate intubators in the emergency department (ED).
Methods An analysis of data from a multicentre prospective registry (Japanese Emergency Airway Network Registry) of 13 academic and community EDs in Japan between April 2010 and August 2012. We included all adult and paediatric patients who underwent repeated attempts at tracheal intubation in the ED. We compared the intubation success rates at the second and third attempts between attempts at intubation by a single intubator who performed the previous attempts, and the attempts by alternate intubators.
Results We recorded 4094 patients (capture rate, 96%); 1289 patients with repeated attempts at tracheal intubation were eligible for this study. Among these, 871 patients (68%) had a second attempt at intubation by single intubators. At the second attempt, tracheal intubation by a single intubator was associated with a decreased success rate (adjusted odds ratio or AOR, 0.50; 95% CI 0.36 to 0.71), compared with alternate intubators. At the third attempt, intubation by a single intubator was also associated with a decreased success rate (58% vs 70%; unadjusted OR, 0.58; 95% CI 0.38 to 0.89). However, after adjustment for potential confounders, the association lost statistical significance (AOR, 0.89; 95% CI 0.52 to 1.56).
Conclusions In this large multicentre study of ED patients undergoing tracheal intubation, second attempts at intubation by a single intubator, compared with those by alternate intubators, were independently associated with a decreased success rate.
C1 [Goto, Tadahiro; Morita, Hiroshi] Univ Fukui Hosp, Dept Emergency Med, Fukui 9101193, Japan.
[Goto, Tadahiro] Osaka Saiseikai Senri Hosp, Senri Crit Care Med Ctr, Suita, Osaka, Japan.
[Watase, Hiroko] Japanese Emergency Med Network, Seattle, WA USA.
[Nagai, Hideya] Fukui Prefectural Hosp, Dept Emergency Med, Fukui, Japan.
[Brown, Calvin A., III] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Brown, David F. M.; Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, 23-3 Shimoaiduki, Fukui 9101193, Japan.
EM qq_gto@yahoo.co.jp
FU St Luke's Life Science Institute; Massachusetts General Hospital;
Brigham and Women's Hospital
FX This study was supported by a grant from St Luke's Life Science
Institute, and a grant from Massachusetts General Hospital and Brigham
and Women's Hospital. The study sponsors have no involvement in the
study design, in the collection, analysis and interpretation of data; in
the writing of the manuscript; and in the decision to submit the
manuscript for publication.
NR 15
TC 1
Z9 1
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1472-0205
EI 1472-0213
J9 EMERG MED J
JI Emerg. Med. J.
PD OCT
PY 2015
VL 32
IS 10
BP 781
EP 786
DI 10.1136/emermed-2013-203473
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA CS0IQ
UT WOS:000361743100007
PM 25552546
ER
PT J
AU Fan, BJ
Pasquale, LR
Kang, JH
Levkovitch-Verbin, H
Haines, JL
Wiggs, JL
AF Fan, Bao J.
Pasquale, Louis R.
Kang, Jae H.
Levkovitch-Verbin, Hani
Haines, Jonathan L.
Wiggs, Janey L.
TI Association of clusterin (CLU) variants and exfoliation syndrome: An
analysis in two Caucasian studies and a meta-analysis
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Exfoliation syndrome; Glaucoma; Clusterin; Genetic variants;
Meta-analysis
ID PSEUDOEXFOLIATION SYNDROME; LOXL1 GENE; SEQUENCE VARIANTS;
UNITED-STATES; RISK ALLELE; GLAUCOMA; POPULATION; SUSCEPTIBILITY;
POLYMORPHISMS; PATHOGENESIS
AB Exfoliation syndrome (XFS) is an important risk factor for glaucoma (XFG) worldwide. LOXL1 variants are highly associated with XFS in most populations; however, the high frequency of risk alleles in normal individuals and the reversal of risk alleles in different ethnic populations suggest that other factors contribute to XFS pathogenesis. Clusterin (CLU) is an extracellular matrix chaperone that prevents protein aggregation and is highly expressed in ocular tissues affected by XFS. Studies examining common CLU variants for association with XFS have been inconsistent. The purpose of this study was to evaluate CLU variants for association with XFS in two independent datasets from the United States (222 cases and 344 controls) and Israel (92 cases and 102 controls). Seven tag SNPs that captured >95% of alleles at r(2) greater than 0.8 across the CLU genomic region were genotyped using TaqMan assays. Genotypes for an additional SNP, rs2279590, were imputed using phased haplotypes of HapMap reference CEU samples. Of the 8 CLU SNPs selected for the study, none were significantly associated with XFS in either case control group (age and sex adjusted P> 0.14 and 0.36, respectively, in the US and Israeli datasets), or when they were meta-analyzed together (age and sex adjusted P> 0.13). Haplotype analysis using all 8 SNPs or only the promoter region SNPs also did not show significant associations of CLU with XFS in the combined US and Israeli dataset (P> 0.28). Meta-analysis of the data from this study and previous studies in Caucasian populations (1184 cases and 978 controls) resulted in statistically significant association of rs2279590 with XFS (summary OR = 1.18, 95% CI: 1.03-1.33, P = 0.01). Significant association between rs2279590 and XFS was also found in Indian populations (summary OR = 0.76, 95% CI: 0.61-0.96; P = 0.02); however, significant heterogeneity between the Caucasian and Indian populations possibly due to reversal of the risk allele precluded an overall meta-analysis for rs2279590 (Q = 0.001, I-2 = 91%). No significant association was identified for rs3087554 in either Caucasian populations (summary OR = 0.90, 95% CI: 0.77-1.05, P = 0.17) or Indian populations (summary OR = 0.89, 95% Cl: 0.72-1.10, P = 0.28), or in both populations combined (1705 cases and 3713 controls; summary OR = 0.90, 95% CI: 0.79-1.01, P = 0.08). Significant heterogeneity precluded the addition of the Japanese data to the meta-analysis for rs3087554 (Q = 0.006, I-2 = 87%). Our results suggest that common CLU variants may contribute to modest XFS risk but even larger datasets are required to confirm these findings. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Fan, Bao J.; Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Pasquale, Louis R.; Kang, Jae H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02114 USA.
[Levkovitch-Verbin, Hani] Tel Aviv Univ, Goldschleger Eye Inst, Chaim Sheba Med Ctr, Tel Hashomer, Israel.
[Haines, Jonathan L.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM janey_wiggs@meei.harvard.edu
OI Fan, Baojian/0000-0002-6851-2737
FU National Eye Institute [R01 EY020928, R01 EY015872, P30 EY014104];
Research to Prevent Blindness; Arthur Ashley Foundation; Massachusetts
Lions Eye Research Fund
FX This work was supported in part by National Eye Institute Grants R01
EY020928, R01 EY015872 and P30 EY014104, Research to Prevent Blindness,
the Arthur Ashley Foundation and The Massachusetts Lions Eye Research
Fund. A Harvard Medical School Ophthalmology Distinguished Scholar Award
supports Dr. Pasquale.
NR 31
TC 2
Z9 2
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD OCT
PY 2015
VL 139
BP 115
EP 122
DI 10.1016/j.exer.2015.08.004
PG 8
WC Ophthalmology
SC Ophthalmology
GA CS0VW
UT WOS:000361781300012
PM 26272660
ER
PT J
AU Wolfsen, HC
Sharma, P
Wallace, MB
Leggett, C
Tearney, G
Wang, KK
AF Wolfsen, Herbert C.
Sharma, Prateek
Wallace, Michael B.
Leggett, Cadman
Tearney, Guillermo
Wang, Kenneth K.
TI Safety and feasibility of volumetric laser endomicroscopy in patients
with Barrett's esophagus (with videos)
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; HIGH-GRADE DYSPLASIA; RANDOMIZED
CONTROLLED-TRIAL; IN-VIVO; INTRAMUCOSAL CARCINOMA; INTESTINAL
METAPLASIA; CONFOCAL MICROSCOPY; CLINICAL UTILITY; HIGH-SPEED; REAL-TIME
AB Background: Volumetric laser endomicroscopy (VLE) produces high-resolution, cross-sectional surface, and subsurface images for detecting neoplasia, targeting biopsies, and guiding real-time treatment.
Objective: To evaluate the safety and feasibility of the Nvision VLE system.
Design: Prospective, multicenter study.
Setting: Tertiary-care medical centers.
Patients: One hundred patients with suspected Barrett's esophagus, including 52 patients with prior endotherapy.
Interventions: The first-generation Nvision VLE Imaging System, a balloon-centered, rotating optical probe provided images of the mucosa and submucosa through a 6-cm segment length and 360 degrees scan of the distal esophagus.
Main Outcome Measurements: Acquisition of a complete, 6-cm scan from the distal esophagus, demographic and procedural data, and final histologic diagnosis.
Results: VLE imaging was successfully performed in 87 cases. After VLE imaging, biopsy specimens were obtained in 77 patients and mucosal resection was performed in 20 patients. The final pathologic diagnoses of the patients studied were adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29 patients), and normal squamous cells (18 patients). VLE was not completed in 13 of 100 (13%) because of optical probe and console issues. There were 2 minor adverse events (mucosal lacerations not requiring therapy).
Limitations: This was a feasibility study with a first-generation device. There was no direct histopathologic correlation with the VLE images or any comparative analysis with white-light endoscopy or narrow-band imaging findings.
Conclusion: VLE is a safe procedure for patients with suspected or confirmed Barrett's esophagus. Real-time VLE images enabled visualization of the mucosa and submucosa in 87% of cases. Further studies are needed to evaluate the in vivo diagnostic accuracy and clinical utility of VLE.
C1 [Wolfsen, Herbert C.; Wallace, Michael B.] Mayo Clin, Dept Gastroenterol, Jacksonville, FL 32224 USA.
[Sharma, Prateek] Kansas City Vet Adm Med Ctr, Gastroenterol Hepatol & Motil, Kansas City, MO USA.
[Leggett, Cadman; Wang, Kenneth K.] Mayo Clin Rochester, Dept Gastroenterol, Rochester, MN USA.
[Tearney, Guillermo] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Wolfsen, HC (reprint author), Mayo Clin Florida, Div Gastroenterol, Med, 4500 San Pablo Rd South, Jacksonville, FL 32224 USA.
FU NinePoint Medical (Cambridge, Mass); Olympus Inc; Cook Medical; CDx
Laboratories; NinePoint Medical; Olympus Inc.; iLumen Medical; Olympus;
Boston Scientific; CSA Medical; Fujinon; CDx Diagnostics; Covidien
(Barrx)
FX Study funding, including volumetric laser endomicroscopy imaging
consoles and optical probes, was provided by NinePoint Medical
(Cambridge, Mass). H. Wolfsen receives research support from Olympus Inc
and NinePoint Medical. He is a consultant for CSA Medical, Mauna Kea
Technologies, Covidien, and Fuji Film. P. Sharma receives grant funding
from Cook Medical, CDx Laboratories, NinePoint Medical, and Olympus Inc.
G. Tearney receives research support from iLumen Medical and NinePoint
Medical. He is a consultant for NinePoint Medical and Samsung.
Massachusetts General Hospital has a licensing arrangement with
NinePoint Medical. G. Tearney has the rights to receive royalties from
this licensing arrangement. M. Wallace receives research funding from
Olympus, Boston Scientific, and NinePoint Medical. K. Wang receives
research support from NinePoint Medical, CSA Medical, Fujinon, and CDx
Diagnostics and is on the advisory boards for NinePoint Medical and CDx
Diagnostics. K. Wang received research support from Covidien (Barrx)
completed within the past 12 months. Mayo Clinic does not endorse any
specific products, advertisers, or services included in this material.
NR 39
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U1 2
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 OCT
PY 2015
VL 82
IS 4
BP 631
EP 640
DI 10.1016/j.gie.2015.03.1968
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR8BB
UT WOS:000361575000007
PM 25956472
ER
PT J
AU Rodriguez, HP
Meredith, LS
Hamilton, AB
Yano, EM
Rubenstein, LV
AF Rodriguez, Hector P.
Meredith, Lisa S.
Hamilton, Alison B.
Yano, Elizabeth M.
Rubenstein, Lisa V.
TI Huddle up!: The adoption and use of structured team communication for VA
medical home implementation
SO HEALTH CARE MANAGEMENT REVIEW
LA English
DT Article
DE huddles; organizational change; practice redesign; team communication;
teamwork
ID TRANSACTIVE MEMORY-SYSTEMS; PRIMARY-CARE; LEARNING ORGANIZATION;
SITUATION AWARENESS; READINESS; FRAMEWORK; BURNOUT
AB Background: Daily clinical team meetings (i.e., huddles) may be helpful in implementing new roles and responsibilities for patient care because they provide a regular opportunity for member learning and feedback.
Purposes: We examined how huddles were implemented in the context of the VA patient-centered medical home (PCMH) transformation, including assessing barriers and facilitators to regular huddling among small teams (teamlets). We assessed the extent to which teamlet members that huddled had higher self-efficacy for PCMH changes, reported better teamwork experiences, and perceived more supportive practice environments.
Methodology/Approach: We used a convergent mixed-methods approach to analyze 79 teamlet member interviews from six VA primary care practices and 418 clinician and staff PCMH survey responses from the six interviewed practices and 13 additional practices in the same region.
Findings: Most members reported participating in teamlet huddles when asked in surveys (85%). A minority of interview participants, however, described routine huddling focused on previsit planning that included all members. When members reported routine teamlet huddling, activities included (a) previsit planning, (b) strategizing treatment plans for patients with special or complex needs, (c) addressing daily workflow and communication issues through collective problem solving, and (d) ensuring awareness of what team members do and what actions are happening on the teamlet and in the practice. Primary care providers (PCPs) were least likely to report routine huddling. PCP huddlers reported greater self-efficacy for implementing PCMH changes. All huddlers, irrespective of role, reported better teamwork and more supportive practice climates. The most common barriers to teamlet huddling were limited time and operational constraints.
Practice Implications: In order to improve the impact of huddles on patient care, practice leaders should clearly communicate the goals, requirements, and benefits of huddling and provide adequate time and resources to ensure that frontline teams use huddle time to improve patient care.
C1 [Rodriguez, Hector P.] Univ Calif Berkeley, Sch Publ Hlth, Ctr Healthcare Org & Innovat Res, Hlth Policy & Management, Berkeley, CA 94720 USA.
[Rodriguez, Hector P.] Univ Calif Berkeley, Sch Publ Hlth, Ctr Healthcare Org & Innovat Res, Berkeley, CA 94720 USA.
[Meredith, Lisa S.] RAND Corp, Behav & Policy Sci Res Dept, Santa Monica, CA USA.
[Hamilton, Alison B.; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Care Syst, HSR&D Ctr Study Healthcare Innovat Implementat &, North Hills, CA USA.
[Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ, Hlth Policy & Management, Los Angeles, CA 90024 USA.
[Rubenstein, Lisa V.] Ctr Implementat Practice & Res Support, North Hills, CA USA.
[Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffen Sch Med, Med, Los Angeles, CA 90095 USA.
[Rubenstein, Lisa V.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Med, Los Angeles, CA 90024 USA.
RP Rodriguez, HP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Ctr Healthcare Org & Innovat Res, Hlth Policy & Management, Berkeley, CA 94720 USA.
EM hrod@berkeley.edu
FU Veterans Health Administration's PACT Demonstration Laboratory
initiative; VA Office of Patient Care Services; VA HSR&D Service Senior
Research Career Scientist award [05-195]
FX This work was undertaken as part of the Veterans Health Administration's
PACT Demonstration Laboratory initiative, supporting and evaluating VA's
transition to a patient-centered medical home. Funding for the PACT
Demonstration Laboratory initiative is provided by the VA Office of
Patient Care Services. Dr. Yano's effort was funded by a VA HSR&D
Service Senior Research Career Scientist award (Project #05-195). The
views expressed within are solely those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs or
the United States government.
NR 32
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Z9 5
U1 3
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0361-6274
EI 1550-5030
J9 HEALTH CARE MANAGE R
JI Health Care Manage. Rev.
PD OCT-DEC
PY 2015
VL 40
IS 4
BP 286
EP 299
DI 10.1097/HMR.0000000000000036
PG 14
WC Health Policy & Services
SC Health Care Sciences & Services
GA CR8LU
UT WOS:000361604800003
PM 25029511
ER
PT J
AU Singer, SJ
Hayes, JE
Gray, GC
Kiang, MV
AF Singer, Sara J.
Hayes, Jennifer E.
Gray, Garry C.
Kiang, Mathew V.
TI Making time for learning-oriented leadership in multidisciplinary
hospital management groups
SO HEALTH CARE MANAGEMENT REVIEW
LA English
DT Article
DE collective learning; leadership; learning-oriented leadership; mixed
methods; safety
ID HEALTH-CARE; TECHNOLOGY IMPLEMENTATION; PSYCHOLOGICAL SAFETY; TEAMS;
PERSPECTIVE; PERFORMANCE; BEHAVIOR; IMPROVEMENT; DYNAMICS; PROGRAM
AB Background: Although the clinical requirements of health care delivery imply the need for interdisciplinary management teams to work together to promote frontline learning, such interdisciplinary, learning-oriented leadership is atypical.
Purpose: We designed this study to identify behaviors enabling groups of diverse managers to perform as learning-oriented leadership teams on behalf of quality and safety.
Approach: We randomly selected 12 of 24 intact groups of hospital managers from one hospital to participate in a Safety Leadership Team Training program. We collected primary data from March 2008 to February 2010 including pre- and post-staff surveys, multiple interviews, observations, and archival data from management groups. We examined the level and trend in frontline perceptions of managers' learning-oriented leadership following the intervention and ability of management groups to achieve objectives on targeted improvement projects. Among the 12 intervention groups, we identified higher- and lower-performing intervention groups and behaviors that enabled higher performers to work together more successfully.
Findings: Management groups that achieved more of their performance goals and whose staff perceived more and greater improvement in their learning-oriented leadership after participation in Safety Leadership Team Training invested in structures that created learning capacity and conscientiously practiced prescribed learning-oriented management and problem-solving behaviors. They made the time to do these things because they envisioned the benefits of learning, valued the opportunity to learn, and maintained an environment of mutual respect and psychological safety within their group.
Practice Implications: Learning in management groups requires vision of what learning can accomplish; will to explore, practice, and build learning capacity; and mutual respect that sustains a learning environment.
C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Sch Med, Hlth Care Management & Policy, Boston, MA 02115 USA.
[Hayes, Jennifer E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hayes, Jennifer E.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Gray, Garry C.] Univ Victoria, Sociol, Victoria, BC V8W 2Y2, Canada.
[Gray, Garry C.] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA.
[Kiang, Mathew V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Sch Med, Hlth Care Management & Policy, 665 Huntington Ave, Boston, MA 02115 USA.
EM ssinger@hsph.harvard.edu
FU Donaghue Foundation of Hartford CT [DF07-212]; Massachusetts General
Hospital, Boston MA
FX The authors wish to thank participants in the Healthcare Adventures
Safety Leadership Team Training Program for their insightful
contributions to this program, to the faculty and staff of the Center
for Medical Simulation, Cambridge, MA, for creating and conducting the
simulations, and to the editor and reviewers for their insightful
suggestions for improving an earlier version of this manuscript. We
gratefully acknowledge financial support for this research from the
Donaghue Foundation of Hartford CT (#DF07-212) and from the
Massachusetts General Hospital, Boston MA. The research described herein
was approved by the institutional review board at participating
institutions.
NR 40
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U1 5
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0361-6274
EI 1550-5030
J9 HEALTH CARE MANAGE R
JI Health Care Manage. Rev.
PD OCT-DEC
PY 2015
VL 40
IS 4
BP 300
EP 312
DI 10.1097/HMR.0000000000000037
PG 13
WC Health Policy & Services
SC Health Care Sciences & Services
GA CR8LU
UT WOS:000361604800004
PM 25029508
ER
PT J
AU Lambiase, MJ
Kubzansky, LD
Thurston, RC
AF Lambiase, Maya J.
Kubzansky, Laura D.
Thurston, Rebecca C.
TI Positive Psychological Health and Stroke Risk: The Benefits of Emotional
Vitality
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE psychological health; emotions; stroke; cardiovascular disease;
prospective
ID CARDIOVASCULAR HEALTH; ASSOCIATION
AB Objective: Stroke is a leading cause of death and disability. Various forms of positive psychological health (e.g., emotional vitality) are associated with lower risk for heart disease. However, it is unclear whether positive psychological health may also be beneficial for stroke risk. The purpose of the present study was to examine prospectively the association between emotional vitality and incident stroke in a nationally representative sample of 6,019 participants in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Methods: Emotional vitality was assessed via self-report at study baseline in 1971-1975. Stroke cases were identified from hospital/nursing home discharge reports and death certificates. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals of incident stroke associated with a 1 SD increase in emotional vitality scores. Models were adjusted for traditional cardiovascular disease risk factors and subsequently for psychological distress. Results: Higher emotional vitality was associated with lower risk of incident stroke over a mean of 16.29 (SD = 4.75) years of follow -up (hazard ratio = 0.89; 95% confidence interval: 0.81, 0.99). Findings persisted when controlling for traditional cardiovascular disease risk factors and psychological distress. Conclusions: Higher levels of emotional vitality were prospectively associated with lower stroke risk in a representative sample of the U.S. population. Associations were independent of psychological distress. Results point to the potential importance of positive psychological functioning for cardiovascular health and for stroke prevention.
C1 [Lambiase, Maya J.] VA Pittsburgh Healthcare Syst, Dept Vet Affairs, Pittsburgh, PA 15240 USA.
[Lambiase, Maya J.; Thurston, Rebecca C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Cambridge, MA 02138 USA.
RP Lambiase, MJ (reprint author), VA Pittsburgh Healthcare Syst, Res Off Bldg 151R,Univ Dr C, Pittsburgh, PA 15240 USA.
EM Maya.Lambiase@va.gov
FU Department of Veterans Affairs Advanced Fellowship in Women's Health, VA
Pittsburgh Healthcare System; National Institute of Mental Health
[MH092707-01]; Robert Wood Johnson Foundation Health and Society
Scholars Implementation [045821]; Robert Wood Johnson Foundation
FX This work is supported by resources and funding from the Department of
Veterans Affairs Advanced Fellowship in Women's Health, VA Pittsburgh
Healthcare System. This work was also supported by the National
Institute of Mental Health (MH092707-01), the Robert Wood Johnson
Foundation Health and Society Scholars Implementation Grant 045821, and
the Robert Wood Johnson Foundation grant, "Exploring the Concept of
Positive Health." The contents do not represent the views of the
Department of Veterans Affairs, Department of Defense, or the United
States Government.
NR 13
TC 2
Z9 2
U1 6
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
EI 1930-7810
J9 HEALTH PSYCHOL
JI Health Psychol.
PD OCT
PY 2015
VL 34
IS 10
BP 1043
EP 1046
DI 10.1037/hea0000228
PG 4
WC Psychology, Clinical; Psychology
SC Psychology
GA CR8XC
UT WOS:000361636600009
PM 25867031
ER
PT J
AU Wang, ZJ
Zhou, YJ
Galper, BZ
Gao, F
Yeh, RW
Mauri, L
AF Wang, Zhi Jian
Zhou, Yu Jie
Galper, Benjamin Z.
Gao, Fei
Yeh, Robert W.
Mauri, Laura
TI Association of body mass index with mortality and cardiovascular events
for patients with coronary artery disease: a systematic review and
meta-analysis
SO HEART
LA English
DT Article
ID OBESITY PARADOX; HEART-DISEASE; MYOCARDIAL-INFARCTION; US ADULTS;
IMPACT; INTERVENTION; PREVALENCE; FITNESS; WEIGHT; COHORT
AB Objectives The association between obesity and prognosis in patients with coronary artery disease (CAD) remains uncertain. We undertook a meta-analysis for the effects of body mass index (BMI) on mortality and cardiovascular events in these patients.
Methods We identified studies that provided risk estimates for mortality or cardiovascular events on the basis of BMI in patients with CAD. Summary estimates of relative risks were obtained for five BMI groups: underweight, normal-weight, overweight, obese and grade II/III obese. Mortality was analysed separately as short-term (<6 months) and long-term (>= 6 months).
Results Data from 89 studies with 1 300 794 patients were included. Mean follow-up of long-term estimates was 3.2 years. Using normal-weight as the reference, underweight was associated with higher risk of short-term mortality (2.24 (1.85 to 2.72)) and long-term mortality (1.70 (1.56 to 1.86)), overweight and obesity were both associated with lower risk of short-term mortality (0.69 (0.64 to 0.75); 0.68 (0.61 to 0.75)) and long-term mortality (0.78 (0.74 to 0.82); 0.79 (0.73 to 0.85)), but the long-term benefit of obesity disappeared after 5 years of follow-up (0.99 (0.91 to 1.08)). Grade II/III obesity was associated with lower risk of mortality in the short term (0.76 (0.62 to 0.91)) but higher risk after 5 years of follow-up (1.25 (1.14 to 1.38)). The similar J-shaped pattern was also seen for cardiovascular mortality and across different treatment strategies. Meta-regression found an attenuation of the inverse association between BMI and risk of mortality over longer follow-up.
Conclusions Our data support a J-shaped relationship between mortality and BMI in patients with CAD. The limitation of current literature warrants better design of future studies.
C1 [Wang, Zhi Jian; Zhou, Yu Jie; Gao, Fei] Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China.
[Wang, Zhi Jian; Galper, Benjamin Z.; Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wang, Zhi Jian; Galper, Benjamin Z.; Yeh, Robert W.; Mauri, Laura] Harvard Univ, Sch Med, Boston, MA USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yeh, Robert W.; Mauri, Laura] Harvard Clin Res Inst, Boston, MA USA.
RP Zhou, YJ (reprint author), Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Anzhen Ave 2, Beijing 100029, Peoples R China.
EM azzyj12@163.com
NR 28
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Z9 20
U1 1
U2 8
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 OCT
PY 2015
VL 101
IS 20
BP 1631
EP 1638
DI 10.1136/heartjnl-2014-307119
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CS1KT
UT WOS:000361824200008
PM 26025084
ER
PT J
AU Faghih, RT
Dahleh, MA
Adler, GK
Klerman, EB
Brown, EN
AF Faghih, Rose T.
Dahleh, Munther A.
Adler, Gail K.
Klerman, Elizabeth B.
Brown, Emery N.
TI Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent
Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Algorithms; biological system modeling; biomedical signal processing;
compressed sensing; parameter estimation
ID MODEL; ALGORITHM; PROFILES; FEEDBACK; FOCUSS; WOMEN; ACTH
AB Pulsatile release of cortisol from the adrenal glands is governed by pulsatile release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. In return, cortisol has a negative feedback effect on ACTH release. Simultaneous recording of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because of several factors: 1) stimulator ACTH pulse activity, 2) kinematics of ACTH and cortisol, 3) the sampling interval, and 4) the measurement error. We model ACTH and cortisol secretion simultaneously using a linear differential equations model with Gaussian errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-min intervals over 24 h from ten healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 h, which is highly consistent with the results of another cortisol data analysis approach. Modeling the interactions between ACTH and cortisol allows for accurate quantification of pulsatile events, and normal and pathological states. This could lay the basis for a more physiologically-based approach for administering cortisol therapeutically. The proposed approach can be adapted to deconvolve other pairs of hormones with similar interactions.
C1 [Faghih, Rose T.; Dahleh, Munther A.] MIT, Cambridge, MA 02139 USA.
[Faghih, Rose T.] Massachusetts Gen Hosp, MIT Harvard Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Adler, Gail K.; Klerman, Elizabeth B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Brown, Emery N.] MIT, Massachusetts Gen Hosp, Cambridge, MA 02139 USA.
[Faghih, Rose T.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Faghih, Rose T.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Faghih, Rose T.] MIT, Lab Informat & Decis Syst, Cambridge, MA 02139 USA.
[Dahleh, Munther A.] MIT, Dept Elect Engn & Comp Sci EECS, EECS, Cambridge, MA 02139 USA.
[Adler, Gail K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Med, Boston, MA 02115 USA.
[Adler, Gail K.] Brigham & Womens Hosp, Harvard Catalyst Clin Res Ctr, Boston, MA 02115 USA.
[Klerman, Elizabeth B.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Analyt & Modeling Unit, Med & Neurol, Boston, MA 02115 USA.
[Brown, Emery N.] MIT, Inst Med Engn & Sci, Med Engn, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Computat Neurosci, Cambridge, MA 02139 USA.
[Brown, Emery N.] Harvard Univ, Sch Med, Anaesthesia, Cambridge, MA 02138 USA.
RP Faghih, RT (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM rfaghih@mit.edu
FU NIH [R01AR43130, M01RR20635, K01AG00661, R01GM 53559, K24 HL103845, DP1
OD003646]; NASA [NCC9-58]; NSBRI; NSF Graduate Research Fellowship;
National Space Biomedical Research Institute through NASA [NIH
P01-AG09975, K24-HL105664, RC2-HL101340, R01-HL-11408, R01-64105018,
HFP01603, HFP02802, NCC 9-58]; NSF [0836720]; [EFRI-0735956]
FX The original data collection was supported under Grant NIH R01AR43130
(GKA), Grant M01RR20635 (BWH GCRC), Grant K01AG00661 (EBK), Grant R01GM
53559 (ENB), and Grant NASA NCC9-58 with the NSBRI. The work of R. T.
Faghih was supported in part by the NSF Graduate Research Fellowship.
The work of M. A. Dahleh was supported in part under Grant EFRI-0735956.
The work of G. K. Adler was supported in part under Grant NIH K24
HL103845. The work of E. B. Klerman was supported in part under Grant
NIH P01-AG09975, Grant K24-HL105664, Grant RC2-HL101340, Grant
R01-HL-11408, Grant R01-64105018, and Grant HFP01603 and Grant HFP02802
from the National Space Biomedical Research Institute through NASA NCC
9-58. The work of E. N. Brown was supported in part by NIH under Grant
DP1 OD003646 and by NSF under Grant 0836720. A preliminary version of
this work was presented in R. T. Faghih's Ph.D. dissertation [4].
Asterisk indicates corresponding author..
NR 28
TC 1
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U1 0
U2 8
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD OCT
PY 2015
VL 62
IS 10
BP 2379
EP 2388
DI 10.1109/TBME.2015.2427745
PG 10
WC Engineering, Biomedical
SC Engineering
GA CR9TZ
UT WOS:000361701300006
PM 25935025
ER
PT J
AU Ghassemi, M
Van Stan, JH
Mehta, DD
Zanartu, M
Cheyne, HA
Hillman, RE
Guttag, JV
AF Ghassemi, Marzyeh
Van Stan, Jarrad H.
Mehta, Daryush D.
Zanartu, Matias
Cheyne, Harold A., II
Hillman, Robert E.
Guttag, John V.
TI Learning to Detect Vocal Hyperfunction From Ambulatory Neck-Surface
Acceleration Features: Initial Results For Vocal Fold Nodules (vol 61,
pg 1668, 2014)
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Correction
C1 [Ghassemi, Marzyeh; Guttag, John V.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Van Stan, Jarrad H.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Van Stan, Jarrad H.; Hillman, Robert E.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
[Mehta, Daryush D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Mehta, Daryush D.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA.
[Zanartu, Matias] Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile.
[Cheyne, Harold A., II] Cornell Univ, Ornithol Lab, Bioacoust Res Program, Ithaca, NY 14853 USA.
RP Ghassemi, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
EM mghassem@mit.edu
NR 1
TC 0
Z9 0
U1 2
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD OCT
PY 2015
VL 62
IS 10
BP 2544
EP 2544
DI 10.1109/TBME.2015.2465051
PG 1
WC Engineering, Biomedical
SC Engineering
GA CR9TZ
UT WOS:000361701300021
PM 26389645
ER
PT J
AU Pringle, PL
Stewart, KO
Peloquin, JM
Sturgeon, HC
Nguyen, D
Sauk, J
Garber, JJ
Yajnik, V
Ananthakrishnan, AN
Chan, AT
Xavier, RJ
Khalili, H
AF Pringle, Patricia L.
Stewart, Kathleen O.
Peloquin, Joanna M.
Sturgeon, Holly C.
Deanna Nguyen
Sauk, Jenny
Garber, John J.
Yajnik, Vijay
Ananthakrishnan, Ashwin N.
Chan, Andrew T.
Xavier, Ramnik J.
Khalili, Hamed
TI Body Mass Index, Genetic Susceptibility, and Risk of Complications Among
Individuals with Crohn's Disease
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE obesity; Crohn's disease complications; genetic predisposition
ID INFLAMMATORY-BOWEL-DISEASE; MESENTERIC ADIPOSE-TISSUE;
NECROSIS-FACTOR-ALPHA; CLINICAL-COURSE; INSULIN-RESISTANCE; ADIPONECTIN;
OBESITY; PROTEIN; IMPACT; COHORT
AB Background:Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear.Methods:We conducted a cross-sectional study of patients with CD enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. A genetic risk score was calculated using previously reported single-nucleotide polymorphisms-associated genome-wide with CD susceptibility. We used logistic regression to estimate the effect of body mass index (BMI) and its interaction with genetic risk on risk of CD complications.Results:Among 846 patients with CD, 350 required surgery, 242 with penetrating disease, 182 with stricturing disease, and 226 with perianal disease. There were no associations between obesity (BMI 30 kg/m(2)) and risk of perianal disease, stricturing disease, or surgery. Compared with normal-weight individuals with BMI < 25 kg/m(2), obesity was associated with lower risk of penetrating disease (odds ratio [OR = 0.56; 95% confidence interval [CI], 0.31-0.99). This association persists among a subgroup of participants with available BMI before development of penetrating disease (OR = 0.40; 95% CI, 0.16-0.88). There were no interactions between BMI and genetic risk score on risk of CD complications (all P-interaction > 0.28).Conclusions:Our data suggest that obesity does not negatively impact long-term progression of CD, even after accounting for genetic predisposition.
C1 [Pringle, Patricia L.; Stewart, Kathleen O.; Peloquin, Joanna M.; Sturgeon, Holly C.; Deanna Nguyen; Sauk, Jenny; Garber, John J.; Yajnik, Vijay; Ananthakrishnan, Ashwin N.; Chan, Andrew T.; Xavier, Ramnik J.; Khalili, Hamed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Xavier, Ramnik J.] Broad Inst, Cambridge, MA USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Khalili, H (reprint author), Massachusetts Gen Hosp, Digest Healthcare Ctr, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM hkhalili@mgh.harvard.edu
FU Crohn's and Colitis Foundation of America (CCFA); American
Gastroenterological Association (AGA); National Institute of Diabetes
and Digestive and Kidney Diseases [K23 DK099681]; [K24 DK098311]
FX A. T. Chan is supported by a senior investigator grant from the Crohn's
and Colitis Foundation of America (CCFA) and K24 DK098311. H. Khalili is
supported by a career development award from the American
Gastroenterological Association (AGA) and by National Institute of
Diabetes and Digestive and Kidney Diseases (K23 DK099681). A. N.
Ananthakrishnan is a member of the scientific advisory board for
Prometheus Inc, and Janssen, Inc. A. T. Chan has served as a consultant
for Bayer Healthcare, Millennium Pharmaceuticals, Pfizer Inc., and Pozen
Inc. R. J. Xavier has served as a consultant for Novartis. V. Yajnik has
served as a consultant for Biogen, UCB, NPS, Jansen, AbbVie, and Takeda.
The remaining authors have no conflict of interest to disclose.
NR 31
TC 4
Z9 4
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD OCT
PY 2015
VL 21
IS 10
BP 2304
EP 2310
DI 10.1097/MIB.0000000000000498
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR6WW
UT WOS:000361489900009
PM 26181430
ER
PT J
AU Ananthakrishnan, AN
Khalili, H
Song, MY
Higuchi, LM
Richter, JM
Nimptsch, K
Wu, K
Chan, AT
AF Ananthakrishnan, Ashwin N.
Khalili, Hamed
Song, Mingyang
Higuchi, Leslie M.
Richter, James M.
Nimptsch, Katharina
Wu, Kana
Chan, Andrew T.
TI High School Diet and Risk of Crohn's Disease and Ulcerative Colitis
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE Crohn's disease; ulcerative colitis; diet; iron; fiber
ID INFLAMMATORY-BOWEL-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; MIDDLE-AGED
WOMEN; LONG-TERM INTAKE; FATTY-ACIDS; IRON SUPPLEMENTATION; PROSPECTIVE
COHORT; ADOLESCENT DIET; OLMSTED COUNTY; NURSES HEALTH
AB Background:Diet may play an important role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC); yet, there are few prospective studies of dietary factors. None have examined the association between adolescent diet and risk of inflammatory bowel diseases (CD and UC).Methods:This study included women enrolled in Nurses' Health Study II who completed a validated high school dietary questionnaire in 1998. We examined the effect of dietary patterns (prudent or Western diet) and individual components of each patterns. We documented incident cases of CD and UC through 2011 based on physician review of medical records and used Cox proportional hazards models adjusting for confounders to estimate hazard ratios and confidence intervals for CD and UC.Results:Over 763,229 person-years of follow-up, we identified 70 incident cases of CD and 103 cases of UC. Compared with women in the lowest quartile of a prudent diet score (characterized by greater intake of fruits, vegetables, and fish), women in the highest quartile had a 53% lower risk of CD (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98; P-trend = 0.04). Specifically, greater intake of fish (P-trend = 0.01) and fiber (P-trend = 0.06) were associated with lower risk of CD. In contrast, Western diet score was not associated with risk of CD. Neither dietary patterns nor individual food or nutrient groups was associated with UC.Conclusions:Adolescent diet is associated with risk of CD, but not UC, offering insights into disease pathogenesis.
C1 [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Richter, James M.; Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Song, Mingyang; Nimptsch, Katharina; Wu, Kana] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Song, Mingyang; Nimptsch, Katharina; Wu, Kana] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Higuchi, Leslie M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA USA.
[Nimptsch, Katharina] Max Delbruck Ctr Mol Med MDC, Mol Epidemiol Res Grp, Berlin, Germany.
[Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@mgh.harvard.edu
RI Song, Mingyang/M-6701-2013;
OI Song, Mingyang/0000-0002-1324-0316; Nimptsch,
Katharina/0000-0001-7877-205X
FU Crohn's and Colitis Foundation of America; National Institutes of Health
[K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742,
K23 DK099681, UM1 CA176276]
FX Supported by a Senior Investigator Award from the Crohn's and Colitis
Foundation of America (to A.T.C.) and the National Institutes of Health
(K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742,
K23 DK099681, and UM1 CA176276). A. N. Ananthakrishnan: Scientific
advisory board for Cubist and Abbvie. J. M. Richter: Consultant for
Policy Analysis, Inc.; A. T. Chan: Consultant for Bayer HealthCare,
Millennium Pharmaceuticals, Pfizer Inc., Pozen Inc. The remaining
authors have no conflict of interest to disclose.
NR 61
TC 5
Z9 5
U1 3
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD OCT
PY 2015
VL 21
IS 10
BP 2311
EP 2319
DI 10.1097/MIB.0000000000000501
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR6WW
UT WOS:000361489900010
PM 26236952
ER
PT J
AU Bengali, R
Vazquez, R
AF Bengali, Raheel
Vazquez, Rafael
TI Inferior Vena Cava Filter Embolus to the Right Ventricle: Anesthesia and
High-Risk Percutaneous Procedures
SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
LA English
DT Article
DE inferior vena cava filter; interventional radiology; IVC filter;
embolization; retrieval; anesthesia for percutaneous procedures
ID EMBOLIZATION; ASSOCIATION; TAMPONADE; PLACEMENT; FRACTURE
C1 [Bengali, Raheel; Vazquez, Rafael] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Bengali, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA.
EM rbengali@partners.org
NR 12
TC 0
Z9 0
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-0770
EI 1532-8422
J9 J CARDIOTHOR VASC AN
JI J. Cardiothorac. Vasc. Anesth.
PD OCT
PY 2015
VL 29
IS 5
BP 1322
EP 1327
DI 10.1053/j.jvca.2014.05.021
PG 6
WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System;
Peripheral Vascular Disease
SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System
GA CS0WM
UT WOS:000361782900035
PM 25304888
ER
PT J
AU Lo, WK
Mashimo, H
AF Lo, Wai-Kit
Mashimo, Hiroshi
TI Critical Assessment of Endoscopic Techniques for Gastroesophageal Reflux
Disease
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Review
DE gastroesophageal reflux disease; advanced endoscopic techniques;
radiofrequency; endoscopic placation; injectable bulking agents
ID TRANSORAL INCISIONLESS FUNDOPLICATION; RADIOFREQUENCY ENERGY DELIVERY;
LOWER ESOPHAGEAL SPHINCTER; FULL-THICKNESS PLICATION; LAPAROSCOPIC
ANTIREFLUX SURGERY; SHAM-CONTROLLED TRIAL; RANDOMIZED CLINICAL-TRIAL;
PUMP INHIBITOR THERAPY; LONG-TERM FAILURE; STRETTA RADIOFREQUENCY
AB Over the past 2 decades, a number of new endoscopic techniques have been developed for management of gastroesophageal (GE) reflux disease symptoms as alternatives to medical management and surgical fundoplication. These devices include application of radiofrequency treatment (Stretta), endoscopic plication (EndoCinch, Plicator, Esophyx, MUSE), and injection of bulking agents (Enteryx, Gatekeeper, Plexiglas, Duragel). Their goal was symptom relief through reduction of tissue compliance and enhancement of anatomic resistance at the GE junction. In this review, we critically assess the research behind the efficacy, safety, and durability of these treatments to better understand their roles in contemporary GE reflux disease management.
C1 [Lo, Wai-Kit; Mashimo, Hiroshi] VA Boston Healthcare Syst, Dept Gastroenterol, West Roxbury, MA 02132 USA.
[Lo, Wai-Kit] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
[Lo, Wai-Kit; Mashimo, Hiroshi] Harvard Univ, Sch Med, Boston, MA USA.
RP Mashimo, H (reprint author), VA Boston Healthcare Syst, Dept Gastroenterol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM hmashimo@hms.harvard.edu
OI Lo, Wai-Kit/0000-0002-1526-352X
NR 52
TC 3
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0192-0790
EI 1539-2031
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD OCT
PY 2015
VL 49
IS 9
BP 720
EP 724
DI 10.1097/MCG.0000000000000389
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR6SR
UT WOS:000361478200002
PM 26241152
ER
PT J
AU Korsten, MA
Spungen, AM
Radulovic, M
Rosman, AS
Hunt, K
Galea, MD
Kornfeld, SD
Lyons, BL
Yen, C
Bauman, WA
AF Korsten, Mark A.
Spungen, Ann M.
Radulovic, Miroslav
Rosman, Alan S.
Hunt, Kristel
Galea, Marinella D.
Kornfeld, Stephen D.
Lyons, Brian L.
Yen, Christina
Bauman, William A.
TI Neostigmine Administered With MoviPrep Improves Bowel Preparation for
Elective Colonoscopy in Patients With Spinal Cord Injury A Randomized
Study
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Article
DE neostigmine; MoviPrep; paraplegia; tetraplegia; colonoscopy
ID ORAL SODIUM-PHOSPHATE; POLYETHYLENE-GLYCOL SOLUTION; MAGNESIUM CITRATE;
CONTROLLED-TRIAL; LAVAGE SOLUTION; GLYCOPYRROLATE; EVACUATION; REGIMENS;
EFFICACY; SAFETY
AB Background:Poor preparation for elective colonoscopy is exceedingly common in persons with spinal cord injury (SCI). This unsatisfactory outcome is likely due to long-standing difficulty with evacuation and decreased colonic motility, which may result in inadequate responses to conventional bowel preparation regimens. We determined whether the addition of neostigmine to MoviPrep before elective colonoscopy produced a higher percentage of acceptable bowel preparations in patients with SCI.Methods:Twenty-seven SCI subjects were prospectively randomized to 1 of 2 arms: low-volume polyethylene glycol-electrolyte lavage with ascorbic acid (MoviPrep) or MoviPrep plus neostigmine methylsulfate and glycopyrrolate (MoviPrep+NG); 28 able-bodied subjects received MoviPrep alone. The quality of the cleansing preparation for colonoscopy was determined by gastroenterologists calibrated to use the Ottawa Scoring System, with an acceptable Ottawa Score (OS) considered to be 3.Results:The administration of MoviPrep alone resulted in suboptimal bowel cleansing in the SCI group compared with the able-bodied group (50% vs. 89% of subjects had an acceptable OS; (2)=7.94, P=0.05). However, when NG was added to MoviPrep in the SCI group, it markedly improved the quality of the bowel preparation, with 85% of patients then having an acceptable OS. The use of NG resulted in minimal bloating and distention before bowel evacuation (P=0.0005), and eye and muscle twitching; these were resolved within 1 hour after NG administration. No significant differences were noted among the preparation groups for adenoma detection rate (P=0.41).Conclusions:The combination of MoviPrep+NG was safe, well tolerated, and an effective approach to prepare the bowel for elective colonoscopy in patients with SCI. The side effects of this preparation were significant compared with the other treatment groups but were considered mild and anticipated.
C1 [Korsten, Mark A.; Spungen, Ann M.; Radulovic, Miroslav; Galea, Marinella D.; Kornfeld, Stephen D.; Lyons, Brian L.; Yen, Christina; Bauman, William A.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA.
[Korsten, Mark A.; Radulovic, Miroslav; Rosman, Alan S.; Hunt, Kristel; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA.
[Korsten, Mark A.; Galea, Marinella D.; Kornfeld, Stephen D.; Bauman, William A.] James J Peters VA Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA.
[Korsten, Mark A.; Spungen, Ann M.; Radulovic, Miroslav; Rosman, Alan S.; Hunt, Kristel; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
[Spungen, Ann M.; Galea, Marinella D.; Kornfeld, Stephen D.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA.
RP Korsten, MA (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Rm 7 A-13 K,130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM mark.korsten@va.gov
FU Department of Veterans Affairs Rehabilitation Research and Development
Service [A6428R, B2468-C, B4162-C]; James J. Peters VA Medical Center
FX Supported by the Department of Veterans Affairs Rehabilitation Research
and Development Service (#A6428R, #B2468-C, #B4162-C) and the James J.
Peters VA Medical Center. None of the authors have financial interests
with Salix, the manufacturer of MoviPrep.
NR 20
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0192-0790
EI 1539-2031
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD OCT
PY 2015
VL 49
IS 9
BP 751
EP 756
DI 10.1097/MCG.0000000000000284
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR6SR
UT WOS:000361478200006
PM 25599220
ER
PT J
AU Alvarez-Breckenridge, CA
Attiah, MA
Zachariah, M
Gummadavelli, A
Yang, J
Codd, PJ
AF Alvarez-Breckenridge, Christopher A.
Attiah, Mark A.
Zachariah, Marcus
Gummadavelli, Abhijeet
Yang, Jimmy
Codd, Patrick J.
TI Ventriculoperitoneal shunt placement for POEMS syndrome
SO JOURNAL OF CLINICAL NEUROSCIENCE
LA English
DT Article
DE Cerebrospinal fluid diversion; Intracranial pressure; Papilledema; POEMS
syndrome; Vascular endothelial growth factor
ID POLYNEUROPATHY
AB We report a 41-year-old woman with a history of an uncomplicated spinal hemangioma resection, who developed acute onset sensory-motor polyneuropathy following influenza vaccine administration. With extensive workup she was diagnosed with POEMS syndrome with progressive headaches, visual loss with papilledema, and repeated elevated lumbar puncture opening pressures despite treatment with acetazolamide and immunosuppressive therapy. Her symptoms dramatically improved following ventriculoperitoneal shunt placement. POEMS syndrome is a paraneoplastic disorder involving a constellation of clinical symptoms including polyneuropathy, organomegaly, endocrinopathy, monoclonal protein elevation, and skin changes. The progression of the disease involves a number of neurovascular sequelae, including symmetric sensory-motor polyneuropathy resembling chronic inflammatory demyelinating polyneuropathy, cerebrovascular accidents, and papilledema associated with increased intracranial pressure. Despite the association of POEMS with papilledema, treatment for this finding typically includes acetazolamide and therapeutic large volume lumbar punctures. To our knowledge, this is the first report of cerebrospinal fluid shunting for the symptomatic management of hydrocephalus associated with POEMS syndrome. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Alvarez-Breckenridge, Christopher A.; Zachariah, Marcus; Yang, Jimmy; Codd, Patrick J.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Attiah, Mark A.] Univ Penn, Dept Neurosurg, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Gummadavelli, Abhijeet] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA.
RP Alvarez-Breckenridge, CA (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, 15 Parkman St Wang 021, Boston, MA 02114 USA.
EM calvarez-breckenridge@partners.org
NR 11
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0967-5868
EI 1532-2653
J9 J CLIN NEUROSCI
JI J. Clin. Neurosci.
PD OCT
PY 2015
VL 22
IS 10
BP 1672
EP 1674
DI 10.1016/j.jocn.2015.03.042
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CS0SS
UT WOS:000361773100024
PM 26077937
ER
PT J
AU Vohringer, PA
Ostacher, MJ
El-Mallakh, RS
Holtzman, NS
Thommi, SB
Whitham, EA
Sullivan, MC
Baldassano, CF
Goodwin, FK
Baldessarini, RJ
Ghaemi, SN
AF Voehringer, Paul A.
Ostacher, Michael J.
El-Mallakh, Rif S.
Holtzman, Niki S.
Thommi, Sairah B.
Whitham, Elizabeth A.
Sullivan, Matthew C.
Baldassano, Claudia F.
Goodwin, Fredrick K.
Baldessarini, Ross J.
Ghaemi, S. Nassir
TI Antidepressants in Type II Versus Type I Bipolar Depression A Randomized
Discontinuation Trial
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE bipolar disorder; antidepressants; maintenance treatment
ID TREATMENT ENHANCEMENT PROGRAM; DISORDER STEP-BD; LITHIUM MONOTHERAPY;
SAFETY; VENLAFAXINE; PLACEBO; DESIGN
AB Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among patients with type II bipolar disorder (BD, BD-II) more than patients with type I BD (BD-I).
Methods Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, BD-I (n = 21) and BD-II (n = 49) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then randomized openly to continue or discontinue ADs for up to 3 years. Outcomes were episode recurrences and changes in standardized symptom ratings.
Results In follow-up averaging 1.64 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in BD-I than in BD-II (for type II, mean [standard deviation] decrease in depressive episodes per year, 0.21 [0.26]; for type I, mean (SD) decrease, 0.35 [0.15]). Subjects with BD-II who continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission.
Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I, except somewhat lower risk of manic/hypomanic episodes.
C1 [Voehringer, Paul A.; Holtzman, Niki S.; Thommi, Sairah B.; Whitham, Elizabeth A.; Sullivan, Matthew C.; Ghaemi, S. Nassir] Tufts Univ, Med Ctr, Dept Psychiat, Mood Disorders Program, Boston, MA 02111 USA.
[Voehringer, Paul A.] Univ Chile, Fac Med, Hosp Clin Univ Chile, Dept Psychiat, Santiago 7, Chile.
[Ostacher, Michael J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[El-Mallakh, Rif S.] Univ Kentucky, Coll Med, Dept Psychiat, Louisville, KY USA.
[Baldassano, Claudia F.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Goodwin, Fredrick K.] George Washington Univ, Sch Med, Ctr Neurosci Med Progress & Soc, Washington, DC USA.
[Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Baldessarini, Ross J.] Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, McLean Div, Belmont, MA USA.
[Ghaemi, S. Nassir] Tufts Univ, Sch Med, Boston, MA 02111 USA.
RP Ghaemi, SN (reprint author), Tufts Med Ctr, 800 Washington St,Box 1007, Boston, MA 02111 USA.
EM nghaemi@tuftsmedicalcenter.org
RI Vohringer, Paul/B-5860-2013;
OI Vohringer, Paul/0000-0002-2460-4680; Ostacher,
Michael/0000-0003-0353-7535
FU National Institute of Mental Health Grant [MH-64189]; Bruce J. Anderson
Foundation; McLean Private Donors Research Fund; Takeda
FX Dr Ghaemi received support from National Institute of Mental Health
Grant MH-64189 and Dr Baldessarini received, in part, grant support from
the Bruce J. Anderson Foundation and the McLean Private Donors Research
Fund.; In the past 36 months, Dr Ghaemi has had a research grant with
Takeda and provided research consultation to Sunovion. All other authors
declare no personal or immediate family business interests that might
seem to represent conflicts of interest.
NR 16
TC 1
Z9 1
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD OCT
PY 2015
VL 35
IS 5
BP 605
EP 608
DI 10.1097/JCP.0000000000000384
PG 4
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA CR0TM
UT WOS:000361036100019
PM 26267418
ER
PT J
AU Jaff, MR
White, CJ
Hiatt, WR
Fowkes, GR
Dormandy, J
Razavi, M
Reekers, J
Norgren, L
AF Jaff, Michael R.
White, Christopher J.
Hiatt, William R.
Fowkes, Gerry R.
Dormandy, John
Razavi, Mahmood
Reekers, Jim
Norgren, Lars
TI An Update on Methods for Revascularization and Expansion of the TASC
Lesion Classification to Include Below-the-Knee Arteries: A Supplement
to the Inter-Society Consensus for the Management of Peripheral Arterial
Disease (TASC II)
SO JOURNAL OF ENDOVASCULAR THERAPY
LA English
DT Article
DE angioplasty; arteries; claudication; critical limb ischemia; occlusion;
peripheral artery disease; revascularization; stenosis; stents; surgery
ID CRITICAL LIMB ISCHEMIA; AORTOILIAC OCCLUSIVE DISEASE; SUPERFICIAL
FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED
CONTROLLED-TRIAL; NITINOL STENT IMPLANTATION; DRUG-ELUTING STENTS;
BARE-METAL STENTS; EXTREMITY BYPASS-SURGERY; VEIN GRAFT FAILURE
AB The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.
C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[White, Christopher J.] Ochsner Clin Fdn, Ochsner Clin School Univ Queensland, New Orleans, LA USA.
[Hiatt, William R.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA.
[Hiatt, William R.] CPC Clin Res, Aurora, CO USA.
[Fowkes, Gerry R.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Dormandy, John] St George Hosp, London, England.
[Razavi, Mahmood] St Josephs Hosp, Orange, CA USA.
[Reekers, Jim] Univ Hosp, Academ Med Ctr, Amsterdam, Netherlands.
[Norgren, Lars] Univ Orebro, Fac Med & Hlth, Dept Surg, SE-70182 Orebro, Sweden.
RP Norgren, L (reprint author), Orebro Univ Hosp, Dept Surg, Surg, SE-70185 Orebro, Sweden.
EM lars.norgren@regionorebrolan.se
FU Aastrom Biosciences; Abbott Vascular; AnGes MG Inc; Bayer Schering
Pharma; Biomedix; Cook; ev3; Mitsubishi Tanabe; Otsuka Pharmaceutical
Co; Sanofi-Aventis; Toray Industries; Medtronic
FX The author(s) report receiving the following financial support for the
research, authorship, and/or publication of this article: VIVA
Physicians [a 501(c)(3) education and research multispecialty
organization] provided an unrestricted grant to the TASC organization.
The development of this TASC II Supplement was supported by unrestricted
educational grants awarded to Discovery London from (in alphabetical
order): Aastrom Biosciences, Abbott Vascular, AnGes MG Inc, Bayer
Schering Pharma, Biomedix, Cook, ev3, Medtronic, Mitsubishi Tanabe,
Otsuka Pharmaceutical Co, Sanofi-Aventis, and Toray Industries. The
companies did not participate in the discussions or in the preparation,
review, or approval of the document.
NR 90
TC 19
Z9 19
U1 4
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1526-6028
EI 1545-1550
J9 J ENDOVASC THER
JI J. Endovascular Ther.
PD OCT
PY 2015
VL 22
IS 5
BP 663
EP 677
DI 10.1177/1526602815592206
PG 15
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS1LQ
UT WOS:000361827200001
ER
PT J
AU Garcia, LA
Jaff, MR
Rocha-Singh, KJ
Zeller, T
Bosarge, C
Kamat, S
McKinsey, JF
AF Garcia, Lawrence A.
Jaff, Michael R.
Rocha-Singh, Krishna J.
Zeller, Thomas
Bosarge, Christopher
Kamat, Suraj
McKinsey, James F.
TI A Comparison of Clinical Outcomes for Diabetic and Nondiabetic Patients
Following Directional Atherectomy in the DEFINITIVE LE Claudicant Cohort
SO JOURNAL OF ENDOVASCULAR THERAPY
LA English
DT Article
DE atherectomy; claudication; diabetes mellitus; directional atherectomy;
infrapopliteal arteries; patency; peripheral artery disease; popliteal
artery; superficial femoral artery; target lesion revascularization
ID PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY ISCHEMIA; RANDOMIZED-TRIAL;
FEMOROPOPLITEAL ARTERIES; ELUTING BALLOON; PRIMARY PATENCY; PREVALENCE;
RESTENOSIS; LESIONS
AB Purpose: To report a subset analysis that evaluated the hypothesis that directional atherectomy for peripheral artery disease in diabetic claudicants has noninferior primary patency at 12 months compared with nondiabetic claudicants. Methods: DEFINITIVE LE, a US/European multicenter study, assessed the effectiveness of directional atherectomy using SilverHawk/TurboHawk systems for treatment of peripheral artery disease in the superficial femoral, popliteal, and infrapopliteal arteries. Of the 800 patients enrolled in the study, only the 598 claudicant patients (mean age 69.5 +/- 10.4 years; 336 men) who were classified at baseline as Rutherford category 1-3 were eligible for this subset analysis. Of these, 46.8% (280/598) had diabetes. Follow-up to 12 months included duplex ultrasound examination, functional assessments, and adverse event evaluations. Independent angiographic and duplex ultrasound core laboratories assessed primary patency and secondary endpoints; a clinical events committee adjudicated adverse events. Results: Although diabetics had significantly more baseline comorbidities, 12-month primary patency (77.0%) was no different than for nondiabetics (77.9%; superiority p=0.98; noninferiority p<0.001) across all anatomic territories treated. Freedom from clinically driven target lesion revascularization was no different between diabetics (83.8%) and nondiabetics (87.5%) overall (p=0.19) or by lesion locations. Secondary clinical outcomes (Rutherford category, ankle-brachial index, and walking impairment) improved at 12 months for both diabetics and nondiabetics. Conclusion: Noninferior 12-month patency rates demonstrate that directional atherectomy is an effective treatment in diabetic as well as nondiabetic claudicants. Directional atherectomy remains an attractive treatment option, improving luminal diameters without stents, which preserves future treatment options for both diabetic and nondiabetic patients with progressive, diffuse vascular disease.
C1 [Garcia, Lawrence A.] Tufts Univ, St Elizabeths Med Ctr, Sch Med, Sect Intervent Cardiol, Boston, MA 02111 USA.
[Garcia, Lawrence A.] Tufts Univ, St Elizabeths Med Ctr, Sch Med, Sect Vasc Med, Boston, MA 02111 USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA.
[Rocha-Singh, Krishna J.] St Johns Hosp, Prairie Heart Inst, Springfield, IL USA.
[Zeller, Thomas] Univ Herzzentrum Freiburg, Bad Krozingen, Germany.
[Bosarge, Christopher] Coastal Vasc & Intervent, Pensacola, FL USA.
[Kamat, Suraj] Christus Spohn Hosp Alice, Alice, TX USA.
[McKinsey, James F.] Univ Hosp Columbia & Cornell, New York Presbyterian Hosp, Div Vasc Surg, New York, NY USA.
RP Garcia, LA (reprint author), St Elizabeths Med Ctr, Sect Intervent Cardiol, 736 Cambridge St, Boston, MA 02135 USA.
EM Lawrence.garcia@steward.org
FU Covidien, Mansfield, MA, USA
FX The author(s) report receiving the following financial support for the
research, authorship, and/or publication of this article: Research
funded by Covidien, Mansfield, MA, USA.
NR 33
TC 3
Z9 3
U1 5
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1526-6028
EI 1545-1550
J9 J ENDOVASC THER
JI J. Endovascular Ther.
PD OCT
PY 2015
VL 22
IS 5
BP 701
EP 711
DI 10.1177/1526602815599550
PG 11
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS1LQ
UT WOS:000361827200006
PM 26250748
ER
PT J
AU Alavi, K
Chan, S
Wise, P
Kaiser, AM
Sudan, R
Bordeianou, L
AF Alavi, Karim
Chan, Sook
Wise, Paul
Kaiser, Andreas M.
Sudan, Ranjan
Bordeianou, Liliana
TI Fecal Incontinence: Etiology, Diagnosis, and Management
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
DE Fecal incontinence; Sacral nerve stimulation; Sphincteroplasty;
Artificial sphincter; Graciloplasty
ID ANTEGRADE CONTINENCE ENEMA; SACRAL NERVE-STIMULATION; QUALITY-OF-LIFE;
RANDOMIZED CONTROLLED-TRIAL; ARTIFICIAL BOWEL SPHINCTER; ANAL
ENDOSONOGRAPHY; SEVERITY INDEX; FOLLOW-UP; BIOFEEDBACK; ADULTS
AB We sought to review the etiology, diagnosis, and treatment of fecal incontinence based on current literature. Additionally, newer treatment methods such as Solesta will be evaluated.
There are many diagnostic modalities available to assess the degree and severity of the patient's incontinence; however, a thorough history and physical exam is critical. Initial attempts at treatment focus on medical management primarily through stool texture modification with the aid of bulking agents. Failure of medical therapy is often followed by a graded increase in the complexity and invasiveness of the available treatment options. The selection of the most appropriate surgical option, such as overlapping sphincteroplasty and neuromodulation, is multifactorial involving both surgeon and patient-related factors. Neuromodulation has received increased attention in the last decade due to its documented therapeutic success, and newer office-based procedures, such as the Solesta injection, are showing promising results in properly selected patients. Finally, diversion remains an option for select patients who have failed all other therapies.
The etiology of fecal incontinence is multifactorial, involving a complex interplay between stool consistency and anatomic integrity. The diagnosis and treatment of fecal incontinence continue to evolve and are showing promising results.
C1 [Alavi, Karim; Chan, Sook] Univ Massachusetts, Div Colon & Rectal Surg, Mem Med Ctr, Worcester, MA 01605 USA.
[Wise, Paul] Washington Univ, Div Colon & Rectal Surg, Sch Med, St Louis, MO USA.
[Kaiser, Andreas M.] Univ So Calif, Keck Sch Med, Div Colon & Rectal Surg, Los Angeles, CA 90033 USA.
[Sudan, Ranjan] Duke Univ, Dept Surg, Sch Med, Durham, NC USA.
[Bordeianou, Liliana] Harvard Univ, Div Colon & Rectal Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Alavi, K (reprint author), Univ Massachusetts, Div Colon & Rectal Surg, Mem Med Ctr, 67 Belmont St, Worcester, MA 01605 USA.
EM karim.alavi@umassmemorial.org
NR 55
TC 1
Z9 1
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
EI 1873-4626
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD OCT
PY 2015
VL 19
IS 10
BP 1910
EP 1921
DI 10.1007/s11605-015-2905-1
PG 12
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA CS0MP
UT WOS:000361754800022
PM 26268955
ER
PT J
AU Ibrahim, SA
AF Ibrahim, S. A.
TI Equity in Lung Cancer Care and Outcomes
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
ID SURVIVAL; COMORBIDITY; SMOKING; RACE
C1 [Ibrahim, S. A.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Ibrahim, S. A.] Philadelphia VA Med Ctr ANNEX, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Ibrahim, SA (reprint author), Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
EM Said.Ibrahim2@va.gov
FU NIAMS NIH HHS [K24AR055259, K24 AR055259]
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1385
EP 1386
DI 10.1007/s11606-015-3346-y
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000002
PM 25903994
ER
PT J
AU Hwang, AS
Atlas, SJ
Cronin, P
Ashburner, JM
Shah, SJ
He, W
Hong, CS
AF Hwang, Andrew S.
Atlas, Steven J.
Cronin, Patrick
Ashburner, Jeffrey M.
Shah, Sachin J.
He, Wei
Hong, Clemens S.
TI Appointment "no-shows" are an independent predictor of subsequent
quality of care and resource utilization outcomes
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE No-show; Identification of high-risk patients; Health disparities;
Psychosocial issues in healthcare
ID PATIENT COMPLEXITY; CO-MORBIDITY; COMORBIDITY; DISPARITIES; VALIDATION;
MANAGEMENT; VISITS; MODEL
AB Identifying individuals at high risk for suboptimal outcomes is an important goal of healthcare delivery systems. Appointment no-shows may be an important risk predictor.
To test the hypothesis that patients with a high propensity to "no-show" for appointments will have worse clinical and acute care utilization outcomes compared to patients with a lower propensity.
We calculated the no-show propensity factor (NSPF) for patients of a large academic primary care network using 5 years of outpatient appointment data. NSPF corrects for patients with fewer appointments to avoid over-weighting of no-show visits in such patients. We divided patients into three NSPF risk groups and evaluated the association between NSPF and clinical and acute care utilization outcomes after adjusting for baseline patient characteristics.
A total of 140,947 patients who visited a network practice from January 1, 2007, through December 31, 2009, and were either connected to a primary care physician or to a primary care practice, based on a previously validated algorithm.
Outcomes of interest were incomplete colorectal, cervical, and breast cancer screening, and above-goal hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) levels at 1-year follow-up, and hospitalizations and emergency department visits in the subsequent 3 years.
Compared to patients in the low NSPF group, patients in the high NSPF group (n=14,081) were significantly more likely to have incomplete preventive cancer screening (aOR 2.41 [2.19-.66] for colorectal, aOR 1.85 [1.65-.08] for cervical, aOR 2.93 [2.62-3.28] for breast cancer), above-goal chronic disease control measures (aOR 2.64 [2.22-3.14] for HbA1c, aOR 1.39 [1.15-1.67] for LDL], and increased rates of acute care utilization (aRR 1.37 [1.31-1.44] for hospitalization, aRR 1.39 [1.35-1.43] for emergency department visits).
NSPF is an independent predictor of suboptimal primary care outcomes and acute care utilization. NSPF may play an important role in helping healthcare systems identify high-risk patients.
C1 [Hwang, Andrew S.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Atlas, Steven J.; Ashburner, Jeffrey M.; Shah, Sachin J.; He, Wei; Hong, Clemens S.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Cronin, Patrick] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA.
RP Hwang, AS (reprint author), Tufts Univ, Sch Med, Boston, MA 02111 USA.
EM andrew.hwang@tufts.edu
NR 29
TC 4
Z9 4
U1 2
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1426
EP 1433
DI 10.1007/s11606-015-3252-3
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000016
PM 25776581
ER
PT J
AU Glover, M
Khalilzadeh, O
Choy, G
Prabhakar, AM
Pandharipande, PV
Gazelle, GS
AF Glover, McKinley
Khalilzadeh, Omid
Choy, Garry
Prabhakar, Anand M.
Pandharipande, Pari V.
Gazelle, G. Scott
TI Hospital Evaluations by Social Media: A Comparative Analysis of Facebook
Ratings among Performance Outliers
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE Performance measurement; Patient satisfaction; Consumer health
informatics
ID QUALITY-OF-CARE; HEALTH-CARE; PATIENT EXPERIENCE; ASSOCIATIONS;
LIMITATIONS
AB An increasing number of hospitals and health systems utilize social media to allow users to provide feedback and ratings. The correlation between ratings on social media and more conventional hospital quality metrics remains largely unclear, raising concern that healthcare consumers may make decisions on inaccurate or inappropriate information regarding quality.
The purpose of this study was to examine the extent to which hospitals utilize social media and whether user-generated metrics on Facebook(A (R)) correlate with a Hospital Compare(A (R)) metric, specifically 30-day all cause unplanned hospital readmission rates.
This was a retrospective cross-sectional study conducted among all U.S. hospitals performing outside the confidence interval for the national average on 30-day hospital readmission rates as reported on Hospital Compare. Participants were 315 hospitals performing better than U.S. national rate on 30-day readmissions and 364 hospitals performing worse than the U.S. national rate.
The study analyzed ratings of hospitals on Facebook's five-star rating scale, 30-day readmission rates, and hospital characteristics including beds, teaching status, urban vs. rural location, and ownership type.
Hospitals performing better than the national average on 30-day readmissions were more likely to use Facebook than lower-performing hospitals (93.3 % vs. 83.5 %; p < 0.01). The average rating for hospitals with low readmission rates (4.15 +/- 0.31) was higher than that for hospitals with higher readmission rates (4.05 +/- 0.41, p < 0.01). Major teaching hospitals were 14.3 times more likely to be in the high readmission rate group. A one-star increase in Facebook rating was associated with increased odds of the hospital belonging to the low readmission rate group by a factor of 5.0 (CI: 2.6-10.3, p < 0.01), when controlling for hospital characteristics and Facebook-related variables.
Hospitals with lower rates of 30-day hospital-wide unplanned readmissions have higher ratings on Facebook than hospitals with higher readmission rates. These findings add strength to the concept that aggregate measures of patient satisfaction on social media correlate with more traditionally accepted measures of hospital quality.
C1 [Glover, McKinley; Khalilzadeh, Omid; Choy, Garry; Pandharipande, Pari V.; Gazelle, G. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02138 USA.
[Prabhakar, Anand M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiovasc Imaging, Boston, MA USA.
[Pandharipande, Pari V.; Gazelle, G. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA.
RP Glover, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02138 USA.
EM mckinley.glover@mgh.harvard.edu
NR 39
TC 6
Z9 6
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1440
EP 1446
DI 10.1007/s11606-015-3236-3
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000018
PM 25749881
ER
PT J
AU Aysola, J
Werner, RM
Keddem, S
SoRelle, R
Shea, JA
AF Aysola, Jaya
Werner, Rachel M.
Keddem, Shimrit
SoRelle, Richard
Shea, Judy A.
TI Asking the Patient About Patient-Centered Medical Homes: A Qualitative
Analysis
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE Patient-centered care; Primary care redesign; Health care delivery;
Health services research; Health policy
ID PRIMARY-CARE; ETHNIC-DIFFERENCES
AB What patients perceive and experience within a patient-centered medical home (PCMH) is an understudied area, and to date, the patient perspective has not been an integral component of existing PCMH measurement standards. However, upcoming guidelines necessitate the use of patient-reported experiences and satisfaction in evaluations of practice and provider performance.
To characterize patients' experiences with care after PCMH adoption and their understanding and perceptions of the PCMH model and its key components, and to compare responses by degree of practice-level PCMH adoption and patient race/ethnicity.
Qualitative study.
Adult patients with diabetes and/or hypertension (n = 48).
We surveyed and ranked all PCMH adult primary care practices affiliated with one academic medical center with at least three providers (n = 23), using an instrument quantifying the degree of PCMH adoption. We purposively sampled minority and non-minority patients from the four highest-ranked and four lowest-ranked PCMH-adopting practices to determine whether responses varied by degree of PCMH adoption or patient race/ethnicity. We conducted semi-structured telephone interviews with patients about their experiences with care and their perceptions and understanding of key PCMH domains. Interviews were recorded, transcribed, and imported into NVivo 10 for coding and analysis, using a modified grounded theory approach.
We found that patients uniformly lacked awareness of the PCMH concept, and the vast majority perceived no PCMH-related structural changes, regardless of the degree of practice-reported PCMH adoption or the patient's race/ethnicity. Despite this lack of awareness, patients overwhelmingly reported positive relationships with their provider and positive overall experiences.
As we continue to redesign primary care delivery with an emphasis on patient experience measures as performance metrics, we need to better understand what, if any, aspects of practice structure relate to patient experience and satisfaction with care.
C1 [Aysola, Jaya; Werner, Rachel M.; Shea, Judy A.] Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Aysola, Jaya; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Keddem, Shimrit; SoRelle, Richard] Univ Penn, Dept Family Med & Community Hlth, Mixed Methods Res Lab, Philadelphia, PA 19104 USA.
RP Aysola, J (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jaysola@upenn.edu
FU AHRQ PCOR [K12 HS021706-01]
FX Jaya Aysola was funded by an AHRQ PCOR Institutional Award (K12
HS021706-01) for the duration of this study.
NR 30
TC 4
Z9 4
U1 3
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1461
EP 1467
DI 10.1007/s11606-015-3312-8
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000021
PM 25876739
ER
PT J
AU Silverman, J
Krieger, J
Kiefer, M
Hebert, P
Robinson, J
Nelson, K
AF Silverman, Julie
Krieger, James
Kiefer, Meghan
Hebert, Paul
Robinson, June
Nelson, Karin
TI The Relationship Between Food Insecurity and Depression, Diabetes
Distress and Medication Adherence Among Low-Income Patients with
Poorly-Controlled Diabetes
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE food insecurity; diabetes; glycemic control
ID GLYCEMIC CONTROL; SELF-MANAGEMENT; SHORT-FORM; HEALTH; SCALE;
INTERVENTION; HYPOGLYCEMIA; VALIDITY; COSTS
AB Food insecurity- lack of dependable access to adequate food-may play a role in poor diabetes control.
We aimed to determine the relationship between food security status and depression, diabetes distress, medication adherence and glycemic control.
Secondary analysis of baseline data from Peer Support for Achieving Independence in Diabetes, a randomized controlled trial that enrolled patients from November 2011 to October 2013.
Participants had poorly controlled type 2 diabetes (A1c a parts per thousand yen 8.0 % on eligibility screen), household income < 250 % of the federal poverty level, were 30-70 years old, and were recruited from a large public hospital, a VA medical center and a community-health center in King County, Washington.
We measured food insecurity determined by the Department of Agriculture's 6-Item Food Security Module. Depression, diabetes distress and medication adherence measured by PHQ-8, Diabetes Distress Scale and Morisky Medication Adherence Scale, respectively. Diet was assessed through Summary of Diabetes Self-Care Activities and Starting the Conversation tool. Incidence of hypoglycemic episodes was by patient report. Glycemic control was assessed with glycosylated hemoglobin (A1c) values from fingerstick blood sample.
The prevalence of food insecurity was 47.4 %. Chi-square tests revealed participants with food insecurity were more likely to be depressed (40.7 % vs. 15.4 %, p < 0.001), report diabetes distress (55.2 % vs. 33.8 %, p < 0.001) and have low medication adherence (52.9 % vs. 37.2 %, p = 0.02). Based on linear regression modeling, those with food insecurity had significantly higher mean A1c levels (beta = 0.51; p = 0.02) after adjusting for sex, age, race/ethnicity, language, education, marital status, BMI, insulin use, depression, diabetes distress and low medication adherence.
Almost half of participants had food insecurity. Food insecurity was associated with depression, diabetes distress, low medication adherence and worse glycemic control. Even with adjustment, people with food insecurity had higher mean A1c levels than their food-secure counterparts, suggesting there may be other mediating factors, such as diet, that explain the relationship between food security status and diabetes control.
C1 [Silverman, Julie; Hebert, Paul; Nelson, Karin] Northwest HSR&D Ctr Excellence, VA Puget Sound Healthcare Syst, Seattle, WA USA.
[Silverman, Julie; Nelson, Karin] Gen Internal Med Serv, VA Puget Sound Healthcare Syst, Seattle, WA USA.
[Silverman, Julie; Krieger, James; Kiefer, Meghan; Nelson, Karin] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Krieger, James; Hebert, Paul; Nelson, Karin] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Krieger, James; Robinson, June] Publ Hlth Seattle & King Cty, Seattle, WA USA.
RP Silverman, J (reprint author), Northwest HSR&D Ctr Excellence, VA Puget Sound Healthcare Syst, Seattle, WA USA.
EM Julie.Silverman@va.gov
FU NIH/NIDDK [5R18DK088072]; Veterans Health Administration (VHA) Diabetes
Quality Enhancement Research Initiative (QUERI)
FX This study was supported by the NIH/NIDDK grant 5R18DK088072 to Drs.
Nelson and Krieger (co-PIs). The sponsor had no role in designing the
study; collecting, analyzing, or interpreting data; writing this
manuscript; or in the decision to submit this manuscript for
publication. Additional funding was provided by the Veterans Health
Administration (VHA) Diabetes Quality Enhancement Research Initiative
(QUERI) to support Veteran recruitment efforts. The views expressed in
this article are those of the authors and do not necessarily reflect the
views of the Department of Veterans Affairs.
NR 32
TC 6
Z9 6
U1 4
U2 38
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1476
EP 1480
DI 10.1007/s11606-015-3351-1
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000023
PM 25917659
ER
PT J
AU Perissinotto, CM
Walter, LC
AF Perissinotto, Carla Maria
Walter, Louise C.
TI Capsule Commentary on Wolff, et al., A Look at Person- and
Family-Centered Care Among Older Adults: Results from a National Survey
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Perissinotto, Carla Maria; Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Perissinotto, CM (reprint author), Univ Calif San Francisco, 3333 Calif St Suite 380, San Francisco, CA 94143 USA.
EM Carla.Perissinotto@ucsf.edu
NR 3
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1536
EP 1536
DI 10.1007/s11606-015-3408-1
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000036
PM 26001544
ER
PT J
AU Fraser, T
Hillmann, W
Lederer, PA
Kasmar, A
Rencic, J
AF Fraser, Traci
Hillmann, William
Lederer, Philip A.
Kasmar, Anne
Rencic, Joseph
TI Solving Summer Fever in Early Pregnancy
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
DE clinical reasoning; infectious diseases; obstetrics
ID BABESIOSIS
C1 [Fraser, Traci; Hillmann, William; Lederer, Philip A.; Kasmar, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Lederer, Philip A.; Kasmar, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA.
[Rencic, Joseph] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Rencic, Joseph] Tufts Med Ctr, Boston, MA USA.
RP Fraser, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, GRB 740,55 Fruit St, Boston, MA 02114 USA.
EM tnfraser@partners.org
NR 13
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD OCT
PY 2015
VL 30
IS 10
BP 1561
EP 1565
DI 10.1007/s11606-015-3361-z
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA CS0MR
UT WOS:000361755000041
PM 25917661
ER
PT J
AU Chen, HY
Clayman, ES
Ma, WF
AF Chen, Hong-Yuan
Clayman, Eric S.
Ma, Wei-Feng
TI Phenotypic Knockout of CXCR4 Expression by a Novel Intrakine Mutant
hSDF-1 alpha/54/KDEL Inhibits Breast Cancer Metastasis
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID CHEMOKINE RECEPTOR CXCR4; TERMINAL ALPHA-HELIX; TUMOR-GROWTH;
CARCINOMA-CELLS; COLON-CARCINOMA; DOWN-REGULATION; OVARIAN-CANCER; MOUSE
MODEL; KDEL; CHEMOTAXIS
AB Many malignant tumors express high levels of the chemokine receptor CXCR4, and the interaction between CXCR4 and its ligand, SDF-1, promotes migration, invasion, and metastasis of breast cancer cells. Therefore, blocking the interaction between CXCR4 and SDF-1 could alter the tumor's metastatic phenotype and control the development and progression of cancers. We used a cellular phenotypic knockout strategy and developed a novel recombinant gene, AdSDF-1/54/KDEL, which contains an adenovirus vector, a mutant form of SDF-1 that lacks a C-terminal -helix, and a KDEL tetrapeptide sequence that promotes retention at the endoplasmic reticulum (ER). We hypothesized that SDF-1/54/KDEL could efficiently block metastasis of breast cancer cells with less inflammatory side effects than SDF-1/KDEL. Using the MCF-7 cell line, which expresses a stable, high level of CXCR4, we found that SDF-1/54/KDEL efficiently becomes localized at the ER of tumor cells, where it specifically binds to newly synthesized CXCR4 and prevents it from reaching the cell surface. Chemotaxis and invasion assays revealed that the cells treated with SDF-1/54/KDEL failed to migrate toward SDF-1. We also found that SDF-1/54/KDEL impaired lung metastasis of metastatic breast cancer by decreasing CXCR4 on the cell surface. The novel recombinant gene, SDF-1/54/KDEL, played an instrumental role in blocking SDF-1/CXCR4-mediated cell migration, and we found that this gene-based strategy for targeting the SDF-1/CXCR4 axis offers a very effective alternative method for preventing metastasis of breast cancer and other cancers expressing high levels of CXCR4.
C1 [Chen, Hong-Yuan] GuangDong Pharmaceut Univ, Sch Basic Courses, Dept Pathogen Biol & Immunol, Guangzhou 510006, Guangdong, Peoples R China.
[Clayman, Eric S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
[Clayman, Eric S.] Harvard Univ, Sch Med, Boston, MA USA.
[Ma, Wei-Feng] Southern Med Univ, Sch Publ Hlth & Trop Med, Dept Microbiol, Guangzhou, Guangdong, Peoples R China.
RP Chen, HY (reprint author), GuangDong Pharmaceut Univ, Dept Pathogen Biol & Immunol, Guangzhou Higher Educ Mega Ctr, 280 Waihuan East Rd, Guangzhou 510006, Guangdong, Peoples R China.
EM hychen1208@126.com
FU 54th China Postdoctoral Science Foundation [2013M542234]; Science and
Technology Project of Guangdong Province, China [2013B021800085];
Science and Technology Project Guangzhou City Grant [2014J4100058]
FX This research was prompted and supported by the 54th China Postdoctoral
Science Foundation No. 2013M542234, the Science and Technology Project
of Guangdong Province, China (No. 2013B021800085), and the Science and
Technology Project Guangzhou City Grant (No. 2014J4100058). We would
also like to thank Professors Jun Du and Shao-Hui Cai for their
excellent recommendations and edits with this manuscript.
NR 35
TC 1
Z9 2
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
EI 1557-7465
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD OCT 1
PY 2015
VL 35
IS 10
BP 771
EP 778
DI 10.1089/jir.2014.0141
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS2HK
UT WOS:000361889600002
PM 25978539
ER
PT J
AU Varadarajan, KM
Zumbrunn, T
Rubash, HE
Malchau, H
Muratoglu, OK
Li, GA
AF Varadarajan, Kartik Mangudi
Zumbrunn, Thomas
Rubash, Harry E.
Malchau, Henrik
Muratoglu, Orhun K.
Li, Guoan
TI Reverse Engineering Nature to Design Biomimetic Total Knee Implants
SO JOURNAL OF KNEE SURGERY
LA English
DT Article
DE total knee arthroplasty; implant design; biomimetic implant; knee
kinematics; normal knee
ID MOTION CHARACTERISTICS; HIGH FLEXION; KINEMATICS; ARTHROPLASTY;
REPLACEMENT; JOINT; ORIENTATION; ROTATION; TKA; STABILITY
AB While contemporary total knee arthroplasty (TKA) provides tremendous clinical benefits, the normal feel and function of the knee is not fully restored. To address this, a novel design process was developed to reverse engineer biomimetic articular surfaces that are compatible with normal soft-tissue envelope and kinematics of the knee. The biomimetic articular surface is created by moving the TKA femoral component along in vivo kinematics of normal knees and carving out the tibial articular surface from a rectangular tibial block. Here, we describe the biomimetic design process. In addition, we utilize geometric comparisons and kinematic simulations to show that; (1) tibial articular surfaces of conventional implants are fundamentally incompatible with normal knee motion, and (2) the anatomic geometry of the biomimetic surface contributes directly to restoration of normal knee kinematics. Such biomimetic implants may enable us to achieve the long sought after goal of a normal knee post-TKA surgery.
C1 [Varadarajan, Kartik Mangudi; Zumbrunn, Thomas; Rubash, Harry E.; Malchau, Henrik; Muratoglu, Orhun K.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
RP Varadarajan, KM (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St,GRJ-1223, Boston, MA 02114 USA.
EM kmangudivaradarajan@partners.org
NR 45
TC 2
Z9 2
U1 1
U2 4
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 1538-8506
EI 1938-2480
J9 J KNEE SURG
JI J. Knee Surg.
PD OCT
PY 2015
VL 28
IS 5
BP 363
EP 369
DI 10.1055/s-0035-1551834
PG 7
WC Orthopedics
SC Orthopedics
GA CS1KK
UT WOS:000361822900004
PM 26166428
ER
PT J
AU Kim, J
Won, HH
Kim, Y
Choi, JR
Yu, N
Lee, KA
AF Kim, Juwon
Won, Hong-Hee
Kim, Yoonjung
Choi, Jong Rak
Yu, Nae
Lee, Kyung-A
TI Breakpoint mapping by whole genome sequencing identifies PTH2R gene
disruption in a patient with midline craniosynostosis and a de novo
balanced chromosomal rearrangement
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID ENDOCHONDRAL BONE-DEVELOPMENT; HORMONE TYPE-2 RECEPTOR; EXPRESSION
AB Background Craniosynostosis (CRS) is a premature closure of calvarial sutures caused by gene mutation or environmental factors or interaction between the two. Only a small proportion of non-syndromic CRS (NSC) patients have a known genetic cause, and thus, it would be meaningful to search for a causative gene disruption for the development NSC. We applied a whole genome sequencing approach on a 15-month-old boy with sagittal and metopic synostosis to identify a gene responsible for the development of the disease.
Methods and results Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34. Array comparative genomic hybridisation did not show any copy number variation. Multicolour banding analysis was carried out and the breakpoints were refined to 2q14 and 2q34. An intronic break of the PTH2R gene was detected by whole genome sequencing and fluorescence in situ hybridisation analysis confirmed disruption of PTH2R.
Conclusions We report PTH2R as a gene that is disrupted in NSC. The disruption of the PTH2R gene may cause uncontrolled proliferation and differentiation of chondrocytes, which in turn results in premature closure of sutures. This addition of PTH2R to the list of genes associated with NSC expands our understanding of the development of NSC.
C1 [Kim, Juwon; Kim, Yoonjung] Yonsei Univ, Wonju Coll Med, Dept Lab Med, Wonju, South Korea.
[Won, Hong-Hee] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Won, Hong-Hee] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Won, Hong-Hee] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02139 USA.
[Choi, Jong Rak; Yu, Nae; Lee, Kyung-A] Yonsei Univ, Coll Med, Dept Lab Med, Seoul 135720, South Korea.
RP Lee, KA (reprint author), Yonsei Univ, Coll Med, Dept Lab Med, 211 Eonju Ro, Seoul 135720, South Korea.
EM kal1119@yuhs.ac
FU Korean Health Technology R&D Project, Ministry of Health & Welfare,
Republic of Korea [A120030]
FX This study was supported by a grant of the Korean Health Technology R&D
Project, Ministry of Health & Welfare, Republic of Korea (A120030).
NR 18
TC 1
Z9 1
U1 1
U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD OCT
PY 2015
VL 52
IS 10
BP 706
EP 709
DI 10.1136/jmedgenet-2015-103001
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA CS0PC
UT WOS:000361763100008
PM 26044810
ER
PT J
AU Hirsch, JA
AF Hirsch, Joshua A.
TI Our changing neurointerventional world
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Editorial Material
DE Political
ID HEALTH-CARE; PRIMER
C1 Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA.
RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA.
EM hirsch@snisonline.org
NR 14
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
EI 1759-8486
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD OCT
PY 2015
VL 7
IS 10
BP 703
EP 704
DI 10.1136/neurintsurg-2015-012009
PG 2
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA CS0MZ
UT WOS:000361756100005
PM 26369730
ER
PT J
AU Jernigan, SC
Stone, SSD
Aronson, JP
Putman, M
Proctor, MR
AF Jernigan, Sarah C.
Stone, Scellig S. D.
Aronson, Joshua P.
Putman, Melissa
Proctor, Mark R.
TI Episodic ventriculomegaly due to hypernatremia mimicking shunt
malfunction: case report
SO JOURNAL OF NEUROSURGERY-PEDIATRICS
LA English
DT Article
DE hypernatremia; ventriculomegaly; hydrocephalus; shunt
ID LOW-PRESSURE HYDROCEPHALUS; BRAIN
AB Patients with shunted hydrocephalus presenting with altered mental status and ventriculomegaly are generally considered to be in shunt failure requiring surgical treatment. The authors describe a case of shunted hydrocephalus secondary to a disseminated neuroectodermal tumor in a pediatric patient in whom rapid fluctuations in sodium levels due to diabetes insipidus repeatedly led to significant changes in ventricle size, with invasively confirmed normal shunt function and low intracranial pressure. This clinical picture exactly mimics shunt malfunction, requires urgent nonsurgical therapy, and underscores the importance of considering serum osmolar abnormalities in the differential diagnosis for ventriculomegaly.
C1 [Jernigan, Sarah C.; Stone, Scellig S. D.; Proctor, Mark R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Putman, Melissa] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA.
[Aronson, Joshua P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Proctor, MR (reprint author), Boston Childrens Hosp, Dept Neurosurg, Hunnewell 2,300 Longwood Ave, Boston, MA 02115 USA.
EM mark.proctor@childrens.harvard.edu
NR 16
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1933-0707
EI 1933-0715
J9 J NEUROSURG-PEDIATR
JI J. Neurosurg.-Pediatr.
PD OCT
PY 2015
VL 16
IS 4
BP 406
EP 409
DI 10.3171/2015.3.PEDS1526
PG 4
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA CS1XS
UT WOS:000361862800008
PM 26186358
ER
PT J
AU Shin, SS
Dixon, CE
AF Shin, Samuel S.
Dixon, C. Edward
TI Alterations in Cholinergic Pathways and Therapeutic Strategies Targeting
Cholinergic System after Traumatic Brain Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Review
DE acetylcholine; cholinergic; nicotinic; traumatic brain injury
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; POSITIVE ALLOSTERIC MODULATOR;
FLUID-PERCUSSION INJURY; CLOSED-HEAD INJURY; SHORT-TERM-MEMORY; IMPROVES
COGNITIVE PERFORMANCE; PROMOTE FUNCTIONAL RECOVERY; RANDOMIZED
CONTROLLED-TRIAL; CONTROLLED CORTICAL IMPACT; REDUCED EVOKED RELEASE
AB Traumatic brain injury (TBI) results in varying degrees of disability in a significant number of persons annually. The mechanisms of cognitive dysfunction after TBI have been explored in both animal models and human clinical studies for decades. Dopaminergic, serotonergic, and noradrenergic dysfunction has been described in many previous reports. In addition, cholinergic dysfunction has also been a familiar topic among TBI researchers for many years. Although pharmacological agents that modulate cholinergic neurotransmission have been used with varying degrees of success in previous studies, improving their function and maximizing cognitive recovery is an ongoing process. In this article, we review the previous findings on the biological mechanism of cholinergic dysfunction after TBI. In addition, we describe studies that use both older agents and newly developed agents as candidates for targeting cholinergic neurotransmission in future studies.
C1 [Shin, Samuel S.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA.
[Shin, Samuel S.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA.
[Shin, Samuel S.; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA.
[Dixon, C. Edward] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Dixon, CE (reprint author), Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA.
EM dixonec@upmc.edu
FU Pittsburgh Foundation Walter Copeland Fund
FX The authors thank The Pittsburgh Foundation Walter Copeland Fund for
their support of our TBI research. No competing financial interests
exist.
NR 147
TC 5
Z9 5
U1 2
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD OCT 1
PY 2015
VL 32
IS 19
BP 1429
EP 1440
DI 10.1089/neu.2014.3445
PG 12
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA CR8NC
UT WOS:000361609500001
PM 25646580
ER
PT J
AU Hage, FG
AF Hage, Fadi G.
TI Training in nuclear cardiology: What's new?
SO JOURNAL OF NUCLEAR CARDIOLOGY
LA English
DT Editorial Material
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.
RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Lyons Harrison Res Bldg 306,1720 2nd AVE S, Birmingham, AL 35294 USA.
EM fadihage@uab.edu
OI Hage, Fadi/0000-0002-1397-4942
NR 2
TC 0
Z9 0
U1 0
U2 0
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 OCT
PY 2015
VL 22
IS 5
BP 861
EP 862
DI 10.1007/s12350-015-0259-4
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CR8RU
UT WOS:000361622400001
PM 26268827
ER
PT J
AU Hage, F
AlJaroudi, W
AF Hage, Fadi G.
AlJaroudi, Wael
TI Review of cardiovascular literature
SO JOURNAL OF NUCLEAR CARDIOLOGY
LA English
DT Review
C1 [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA.
[AlJaroudi, Wael] Clemenceau Med Ctr, Beirut, Lebanon.
RP AlJaroudi, W (reprint author), Clemenceau Med Ctr, Beirut, Lebanon.
EM Wael.jaroudi@cmc.com.lb
OI Hage, Fadi/0000-0002-1397-4942
NR 0
TC 0
Z9 0
U1 0
U2 2
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 OCT
PY 2015
VL 22
IS 5
BP 874
EP 876
DI 10.1007/s12350-015-0220-6
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CR8RU
UT WOS:000361622400004
PM 26134887
ER
PT J
AU Ring, D
Horst, TA
AF Ring, David
Horst, Taylor A.
TI Coronoid Fractures
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE elbow fracture; coronoid process; dislocation; open reduction and
internal fixation
ID TERRIBLE TRIAD INJURIES; ANTEROMEDIAL FACET; ELBOW TRAUMA; RADIAL HEAD;
ULNA; DISLOCATIONS; STABILITY; POSTERIOR; FIXATION; PATTERNS
AB Fractures of the coronoid process of the ulna are usually part of a more complex injury. The type of coronoid fracture corresponds with a specific pattern of injury with known pitfalls and recommended treatments. Tip fractures usually correspond with dislocation of the elbow and fracture of the radial head (the so-called terrible triad of the elbow because it is prone to redislocation, subluxation, and arthrosis) and are best repaired with a suture passed through drill holes along with repair or replacement of the fractured radial head and reattachment of the lateral collateral ligament to the lateral epicondyle. Anteromedial fractures are usually part of a subluxation injury and are best addressed with a medial buttress plate and reattachment of the lateral collateral ligament. Large basilar coronoid fractures are usually part of an olecranon fracture-dislocation and are usually repaired with 1 or 2 plates and screws. Tenuous fixation is protected with temporary external fixation or cross-pinning of the joint because healing of the coronoid with concentric elbow alignment is critical.Level of Evidence:Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
C1 [Ring, David; Horst, Taylor A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@mgh.harvard.edu
FU Skeletal Dynamics
FX D. Ring has received honoraria from various universities, AO North
America, and AO International; is currently receiving a grant from
Skeletal Dynamics; and is a consultant for Acumed and Biomet. T. A.
Horst reports no conflict of interest.
NR 25
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0890-5339
EI 1531-2291
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD OCT
PY 2015
VL 29
IS 10
BP 437
EP 440
DI 10.1097/BOT.0000000000000326
PG 4
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA CR8LD
UT WOS:000361602400001
PM 25785359
ER
PT J
AU Teunis, T
Bot, AGJ
Thornton, ER
Ring, D
AF Teunis, Teun
Bot, Arjan G. J.
Thornton, Emily R.
Ring, David
TI Catastrophic Thinking Is Associated With Finger Stiffness After Distal
Radius Fracture Surgery
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE catastrophic thinking; distal radius; finger stiffness; fracture;
predictors; trauma
ID SYNDROME TYPE-I; LOW-BACK-PAIN; PSYCHOLOGICAL-FACTORS; ALGODYSTROPHY;
DISABILITY; VALIDITY; TRAUMA; SCALE
AB Objectives:To identify demographic, injury-related, or psychologic factors associated with finger stiffness at suture removal and 6 weeks after distal radius fracture surgery. We hypothesize that there are no factors associated with distance to palmar crease at suture removal.Design:Prospective cohort study.Setting:Level I Academic Urban Trauma Center.Patients:One hundred sixteen adult patients underwent open reduction and internal fixation of their distal radius fractures; 96 of whom were also available 6 weeks after surgery.Intervention:None.Main Outcome Measurements:At suture removal, we recorded patients' demographics, AO fracture type, carpal tunnel release at the time of surgery, pain catastrophizing scale, Whiteley Index, Patient Health Questionnaire-9, and disabilities of the arm, shoulder, and hand questionnaire, 11-point ordinal measure of pain intensity, distance to palmar crease, and active flexion of the thumb through the small finger. At 6 weeks after surgery, we measured motion, disabilities of the arm, shoulder, and hand, and pain intensity. Prereduction and postsurgery radiographic fracture characteristics were assessed.Results:Female sex, being married, specific surgeons, carpal tunnel release, AO type C fractures, and greater catastrophic thinking were associated with increased distance to palmar crease at suture removal. At 6 weeks, greater catastrophic thinking was the only factor associated with increased distance to palmar crease.Conclusions:Catastrophic thinking was a consistent and major determinant of finger stiffness at suture removal and 6 weeks after injury. Future research should assess if treatments that ameliorate catastrophic thinking can facilitate recovery of finger motion after operative treatment of a distal radius fracture.Level of Evidence:Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.
C1 [Teunis, Teun; Thornton, Emily R.; Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Bot, Arjan G. J.] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands.
RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA.
EM dring@mgh.harvard.edu
FU Wright Medical (US) (Memphis, TN); Skeletal Dynamics (US) (Miami, FL);
Biomet (US) (Warsaw, IN); AO North America (US) (Paoli, PA); AO
International (US) (Dubendorf, Switzerland)
FX D. Ring certifies that he, or a member of his immediate family, has or
may receive payments or benefits, during the study period from Wright
Medical (US $ < 10,000) (Memphis, TN); Skeletal Dynamics (US $ < 10,000)
(Miami, FL); Biomet (US $ < 10,000) (Warsaw, IN); AO North America (US $
< 10,000) (Paoli, PA); and AO International (US $ < 10,000) (Dubendorf,
Switzerland). The remaining authors report no conflict of interest.
NR 27
TC 3
Z9 3
U1 2
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0890-5339
EI 1531-2291
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD OCT
PY 2015
VL 29
IS 10
BP e414
EP e420
DI 10.1097/BOT.0000000000000342
PG 7
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA CR8LB
UT WOS:000361602200013
PM 25866942
ER
PT J
AU Mallo, GC
Burton, L
Coats-Thomas, M
Daniels, SD
Sinz, NJ
Warner, JJP
AF Mallo, Gregory C.
Burton, Lauren
Coats-Thomas, Margaret
Daniels, S. David
Sinz, Nathan J.
Warner, Jon J. P.
TI Assessment of painful total shoulder arthroplasty using computed
tomography arthrography
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE Shoulder; CT arthrography; arthroplasty; total shoulder arthroplasty;
glenoid loosening; component loosening
ID REPLACEMENT; ARTHROSCOPY; REMOVAL
AB Background: This study assessed the accuracy of computed tomography (CT) arthrography when evaluating glenoid component stability in the setting of postarthroplasty shoulder pain.
Methods: We retrospectively reviewed all patients presenting to the clinic during a 5.5-year period to identify those with a painful shoulder arthroplasty more than 1 year after the index procedure. We excluded reverse and hemiarthroplasty procedures, patients with a clearly identifiable cause for pain, such as rotator cuff insufficiency or gross component loosening as seen on plain radiographs, and those with culture-positive aspiration. There were 14 patients with suspected glenoid component loosening but inconclusive plain radiographs. Each of the 14 patients underwent a CT arthrogram that was evaluated by the senior author (J.J.P.W.) for the presence or absence of contrast material underneath the polyethylene component. Operative reports and surgical videos from subsequent arthroscopy were reviewed to assess glenoid component stability as determined by direct arthroscopic visualization.
Results: CT arthrography suggested glenoid component loosening in 8 of 14 patients (57.1%), and arthroscopic inspection identified loosening in 10 of 14 patients (71.4%). In 3 of 10 patients (30%), CTA suggested a well-fixed glenoid component, but gross loosening was identified during arthroscopy. In this study, CTA yielded a sensitivity of 70%, a specificity of 75%, a positive predictive value of 87.5%, and a negative predictive value of 50.0%.
Conclusion: CTA had a low negative predictive value (50%), and therefore, the prediction of component stability based on the absence of contrast between the glenoid component and the bone-cement interface does not always reflect true stability. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Mallo, Gregory C.; Burton, Lauren; Coats-Thomas, Margaret; Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Shoulder Inst, Boston, MA USA.
[Daniels, S. David; Sinz, Nathan J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston Shoulder Inst, Boston, MA 02115 USA.
RP Mallo, GC (reprint author), Massachusetts Gen Hosp, Boston Shoulder Inst, 55 Fruit St,Ste 3200,3G, Boston, MA 02114 USA.
EM gregorymallo@gmail.com
NR 13
TC 2
Z9 2
U1 0
U2 1
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 OCT
PY 2015
VL 24
IS 10
BP 1507
EP 1511
DI 10.1016/j.jse.2015.06.027
PG 5
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA CR7ZT
UT WOS:000361571600006
PM 26234665
ER
PT J
AU Menendez, ME
Baker, DK
Fryberger, CT
Ponce, BA
AF Menendez, Mariano E.
Baker, Dustin K.
Fryberger, Charles T.
Ponce, Brent A.
TI Predictors of extended length of stay after elective shoulder
arthroplasty
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE Shoulder arthroplasty; Nationwide Inpatient Sample; length of stay;
reverse total shoulder; anatomic total shoulder; NIS
ID UNITED-STATES; ORTHOPEDIC-SURGERY; INPATIENT SAMPLE; HOSPITAL STAY;
RISK-FACTOR; FOLLOW-UP; OUTCOMES; COMPLICATIONS; TRENDS; COST
AB Background: With policymakers and hospitals increasingly looking to cut costs, length of stay after surgery has come into focus as an area for improvement. Despite the increasing popularity of total shoulder arthroplasty, there is limited research about the factors contributing to prolonged hospital stay. We sought to identify preoperative and postoperative predictors of prolonged hospital stay in patients undergoing anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA).
Methods: Using the 2011 Nationwide Inpatient Sample, we identified an estimated 40,869 patients who underwent elective total shoulder arthroplasty (62.5% ATSA; 37.5% RTSA) and separated them into those with normal length of stay (<75th percentile) and prolonged length of stay (>75th percentile). Multivariate logistic regression modeling was performed to identify factors associated with prolonged length of stay.
Results: Patient-level factors associated with prolonged length of stay common to patients undergoing ATSA or RTSA included increasing age, female sex, congestive heart failure, renal failure, chronic pulmonary disease, and preoperative anemia. Provider-related factors were lower volume and location in the South or Northeast. Postoperative complications showed a significant influence as well.
Conclusion: Our data can be used to promptly identify patients at higher risk of prolonged hospitalization after elective shoulder arthroplasty and to ultimately improve quality of care and cost containment. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Menendez, Mariano E.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Baker, Dustin K.; Fryberger, Charles T.; Ponce, Brent A.] Univ Alabama Birmingham, Div Orthopaed Surg, Birmingham, AL 35205 USA.
[Baker, Dustin K.] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA.
RP Ponce, BA (reprint author), Univ Alabama Birmingham, Div Orthopaed Surg, 1313 13th St S,Ste 203, Birmingham, AL 35205 USA.
EM bponce@uabmc.edu
NR 42
TC 6
Z9 6
U1 3
U2 3
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 OCT
PY 2015
VL 24
IS 10
BP 1527
EP 1533
DI 10.1016/j.jse.2015.02.014
PG 7
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA CR7ZT
UT WOS:000361571600009
PM 25865089
ER
PT J
AU Claessen, FMAP
van den Ende, KIM
Doornberg, JN
Guitton, TG
Eygendaal, D
van den Bekerom, MPJ
AF Claessen, Femke M. A. P.
van den Ende, Kimberly I. M.
Doornberg, Job N.
Guitton, Thierry G.
Eygendaal, Denise
van den Bekerom, Michel P. J.
CA Shoulder Elbow Platform Sci Variat
TI Osteochondritis dissecans of the humeral capitellum: reliability of four
classification systems using radiographs and computed tomography
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE Osteochondritis dissecans; humeral capitellum; classification;
interobserver study; arthroscopy; sport traumatology
ID INTEROBSERVER RELIABILITY; PATIENT PREFERENCES; SURGICAL-TREATMENT;
PEDIATRIC ATHLETE; 3-DIMENSIONAL CT; DECISION-MAKING; ELBOW INJURIES;
TALUS; FRACTURES; LESIONS
AB Background: The radiographic appearance of osteochondritis dissecans (OCD) of the humeral capitellum varies according to the stage of the lesion. It is important to evaluate the stage of OCD lesion carefully to guide treatment. We compared the interobserver reliability of currently used classification systems for OCD of the humeral capitellum to identify the most reliable classification system.
Methods: Thirty-two musculoskeletal radiologists and orthopaedic surgeons specialized in elbow surgery from several countries evaluated anteroposterior and lateral radiographs and corresponding computed tomography (CT) scans of 22 patients to classify the stage of OCD of the humeral capitellum according to the classification systems developed by (1) Minami, (2) Berndt and Harty, (3) Ferkel and Sgaglione, and (4) Anderson on a Web-based study platform including a Digital Imaging and Communications in Medicine viewer. Magnetic resonance imaging was not evaluated as part of this study. We measured agreement among observers using the Siegel and Castellan multirater kappa.
Results: All OCD classification systems, except for Berndt and Harty, which had poor agreement among observers (kappa = 0.20), had fair interobserver agreement: k was 0.27 for the Minami, 0.23 for Anderson, and 0.22 for Ferkel and Sgaglione classifications. The Minami Classification was significantly more reliable than the other classifications (P < .001).
Conclusions: The Minami Classification was the most reliable for classifying different stages of OCD of the humeral capitellum. However, it is unclear whether radiographic evidence of OCD of the humeral capitellum, as categorized by the Minami Classification, guides treatment in clinical practice as a result of this fair agreement. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Claessen, Femke M. A. P.; Doornberg, Job N.; Guitton, Thierry G.] Univ Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands.
[Claessen, Femke M. A. P.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[van den Ende, Kimberly I. M.] Erasmus MC, Dept Orthopaed Surg, Rotterdam, Netherlands.
[Eygendaal, Denise] Amphia Hosp, Dept Orthoped Surg, Upper Limb Unit, Breda, Netherlands.
[van den Bekerom, Michel P. J.] Onze Lieve Vrouw Hosp, Shoulder & Elbow Unit, Amsterdam, Netherlands.
RP Claessen, FMAP (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, 55 Fruit St, Boston, MA 02114 USA.
EM fclaessen@mgh.harvard.edu
OI Van Tongel, Alexander/0000-0003-3590-6614
FU Prins Bernhard Cultuur Foundation; Trust Foundation; VSB Foundation; Van
Beek-Donner Foundation
FX Femke M.A.P. Claessen has received a research grant from the Prins
Bernhard Cultuur Foundation, the Trust Foundation, the VSB Foundation,
and the Van Beek-Donner Foundation.
NR 46
TC 0
Z9 0
U1 3
U2 10
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 OCT
PY 2015
VL 24
IS 10
BP 1613
EP 1618
DI 10.1016/j.jse.2015.03.029
PG 6
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA CR7ZT
UT WOS:000361571600021
PM 25953486
ER
PT J
AU Colman, MW
Hornicek, FJ
Schwab, JH
AF Colman, Matthew W.
Hornicek, Francis J.
Schwab, Joseph H.
TI Spinal Cord Blood Supply and Its Surgical Implications
SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
LA English
DT Review
ID BILATERAL SEGMENTAL ARTERIES; THORACOABDOMINAL ANEURYSM REPAIR;
SOMATOSENSORY-EVOKED-POTENTIALS; AORTIC-ANEURYSMS; VESSEL LIGATION;
TEMPORARY OCCLUSION; NEUROLOGIC FUNCTION; FLUID DRAINAGE; DOG-MODEL;
PARAPLEGIA
AB The blood supply to the spine is based on a predictable segmental vascular structure at each spinal level, but true radiculomedullary arteries, which feed the dominant cord supply vessel, the anterior spinal artery, are relatively few and their locations variable. Under pathologic conditions, such as aortic stent grafting, spinal deformity surgery, or spinal tumor resection, sacrifice of a dominant radiculomedullary vessel may or may not lead to spinal cord ischemia, depending on dynamic autoregulatory or collateral mechanisms to compensate for its loss. Elucidation of the exact mechanisms for this compensation requires further study but will be aided by preoperative, intraoperative, and postoperative comparative angiography. Protocols in place at our center and others minimize the risk of spinal cord ischemia during planned radiculomedullary vessel sacrifice.
C1 [Colman, Matthew W.; Hornicek, Francis J.; Schwab, Joseph H.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Colman, MW (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
FU Stryker; Biom'up
FX Dr. Hornicek or an immediate family member has received research or
institutional support from Stryker; has received nonincome support (such
as equipment or services), commercially derived honoraria, or other
non-research-related funding (such as paid travel) from Biomet; and
serves as a board member, owner, officer, or committee member of the
American Association of Tissue Banks and the International Society of
Limb Salvage. Dr. Schwab or an immediate family member is a member of a
speakers' bureau or has made paid presentations on behalf of Synthes and
Stryker Spine; serves as a paid consultant to and serves as a board
member, owner, officer, or committee member of Biom'up; and has received
nonincome support (such as equipment or services), commercially derived
honoraria, or other non-research-related funding (such as paid travel)
from Globus Medical and Stryker. Neither Dr. Colman 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.
NR 53
TC 1
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1067-151X
EI 1940-5480
J9 J AM ACAD ORTHOP SUR
JI J. Am. Acad. Orthop. Surg.
PD OCT
PY 2015
VL 23
IS 10
BP 581
EP 591
DI 10.5435/JAAOS-D-14-00219
PG 11
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA CS0ON
UT WOS:000361761300001
PM 26377671
ER
PT J
AU Marx, A
Chan, JKC
Coindre, JM
Detterbeck, F
Girard, N
Harris, NL
Jaffe, ES
Kurrer, MO
Marom, EM
Moreira, AL
Mukai, K
Orazi, A
Strobel, P
AF Marx, Alexander
Chan, John K. C.
Coindre, Jean-Michel
Detterbeck, Frank
Girard, Nicolas
Harris, Nancy L.
Jaffe, Elaine S.
Kurrer, Michael O.
Marom, Edith M.
Moreira, Andre L.
Mukai, Kiyoshi
Orazi, Attilio
Stroebel, Philipp
TI The 2015 World Health Organization Classification of Tumors of the
Thymus Continuity and Changes
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Review
DE Classification; Thymus; Thymoma; Atypical type A thymoma; Thymic
carcinoma; Adenocarcinoma; NUT carcinoma; Carcinoid; Neuroendocrine;
Combined large-cell neuroendocrine carcinoma; Combined thymic carcinoma;
Mediastinal; Mediastinum; Germ cell tumor; Lymphoma; Primary mediastinal
large B-cell lymphoma; Grey zone lymphoma; Hodgkin lymphoma; Dendritic
cell tumor; Sarcoma; Neuroblastoma; Metastasis; Ectopic tumor; Positron
emission tomography; Computed tomography; Cytology; Histology;
Pathology; Immunohistochemistry; Immunohistology; Staging; Genetic;
GTF2I; International Thymic Malignancy Interest Group; World Health
Organization
ID B-CELL LYMPHOMA; FORTHCOMING 8TH EDITION; NUT MIDLINE CARCINOMA;
CLASSICAL HODGKINS LYMPHOMA; STAGING PROJECT PROPOSALS; MALIGNANCY
INTEREST GROUP; GRAY ZONE LYMPHOMA; EPITHELIAL TUMORS; MUCOEPIDERMOID
CARCINOMA; TNM CLASSIFICATION
AB This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1-B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.
C1 [Marx, Alexander] Heidelberg Univ, Univ Med Ctr Mannheim, Inst Pathol, D-68167 Mannheim, Germany.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Coindre, Jean-Michel] Inst Bergonie, Dept Pathol, Bordeaux, France.
[Detterbeck, Frank] Yale Univ, Sch Med, Dept Thorac Surg, New Haven, CT USA.
[Girard, Nicolas] Hosp Civils Lyon, Louis Pradel Hosp, Dept Resp Med, Lyon, France.
[Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kurrer, Michael O.] Gemeinschaftspraxis Pathol, Zurich, Switzerland.
[Marom, Edith M.] Chaim Sheba Med Ctr, Dept Diagnost Imaging, IL-52621 Tel Hashomer, Israel.
[Moreira, Andre L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Mukai, Kiyoshi] Saiseikai Cent Hosp, Dept Diagnost Pathol, Tokyo, Japan.
[Orazi, Attilio] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY USA.
[Stroebel, Philipp] Univ Gottingen, Dept Pathol, Univ Med Ctr Gottingen, Inst Pathol, Gottingen, Germany.
RP Marx, A (reprint author), Heidelberg Univ, Univ Med Ctr Mannheim, Inst Pathol, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
EM alexander.marx@umm.de
FU Intramural NIH HHS [Z01 BC011070-01]
NR 91
TC 21
Z9 21
U1 3
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2015
VL 10
IS 10
BP 1383
EP 1395
DI 10.1097/JTO.0000000000000654
PG 13
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA CS0AP
UT WOS:000361719200001
PM 26295375
ER
PT J
AU Poghosyan, H
Stock, S
Sheldon, LK
Cromwell, J
Cooley, ME
Nerenz, DR
AF Poghosyan, Hermine
Stock, Shannon
Sheldon, Lisa Kennedy
Cromwell, Jerry
Cooley, Mary E.
Nerenz, David R.
TI Racial Disparities in Health-Related Quality of Life After Lung Cancer
Surgery Findings From the Cancer Care Outcomes Research and Surveillance
Consortium
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Non-small-cell lung cancer; Surgery; Racial disparities; Health-related
quality of life
ID NONSMALL CELL; AFRICAN-AMERICANS; PSYCHOSOCIAL CARE; INSURANCE STATUS;
WHITE PATIENTS; EARLY-STAGE; SURVIVAL; RACE; COMORBIDITY; DEPRESSION
AB Introduction: This study investigated racial disparities in postsurgical health-related quality of life (HRQOL) among patients with non-small-cell lung cancer (NSCLC).
Methods: Data were collected by the Cancer Care Outcomes Research and Surveillance Consortium. Inclusion criteria were greater than or equal to 21 years of age, NSCLC, and receipt of surgery. HRQOL data were available from patients' surveys, and complete medical record abstraction was performed to obtain clinical data. HRQOL was assessed by the physical/mental component summary scores (PCS/MCS) of the 12-item Short-Form Health Survey at two time points. Mean time between surgery and the initial assessment (time 1) after surgery was 4.1 (SD 2.2) months and between surgery and second assessment (time 2) was 12.7 (SD 3.8) months. Multivariable linear regression models were used to examine associations between race and HRQOL.
Results: Of 650 patients, 80.5% were White, 8.8% Black, and 10.7% other races. At second assessment, Blacks reported lower MCS than Whites (47.4 versus 52.6, p = 0.002). In multivariable analysis, Blacks had lower MCS compared with Whites. No difference was found between Whites and Blacks on PCS. Those with less than high school education reported lower MCSs. Older age and receipt of adjuvant chemotherapy after surgery were associated with gain in MCS. Male, less than college education, and comorbidities were associated with impaired PCS. Older age was associated with improved PCS.
Conclusion: Racial disparities exist in postoperative mental HRQOL. Results highlight the need for interventions after lung cancer surgery to improve mental health in Black and younger patients.
C1 [Poghosyan, Hermine; Sheldon, Lisa Kennedy] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
[Stock, Shannon] Coll Holy Cross, Dept Math & Comp Sci, Worcester, MA 01610 USA.
[Cromwell, Jerry] RTI Int, Waltham, MA USA.
[Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA.
[Nerenz, David R.] Henry Ford Hlth Syst, Detroit, MI USA.
RP Poghosyan, H (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Sch Nursing, 408 Robinson Hall, Boston, MA 02115 USA.
EM h.poghosyan@neu.edu
OI Sheldon, Lisa Kennedy/0000-0002-5958-8529
FU National Cancer Institute (NCI) [U01 CA093344]; NCI [U01 CA093332, U01
CA093324, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA 093326];
Department of Veteran's Affairs [VA HSRD CRS-02-164]
FX The work of the CanCORS consortium was supported by grants from the
National Cancer Institute (NCI) to the Statistical Coordinating Center
(U01 CA093344) and the NCI supported 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 CA 093326) and by a Department of Veteran's Affairs
grant to the Durham VA Medical Center VA HSRD CRS-02-164).
NR 50
TC 2
Z9 2
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2015
VL 10
IS 10
BP 1404
EP 1412
DI 10.1097/JTO.0000000000000629
PG 9
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA CS0AP
UT WOS:000361719200003
PM 26200452
ER
PT J
AU Durham, CA
Aranson, NJ
Ergul, EA
Wang, LJ
Patel, VI
Cambria, RP
Conrad, MF
AF Durham, Christopher A.
Aranson, Nathan J.
Ergul, Emel A.
Wang, Linda J.
Patel, Virendra I.
Cambria, Richard P.
Conrad, Mark F.
TI Aneurysmal degeneration of the thoracoabdominal aorta after medical
management of type B aortic dissections
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 41st Joint Annual Meeting of the
New-England-Society-for-Vascular-Surgery (NESVS) and
Eastern-Vascular-Society (EVS)
CY SEP 11-14, 2014
CL Boston, MA
SP New England Soc Vasc Surg, Eastern Vasc Soc
ID PATENT FALSE LUMEN; INTERNATIONAL REGISTRY; FOLLOW-UP; RUPTURE;
PREDICTORS; RISK; SIZE; MULTICENTER; DILATATION; SURVIVAL
AB Background: Patients with uncomplicated type B aortic dissections who are managed medically are at risk of aortic aneurysmal degeneration over time. However, the effect of improvement in antihypertensive medications and stricter blood pressure control is unknown. The goal of this study was to determine the rate of aneurysmal degeneration in a contemporary cohort of patients with medically treated type B dissection.
Methods: Included were all patients with acute uncomplicated type B aortic dissection who were initially managed medically between March 1999 and March 2011 and had follow-up axial imaging studies. Maximum aortic growth was calculated by comparing the initial imaging study to the most current scan or imaging obtained just before any aortic-related intervention. An increase of >= 5 mm was the threshold considered as aortic growth. Predictors of aortic aneurysmal degeneration were determined using Cox proportional hazards models.
Results: We identified 200 patients (61% men) with medically managed acute type B dissections receiving multiple imaging studies. Patients were an average age of 63.4 years, and 75.5% had a history of hypertension. Mean follow-up was 5.3 years (range, 0.1-14.7 years). Mean time between the initial and final imaging studies was 3.2 years (range, 0.1-12.9 years). At 5 years, only 51% were free from aortic growth. Fifty-six patients (28%) required operative intervention (50 open, 6 endovascular repair) for aneurysmal degeneration, and the actuarial 5-year freedom from intervention was 76%. After excluding five patients (2.5%) with early rapid degeneration requiring intervention within the first 2 weeks, the mean rate of aortic growth was 12.3 mm/y for the total aortic diameter, 3.8 mm/y for the true lumen diameter, and 8.6 mm/y for the false lumen diameter. Only aortic diameter at index presentation >3.5 cm was a risk factor for future growth (odds ratio, 2.54; 95% confidence interval, 1.34-4.81; P < .01). Complete thrombosis of the false lumen was protective against growth (odds ratio, 0.19; 95% confidence interval, 0.11-0.42; P < .01).
Conclusions: Although medical management of uncomplicated acute, type B aortic dissections has been the standard of care, at 5 years, a significant number of patients will require operative intervention for aneurysmal degeneration. Further studies of early intervention (eg, thoracic endovascular aortic repair) for type B aortic dissection to prevent late aneurysm formation are needed.
C1 [Durham, Christopher A.; Aranson, Nathan J.; Ergul, Emel A.; Wang, Linda J.; Patel, Virendra I.; Cambria, Richard P.; Conrad, Mark F.] Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, Boston, MA 02114 USA.
RP Conrad, MF (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 440, Boston, MA 02114 USA.
EM mconrad@partners.org
OI Aranson, Nathan/0000-0001-8833-4643
NR 33
TC 6
Z9 6
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 OCT
PY 2015
VL 62
IS 4
BP 900
EP 906
DI 10.1016/j.jvs.2015.04.423
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800011
PM 26071613
ER
PT J
AU Brothers, TE
Ricotta, JJ
Gillespie, DL
Geraghty, PJ
Kenwood, CT
Siami, FS
Ricotta, JJ
White, RA
AF Brothers, Thomas E.
Ricotta, Joseph J., II
Gillespie, David L.
Geraghty, Patrick J.
Kenwood, Christopher T.
Siami, Flora S.
Ricotta, John J.
White, Rodney A.
TI Contemporary results of carotid endarterectomy in "normal-risk" patients
from the Society for Vascular Surgery Vascular Registry
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery
CY MAR 12-16, 2013
CL Miami Beach, FL
SP Soc Clin Vasc Surg
ID ARTERY STENOSIS; OCCLUSION; MEDICARE; TRIAL; AGE
AB Objective: Acceptable complication rates after carotid endarterectomy (CEA) are drawn from decades-old data. The recent Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated improved stroke and mortality outcomes after CEA compared with carotid artery stenting, with 30-day periprocedural CEA stroke rates of 3.2% and 1.4% for symptomatic (SX) and asymptomatic (ASX) patients, respectively. It is unclear whether these target rates can be attained in "normal-risk" (NR) patients experienced outside of the trial. This study was done to determine the contemporary results of CEA from a broader selection of NR patients.
Methods: The Society for Vascular Surgery (SVS) Vascular Registry was examined to determine in-hospital and 30-day event rates for NR, SX, and ASX patients undergoing CEA. NR was defined as patients without anatomic or physiologic risk factors as defined by SVS Carotid Practice Guidelines. Raw data and risk-adjusted rates of death, stroke, and myocardial infarction (MI) were compared between the ASX and SX cohorts.
Results: There were 3977 patients (1456 SX, 2521 ASX) available for comparison. The SX group consisted of more men (61.7% vs 57.0%; P = .0045) but reflected a lower proportion of white patients (91.3% vs 94.4%; P = .0002), with lower prevalence of coronary artery disease (P < .0001), prior MI (P < .0001), peripheral vascular disease (P = .0017), and hypertension (P = .029), although New York Heart Association grade >3 congestive heart failure was equally present in both groups (P = .30). Baseline stenosis >80% on duplex imaging was less prevalent among SX patients (54.2% vs 67.8%; P < .0001). Perioperative stroke rates were higher for SX patients in the hospital (2.8% vs 0.8%; P < .0001) and at 30 days (3.4% vs 1.0%; P < .0001), which contributed to the higher composite death, stroke, andMI rates in the hospital (3.6% vs 1.8; P = .0003) and at 30 days (4.5% vs 2.2%; P < .0001) observed in SX patients. After risk adjustment, the rate of stroke/death was greater among SX patients in the hospital (odds ratio, 2.05; 95% confidence interval, 1.18-3.58) although not at 30 days (odds ratio, 1.36; 95% confidence interval, 0.85-2.17). No in-hospital or 30-day differences were observed for death or MI by symptom status.
Conclusions: The SVS Vascular Registry results for CEA in NR patients are similar by symptom status to those reported for CREST and may serve as a benchmark for comparing results of alternative therapies for treatment of carotid stenosis in NR patients outside of monitored clinical trials. The contemporary perioperative risk of stroke after CEA in NR patients continues to be higher for SX than for ASX patients.
C1 [Brothers, Thomas E.] Med Univ S Carolina, Surg Sect, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA.
[Brothers, Thomas E.] Med Univ S Carolina, Div Vasc Surg, Charleston, SC 29425 USA.
[Ricotta, Joseph J., II] Northside Vasc Surg, Dept Vasc Surg & Endovasc Therapy, Atlanta, GA USA.
[Gillespie, David L.] Southcoast Hlth Syst, Dept Vasc & Endovasc Surg, Fall River, MA USA.
[Geraghty, Patrick J.] Washington Univ, Div Gen Surg, Vasc Surg Sect, St Louis, MO USA.
[Kenwood, Christopher T.; Siami, Flora S.] New England Res Inst Inc, Inst Clin Trials & Registries, Watertown, MA 02472 USA.
[Ricotta, John J.] Washington Hosp Ctr, Dept Vasc Surg, Washington, DC 20010 USA.
[White, Rodney A.] Harbor UCLA, Div Vasc Surg, Los Angeles, CA USA.
RP Siami, FS (reprint author), New England Res Inst Inc, 480 Pleasant St,Ste A100, Watertown, MA 02472 USA.
EM ssiami@neriscience.com
NR 20
TC 2
Z9 2
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 OCT
PY 2015
VL 62
IS 4
BP 923
EP 928
DI 10.1016/j.jvs.2015.05.003
PG 6
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800014
PM 26194815
ER
PT J
AU Aranson, NJ
Patel, VI
Durham, CA
Conrad, MF
Lancaster, RT
MacGillivray, TE
Isselbacher, E
Cambria, RP
AF Aranson, Nathan J.
Patel, Virendra I.
Durham, Christopher A.
Conrad, Mark F.
Lancaster, R. Todd
MacGillivray, Thomas E.
Isselbacher, Eric
Cambria, Richard P.
TI Presentation, Surgical Intervention, and Long-Term Survival in Patients
With Marfan Syndrome
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Aranson, Nathan J.; Patel, Virendra I.; Durham, Christopher A.; Conrad, Mark F.; Lancaster, R. Todd; MacGillivray, Thomas E.; Isselbacher, Eric; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
OI Aranson, Nathan/0000-0001-8833-4643
NR 0
TC 0
Z9 0
U1 0
U2 1
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 OCT
PY 2015
VL 62
IS 4
BP 1094
EP 1094
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800046
ER
PT J
AU Conrad, MF
Tuchek, J
Feezor, R
Bavaria, J
Fairman, R
White, R
AF Conrad, Mark F.
Tuchek, James
Feezor, Robert
Bavaria, Joseph
Fairman, Ronald
White, Rodney
TI Five-Year Results of the Valor II Trial of the Medtronic Valiant
Thoracic Stent Graft
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tuchek, James] Loyola Univ, Maywood, IL 60153 USA.
[Feezor, Robert] Univ Florida, Gainesville, FL USA.
[Bavaria, Joseph; Fairman, Ronald] Univ Penn, Philadelphia, PA 19104 USA.
[White, Rodney] Univ Calif Los Angeles, Torrance, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD OCT
PY 2015
VL 62
IS 4
BP 1094
EP 1094
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800045
ER
PT J
AU Clouse, WD
Ergul, EA
Cambria, RP
Brewster, DC
Kwolek, CJ
Watkins, MT
LaMuraglia, GM
Patel, VI
Conrad, MF
AF Clouse, W. Darrin
Ergul, Emel A.
Cambria, Richard P.
Brewster, David C.
Kwolek, Christopher J.
Watkins, Michael T.
LaMuraglia, Glenn M.
Patel, Virendra I.
Conrad, Mark F.
TI Carotid Endarterectomy with Retrograde Proximal Stenting: Not a Simple
Solution
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Clouse, W. Darrin; Ergul, Emel A.; Cambria, Richard P.; Brewster, David C.; Kwolek, Christopher J.; Watkins, Michael T.; LaMuraglia, Glenn M.; Patel, Virendra I.; Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD OCT
PY 2015
VL 62
IS 4
BP 1096
EP 1096
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800051
ER
PT J
AU Klarin, D
Lancaster, R
Ergul, E
Bertges, D
Goodney, P
Conrad, M
Cambria, RP
Patel, V
AF Klarin, Derek
Lancaster, Robert
Ergul, Emel
Bertges, Daniel
Goodney, Phillip
Conrad, Mark
Cambria, Richard P.
Patel, Virendra
TI Perioperative and Long-Term Impact of Chronic Kidney Disease on Carotid
Artery Interventions
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Klarin, Derek; Lancaster, Robert; Ergul, Emel; Conrad, Mark; Cambria, Richard P.; Patel, Virendra] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bertges, Daniel] Univ Vermont, Med Ctr, Burlington, VT USA.
[Goodney, Phillip] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD OCT
PY 2015
VL 62
IS 4
BP 1099
EP 1099
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800057
ER
PT J
AU Corey, M
Ergul, E
Patel, V
Lancaster, RT
Kwolek, C
Cambria, R
Conrad, M
AF Corey, Michael
Ergul, Emel
Patel, Virendra
Lancaster, R. Todd
Kwolek, Christopher
Cambria, Richard
Conrad, Mark
TI The Presentation and Management of Gastroduodenal and
Pancreaticoduodenal Artery Aneurysms
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Corey, Michael; Ergul, Emel; Patel, Virendra; Lancaster, R. Todd; Kwolek, Christopher; Cambria, Richard; Conrad, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD OCT
PY 2015
VL 62
IS 4
BP 1100
EP 1101
PG 4
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800060
ER
PT J
AU Lancaster, RT
Ergul, EA
Buck, DB
Schermerhorn, ML
Schanzer, A
Conrad, MF
Cambria, RP
Patel, VI
AF Lancaster, Robert T.
Ergul, Emel A.
Buck, Dominique B.
Schermerhorn, Marc L.
Schanzer, Andres
Conrad, Mark F.
Cambria, Richard P.
Patel, Virendra I.
TI Similar Outcomes of Open and Endovascular Repair for Complex Aortic
Aneurysms
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT 42nd New-England-Society for Vascular Surgery Annual Meeting
CY OCT 02-04, 2015
CL Newport, RI
SP New England Soc
C1 [Lancaster, Robert T.; Ergul, Emel A.; Conrad, Mark F.; Cambria, Richard P.; Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Buck, Dominique B.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Schanzer, Andres] UMass Mem Med Ctr, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD OCT
PY 2015
VL 62
IS 4
BP 1101
EP 1102
PG 5
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CS2GC
UT WOS:000361885800062
ER
PT J
AU Hosseini, A
Qi, W
Tsai, TY
Liu, YJ
Rubash, H
Li, GA
AF Hosseini, Ali
Qi, Wei
Tsai, Tsung-Yuan
Liu, Yujie
Rubash, Harry
Li, Guoan
TI In vivo length change patterns of the medial and lateral collateral
ligaments along the flexion path of the knee
SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
LA English
DT Article
DE In vivo length change pattern; Medial collateral ligament; Lateral
collateral ligament; Lunge
ID ANTERIOR CRUCIATE LIGAMENT; ARTHROPLASTY; JOINT; KINEMATICS; PROSTHESES;
ELONGATION; BUNDLES; MOTION; RANGE; MODEL
AB The knowledge of the function of the collateral ligaments-i.e., superficial medial collateral ligament (sMCL), deep medial collateral ligament (dMCL) and lateral collateral ligament (LCL)-in the entire range of knee flexion is important for soft tissue balance during total knee arthroplasty (TKA). The objective of this study was to investigate the length changes of different portions (anterior, middle and posterior) of the sMCL, dMCL and LCL during in vivo weightbearing flexion from full extension to maximal knee flexion.
Using a dual fluoroscopic imaging system, eight healthy knees were imaged while performing a lunge from full extension to maximal flexion. The length changes of each portion of the collateral ligaments were measured along the flexion path of the knee.
All anterior portions of the collateral ligaments were shown to have increasing length with flexion except that of the sMCL, which showed a reduction in length at high flexion. The middle portions showed minimal change in lengths except that of the sMCL, which showed a consistent reduction in length with flexion. All posterior portions showed reduction in lengths with flexion.
These data indicated that every portion of the ligaments may play important roles in knee stability at different knee flexion range. The soft tissue releasing during TKA may need to consider the function of the ligament portions along the entire flexion path including maximum flexion.
III.
C1 [Hosseini, Ali; Qi, Wei; Tsai, Tsung-Yuan; Rubash, Harry; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA.
[Qi, Wei; Liu, Yujie] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed Surg, Beijing 100853, Peoples R China.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM gli1@partners.org
OI Tsai, Tsung-Yuan/0000-0003-1522-2987
FU National Institutes of Health [R01 AR055612]; Chinese PLA General
Hospital
FX The authors gratefully acknowledge the support of the National
Institutes of Health (R01 AR055612) and the scholarship provided by the
Chinese PLA General Hospital.
NR 34
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-2056
EI 1433-7347
J9 KNEE SURG SPORT TR A
JI Knee Surg. Sports Traumatol. Arthrosc.
PD OCT
PY 2015
VL 23
IS 10
BP 3055
EP 3061
DI 10.1007/s00167-014-3306-9
PG 7
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA CS0EB
UT WOS:000361729400039
PM 25239504
ER
PT J
AU Park, ER
Psaros, C
Traeger, L
Stagg, A
Jacquart, J
Willett, J
Alert, MD
LaRoche, KL
Ecker, JL
AF Park, E. R.
Psaros, C.
Traeger, L.
Stagg, A.
Jacquart, J.
Willett, J.
Alert, M. D.
LaRoche, K. L.
Ecker, J. L.
TI Development of a Postpartum Stressor Measure
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Stress perception; Stress measure; Postpartum stressors
ID POSTNATAL DEPRESSION SCALE; SOCIAL SUPPORT; PERCEIVED STRESS; MATERNAL
STRESS; WOMENS HEALTH; PREGNANCY; SMOKING; CHILDBIRTH; SYMPTOMS;
DISTRESS
AB To develop a brief self-report assessment of the type and magnitude of stressors during the postpartum period. A cross-sectional study of a convenience sample of 138 women at Massachusetts General Hospital in Boston, MA completed a measure of postpartum stressors at their 6-week postpartum visit. Item analyses were conducted; items were eliminated based on low relevance, low endorsement, and cross-loadings, resulting in a 9-item measure. Items were summed to create a total postpartum stressors score. To establish concurrent validity with perceived stress, the total postpartum stressors score was correlated with the 4-item Perceived Stress Scale (PSS-4). The stressors score was tested for bivariate associations with depression (Patient Health Questionnaire-2) and with social support (three items adapted from the MOS Social Support Scale). The 9-item measure, which was comprised of three factors (baby care, well-being, and work) demonstrated good reliability (Cronbach's alpha = .74) and concurrent validity with the PSS-4 (r = .53; p < .001) in the current sample. The stressors total score was negatively associated with social support (p < .001) and was positively associated with depression symptoms (p < .001). The early psychometric results on this measure are promising and associated with postpartum social support and depressive symptoms. With additional research to enhance external validity, this measure could be used and tested in an intervention study at the 6-week postpartum visit to identify women at risk for distress.
C1 [Park, E. R.; Psaros, C.; Traeger, L.; Jacquart, J.; Willett, J.; Alert, M. D.; LaRoche, K. L.] Harvard Univ, Sch Med, MGH, Benson Henry Inst Mind Body Med, Boston, MA USA.
[Park, E. R.; Psaros, C.; Traeger, L.] Harvard Univ, Sch Med, Dept Psychiat, MGH, Boston, MA 02115 USA.
[Park, E. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Stagg, A.] Harvard Univ, Sch Med, MGH, Dept Gen Med, Boston, MA USA.
[Stagg, A.; Ecker, J. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ecker, J. L.] MGH, Vincent Dept Obstet & Gynecol, Boston, MA USA.
RP Park, ER (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 901, Boston, MA 02114 USA.
EM epark@mgh.harvard.edu; CPSAROS@mgh.harvard.edu;
02114LTRAEGER@mgh.harvard.edu; ASTAGG1@mgh.harvard.edu;
jolene.jacquart@gmail.com; jessica.willett21@gmail.com;
marissa1787@gmail.com; KLAROCHE@mgh.harvard.edu; JECKER@PARTNERS.ORG
FU CDC [R01DP000339]
FX Research was supported by the CDC Grant R01DP000339.
NR 42
TC 1
Z9 1
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD OCT
PY 2015
VL 19
IS 10
BP 2094
EP 2101
DI 10.1007/s10995-015-1731-0
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR8SV
UT WOS:000361625100002
PM 25682113
ER
PT J
AU Derrington, TM
Bernstein, J
Belanoff, C
Cabral, HJ
Babakhanlou-Chase, H
Diop, H
Evans, SR
Kotelchuck, M
AF Derrington, Taletha Mae
Bernstein, Judith
Belanoff, Candice
Cabral, Howard J.
Babakhanlou-Chase, Hermik
Diop, Hafsatou
Evans, Stephen R.
Kotelchuck, Milton
TI Refining Measurement of Substance Use Disorders Among Women of
Child-Bearing Age Using Hospital Records: The Development of the
Explicit-Mention Substance Abuse Need for Treatment in Women (EMSANT-W)
Algorithm
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Diagnosis code grouper; Hospital discharge data; Prevalence; Substance
abuse; Women
ID ILLICIT-DRUG; ALCOHOL-USE; PREGNANCY; MASSACHUSETTS; LINKAGE; CARE
AB Substance use disorder (SUD) in women of reproductive age is associated with adverse health consequences for both women and their offspring. US states need a feasible population-based, case-identification tool to generate better approximations of SUD prevalence, treatment use, and treatment outcomes among women. This article presents the development of the Explicit Mention Substance Abuse Need for Treatment in Women (EMSANT-W), a gender-tailored tool based upon existing International Classification of Diseases, 9th Edition, Clinical Modification diagnostic code-based groupers that can be applied to hospital administrative data. Gender-tailoring entailed the addition of codes related to infants, pregnancy, and prescription drug abuse, as well as the creation of inclusion/exclusion rules based on other conditions present in the diagnostic record. Among 1,728,027 women and associated infants who accessed hospital care from January 1, 2002 to December 31, 2008 in Massachusetts, EMSANT-W identified 103,059 women with probable SUD. EMSANT-W identified 4,116 women who were not identified by the widely used Clinical Classifications Software for Mental Health and Substance Abuse (CCS-MHSA) and did not capture 853 women identified by CCS-MHSA. Content and approach innovations in EMSANT-W address potential limitations of the Clinical Classifications Software, and create a methodologically sound, gender-tailored and feasible population-based tool for identifying women of reproductive age in need of further evaluation for SUD treatment. Rapid changes in health care service infrastructure, delivery systems and policies require tools such as the EMSANT-W that provide more precise identification methods for sub-populations and can serve as the foundation for analyses of treatment use and outcomes.
C1 [Derrington, Taletha Mae] SRI Int, Ctr Educ & Human Serv, Educ Div, Menlo Pk, CA 94025 USA.
[Derrington, Taletha Mae; Bernstein, Judith; Belanoff, Candice; Evans, Stephen R.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA.
[Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Babakhanlou-Chase, Hermik] Massachusetts Dept Publ Hlth, Bur Subst Abuse Serv, Boston, MA USA.
[Diop, Hafsatou] Massachusetts Dept Publ Hlth, Bur Family Hlth & Nutr, Off Data Translat, Boston, MA USA.
[Kotelchuck, Milton] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA.
RP Derrington, TM (reprint author), SRI Int, Ctr Educ & Human Serv, Educ Div, 333 Ravenswood Ave,BS179, Menlo Pk, CA 94025 USA.
EM taletha.derrington@sri.com
FU National Institute on Alcohol Abuse and Alcoholism [R21 AA018395];
National Institute on Drug Abuse of the National Institutes of Health
[R21 DA027181]; Massachusetts Department of Public Health; CDC (PELL
Data System Expansion and Associated Analyses) [200-2009-31671]
FX This work was supported by two R21 grants from National Institute on
Alcohol Abuse and Alcoholism (grant R21 AA018395) and the National
Institute on Drug Abuse (grant R21 DA027181) of the National Institutes
of Health. PELL is currently administered and funded by the
Massachusetts Department of Public Health. From its inception in 2001 to
2012, it was a university-government partnership between the Boston
University School of Public Health, the Massachusetts Department of
Public Health, and the Centers for Disease Control and Prevention (CDC)
and was funded by the CDC (PELL Data System Expansion and Associated
Analyses Contract No. 200-2009-31671). The findings and conclusions in
this report are those of the authors and do not necessarily represent
the official position of the National Institutes of Health or the
Massachusetts Department of Public Health. Dr. William McAuliffe
provided many hours of invaluable assistance to the study team,
explaining the rationale behind the inclusion and exclusion criteria
used in the SNI, and challenging investigators to examine assumptions
and support them with evidence. While his index was designed with
another purpose in mind, it forms the foundation that made it possible
to undertake this work.
NR 38
TC 2
Z9 2
U1 0
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD OCT
PY 2015
VL 19
IS 10
BP 2168
EP 2178
DI 10.1007/s10995-015-1730-1
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR8SV
UT WOS:000361625100010
PM 25680703
ER
PT J
AU England, L
Kotelchuck, M
Wilson, HG
Diop, H
Oppedisano, P
Kim, SY
Cui, XH
Shapiro-Mendoza, CK
AF England, Lucinda
Kotelchuck, Milton
Wilson, Hoyt G.
Diop, Hafsatou
Oppedisano, Paul
Kim, Shin Y.
Cui, Xiaohui
Shapiro-Mendoza, Carrie K.
TI Estimating the Recurrence Rate of Gestational Diabetes Mellitus (GDM) in
Massachusetts 1998-2007: Methods and Findings
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Diabetes; Gestational diabetes mellitus; Diabetes recurrence; Sequential
pregnancies; Pregnancy
ID LIFE-STYLE INTERVENTION; PREPREGNANCY OBESITY; PREGNANT-WOMEN;
HIGH-RISK; TRENDS; PREVALENCE; OUTCOMES; PRESERVATION; POPULATION;
PROGRAM
AB Women with gestational diabetes mellitus (GDM) may be able to reduce their risk of recurrent GDM and progression to type 2 diabetes mellitus through lifestyle change; however, there is limited population-based information on GDM recurrence rates.
We used data from a population of women delivering two sequential live singleton infants in Massachusetts (1998-2007) to estimate the prevalence of chronic diabetes mellitus (CDM) and GDM in parity one pregnancies and recurrence of GDM and progression from GDM to CDM in parity two pregnancies. We examined four diabetes classification approaches; birth certificate (BC) data alone, hospital discharge (HD) data alone, both sources hierarchically combined with a diagnosis of CDM from either source taking priority over a diagnosis of GDM, and both sources combined including only pregnancies with full agreement in diagnosis. Descriptive statistics were used to describe population characteristics, prevalence of CDM and GDM, and recurrence of diabetes in successive pregnancies. Diabetes classification agreement was assessed using the Kappa statistic. Associated maternal characteristics were examined through adjusted model-based t tests and Chi square tests.
A total of 134,670 women with two sequential deliveries of parities one and two were identified. While there was only slight agreement on GDM classification across HD and BC records, estimates of GDM recurrence were fairly consistent; nearly half of women with GDM in their parity one pregnancy developed GDM in their subsequent pregnancy. While estimates of progression from GDM to CDM across sequential pregnancies were more variable, all approaches yielded estimates of a parts per thousand currency sign5 %. The development of either GDM or CDM following a parity one pregnancy with no diagnosis of diabetes was < 3 % across approaches. Women with recurrent GDM were disproportionately older and foreign born.
Recurrent GDM is a serious life course public health issue; the inter-pregnancy interval provides an important window for diabetes prevention.
C1 [England, Lucinda; Kim, Shin Y.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA.
[Kotelchuck, Milton] Harvard Univ, MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Res & Policy, Sch Med, Boston, MA 02115 USA.
[Wilson, Hoyt G.] DB Consulting Grp Inc, Silver Spring, MD 20910 USA.
[Diop, Hafsatou; Cui, Xiaohui] Massachusetts Dept Publ Hlth, Bur Family Hlth & Nutr, Boston, MA 02108 USA.
[Oppedisano, Paul] Massachusetts Dept Publ Hlth, Boston, MA 02108 USA.
[Shapiro-Mendoza, Carrie K.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30341 USA.
RP Kotelchuck, M (reprint author), Harvard Univ, MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Res & Policy, Sch Med, 100 Cambridge St,Room 15-1545, Boston, MA 02115 USA.
EM lbe@cdc.gov; mkotelchuck@partners.org; hgw0@att.net;
hafsatou.diop@state.ma.us; paul.oppedisano@state.ma.us; skim1@cdc.gov;
xiaohui.cui@state.ma.usa; ayn9@cdc.gov
FU Intramural CDC HHS [CC999999]
NR 35
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD OCT
PY 2015
VL 19
IS 10
BP 2303
EP 2313
DI 10.1007/s10995-015-1750-x
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CR8SV
UT WOS:000361625100024
PM 26045058
ER
PT J
AU Agarwal, I
Glazer, NL
Barasch, E
Djousse, L
Gottdiener, JS
Ix, JH
Kizer, JR
Rimm, EB
Siscovick, DS
King, GL
Mukamal, KJ
AF Agarwal, Isha
Glazer, Nicole L.
Barasch, Eddy
Djousse, Luc
Gottdiener, John S.
Ix, Joachim H.
Kizer, Jorge R.
Rimm, Eric B.
Siscovick, David S.
King, George L.
Mukamal, Ken J.
TI Associations between metabolic dysregulation and circulating biomarkers
of fibrosis: the Cardiovascular Health Study
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Fibrosis; Growth factors; Hyperglycemia; Insulin resistance
ID GROWTH-FACTOR-BETA; GENE-EXPRESSION; TGF-BETA; INSULIN-RESISTANCE;
TRANSFORMING GROWTH-FACTOR-BETA-1; COLLAGEN TURNOVER; OLDER-ADULTS; HIGH
GLUCOSE; ACTIVATION; COMPLICATIONS
AB Aim. Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-beta (TGF-beta) and procollagen type III N-terminal propeptide (PIIINP).
Methods. We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-estelified fatty acids, with circulating levels of TGF-beta (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study.
Results. Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-beta (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP.
Conclusions. Isolated hyperglycemia is associated with higher serum concentrations of TGF-beta, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Agarwal, Isha; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Agarwal, Isha; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Glazer, Nicole L.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Barasch, Eddy] St Francis Hosp, Ctr Heart, Dept Res & Educ, Roslyn, NY USA.
[Barasch, Eddy] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Gottdiener, John S.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Populat Hlth, Bronx, NY 10467 USA.
[Rimm, Eric B.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Siscovick, David S.] New York Acad Med, New York, NY 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.
[King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[King, George L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Mukamal, Ken J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Agarwal, I (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM Isha_Agarwal@hms.harvard.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute (NHLBI) [HL118775, HL094555,
HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295];
National Institute on Aging (NIA) [AG023629]
FX This research was supported by contracts HL118775, HL094555,
HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant
HL080295 from the National Heart, Lung, and Blood Institute (NHLBI),
with additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided by
AG023629 from the National Institute on Aging (NIA). A full list of
principal CHS investigators and institutions can be found at
CHS-NHLBI.org.
NR 32
TC 2
Z9 2
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD OCT
PY 2015
VL 64
IS 10
BP 1316
EP 1323
DI 10.1016/j.metabol.2015.07.013
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CR8ZG
UT WOS:000361642400015
PM 26282733
ER
PT J
AU Papakostas, GI
Ionescu, DF
AF Papakostas, G. I.
Ionescu, D. F.
TI Towards new mechanisms: an update on therapeutics for
treatment-resistant major depressive disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Review
ID TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIAL;
PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITOR; D-ASPARTATE
ANTAGONIST; FUNCTIONAL PARTIAL AGONIST; DOUBLE-BLIND; ANTIDEPRESSANT
TREATMENT; CLINICAL-TRIAL; TESTOSTERONE GEL
AB Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments-especially for treatment-resistant depression (TRD)-are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.
C1 [Papakostas, G. I.; Ionescu, D. F.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA.
RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Clin Trials Network & Inst, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA.
EM gpapakostas@partners.org
RI Ionescu, Dawn/K-5675-2015
FU AstraZeneca; Bristol-Myers Squibb Company; Forest Pharmaceuticals;
National Institute of Mental Health; PAMLAB; Pfizer; Ridge Diagnostics;
Sunovion Pharmaceuticals; Theracos
FX Dr Papakostas has served as a consultant for Abbott Laboratories,
AstraZeneca, Avanir Pharmaceuticals, Brainsway, Bristol-Myers Squibb
Company, Cephalon, Dey Pharma, Eli Lilly, GlaxoSmithKline, Evotec AG, H.
Lundbeck A/S, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Novartis
Pharma AG, Otsuka Pharmaceuticals, PAMLAB, Pfizer, Pierre Fabre
Laboratories, Ridge Diagnostics (formerly known as Precision Human
Biolaboratories), Shire Pharmaceuticals, Sunovion Pharmaceuticals,
Takeda Pharmaceutical Company, Theracos and Wyeth. Dr Papakostas has
received honoraria from Abbott Laboratories, Astra Zeneca, Avanir
Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway, Cephalon, Dey
Pharma, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc
Pharmaceuticals, Jazz Pharmaceuticals, H. Lundbeck A/S, Novartis Pharma
AG, Otsuka Pharmaceuticals, PAMLAB, Pfizer, Pierre Fabre Laboratories,
Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals,
Takeda Pharmaceutical Company, Theracos, Titan Pharmaceuticals and
Wyeth. Dr Papakostas has received research support from AstraZeneca,
Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National
Institute of Mental Health, PAMLAB, Pfizer, Ridge Diagnostics (formerly
known as Precision Human Biolaboratories), Sunovion Pharmaceuticals and
Theracos. Dr Papakostas has served (not currently) on the speaker's
bureau for Bristol-Myers Squibb and Pfizer. Dr Ionescu has no conflict
of interest to disclose, financial or otherwise.
NR 107
TC 9
Z9 9
U1 6
U2 20
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 OCT
PY 2015
VL 20
IS 10
BP 1142
EP 1150
DI 10.1038/mp.2015.92
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CS2OE
UT WOS:000361909800001
PM 26148812
ER
PT J
AU Gottlieb, DJ
Hek, K
Chen, TH
Watson, NF
Eiriksdottir, G
Byrne, EM
Cornelis, M
Warby, SC
Bandinelli, S
Cherkas, L
Evans, DS
Grabe, HJ
Lahti, J
Li, M
Lehtimaki, T
Lumley, T
Marciante, KD
Perusse, L
Psaty, BM
Robbins, J
Tranah, GJ
Vink, JM
Wilk, JB
Stafford, JM
Bellis, C
Biffar, R
Bouchard, C
Cade, B
Curhan, GC
Eriksson, JG
Ewert, R
Ferrucci, L
Fulop, T
Gehrman, PR
Goodloe, R
Harris, TB
Heath, AC
Hernandez, D
Hofman, A
Hottenga, JJ
Hunter, DJ
Jensen, MK
Johnson, AD
Kahonen, M
Kao, L
Kraft, P
Larkin, EK
Lauderdale, DS
Luik, AI
Medici, M
Montgomery, GW
Palotie, A
Patel, SR
Pistis, G
Porcu, E
Quaye, L
Raitakari, O
Redline, S
Rimm, EB
Rotter, JI
Smith, AV
Spector, TD
Teumer, A
Uitterlinden, AG
Vohl, MC
Widen, E
Willemsen, G
Young, T
Zhang, X
Liu, Y
Blangero, J
Boomsma, DI
Gudnason, V
Hu, F
Mangino, M
Martin, NG
O'Connor, GT
Stone, KL
Tanaka, T
Viikari, J
Gharib, SA
Punjabi, NM
Raikkonen, K
Volzke, H
Mignot, E
Tiemeier, H
AF Gottlieb, D. J.
Hek, K.
Chen, T-h
Watson, N. F.
Eiriksdottir, G.
Byrne, E. M.
Cornelis, M.
Warby, S. C.
Bandinelli, S.
Cherkas, L.
Evans, D. S.
Grabe, H. J.
Lahti, J.
Li, M.
Lehtimaki, T.
Lumley, T.
Marciante, K. D.
Perusse, L.
Psaty, B. M.
Robbins, J.
Tranah, G. J.
Vink, J. M.
Wilk, J. B.
Stafford, J. M.
Bellis, C.
Biffar, R.
Bouchard, C.
Cade, B.
Curhan, G. C.
Eriksson, J. G.
Ewert, R.
Ferrucci, L.
Fulop, T.
Gehrman, P. R.
Goodloe, R.
Harris, T. B.
Heath, A. C.
Hernandez, D.
Hofman, A.
Hottenga, J-J
Hunter, D. J.
Jensen, M. K.
Johnson, A. D.
Kahonen, M.
Kao, L.
Kraft, P.
Larkin, E. K.
Lauderdale, D. S.
Luik, A. I.
Medici, M.
Montgomery, G. W.
Palotie, A.
Patel, S. R.
Pistis, G.
Porcu, E.
Quaye, L.
Raitakari, O.
Redline, S.
Rimm, E. B.
Rotter, J. I.
Smith, A. V.
Spector, T. D.
Teumer, A.
Uitterlinden, A. G.
Vohl, M-C
Widen, E.
Willemsen, G.
Young, T.
Zhang, X.
Liu, Y.
Blangero, J.
Boomsma, D. I.
Gudnason, V.
Hu, F.
Mangino, M.
Martin, N. G.
O'Connor, G. T.
Stone, K. L.
Tanaka, T.
Viikari, J.
Gharib, S. A.
Punjabi, N. M.
Raikkonen, K.
Volzke, H.
Mignot, E.
Tiemeier, H.
TI Novel loci associated with usual sleep duration: the CHARGE Consortium
Genome-Wide Association Study
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID BODY-MASS INDEX; OSTEOPOROTIC FRACTURES; HYPOTHYROID PATIENTS; COHORT
PROFILE; PHASE SYNDROME; DESIGN; RISK; VARIANTS; WOMEN; GENE
AB Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P = 1.1 x 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P = 9.3 x 10(-4)). The strongest combined association was at rs1823125 (P = 1.5 x 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
C1 [Gottlieb, D. J.; Chen, T-h] VA Boston Healthcare Syst, West Roxbury, MA 02132 USA.
[Gottlieb, D. J.; Cade, B.; Patel, S. R.; Redline, S.] Brigham & Womens Hosp, Dept Med, Div Sleep & Circadian Disorders, Boston, MA 02115 USA.
[Gottlieb, D. J.; Chen, T-h; O'Connor, G. T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Gottlieb, D. J.; O'Connor, G. T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hek, K.; Tiemeier, H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hek, K.; Hofman, A.; Luik, A. I.; Uitterlinden, A. G.; Tiemeier, H.] Erasmus MC, Dept Psychiat, Epidemiol & Social Psychiat Res Inst, Rotterdam, Netherlands.
[Watson, N. F.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Watson, N. F.; Gharib, S. A.] Univ Washington, UW Med Sleep Ctr, Seattle, WA 98195 USA.
[Eiriksdottir, G.; Smith, A. V.; Gudnason, V.] Icelandic Heart Assoc, Kopavogur, Iceland.
[Byrne, E. M.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia.
[Byrne, E. M.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Cornelis, M.; Jensen, M. K.; Rimm, E. B.; Hu, F.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Cornelis, M.; Curhan, G. C.; Rimm, E. B.; Hu, F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Warby, S. C.; Mignot, E.] Stanford Univ, Ctr Sleep Sci & Med, Palo Alto, CA 94304 USA.
[Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Cherkas, L.; Quaye, L.; Spector, T. D.; Mangino, M.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Evans, D. S.; Tranah, G. J.; Stone, K. L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Grabe, H. J.] Univ Med Greifswald, HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Lahti, J.; Raikkonen, K.] Univ Helsinki, Dept Behav Sci, Helsinki, Finland.
[Lahti, J.; Eriksson, J. G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Li, M.; Kao, L.; Punjabi, N. M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lehtimaki, T.] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland.
[Lehtimaki, T.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Lumley, T.] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Marciante, K. D.; Psaty, B. M.; Gharib, S. A.] Univ Washington, Dept Med, Seattle, WA USA.
[Marciante, K. D.; Psaty, B. M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Perusse, L.] Univ Laval, Dept Kinesiol, Quebec City, PQ, Canada.
[Perusse, L.; Vohl, M-C] Univ Laval, Inst Nutr & Funct Foods, Quebec City, PQ, Canada.
[Psaty, B. M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA USA.
[Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Robbins, J.] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA.
[Vink, J. M.; Hottenga, J-J; Willemsen, G.; Boomsma, D. I.] Vrije Univ Amsterdam, Netherlands Twin Register, Dept Biol Psychol, Amsterdam, Netherlands.
[Wilk, J. B.] Precis Med, Cambridge, MA USA.
[Stafford, J. M.; Liu, Y.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Bellis, C.; Blangero, J.] Texas Biomed Res Inst, San Antonio, TX USA.
[Biffar, R.] Univ Med Greifswald, Ctr Oral Hlth, Dept Prosthodont Gerodontol & Dent Mat, Greifswald, Germany.
[Bouchard, C.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Curhan, G. C.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Hu, F.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Eriksson, J. G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, J. G.] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Eriksson, J. G.] Natl Inst Hlth & Welf, Helsinki, Finland.
Vasa Cent Hosp, Vaasa, Finland.
[Ewert, R.] Univ Med Greifswald, Dept Internal Med B, Cardiol Pulm Med Infect Dis & Intens Care Med, Greifswald, Germany.
[Ferrucci, L.; Tanaka, T.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Fulop, T.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Gehrman, P. R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Goodloe, R.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Heath, A. C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Hernandez, D.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Hunter, D. J.; Kraft, P.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Johnson, A. D.; Zhang, X.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA USA.
[Kahonen, M.] Univ Tampere, Tampere Univ Hosp, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, M.] Univ Tampere, Tampere Univ Hosp, Sch Med, FIN-33101 Tampere, Finland.
[Larkin, E. K.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Lauderdale, D. S.] Univ Chicago, Dept Hlth Studies, Chicago, IL USA.
[Medici, M.; Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Palotie, A.; Widen, E.] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Palotie, A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Palotie, A.] Broad Inst MIT & Harvard, Genet Anal Platform, Cambridge, MA USA.
[Palotie, A.] Wellcome Trust Sanger Inst, Cambridge, England.
[Pistis, G.] San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy.
[Pistis, G.] Univ Trieste, Trieste, Italy.
[Pistis, G.; Porcu, E.] CNR, IRGB, Cagliari, Italy.
[Pistis, G.; Porcu, E.] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Raitakari, O.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, O.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Rotter, J. I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Rotter, J. I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Smith, A. V.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland.
[Teumer, A.] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Teumer, A.; Volzke, H.] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Uitterlinden, A. G.] Netherlands Consortium Healthy Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Vohl, M-C] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ, Canada.
[Young, T.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
[Viikari, J.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Viikari, J.] Univ Turku, Turku, Finland.
[Punjabi, N. M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Tiemeier, H.] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
RP Gottlieb, DJ (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy 111PI, West Roxbury, MA 02132 USA.
EM djgottlieb@partners.org
RI Johnson, Andrew/G-6520-2013; Montgomery, Grant/B-7148-2008; Bouchard,
Claude/A-7637-2009; Smith, Albert/K-5150-2015; mangino,
massimo/F-5134-2011
OI Tiemeier, Henning/0000-0002-4395-1397; Patel,
Sanjay/0000-0002-9142-5172; Lahti, Jari/0000-0002-4310-5297; Martin,
Nicholas/0000-0003-4069-8020; Montgomery, Grant/0000-0002-4140-8139;
Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470
FU National Heart, Lung and Blood Institute [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research
Institute [U01HG004402]; National Institutes of Health
[HHSN268200625226C, UL1RR025005, HHSN268200782096C, , ];
NIH Roadmap for Medical Research [, U01 AR45580, U01 AR45614, U01
AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197,
U01-AG027810, UL1 RR024140]; NHLBI [, HHSN268201200036C,
N01-HC-85239, N01-HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081,
N01-HC-85082, N01-HC-85083, N01-HC-85086, HL080295, HL087652,
HL105756]; National Institute on Aging (NIA) [, AG023629,
R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01
AG027574, R01 AG027576, R01 AG026720]; National Center for
Advancing Translational Sciences CTSI grant [,
UL1TR000124]; National Institute of Diabetes and Digestive and
Kidney Disease [, DK063491]; 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; NIA [N01-AG-62101, N01-AG-62103,
N01-AG-62106, 1R01AG032098-01A1, 1R01AG030474-01A1]; NIH, NIA; Academy
of Finland [134309, 126925, 121584, 124282, 129378, 117787, 41071];
Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo
Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg
Foundation; University of Helsinki; Ministry of Education; Ahokas
Foundation; Emil Aaltonen Foundation; Juho Vainio Foundation; Wellcome
Trust [WT089062]; National Institutes of Health [NCI] [CA40356,
CA087969, CA055075, CA98233]; National Institutes of Health [NIDDK]
[DK058845, DK070756]; National Institutes of Health [NHGRI] [HG004399];
National Institutes of Health [NHLBI] [HL35464]; Merck/Rosetta Research
Laboratories, North Wales, PA; Italian Ministry of Health
[ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263
MD 821336]; National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) [RC2ARO58973]; National Center for Research Resources
(NCRR); National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071194,
R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837,
R01 HL070838, R01 HL070839]; NIAMS [RC2ARO58973]; Medical Research
Council of Canada; Canadian Institutes for Health Research
[FRN-CCT-83028]; Australian National Health and Medical Research Council
[241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981,
496739, 552485, 552498]; Australian Research Council [A7960034,
A79906588, A79801419, DP0770096, DP0212016, DP0343921]; FP-5 GenomEUtwin
Project [QLG2-CT-2002-01254]; US National Institutes of Health (NIH)
[AA07535, AA10249, AA11998, AA13320, AA13321, AA13326, AA14041,
MH66206]; Netherlands Scientific Organization [NWO 480-05-003]; NHMRC
grant [613608]; Netherlands Organisation of Scientific Research NWO
Investments [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly (RIDE2) [014-93-015]; Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
[050-060-810]; Erasmus MC; Erasmus MC, Rotterdam; Erasmus University,
Rotterdam; Netherlands Organization for the Health Research and
Development (ZonMw); Ministry of Education, Culture and Science;
Ministry for Health, Welfare and Sports; European Commission;
Municipality of Rotterdam; VIDI grant of ZonMw [2009-017.106.370];
BavoEuropoort; Netherlands Organization for Scientific Research (NWO:
MagW/ZonMW) [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717,
Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192];
Center for Medical Systems Biology (CSMB, NWO Genomics)
[NBIC/BioAssist/RK(2008.024)]; Biobanking and Biomolecular Resources
Research Infrastructure (BBMRI -NL) [184.021.007]; VU University's
Institute for Health and Care Research (EMGO+ ); Neuroscience Campus
Amsterdam (NCA); European Science Foundation (ESF) [EU/QLRT-2001-01254];
European Community [HEALTH-F4-2007-201413]; ENGAGE
[HEALTH-F4-2007-201413]; European Science Council [ERC 230374]; Rutgers
University Cell and DNA Repository [NIMH U24 MH068457-06]; Avera
Institute, Sioux Falls, South Dakota (USA); National Institutes of
Health (NIH) [R01D0042157-01A, 1RC2MH089951-01, 1RC2 MH089995-01];
Genetic Association Information Network (GAIN) of the Foundation for the
National Institutes of Health; Federal Ministry of Education and
Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural
Affairs; Social Ministry of the Federal State of Mecklenburg-West
Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of
Mecklenburg-West Pomerania; Department of Health via the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre award; King's College London; National Eye Institute via an
NIH/CIDR genotyping project; National Heart, Lung, and Blood Institute
[R01HL62252]; National Center for Research Resources [1UL1RR025011];
Social Insurance Institution of Finland, Kuopio, Tampere; Turku
University Hospital Medical Funds [9M048 for 9N035]; Paavo Nurmi
Foundation; Finnish Foundation of Cardiovascular Research; Tampere
Tuberculosis Foundation; Finnish Cultural Foundation; [NS23724]
FX The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung and Blood
Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367 and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by Grant Number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. The Cardiovascular Health Study was
supported by NHLBI contracts HHSN268201200036C, N01-HC-85239,
N01-HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082,
N01-HC-85083, N01-HC-85086; and NHLBI grants HL080295, HL087652,
HL105756 with additional contribution from the National Institute of
Neurological Disorders and Stroke (NINDS). Additional support was
provided through AG023629 from the National Institute on Aging (NIA).
DNA handling and genotyping was supported in part by the National Center
for Research Resources grant UL1RR033176, now at the National Center for
Advancing Translational Sciences CTSI grant UL1TR000124; the National
Institute of Diabetes and Digestive and Kidney Disease grant DK063491 to
the Southern California Diabetes Endocrinology Research Center. This
research 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 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 (SHARe) 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) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center. The Health, Aging and Body Composition Study supported by NIA
contracts N01-AG-62101, N01-AG-62103 and N01-AG-62106 and NIA grants
1R01AG032098-01A1 and 1R01AG030474-01A1. Genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
fully funded through a federal contract from the National Institutes of
Health to The Johns Hopkins University, contract number
HHSN268200782096C. This research was supported in part by the Intramural
Research Program of the NIH, NIA. The Helsinki Birth Cohort Study has
been supported by grants from the Academy of Finland, the Finnish
Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk
Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg
Foundation, University of Helsinki, Ministry of Education, Ahokas
Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation, and
Wellcome Trust (grant number WT089062). The Nurses Health Study and
Health Professional Follow-Up Study GWAS were supported by grants from
the National Institutes of Health [NCI (CA40356, CA087969, CA055075,
CA98233), NIDDK (DK058845, DK070756), NHGRI (HG004399), NHLBI (HL35464)]
with additional support from Merck/Rosetta Research Laboratories, North
Wales, PA. The Invecchiare in CHIANTI study baseline (1998 2000) was
supported as a 'targeted project' (ICS110.1/RF97.; 71) by the Italian
Ministry of Health and in part by the U.S. National Institute on Aging
(Contracts: 263 MD 9164 and 263 MD 821336). The Osteoporotic Fractures
in Men (MrOS) Study is supported by National Institutes of Health
funding. The following institutes provide support: the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
the National Institute on Aging (NIA), the National Center for Research
Resources (NCRR), and NIH Roadmap for Medical Research under the
following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01
AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1
RR024140. The National Heart, Lung, and Blood Institute (NHLBI) provides
funding for the MrOS Sleep ancillary study 'Outcomes of Sleep Disorders
in Older Men' under the following grant numbers: R01 HL071194, R01
HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01
HL070838, and R01 HL070839'. The NIAMS provides funding for the MrOS
ancillary study 'GWAS in MrOS and SOF' under the grant number
RC2ARO58973. The Quebec Family Study was funded by multiple grants from
the Medical Research Council of Canada and the Canadian Institutes for
Health Research. This work was supported by a team grant from the
Canadian Institutes for Health Research (FRN-CCT-83028). Funding for the
Queensland Institute of Medical Research Twin Study was provided by the
Australian National Health and Medical Research Council (241944, 339462,
389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485,
552498), the Australian Research Council (A7960034, A79906588,
A79801419, DP0770096, DP0212016, DP0343921), the FP-5 GenomEUtwin
Project (QLG2-CT-2002-01254) and the US National Institutes of Health
(NIH grants AA07535, AA10249, AA11998, AA13320, AA13321, AA13326,
AA14041, MH66206). A portion of the genotyping on which this study was
based (Illumina 370K scans) was carried out at the Center for Inherited
Disease Research, Baltimore (CIDR), through an access award to our late
colleague Dr Richard Todd (Psychiatry, Washington University School of
Medicine, St Louis). Statistical analyses were carried out on the
Genetic Cluster Computer, which is financially supported by the
Netherlands Scientific Organization (NWO 480-05-003). EMB is supported
by NHMRC grant 613608. The generation and management of GWAS genotype
data for the Rotterdam Study are supported by the Netherlands
Organisation of Scientific Research NWO Investments (no.
175.010.2005.011, 911-03-012). This study is funded by the Research
Institute for Diseases in the Elderly (014-93-015; RIDE2), the
Netherlands Genomics Initiative (NGI)/Netherlands Organisation for
Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study
is funded by Erasmus MC and Erasmus University, Rotterdam, Netherlands
Organization for the Health Research and Development (ZonMw), the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam. Henning Tiemeier was supported by the VIDI
grant of ZonMw (2009-017.106.370). Karin Hek was supported by a grant
from BavoEuropoort. Netherlands Twin Registry funding was obtained from
the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW
grants 904-61-090, 985-10-002, 904-61-193,480-04-004, 400-05-717,
Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192),
Center for Medical Systems Biology (CSMB, NWO Genomics),
NBIC/BioAssist/RK(2008.; 024), Biobanking and Biomolecular Resources
Research Infrastructure (BBMRI -NL, 184.021.007), VU University's
Institute for Health and Care Research (EMGO+ ) and Neuroscience Campus
Amsterdam (NCA), European Science Foundation (ESF, EU/QLRT-2001-01254),
the European Community's Seventh Framework Program (FP7/2007-2013),
ENGAGE (HEALTH-F4-2007-201413); European Science Council (ERC 230374),
Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the
Avera Institute, Sioux Falls, South Dakota (USA), and the National
Institutes of Health (NIH, R01D0042157-01A, Grand Opportunity grants
1RC2MH089951-01 and 1RC2 MH089995-01). Part of the genotyping and
analyses were funded by the Genetic Association Information Network
(GAIN) of the Foundation for the National Institutes of Health. The
Study of Health in Pomerania is part of the Community Medicine Research
net of the University of Greifswald, Germany, which is funded by the
Federal Ministry of Education and Research (grants no. 01ZZ9603,
01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs and the Social
Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide
data have been supported by the Federal Ministry of Education and
Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare,
Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania.
The University of Greifswald is a member of the 'Center of Knowledge
Interchange' program of the Siemens AG and the Cache Campus program of
the InterSystems GmbH. The Study of Osteoporotic Fractures is supported
by National Institutes of Health funding. The National Institute on
Aging (NIA) provides support under the following grant numbers: R01
AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01
AG027574, R01 AG027576, and R01 AG026720. The National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding
for the ancillary study 'GWAS in MrOS and SOF' under the grant number
RC2ARO58973. TwinsUK was funded by the Wellcome Trust; European
Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE project
grant agreement (HEALTH-F4-2007-201413). The study also receives support
from the Department of Health via the National Institute for Health
Research (NIHR) comprehensive Biomedical Research Centre award to Guy's
& St Thomas' NHS Foundation Trust in partnership with King's College
London. Genotyping was performed by the Wellcome Trust Sanger Institute,
support of the National Eye Institute via an NIH/CIDR genotyping
project. This research was supported for the Wisconsin Sleep Cohort
Study by the National Heart, Lung, and Blood Institute (R01HL62252) and
National Center for Research Resources (1UL1RR025011) and by NS23724.
The Young Finns Study has been financially supported by the Academy of
Finland: grants 134309 (Eye), 126925, 121584, 124282, 129378 (Salve),
117787 (Gendi), and 41071 (Skidi), the Social Insurance Institution of
Finland, Kuopio, Tampere and Turku University Hospital Medical Funds
(grant 9M048 for 9N035 for TeLeht), Juho Vainio Foundation, Paavo Nurmi
Foundation, Finnish Foundation of Cardiovascular Research and Finnish
Cultural Foundation, Tampere Tuberculosis Foundation and Emil Aaltonen
Foundation.
NR 61
TC 14
Z9 14
U1 3
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 OCT
PY 2015
VL 20
IS 10
BP 1232
EP 1239
DI 10.1038/mp.2014.133
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CS2OE
UT WOS:000361909800011
PM 25469926
ER
PT J
AU Zhang, SY
Bellinger, AM
Glettig, DL
Barman, R
Lee, YAL
Zhu, JH
Cleveland, C
Montgomery, VA
Gu, L
Nash, LD
Maitland, DJ
Langer, R
Traverso, G
AF Zhang, Shiyi
Bellinger, Andrew M.
Glettig, Dean L.
Barman, Ross
Lee, Young-Ah Lucy
Zhu, Jiahua
Cleveland, Cody
Montgomery, Veronica A.
Gu, Li
Nash, Landon D.
Maitland, Duncan J.
Langer, Robert
Traverso, Giovanni
TI A pH-responsive supramolecular polymer gel as an enteric elastomer for
use in gastric devices
SO NATURE MATERIALS
LA English
DT Article
ID DRUG-DELIVERY SYSTEMS; BIOENTERICS INTRAGASTRIC BALLOON; RELEASE
COATINGS; DOSAGE FORMS; RESIDENCE; RETENTION; DOGS; BOND
AB Devices resident in the stomach-used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric-retentive dosage forms for prolonged drug delivery-typically incorporate elastic polymers to compress the devices during delivery through the oesophagus and other narrow orifices in the digestive system. However, in the event of accidental device fracture or migration, the non-degradable nature of these materials risks intestinal obstruction. Here, we show that an elastic, pH-responsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines. In a large animal model, prototype devices with these materials as the key component demonstrated prolonged gastric retention and safe passage. These enteric elastomers should increase the safety profile for a wide range of gastric-retentive devices.
C1 [Zhang, Shiyi; Bellinger, Andrew M.; Glettig, Dean L.; Barman, Ross; Lee, Young-Ah Lucy; Cleveland, Cody; Montgomery, Veronica A.; Gu, Li; Langer, Robert; Traverso, Giovanni] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Zhang, Shiyi; Bellinger, Andrew M.; Glettig, Dean L.; Barman, Ross; Lee, Young-Ah Lucy; Cleveland, Cody; Montgomery, Veronica A.; Gu, Li; Langer, Robert; Traverso, Giovanni] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Bellinger, Andrew M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA.
[Barman, Ross; Traverso, Giovanni] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Zhu, Jiahua] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
[Nash, Landon D.; Maitland, Duncan J.] Texas A&M Univ, Biomed Device Lab, Dept Biomed Engn, College Stn, TX 77843 USA.
[Langer, Robert] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM rlanger@mit.edu; ctraverso@partners.org
RI Zhu, Jiahua/F-3204-2012
OI Zhu, Jiahua/0000-0003-2889-3421
FU Bill and Melinda Gates Foundation [OPP1096734]; NIH [EB000244, T32
5T32HL007604-29]; Alexander von Humboldt Foundation under the Max Planck
Research Award; Federal Ministry of Education and Research; Laboratory
Directed Research and Development program at Oak Ridge National
Laboratory; Scientific User Facilities Division, Office of Basic Energy
Sciences, US Department of Energy; US DOE [DE-AC02-06CH11357]
FX This work was funded in part by the Bill and Melinda Gates Foundation
Grant OPP1096734 (to R.L.) and the NIH Grant EB000244 (to R.L.). The
paper was partly sponsored by the Alexander von Humboldt Foundation
under the auspices of the Max Planck Research Award to R.L. funded by
the Federal Ministry of Education and Research. A.M.B. was supported in
part by NIH T32 5T32HL007604-29. J.Z. was supported by the Laboratory
Directed Research and Development program at Oak Ridge National
Laboratory, which is sponsored by the Scientific User Facilities
Division, Office of Basic Energy Sciences, US Department of Energy. Use
of the Advanced Photon Source, an Office of Science User Facility
operated for the US Department of Energy (DOE) Office of Science by
Argonne National Laboratory, was supported by the US DOE under Contract
No. DE-AC02-06CH11357. We would like to thank J. Haupt and M. Jamiel for
expert veterinary support. We are indebted to L. Wood, P. Eckhoff, D.
Hartman, S. Kern, S. Hershenson and B. Nikolic for fruitful discussions
that stimulated the development of this material. The findings and
conclusions reported in this paper are those of the authors and do not
necessarily reflect positions or policies of the Bill and Melinda Gates
Foundation.
NR 44
TC 31
Z9 33
U1 39
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1476-1122
EI 1476-4660
J9 NAT MATER
JI Nat. Mater.
PD OCT
PY 2015
VL 14
IS 10
BP 1065
EP +
DI 10.1038/NMAT4355
PG 9
WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics,
Applied; Physics, Condensed Matter
SC Chemistry; Materials Science; Physics
GA CS0SF
UT WOS:000361771800028
PM 26213897
ER
PT J
AU Jeselsohn, R
Buchwalter, G
De Angelis, C
Brown, M
Schiff, R
AF Jeselsohn, Rinath
Buchwalter, Gilles
De Angelis, Carmine
Brown, Myles
Schiff, Rachel
TI ESR1 mutations-a mechanism for acquired endocrine resistance in breast
cancer
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; DEPENDENT PROBE AMPLIFICATION; CIRCULATING
TUMOR DNA; KINASE 4/6 INHIBITOR; HIGH-DOSE TAMOXIFEN; POSTMENOPAUSAL
WOMEN; GENETIC-HETEROGENEITY; MOLECULAR PORTRAITS; CLONAL EVOLUTION;
K303R MUTATION
AB Approximately 70% of breast cancers are oestrogen receptor a (ER) positive, and are, therefore, treated with endocrine therapies. However, about 25% of patients with primary disease and almost all patients with metastases will present with or eventually develop endocrine resistance. Despite the magnitude of this clinical challenge, the mechanisms underlying the development of resistance remain largely unknown. In the past 2 years, several studies unveiled gain-of-function mutations in ESR1, the gene encoding the ER, in approximately 20% of patients with metastatic ER-positive disease who received endocrine therapies, such as tamoxifen and aromatase inhibitors. These mutations are clustered in a 'hotspot' within the ligand-binding domain (LBD) of the ER and lead to ligand-independent ER activity that promotes tumour growth, partial resistance to endocrine therapy, and potentially enhanced metastatic capacity; thus, ER LBD mutations might account for a mechanism of acquired endocrine resistance in a substantial fraction of patients with metastatic disease. In general, the absence of detectable ESR1 mutations in patients with treatment-naive disease, and the correlation between the frequency of patients with tumours harbouring these mutations and the number of endocrine treatments received suggest that, under selective treatment pressure, clonal expansion of rare mutant clones occurs, leading to resistance. Preclinical and clinical development of rationale-based novel therapeutic strategies that inhibit these ER mutants has the potential to substantially improve treatment outcomes. We discuss the contribution of ESR1 mutations to the development of acquired resistance to endocrine therapy, and evaluate how mutated ER can be detected and targeted to overcome resistance and improve patient outcomes.
C1 [Jeselsohn, Rinath; Brown, Myles] Harvard Univ, Breast Oncol Ctr, Sch Med, Boston, MA 02215 USA.
[Buchwalter, Gilles] Harvard Univ, Ctr Funct Canc Epigenet, Dana Farber Canc Inst, Boston, MA 02215 USA.
[De Angelis, Carmine; Schiff, Rachel] Baylor Coll Med, Dept Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[De Angelis, Carmine; Schiff, Rachel] Baylor Coll Med, Dept Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[De Angelis, Carmine; Schiff, Rachel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Schiff, R (reprint author), Baylor Coll Med, Dept Med, Lester & Sue Smith Breast Ctr, One Baylor Plaza,BCM 600, Houston, TX 77030 USA.
EM rschiff@bcm.edu
OI Brown, Myles/0000-0002-8213-1658
FU NCI [P50 CA58183, P50 CA186784-01, P30 CA125123, P50 CA168508]; Susan G.
Komen for the Cure Promise [PG12221410]; Breast Cancer Research
Foundation; Cancer Prevention and Research Institute of Texas (CPRIT)
[RP140102]; Baylor College of Medicine; Claudia Adams Barr Award
FX R.S. has been funded in part by NCI grants P50 CA58183 and P50
CA186784-01 (SPORE) and P30 CA125123, as well as by the Susan G. Komen
for the Cure Promise Grant PG12221410, and the Breast Cancer Research
Foundation. C.D.A. has been funded by the Cancer Prevention and Research
Institute of Texas (CPRIT) programme RP140102 and the Baylor College of
Medicine Comprehensive Cancer Training Program. R.J. has been funded in
part by the Claudia Adams Barr Award and by the NCI grant P50 CA168508
(SPORE) Career Development Award.
NR 108
TC 35
Z9 36
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD OCT
PY 2015
VL 12
IS 10
BP 573
EP 583
DI 10.1038/nrclinonc.2015.117
PG 11
WC Oncology
SC Oncology
GA CS0SG
UT WOS:000361771900005
PM 26122181
ER
PT J
AU Green, MF
Horan, WP
Lee, J
AF Green, Michael F.
Horan, William P.
Lee, Junghee
TI Social cognition in schizophrenia
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID EVENT-RELATED POTENTIALS; EMOTION REGULATION; BIPOLAR DISORDER; EMPATHIC
ACCURACY; NEURAL RESPONSE; HUMAN BRAIN; NEUROCOGNITIVE DEFICITS;
NEUROIMAGING LITERATURE; 1ST-EPISODE PSYCHOSIS; SENSORY CONTRIBUTIONS
AB Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder.
C1 [Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
US Dept Vet Affairs, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA.
RP Green, MF (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,Room 27-462, Los Angeles, CA 90024 USA.
EM mgreen@ucla.edu
RI Lee, Junghee/C-5226-2014
OI Lee, Junghee/0000-0001-9567-8700
NR 200
TC 52
Z9 53
U1 20
U2 63
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 OCT
PY 2015
VL 16
IS 10
BP 620
EP 631
DI 10.1038/nrn4005
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA CR9QP
UT WOS:000361691900009
PM 26373471
ER
PT J
AU Shang, LS
Cho, MT
Retterer, K
Folk, L
Humberson, J
Rohena, L
Sidhu, A
Saliganan, S
Iglesias, A
Vitazka, P
Juusola, J
O'Donnell-Luria, AH
Shen, YF
Chung, WK
AF Shang, Linshan
Cho, Megan T.
Retterer, Kyle
Folk, Leandra
Humberson, Jennifer
Rohena, Luis
Sidhu, Alpa
Saliganan, Sheila
Iglesias, Alejandro
Vitazka, Patrik
Juusola, Jane
O'Donnell-Luria, Anne H.
Shen, Yufeng
Chung, Wendy K.
TI Mutations in ARID2 are associated with intellectual disabilities
SO NEUROGENETICS
LA English
DT Article
DE ARID2; Intellectual disabilities; Whole exome sequencing; De novo
mutations; SWI/SNF chromatin modifier
ID CHROMATIN-REMODELING COMPLEX; COFFIN-SIRIS SYNDROME; GENE-EXPRESSION;
NEURAL DEVELOPMENT; SWI/SNF COMPLEXES; FAMILY PROTEINS; CHARGE-SYNDROME;
PHENOTYPE; SUBUNIT; PBAF
AB The etiology of intellectual disabilities (ID) remains unknown for the majority of patients. Due to reduced reproductive fitness in many individuals with ID, de novo mutations account for a significant portion of severe ID. The ATP-dependent SWI/SNF chromatin modifier has been linked with neurodevelopmental disorders including ID and autism. ARID2 is an intrinsic component of polybromo-associated BAF (PBAF), the SWI/SNF subcomplex. In this study, we used clinical whole exome sequencing (WES) in proband-parent-trios to identify the etiology of ID. We identified four independent, novel, loss of function variants in ARID2 gene in four patients, three of which were confirmed to be de novo. The patients all have ID and share other clinical characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic facial features, and Wormian bones. All four novel variants are predicted to lead to a premature termination with the loss of the two conservative zinc finger motifs. This is the first report of mutations in ARID2 associated with developmental delay and ID.
C1 [Shang, Linshan; Iglesias, Alejandro] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
[Cho, Megan T.; Retterer, Kyle; Folk, Leandra; Vitazka, Patrik; Juusola, Jane] GeneDx, Gaithersburg, MD USA.
[Humberson, Jennifer] Univ Virginia, Dept Pediat, Div Genet & Metab, Charlottesville, VA USA.
[Rohena, Luis] San Antonio Mil Med Ctr, Div Genet, Dept Pediat, San Antonio, TX USA.
[Sidhu, Alpa; Saliganan, Sheila] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA.
[O'Donnell-Luria, Anne H.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[O'Donnell-Luria, Anne H.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[O'Donnell-Luria, Anne H.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA.
[Shen, Yufeng] Columbia Univ, Med Ctr, Dept Syst Biol & Biomed Informat, New York, NY USA.
[Chung, Wendy K.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
RP Chung, WK (reprint author), Columbia Univ, Med Ctr, Dept Pediat, 1150 St Nicholas Ave, New York, NY 10032 USA.
EM wkc15@columbia.edu
OI O'Donnell-Luria, Anne/0000-0001-6418-9592
FU Simons Foundation
FX We thank the families for their generous contributions. We thank the
data review support from ExAC consortium. This work was supported in
part by a grant from the Simons Foundation.
NR 54
TC 7
Z9 7
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
EI 1364-6753
J9 NEUROGENETICS
JI Neurogenetics
PD OCT
PY 2015
VL 16
IS 4
BP 307
EP 314
DI 10.1007/s10048-015-0454-0
PG 8
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA CR7VG
UT WOS:000361559100006
PM 26238514
ER
PT J
AU Cohen, RG
Gurfinkel, VS
Kwak, E
Warden, AC
Horak, FB
AF Cohen, Rajal G.
Gurfinkel, Victor S.
Kwak, Elizabeth
Warden, Amelia C.
Horak, Fay B.
TI Lighten Up: Specific Postural Instructions Affect Axial Rigidity and
Step Initiation in Patients With Parkinson's Disease
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE Parkinson's disease; postural sway; postural alignment; rigidity; gait
initiation; Alexander Technique; mindfulness
ID RANDOMIZED CONTROLLED-TRIAL; ALEXANDER TECHNIQUE LESSONS; LOW-BACK-PAIN;
GAIT INITIATION; OLDER-ADULTS; TAI-CHI; INSTABILITY; MOVEMENT;
ADJUSTMENTS; IMPROVEMENT
AB Background. Parkinson's disease (PD) is associated with stooped postural alignment, increased postural sway, and reduced mobility. The Alexander Technique (AT) is a mindfulness-based approach to improving posture and mobility by reducing muscular interference while maintaining upward intentions. Evidence suggests that AT can reduce disability associated with PD, but a mechanism for this effect has not yet been established. Objective. We investigated whether AT-based instructions reduce axial rigidity and increase upright postural alignment, and whether these instructions have different effects on postural alignment, axial rigidity, postural sway, and mobility than effort-based instructions regarding posture. Method. Twenty subjects with PD practiced 2 sets of instructions and then attempted to implement both approaches (as well as a relaxed control condition) during quiet standing and step initiation. The Lighten Up instructions relied on AT principles of reducing excess tension while encouraging length. The Pull Up instructions relied on popular concepts of effortful posture correction. We measured kinematics, resistance to axial rotation, and ground reaction forces. Results. Both sets of experimental instructions led to increases in upright postural alignment relative to the control condition. Only the Lighten Up instructions led to reduced postural sway, reduced axial postural tone, greater modifiability of tone, and a smoother center of pressure trajectory during step initiation, possibly indicating greater movement efficiency. Conclusion. Mindful movement approaches such as AT may benefit balance and mobility in subjects with PD by acutely facilitating increased upright postural alignment while decreasing rigidity.
C1 [Cohen, Rajal G.; Warden, Amelia C.] Univ Idaho, Moscow, ID 83844 USA.
[Gurfinkel, Victor S.; Horak, Fay B.] Oregon Hlth & Sci Univ, Beaverton, OR USA.
[Kwak, Elizabeth] Macalester Coll, St Paul, MN 55105 USA.
[Horak, Fay B.] Portland VA Med Ctr, Portland, OR USA.
RP Cohen, RG (reprint author), Univ Idaho, Dept Psychol & Commun Studies, 875 Perimeter Dr MS 3043, Moscow, ID 83844 USA.
EM rcohen@uidaho.edu
FU National Institutes of Health [AG-006457, T32-NS045553, T32-AT002688];
Medical Research Foundation of Oregon; University of Idaho College of
Letters, Arts, and Social Sciences
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 Institutes of Health (grants AG-006457,
T32-NS045553, and T32-AT002688); Medical Research Foundation of Oregon;
and University of Idaho College of Letters, Arts, and Social Sciences.
NR 51
TC 5
Z9 5
U1 2
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
EI 1552-6844
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD OCT
PY 2015
VL 29
IS 9
BP 878
EP 888
DI 10.1177/1545968315570323
PG 11
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA CS2JW
UT WOS:000361897800008
PM 25665828
ER
PT J
AU Lebwohl, M
Strober, B
Menter, A
Gordon, K
Weglowska, J
Puig, L
Papp, K
Spelman, L
Toth, D
Kerdel, F
Armstrong, AW
Stingl, G
Kimball, AB
Bachelez, H
Wu, JJ
Crowley, J
Langley, RG
Blicharski, T
Paul, C
Lacour, JP
Tyring, S
Kircik, L
Chimenti, S
Duffin, KC
Bagel, J
Koo, J
Aras, G
Li, J
Song, W
Milmont, CE
Shi, Y
Erondu, N
Klekotka, P
Kotzin, B
Nirula, A
AF Lebwohl, M.
Strober, B.
Menter, A.
Gordon, K.
Weglowska, J.
Puig, L.
Papp, K.
Spelman, L.
Toth, D.
Kerdel, F.
Armstrong, A. W.
Stingl, G.
Kimball, A. B.
Bachelez, H.
Wu, J. J.
Crowley, J.
Langley, R. G.
Blicharski, T.
Paul, C.
Lacour, J. -P.
Tyring, S.
Kircik, L.
Chimenti, S.
Duffin, K. C.
Bagel, J.
Koo, J.
Aras, G.
Li, J.
Song, W.
Milmont, C. E.
Shi, Y.
Erondu, N.
Klekotka, P.
Kotzin, B.
Nirula, A.
TI Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; QUALITY-OF-LIFE; CLINICAL-RESPONSE; PLAQUE
PSORIASIS; MODERATE; SKIN; INTERLEUKIN-17; ANTIBODY; CELLS; CANDIDIASIS
AB BACKGROUND
Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.
METHODS
In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight <= 100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).
RESULTS
At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P = 0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P = 0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.
CONCLUSIONS
Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis.
C1 [Lebwohl, M.; Kircik, L.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Strober, B.] Univ Connecticut, Sch Med, Farmington, CT USA.
[Strober, B.; Spelman, L.; Toth, D.] Prob Med Res, Windsor, ON, Canada.
[Toth, D.] XLR8 Med Res, Windsor, ON, Canada.
[Papp, K.] K Papp Med Res, Waterloo, ON, Canada.
[Langley, R. G.] Dalhousie Univ, Halifax, NS, Canada.
[Menter, A.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Gordon, K.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Weglowska, J.] Niepubl Zaklad Opieki Zdrowotnej MultiMed, Wroclaw, Poland.
[Blicharski, T.] Lubelskie Ctr Diagnost, Swidnik, Poland.
[Puig, L.] Hosp Santa Creu & Sant Pau, Barcelona, Spain.
[Spelman, L.] Verac Clin Res, Woolloongabba, Qld, Australia.
[Kerdel, F.] Florida Acad Dermatol Ctr, Miami, FL USA.
[Armstrong, A. W.] Univ Colorado, Denver, CO 80202 USA.
[Stingl, G.] Med Univ Wien, Vienna, Austria.
[Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kimball, A. B.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Bachelez, H.] Univ Paris Diderot, Sorbonne Paris Cite, AP HP, Hop St Louis, Paris, France.
[Paul, C.] Univ Toulouse 3, F-31062 Toulouse, France.
[Lacour, J. -P.] Univ Hosp Nice, Nice, France.
[Wu, J. J.] Kaiser Permanente Los Angeles Med Ctr, Los Angeles, CA USA.
[Crowley, J.] Bakersfield Dermatol & Skin Canc Med Grp, Bakersfield, CA USA.
[Koo, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Aras, G.; Li, J.; Song, W.; Milmont, C. E.; Shi, Y.; Erondu, N.; Klekotka, P.; Kotzin, B.; Nirula, A.] Amgen Inc, Thousand Oaks, CA USA.
[Tyring, S.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA.
[Kircik, L.] DermResearch, Louisville, KY USA.
[Chimenti, S.] Univ Roma Tor Vergata, Rome, Italy.
[Duffin, K. C.] Univ Utah, Med Ctr, Salt Lake City, UT USA.
[Bagel, J.] Psoriasis Treatment Ctr Cent New Jersey, East Windsor, NJ USA.
RP Lebwohl, M (reprint author), Icahn Med Inst, 2nd Fl,1425 Madison Ave, New York, NY 10029 USA.
EM mark.lebwohl@mountsinai.org
OI Lacour, Jean-Philippe/0000-0001-7663-2053
FU Amgen
FX Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers,
NCT01708603 and NCT01708629.
NR 24
TC 66
Z9 70
U1 4
U2 15
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 OCT 1
PY 2015
VL 373
IS 14
BP 1318
EP 1328
DI 10.1056/NEJMoa1503824
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS3CI
UT WOS:000361948600006
PM 26422722
ER
PT J
AU Lennerz, JK
Ramamurthy, L
AF Lennerz, Jochen K.
Ramamurthy, Lakshman
TI ClinGen and Genetic Testing
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID FDA
C1 [Lennerz, Jochen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ramamurthy, Lakshman] Avalere Hlth, Washington, DC USA.
RP Lennerz, JK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM jlennerz@partners.org
NR 5
TC 0
Z9 0
U1 1
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 1
PY 2015
VL 373
IS 14
BP 1377
EP 1378
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS3CI
UT WOS:000361948600025
PM 26422740
ER
PT J
AU Warshaw, AL
AF Warshaw, Andrew L.
TI Appropriate Health Care: A Surgeon's View of the Patient With Pancreatic
Disease The Paul Webster Clinical State of the Art Lecture American
Pancreatic Association, November 2014
SO PANCREAS
LA English
DT Article
C1 [Warshaw, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA.
[Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Bulf 370C,55 Fruit St, Boston, MA 02114 USA.
EM awarshaw@partners.org
NR 3
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD OCT
PY 2015
VL 44
IS 7
BP 1003
EP 1005
DI 10.1097/MPA.0000000000000387
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR8LW
UT WOS:000361605100001
PM 26355543
ER
PT J
AU Ruben, MA
van Osch, M
Blanch-Hartigan, D
AF Ruben, Mollie A.
van Osch, Mara
Blanch-Hartigan, Danielle
TI Healthcare providers' accuracy in assessing patients' pain: A systematic
review
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article; Proceedings Paper
CT Conference of the European-Association-for-Communication-in-Healthcare
(EACH)
CY SEP 28-OCT 01, 2014
CL Amsterdam, NETHERLANDS
DE Pain assessment; Provider accuracy; Clinical experience; Chronic pain;
Acute pain
ID QUALITY-OF-LIFE; ADVANCED CANCER-PATIENTS; LOW-BACK-PAIN; FAMILY
CAREGIVERS; SELF-REPORT; HOSPITALIZED-PATIENTS; EMERGENCY-DEPARTMENT;
PERCEPTION ACCURACY; FACIAL EXPRESSION; REPORTED SYMPTOMS
AB Objective: Healthcare providers satisfy an important role in providing appropriate care in the prevention and management of acute and chronic pain, highlighting the importance of providers' abilities to accurately assess patients' pain. We systematically reviewed the literature on healthcare providers' pain assessment accuracy.
Methods: A systematic literature search was conducted in PubMed and PsycINFO to identify studies addressing providers' pain assessment accuracy, or studies that compared patients' self-report of pain with providers' assessment of pain.
Results: 60 studies met the inclusion criteria. Healthcare providers had moderate to good pain assessment accuracy. Physicians and nurses showed similar pain assessment accuracy. Differences in pain assessment accuracy were found according to providers' clinical experience, the timing of the pain assessment, vulnerable patient populations and patients' pain intensity.
Conclusion: Education and training aimed at improving providers with poor pain assessment accuracy is discussed especially in relation to those with limited clinical experience (<4 years) or a great deal of clinical experience (>10 years) and those providing care for vulnerable patient populations.
Practice implications: More research on characteristics that influence providers' pain assessment accuracy and trainings to improve pain assessment accuracy in medical and continuing education may improve pain treatment for patients. Published by Elsevier Ireland Ltd.
C1 [Ruben, Mollie A.] US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA.
[van Osch, Mara] NIVEL Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.
[Blanch-Hartigan, Danielle] Bentley Univ, Dept Nat & Appl Sci, Waltham, MA USA.
RP Ruben, MA (reprint author), US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA.
EM Mollie.Ruben@va.gov
OI Ruben, Mollie/0000-0001-8918-8932
NR 122
TC 2
Z9 2
U1 1
U2 7
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 OCT
PY 2015
VL 98
IS 10
SI SI
BP 1197
EP 1206
DI 10.1016/j.pec.2015.07.009
PG 10
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA CS1XR
UT WOS:000361862700005
PM 26223850
ER
PT J
AU Wittenberg, E
Bharel, M
Saada, A
Santiago, E
Bridges, JFP
Weinreb, L
AF Wittenberg, Eve
Bharel, Monica
Saada, Adrianna
Santiago, Emely
Bridges, John F. P.
Weinreb, Linda
TI Measuring the Preferences of Homeless Women for Cervical Cancer
Screening Interventions: Development of a Best-Worst Scaling Survey
SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH
LA English
DT Article
ID CONJOINT-ANALYSIS APPLICATIONS; DISCRETE-CHOICE EXPERIMENTS;
HEALTH-CARE; DISPARITIES; BEHAVIORS; ACCESS; ADULTS
AB Despite having multiple risk factors, women experiencing homelessness are screened for cervical cancer at a lower rate than women in the general US population. We report on the design of a stated preference study to assess homeless women's preferences for cervical cancer screening interventions, to inform efforts to overcome this disparity.
We conducted focus groups with homeless women (n = 8) on cervical cancer screening decisions and analyzed the data using thematic analysis. We applied inclusion criteria to select factors for a stated preference survey: importance to women, relevance to providers, feasibility, and consistency with clinical experience. We conducted pretests (n = 35) to assess survey procedures (functionality, recruitment, administration) and content (understanding, comprehension, wording/language, length).
We chose best-worst scaling (BWS)-also known as object scaling-to identify decision-relevant screening intervention factors. We chose an experimental design with 11 "objects" (i.e., factors relevant to women's screening decision) presented in 11 subsets of five objects each. Of 25 objects initially identified, we selected 11 for the BWS instrument: provider-related factors: attitude, familiarity, and gender; setting-related factors: acceptance and cost; procedure-related factors: explanation during visit and timing/convenience of visit; personal fears and barriers: concerns about hygiene, addiction, and delivery/fear of results; and a general factor of feeling overwhelmed.
Good practices for the development of stated preference surveys include considered assessment of the experimental design that is used and the preference factors that are included, and pretesting of the presentation format. We demonstrate the development of a BWS study of homeless women's cervical cancer screening intervention preferences. Subsequent research will identify screening priorities to inform intervention design.
C1 [Wittenberg, Eve; Saada, Adrianna] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
[Bharel, Monica; Santiago, Emely] Boston Hlth Care Homeless Program, Boston, MA USA.
[Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Bharel, Monica] Boston Med Ctr, Dept Med, Boston, MA USA.
[Bridges, John F. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
[Wittenberg, Eve] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA.
RP Wittenberg, E (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA.
EM ewittenb@hsph.harvard.edu
FU National Cancer Institute of the National Institutes of Health
[R21CA164712]
FX The research reported in this publication was supported by the National
Cancer Institute of the National Institutes of Health, under Award
Number R21CA164712. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health. The funding agreement guaranteed the
authors' independence in the research.
NR 29
TC 4
Z9 4
U1 4
U2 6
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1178-1653
EI 1178-1661
J9 PATIENT
JI Patient
PD OCT
PY 2015
VL 8
IS 5
BP 455
EP 467
DI 10.1007/s40271-014-0110-z
PG 13
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA CR8UR
UT WOS:000361630100008
PM 25586646
ER
PT J
AU Frigerio, A
Heaton, JT
Cavallari, P
Knox, C
Hohman, MH
Hadlock, TA
AF Frigerio, Alice
Heaton, James T.
Cavallari, Paolo
Knox, Chris
Hohman, Marc H.
Hadlock, Tessa A.
TI Electrical Stimulation of Eye Blink in Individuals with Acute Facial
Palsy: Progress toward a Bionic Blink
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID ORBICULARIS OCULI; ARTIFICIAL MUSCLE; PARALYSIS; RESTORATION;
ELECTROMYOGRAPHY; ASYMMETRY; SYSTEM
AB Background: Elicitation of eye closure and other movements via electrical stimulation may provide effective treatment for facial paralysis. The authors performed a human feasibility study to determine whether transcutaneous neural stimulation can elicit a blink in individuals with acute facial palsy and to obtain feedback from participants regarding the tolerability of surface electrical stimulation for daily blink restoration.
Methods: Forty individuals with acute unilateral facial paralysis, HB grades 4 through 6, were prospectively studied between 6 and 60 days of onset. Unilateral stimulation of zygomatic facial nerve branches to elicit eye blink was achieved with brief bipolar, charge-balanced pulse trains, delivered transcutaneously by adhesive electrode placement; results were recorded on a high-speed video camera. The relationship between stimulation parameters and cutaneous sensation was analyzed using the Wong-Baker Faces Pain Rating Scale.
Results: Complete eye closure was achieved in 55 percent of participants using stimulation parameters reported as tolerable. In those individuals, initial eye twitch was observed at an average current of 4.6 mA (1.7; average pulse width of 0.7 ms, 100 to 150 Hz), with complete closure requiring a mean of 7.2 mA (2.6).
Conclusions: Transcutaneous facial nerve stimulation may artificially elicit eye blink in a majority of patients with acute facial paralysis. Although individuals varied widely in their reported degrees of discomfort from blink-eliciting stimulation, most of them indicated that such stimulation would be tolerable if it could restore eye closure. These patients would therefore benefit from a biomimetic device to facilitate eye closure until the recovery process is complete.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
C1 Univ Milan, Human Physiol Sect, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy.
Harvard Univ, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, Div Facial Plast & Reconstruct Surg,Sch Med, Facial Nerve Ctr,Dept Otol & Laryngol,Massachuset, Cambridge, MA 02138 USA.
Harvard Univ, Med School, Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
RP Frigerio, A (reprint author), Massachusetts Eye & Ear Infirm, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, 243 Charles St, Boston, MA 02114 USA.
EM alice_frigerio@meei.harvard.edu
NR 23
TC 3
Z9 3
U1 3
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0032-1052
EI 1529-4242
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD OCT
PY 2015
VL 136
IS 4
BP 515E
EP 523E
DI 10.1097/PRS.0000000000001639
PG 9
WC Surgery
SC Surgery
GA CS0IT
UT WOS:000361743400001
PM 26397271
ER
PT J
AU Fairbairn, NG
Ng-Glazier, J
Meppelink, AM
Randolph, MA
Valerio, IL
Fleming, ME
Winograd, JM
Redmond, RW
AF Fairbairn, Neil G.
Ng-Glazier, Joanna
Meppelink, Amanda M.
Randolph, Mark A.
Valerio, Ian L.
Fleming, Mark E.
Winograd, Jonathan M.
Redmond, Robert W.
TI Light-Activated Sealing of Nerve Graft Coaptation Sites Improves Outcome
following Large Gap Peripheral Nerve Injury
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID RAT SCIATIC-NERVE; CROSS-LINKED COLLAGEN; FIBRIN GLUE; FACIAL-NERVE;
HUMAN AMNION; CLINICAL-APPLICATIONS; MECHANICAL-PROPERTIES; AXONAL
REGENERATION; SINGLET OXYGEN; IN-VIVO
AB Background: Nerve repair using photochemically bonded human amnion nerve wraps can result in superior outcomes in comparison with standard suture. When applied to nerve grafts, efficacy has been limited by proteolytic degradation of bonded amnion during extended periods of recovery. Chemical cross-linking of amnion before bonding may improve wrap durability and efficacy.
Methods: Three nerve wraps (amnion, cross-linked amnion, and cross-linked swine intestinal submucosa) and three fixation methods (suture, fibrin glue, and photochemical bonding) were investigated. One hundred ten Lewis rats had 15-mm left sciatic nerve gaps repaired with isografts. Nine groups (n = 10) had isografts secured by one of the aforementioned wrap/fixation combinations. Positive and negative control groups (n = 10) were repaired with graft and suture and no repair, respectively. Outcomes were assessed using sciatic function index, muscle mass retention, and histomorphometry. Statistical analysis was performed using analysis of variance and the post hoc Bonferroni test (p < 0.05).
Results: Cross-linking improved amnion durability. Photochemically bonded cross-linked amnion recovered the greatest sciatic function index, although this was not significant in comparison with graft and suture. Photochemically bonded cross-linked amnion recovered significantly greater muscle mass (67.3 4.4 percent versus 60.0 +/- 5.2 percent; p = 0.02), fiber diameter, axon diameter, and myelin thickness (6.87 +/- 2.23 m versus 5.47 +/- 1.70 m; 4.51 +/- 1.83 m versus 3.50 +/- 1.44 m; and 2.35 +/- 0.64 m versus 1.96 +/- 0.47 m, respectively) in comparison with graft and suture.
Conclusion: Light-activated sealing of cross-linked human amnion results in superior outcomes when compared with conventional suture.
C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
Walter Reed Natl Mil Med Ctr, Plast Surg Serv, Bethesda, MD USA.
Walter Reed Natl Mil Med Ctr, Dept Orthoped, Bethesda, MD USA.
RP Fairbairn, NG (reprint author), Massachusetts Gen Hosp, Dept Plast Surg, 55 Fruit St, Boston, MA 02114 USA.
EM ngf174@hotmail.com
FU Department of Defense [USMRAA W81XWH-12-1-0511]
FX This article was funded by the Department of Defense (USMRAA
W81XWH-12-1-0511). The content of this article does not necessarily
reflect the position or the policy of the U.S. government, and no
official endorsement should be inferred.
NR 53
TC 4
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0032-1052
EI 1529-4242
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD OCT
PY 2015
VL 136
IS 4
BP 739
EP 750
DI 10.1097/PRS.0000000000001617
PG 12
WC Surgery
SC Surgery
GA CS0GA
UT WOS:000361735100001
PM 26397251
ER
PT J
AU Williams, ED
Stebbins, MJ
Cavanagh, PR
Haynor, DR
Chu, BC
Fassbind, MJ
Isvilanonda, V
Ledoux, WR
AF Williams, Evan D.
Stebbins, Michael J.
Cavanagh, Peter R.
Haynor, David R.
Chu, Baocheng
Fassbind, Michael J.
Isvilanonda, Vara
Ledoux, William R.
TI The design and validation of a magnetic resonance imaging-compatible
device for obtaining mechanical properties of plantar soft tissue via
gated acquisition
SO PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF
ENGINEERING IN MEDICINE
LA English
DT Article
DE Heel pad; diabetes; magnetic resonance imaging-compatible; mechanical
properties
ID HEEL-PAD COMPRESSIBILITY; DIABETIC FOOT; THICKNESS; GAIT; MRI
AB Changes in the mechanical properties of the plantar soft tissue in people with diabetes may contribute to the formation of plantar ulcers. Such ulcers have been shown to be in the causal pathway for lower extremity amputation. The hydraulic plantar soft tissue reducer (HyPSTER) was designed to measure in vivo, rate-dependent plantar soft tissue compressive force and three-dimensional deformations to help understand, predict, and prevent ulcer formation. These patient-specific values can then be used in an inverse finite element analysis to determine tissue moduli, and subsequently used in a foot model to show regions of high stress under a wide variety of loading conditions. The HyPSTER uses an actuator to drive a magnetic resonance imaging-compatible hydraulic loading platform. Pressure and actuator position were synchronized with gated magnetic resonance imaging acquisition. Achievable loading rates were slower than those found in normal walking because of a water-hammer effect (pressure wave ringing) in the hydraulic system when the actuator direction was changed rapidly. The subsequent verification tests were, therefore, performed at 0.2Hz. The unloaded displacement accuracy of the system was within 0.31%. Compliance, presumably in the system's plastic components, caused a displacement loss of 5.7mm during a 20-mm actuator test at 1354N. This was accounted for with a target to actual calibration curve. The positional accuracy of the HyPSTER during loaded displacement verification tests from 3 to 9mm against a silicone backstop was 95.9% with a precision of 98.7%. The HyPSTER generated minimal artifact in the magnetic resonance imaging scanner. Careful analysis of the synchronization of the HyPSTER and the magnetic resonance imaging scanner was performed. With some limitations, the HyPSTER provided key functionality in measuring dynamic, patient-specific plantar soft tissue mechanical properties.
C1 [Williams, Evan D.; Stebbins, Michael J.; Fassbind, Michael J.; Isvilanonda, Vara; Ledoux, William R.] VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA.
[Williams, Evan D.; Stebbins, Michael J.; Cavanagh, Peter R.; Isvilanonda, Vara; Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Cavanagh, Peter R.; Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
[Haynor, David R.; Chu, Baocheng] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA.
EM wrledoux@uw.edu
FU United States (U.S.) Department of Veterans Affairs Rehabilitation
Research and Development Service [A6973R]
FX This work was supported by Merit Review Award A6973R from the United
States (U.S.) Department of Veterans Affairs Rehabilitation Research and
Development Service.
NR 24
TC 1
Z9 1
U1 3
U2 10
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0954-4119
EI 2041-3033
J9 P I MECH ENG H
JI Proc. Inst. Mech. Eng. Part H-J. Eng. Med.
PD OCT
PY 2015
VL 229
IS 10
BP 732
EP 742
DI 10.1177/0954411915606150
PG 11
WC Engineering, Biomedical
SC Engineering
GA CS2KH
UT WOS:000361899000005
PM 26405098
ER
PT J
AU Willers, H
Gheorghiu, L
Liu, Q
Efstathiou, JA
Wirth, LJ
Krause, M
von Neubeck, C
AF Willers, Henning
Gheorghiu, Liliana
Liu, Qi
Efstathiou, Jason A.
Wirth, Lori J.
Krause, Mechthild
von Neubeck, Claere
TI DNA Damage Response Assessments in Human Tumor Samples Provide
Functional Biomarkers of Radiosensitivity
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; COLLAPSED
REPLICATION FORKS; ORGANOTYPIC SLICE CULTURES; GAMMA-H2AX FOCI
FORMATION; PROSTATE-CANCER PATIENTS; PARP INHIBITOR ABT-888; EX-VIVO
ASSAY; IN-VIVO; HOMOLOGOUS RECOMBINATION
AB Predictive biomarkers are urgently needed for individualization of radiation therapy and treatment with radiosensitizing anticancer agents. Genomic profiling of human cancers provides us with unprecedented insight into the mutational landscape of genes directly or indirectly involved in the response to radiation-induced DNA damage. However, to what extent this wealth of structural information about the cancer genome produces biomarkers of sensitivity to radiation remains to be seen. Investigators are increasingly studying the subnuclear accumulation (ie, foci) of proteins in the DNA damage response (DDR), such as gamma-H2AX, 53BP1, or RAD51, as a surrogate of treatment sensitivity. Recent findings from preclinical studies have demonstrated the predictive potential of DDR foci by correlating foci with clinically relevant end points such as tumor control probability. Therefore, preclinical investigations of DDR foci responses are increasingly moving into cells and tissues from patients, which is the major focus of this review. The advantage of using DDR foci as functional biomarkers is that they can detect alterations in DNA repair due to various mechanisms. Moreover, they provide a global measurement of DDR network function without needing to know the identities of all the components, many of which remain unknown. Foci assays are thus expected to yield functional insight that may complement or supersede genomic information, thereby giving radiation oncologists unique opportunities to individualize cancer treatments in the near future. Semin Radiat Oncol 25:237-250 (C) 2015 Elsevier Inc. All rights reserved.
C1 [Willers, Henning; Gheorghiu, Liliana; Liu, Qi; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Krause, Mechthild] German Canc Consortium DKTK Dresden, Heidelberg, Germany.
[Krause, Mechthild] German Canc Res Ctr, Heidelberg, Germany.
[Krause, Mechthild] Fac Med, Dept Radiat Oncol, Dresden, Germany.
[Krause, Mechthild; von Neubeck, Claere] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany.
[Krause, Mechthild; von Neubeck, Claere] Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany.
[Krause, Mechthild] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol, Dresden, Germany.
RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM hwillers@mgh.harvard.edu
FU Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer; NCI [P50
CA090578]; American Cancer Society, USA [123420RSG-12-224-01-DMC]; U.S.
Department of Defense, USA [W81XWH-06-1-0309]; Susan G. Komen for the
Cure of Breast Cancer [BCTR0504040]; Federal Share of program income
earned by Massachusetts General Hospital, USA [C06 CA059267]; Proton
Therapy Research and Treatment Center
FX In part supported by Dana-Farber/Harvard Cancer Center SPORE in Lung
Cancer, NCI P50 CA090578 (H.W.), American Cancer Society, USA
123420RSG-12-224-01-DMC (H. W.), U.S. Department of Defense, USA
W81XWH-06-1-0309 (H.W.), Susan G. Komen for the Cure of Breast Cancer
BCTR0504040 (H.W.), Federal Share of program income earned by
Massachusetts General Hospital, USA on C06 CA059267, Proton Therapy
Research and Treatment Center (J.A.E., H.W.). L.J.W. and H.W. wish to
thank Tay Morgan for his support.
NR 129
TC 6
Z9 6
U1 1
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-4296
EI 1532-9461
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD OCT
PY 2015
VL 25
IS 4
BP 237
EP 250
DI 10.1016/j.semradonc.2015.05.007
PG 14
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CS1YM
UT WOS:000361864800003
PM 26384272
ER
PT J
AU Whitley, MJ
Weissleder, R
Kirsch, DG
AF Whitley, Melodi J.
Weissleder, Ralph
Kirsch, David G.
TI Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect
Residual Cancer
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID SOFT-TISSUE SARCOMA; BREAST-CANCER; 5-AMINOLEVULINIC ACID;
OVARIAN-CANCER; REAL-TIME; CYSTEINE CATHEPSINS; RAMAN-SPECTROSCOPY;
FLUORESCENT-PROBE; LOCAL RECURRENCE; RANDOMIZED-TRIAL
AB For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. Moreover, some of these approaches have been translated from the preclinical arena into clinical trials. Here, we review different types of intraoperative molecular imaging systems for cancer. Optical imaging techniques like epi-illumination, fluorescence molecular tomography and optoacoustic imaging can be coupled with exogenous fluorescent imaging probes that accumulate in tumors passively via the enhanced permeability and retention effect or are targeted to tumor tissues based on affinity or enzyme activity. In these approaches, detection of fluorescence in the tumor bed may indicate residual disease. Protease activated probes have generated great interest because of their potential for leading to high tumor to normal contrast. Recently, the first Phase I clinical trial to assess the safety and activation of a protease activated probe was conducted. Spectroscopic methods like radiofrequency spectroscopy and Raman spectroscopy, which are based on energy absorption and scattering, respectively, have also been tested in humans and are able to distinguish between normal and tumors tissues intraoperatively. Most recently, multimodal contrast agents have been developed that target tumors and contain both fluorescent dyes and magnetic resonance imaging contrast agents, allowing for preoperative planning and intraoperative margin assessment with a single contrast agent. Further clinical testing of these various intraoperative imaging approaches may lead to more accurate methods for margin assessment and the intraoperative detection of microscopic residual disease, which could guide further resection and the use of adjuvant radiation therapy. Semin Radiat Oncol 25:313-321 (C) 2015 Elsevier Inc. All rights reserved.
C1 [Whitley, Melodi J.; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA.
RP Kirsch, DG (reprint author), Duke Univ, Med Ctr, Radiat Oncol, Durham, NC 27710 USA.
EM david.kirsch@duke.edu
FU NIGMS NIH HHS [T32 GM007171]
NR 66
TC 3
Z9 3
U1 1
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-4296
EI 1532-9461
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD OCT
PY 2015
VL 25
IS 4
BP 313
EP 321
DI 10.1016/j.semradonc.2015.05.005
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CS1YM
UT WOS:000361864800010
PM 26384279
ER
PT J
AU Wiederhold, NP
Patterson, TF
AF Wiederhold, Nathan P.
Patterson, Thomas F.
TI Emergence of Azole Resistance in Aspergillus
SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Review
DE Aspergillus fumigatus; azole resistance; aspergillosis; voriconazole;
itraconazole; posaconazole; CYP51A
ID INVASIVE PULMONARY ASPERGILLOSIS; ANTIFUNGAL DRUG-RESISTANCE;
AMPHOTERICIN-B; CYP51A GENE; NEOSARTORYA-PSEUDOFISCHERI; ITRACONAZOLE
RESISTANCE; ISAVUCONAZOLE BAL4815; FUMIGATUS; VORICONAZOLE; POSACONAZOLE
AB Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. Some resistant isolates also contain a tandem repeat in the promoter region of this gene that causes increased expression. These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated to cause resistance to azole fungicides used in agriculture, thus raising the concern of environmental spread of resistance. Treatment options are limited in patients with infections caused by azole-resistant isolates and include amphotericin B formulations or combination therapy involving an echinocandin. However, there are few clinical data available to help guide therapy, and infections caused by resistant A. fumigatus isolates have been reported to have high mortality rates.
C1 [Wiederhold, Nathan P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA.
[Wiederhold, Nathan P.; Patterson, Thomas F.] UTHSCSA, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA.
[Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Patterson, TF (reprint author), UTHSCSA, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,MC 7750, San Antonio, TX 78229 USA.
EM patterson@uthscsa.edu
OI Patterson, Thomas /0000-0002-9513-7127; Wiederhold,
Nathan/0000-0002-2225-5122
NR 75
TC 3
Z9 3
U1 3
U2 9
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1069-3424
EI 1098-9048
J9 SEMIN RESP CRIT CARE
JI Semin. Respir. Crit. Care Med.
PD OCT
PY 2015
VL 36
IS 5
BP 673
EP 680
DI 10.1055/s-0035-1562894
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CR8ZL
UT WOS:000361642900005
PM 26398534
ER
PT J
AU Balboni, MJ
AF Balboni, Michael J.
TI Everyday Religion in Hospitals
SO SOCIETY
LA English
DT Article
ID QUALITY-OF-LIFE; ADVANCED CANCER; SPIRITUAL CARE; NEAR-DEATH;
PHYSICIANS; END; ASSOCIATIONS; PROVISION; MEDICINE; NURSES
C1 Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA.
RP Balboni, MJ (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA.
EM michael_balboni@dfci.harvard.edu
NR 24
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0147-2011
EI 1936-4725
J9 SOCIETY
JI Society
PD OCT
PY 2015
VL 52
IS 5
BP 413
EP 417
DI 10.1007/s12115-015-9923-1
PG 5
WC Social Sciences, Interdisciplinary; Sociology
SC Social Sciences - Other Topics; Sociology
GA CS0IR
UT WOS:000361743200003
ER
PT J
AU Pagano, TB
Wojcik, S
Costagliola, A
De Biase, D
Iovino, S
Iovane, V
Russo, V
Papparella, S
Paciello, O
AF Pagano, Teresa B.
Wojcik, Slawomir
Costagliola, Alessandro
De Biase, Davide
Iovino, Salvatore
Iovane, Valentina
Russo, Valeria
Papparella, Serenella
Paciello, Orlando
TI Age related skeletal muscle atrophy and upregulation of autophagy in
dogs
SO VETERINARY JOURNAL
LA English
DT Article
DE Autophagy; Sarcopenia; Muscle atrophy; Ageing; Canine
ID IN-VIVO; SARCOPENIA; DEGRADATION; PATHWAYS; DISEASE; CELLS
AB Sarcopenia, the age related loss of muscle mass and strength, is a multifactorial condition that occurs in a variety of species and represents a major healthcare concern for older adults in human medicine. In veterinary medicine, skeletal muscle atrophy is often observed in dogs as they reach old age, but the process is not well understood. Autophagy is a mechanism for degradation and recycling of cellular constituents and is potentially involved in sarcopenia. The aim of the present study was to evaluate the expression of three markers of autophagy, Beclin 1, LC3 and p62, in muscle wasting of geriatric dogs, to establish whether the levels of autophagy change with increasing age.
Muscle biopsies from 25 geriatric dogs were examined and compared with those from five healthy young dogs. Samples from older dogs, assessed by routine histology, histoenzymatic staining and immunohistochemistry, showed evidence of muscle atrophy, sarcoplasmic vacuolisation and mitochondrial alterations. Furthermore, in 80% of the muscle samples from the older dogs, marked intracytoplasmic staining for Beclin 1 and LC3 was observed, Significantly greater expression of LC3 II and Beclin 1, but lower expression of p62, was found by Western blotting, comparing muscle samples from old vs. young dogs. The results of the study suggest that enhanced autophagy might be one of the factors underlying muscle atrophy in dogs as they age. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Pagano, Teresa B.; Costagliola, Alessandro; De Biase, Davide; Iovane, Valentina; Russo, Valeria; Papparella, Serenella; Paciello, Orlando] Univ Naples Federico II, Lab Comparat Neuromuscular Dis, Dept Vet Med & Anim Prod, I-80137 Naples, Italy.
[Wojcik, Slawomir] Med Univ Gdansk, Dept Anat & Neurobiol, PL-80211 Gdansk, Poland.
[Iovino, Salvatore] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
RP Paciello, O (reprint author), Univ Naples Federico II, Lab Comparat Neuromuscular Dis, Dept Vet Med & Anim Prod, Via Delpino 1, I-80137 Naples, Italy.
EM paciello@unina.it
FU University of Naples Federico II
FX This study was supported, in part, by The University of Naples Federico
II. The authors thank Raffaele Ilsami for his valuable technical
assistance.
NR 30
TC 3
Z9 3
U1 3
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1090-0233
EI 1532-2971
J9 VET J
JI Vet. J.
PD OCT
PY 2015
VL 206
IS 1
BP 54
EP 60
DI 10.1016/j.tvjl.2015.07.005
PG 7
WC Veterinary Sciences
SC Veterinary Sciences
GA CS1ZV
UT WOS:000361868500009
PM 26257260
ER
PT J
AU Pery, E
Sheehy, A
Nebane, NM
Misra, V
Mankowski, MK
Rasmussen, L
White, EL
Ptak, RG
Gabuzda, D
AF Pery, Erez
Sheehy, Ann
Nebane, N. Miranda
Misra, Vikas
Mankowski, Marie K.
Rasmussen, Lynn
White, E. Lucile
Ptak, Roger G.
Gabuzda, Dana
TI Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments
APOBEC3G antiviral activity against human immunodeficiency virus type 1
SO VIROLOGY
LA English
DT Article
DE HIV-1; Vif; APOBEC3G; Antiviral; Redoxal; Pyrimidine synthesis
ID ANTIRETROVIRAL DRUG-RESISTANCE; SMALL-MOLECULE INHIBITION; VIRAL LOAD
STANDARDS; AMINO-ACID-RESIDUES; GROUP M SUBTYPES; HIV-1 INFECTION; VIF
PROTEIN; REVERSE TRANSCRIPTION; CBF-BETA; DIHYDROOROTATE DEHYDROGENASE
AB APOBEC3G (A3G) is a cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA; deamination-independent mechanisms are also implicated. HIV-1 Vif protein counteracts A3G by inducing its proteasomal degradation. Thus, the Vif-A3G axis is a potential therapeutic target. To identify compounds that inhibit Vif:A3G interaction, a 307,520 compound library was tested in a TR-FRET screen. Two identified compounds, redoxal and lomofungin, inhibited HIV-1 replication in peripheral blood mononuclear cells. Lomofungin activity was linked to A3G, but not pursued further due to cytotoxicity. Redoxal displayed A3G-dependent restriction, inhibiting viral replication by stabilizing A3G protein levels and increasing A3G in virions. A3G-independent activity was also detected. Treatment with uridine or orotate, intermediates of pyrimidine synthesis, diminished redoxal-induced stabilization of A3G and antiviral activity. These results identify redoxal as an inhibitor of HIV-1 replication and suggest its ability to inhibit pyrimidine biosynthesis suppresses viral replication by augmenting MG antiviral activity. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pery, Erez; Misra, Vikas; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Pery, Erez] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol Microbiol, Boston, MA 02115 USA.
[Sheehy, Ann] Coll Holy Cross, Dept Biol, Worcester, MA 01610 USA.
[Nebane, N. Miranda; Rasmussen, Lynn; White, E. Lucile] Southern Res Inst High Throughput Screening Ctr, Birmingham, AL 35205 USA.
[Mankowski, Marie K.; Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD 21701 USA.
RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, CLS 1010,450 Brookline Ave, Boston, MA 02215 USA.
EM dana_gabuzda@dfci.harvard.edu
FU National Institutes of Health [AI67032, AI87458]; Division of AIDS
(DAIDS), National Institute of Allergy and Infectious Diseases, National
Institutes of Health [HHSN272200700041C, HHSN272200700042C]; Harvard
Center for AIDS Research Grant [P30 AI060354]; Dana-Farber Cancer
Institute/Harvard Cancer Center Research Grant [P30 CA06516]
FX We thank Dr. Caroline Shamu and staff at the Institute of Chemistry and
Cell Biology Longwood Screening Facility, Harvard Medical School,
Boston, MA, for helpful discussions and advice during performance of the
HIS and Dr. Marintha Heil, Southern Research Institute Department of
Infectious Disease Research and Dr. Sara Burhlage, Dana-Farber Cancer
Institute, for helpful discussions and advice. The complete results of
the HIS can be found at Pubchem under AID 1117320
(https://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=1117320). This
work was supported by the National Institutes of Health Grants AI67032
and AI87458 to D.G. and was also conducted in part by Southern Research
Institute using federal funds from the Division of AIDS (DAIDS),
National Institute of Allergy and Infectious Diseases, National
Institutes of Health under contracts HHSN272200700041C and
HHSN272200700042C entitled "In Vitro Testing Resources for AIDS
Therapeutic Development, PART A: Confirmatory In Vitro Evaluations of
HIV Therapeutics and PART B: Specialized In Vitro Virological Assays for
HIV Therapeutics and Topical Microbicides" under the direction of Dr.
Roger Miller (DHHS, NIH, NIAID, DAIDS, BSP; contract Part B) and Dr.
Steven Turk (DHHS, NIH, NIAID, DAIDS, TRP, DDCSB; contract Part A). Core
facilities received support from the Harvard Center for AIDS Research
Grant (P30 AI060354) and Dana-Farber Cancer Institute/Harvard Cancer
Center Research Grant (P30 CA06516).
NR 87
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD OCT
PY 2015
VL 484
BP 276
EP 287
DI 10.1016/j.virol.2015.06.014
PG 12
WC Virology
SC Virology
GA CR8CG
UT WOS:000361578100030
PM 26141568
ER
PT J
AU Ben Nasr, M
Vergani, A
Avruch, J
Liu, LY
Kefaloyianni, E
D'Addio, F
Tezza, S
Corradi, D
Bassi, R
Valderrama-Vasquez, A
Usuelli, V
Kim, J
Azzi, J
El Essawy, B
Markmann, J
Abdi, R
Fiorina, P
AF Ben Nasr, Moufida
Vergani, Andrea
Avruch, James
Liu, Liye
Kefaloyianni, Eirini
D'Addio, Francesca
Tezza, Sara
Corradi, Domenico
Bassi, Roberto
Valderrama-Vasquez, Alessandro
Usuelli, Vera
Kim, James
Azzi, Jamil
El Essawy, Basset
Markmann, James
Abdi, Reza
Fiorina, Paolo
TI Co-transplantation of autologous MSCs delays islet allograft rejection
and generates a local immunoprivileged site
SO ACTA DIABETOLOGICA
LA English
DT Article
DE Islet transplantation; Mesenchymal stem cells; Immunoprivileged site;
Immunoregulation
ID MESENCHYMAL STEM-CELLS; BONE-MARROW; CARDIOVASCULAR-DISEASE;
DIABETIC-PATIENTS; STROMAL CELLS; NOD MICE; AUTOIMMUNE; SURVIVAL;
FEATURES; THERAPY
AB Aims Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory properties. We tested the ability of MSCs to delay islet allograft rejection.
Methods Mesenchymal stem cells were generated in vitro from C57BL/6 and BALB/c mice bone marrow, and their immunomodulatory properties were tested in vitro. We then tested the effect of a local or systemic administration of heterologous and autologous MSCs on graft survival in a fully allogeneic model of islet transplantation (BALB/c islets into C57BL/6 mice).
Results In vitro, autologous, but not heterologous, MSCs abrogated immune cell proliferation in response to alloantigens and skewed the immune response toward a Th2 profile. A single dose of autologous MSCs co-transplanted under the kidney capsule with allogeneic islets delayed islet rejection, reduced graft infiltration, and induced long-term graft function in 30 % of recipients. Based on ex vivo analysis of recipient splenocytes, the use of autologous MSCs did not appear to have any systemic effect on the immune response toward graft alloantigens. The systemic injection of autologous MSCs or the local injection of heterologous MSCs failed to delay islet graft rejection.
Conclusion Autologous, but not heterologous, MSCs showed multiple immunoregulatory properties in vitro and delayed allograft rejection in vivo when co-transplanted with islets; however, they failed to prevent rejection when injected systemically. Autologous MSCs thus appear to produce a local immunoprivileged site, which promotes graft survival.
C1 [Ben Nasr, Moufida; Vergani, Andrea; D'Addio, Francesca; Tezza, Sara; Bassi, Roberto; Fiorina, Paolo] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Nephrol, Boston, MA 02138 USA.
[Ben Nasr, Moufida; Vergani, Andrea; D'Addio, Francesca; Valderrama-Vasquez, Alessandro; Usuelli, Vera; Fiorina, Paolo] Univ Milan, Osped San Raffaele, Transplant Med, I-20127 Milan, Italy.
[Avruch, James; Liu, Liye; Kim, James; Markmann, James] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit,Dept Surg, Boston, MA 02114 USA.
[Kefaloyianni, Eirini] Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Inst Med,HIM510,Div Renal, Boston, MA 02115 USA.
[Corradi, Domenico] Univ Parma, Pathol & Lab Med, I-43100 Parma, Italy.
[Azzi, Jamil; Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Div Nephrol, Boston, MA USA.
[El Essawy, Basset] Al Azhar Univ, Dept Med, Cairo, Egypt.
RP Fiorina, P (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Nephrol, Enders Bldg 5th Floor Room EN511,300 Longwood Ave, Boston, MA 02138 USA.
EM paolo.fiorina@childrens.harvard.edu
RI Corradi, Domenico/O-1666-2015; D'Addio, Francesca/F-3417-2017
OI Corradi, Domenico/0000-0002-8836-4778; D'Addio,
Francesca/0000-0002-0345-0694
FU JDRF Career Development Award; ASN Career Development Award; ADA
Mentor-based Fellowship Grant; Translational Research Program (TRP) from
Boston Children's Hospital; Harvard Stem Cell Institute Grant ("Diabetes
Program'') [DP-0123-12-00]; Italian Ministry of Health [RF-
2010-2303119, RF- FSR-2008-1213704]; AMD-SID Pasquale di Coste
Scolarship; Italian Scientists and Scholars of North America Foundation
(ISSNAF)-Fondazione Marche Fellowship; AST Genentech Clinical Science
Fellowship Grant
FX Paolo Fiorina is the recipient of a JDRF Career Development Award, an
ASN Career Development Award, and an ADA Mentor-based Fellowship Grant.
P.F. is also supported by a Translational Research Program (TRP) Grant
from Boston Children's Hospital; Harvard Stem Cell Institute Grant
("Diabetes Program'' DP-0123-12-00); Italian Ministry of Health Grant
RF- 2010-2303119. P. F. and Andrea Vergani are supported of an Italian
Ministry of Health Grant: ("Staminali'' RF- FSR-2008-1213704). A. V. is
supported by the "AMD-SID Pasquale di Coste Scolarship''. Francesca
D'Addio is a recipient of Italian Scientists and Scholars of North
America Foundation (ISSNAF)-Fondazione Marche Fellowship. Roberto Bassi
is supported by an ADA Mentor-based Fellowship Grant to P. F and by an
AST Genentech Clinical Science Fellowship Grant. A. V. conducted this
study as partial fulfillment of his PhD in Molecular Medicine, San
Raffaele University, Milan, Italy.
NR 52
TC 13
Z9 14
U1 0
U2 2
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 0940-5429
EI 1432-5233
J9 ACTA DIABETOL
JI Acta Diabetol.
PD OCT
PY 2015
VL 52
IS 5
BP 917
EP 927
DI 10.1007/s00592-015-0735-y
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CR4YR
UT WOS:000361346500012
PM 25808641
ER
PT J
AU Burton, BK
Berger, KI
Lewis, GD
Tarnopolsky, M
Treadwell, M
Mitchell, JJ
Muschol, N
Jones, SA
Sutton, VR
Pastores, GM
Lau, H
Sparkes, R
Genter, F
Shaywitz, AJ
Harmatz, P
AF Burton, Barbara K.
Berger, Kenneth I.
Lewis, Gregory D.
Tarnopolsky, Mark
Treadwell, Marsha
Mitchell, John J.
Muschol, Nicole
Jones, Simon A.
Sutton, V. Reid
Pastores, Gregory M.
Lau, Heather
Sparkes, Rebecca
Genter, Fred
Shaywitz, Adam J.
Harmatz, Paul
TI Safety and physiological effects of two different doses of elosulfase
alfa in patients with morquio a syndrome: A randomized, double-blind,
pilot study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE mucopolysaccharidosis IV; cardiopulmonary exercise test; safety;
respiratory function tests; muscle strength; physical endurance; GALNS
protein; human [supplementary concept]; enzyme replacement therapy
ID ENZYME REPLACEMENT THERAPY; MUCOPOLYSACCHARIDOSIS TYPE IVA; 6-MINUTE
WALK TEST; OPEN-LABEL; BMN 110; CHILDREN; DISEASE; ADOLESCENTS;
GUIDELINES; EFFICACY
AB The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged 7 years and able to walk 200m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0mg/kg/week and 10 to 4.0mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. (c) 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.
C1 [Burton, Barbara K.] Ann & Robert H Lurie Childrens Hosp, Chicago, IL USA.
[Burton, Barbara K.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Berger, Kenneth I.; Pastores, Gregory M.; Lau, Heather] NYU, Sch Med, New York, NY USA.
[Lewis, Gregory D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tarnopolsky, Mark] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Treadwell, Marsha; Harmatz, Paul] UCSF Benioff Childrens Hosp Oakland, Oakland, CA 94609 USA.
[Mitchell, John J.] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada.
[Muschol, Nicole] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Jones, Simon A.] Univ Manchester, St Marys Hosp, Willink Unit, CMFT,MAHSC, Manchester M13 0JH, Lancs, England.
[Sutton, V. Reid] Texas Childrens Hosp, Houston, TX 77030 USA.
[Sutton, V. Reid] Baylor Coll Med, Houston, TX 77030 USA.
[Pastores, Gregory M.] Mater Misericordiae Univ Hosp, Dublin, Ireland.
[Sparkes, Rebecca] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada.
[Genter, Fred; Shaywitz, Adam J.] BioMarin Pharmaceut Inc, Novato, CA USA.
RP Harmatz, P (reprint author), UCSF Benioff Childrens Hosp Oakland, 747 52nd St, Oakland, CA 94609 USA.
EM pharmatz@mail.cho.org
OI Berger, Kenneth/0000-0003-4879-6071
FU BioMarin Pharmaceutical Inc.; BioMarin; National Center for Advancing
Translational Sciences, National Institutes of Health, through UCSF-CTSI
[UL1 TR000004]
FX We acknowledge the participation of study patients and their families
and the expert assistance of all study site coordinators and personnel.
The authors are also grateful to Ismar Healthcare NV, funded by BioMarin
Pharmaceutical Inc., for support in the process of manuscript
development. The authors also acknowledge the Manchester NIHR/WTCRF.
This study was sponsored by BioMarin and supported, in part, by the
National Center for Advancing Translational Sciences, National
Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004 (Dr.
Harmatz). Its contents are solely the responsibility of the authors and
do not necessarily represent the official views of the NIH.
NR 22
TC 5
Z9 5
U1 0
U2 4
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 OCT
PY 2015
VL 167
IS 10
BP 2272
EP 2281
DI 10.1002/ajmg.a.37172
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CR2TS
UT WOS:000361184100008
PM 26069231
ER
PT J
AU Turalba, A
Payal, AR
Gonzalez-Gonzalez, LA
Cakiner-Egilmez, T
Chomsky, AS
Vollman, DE
Baze, EF
Lawrence, M
Daly, MK
AF Turalba, Angela
Payal, Abhishek R.
Gonzalez-Gonzalez, Luis A.
Cakiner-Egilmez, Tulay
Chomsky, Amy S.
Vollman, David E.
Baze, Elizabeth F.
Lawrence, Mary
Daly, Mary K.
TI Cataract Surgery Outcomes in Glaucomatous Eyes: Results From the
Veterans Affairs Ophthalmic Surgery Outcomes Data Project
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; OPEN-ANGLE GLAUCOMA; PERFORMED PHACOEMULSIFICATION
SURGERY; RISK-FACTORS; INTRAOCULAR-PRESSURE; PSEUDOEXFOLIATION SYNDROME;
AQUEOUS-HUMOR; COMPLICATIONS; EXTRACTION; TRABECULECTOMY
AB PURPOSE: To compare visual acuity outcomes, vision-related quality of life, and complications related to cataract surgery in eyes with and without glaucoma.
DESIGN: Retrospective cohort study.
METHODS: Cataract surgery outcomes in cases with and without glaucoma from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project were compared.
RESULTS: We identified 608 glaucoma cases and 4306 controls undergoing planned cataract surgery alone. After adjusting for age, pseudoexfoliation, small pupil, prior ocular surgery, and anterior chamber depth, we found that glaucoma cases were more likely to have posterior capsular tear with vitrectomy (odds ratio [OR] 1.8, P =.03) and sulcus intraocular lens placement (OR 1.65, P =.03) during cataract surgery. Glaucoma cases were more likely to have postoperative inflammation (OR 1.73, P <.0001), prolonged elevated intraocular pressure (OR 2.96, P =.0003), and additional surgery within 30 days (OR 1.92, P =.03). Mean best-corrected visual acuity (BCVA) and Visual Function Questionnaire (VFQ) scores significantly improved after cataract surgery in both groups (P <.0001), but there were larger improvements in BCVA (P =.01) and VFQ composite scores (P <.0001) in the nonglaucoma vs the glaucoma group. A total of 3621 nonglaucoma cases (94.1%) had postoperative BCVA 20/40 or better, compared to 466 glaucoma cases (89.6%) (P. =.0003).
CONCLUSIONS: Eyes with glaucoma are at increased risk for complications and have more modest visual outcomes after cataract surgery compared to eyes without glaucoma. Despite this, glaucoma patients still experience significant improvement in vision-related outcomes after cataract extraction. Further study is needed to explore potential factors that influence cataract surgery outcomes in glaucomatous eyes. Published by Elsevier Inc.
C1 [Turalba, Angela; Payal, Abhishek R.; Gonzalez-Gonzalez, Luis A.; Cakiner-Egilmez, Tulay; Daly, Mary K.] VA Boston Healthcare Syst, Dept Ophthalmol, Jamaica Plain, MA USA.
[Daly, Mary K.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02130 USA.
[Turalba, Angela; Payal, Abhishek R.; Daly, Mary K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02130 USA.
[Chomsky, Amy S.] Vet Affairs Tennessee Valley Healthcare Syst Ctr, Nashville, TN USA.
[Chomsky, Amy S.] Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Nashville, TN USA.
[Vollman, David E.] St Louis Vet Affairs Healthcare Syst, St Louis, MO USA.
[Vollman, David E.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Baze, Elizabeth F.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Baze, Elizabeth F.] Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA.
[Lawrence, Mary] Vet Affairs Vis Ctr Excellence, Dept Def, Bethesda, MD USA.
RP Daly, MK (reprint author), VA Boston Healthcare Syst, Ophthalmol, 150 South Huntington Ave,Suite 8C-29, Boston, MA 02130 USA.
EM mary.daly2@va.gov
OI Payal, Abhishek/0000-0002-4484-8279
NR 38
TC 3
Z9 3
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2015
VL 160
IS 4
BP 693
EP 701
DI 10.1016/j.ajo.2015.07.020
PG 9
WC Ophthalmology
SC Ophthalmology
GA CR7BR
UT WOS:000361503400010
PM 26210863
ER
PT J
AU Kuehlewein, L
Bansal, M
Lenis, TL
Iafe, NA
Sadda, SR
Bonin, MA
De Carlo, TE
Waheed, NK
Duker, JS
Sarraf, D
AF Kuehlewein, Laura
Bansal, Mayank
Lenis, Tamara L.
Iafe, Nicholas A.
Sadda, Srinivas R.
Bonin Filho, Marco A.
De Carlo, Talisa E.
Waheed, Nadia K.
Duker, Jay S.
Sarraf, David
TI Optical Coherence Tomography Angiography of Type 1 Neovascularization in
Age-Related Macular Degeneration
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CHOROIDAL NEOVASCULARIZATION; FLUORESCEIN ANGIOGRAPHY; MOTION
CORRECTION; EYES; AMD; CLASSIFICATION
AB PURPOSE: To analyze type 1 neovascular membranes in age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography, to correlate morphologic characteristics with imaging and clinical criteria, and to analyze structural features of type 1 neovascularization sequentially after anti-vascular endothelial growth factor (VEGF) therapy.
DESIGN: Prospective interventional Case series.
METHODS: Macular OCT angiography images were acquired using the RTVue XR Avanti with AngioVue. Distinct morphologic patterns and quantifiable features of the neovascular membranes were studied on en face projection images at baseline and follow-up.
RESULTS: Thirty-three eyes of 25 patients were included. In 75% of the eyes, a highly organized vascular complex could be identified. A large main central vessel trunk/feeder vessel could be seen in 72% of these eyes, with vessels radiating in a branching pattern either in all directions from the center of the lesion ("medusa" pattern), or from one side of the lesion ("seafan" pattern). Of the 18 eyes with follow-up OCT angiography, the lesion area and vessel density remained unchanged, even after anti-vascular endothelial growth factor (VEGF) therapy, indicating a more mature longstanding neovascular complex resistant to anti-VEGF therapy.
CONCLUSIONS: OCT angiography provides a unique opportunity to study the morphology of occult type 1 neovascular membranes in AMP and allows precise structural and vascular assessment noninvasively. We identified a large mature neovascular complex in approximately 75% of eyes, typically consisting of a feeder vessel and large branching vessels resistant to anti-VEGF therapy. OCT angiography may better guide evaluation and treatment of neovascular AMD, and may contribute to the development of improved therapies. (C) 2015 by Elsevier Inc. All rights reserved.
C1 [Kuehlewein, Laura; Sadda, Srinivas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Kuehlewein, Laura; Bansal, Mayank; Lenis, Tamara L.; Iafe, Nicholas A.; Sadda, Srinivas R.; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
[Bansal, Mayank; Lenis, Tamara L.; Iafe, Nicholas A.; Sarraf, David] Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
[Bonin Filho, Marco A.; De Carlo, Talisa E.; Waheed, Nadia K.; Duker, Jay S.] Tufts Univ, New England Eye Ctr, Boston, MA 02111 USA.
[Bonin Filho, Marco A.; De Carlo, Talisa E.; Waheed, Nadia K.; Duker, Jay S.] Tufts Univ, Tufts Med Ctr, Boston, MA 02111 USA.
[Bonin Filho, Marco A.] Minist Educ Brazil, CAPES Fdn, Brasilia, DF, Brazil.
[De Carlo, Talisa E.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[De Carlo, Talisa E.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
[Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
FU Allergan, Irvine, California, USA; Carl Zeiss Meditec, Dublin,
California, USA; Genentech, South San Francisco, California, USA; Optos,
Marlborough, Massachusetts, USA; Carl Zeiss Meditec; Massachusetts Lions
Club, South Attleboro, Massachusetts, USA; OptoVue, Fremont, California,
USA; Research to Prevent Blindness, Columbia, Maryland, USA; Genentech;
OptoVue; Regeneron, Tarrytown, New York, USA
FX SriniVas R. Sadda: Research support, Allergan, Irvine, California, USA;
Carl Zeiss Meditec, Dublin, California, USA; Genentech, South San
Francisco, California, USA; and Optos, Marlborough, Massachusetts, USA;
Nadia K. Waheed: Research support, Carl Zeiss Meditec; Jay S. Duker:
Research support, Carl Zeiss Meditec; Grant, Massachusetts Lions Club,
South Attleboro, Massachusetts, USA; Research support, OptoVue, Fremont,
California, USA; Grant, Research to Prevent Blindness, Columbia,
Maryland, USA; David Sarraf: Research grant, Genentech; OptoVue; and
Regeneron, Tarrytown, New York, USA. All authors attest that they meet
the current ICIvIJE requirements to qualify as authors.
NR 27
TC 57
Z9 60
U1 3
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2015
VL 160
IS 4
BP 739
EP 748
DI 10.1016/j.ajo.2015.06.030
PG 10
WC Ophthalmology
SC Ophthalmology
GA CR7BR
UT WOS:000361503400016
PM 26164826
ER
PT J
AU Leung, LSB
Neal, JW
Wakelee, HA
Sequist, LV
Marmor, MF
AF Leung, Loh-Shan B.
Neal, Joel W.
Wakelee, Heather A.
Sequist, Lecia V.
Marmor, Michael F.
TI Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given
for Cancer Therapy
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID ADVANCED SOLID TUMORS; PHASE-I TRIAL; RHEUMATOID-ARTHRITIS; RETINOPATHY;
TEMOZOLOMIDE; INHIBITION; AUTOPHAGY; MELANOMA
AB PURPOSE: To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non small cell lung cancer.
DESIGN: Retrospective observational case series.
METHODS: Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non small cell lung cancer. The US Food & Drug Administration recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG).
RESULTS: Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss.
CONCLUSIONS: These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.
C1 [Leung, Loh-Shan B.; Marmor, Michael F.] Stanford Univ, Byers Eye Inst, Dept Ophthalmol, Sch Med, Palo Alto, CA 94303 USA.
[Neal, Joel W.; Wakelee, Heather A.] Stanford Univ, Stanford Canc Inst, Dept Med, Div Oncol, Palo Alto, CA 94303 USA.
[Sequist, Lecia V.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA.
[Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA.
RP Leung, LSB (reprint author), Stanford Univ, Byers Eye Inst, Dept Ophthalmol, 2405 Watson Ct, Palo Alto, CA 94303 USA.
EM lbleung@stanford.edu
FU Genentech/Roche (South San Francisco, California)
FX Genentech/Roche (South San Francisco, California) provided funding for
the trial and for ophthalmic screening examinations. All authors attest
that they meet the current ICMJE requirements to qualify as authors.
NR 12
TC 6
Z9 6
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2015
VL 160
IS 4
BP 799
EP 805
DI 10.1016/j.ajo.2015.07.012
PG 7
WC Ophthalmology
SC Ophthalmology
GA CR7BR
UT WOS:000361503400022
PM 26189086
ER
PT J
AU Gopalan, A
Lorincz, IS
Wirtalla, C
Marcus, SC
Long, JA
AF Gopalan, Anjali
Lorincz, Ilona S.
Wirtalla, Christopher
Marcus, Steven C.
Long, Judith A.
TI Awareness of Prediabetes and Engagement in Diabetes Risk-Reducing
Behaviors
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; INCIDENT CARDIOVASCULAR EVENTS; IMPAIRED
GLUCOSE-TOLERANCE; PREVENTION PROGRAM; WEIGHT-LOSS; REDUCTION;
COMMUNITY; EXERCISE; MELLITUS; DIET
AB Introduction: Studies have demonstrated the benefit of weight loss and physical activity for diabetes prevention among those with prediabetes. Despite this evidence, only about half of people with prediabetes report engaging in these behaviors. One presumed barrier is low patient awareness of prediabetes. The purpose of this study is to examine the impact of prediabetes awareness on the odds of engagement in diabetes risk-reduction behaviors.
Methods: A pooled cross-sectional analysis of adults from two cycles (2007-2008, 2009-2010) of the National Health and Nutrition Examination Survey was conducted. Those with prediabetes were identified by excluding people with self-reported diabetes and then screening for hemoglobin A1c values between 5.7% and 6.4%. This group was then divided based on self-reported prediabetes. Multivariate logistic regression was used to estimate the effect of prediabetes awareness on the odds of engagement in physical activity, weight management, and the combination of physical activity and weight management.
Results: Of those meeting the defined criteria for prediabetes (n=2,694), only 11.8% (n=288) were aware of their status. Prediabetes-aware individuals had higher odds of engagement in the combination of moderate physical activity plus BMI-appropriate weight management (AOR=1.5, 95% CI=1.1, 2.0), and the combination of at least 150 minutes/week of moderate activity and 7% weight loss in the past year (AOR=2.4, 95% CI=1.1, 5.6).
Conclusions: Prediabetes-aware adults have increased odds of engagement in physical activity and weight management. Increasing patients' awareness of prediabetes could result in increased performance of exercise and weight management behaviors and, most importantly, decreased risk of future diabetes. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Gopalan, Anjali; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Gopalan, Anjali] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA.
[Lorincz, Ilona S.] Univ Penn, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Long, Judith A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Wirtalla, Christopher] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Marcus, Steven C.; Long, Judith A.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA.
RP Gopalan, A (reprint author), Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM agopalan@upenn.edu
NR 23
TC 6
Z9 6
U1 3
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD OCT
PY 2015
VL 49
IS 4
BP 512
EP 519
DI 10.1016/j.amepre.2015.03.007
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CR5YV
UT WOS:000361421200003
PM 26091928
ER
PT J
AU Barry, MJ
Wexler, RM
Brackett, CD
Sepucha, KR
Simmons, LH
Gerstein, BS
Stringfellow, VL
Fowler, FJ
AF Barry, Michael J.
Wexler, Richard M.
Brackett, Charles D.
Sepucha, Karen R.
Simmons, Leigh H.
Gerstein, Bethany S.
Stringfellow, Vickie L.
Fowler, Floyd J., Jr.
TI Responses to a Decision Aid on Prostate Cancer Screening in Primary Care
Practices
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; RECOMMENDATION; PHYSICIANS; STATEMENT;
GUIDELINE; MORTALITY
AB Introduction: Prostate-specific antigen (PSA) testing remains controversial, with most guidelines recommending shared decision making. This study describes men's PSA screening preferences before and after viewing a decision aid and relates these preferences to subsequent clinician visit content.
Methods: Men were recruited from two health systems in 2009-2013. Participants answered a questionnaire before and after decision aid viewing addressing PSA screening preferences and five basic knowledge questions. At one health system, participants also answered a survey after a subsequent clinician visit. Data were analyzed in 2014.
Results: One thousand forty-one predominantly white, well-educated men responded to the pre- and post-viewing questionnaire (25% and 29% response rates at the two sites). After viewing, the proportion of patients leaning away from PSA screening increased significantly (p < 0.001), with 386 (38%) leaning toward PSA screening versus 436 (43%) before viewing; 174 (17%) unsure versus 319 (32%) before; and 448 (44%) leaning away versus 253 (25%) before. Higher knowledge scores were associated with being more likely to lean against screening and less likely to be unsure (p < 0.001). Among 278 men who also completed a questionnaire after a subsequent clinician visit, participants who planned to discuss PSA screening with their clinicians were significantly more likely to report such discussions than participants who did not (148/217 [68%] vs 16/46 [35%], respectively [p < 0.001]).
Conclusions: A decision aid reduces men's interest in PSA screening, particularly among the initially unsure. Men who plan to discuss PSA screening with their clinician after a decision aid are more likely to do so. (C) 2015 American Journal of Preventive Medicine
C1 [Barry, Michael J.; Wexler, Richard M.; Gerstein, Bethany S.; Stringfellow, Vickie L.; Fowler, Floyd J., Jr.] Informed Med Decis Fdn, Boston, MA 02114 USA.
[Sepucha, Karen R.; Simmons, Leigh H.] Massachusetts Gen Hosp, Decis Sci Unit, Div Gen Med, Boston, MA 02114 USA.
[Brackett, Charles D.] Dartmouth Hitchcock Med Ctr, Dartmouth Inst, Hanover, NH USA.
RP Barry, MJ (reprint author), Informed Med Decis Fdn, 40 Court St,Suite 300, Boston, MA 02114 USA.
EM mbarry@imdfoundation.org
FU Informed Medical Decisions Foundation, Healthwise; Informed Medical
Decisions Foundation
FX MJB, RW, BG, VS, and FJF receive salary support from the Informed
Medical Decisions Foundation, which is now a part of Healthwise, a
not-for-profit foundation that develops and distributes patient
education and decision support materials. The Foundation co-produced the
prostate-specific antigen decision aid used in this study with Health
Dialog, and had a royalty relationship with Health Dialog that ended
December 31, 2013. MJB, CDB, and KS have received grant support from the
Informed Medical Decisions Foundation.
NR 13
TC 4
Z9 4
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD OCT
PY 2015
VL 49
IS 4
BP 520
EP 525
DI 10.1016/j.amepre.2015.03.002
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CR5YV
UT WOS:000361421200004
PM 25960395
ER
PT J
AU Katon, JG
Lehavot, K
Simpson, TL
Williams, EC
Barnett, SB
Grossbard, JR
Schure, MB
Gray, KE
Reiber, GE
AF Katon, Jodie G.
Lehavot, Keren
Simpson, Tracy L.
Williams, Emily C.
Barnett, Sarah Beth
Grossbard, Joel R.
Schure, Mark B.
Gray, Kristen E.
Reiber, Gayle E.
TI Adverse Childhood Experiences, Military Service, and Adult Health
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA EXPOSURE; MENTAL-HEALTH; NATIONAL
SAMPLE; PHYSICAL HEALTH; WOMEN VETERANS; SEXUAL-ABUSE; LIFE; CARE;
MALTREATMENT
AB Introduction: Prevalence of adverse childhood experiences (ACE) and associations with adult health may vary by gender and military service. This study compares the gender-specific prevalence of ACE by military service and determines the associations of ACE with adult health risk factors and health-related quality of life (HRQOL).
Methods: This 2014 analysis used data from the 2011 and 2012 CDC Behavioral Risk Factor Surveillance System. Total ACE was operationalized as the number of reported ACE. Associations of total ACE with adult health risk factors were estimated using general linear models; associations with HRQOL were estimated using negative binomial regression. All analyses adjusted for age and race/ethnicity.
Results: Those with military service had more total ACE than civilians. Higher ACE was associated with poorer HRQOL among women (physical health, military service, relative risk [RR]=1.20, 95% CI=1.09, 1.33; civilians, RR=1.18, 95% CI=1.17, 1.20; mental health, military service, RR=1.21, 95% CI=1.12, 1.32; civilians, RR=1.25, 95% CI=1.23, 1.26). Among men, these associations were somewhat attenuated in those with military service relative to civilians (physical health, military service, RR=1.13, 95% CI=1.09, 1.18; civilians, RR=1.20, 95% CI=1.17, 1.24; mental health, military service, RR=1.21, 95% CI=1.16, 1.27; civilians, RR=1.30, 95% CI=1.27, 1.34).
Conclusions: Relative to civilians, men and women with military service report more ACE, but associations of ACE with adult HRQOL are weaker among men with military service relative to civilians. There is a need to implement and disseminate evidence-based programs to prevent ACE and for research on the long-term health consequences of ACE in military populations. Published by Elsevier Inc.
C1 [Katon, Jodie G.; Williams, Emily C.; Grossbard, Joel R.; Schure, Mark B.; Gray, Kristen E.; Reiber, Gayle E.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Lehavot, Keren; Simpson, Tracy L.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Simpson, Tracy L.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA.
[Katon, Jodie G.; Williams, Emily C.; Barnett, Sarah Beth; Schure, Mark B.; Gray, Kristen E.; Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Katon, Jodie G.] Dept Vet Affairs, Off Womens Hlth Serv, Vet Affairs Off Patient Care Serv, Washington, DC USA.
RP Katon, JG (reprint author), 1660 South Columbian Way S-152, Seattle, WA 98108 USA.
EM jodie.katon@va.gov
FU Denver-Seattle Veterans Affairs (VA) Health Services Research and
Development (HSR&D) Center of Innovation; VA Office Women's Health
Services; VA Career Development Award from CSRD [CX000867]; VA Career
Development Award from HSRD [CDA 12-276]; National Institute of Mental
Health [R25 MH080916-01A2]; VA HSR&D, Quality Enhancement Research
Initiative; Office of Academic Affiliations' Associated Health
Postdoctoral Fellowships [TPP 61-026, TPP 61-028]; VA HSR&D Senior
Career Scientist Award [RCS 98-353]
FX This work was supported by the Denver-Seattle Veterans Affairs (VA)
Health Services Research and Development (HSR&D) Center of Innovation
and the VA Office Women's Health Services. The authors declare no
conflicts of interest. Drs. Lehavot and Williams are supported by VA
Career Development Awards from CSR&D (CX000867) and HSR&D (CDA 12-276),
respectively. Dr. Williams is also an investigator with the
Implementation Research Institute (IRI) at the George Warren Brown
School of Social Work at Washington University. IRI is supported through
an award from the National Institute of Mental Health (R25
MH080916-01A2) and the VA HSR&D, Quality Enhancement Research
Initiative. Drs. Gray and Schure are supported by the Office of Academic
Affiliations' Associated Health Postdoctoral Fellowships (TPP 61-026 and
TPP 61-028, respectively), and Dr. Reiber is supported by a VA HSR&D
Senior Career Scientist Award (RCS 98-353). The views expressed in this
article are those of the authors and do not necessarily reflect the
position or policy of the VA.
NR 48
TC 5
Z9 5
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD OCT
PY 2015
VL 49
IS 4
BP 573
EP 582
DI 10.1016/j.amepre.2015.03.020
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CR5YV
UT WOS:000361421200010
PM 26091925
ER
PT J
AU Liao, GS
Chou, YC
Golshan, M
Hsu, HM
Hong, ZJ
Yu, JC
Zhu, JH
AF Liao, Guo-Shiou
Chou, Yu-Ching
Golshan, Mehra
Hsu, Huan-Ming
Hong, Zhi-Jie
Yu, Jyh-Cherng
Zhu, Ji-Hong
TI Prognostic value of the lymph node ratio in breast cancer subtypes
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Lymph node ratio; Traditional lymph node-positive stratification; Breast
cancer subtypes; Overall survival
ID MOLECULAR SUBTYPES; CLINICOPATHOLOGICAL FEATURES; SURVIVAL;
IMMUNOHISTOCHEMISTRY; INVOLVEMENT; BIOMARKERS; PREDICTS; HORMONE
AB BACKGROUND: Several studies indicate that lymph node (LN) ratio (LNR) is more predictive than the traditional LN-positive stratification (pNs). We assessed whether LNR can provide additional prognostic information on node-positive breast cancer patients, particularly with breast cancer subtypes (BCS).
METHODS: We retrospectively reviewed the medical records of 2,049 patients with primary breast cancer treated between January 2006 and December 2011 and identified 511 subjects with positive axillary LN. Clinicopathological findings, types of treatment, and the 5-year overall survival (OS) were included.
RESULTS: The results of multivariate analysis of the cohort showed that the correlations of pNs and LNR in regard to OS were P < .001 and P < .001, respectively, with adjustment for tumor characteristics and treatment factors. Moreover, our data revealed that LNR was more predictive in luminal A, luminal B, and luminal human epidermal growth factor receptor 2 in a comparison of pNs and LNR with regard to OS among BCS.
CONCLUSION: LNR and pNs are important prognostic factors with regard to OS for patients with node-positive breast cancer, but LNR has a more correlated value in BCS. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Liao, Guo-Shiou; Hsu, Huan-Ming; Hong, Zhi-Jie; Yu, Jyh-Cherng; Zhu, Ji-Hong] Triserv Gen Hosp, Dept Surg, Div Gen Surg, Taipei, Taiwan.
[Chou, Yu-Ching] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan.
[Golshan, Mehra] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Yu, JC (reprint author), Triserv Gen Hosp, Dept Surg, Div Gen Surg, Taipei, Taiwan.
EM doc20106@ndmctsgh.edu.tw
NR 29
TC 7
Z9 7
U1 0
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
EI 1879-1883
J9 AM J SURG
JI Am. J. Surg.
PD OCT
PY 2015
VL 210
IS 4
BP 749
EP 754
DI 10.1016/j.amjsurg.2014.12.054
PG 6
WC Surgery
SC Surgery
GA CR7AJ
UT WOS:000361499400015
PM 26130268
ER
PT J
AU Driver, JA
Zhou, XZ
Lu, KP
AF Driver, Jane A.
Zhou, Xiao Zhen
Lu, Kun Ping
TI Pin1 dysregulation helps to explain the inverse association between
cancer and Alzheimer's disease
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Pin1; Phosphorylation signaling; Cancer; Alzheimer's disease
ID PROLYL-ISOMERASE PIN1; AMYLOID PRECURSOR PROTEIN; PROLINE-DIRECTED
PHOSPHORYLATION; TANGLE MOUSE MODEL; TAU-PROTEIN; CELL-CYCLE;
NEUROFIBRILLARY TANGLES; REGULATORY MECHANISM; BREAST-CANCER; DNA-DAMAGE
AB Background: Pin1 is an intracellular signaling molecule which plays a critical but opposite role in the pathogenesis of Alzheimer's disease (AD) and many human cancers.
Scope of review: We review the structure and function of the Pin1 enzyme, the diverse roles it plays in cycling cells and neurons, the epidemiologic evidence for the inverse association between cancer and AD, and the potential therapeutic implications of Pin1-based therapies.
Major conclusions: Pin1 is a unique enzyme that has effects on the function of target proteins by "twisting" them into different shapes. Cycling cells use Pin1 to help coordinate cell division. It is over-expressed and/or activated by multiple mechanisms in many common human cancers, and acts on multiple signal pathways to promote tumorigenesis. Inhibition of Pin1 in animal models has profound anti-tumor effects. In contrast, Pin1 is down-regulated or inactivated by multiple mechanisms in AD brains. The absence of Pin1 impairs tau function and amyloid precursor protein processing, leading to tangle-and amyloid-related pathologies and neurodegeneration in an age-dependent manner, resembling human AD. We have developed cis and trans conformation-specific antibodies to provide the first direct evidence that tau exists in distinct cis and trans conformations and that Pin1 accelerates its cis to trans conversion, thereby protecting against tangle formation in AD.
General significance: Available studies on Pin1 suggest that cancer and AD may share biological pathways that are deregulated in different directions. Pin1 biology opens exciting preventive and therapeutic horizons for both cancer and neurodegeneration. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Driver, Jane A.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02132 USA.
[Driver, Jane A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA.
[Zhou, Xiao Zhen; Lu, Kun Ping] Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Canc Res Inst, Boston, MA USA.
[Zhou, Xiao Zhen; Lu, Kun Ping] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Driver, JA (reprint author), VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02132 USA.
EM jdriver@partners.org; xzhou@bidmc.harvard.edu; Idu@bidmc.harvard.edu
FU CSRD VA [I01 CX000934]; NIA NIH HHS [R01 AG039405, R01 AG046319, R01
AG022082, R01 AG017870]
NR 106
TC 12
Z9 13
U1 3
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD OCT
PY 2015
VL 1850
IS 10
SI SI
BP 2069
EP 2076
DI 10.1016/j.bbagen.2014.12.025
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CR3WL
UT WOS:000361263700012
PM 25583562
ER
PT J
AU Fay, AP
Bellmunt, J
AF Fay, Andre P.
Bellmunt, Joaquim
TI Is angiogenesis still an attractive target in metastatic
castration-resistant prostate cancer?
SO BJU INTERNATIONAL
LA English
DT Editorial Material
ID BEVACIZUMAB
C1 [Fay, Andre P.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Fay, Andre P.] Pontificia Univ Catolica Rio Grande do Sul, Fac Med, Porto Alegre, RS, Brazil.
[Bellmunt, Joaquim] IMIM, Univ Hosp del Mar, Barcelona, Spain.
RP Fay, AP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
NR 6
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD OCT
PY 2015
VL 116
IS 4
BP 500
EP 501
DI 10.1111/bju.13070
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA CR3GA
UT WOS:000361217900005
PM 26350576
ER
PT J
AU Phitayakorn, R
Lachman, N
AF Phitayakorn, Roy
Lachman, Nirusha
TI Getting back together after a break-up: Relationship advice for
anatomists and surgeons
SO CLINICAL ANATOMY
LA English
DT Article
DE surgery education; ACGME; graduate medical education; collaboration
ID TEMPORAL BONE DISSECTION; SURGICAL SKILL; UNDERGRADUATE; ACQUISITION;
SIMULATION; EDUCATORS; RESIDENTS; MODELS
AB The surgeon-anatomist was originally a single individual who self-pursued knowledge and understanding of anatomy as the foundation for successful surgical outcomes. However, recent advances in medical education have ironically led to the separation of anatomy and surgery. This physical and emotional divorce of anatomists and surgeons into separate individuals has created several critical educational issues for medical and surgical educators including a general lack of anatomical knowledge in medical students and misalignment of graduate medical education procedural specialty training with the Accreditation Council of Graduate Medical Education Core Competencies and now the Next Accreditation System. There are numerous opportunities for anatomists and surgeons to work together to improve educational instruction of established difficult anatomical regions, procedural training, or even develop new techniques and procedures. Similarly, anatomists with specialized training in medical education would be invaluable partners to ensure that procedural assessments align with instructional technologies for truly longitudinal curricula that starts at the medical student level, but stops at the patient outcomes of attending surgeons. This mutually beneficial relationship would be similar to multidisciplinary care teams and current surgeon and PhD/EdD partnerships. The restoration of the relationship between anatomists and surgeons would be invaluable to surgical education and remains an exciting research opportunity. Clin. Anat. 28:931-934, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Phitayakorn, Roy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
[Lachman, Nirusha] Mayo Clin, Coll Med, Dept Anat, Rochester, MN USA.
RP Phitayakorn, R (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang ACC,Suite 460,15 Parkman St, Boston, MA 02114 USA.
EM rphitayakorn@mgh.harvard.edu
OI Phitayakorn, Roy/0000-0002-8327-1484
NR 41
TC 3
Z9 3
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0897-3806
EI 1098-2353
J9 CLIN ANAT
JI Clin. Anat.
PD OCT
PY 2015
VL 28
IS 7
BP 931
EP 934
DI 10.1002/ca.22596
PG 4
WC Anatomy & Morphology
SC Anatomy & Morphology
GA CR3OK
UT WOS:000361242400021
PM 26174432
ER
PT J
AU Alabed, YZ
Sakellis, C
AF Alabed, Yazan Z.
Sakellis, Christopher
TI Umbilical Plugoma Mimics Melanoma Metastasis on FDG PET/CT
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
ID HERNIA REPAIR; VENTRAL HERNIA; MESH; APPEARANCE; CT
AB An 84-year-old man with history of left forehead melanoma was found on a restaging F-18-FDG PET/CT scan with hypermetabolic lung nodules and a mildly FDG-avid soft tissue nodule posterior to the umbilicus. Biopsy of a right lower lobe nodule revealed metastatic melanoma. Follow-up posttreatment PET/CT scan showed complete resolution of lung nodules and unchanged FDG uptake at the level of the umbilicus. Review of the patient's medical history revealed a remote history of umbilical hernia repair. We present a case of postsurgical plugoma mimicking the appearance of melanoma metastasis on FDG PET/CT.
C1 [Alabed, Yazan Z.; Sakellis, Christopher] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA.
[Alabed, Yazan Z.; Sakellis, Christopher] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Alabed, YZ (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA.
EM ziyazan_alabed@dfci.harvard.edu
NR 8
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD OCT
PY 2015
VL 40
IS 10
BP 812
EP 813
DI 10.1097/RLU.0000000000000859
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CR6JB
UT WOS:000361451300012
PM 26164172
ER
PT J
AU Neto, AS
Simonis, FD
Barbas, CSV
Biehl, M
Determann, RM
Elmer, J
Friedman, G
Gajic, O
Goldstein, JN
Linko, R
de Oliveira, RP
Sundar, S
Talmor, D
Wolthuis, EK
de Abreu, MG
Pelosi, P
Schultz, MJ
AF Neto, Ary Serpa
Simonis, Fabienne D.
Barbas, Carmen S. V.
Biehl, Michelle
Determann, Rogier M.
Elmer, Jonathan
Friedman, Gilberto
Gajic, Ognjen
Goldstein, Joshua N.
Linko, Rita
de Oliveira, Roselaine Pinheiro
Sundar, Sugantha
Talmor, Daniel
Wolthuis, Esther K.
de Abreu, Marcelo Gama
Pelosi, Paolo
Schultz, Marcus J.
CA PROtective Ventilation Network
TI Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of
Pulmonary Complications in Patients Without Acute Respiratory Distress
Syndrome: A Systematic Review and Individual Patient Data Analysis
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute respiratory distress syndrome; individual patient analysis;
intensive care unit and in-hospital stay; mechanical ventilation;
mortality; pulmonary complications; tidal volume
ID MECHANICAL VENTILATION; ABDOMINAL-SURGERY; INJURY; PREVENTION;
PNEUMONIA; MORTALITY; SEDATION; STRATEGY; TRIAL
AB Objective: Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients.
Design: Individual patient data analysis.
Patients: ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation.
Interventions: Mechanical ventilation with low tidal volume.
Measurements and Main Results: The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a low tidal volume group (tidal volumes 7 mL/kg predicted body weight), an intermediate tidal volume group (> 7 and < 10 mL/kg predicted body weight), and a high tidal volume group ( 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52-0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 10.9 vs 13.8 +/- 11.6 d; p < 0.01 and 6.1 +/- 8.1 vs 8.9 +/- 9.4 d; p < 0.01) and an increased hospital mortality (49.5% vs 35.6%; p < 0.01).
Conclusions: Ventilation with low tidal volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.
C1 [Neto, Ary Serpa; Simonis, Fabienne D.; Determann, Rogier M.; Wolthuis, Esther K.; Schultz, Marcus J.] Univ Amsterdam, Acad Med Ctr, Dept Intens Care, NL-1105 AZ Amsterdam, Netherlands.
[Neto, Ary Serpa] Fac Med ABC FMABC, Program Postgrad Res & Innovat, Santo Andre, Brazil.
[Neto, Ary Serpa; Barbas, Carmen S. V.] Hosp Israelita Albert Einstein, Dept Crit Care Med, Sao Paulo, Brazil.
[Biehl, Michelle; Gajic, Ognjen] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA.
[Elmer, Jonathan; Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Friedman, Gilberto] Univ Fed Rio Grande do Sul, Sch Med, Porto Alegre, RS, Brazil.
[Linko, Rita] Peijas Hosp, Helsinki Univ Hosp, Dept Anaesthesia & Intens Care Med, Vantaa, Finland.
[de Oliveira, Roselaine Pinheiro] Univ Fed Ciencias Saude Porto Alegre, Sch Med, Porto Alegre, RS, Brazil.
[Sundar, Sugantha; Talmor, Daniel] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA.
[Sundar, Sugantha; Talmor, Daniel] Harvard Univ, Sch Med, Boston, MA USA.
[de Abreu, Marcelo Gama] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, D-01062 Dresden, Germany.
[Pelosi, Paolo] Univ Genoa, IRCCS San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy.
[Schultz, Marcus J.] Univ Amsterdam, Acad Med Ctr, Lab Expt Intens Care & Anesthesiol, NL-1105 AZ Amsterdam, Netherlands.
RP Neto, AS (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Intens Care, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM aryserpa@terra.com.br
RI Goldstein, Joshua/H-8953-2016; Serpa Neto, Ary/D-1927-2012
OI Serpa Neto, Ary/0000-0003-1520-9387
NR 31
TC 30
Z9 32
U1 4
U2 22
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 OCT
PY 2015
VL 43
IS 10
BP 2155
EP 2163
DI 10.1097/CCM.0000000000001189
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA CR5DC
UT WOS:000361358900014
PM 26181219
ER
PT J
AU Kherada, N
Heimowitz, T
Rosendorff, C
AF Kherada, Nisharahmed
Heimowitz, Todd
Rosendorff, Clive
TI Antihypertensive Therapies and Cognitive Function: a Review
SO CURRENT HYPERTENSION REPORTS
LA English
DT Review
DE Dementia; Cognition; Alzheimer's disease; Stroke; Antihypertensive
therapies
ID RENIN-ANGIOTENSIN SYSTEM; ELDERLY HYPERTENSIVE PATIENTS; CARDIOVASCULAR
RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; SYSTOLIC BLOOD-PRESSURE;
ALZHEIMERS-DISEASE; OLDER-ADULTS; DOUBLE-BLIND; INTERVENTION TRIAL;
GINKGO EVALUATION
AB Increasing life expectancy has made old age-related health problems like dementia and cognitive decline more prevalent, and these are rapidly becoming important causes of disability and poor quality of life, causing significant add-ons to health-care costs worldwide. Hypertension is the most important modifiable vascular risk factor for the development and progression of both cognitive decline and dementia. In many observational and randomized studies, antihypertensive therapies have been shown to be beneficial in slowing cognitive decline. However, due to observed discrepancies by these studies, there is a lack of consensus on the best antihypertensive strategy for the prevention or slowing of cognitive decline. It is also not clear whether the beneficial effect of antihypertensive therapy is due to the use of a specific class of agents or combination therapy. Thus, we present a comprehensive review of overall antihypertensive therapies and cognition and of the individual antihypertensive therapy classes with their specific protective mechanisms and available clinical evidence behind their effect on cognitive function.
C1 [Kherada, Nisharahmed; Heimowitz, Todd] Columbia Univ, Mt Sinai Med Ctr, Dept Cardiol, Miami Beach, FL 33140 USA.
[Rosendorff, Clive] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, Dept Cardiol, Bronx, NY 10468 USA.
RP Kherada, N (reprint author), Columbia Univ, Mt Sinai Med Ctr, Dept Cardiol, 4300 Alton Rd,Suite 2070, Miami Beach, FL 33140 USA.
EM kherada.1@gmail.com; Todd.Heimowitz@msmc.com; Clive.Rosendorff@va.gov
NR 70
TC 4
Z9 4
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1522-6417
EI 1534-3111
J9 CURR HYPERTENS REP
JI Curr. Hypertens. Rep.
PD OCT
PY 2015
VL 17
IS 10
AR 79
DI 10.1007/s11906-015-0592-7
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR6IR
UT WOS:000361450100003
PM 26298567
ER
PT J
AU Elder, GA
AF Elder, Gregory A.
TI Update on TBI and Cognitive Impairment in Military Veterans
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Alzheimer's disease; Blast; Chronic traumatic encephalopathy; Dementia;
Traumatic brain injury; Military veterans
ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; DEPLOYED US
MILITARY; ALZHEIMERS-DISEASE; HEAD-INJURY; SERVICE MEMBERS; ACUTE
CONCUSSION; OLDER VETERANS; DEMENTIA RISK; ENCEPHALOPATHY
AB Traumatic brain injury (TBI) is a common cause of morbidity and mortality in military life. Interest in military TBI has increased recently due to the conflicts in Iraq and Afghanistan. Certain types of TBI are relatively unique to the military, the most prominent being blast-related TBI. Blast-related mild TBI has been of particular concern in veterans from the most recent conflicts although controversy remains concerning its separation from post-traumatic stress disorder. TBI is also a risk factor for the later development of neurodegenerative diseases in which cognitive impairment is prominent putting veterans at risk for disorders including Alzheimer's disease and chronic traumatic encephalopathy. Recent evidence associating TBI with chronic cognitive impairment is reviewed in the context of its relevance to military veterans.
C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA.
[Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
[Elder, Gregory A.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM gregory.elder@va.gov
FU Department of Veterans Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service Awards [1I01RX000179-01,
1I01RX000996-01]
FX The author has received research support from the Department of Veterans
Affairs, Veterans Health Administration, Rehabilitation Research and
Development Service Awards 1I01RX000179-01 and 1I01RX000996-01.
NR 82
TC 1
Z9 1
U1 2
U2 9
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 OCT
PY 2015
VL 15
IS 10
AR 68
DI 10.1007/s11910-015-0591-8
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CR6HO
UT WOS:000361446400004
PM 26299275
ER
PT J
AU Seol, JY
Mihich, E
Berleth, ES
AF Seol, Ji-Yeon
Mihich, Enrico
Berleth, Erica S.
TI TNF Apoptosis Protection Fraction (TAPF) prevents apoptosis induced by
TNF, but not by Fas or TRAIL, via NF-kappa B-induced increase in cFLIP
SO CYTOKINE
LA English
DT Article
DE TNF; Apoptosis; TRAIL; Fas; cFLIP
ID TUMOR-NECROSIS-FACTOR; SIGNALING PATHWAYS; HUMAN FIBROBLASTS; PROTEIN;
ALPHA; TIP-B1; SUPERFAMILY; MECHANISMS; INDUCTION; DISEASES
AB Tumor Necrosis Factor alpha (TNF alpha) induces both the apoptotic pathway and anti-apoptotic factors. Incubation of human dermal fibroblasts with TAPF (TNF Apoptosis Protection Fraction) protects them from apoptosis induced by the subsequent addition of TNF and cycloheximide (CHX). TAPF does not protect against apoptosis induced by CHX in combination with either TRAIL (TNF related apoptosis inducing ligand) or an agonistic Fas antibody, or against apoptosis induced by the chemotherapeutic agent doxorubicin. Incubation with TAPF does not affect the quantity of TNF that binds to the cell. TAPF prevents TNF-induced cleavage of caspases 8, 9, 3 and 7 and the apoptotic substrate PARP (poly-ADP ribose polymerase), but has no effect when these molecules are induced by an agonistic Fas antibody. TAPF induces rapid phosphorylation of the NF-kappa B/p65 (nuclear factor-kappa B) transcription factor at serine 536 which is indicative of its activation. TAPF increases the expression of cFLIP (cellular FLICE-inhibitory protein) which is a potent inhibitor of apoptosis that acts by preventing the cleavage of caspase 8. This increase in cFLIP is coincident with protection from TNF-induced apoptosis. Decreasing cFLIP levels using shRNA (short hairpin RNA) decreases protection by TAPF. TAPF also induced the anti-apoptotic A20 protein. These data indicate that TAPF protects human dermal fibroblasts from TNF-induced apoptosis by induction of cFLIP and subsequent inhibition of caspase 8 cleavage. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Seol, Ji-Yeon; Mihich, Enrico; Berleth, Erica S.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA.
RP Mihich, E (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM jseol@yahoo.com; enrico_mihich@dfci.harvard.edu; erica.berleth@gmail.com
FU National Cancer Institute [R01 CA093594]; Cancer Center Support Grant
[P30 CA016056]
FX We thank and acknowledge Dr. M.M. Ip, as well as members of her
laboratory, for helpful discussion, gifts of reagents and critical
review of the manuscript. We also acknowledge the Asahi Chemical
Industry Co., Ltd. for the generous gift of TNF and the National Cancer
Institute for funding support to E. Berleth (R01 CA093594) and the core
resources provided through the Cancer Center Support Grant to Roswell
Park Cancer Institute (P30 CA016056).
NR 22
TC 1
Z9 1
U1 2
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD OCT
PY 2015
VL 75
IS 2
BP 321
EP 329
DI 10.1016/j.cyto.2015.05.027
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CR3TQ
UT WOS:000361256400016
PM 26198031
ER
PT J
AU Stucky, EC
Schloss, RS
Yarmush, ML
Shreiber, DI
AF Stucky, Elizabeth C.
Schloss, Rene S.
Yarmush, Martin L.
Shreiber, David I.
TI Alginate micro-encapsulation of mesenchymal stromal cells enhances
modulation of the neuro-inflammatory response
SO CYTOTHERAPY
LA English
DT Article
DE co-culture; inflammation mediators; mesenchymal stromal cells; organ
culture; traumatic brain injury
ID TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR;
PGE(2) EP2 RECEPTOR; BONE-MARROW; STEM-CELLS; CEREBRAL-ISCHEMIA;
PROSTAGLANDIN E-2; ANTIINFLAMMATORY PROPERTIES; INDUCIBLE CYCLOOXYGENASE
AB Background aims. Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocarnpal slice cultures (OHSC). Methods. OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) produced by OHSC, as well as MSC-produced trophic mediators. Results. Encapsulated MSCs reduced TNF-alpha more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E-2 (PGE(2)) and reduction of TNF-alpha. In contrast to monolayer MS Cs, inflammatory signals were not required to stimulate PGE(2) production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-alpha levels were identified. Conclusions. These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation.
C1 [Stucky, Elizabeth C.; Yarmush, Martin L.] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA.
[Schloss, Rene S.; Yarmush, Martin L.; Shreiber, David I.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
[Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA.
EM yarmush@rci.rutgers.edu; shreiber@rci.rutgers.edu
OI Stucky Hunter, Elizabeth/0000-0003-0797-9453
FU New Jersey Commission on Brain Injury Research
[SNJ-DHSS-CBIR-CBIE12IPG019, 10-3215-BIR-E-0]; National Institute of
Health [P41EB002503]; Rutgers-UMDNJ Biotechnology Training Fellowship
[T32GM00008339-21]; NSF Stem Cell IGERT Fellowship [0801620]
FX We would like to acknowledge Serom Lee, PhD, and Andrea Gray for their
assistance and contribution to the statistical analyses, and Mehdi
Ghodbane, PhD, for assistance with multiplex assay and analysis. This
research was supported by the New Jersey Commission on Brain Injury
Research (SNJ-DHSS-CBIR-CBIE12IPG019 and 10-3215-BIR-E-0), National
Institute of Health Grant P41EB002503, Rutgers-UMDNJ Biotechnology
Training Fellowship T32GM00008339-21 and NSF Stem Cell IGERT Fellowship
0801620. These funding agencies were not involved in the conduct of the
research or preparation of the article.
NR 58
TC 4
Z9 4
U1 2
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD OCT
PY 2015
VL 17
IS 10
BP 1353
EP 1364
DI 10.1016/j.jcyt.2015.05.002
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CR5XX
UT WOS:000361418800004
PM 26210574
ER
PT J
AU Chacko, L
Macaron, C
Burke, CA
AF Chacko, Lyssa
Macaron, Carole
Burke, Carol A.
TI Clinical Practice Patterns Suggest Female Patients Prefer Female
Endoscopists Reply
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Letter
C1 [Chacko, Lyssa] Denver Vet Affairs Med Ctr, Dept Gastroenterol & Hepatol, Denver, CO USA.
[Macaron, Carole] Cleveland Vet Affairs Med Ctr, Gastroenterol Sect, Cleveland, OH USA.
[Burke, Carol A.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA.
RP Burke, CA (reprint author), Cleveland Clin, Dept Gastroenterol & Hepatol, Desk 30,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM Burkec1@ccf.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD OCT
PY 2015
VL 60
IS 10
BP 3150
EP 3150
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CR6ZU
UT WOS:000361497900043
ER
PT J
AU Mitra, M
Long-Bellil, LM
Smeltzer, SC
Iezzoni, LI
AF Mitra, Monika
Long-Bellil, Linda M.
Smeltzer, Suzanne C.
Iezzoni, Lisa I.
TI A perinatal health framework for women with physical disabilities
SO DISABILITY AND HEALTH JOURNAL
LA English
DT Article
DE Disability; Pregnancy; Perinatal health; Framework; Women with physical
disabilities
ID MULTIPLE-SCLEROSIS; CURRENT PREGNANCY; MATERNITY CARE; US WOMEN;
EXPERIENCES; MOTHERS; PEOPLE; ACCESS; MASSACHUSETTS; PREVALENCE
AB Background: Studies suggest that women with disabilities experience health and health care disparities before, during, and after pregnancy. However, existing perinatal health and health care frameworks do not address the needs and barriers faced by women with physical disabilities around the time of pregnancy. A new framework that addresses perinatal disparities among women with physical disabilities is needed.
Objective: To propose a framework for examining perinatal health and health care disparities among women with physical disabilities.
Methods: We developed a perinatal health framework guided by the International Classification of Functioning, Disability and Health (ICF) and the integrated perinatal health framework by Misra et al.
Results: The proposed framework uses a life span perspective in a manner that directly addresses the multiple determinants specific to women with physical disabilities around the time of pregnancy. The framework is based on longitudinal and integrated perspectives that take into account women's functional status and environment over their life course.
Conclusion: The perinatal health framework for women with physical disabilities was developed to inform the way researchers and health care professionals address disparities in perinatal health and health care among women with physical disabilities. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Mitra, Monika; Long-Bellil, Linda M.] Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, Shrewsbury, MA 01545 USA.
[Smeltzer, Suzanne C.] Villanova Univ, Ctr Nursing Res, Coll Nursing, Villanova, PA 19085 USA.
[Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
RP Mitra, M (reprint author), Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, 333 South St, Shrewsbury, MA 01545 USA.
EM monika.mitra@umassmed.edu
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health & Human Development [R01HD074581]
FX This research is funded by a grant from the National Institutes of
Health, Eunice Kennedy Shriver National Institute of Child Health &
Human Development. Award number: R01HD074581.
NR 63
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 1936-6574
EI 1876-7583
J9 DISABIL HEALTH J
JI Disabil. Health J.
PD OCT
PY 2015
VL 8
IS 4
BP 499
EP 506
DI 10.1016/j.dhjo.2015.05.007
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health; Rehabilitation
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Rehabilitation
GA CR3RD
UT WOS:000361249900007
PM 26189010
ER
PT J
AU Marino, ME
Meterko, M
Marfeo, EE
McDonough, CM
Jette, AM
Ni, PS
Bogusz, K
Rasch, EK
Brandt, DE
Chan, L
AF Marino, Molly Elizabeth
Meterko, Mark
Marfeo, Elizabeth E.
McDonough, Christine M.
Jette, Alan M.
Ni, Pengsheng
Bogusz, Kara
Rasch, Elizabeth K.
Brandt, Diane E.
Chan, Leighton
TI Work-related measures of physical and behavioral health function:
Test-retest reliability
SO DISABILITY AND HEALTH JOURNAL
LA English
DT Article
DE Disability evaluation; Psychometrics; United States Social Security
Administration; Computer-adaptive test; Reliability
ID INTRACLASS CORRELATION-COEFFICIENTS; ITEM POOL CONSTRUCTION;
QUALITY-OF-LIFE; DISABILITY EVALUATION; FUNCTION INSTRUMENT; OUTCOMES;
VALIDITY; SYSTEM
AB Background: The Work Disability Functional Assessment Battery (WD-FAB), developed for potential use by the US Social Security Administration to assess work-related function, currently consists of five multi-item scales assessing physical function and four multi-item scales assessing behavioral health function; the WD-FAB scales are administered as Computerized Adaptive Tests (CATs).
Objective: The goal of this study was to evaluate the test-retest reliability of the WD-FAB Physical Function and Behavioral Health CATs.
Methods: We administered the WD-FAB scales twice, 7-10 days apart, to a sample of 376 working age adults and 316 adults with work-disability. Intraclass correlation coefficients were calculated to measure the consistency of the scores between the two administrations. Standard error of measurement (SEM) and minimal detectable change (MDC90) were also calculated to measure the scales precision and sensitivity.
Results: For the Physical Function CAT scales, the ICCs ranged from 0.76 to 0.89 in the working age adult sample, and 0.77-0.86 in the sample of adults with work-disability. ICCs for the Behavioral Health CAT scales ranged from 0.66 to 0.70 in the working age adult sample, and 0.77-0.80 in the adults with work-disability. The SEM ranged from 3.25 to 4.55 for the Physical Function scales and 5.27-6.97 for the Behavioral Health function scales. For all scales in both samples, the MDC90 ranged from 7.58 to 16.27.
Conclusion: Both the Physical Function and Behavioral Health CATs of the WD-FAB demonstrated good test-retest reliability in adults with work-disability and general adult samples, a critical requirement for assessing work related functioning in disability applicants and in other contexts. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Marino, Molly Elizabeth; Meterko, Mark; Marfeo, Elizabeth E.; McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
[Meterko, Mark] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Rasch, Elizabeth K.; Brandt, Diane E.; Chan, Leighton] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Marino, ME (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St,T5W, Boston, MA 02118 USA.
EM memarino@bu.edu
FU Social Security Administration-National Institutes of Health under the
National Institutes of Health [HHSN269200900004C, HHSN269201000011C,
HHSN269201100009I]; National Institutes of Health Intramural Research
Program
FX This study was supported by Social Security Administration-National
Institutes of Health Interagency Agreements under the National
Institutes of Health (contract nos. HHSN269200900004C,
HHSN269201000011C, HHSN269201100009I), and by the National Institutes of
Health Intramural Research Program.
NR 25
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-6574
EI 1876-7583
J9 DISABIL HEALTH J
JI Disabil. Health J.
PD OCT
PY 2015
VL 8
IS 4
BP 652
EP 657
DI 10.1016/j.dhjo.2015.04.001
PG 6
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health; Rehabilitation
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Rehabilitation
GA CR3RD
UT WOS:000361249900027
PM 25991419
ER
PT J
AU Siddiqi, OK
Smoot, KJ
Dufour, AB
Cho, K
Young, M
Gagnon, DR
Ly, S
Temiyasathit, S
Faxon, DP
Gaziano, JM
Kinlay, S
AF Siddiqi, Omar K.
Smoot, Kyle J.
Dufour, Alyssa B.
Cho, Kelly
Young, Melissa
Gagnon, David R.
Ly, Samantha
Temiyasathit, Sara
Faxon, David P.
Gaziano, J. Michael
Kinlay, Scott
TI Outcomes with prolonged clopidogrel therapy after coronary stenting in
patients with chronic kidney disease
SO HEART
LA English
DT Article
ID DUAL-ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; MODERATE
RENAL-INSUFFICIENCY; GLOMERULAR-FILTRATION-RATE; LONG-TERM OUTCOMES;
BARE-METAL; MYOCARDIAL-INFARCTION; RISK-FACTORS; IMPLANTATION; TRIAL
AB Objectives Patients with chronic kidney disease (CKD) are at high risk of death or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We assessed whether prolonged dual antiplatelet therapy beyond the recommended 12 months may prevent adverse outcomes in patients with CKD receiving drug-eluting stents (DES) or bare-metal stents (BMS).
Methods We studied all Veterans receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA) Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular filtration rate < 60 mL/min) or normal renal function. We used landmark analyses from 12 months after PCI with Cox proportional hazards multivariable and propensity-adjusted models to assess the effect of prolonged clopidogrel (more than 12 months) versus 12 months or less after PCI on clinical outcomes from 1 year to 4 years after PCI.
Results Of 23 042 eligible subjects receiving PCI, 4880 (21%) had CKD. Compared with normal renal function, patients with CKD had higher risks of death or MI 1-4 years after DES (21% vs 12%, HR=1.75; 95% CI 1.51 to 2.04) or BMS (28% vs 15%, HR=2.10; 95% CI 1.90 to 2.32). In patients with CKD receiving DES, clopidogrel use of more than 12 months after PCI was associated with lower risks of death or MI (18% vs 24%, HR=0.74; 95% CI 0.58 to 0.95), and death (15% vs 23%, HR=0.61; 95% CI 0.47 to 0.80), but had no effect on repeat revascularisation 1-4 years after PCI.
Conclusions In patients with CKD, prolonging clopidogrel beyond 12 months after PCI may decrease the risk of death or MI only in patients receiving first-generation DES. These results support a patient-tailored approach to prolonging clopidogrel after PCI.
C1 [Siddiqi, Omar K.; Smoot, Kyle J.; Dufour, Alyssa B.; Cho, Kelly; Young, Melissa; Gagnon, David R.; Ly, Samantha; Temiyasathit, Sara; Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] VA Boston Healthcare Syst, Cardiovasc Div, West Roxbury, MA 02132 USA.
[Siddiqi, Omar K.] Boston Med Ctr, Cardiovasc Div, Boston, MA USA.
[Smoot, Kyle J.; Dufour, Alyssa B.; Cho, Kelly; Young, Melissa; Gagnon, David R.; Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, MAVERIC, Boston, MA USA.
[Dufour, Alyssa B.; Cho, Kelly; Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA.
[Dufour, Alyssa B.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Gagnon, David R.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Cardiovasc Div, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM scott.kinlay@va.gov
OI Dufour, Alyssa/0000-0001-8061-9599
FU CSRD VA [I01 CX000440]; Intramural VA [VA999999]
NR 30
TC 9
Z9 10
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD OCT
PY 2015
VL 101
IS 19
BP 1569
EP 1576
DI 10.1136/heartjnl-2014-307168
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR2OB
UT WOS:000361168800011
PM 26209334
ER
PT J
AU Cong, J
Fan, TP
Yang, XQ
Shen, JS
Cheng, GM
Zhang, Z
AF Cong, Juan
Fan, Tingpan
Yang, Xiaoqian
Shen, Jacson
Cheng, Guomei
Zhang, Zhan
TI Maternal cardiac remodeling and dysfunction in preeclampsia: a
three-dimensional speckle-tracking echocardiography study
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Preeclampsia; Strain; Three-dimension; Speckle-tracking;
Echocardiography
ID LEFT-VENTRICULAR FUNCTION; CONSENSUS STATEMENT; SOCIETY; QUANTIFICATION;
HYPERTENSION; PREGNANCY; DIAGNOSIS; DISEASE; STRAIN
AB Aims preeclampsia (PE) is a pregnancy complication that remains a main cause of maternal morbidity and mortality. The aims of this study were to investigate left ventricle (LV) performance in PE and to compare maternal cardiac function between early-onset preeclampsia (EP) and late-onset preeclampsia (LP) by novel threedimensional (3D) speckle-tracking echocardiography (STE) parameters while considering LV loading and shape. Methods and Results Two-dimensional echocardiography and 3D STE were performed in 43 women with EP, 41 women with LP, and 81 normal pregnancies. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured using 3D speckle-tracking software. There was eccentric hypertrophy and reduced LV ejection fraction (EF) in PE; meanwhile, GLS in EP and LP, GCS in LP, as well as GAS and GRS in EP significantly decreased in PE versus controls. All 3D strain indices were correlated with gestation age. Increased left atrial (LA) volume index was detected in PE. Higher LV mass index and lower 3D-derived strain value were present in women with EP compared to that in women with LP. Conclusion PE cases exhibited significant eccentric hypertrophy, ventricular dysfunction, and LA remodeling. Furthermore, myocardial deformation abnormalities preceded chamber dysfunction in this hypertensive disorder complicated pregnancy. Compared with LP, women with EP demonstrated more remarkable cardiac damage.
C1 [Cong, Juan; Fan, Tingpan] Zhengzhou Univ, Affiliated Hosp 3, Dept Ultrason Diag, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Prov Engn Res Ctr Perinatal Med, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Translat Med Engn Lab Maternal & Childrens, Zhengzhou 450052, Henan Province, Peoples R China.
[Shen, Jacson] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
RP Zhang, Z (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China.
EM zhangzhanmd27@126.com
FU Henan Provincial Health research program [ID_201203048]; Henan Province
Medical Academic Technology Leaders of Overseas Training Program
[ID_201201055]
FX We thank Songyan Liu and Tianwei Zhao for valuable contributions. This
work was supported partially by the Henan Provincial Health research
program (Grant ID_201203048) and partially by Henan Province Medical
Academic Technology Leaders of Overseas Training Program (Grant
ID_201201055).
NR 24
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
EI 1573-0743
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD OCT
PY 2015
VL 31
IS 7
BP 1361
EP 1368
DI 10.1007/s10554-015-0694-y
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CR6YP
UT WOS:000361494800011
PM 26077816
ER
PT J
AU Marshall, DC
Punglia, RS
Fox, D
Recht, A
Hattangadi-Gluth, JA
AF Marshall, Deborah C.
Punglia, Rinaa S.
Fox, Dov
Recht, Abram
Hattangadi-Gluth, Jona A.
TI Medical Malpractice Claims in Radiation Oncology: A Population-Based
Study 1985-2012
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID CANCER; RISK; LITIGATION; SYSTEM; REFORM
AB Purpose: The purpose of this study was to determine trends in radiation oncology malpractice claims and expenses during the last 28 years and to compare radiation oncology malpractice claims to those of other specialties.
Methods and Materials: We performed a retrospective analysis of closed malpractice claims filed from 1985 to 2012, collected by a nationwide medical liability insurance trade association. We analyzed characteristics and trends among closed claims, indemnity payments (payments to plaintiff), and litigation expenses. We also compared radiation oncology malpractice claims to those of 21 other medical specialties. Time series dollar amounts were adjusted for inflation (2012 was the index year).
Results: There were 1517 closed claims involving radiation oncology, of which 342 (22.5%) were paid. Average and median indemnity payments were $276,792 and $122,500, respectively, ranking fifth and eighth, respectively, among the 22 specialty groups. Linear regression modeling of time trends showed decreasing total numbers of claims (beta = -1.96 annually, P =. 003), increasing average litigation expenses paid (beta = +$1472 annually, P <= .001), and no significant changes in average indemnity payments (beta = -$ 681, P = . 89).
Conclusions: Medical professional liability claims filed against radiation oncologists are not common and have declined in recent years. However, indemnity payments in radiation oncology are large relative to those of many other specialties. In recent years, the average indemnity payment has been stable, whereas litigation expenses have increased. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Marshall, Deborah C.; Hattangadi-Gluth, Jona A.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA.
[Punglia, Rinaa S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Punglia, Rinaa S.; Recht, Abram] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Dov] Univ San Diego, Sch Law, San Diego, CA 92110 USA.
[Recht, Abram] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
RP Hattangadi-Gluth, JA (reprint author), Univ Calif San Diego, Moores Canc Ctr, Dept Radiat Med & Appl Sci, 3960 Hlth Sci Dr,Mail Code 0865, La Jolla, CA 92093 USA.
EM jhattangadi@ucsd.edu
FU Joint Center for Radiation Therapy Foundation; US National Institutes of
Health [TL1TR00098, KL2TR00099, UL1TR000100]
FX Supported in part by the Joint Center for Radiation Therapy Foundation
(J.A.H-G.), US National Institutes of Health grants TL1TR00098 (D.M.),
KL2TR00099 (J.A.H-G.), and UL1TR000100 (J.A.H-G.).
NR 35
TC 0
Z9 0
U1 0
U2 8
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 OCT 1
PY 2015
VL 93
IS 2
BP 241
EP 250
DI 10.1016/j.ijrobp.2015.05.040
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CR3RF
UT WOS:000361250100004
PM 26232856
ER
PT J
AU Rosenthal, SA
Hunt, D
Sartor, O
Pienta, KJ
Gomella, L
Grignon, D
Rajan, R
Kerlin, KJ
Jones, CU
Dobelbower, M
Shipley, WU
Zeitzer, K
Hamstra, DA
Donavanik, V
Rotman, M
Hartford, AC
Michalski, J
Seider, M
Kim, H
Kuban, DA
Moughan, J
Sandler, H
AF Rosenthal, Seth A.
Hunt, Daniel
Sartor, Oliver
Pienta, Kenneth J.
Gomella, Leonard
Grignon, David
Rajan, Raghu
Kerlin, Kevin J.
Jones, Christopher U.
Dobelbower, Michael
Shipley, William U.
Zeitzer, Kenneth
Hamstra, Daniel A.
Donavanik, Viroon
Rotman, Marvin
Hartford, Alan C.
Michalski, Jeffrey
Seider, Michael
Kim, Harold
Kuban, Deborah A.
Moughan, Jennifer
Sandler, Howard
TI A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy
With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer:
Final Results of Radiation Therapy Oncology Group Phase 3 Randomized
Trial NRG Oncology RTOG 9902
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID GROUP PROTOCOL 92-02; ORAL ETOPOSIDE; COMPETING RISK; III TRIAL;
RADIOTHERAPY; DEPRIVATION; DURATION; ESTRAMUSTINE; PACLITAXEL; CARCINOMA
AB Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).
Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20100 ng/mL and Gleason score [GS] >= 7 or clinical stage >= T2 and GS >= 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05.
Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P = . 81), biochemical failure (58% vs 54%; P = . 82), local progression (11% vs 7%; P = . 09), distant metastases (16% vs 14%; P = . 42), or disease-free survival (22% vs 26%; P = . 61).
Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Rosenthal, Seth A.; Jones, Christopher U.] Sutter Canc Cent, Radiat Oncol, Roseville, CA USA.
[Hunt, Daniel; Moughan, Jennifer] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA.
[Sartor, Oliver] Tulane Univ, Med Ctr, New Orleans, LA USA.
[Pienta, Kenneth J.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Gomella, Leonard] Thomas Jefferson Univ Hosp, Philadelphia, PA USA.
[Grignon, David] Indiana Univ, Bloomington, IN USA.
[Rajan, Raghu] McGill Univ, Montreal, PQ, Canada.
[Kerlin, Kevin J.] Southeast Canc Control Consortium Inc, Community Clin Oncol Program, Winston Salem, NC USA.
[Jones, Christopher U.] Radiol Associates Sacramento, Sacramento, CA USA.
[Dobelbower, Michael] Univ Alabama Birmingham, Birmingham Med Ctr, Birmingham, AL USA.
[Shipley, William U.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shipley, William U.] Harvard Univ, Sch Med, Boston, MA USA.
[Zeitzer, Kenneth] Albert Einstein Med Ctr, Bronx, NY USA.
[Hamstra, Daniel A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Donavanik, Viroon] Christiana Care Hlth Serv Inc, Wilmington, DE USA.
[Rotman, Marvin] SUNY Hlth Sci Ctr, Brooklyn, NY USA.
[Hartford, Alan C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH USA.
[Michalski, Jeffrey] Washington Univ, St Louis, MO USA.
[Seider, Michael] Akron City Hosp, Akron, OH USA.
[Kim, Harold] Wayne State Univ, Detroit, MI USA.
[Kuban, Deborah A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Sandler, Howard] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
RP Rosenthal, SA (reprint author), Sutter Med Grp, Roseville Radiat Oncol, 2 Med Plaza,Suite 180, Roseville, CA 95661 USA.
EM rosents@sutterhealth.org
FU National Cancer Institute [RTOG U10CA21661, NRG U10CA180868, NRG
U10CA180822]; Bristol Myers Squibb; Pfizer
FX This project was supported by grants RTOG U10CA21661, NRG U10CA180868,
and NRG U10CA180822 from the National Cancer Institute, and by Bristol
Myers Squibb and Pfizer.
NR 23
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 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD OCT 1
PY 2015
VL 93
IS 2
BP 294
EP 302
DI 10.1016/j.ijrobp.2015.05.024
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CR3RF
UT WOS:000361250100011
PM 26209502
ER
PT J
AU Lam, TC
Uno, H
Krishnan, M
Lutz, S
Groff, M
Cheney, M
Balboni, T
AF Lam, Tai-Chung
Uno, Hajime
Krishnan, Monica
Lutz, Steven
Groff, Michael
Cheney, Matthew
Balboni, Tracy
TI Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated
Spine Metastases: Role of Spinal Instability and Single-Fraction
Radiation Therapy
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID PAINFUL BONE METASTASES; ONCOLOGY STUDY-GROUP; RANDOMIZED-TRIAL; 8 GY;
MULTIPLE FRACTIONS; NEOPLASTIC SCORE; RADIOTHERAPY TRIALS; CANCER;
RELIABILITY; SURVIVAL
AB Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases.
Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs.
Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] Z 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS >= 11 (HRZ2.5, 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HRZ3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT.
Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS >= 11 and SF RT were associated with a higher rate of SAEs. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Lam, Tai-Chung; Krishnan, Monica; Balboni, Tracy] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
[Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Lutz, Steven] Blanchard Valley Reg Med Ctr, Dept Radiat Oncol, Findlay, OH USA.
Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Cheney, Matthew] Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Balboni, Tracy] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Lam, TC (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave,DA 1101, Boston, MA 02215 USA.
EM lamtaichung@gmail.com
OI Cheney, Matthew/0000-0001-8367-3427
FU American Society of Clinical Oncology Conquer Cancer Foundation Career
Development Award
FX Supported in part by an American Society of Clinical Oncology Conquer
Cancer Foundation Career Development Award to Dr T. Balboni.
NR 25
TC 3
Z9 4
U1 0
U2 4
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 OCT 1
PY 2015
VL 93
IS 2
BP 373
EP 381
DI 10.1016/j.ijrobp.2015.06.006
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CR3RF
UT WOS:000361250100021
PM 26279324
ER
PT J
AU Pulsifer, MB
Sethi, RV
Kuhlthau, KA
MacDonald, SM
Tarbell, NJ
Yock, TI
AF Pulsifer, Margaret B.
Sethi, Roshan V.
Kuhlthau, Karen A.
MacDonald, Shannon M.
Tarbell, Nancy J.
Yock, Torunn I.
TI Early Cognitive Outcomes Following Proton Radiation in Pediatric
Patients With Brain and Central Nervous System Tumors
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID CRANIOSPINAL IRRADIATION; CLINICAL-OUTCOMES; NEUROCOGNITIVE
CONSEQUENCES; ONCOLOGY-GROUP; GRADE GLIOMA; THERAPY; MEDULLOBLASTOMA;
CHILDHOOD; SURVIVORS; RADIOTHERAPY
AB Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors.
Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged >= 6 years at baseline to ensure consistency in neurocognitive measures.
Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection.
Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Sethi, Roshan V.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Kuhlthau, Karen A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Pulsifer, MB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM mpulsifer@mgh.harvard.edu
FU National Cancer Institute [P01CA021239]; Federal Share of program,
Proton Therapy Research and Treatment Center [C06 CA059267]
FX The project described was supported by award no. P01CA021239 from the
National Cancer Institute. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health.; The
project was supported by the Federal Share of program income earned by
Massachusetts General Hospital (MGH) on C06 CA059267, Proton Therapy
Research and Treatment Center.
NR 34
TC 10
Z9 10
U1 3
U2 11
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 OCT 1
PY 2015
VL 93
IS 2
BP 400
EP 407
DI 10.1016/j.ijrobp.2015.06.012
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CR3RF
UT WOS:000361250100024
PM 26254679
ER
PT J
AU Miller, PE
Martin, SS
Toth, PP
Santos, RD
Blaha, MJ
Nasir, K
Virani, SS
Post, WS
Blumenthal, RS
Jones, SR
AF Miller, P. Elliott
Martin, Seth S.
Toth, Peter P.
Santos, Raul D.
Blaha, Michael J.
Nasir, Khurram
Virani, Salim S.
Post, Wendy S.
Blumenthal, Roger S.
Jones, Steven R.
TI Screening and advanced lipid phenotyping in familial
hypercholesterolemia: The Very Large Database of Lipids Study-17
(VLDL-17)
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE Familial hypercholesterolethia; Screening; Lipid phenotyping; Friedewald
equation; Low-density lipoprotein cholesterol; Lipoprotein(a); Remnant
lipoprotein cholesterol
ID DENSITY-LIPOPROTEIN CHOLESTEROL; ASSOCIATION EXPERT PANEL;
ISCHEMIC-HEART-DISEASE; REMNANT CHOLESTEROL; GENERAL-POPULATION;
UNITED-STATES; DIAGNOSIS; MANAGEMENT; GUIDANCE; RISK
AB BACKGROUND: Familial hypercholesterolernia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes.
METHODS: We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels.
RESULTS: Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population
CONCLUSIONS: Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future
C1 [Miller, P. Elliott; Martin, Seth S.; Toth, Peter P.; Blaha, Michael J.; Post, Wendy S.; Blumenthal, Roger S.; Jones, Steven R.] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA.
[Toth, Peter P.] CGH Med Ctr, Dept Prevent Cardiol, Sterling, IL USA.
[Toth, Peter P.] Univ Illinois, Coll Med, Peoria, IL 61656 USA.
[Santos, Raul D.] InCor Univ Sao Paulo, Lipid Clin Heart Inst, Prevent Med Ctr, Hosp Israelita Albert Einstein,Med Sch Hosp, Sao Paulo, Brazil.
[Nasir, Khurram] Ctr Prevent & Wellness Res, Baptist Hlth Med Grp, Miami, FL USA.
[Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Cardiovasc Res, Houston, TX 77030 USA.
RP Miller, PE (reprint author), Johns Hopkins Univ Hosp, Dept Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM elliottmiller@jhmi.edu
RI Santos, Raul/A-1170-2010;
OI Santos, Raul/0000-0002-9860-6582; Virani, Salim/0000-0001-9541-6954
FU Pollin Cardiovascular Prevention Fellowship; Marie-Josee and Henry R.
Kravis endowed fellowship; National Institutes of Health [T32HL07024];
US Food and Drug Administration; Department of Veterans Affairs;
American Heart Association; American Diabetes Association
FX S.S.M. is supported by the Pollin Cardiovascular Prevention Fellowship,
Marie-Josee and Henry R. Kravis endowed fellowship, and a National
Institutes of Health training grant (T32HL07024). The article has no
funding.; Dr Martin and Dr Jones are listed as coinventors on a pending
patent filed by Johns Hopkins University for a method of low-density
lipoprotein cholesterol estimation. Dr Blaha reports pending grant
funding from the National Institutes of Health and the US Food and Drug
Administration and participating in a roundtable discussion with
Regeneron. Dr Virani reports having received research funding from the
Department of Veterans Affairs, American Heart Association, and the
American Diabetes Association. Dr Toth serves on the medical advisory
board for Atherotech Diagnostic Lab and has received compensation for
consultancy and lecturers from Abbvie, Aegerion, Amgen, AstraZeneca,
Glaxo-SmithKline, Kowa, and Merck & Co, Novartis, and Regeneron. Dr
Jones serves on the medical advisory board for Atherotech Diagnostic Lab
and as an advisor to Sanofi and Regeneron. Dr Santos has received
honoraria for consulting and speaker activities from AstraZeneca, Amgen,
Biolab, Boehringher-Ingelheim, Bristol Myers Squibb, Eli-Lilly, Jansen,
Merck, Novartis, Pfizer, Praxis, Sanofi/Regeneron, Unilever.
NR 36
TC 4
Z9 4
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
EI 1876-4789
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD OCT
PY 2015
VL 9
IS 5
BP 676
EP 683
DI 10.1016/j.jacl.2015.06.015
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CR5WQ
UT WOS:000361415500009
PM 26350814
ER
PT J
AU Forman, MS
Chuang, SK
August, M
AF Forman, Michael S.
Chuang, Sung-Kiang
August, Meredith
TI The Accuracy of Clinical Diagnosis of Oral Lesions and Patient-Specific
Risk Factors that Affect Diagnosis
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID DENTAL PRACTITIONERS; CARCINOMA
AB Purpose: To examine the rate of discrepancy between clinical impression and histologic diagnosis of oral lesions in patients undergoing biopsy examination and to determine whether there are patient-specific variables associated with a higher rate of discrepancy.
Materials and Methods: The authors designed and implemented a retrospective cohort study that consisted of patients who underwent biopsy examination of oral lesions from 2005 through 2013 by oral and maxillofacial surgeons at the Massachusetts General Hospital. Accuracy was determined by comparing the clinical impression with the final histologic diagnosis. Clinical and histologic diagnoses were categorized as premalignant or malignant (group 1) or benign (group 2). The primary outcome variable was concordance (yes vs no) between clinical impression and histopathologic diagnosis. The effect of individual predictor variables (age, gender, duration, American Society of Anesthesiology status, cancer history, radiation therapy history, medications, alcohol abuse, and tobacco history) on outcome also was evaluated through univariate and multivariate regression analyses.
Results: The study sample was composed of 1,003 oral lesions (74 pathologically confirmed premalignant or malignant and 929 benign) from patients with a mean age of 44.8 years. Of the lesions evaluated, concordance between exact clinical and histologic diagnoses was found in 61% of cases. Overall, the clinical impression, reported as benign versus premalignant or malignant, was 48.6% sensitive and 98.1% specific. Clinicians accurately identified lesions as benign in 95.9% of cases. The most common of these were fibromas (positive predictive value [PPV], 99.2%), mucoceles (PPV, 98.1%), and squamous papillomas (PPV, 96.3%). Several independent risk factors were associated with discrepancy: radiation therapy history (P = .0102), male gender (P = .0381), and patient age (P = .0468).
Conclusion: The results of this study suggest that the clinical impression, although highly accurate for common benign conditions, is not an acceptable alternative to definitive biopsy findings in other cases, particularly in cases of premalignancy or malignancy. In addition, patients with identified independent risk factors (age, gender, and radiation therapy) should receive timely biopsy examination. (C) 2015 American Association of Oral and Maxillofacial Surgeons
C1 [Forman, Michael S.; Chuang, Sung-Kiang; August, Meredith] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Chuang, Sung-Kiang; August, Meredith] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP August, M (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA.
EM maugust@partners.org
FU Department of Oral and Maxillofacial Surgery, Massachusetts General
Hospital; Harvard Medical School Scholars in Medicine Office; Oral and
Maxillofacial Surgery Foundation
FX This study was funded by the Education and Research Fund, Department of
Oral and Maxillofacial Surgery, Massachusetts General Hospital and the
Harvard Medical School Scholars in Medicine Office.; This investigation
was supported (in part) by a Student Research Training Award from the
Oral and Maxillofacial Surgery Foundation.
NR 12
TC 1
Z9 1
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 0278-2391
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD OCT
PY 2015
VL 73
IS 10
BP 1932
EP 1937
DI 10.1016/j.joms.2015.04.026
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CR3MO
UT WOS:000361237300016
PM 25981860
ER
PT J
AU Peacock, ZS
Magill, JC
Tricomi, BJ
Murphy, BA
Nikonovskiy, V
Hata, N
Chauvin, L
Troulis, MJ
AF Peacock, Zachary S.
Magill, John C.
Tricomi, Brad J.
Murphy, Brian A.
Nikonovskiy, Vladimir
Hata, Nobuhiko
Chauvin, Laurent
Troulis, Maria J.
TI Assessment of the OsteoMark-Navigation System for Oral and Maxillofacial
Surgery
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID DISTRACTION OSTEOGENESIS; MANDIBULAR DISTRACTION; ORTHOGNATHIC SURGERY;
SURGICAL NAVIGATION; RECONSTRUCTION; EXPERIENCE; NEURONAVIGATION;
ACCURACY; GUIDE; HEAD
AB Purpose: To assess the accuracy of a novel navigation system for maxillofacial surgery using human cadavers and a live minipig model.
Materials and Methods: We tested an electromagnetic tracking system (OsteoMark-Navigation) that uses simple sensors to determine the position and orientation of a hand-held pencil-like marking device. The device can translate 3-dimensional computed tomographic data intraoperatively to allow the surgeon to localize and draw a proposed osteotomy or the resection margins of a tumor on bone. The accuracy of the OsteoMark-Navigation system in locating and marking osteotomies and screw positions in human cadaver heads was assessed. In group 1 (n = 3, 6 sides), OsteoMark-Navigation marked osteotomies and screw positions were compared to virtual treatment plans. In group 2 (n = 3, 6 sides), marked osteotomies and screw positions for distraction osteogenesis devices were compared with those performed using fabricated guide stents. Three metrics were used to document the precision and accuracy. In group 3 (n = 1), the system was tested in a standard operating room environment.
Results: For group 1, the mean error between the points was 0.7 mm (horizontal) and 1.7 mm (vertical). Compared with the posterior and inferior mandibular border, the mean error was 1.2 and 1.7 mm, respectively. For group 2, the mean discrepancy between the points marked using the OsteoMark-Navigation system and the surgical guideswas 1.9 mm (range 0 to 4.1). The system maintained accuracy on a live minipig in a standard operating room environment.
Conclusion: Based on this research OsteoMark-Navigation is a potentially powerful tool for clinical use in maxillofacial surgery. It has accuracy and precision comparable to that of existing clinical applications. (C) 2015 American Association of Oral and Maxillofacial Surgeons
C1 [Peacock, Zachary S.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Magill, John C.; Murphy, Brian A.; Nikonovskiy, Vladimir] Phys Sci Inc, Andover, MA USA.
[Tricomi, Brad J.] Univ Massachusetts, Boston, MA 02125 USA.
[Tricomi, Brad J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hata, Nobuhiko] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Hata, Nobuhiko; Chauvin, Laurent] Brigham & Womens Hosp, Surg Nav & Robot Lab, Boston, MA 02115 USA.
RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA.
EM zpeacock@partners.org
FU National Institutes of Health/National Institute of Dental and
Craniofacial Research Small Business Innovation Research
[5R44DE019047-03]; Massachusetts General Hospital Department of Oral and
Maxillofacial Surgery Education and Research Fund; Hanson Foundation
(Boston, MA)
FX This work was funded by the National Institutes of Health/National
Institute of Dental and Craniofacial Research Small Business Innovation
Research (grant 5R44DE019047-03), the Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery Education and Research
Fund, and the Hanson Foundation (Boston, MA).
NR 28
TC 1
Z9 1
U1 1
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 0278-2391
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD OCT
PY 2015
VL 73
IS 10
BP 2005
EP 2016
DI 10.1016/j.joms.2015.03.017
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CR3MO
UT WOS:000361237300028
PM 25865717
ER
PT J
AU Susarla, SM
Swanson, EW
Lopez, J
Peacock, ZS
Dodson, TB
AF Susarla, Srinivas M.
Swanson, Edward W.
Lopez, Joseph
Peacock, Zachary S.
Dodson, Thomas B.
TI Does Self-Citation Influence Quantitative Measures of Research
Productivity Among Academic Oral and Maxillofacial Surgeons?
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID H-INDEX; UNITED-STATES; IMPACT FACTOR; JOURNALS; PUBLICATION; RADIOLOGY
AB Purpose: Quantitative measures of research productivity depend on the citation frequency of a publication. Citation-based metrics, such as the h-index (total number of publications h that have at least h citations), can be susceptible to self-citation, resulting in an inflated measure of research productivity. The purpose of the present study was to estimate the effect of self-citation on the h-index among academic oral and maxillofacial surgeons (OMSs).
Materials and Methods: The present study was a cross-sectional study of full-time academic OMSs in the United States. The predictor variable was the frequency of self-citation. The primary outcome of interest was the h-index. Other study variables included demographic factors and citation metrics. Descriptive, bivariate, and regression statistics were computed.
Results: The study sample consisted of 325 full-time academic OMSs. Most surgeons were men (88.3%); approximately 40% had medical degrees. The study subjects had an average of 23.5 +/- 37.1 publications. The mean number of self-citations was 15 + 56. The sample's mean h-index was 6.6 +/- 7.6 and was associated with self-citation (r = 0.71, P < .001). Approximately 9% of subjects had a change in their h-index after removing self-citations. After adjusting for PhD degree, total number of publications, and academic rank, an increasing self-citation rate influenced the h-index (r = 0.006, P < .001). Surgeons with more than 14 self-citations were more likely to have their h-index influenced by self-citation.
Conclusion: Self-citation among full-time academic OMSs does not substantially affect the h-index. Surgeons in the top quartile of self-citation rates are more likely to influence their h-index. (C) 2015 American Association of Oral and Maxillofacial Surgeons
C1 [Susarla, Srinivas M.; Swanson, Edward W.; Lopez, Joseph] Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA.
[Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Dodson, Thomas B.] Univ Washington, Sch Dent, Dept Oral & Maxillofacial Surg, Seattle, WA 98195 USA.
RP Susarla, SM (reprint author), Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, 601 North Caroline St,JHOC8, Baltimore, MD 21287 USA.
EM ssusarl1@jhmi.edu
OI Susarla, Srinivas/0000-0003-0155-8260
NR 25
TC 0
Z9 0
U1 3
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD OCT
PY 2015
VL 73
IS 10
DI 10.1016/j.joms.2015.05.018
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CR3MO
UT WOS:000361237300024
ER
PT J
AU Chua, AS
Egorova, S
Anderson, MC
Polgar-Turcsanyi, M
Chitnis, T
Weiner, HL
Guttmann, CRG
Bakshi, R
Healy, BC
AF Chua, Alicia S.
Egorova, Svetlana
Anderson, Mark C.
Polgar-Turcsanyi, Mariann
Chitnis, Tanuja
Weiner, Howard L.
Guttmann, Charles R. G.
Bakshi, Rohit
Healy, Brian C.
TI Using multiple imputation to efficiently correct cerebral MRI whole
brain lesion and atrophy data in patients with multiple sclerosis
SO NEUROIMAGE
LA English
DT Article
DE Multiple sclerosis; Multiple imputation; Magnetic resonance imaging;
Brain atrophy; T2 hyperintense lesion; Missing data
ID MAGNETIC-RESONANCE TECHNIQUES; QUANTITATIVE-ANALYSIS; MISSING DATA;
IMPAIRMENT; DISABILITY; BURDEN; AIDS; EDSS
AB Automated segmentation of brain MRI scans into tissue classes is commonly used for the assessment of multiple sclerosis (MS). However, manual correction of the resulting brain tissue label maps by an expert reader remains necessary in many cases. Since automated segmentation data awaiting manual correction are "missing", we proposed to use multiple imputation (MI) to fill-in the missing manually-corrected MRI data for measures of normalized whole brain volume (brain parenchymal fraction-BPF) and T2 hyperintense lesion volume (T2LV). Automated and manually corrected MRI measures from 1300 patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brighamand Women's Hospital (CLIMB) were identified. Simulation studies were conducted to assess the performance of MI with missing data both missing completely at random and missing at random. An imputation model including the concurrent automated data as well as clinical and demographic variables explained a high proportion of the variance in the manually corrected BPF (R-2 = 0.97) and T2LV (R-2 = 0.89), demonstrating the potential to accurately impute the missing data. Further, our results demonstrate that MI allows for the accurate estimation of group differences with little to no bias and with similar precision compared to an analysis with no missing data. We believe that our findings provide important insights for efficient correction of automated MRI measures to obviate the need to perform manual correction on all cases. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Chua, Alicia S.; Egorova, Svetlana; Anderson, Mark C.; Polgar-Turcsanyi, Mariann; Chitnis, Tanuja; Weiner, Howard L.; Guttmann, Charles R. G.; Bakshi, Rohit; Healy, Brian C.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA.
[Egorova, Svetlana; Chitnis, Tanuja; Weiner, Howard L.; Bakshi, Rohit; Healy, Brian C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Guttmann, Charles R. G.; Bakshi, Rohit] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Healy, BC (reprint author), Brigham & Womens Hosp, Partners MS Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
EM bchealy@partners.org
OI Egorova, Svetlana/0000-0002-9873-092X
FU Nancy Davis Foundation; Merck Serono S.A.
FX We would like to thank the reviewers for their constructive comments.
The CLIMB study is funded in part by the Nancy Davis Foundation and
Merck Serono S.A.
NR 29
TC 0
Z9 0
U1 0
U2 4
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 OCT 1
PY 2015
VL 119
BP 81
EP 88
DI 10.1016/j.neuroimage.2015.06.037
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CR2TB
UT WOS:000361182400009
PM 26093330
ER
PT J
AU Wood, KH
Wheelock, MD
Shumen, JR
Bowen, KH
Hoef, LWV
Knight, DC
AF Wood, Kimberly H.
Wheelock, Muriah D.
Shumen, Joshua R.
Bowen, Kenton H.
Hoef, Lawrence W. Ver
Knight, David C.
TI Controllability modulates the neural response to predictable but not
unpredictable threat in humans
SO NEUROIMAGE
LA English
DT Article
DE Prefrontal cortex; Hippocampus; Controllability; Predictability; Stress
resilience
ID POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; MEDIAL
PREFRONTAL CORTEX; DORSAL RAPHE NUCLEUS; SKIN-CONDUCTANCE RESPONSE;
INDIVIDUAL-DIFFERENCES; BRAIN ACTIVITY; PERCEIVED CONTROLLABILITY;
PHYSIOLOGICAL CONDITION; CONDITIONED DIMINUTION
AB Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Wood, Kimberly H.; Wheelock, Muriah D.; Shumen, Joshua R.; Bowen, Kenton H.; Knight, David C.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
[Hoef, Lawrence W. Ver] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Hoef, Lawrence W. Ver] Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
RP Knight, DC (reprint author), CIRC 235H,1720 2nd Ave S, Birmingham, AL 35294 USA.
EM knightdc@uab.edu
FU National Institutes of Health [MH098348]
FX This research was supported by National Institutes of Health grant
MH098348 (DCK).
NR 108
TC 3
Z9 4
U1 10
U2 19
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 OCT 1
PY 2015
VL 119
BP 371
EP 381
DI 10.1016/j.neuroimage.2015.06.086
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CR2TB
UT WOS:000361182400036
PM 26149610
ER
PT J
AU Cardenas, DP
Muir, ER
Huang, SL
Boley, A
Lodge, D
Duong, TQ
AF Cardenas, Damon P.
Muir, Eric R.
Huang, Shiliang
Boley, Angela
Lodge, Daniel
Duong, Timothy Q.
TI Functional MRI during hyperbaric oxygen: Effects of oxygen on
neurovascular coupling and BOLD fMRI signals
SO NEUROIMAGE
LA English
DT Article
DE Forepaw stimulation; CBF; Oxygen therapy; BOLD
ID CEREBRAL-BLOOD-FLOW; BRAIN; HYPEROXIA; HYPOXIA; HYPERCAPNIA; PERFUSION;
TENSION; DISEASE
AB Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) were compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2*-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O-2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2*-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Cardenas, Damon P.; Duong, Timothy Q.] Univ Texas San Antonio, Grad Sch Biomed Engn, San Antonio, TX USA.
[Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Muir, Eric R.; Huang, Shiliang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Boley, Angela; Lodge, Daniel] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA.
RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
FU NIH/NINDS [R01 NS45879]; NIH/NIMH [R01 MH090067]; NIH [T32HL007446]
FX This work was supported in part by the NIH/NINDS (R01 NS45879), NIH/NIMH
(R01 MH090067) and by NIH T32HL007446.
NR 17
TC 5
Z9 5
U1 1
U2 4
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 OCT 1
PY 2015
VL 119
BP 382
EP 389
DI 10.1016/j.neuroimage.2015.06.082
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CR2TB
UT WOS:000361182400037
PM 26143203
ER
PT J
AU Lin, Y
Mallen-St Clair, J
Luo, J
Sharma, S
Dubinett, S
St John, M
AF Lin, Yuan
Mallen-St Clair, Jon
Luo, Jie
Sharma, Sherven
Dubinett, Steven
St John, Maie
TI p53 modulates NF-kappa B mediated epithelial-to-mesenchymal transition
in head and neck squamous cell carcinoma
SO ORAL ONCOLOGY
LA English
DT Article
DE Head and neck cancer; Epithelial-to-mesenchymal transition; p53;
NF-kappa B; p65
ID ALPHA-INDUCED APOPTOSIS; TNF-ALPHA; CANCER-CELLS; CROSS-TALK;
ACTIVATION; EXPRESSION; BCL-2; PHOSPHORYLATION; TRANSCRIPTION;
PROGRESSION
AB Objectives: To investigate the role of p53 in NF-kappa B mediated epithelial-to-mesenchymal (EMT) in head and neck squamous cell carcinoma (HNSCC).
Materials and methods: We utilized HNSCC and normal oral epithelial cell lines as our model system. We used a lentiviral shRNA system to silence the expression of p65 and p53 in these cell lines. Mutant and wild-type (WT) p53 background genotypes were analyzed. The expression of epithelial and mesenchymal markers was determined using western blotting and quantitative PCR assays. Cell morphology, growth, and invasion were determined using a 3-dimensional spheroid culture and anchorage independent growth (AIG) assays.
Results: In HNSCC cells with mutant p53 we found that silencing p65 expression promoted EMT. In contrast, in the context of WT p53, ectopic p65 over-expression promoted EMT. Ablation of WT p53 in normal oral epithelial cells blocked EMT induced by p65 over-expression. We demonstrate that AIG and apoptosis induced by NF-kappa B activation is regulated by p53.
Conclusion: Our data demonstrates that p53 mutational status is critical in determining the outcome of NF-kappa B activation in HNSCC. In the presence of WT p53, excess p65 signal can promote EMT. Conversely, ablation of p65 in the context of mutant p53 drives EMT. These results demonstrate that p53 mutational status alters the outcome of NF-kappa B signaling. These results, though preliminary, demonstrate the critical role of p53 mutational status in determining the outcome of NF-kappa B signaling and suggest that monitoring p53 status may inform the utility of NF-kappa B inhibitor treatment in HNSCC. (c) 2015 Elsevier Ltd. All rights reserved.
C1 [Lin, Yuan; Mallen-St Clair, Jon; St John, Maie] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA.
[Lin, Yuan; Luo, Jie; Sharma, Sherven; Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA.
[Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Lin, Yuan; Sharma, Sherven; Dubinett, Steven; St John, Maie] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Sharma, Sherven; Dubinett, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP St John, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM mstjohn@mednet.ucla.edu
NR 41
TC 5
Z9 5
U1 0
U2 2
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 OCT
PY 2015
VL 51
IS 10
BP 921
EP 928
DI 10.1016/j.oraloncology.2015.07.006
PG 8
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA CR3NP
UT WOS:000361240200008
PM 26306422
ER
PT J
AU DePalo, J
Chai, X
Lee, SJ
Cutler, CS
Treister, N
AF DePalo, Joseph
Chai, Xiaoyu
Lee, Stephanie J.
Cutler, Corey S.
Treister, Nathaniel
TI Assessing the relationship between oral chronic graft-versus-host
disease and global measures of quality of life
SO ORAL ONCOLOGY
LA English
DT Article
DE Oral chronic graft-versus-host disease; Quality of life; Stem cell
transplantation
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; LONG-TERM
SURVIVORS; CLINICAL-TRIALS; CHRONIC GVHD; MARROW-TRANSPLANTATION;
FUNCTIONAL ASSESSMENT; CELL TRANSPLANTATION; IMPACT; CRITERIA
AB Objective: Chronic GVHD (cGVHD) is a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT) and affects multiple organ systems, with the oral cavity being one of the most frequently affected sites. Patients with cGVHD experience reduced quality of life (QOL), yet the specific impact of oral cGVHD on QOL is poorly understood. The objective of this study was to characterize the impact of oral cGVHD on global measures of QOL.
Materials and methods: QOL data were collected using the FACT-BMT and SF-36 instruments for 569 patients enrolled in the Chronic GVHD Consortium, with a total of 1915 follow-up visits. At study enrollment, patients were categorized as isolated oral cGVHD (n = 22), oral and concomitant extra-oral cGVHD (n = 420), and only extra-oral cGVHD (n = 127). Utilizing all longitudinal data, QOL scores were compared using a multivariable linear model controlling for demographic, transplant, and cGVHD characteristics.
Results: Patients with isolated oral cGVHD reported better physical well-being (P = 0.009), BMT wellbeing (P = 0.01), and decreased bodily pain (P = 0.01) compared to patients with oral and concomitant extra-oral cGVHD, but the differences in scores did not reach the defined threshold for clinical significance (6 points for FACT-BMT domains and 5 points for SF-36 domains).
Conclusions: Global QOL scores are similar in patients with isolated oral cGVHD and patients with oral and concomitant extra-oral cGVHD. (c) 2015 Elsevier Ltd. All rights reserved.
C1 [DePalo, Joseph] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Chai, Xiaoyu; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Cutler, Corey S.] Dana Farber Canc Inst, Hematol Malignancies, Boston, MA 02215 USA.
[Treister, Nathaniel] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA.
RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC 3-028, Boston, MA 02120 USA.
EM ntreister@partners.org
FU NCI NIH HHS [U01 CA118953, CA118953, R01 CA118953]
NR 30
TC 2
Z9 2
U1 1
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 OCT
PY 2015
VL 51
IS 10
BP 944
EP 949
DI 10.1016/j.oraloncology.2015.07.009
PG 6
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA CR3NP
UT WOS:000361240200011
PM 26277616
ER
PT J
AU Phillippe, M
AF Phillippe, Mark
TI Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition
SO REPRODUCTIVE SCIENCES
LA English
DT Review
DE parturition; cell-free fetal DNA; telomeres; placental DNA; apoptosis;
toll-like receptor-9; interleukin-10
ID SPONTANEOUS PRETERM DELIVERY; TOLL-LIKE RECEPTORS; NONINVASIVE
PRENATAL-DIAGNOSIS; MOUSE PERITONEAL-MACROPHAGES; MOLECULAR-PATTERNS
DAMPS; LOW-BIRTH-WEIGHT; MATERNAL PLASMA; HUMAN FIBROBLASTS;
GESTATIONAL-AGE; BACTERIAL-DNA
AB Multiple previous reports have provided compelling support for the premise that spontaneous parturition is mediated by activation of inflammation-related signaling pathways leading to increased secretion of cytokines and chemokines, the influx of neutrophils and macrophages into the pregnant uterus, increased production of uterine activation proteins (eg, connexin-43, cyclo-oxygenase-2, oxytocin receptors, etc), activation of matrix metalloproteinases, and the release of uterotonins leading to cervical ripening, membrane rupture, and myometrial contractions. The missing link has been the fetal/placental signal that triggers these proinflammatory events in the absence of microbial invasion and intrauterine infection. This article reviews the biomedical literature regarding the increase in cell-free fetal DNA (cffDNA), which is released during apoptosis in the placenta and fetal membranes at term, the ability of apoptosis modified vertebrate DNA to stimulate toll-like receptor-9 (TLR9) leading to increased release of cytokines and chemokines, and the potential fail-safe role for the anti-inflammatory cytokine IL-10. This article also reviews the literature supporting the key role that telomere loss plays in regard to increasing the ability of vertebrate (including placental) DNA to stimulate TLR9, and in regard to signaling the onset of apoptosis in the placenta and fetal membranes, thereby providing a biologic clock that determines the length of gestation and the timing for the onset of parturition. In summary, this literature review provides a strong rationale for future research to test the hypothesis that telomere loss and increased cffDNA levels trigger the proinflammatory events leading to the spontaneous onset of parturition in mammals: the cffDNA/telomere hypothesis.
C1 [Phillippe, Mark] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
RP Phillippe, M (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, 55 Fruit St,Thier Bldg 911, Boston, MA 02114 USA.
EM MPhillippe@MGH.Harvard.Edu
FU Vincent Center for Reproductive Biology, Massachusetts General Hospital,
Boston, MA
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: I received
financial support for the research, authorship and publication of this
article from the Vincent Center for Reproductive Biology, Massachusetts
General Hospital, Boston, MA.
NR 143
TC 5
Z9 5
U1 4
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD OCT
PY 2015
VL 22
IS 10
BP 1186
EP 1201
DI 10.1177/1933719115592714
PG 16
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CR7LD
UT WOS:000361530300002
PM 26134037
ER
PT J
AU Tiourin, E
Velasco, VS
Rosales, MA
Sullivan, PS
Janzen, DM
Memarzadeh, S
AF Tiourin, Ekaterina
Velasco, Victor S.
Rosales, Miguel A.
Sullivan, Peggy S.
Janzen, Deanna M.
Memarzadeh, Sanaz
TI Tubal Ligation Induces Quiescence in the Epithelia of the Fallopian Tube
Fimbria
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE fallopian epithelial progenitors; tubal ligation; fallopian tube
epithelial proliferation
ID SEROUS OVARIAN-CANCER; DIVERTING COLOSTOMY; IMAGE-ANALYSIS;
STERILIZATION; ANASTOMOSIS; CARCINOMA; CELLS; RISK; EXPRESSION; SYSTEM
AB Tubal ligation keeps the fimbriated end of the fallopian tube intact while interrupting the conduit for sperm and egg between the uterus and ovary. Tubal ligation is associated with an approximately 20% decreased risk of high-grade serous ovarian cancers, which mounting evidence suggests arise from the distal fallopian tube epithelium. We postulated that biological changes at the epithelial cellular level of the distal fallopian tube may account for the surgical procedure's observed risk reduction. We compared the histology, presence of epithelial progenitors (basally located CD44-positive cells), and degree of epithelial proliferation (Ki67-positive cells) of distal fallopian tube from 10 patients with previous tubal ligation and 10 age-matched patients with uncut fallopian tubes. A significantly reduced population of proliferating epithelial progenitors (basally located CD44/Ki67 dual-positive cells) was detected in the tubal ligated specimens (P = .0002). To functionally assess the effect of tubal ligation, a murine model was utilized to compare the growth capacity of distal fallopian tube epithelial cells isolated from either ligated or sham-operated tubal epithelia. Murine fallopian tube epithelial cells isolated after tubal ligation showed a significantly reduced capacity to grow organoids in culture compared to sham-operated controls (P = .002). The findings of this study show that tubal ligation is associated with a reduced presence and decreased proliferation of progenitor cells in the distal fallopian tube epithelium. These compositional and functional changes suggest that tubal ligation induces quiescence of distal fallopian tube epithelial cells.
C1 [Tiourin, Ekaterina; Velasco, Victor S.; Rosales, Miguel A.; Janzen, Deanna M.; Memarzadeh, Sanaz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Sullivan, Peggy S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Memarzadeh, Sanaz] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
[Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
RP Memarzadeh, S (reprint author), Univ Calif Los Angeles, 555 Westwood Plaza,Level B,Box 957243, Los Angeles, CA 90095 USA.
EM smemarzadeh@mednet.ucla.edu
FU VA CDA-2 Award; CDU/UCLA NIH/NCI [U54-CA-143931]; Sidney Kimmel
Foundation; Concern foundation; Jonsson Comprehensive Cancer Center Seed
grant; NIH/National Center for Advancing Translational Science (NCATS)
UCLA CTSI [UL1TR000124]; Leath L. and Marcia L. Millen Family Fund;
Ovarian Cancer Circle; Gynecologic Oncology (GO) Discovery Lab
Foundation
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: SM is
supported by a VA CDA-2 Award, the CDU/UCLA NIH/NCI Grant #U54-CA-143931
award, a Sidney Kimmel Foundation award, the Concern foundation, The
Jonsson Comprehensive Cancer Center Seed grant, the NIH/National Center
for Advancing Translational Science (NCATS) UCLA CTSI Grant Number
UL1TR000124, the Leath L. and Marcia L. Millen Family Fund, the Ovarian
Cancer Circle Inspired by Robin Babbini, and the Gynecologic Oncology
(GO) Discovery Lab Foundation.
NR 43
TC 0
Z9 0
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD OCT
PY 2015
VL 22
IS 10
BP 1262
EP 1271
DI 10.1177/1933719115574345
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CR7LD
UT WOS:000361530300010
PM 25736327
ER
PT J
AU Rosenberg, SM
Newman, LA
Partridge, AH
AF Rosenberg, Shoshana M.
Newman, Lisa A.
Partridge, Ann H.
TI Breast Cancer in Young Women Rare Disease or Public Health Problem?
SO JAMA ONCOLOGY
LA English
DT Editorial Material
C1 [Rosenberg, Shoshana M.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Newman, Lisa A.] Univ Michigan, Ctr Comprehens Canc, Breast Care Ctr, Ann Arbor, MI 48109 USA.
RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM ann_partridge@dfci.harvard.edu
NR 7
TC 6
Z9 6
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 877
EP 878
DI 10.1001/jamaoncol.2015.2112
PG 2
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900002
PM 26204453
ER
PT J
AU MacConaill, LE
Lindeman, NI
Rollins, BJ
AF MacConaill, Laura E.
Lindeman, Neal I.
Rollins, Barrett J.
TI Brave-ish New World-What's Needed to Make Precision Oncology a Practical
Reality
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID LUNG-CANCER; MUTATIONS; GEFITINIB; PARADIGM
C1 [MacConaill, Laura E.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[MacConaill, Laura E.; Lindeman, Neal I.; Rollins, Barrett J.] Havard Med Sch, Boston, MA USA.
[Rollins, Barrett J.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM barrett_rollins@dfci.harvard.edu
NR 9
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 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 879
EP 880
DI 10.1001/jamaoncol.2015.1540
PG 2
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900003
PM 26181886
ER
PT J
AU Gray, PJ
Zietman, AL
AF Gray, Phillip J.
Zietman, Anthony L.
TI Dose-Escalated Radiotherapy for Prostate Cancer Is the Sky the Limit?
SO JAMA ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PROTON RADIATION; THERAPY; COLLEGE
C1 [Gray, Phillip J.; Zietman, Anthony L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA.
RP Gray, PJ (reprint author), Massachusetts Gen, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA.
EM pjgray@partners.org
NR 14
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 883
EP 884
DI 10.1001/jamaoncol.2015.2419
PG 3
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900005
PM 26181340
ER
PT J
AU Rettig, EM
Wentz, A
Posner, MR
Gross, ND
Haddad, RI
Gillison, ML
Fakhry, C
Quon, H
Sikora, AG
Stott, WJ
Lorch, JH
Gourin, CG
Guo, YS
Xiao, WH
Miles, BA
Richmon, JD
Andersen, PE
Misiukiewicz, KJ
Chung, CH
Gerber, JE
Rajan, SD
D'Souza, G
AF Rettig, Eleni M.
Wentz, Alicia
Posner, Marshall R.
Gross, Neil D.
Haddad, Robert I.
Gillison, Maura L.
Fakhry, Carole
Quon, Harry
Sikora, Andrew G.
Stott, William J.
Lorch, Jochen H.
Gourin, Christine G.
Guo, Yingshi
Xiao, Weihong
Miles, Brett A.
Richmon, Jeremy D.
Andersen, Peter E.
Misiukiewicz, Krzysztof J.
Chung, Christine H.
Gerber, Jennifer E.
Rajan, Shirani D.
D'Souza, Gypsyamber
TI Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA
Detection in Oral Rinses for Human Papillomavirus-Related Oropharyngeal
Carcinoma
SO JAMA ONCOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HPV INFECTION; NECK-CANCER; UNITED-STATES;
HEAD; SURVIVAL; RISK; RECURRENT; PROGRESSION; TRIAL
AB IMPORTANCE Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear.
OBJECTIVE To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival.
DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study.
MAIN OUTCOMES AND MEASURES Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis.
RESULTS Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92%(95% CI, 94%-100%) and 98%(95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.
CONCLUSIONS AND RELEVANCE Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.
C1 [Rettig, Eleni M.; Fakhry, Carole; Gourin, Christine G.; Richmon, Jeremy D.; Chung, Christine H.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
[Wentz, Alicia; Fakhry, Carole; D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6132B, Baltimore, MD 21205 USA.
[Posner, Marshall R.; Misiukiewicz, Krzysztof J.] Mt Sinai Med Ctr, Icahn Sch Med, Head & Neck Oncol Ctr, Tisch Canc Inst, New York, NY 10029 USA.
[Gross, Neil D.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Div Surg, Houston, TX 77030 USA.
[Haddad, Robert I.; Lorch, Jochen H.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Gillison, Maura L.; Guo, Yingshi; Xiao, Weihong] Ohio State Univ, Ctr Comprehens Canc, Viral Oncol Program, Columbus, OH 43210 USA.
[Quon, Harry] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD USA.
[Sikora, Andrew G.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA.
[Stott, William J.; Andersen, Peter E.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA.
[Miles, Brett A.] Mt Sinai Med Ctr, Icahn Sch Med, Dept Otolaryngol, New York, NY 10029 USA.
[Chung, Christine H.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Gerber, Jennifer E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Rajan, Shirani D.] Louisiana State Univ, Sch Med, New Orleans, LA USA.
RP D'Souza, G (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6132B, Baltimore, MD 21205 USA.
EM gdsouza2@jhu.edu
FU Johns Hopkins Richard Gelb Cancer Prevention Award; Oral Cancer
Foundation; National Institute of Dental and Craniofacial Research and
National Institutes of Health (NIH) Research Training in Otolaryngology
[2T32DC000027-26]
FX This research was supported financially by the Johns Hopkins Richard
Gelb Cancer Prevention Award (Dr D'Souza), the Oral Cancer Foundation
(Dr D'Souza), and the National Institute of Dental and Craniofacial
Research and National Institutes of Health (NIH) Research Training in
Otolaryngology grant 2T32DC000027-26 (Dr Rettig).
NR 26
TC 12
Z9 12
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 907
EP 915
DI 10.1001/jamaoncol.2015.2524
PG 9
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900008
PM 26226294
ER
PT J
AU Tanguturi, S
Bellon, JR
AF Tanguturi, ShyamK.
Bellon, Jennifer R.
TI Hypofractionation for Early-Stage Breast Cancer No More Excuses
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID RADIOTHERAPY HYPOFRACTIONATION; UK STANDARDIZATION; RADIATION-THERAPY;
TRIALS
C1 [Tanguturi, ShyamK.] Harvard Radiat Oncol Program, Boston, MA USA.
[Bellon, Jennifer R.] Harvard Med Sch, Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA.
RP Bellon, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM jbellon@lroc.harvard.edu
NR 9
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 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 941
EP 942
DI 10.1001/jamaoncol.2015.2605
PG 3
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900012
PM 26247338
ER
PT J
AU Desmond, A
Kurian, A
Gabree, M
Mills, MA
Anderson, MJ
Kobayashi, Y
Horick, N
Yang, S
Shannon, KM
Tung, N
Ford, J
Lincoln, SE
Ellisen, L
AF Desmond, Andrea
Kurian, AllisonW.
Gabree, Michele
Mills, Meredith A.
Anderson, Michael J.
Kobayashi, Yuya
Horick, Nora
Yang, Shan
Shannon, Kristen M.
Tung, Nadine
Ford, JamesM.
Lincoln, Stephen E.
Ellisen, Leifw.
TI Clinical Actionability of Multigene Panel Testing for Hereditary Breast
and Ovarian Cancer Risk Assessment
SO JAMA ONCOLOGY
LA English
DT Article
ID NEXT-GENERATION; GERMLINE MUTATIONS; GENES; SUSCEPTIBILITY; FAMILIES;
GENETICS; RAD51C; WOMEN; PALB2; ATM
AB IMPORTANCE The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown.
OBJECTIVE To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort.
DESIGN, SETTING, AND PARTICIPANTS Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations.
INTERVENTIONS We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals.
MAIN OUTCOMES AND MEASURES We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history.
RESULTS Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients.
CONCLUSIONS AND RELEVANCE In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.
C1 [Desmond, Andrea; Gabree, Michele; Horick, Nora; Shannon, Kristen M.; Ellisen, Leifw.] Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,GRJ 904, Boston, MA 02114 USA.
[Kurian, AllisonW.; Mills, Meredith A.; Ford, JamesM.] Stanford Univ, Sch Med, Stanford, CA USA.
[Anderson, Michael J.; Kobayashi, Yuya; Yang, Shan; Lincoln, Stephen E.] Invitae Corp, San Francisco, CA USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tung, Nadine; Ellisen, Leifw.] Harvard Med Sch, Boston, MA USA.
RP Ellisen, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,GRJ 904, Boston, MA 02114 USA.
EM lellisen@mgh.harvard.edu
FU MGH Friends Fighting Breast Cancer; Tracey Davis Memorial Fund; Breast
Cancer Research Foundation
FX This study was funded by unrestricted philanthropic gifs from the MGH
Friends Fighting Breast Cancer and the Tracey Davis Memorial Fund (Ms
Desmond and Dr Ellisen) and by the Breast Cancer Research Foundation
(Drs Kurian and Ford).
NR 32
TC 29
Z9 29
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 943
EP 951
DI 10.1001/jamaoncol.2015.2690
PG 9
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900013
PM 26270727
ER
PT J
AU Shoag, J
Halpern, J
Eisner, B
Lee, R
Mittal, S
Barbieri, CE
Shoag, D
AF Shoag, Jonathan
Halpern, Joshua
Eisner, Brian
Lee, Richard
Mittal, Sameer
Barbieri, Christopher E.
Shoag, Daniel
TI Efficacy of Prostate-Specific Antigen Screening: Use of Regression
Discontinuity in the PLCO Cancer Screening Trial
SO JAMA ONCOLOGY
LA English
DT Letter
ID RANDOMIZED PROSTATE
C1 [Shoag, Jonathan; Halpern, Joshua; Lee, Richard; Mittal, Sameer; Barbieri, Christopher E.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Urol, 525 E 68th St,Starr 900, New York, NY 10021 USA.
[Eisner, Brian] Massachusetts Gen Hosp, Dept Urol, Boston, MA USA.
[Shoag, Daniel] Harvard Kennedy Sch, Dept Publ Policy, Cambridge, MA USA.
RP Shoag, J (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Urol, 525 E 68th St,Starr 900, New York, NY 10021 USA.
EM Jes9171@nyp.org
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD OCT
PY 2015
VL 1
IS 7
BP 983
EP 986
DI 10.1001/jamaoncol.2015.2993
PG 4
WC Oncology
SC Oncology
GA DW5HX
UT WOS:000383675900022
ER
PT J
AU Ruggiero, KJ
Bunnell, BE
Andrews, AR
Davidson, TM
Hanson, RF
Danielson, CK
Saunders, BE
Soltis, K
Yarian, C
Chu, B
Adams, ZW
AF Ruggiero, Kenneth J.
Bunnell, Brian E.
Andrews, Arthur R., III
Davidson, Tatiana M.
Hanson, Rochelle F.
Danielson, Carla Kmett
Saunders, Benjamin E.
Soltis, Kathryn
Yarian, Caleb
Chu, Brian
Adams, Zachary W.
TI Development and Pilot Evaluation of a Tablet-Based Application to
Improve Quality of Care in Child Mental Health Treatment
SO JMIR RESEARCH PROTOCOLS
LA English
DT Article
DE technology; mobile health; child mental health treatment; feasibility
test; fidelity; patient engagement; traumatic stress
ID REPLICATION-ADOLESCENT SUPPLEMENT; POSTTRAUMATIC-STRESS-DISORDER;
RANDOMIZED-CONTROLLED-TRIAL; PROVIDERS PERSPECTIVES; COMMUNITY
TREATMENT; PHONE APPLICATION; TRAUMATIC EVENTS; PTSD SYMPTOMS;
DEPRESSION; FIDELITY
AB Background: Children need access to high quality mental health care. Effective treatments now exist for a wide range of mental health conditions. However, these interventions are delivered with variable effectiveness in traditional mental health service settings. Innovative solutions are needed to improve treatment delivery quality and effectiveness.
Objective: The aim of this study was to develop a scalable, sustainable technology-based approach to improve the quality of care in child mental health treatment.
Methods: A tablet-based resource was developed with input from mental health training experts, mental health providers, and patients. A series of qualitative data collection phases (ie, expert interviews, patient and provider focus groups, usability testing) guided the initial concept and design of the resource, and then its refinement. The result was an iPad-based "e-workbook" designed to improve child engagement and provider fidelity in implementation of a best-practice treatment. We are currently conducting a small scale randomized controlled trial to evaluate the feasibility of e-workbook facilitated child mental health treatment with 10 providers and 20 families recruited from 4 local community-based mental health clinics.
Results: Usability and focus group testing yielded a number of strong, favorable reactions from providers and families. Recommendations for refining the e-workbook also were provided, and these guided several improvements to the resource prior to initiating the feasibility trial, which is currently underway.
Conclusions: This study aimed to develop and preliminarily evaluate a tablet-based application to improve provider fidelity and child engagement in child mental health treatment. If successful, this approach may serve as a key step toward making best-practice treatment more accessible to children and families. As various technologies continue to increase in popularity worldwide and within the health care field more specifically, it is essential to rigorously test the usability, feasibility, acceptability, and effectiveness of novel health technology solutions. It is also essential to ensure that patients and providers drive decision making that supports the development of these resources to ensure that they can be seamlessly integrated into practice.
C1 [Ruggiero, Kenneth J.; Bunnell, Brian E.; Davidson, Tatiana M.; Soltis, Kathryn] Med Univ South Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, 99 Jonathan Lucas St, Charleston, SC 29425 USA.
[Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Andrews, Arthur R., III; Davidson, Tatiana M.; Hanson, Rochelle F.; Danielson, Carla Kmett; Saunders, Benjamin E.; Soltis, Kathryn; Adams, Zachary W.] Med Univ South Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 171 Ashley Ave, Charleston, SC 29425 USA.
[Yarian, Caleb] Fuzzco, Charleston, SC USA.
[Chu, Brian] Rutgers State Univ, Piscataway, NJ USA.
RP Ruggiero, KJ (reprint author), Med Univ South Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, 99 Jonathan Lucas St, Charleston, SC 29425 USA.
EM ruggierk@musc.edu
OI Andrews III, Arthur/0000-0001-9071-0089; Chu, Brian/0000-0003-0275-1599
FU National Institute of Mental Health [R34-MH096907, R01-MH81056,
R34-MH104470, T32-MH18869]; National Institute on Drug Abuse
[K12-DA031794, K23-DA038257, R01-DA031285]; Substance Abuse and Mental
Health Services Administration [U79-SM061269]
FX We thank Judy Cohen, MD, Esther Deblinger, PhD, and Anthony Mannarino,
PhD, who developed TF-CBT and have provided valuable input and feedback
throughout every phase of this project. We thank Ben Jacobs of Fuzzco
for his significant role in the design and development process of the
TF-CBT e-workbook. We thank Josh Nissenboim of Fuzzco for his leadership
and partnership in support of this project and related research. We
thank Joel Sherrill of NIMH for his thoughtful feedback on early
conceptualizations of this project. We also thank the families and
providers who participated in this study for their time and insights.
This research and the authors' time and effort were supported by
National Institute of Mental Health grants R34-MH096907, R01-MH81056,
R34-MH104470, and T32-MH18869; National Institute on Drug Abuse grants
K12-DA031794, K23-DA038257, and R01-DA031285; and Substance Abuse and
Mental Health Services Administration grant U79-SM061269. None of these
funding agencies were involved in the design of the study; the
collection, analysis, or interpretation of data; the writing of the
manuscript, or the decision to submit the manuscript for publication.
NR 62
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U1 0
U2 0
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1929-0748
J9 JMIR RES PROTOC
JI JMIR RES. Protoc.
PD OCT-DEC
PY 2015
VL 4
IS 4
AR e143
DI 10.2196/resprot.4416
PG 18
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA EI2LT
UT WOS:000392319500010
PM 26717906
ER
PT J
AU Lien, YAS
Calabrese, CR
Michener, CM
Murray, EH
Van Stan, JH
Mehta, DD
Hillman, RE
Noordzij, JP
Stepp, CE
AF Lien, Yu-An S.
Calabrese, Carolyn R.
Michener, Carolyn M.
Murray, Elizabeth Heller
Van Stan, Jarrad H.
Mehta, Daryush D.
Hillman, Robert E.
Noordzij, J. Pieter
Stepp, Cara E.
TI Voice Relative Fundamental Frequency Via Neck-Skin Acceleration in
Individuals With Voice Disorders
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Article
ID VOCAL HYPERFUNCTION; SPASMODIC DYSPHONIA; OFFSET; ONSET; ACCUMULATOR;
SPEAKERS; DISEASE
AB Purpose: This study investigated the use of neck-skin acceleration for relative fundamental frequency (RFF) analysis.
Method: Forty individuals with voice disorders associated with vocal hyperfunction and 20 age-and sex-matched control participants were recorded with a subglottal neck-surface accelerometer and a microphone while producing speech stimuli appropriate for RFF. Rater reliabilities, RFF means, and RFF standard deviations derived from the accelerometer were compared with those derived from the microphone.
Results: RFF estimated from the accelerometer had slightly higher intrarater reliability and identical interrater reliability compared with values estimated with the microphone. Although sensor type and the Vocal Cycle x Sensor and Vocal Cycle x Sensor x Group interactions showed significant effects on RFF means, the typical RFF pattern could be derived from either sensor. For both sensors, the RFF of individuals with vocal hyperfunction was lower than that of the controls. Sensor type and its interactions did not have significant effects on RFF standard deviations.
Conclusions: RFF can be reliably estimated using an accelerometer, but these values cannot be compared with those collected via microphone. Future studies are needed to determine the physiological basis of RFF and examine the effect of sensors on RFF in practical voice assessment and monitoring settings.
C1 [Lien, Yu-An S.; Calabrese, Carolyn R.; Michener, Carolyn M.; Murray, Elizabeth Heller; Noordzij, J. Pieter; Stepp, Cara E.] Boston Univ, Boston, MA 02215 USA.
[Van Stan, Jarrad H.; Mehta, Daryush D.; Hillman, Robert E.] MGH Inst Hlth Profess, Boston, MA USA.
[Van Stan, Jarrad H.; Mehta, Daryush D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Mehta, Daryush D.; Hillman, Robert E.] Harvard Med Sch, Cambridge, MA USA.
[Noordzij, J. Pieter; Stepp, Cara E.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Stepp, CE (reprint author), Boston Univ, Boston, MA 02215 USA.
EM cstepp@bu.edu
FU National Institute on Deafness and Other Communication Disorders
[DC012651, DC011588]; New Century Scholars Research Grant from the
American Speech-Language-Hearing Foundation
FX This work was supported by National Institute on Deafness and Other
Communication Disorders Grants DC012651 (awarded to Cara E. Stepp) and
DC011588 (awarded to Robert E. Hillman) and a New Century Scholars
Research Grant from the American Speech-Language-Hearing Foundation
(awarded to Cara E. Stepp). Thanks to Defne Abur, Christina Stevens, and
Alexandra Martinson for assistance with data recording and to Melissa
Cooke, Amanda Fryd, and Molly Bresnahan for help with recording
segmentation. We disclose that author Robert E. Hillman has a financial
relationship with Pentax Medical with respect to the Ambulatory
Phonation Monitor.
NR 31
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U1 0
U2 0
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 2200 RESEARCH BLVD, #271, ROCKVILLE, MD 20850-3289 USA
SN 1092-4388
EI 1558-9102
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD OCT
PY 2015
VL 58
IS 5
BP 1482
EP 1487
DI 10.1044/2015_JSLHR-S-15-0126
PG 6
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA DX6XL
UT WOS:000384529200007
PM 26134171
ER
PT J
AU Deliyski, DD
Hillman, RE
Mehta, DD
AF Deliyski, Dimitar D.
Hillman, Robert E.
Mehta, Daryush D.
TI Laryngeal High-Speed Videoendoscopy: Rationale and Recommendation for
Accurate and Consistent Terminology
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Letter
ID VOCAL-FOLD VIBRATIONS; HEALTHY-SUBJECTS; OPEN QUOTIENT; IMAGES; FORM;
ASYMMETRY; PHONOVIBROGRAPHY; STROBOSCOPY; RECORDINGS; PHYSIOLOGY
AB Purpose: The authors discuss the rationale behind the term laryngeal high-speed videoendoscopy to describe the application of high-speed endoscopic imaging techniques to the visualization of vocal fold vibration.
Method: Commentary on the advantages of using accurate and consistent terminology in the field of voice research is provided. Specific justification is described for each component of the term high-speed videoendoscopy, which is compared and contrasted with alternative terminologies in the literature.
Results: In addition to the ubiquitous high-speed descriptor, the term endoscopy is necessary to specify the appropriate imaging technology and distinguish among modalities such as ultrasound, magnetic resonance imaging, and nonendoscopic optical imaging. Furthermore, the term video critically indicates the electronic recording of a sequence of optical still images representing scenes in motion, in contrast to strobed images using high-speed photography and nonoptical high-speed magnetic resonance imaging. High-speed videoendoscopy thus concisely describes the technology and can be appended by the desired anatomical nomenclature such as laryngeal.
Conclusions: Laryngeal high-speed videoendoscopy strikes a balance between conciseness and specificity when referring to the typical high-speed imaging method performed on human participants. Guidance for the creation of future terminology provides clarity and context for current and future experiments and the dissemination of results among researchers.
C1 [Deliyski, Dimitar D.] Cincinnati Childrens Hosp Med Ctr, Commun Sci Res Ctr, Cincinnati, OH 45229 USA.
[Deliyski, Dimitar D.] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Hillman, Robert E.; Mehta, Daryush D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Hillman, Robert E.; Mehta, Daryush D.] Harvard Med Sch, Boston, MA USA.
[Hillman, Robert E.; Mehta, Daryush D.] Massachusetts Gen Hosp, Inst Hlth Profess, Charlestown, MA USA.
RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
EM daryush.mehta@alum.mit.edu
FU National Institute on Deafness and Other Communication Disorders [R01
DC007640]; Voice Health Institute
FX This work was supported by a grant from the National Institute on
Deafness and Other Communication Disorders (R01 DC007640), awarded to
Dimitar D. Deliyski, and by the Voice Health Institute. The article's
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health.
NR 57
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Z9 1
U1 0
U2 0
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 2200 RESEARCH BLVD, #271, ROCKVILLE, MD 20850-3289 USA
SN 1092-4388
EI 1558-9102
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD OCT
PY 2015
VL 58
IS 5
BP 1488
EP 1492
DI 10.1044/2015_JSLHR-S-14-0253
PG 5
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA DX6XL
UT WOS:000384529200008
PM 26375398
ER
PT J
AU Adler, JT
Yeh, H
Markmann, JF
Nguyen, LL
AF Adler, Joel T.
Yeh, Heidi
Markmann, James F.
Nguyen, Louis L.
TI The pathway to renal transplantation: obstacles and contributions to
disparities
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 101st Annual Clinical Congress of the American-College-of-Surgeons (ACS)
CY OCT 04-10, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Adler, Joel T.; Yeh, Heidi; Markmann, James F.; Nguyen, Louis L.] Massachusetts Gen Hosp, Brigham & Womens Hosptial, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 2
BP E138
EP E138
PG 1
WC Surgery
SC Surgery
GA EA8PP
UT WOS:000386899000338
ER
PT J
AU De Gregorio, L
Lubitz, CC
Hunter, GJ
Hodin, RA
Gaz, RD
Parangi, S
Stephen, AE
AF De Gregorio, Lucia
Lubitz, Carrie C.
Hunter, George J.
Hodin, Richard A.
Gaz, Randall D.
Parangi, Sareh
Stephen, Antonia E.
TI Should 4DCT replace sestamibi as a primary localization modality in
primary hyperparathyroidism?
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 101st Annual Clinical Congress of the American-College-of-Surgeons (ACS)
CY OCT 04-10, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [De Gregorio, Lucia; Lubitz, Carrie C.; Hunter, George J.; Hodin, Richard A.; Gaz, Randall D.; Parangi, Sareh; Stephen, Antonia E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 2
BP E80
EP E80
PG 1
WC Surgery
SC Surgery
GA EA8PP
UT WOS:000386899000191
ER
PT J
AU Hall, DE
Stone, RA
Feske, U
Ling, B
Shasha, G
Zickmund, S
Zhang, SJ
Arnold, R
AF Hall, Daniel E.
Stone, Roslyn A.
Feske, Ulrike
Ling, Bruce
Shasha, Gao
Zickmund, Susan
Zhang, Sijian
Arnold, Robert
TI Systematic bias against expedited review procedures across institutional
review boards (IRBs) in the Veterans Health Administration (VHA)
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 101st Annual Clinical Congress of the American-College-of-Surgeons (ACS)
CY OCT 04-10, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 2
BP E14
EP E14
PG 1
WC Surgery
SC Surgery
GA EA8PP
UT WOS:000386899000031
ER
PT J
AU Hall, DE
AF Hall, Daniel E.
TI Practical wisdom provides ethical justification for the negotiation and
enforcement of surgical buy-in
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 101st Annual Clinical Congress of the American-College-of-Surgeons (ACS)
CY OCT 04-10, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Hall, Daniel E.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 2
BP E13
EP E14
PG 2
WC Surgery
SC Surgery
GA EA8PP
UT WOS:000386899000030
ER
PT J
AU Bassett, IV
Regan, S
Mbonambi, H
Blossom, J
Bogan, S
Bearnot, B
Robine, M
Walensky, RP
Mhlongo, B
Freedberg, KA
Thulare, H
Losina, E
AF Bassett, Ingrid V.
Regan, Susan
Mbonambi, Hlengiwe
Blossom, Jeffrey
Bogan, Stacy
Bearnot, Benjamin
Robine, Marion
Walensky, Rochelle P.
Mhlongo, Bright
Freedberg, Kenneth A.
Thulare, Hilary
Losina, Elena
TI Finding HIV in Hard to Reach Populations: Mobile HIV Testing and
Geospatial Mapping in Umlazi Township, Durban, South Africa
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Geospatial analysis; HIV mobile testing; South Africa
ID RURAL MOZAMBIQUE; CARE; HIV/AIDS; INITIATION; COMMUNITY; SERVICES;
LINKAGE; SYSTEM; STIGMA; RISK
AB Mobile, community-based HIV testing may help achieve universal HIV testing in South Africa. We compared the yield, geographic distribution, and demographic characteristics of populations tested by mobile- and clinic-based HIV testing programs deployed by iThembalabantu Clinic in Durban, South Africa. From July to November 2011, 4,701 subjects were tested; HIV prevalence was 35 % among IPHC testers and 10 % among mobile testers (p < 0.001). Mobile testers varied in mean age (22-37 years) and % males (26-67 %). HIV prevalence at mobile sites ranged from 0 to 26 %. Testers traveled further than the clinic closest to their home; mobile testers were more likely to test a parts per thousand yen5 km away from home. Mobile HIV testing can improve testing access and identify testing sites with high HIV prevalence. Individuals often access mobile testing sites farther from home than their nearest clinic. Geospatial techniques can help optimize deployment of mobile units to maximize yield in hard-to-reach populations.
C1 [Bassett, Ingrid V.; Regan, Susan; Robine, Marion; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Bassett, Ingrid V.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Bassett, Ingrid V.; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Harvard Ctr AIDS Res, Boston, MA 02115 USA.
[Bassett, Ingrid V.; Bearnot, Benjamin; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Mbonambi, Hlengiwe; Mhlongo, Bright; Thulare, Hilary] AIDS Healthcare Fdn, iThembalabantu Peoples Hope Clin, Durban, South Africa.
[Blossom, Jeffrey; Bogan, Stacy] Harvard Ctr Geog Anal, Cambridge, MA USA.
[Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,Floor 9, Boston, MA 02114 USA.
EM ibassett@partners.org
FU National Institute of Allergy and Infectious Diseases; National
Institute of Mental Health of the National Institutes of Health [R01
MH090326, R01 AI058736, R01 MH073445]; AIDS Healthcare Foundation;
Harvard Center for AIDS Research [P30 AI042851]
FX We would like to acknowledge the assistance of Njabulo Mabaso and
Philisiwe Luthuli and the dedication of the research team at the
iThembalabantu People's Hope Clinic. Research reported in this
publication was supported by the National Institute of Allergy and
Infectious Diseases and National Institute of Mental Health of the
National Institutes of Health under Awards R01 MH090326, R01 AI058736
and R01 MH073445. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health. This Project was also supported by the
AIDS Healthcare Foundation and the Harvard Center for AIDS Research (P30
AI042851).
NR 34
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Z9 4
U1 2
U2 7
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 OCT
PY 2015
VL 19
IS 10
BP 1888
EP 1895
DI 10.1007/s10461-015-1012-3
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CR0HK
UT WOS:000360999000016
PM 25874754
ER
PT J
AU Holland, CM
Ritchie, ND
Du Bois, SN
AF Holland, Christine M.
Ritchie, Natalie D.
Du Bois, Steve N.
TI iTunes Song-Gifting is a Low-Cost, Efficient Recruitment Tool to Engage
High-Risk MSM in Internet Research
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Internet research methodology; Recruitment; Incentives; Men who have sex
with men; HIV/STI prevention
ID MEN; SEX; PREVENTION; GAY
AB This brief report describes methodology and results of a novel, efficient, and low-cost recruitment tool to engage high-risk MSM in online research. We developed an incentivization protocol using iTunes song-gifting to encourage participation of high-risk MSM in an Internet-based survey of HIV status, childhood sexual abuse, and adult behavior and functioning. Our recruitment methodology yielded 489 participants in 4.5 months at a total incentive cost of $1.43USD per participant. The sample comprised a critically high-risk group of MSM, including 71.0 % who reported recent condomless anal intercourse. We offer a "how-to" guide to aid future investigators in using iTunes song-gifting incentives.
C1 [Holland, Christine M.] VA Greater Los Angeles Healthcare Syst, Dept Mental Hlth, Los Angeles, CA USA.
[Ritchie, Natalie D.] Denver Hlth & Hosp Author, Denver Hlth Managed Care, Denver, CO 80204 USA.
[Du Bois, Steve N.] Northwestern Univ, Family Inst, Evanston, IL USA.
[Du Bois, Steve N.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA.
RP Ritchie, ND (reprint author), Denver Hlth & Hosp Author, Denver Hlth Managed Care, 777 Bannock St,MC 6000, Denver, CO 80204 USA.
EM natalie.ritchie@dhha.org
FU University of Illinois at Chicago Chancellor's Committee on the Status
of Lesbian, Gay, Bisexual, and Transgender Issues
FX This work was supported by the University of Illinois at Chicago
Chancellor's Committee on the Status of Lesbian, Gay, Bisexual, and
Transgender Issues.
NR 11
TC 1
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U1 1
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 OCT
PY 2015
VL 19
IS 10
BP 1914
EP 1918
DI 10.1007/s10461-015-1130-y
PG 5
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CR0HK
UT WOS:000360999000019
PM 26174208
ER
PT J
AU Hughes, KS
Cusack, JC
AF Hughes, Kevin S.
Cusack, James C.
TI Genetics, Genomics, and Pharmacogenomics
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Editorial Material
ID CLINICAL DECISION-SUPPORT; BREAST-CANCER; RANDOMIZED-TRIAL;
OVARIAN-CANCER; FLUOROURACIL; TAMOXIFEN; ASSOCIATION; LEUCOVORIN;
THERAPY; CYP2D6
C1 [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA.
[Hughes, Kevin S.] Bermuda Canc Genet & Risk Assessment Clin, Boston, MA USA.
[Cusack, James C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA.
EM kshughes@partners.org
NR 25
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Z9 0
U1 1
U2 14
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 OCT
PY 2015
VL 22
IS 11
BP 3414
EP 3417
DI 10.1245/s10434-015-4705-y
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA CR1EX
UT WOS:000361067900003
PM 26215191
ER
PT J
AU Gupta, A
Mutebi, M
Bardia, A
AF Gupta, Arjun
Mutebi, Miriam
Bardia, Aditya
TI Gene-Expression-Based Predictors for Breast Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID 21-GENE RECURRENCE SCORE; 70-GENE PROGNOSIS-SIGNATURE; GENOMIC GRADE
INDEX; LATE DISTANT RECURRENCE; SUB-SAHARAN AFRICA; CORE BIOPSY-TISSUE;
ESTROGEN-RECEPTOR; ONCOTYPE DX; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIALS
AB An important and often complicated management decision in early stage hormone receptor (HR)-positive breast cancer relates to the use of adjuvant systemic chemotherapy. Although traditional clinicopathologic markers exist, tremendous progress has been achieved in the field of predictive biomarkers and genomics with both prognostic and predictive capabilities to identify patients who will potentially benefit from additional therapy. The use of these genomic tests in the neoadjuvant setting is also being studied and may lead to these tests providing clinical benefit even earlier in the disease course. Landmark articles published in the last few years have expanded our knowledge of breast cancer genomics to an unprecedented level, and mutational analysis via next-generation sequencing methods allows the identification of molecular targets for novel targeted therapeutic agents and clinical trials testing efficacy of targeted therapies, such as PI3K inhibitors, in addition to endocrine therapy for HR-positive breast cancer, are ongoing. We provide an in-depth review on the role of gene expression-based predictors in early stage breast cancer and an overview of future directions, including next-generation sequencing. Over the coming years, we anticipate a significant increase in utilization of genomic-based predictors for individualized selection and duration of endocrine therapy with and without genotype-driven targeted therapy, and a major decrease in the use of chemotherapy, possibly even leading to a chemotherapy-free road for early stage HR-positive breast cancer.
C1 [Gupta, Arjun] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Mutebi, Miriam] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Gupta, A (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
EM Bardia.Aditya@mgh.harvard.edu
NR 84
TC 0
Z9 0
U1 0
U2 3
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 OCT
PY 2015
VL 22
IS 11
BP 3418
EP 3432
DI 10.1245/s10434-015-4703-0
PG 15
WC Oncology; Surgery
SC Oncology; Surgery
GA CR1EX
UT WOS:000361067900004
PM 26215189
ER
PT J
AU Erstad, DJ
Tumusiime, G
Cusack, JC
AF Erstad, Derek J.
Tumusiime, Gerald
Cusack, James C., Jr.
TI Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications
for the Clinical Surgeon
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Review
ID ISLAND METHYLATOR PHENOTYPE; III COLON-CANCER; GENOME-WIDE ASSOCIATION;
GENE COPY NUMBER; TUMOR MICROSATELLITE-INSTABILITY; THYMIDYLATE SYNTHASE
EXPRESSION; EGFR MONOCLONAL-ANTIBODIES; LONG-TERM PROGNOSIS;
POOR-PROGNOSIS; RECTAL-CANCER
AB Colorectal cancer is a heterogeneous disease with a wide range of long-term outcomes and responses to treatment. Recent advances in the genetic and molecular characterization of tumors has yielded a set of prognostic and predictive biomarkers that aid the identification of patients at higher risk for disease recurrence and progression, and in some cases indicate the likelihood of response to a specific treatment. Increasingly, these biomarkers have become integral to the treatment algorithm for managing patients with colorectal cancer. Prognostic and predictive factors in colorectal cancer can broadly be categorized into treatment impact, clinicopathologic factors, and molecular markers. This review will focus primarily on molecular markers, which are foundational to the paradigmatic shift toward personalized cancer therapy.
C1 [Erstad, Derek J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Tumusiime, Gerald] Makerere Univ, Coll Hlth Sci, Dept Gen Surg, Kampala, Uganda.
[Cusack, James C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA USA.
RP Erstad, DJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM jcusack@mgh.harvard.edu
NR 252
TC 4
Z9 4
U1 1
U2 9
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 OCT
PY 2015
VL 22
IS 11
BP 3433
EP 3450
DI 10.1245/s10434-015-4706-x
PG 18
WC Oncology; Surgery
SC Oncology; Surgery
GA CR1EX
UT WOS:000361067900005
PM 26215192
ER
PT J
AU DePeralta, DK
Boland, GM
AF DePeralta, Danielle K.
Boland, Genevieve M.
TI Melanoma: Advances in Targeted Therapy and Molecular Markers
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; METASTATIC MELANOMA; CUTANEOUS MELANOMA; MUTANT
MELANOMA; OPEN-LABEL; IMPROVED SURVIVAL; COMPLETE RESPONSE; MUCOSAL
MELANOMA; MEK INHIBITION; BRAF MUTATIONS
AB In recent years, there have been dramatic improvements in the diagnosis and treatment of patients with melanoma. The development of molecular markers and associated targeted therapies have given new hope to subsets of patients with advanced disease. Here we discuss the most important advances in molecular targeted therapy and how these developments are likely to affect the practice of the clinical surgeon.
Germ-line and somatic mutations are common in melanoma and provide prognostic information that can now be harnessed to provide a more personalized approach to cancer treatment. BRAF mutation at the V600 position is the most commonly identified mutation in patients with melanoma. Treatment with targeted inhibitors in patients with BRAF-mutant melanoma has afforded dramatic responses in about half of selected patients. Unfortunately, disease control is not durable and recurrences are common. We predict an increasing role for the surgeon in the multidisciplinary treatment of patients with metastatic disease, as well as a role for molecular profiling in patients with high-risk early stage disease. Further, we are only beginning to understand the prognostic significance of various gene mutations in patients with melanoma.
C1 [DePeralta, Danielle K.; Boland, Genevieve M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02163 USA.
RP DePeralta, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02163 USA.
EM genevieveboland@gmail.com
NR 68
TC 5
Z9 5
U1 0
U2 2
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 OCT
PY 2015
VL 22
IS 11
BP 3451
EP 3458
DI 10.1245/s10434-015-4702-1
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA CR1EX
UT WOS:000361067900006
PM 26224403
ER
PT J
AU Azzoli, CG
AF Azzoli, Christopher G.
TI Practical Value of Molecular Pathology in Stage I-III Lung Cancer:
Implications for the Clinical Surgeon
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; PHASE-III; CLONAL RELATIONSHIPS; ADJUVANT
ERLOTINIB; MUTATION STATUS; POOLED ANALYSIS; GEFITINIB; EGFR; SURVIVAL;
TUMORS
AB Over a decade since the discovery of EGFR mutation, and 6 years since prospective clinical trial data proved that routine molecular pathology tests improve survival in stage IV lung cancer, there is still debate whether to test patients with earlier stages of disease (stage I-III). As discoveries of targeted drugs for stage IV patients accelerate-prompting routine testing for ALK, ROS1, RET, BRAF V600E, and HER2, among others-there is an argument that all lung cancers should be genotyped for the purpose of classification, regardless of stage of disease. The counterargument is that because targeted drugs have only been validated for use in stage IV disease, these molecular tests need only be conducted at the time of disease recurrence. This review will describe current, practical applications of molecular pathology testing in early stage lung cancer, focusing on the immediate diagnostic, prognostic, and therapeutic implications for individual patient management. Meanwhile, large-scale clinical trials are underway to test targeted drugs as adjuvant therapies in patients with early stage disease.
C1 Massachusetts Gen Hosp, Ctr Canc, Thorac Oncol Program, Boston, MA 02114 USA.
RP Azzoli, CG (reprint author), Massachusetts Gen Hosp, Ctr Canc, Thorac Oncol Program, Boston, MA 02114 USA.
EM cazzoli@mgh.harvard.edu
NR 37
TC 1
Z9 1
U1 1
U2 8
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 OCT
PY 2015
VL 22
IS 11
BP 3459
EP 3465
DI 10.1245/s10434-015-4704-z
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA CR1EX
UT WOS:000361067900007
PM 26215190
ER
PT J
AU Neogi, T
Jansen, TLTA
Dalbeth, N
Fransen, J
Schumacher, HR
Berendsen, D
Brown, M
Choi, H
Edwards, NL
Janssens, HJEM
Liote, F
Naden, RP
Nuki, G
Ogdie, A
Perez-Ruiz, F
Saag, K
Singh, JA
Sundy, JS
Tausche, AK
Vaquez-Mellado, J
Yarows, SA
Taylor, WJ
AF Neogi, Tuhina
Jansen, Tim L. Th A.
Dalbeth, Nicola
Fransen, Jaap
Schumacher, H. Ralph
Berendsen, Dianne
Brown, Melanie
Choi, Hyon
Edwards, N. Lawrence
Janssens, Hein J. E. M.
Liote, Frederic
Naden, Raymond P.
Nuki, George
Ogdie, Alexis
Perez-Ruiz, Fernando
Saag, Kenneth
Singh, Jasvinder A.
Sundy, John S.
Tausche, Anne-Kathrin
Vaquez-Mellado, Janitzia
Yarows, Steven A.
Taylor, William J.
TI 2015 Gout classification criteria: an American College of
Rheumatology/European League Against Rheumatism collaborative initiative
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID SYSTEMIC-SCLEROSIS; PRIMARY-CARE; ARTHRITIS; IDENTIFICATION; UK;
QUESTIONNAIRE; POPULATION; PREVALENCE; MANAGEMENT
AB Objective Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.
Methods An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
Results The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
Conclusions The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
C1 [Neogi, Tuhina; Choi, Hyon] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Jansen, Tim L. Th A.] Viecuri Med Ctr, Venlo, Netherlands.
[Jansen, Tim L. Th A.; Fransen, Jaap; Berendsen, Dianne; Janssens, Hein J. E. M.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Dalbeth, Nicola] Univ Auckland, Auckland 1, New Zealand.
[Schumacher, H. Ralph; Ogdie, Alexis] Univ Penn, Philadelphia, PA 19104 USA.
[Brown, Melanie; Taylor, William J.] Univ Otago, Wellington, New Zealand.
[Edwards, N. Lawrence] Univ Florida, Gainesville, FL USA.
[Liote, Frederic] Hop Lariboisiere, AP HP, INSERM, UMR 1132, F-75475 Paris, France.
[Liote, Frederic] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
[Naden, Raymond P.] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Nuki, George] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Perez-Ruiz, Fernando] Hosp Univ Cruces, Vizcaya, Spain.
[Perez-Ruiz, Fernando] BioCruces Hlth Res Inst, Vizcaya, Spain.
[Saag, Kenneth] Univ Alabama Birmingham, Birmingham, AL USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Rochester, MN USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Rochester, MN USA.
[Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA.
[Sundy, John S.] Duke Univ, Durham, NC USA.
[Sundy, John S.] Duke Univ, Med Ctr, Durham, NC USA.
[Sundy, John S.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Tausche, Anne-Kathrin] Univ Hosp Carl Gustav Carus, Dresden, Germany.
[Vaquez-Mellado, Janitzia] Hosp Gen Mexico City, Mexico City, DF, Mexico.
[Yarows, Steven A.] Univ Michigan Hlth Syst, Chelsea, MI USA.
RP Neogi, T (reprint author), Boston Univ, Sch Med, X Bldg,Suite 200,650 Albany St, Boston, MA 02118 USA.
EM tneogi@bu.edu
RI Fransen, J./L-4310-2015;
OI Ogdie, Alexis/0000-0002-4639-0775; Neogi, Tuhina/0000-0002-9515-1711;
Perez-Ruiz, Fernando/0000-0002-5268-1894
FU American College of Rheumatology; European League Against Rheumatism;
NIH [P60-AR-47785, K23-AR-055127]; Agency for Healthcare Research and
Quality (Center for Education and Research on Therapeutics programme);
NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases); NIH (National Institute on Aging); NIH (National Cancer
Institute); Arthritis New Zealand
FX Supported jointly by the American College of Rheumatology and the
European League Against Rheumatism. TN's work was supported by the NIH
(grants P60-AR-47785 and K23-AR-055127). JAS' work was supported by the
NIH (grants from the National Institute of Arthritis and Musculoskeletal
and Skin Diseases, the National Institute on Aging, and the National
Cancer Institute) and the Agency for Healthcare Research and Quality
(Center for Education and Research on Therapeutics programme). WJT's
work was supported by Arthritis New Zealand.
NR 35
TC 38
Z9 48
U1 4
U2 17
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 OCT
PY 2015
VL 74
IS 10
BP 1789
EP 1798
DI 10.1136/annrheumdis-2015-208237
PG 10
WC Rheumatology
SC Rheumatology
GA CR0WC
UT WOS:000361043200005
PM 26359487
ER
PT J
AU Neogi, T
Jansen, TLTA
Dalbeth, N
Fransen, J
Schumacher, HR
Berendsen, D
Brown, M
Choi, H
Edwards, NL
Janssens, HJEM
Liote, F
Naden, RP
Nuki, G
Ogdie, A
Perez-Ruiz, F
Saag, K
Singh, JA
Sundy, JS
Tausche, AK
Vaquez-Mellado, J
Yarows, SA
Taylor, WJ
AF Neogi, Tuhina
Jansen, Tim L. Th. A.
Dalbeth, Nicola
Fransen, Jaap
Schumacher, H. Ralph
Berendsen, Dianne
Brown, Melanie
Choi, Hyon
Edwards, N. Lawrence
Janssens, Hein J. E. M.
Liote, Frederic
Naden, Raymond P.
Nuki, George
Ogdie, Alexis
Perez-Ruiz, Fernando
Saag, Kenneth
Singh, Jasvinder A.
Sundy, John S.
Tausche, Anne-Kathrin
Vaquez-Mellado, Janitzia
Yarows, Steven A.
Taylor, William J.
TI 2015 Gout Classification Criteria An American College of
Rheumatology/European League Against Rheumatism Collaborative Initiative
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID PRIMARY-CARE; ARTHRITIS; IDENTIFICATION; POPULATION; PREVALENCE; UK;
MANAGEMENT
AB ObjectiveExisting criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.
MethodsAn international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
ResultsThe entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
ConclusionThe new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
C1 [Neogi, Tuhina; Choi, Hyon] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Jansen, Tim L. Th. A.] Viecuri Med Ctr, Venlo, Netherlands.
[Jansen, Tim L. Th. A.; Fransen, Jaap; Berendsen, Dianne; Janssens, Hein J. E. M.] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands.
[Dalbeth, Nicola] Univ Auckland, Auckland 1, New Zealand.
[Schumacher, H. Ralph; Ogdie, Alexis] Univ Penn, Philadelphia, PA 19104 USA.
[Brown, Melanie; Taylor, William J.] Univ Otago, Wellington, New Zealand.
[Edwards, N. Lawrence] Univ Florida, Gainesville, FL USA.
[Liote, Frederic] Hop Lariboisiere, AP HP, INSERM, UMR 1132, F-75475 Paris, France.
[Liote, Frederic] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
[Naden, Raymond P.] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Nuki, George] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Perez-Ruiz, Fernando] Hosp Univ Cruces, Vizcaya, Spain.
[Perez-Ruiz, Fernando] BioCruces Hlth Res Inst, Vizcaya, Spain.
[Saag, Kenneth; Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL 35487 USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA.
[Sundy, John S.] Duke Univ, Durham, NC USA.
[Sundy, John S.] Duke Univ, Med Ctr, Durham, NC USA.
[Tausche, Anne-Kathrin] Univ Hosp Carl Gustav Carus, Dresden, Germany.
[Vaquez-Mellado, Janitzia] Hosp Gen Mexico City, Mexico City, DF, Mexico.
[Yarows, Steven A.] Univ Michigan Hlth Syst, Chelsea, MI USA.
RP Neogi, T (reprint author), Boston Univ, Sch Med, X Bldg,Suite 200,650 Albany St, Boston, MA 02118 USA.
EM tneogi@bu.edu
RI Fransen, J./L-4310-2015; Jansen, T.L.Th.A./L-4407-2015;
OI Ogdie, Alexis/0000-0002-4639-0775; Perez-Ruiz,
Fernando/0000-0002-5268-1894
FU American College of Rheumatology; European League Against Rheumatism;
NIH [P60-AR-47785, K23-AR-055127]; Agency for Healthcare Research and
Quality (Center for Education and Research on Therapeutics program);
Arthritis New Zealand; NIH (National Institute of Arthritis and
Musculoskeletal and Skin Diseases); NIH (National Institute on Aging);
NIH (National Cancer Institute); AbbVie; Bristol-Myers Squibb; Roche;
Janssen; Novartis; Menarini; Takeda; Teijin; Pfizer; Fonterra;
AstraZeneca/Ardea; Regeneron; AstraZeneca; Metabolex; Crealta; CymaBay;
Ardea; Ipsen; Savient; Mayoly-Spindler; Amgen; Allergan; Merck; Lilly;
Navigant; Berlin-Chemie Menarini
FX Supported jointly by the American College of Rheumatology and the
European League Against Rheumatism. Dr. Neogi's work was supported by
the NIH (grants P60-AR-47785 and K23-AR-055127). Dr. Singh's work was
supported by the NIH (grants from the National Institute of Arthritis
and Musculoskeletal and Skin Diseases, the National Institute on Aging,
and the National Cancer Institute) and the Agency for Healthcare
Research and Quality (Center for Education and Research on Therapeutics
program). Dr. Taylor's work was supported by Arthritis New Zealand.; Dr.
Jansen has received consulting fees, speaking fees, and/or honoraria
from AbbVie, Bristol-Myers Squibb, Roche, Janssen, Novartis, and
Menarini (less than $10,000 each). Dr. Dalbeth has received consulting
fees, speaking fees, and/or honoraria from Takeda, Teijin, Menarini,
Pfizer, and Fonterra (less than $10,000 each) and AstraZeneca/Ardea
(more than $10,000); she holds a patent for Fonterra milk products for
gout. Dr. Schumacher has received consulting fees from Novartis,
Regeneron, AstraZeneca, and Metabolex (less than $10,000 each). Dr. Choi
has received consulting fees, speaking fees, and/or honoraria from
AstraZeneca (less than $10,000) and Takeda (more than $10,000). Dr.
Edwards has received consulting fees, speaking fees, and/or honoraria
from AstraZeneca, Crealta, CymaBay, and Takeda (less than $10,000 each).
Dr. Liote has received consulting fees, speaking fees, and/or honoraria
from Novartis, Ardea, AstraZeneca, Ipsen, Menarini, and Savient (less
than $10,000 each) and unrestricted academic grants from Novartis,
AstraZeneca, Ipsen, Menarini, Savient, and Mayoly-Spindler. Dr.
Perez-Ruiz has received consulting fees, speaking fees, and/or honoraria
from AstraZeneca, Menarini, Pfizer, and CymaBay (less than $10,000
each). Dr. Saag has received consulting fees, speaking fees, and/or
honoraria from Amgen, AstraZeneca/Ardea, Crealta, and Takeda (less than
$10,000 each). Dr. Singh has received consulting fees, speaking fees,
and/or honoraria from Regeneron, Allergan, and Savient (less than
$10,000 each) and Takeda (more than $10,000) and research grants from
Savient and Takeda. Dr. Sundy has received consulting fees from Merck,
Lilly, AstraZeneca, Metabolex, Novartis, and Navigant (less than $10,000
each). Dr. Tausche has received consulting fees, speaking fees, and/or
honoraria from Berlin-Chemie Menarini (less than $10,000) and has served
as an expert witness on behalf of Ardea Biosciences/AstraZeneca and
Novartis. Dr. Taylor has received consulting fees, speaking fees, and/or
honoraria from Pfizer, AstraZeneca, AbbVie, and Roche (less than $10,000
each).
NR 35
TC 26
Z9 26
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD OCT
PY 2015
VL 67
IS 10
BP 2557
EP 2568
DI 10.1002/art.39254
PG 12
WC Rheumatology
SC Rheumatology
GA CR3QS
UT WOS:000361248600001
PM 26352873
ER
PT J
AU Deason, RG
Hussey, EP
Flannery, S
Ally, BA
AF Deason, Rebecca G.
Hussey, Erin P.
Flannery, Sean
Ally, Brandon A.
TI Preserved conceptual implicit memory for pictures in patients with
Alzheimer's disease
SO BRAIN AND COGNITION
LA English
DT Article
DE Conceptual implicit memory; Picture superiority effect; Familiarity;
Alzheimer's disease
ID MILD COGNITIVE IMPAIRMENT; SEMANTIC MEMORY; RECOGNITION MEMORY; SHARED
FEATURES; REMAINS INTACT; SUPERIORITY; FAMILIARITY; DEMENTIA; TASKS;
IMAGERY
AB The current study examined different aspects of conceptual implicit memory in patients with mild Alzheimer's disease (AD). Specifically, we were interested in whether priming of distinctive conceptual features versus general semantic information related to pictures and words would differ for the mild AD patients and healthy older adults. In this study, 14 healthy older adults and 15 patients with mild AD studied both pictures and words followed by an implicit test section, where they were asked about distinctive conceptual or general semantic information related to the items they had previously studied (or novel items). Healthy older adults and patients with mild AD showed both conceptual priming and the picture superiority effect, but the AD patients only showed these effects for the questions focused on the distinctive conceptual information. We found that patients with mild AD showed intact conceptual picture priming in a task that required generating a response (answer) from a cue (question) for cues that focused on distinctive conceptual information. This experiment has helped improve our understanding of both the picture superiority effect and conceptual implicit memory in patients with mild AD in that these findings support the notion that conceptual implicit memory might potentially help to drive familiarity-based recognition in the face of impaired recollection in patients with mild AD. (c) 2015 Published by Elsevier Inc.
C1 [Deason, Rebecca G.] Texas State Univ, Dept Psychol, San Marcos, TX USA.
[Hussey, Erin P.; Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN 37235 USA.
[Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37235 USA.
[Ally, Brandon A.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
[Flannery, Sean] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA USA.
[Flannery, Sean] Boston Univ, Sch Med, Boston Univ Alzheimers Dis Ctr, Boston, MA 02118 USA.
RP Ally, BA (reprint author), Dept Neurol, A-0118 Med Ctr North,1161 21st Ave South, Nashville, TN 37232 USA.
EM brandon.ally@vanderbilt.edu
FU National Institute on Aging [AG038471, AG031925]; Department of Veterans
Affairs, Veterans Health Administration, VISN 1 Early Career Development
Award
FX This research was supported by National Institute on Aging grants
AG038471 (BAA), AG031925 (BAA), and a Department of Veterans Affairs,
Veterans Health Administration, VISN 1 Early Career Development Award to
RGD. We would like to thank Bruno Frustace for assistance with data
collection. This material is also the result of work supported with
resources and the use of facilities at the Bedford VA Hospital in
Bedford, MA and the VA Boston Healthcare System, Boston, MA.
NR 46
TC 1
Z9 1
U1 2
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
EI 1090-2147
J9 BRAIN COGNITION
JI Brain Cogn.
PD OCT
PY 2015
VL 99
BP 112
EP 117
DI 10.1016/j.bandc.2015.07.008
PG 6
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA CR2LD
UT WOS:000361160200012
PM 26291521
ER
PT J
AU Kaji, I
Akiba, Y
Said, H
Narimatsu, K
Kaunitz, JD
AF Kaji, I.
Akiba, Y.
Said, H.
Narimatsu, K.
Kaunitz, J. D.
TI Luminal 5-HT stimulates colonic bicarbonate secretion in rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
ID NITRIC-OXIDE; ION-TRANSPORT; CONCISE GUIDE; ELECTROLYTE TRANSPORT;
ARRIVE GUIDELINES; SEROTONIN RELEASE; ANION SECRETION; G-PROTEIN;
5-HYDROXYTRYPTAMINE; RECEPTORS
AB Background and PurposeThe bioactive monoamine 5-HT, implicated in the pathogenesis of functional gastrointestinal disorders, is abundantly synthesized and stored in rat proximal colonic mucosa and released to the gut lumen and subepithelial space. Despite much data regarding its expression and function, the effects of luminal 5-HT on colonic anion secretion have not been fully investigated.
Experimental ApproachWe measured short-circuit current (I-sc) as an indicator of ion transport in mucosa-submucosa or mucosa-only preparations of rat proximal colon. Total CO2 output was measured in vitro and in vivo. Immunohistochemistry was performed to investigate the localization of 5-HT4, NOS1 and NOS2.
Key ResultsLuminal 5-HT gradually increased the amplitude and sustained the elevation of I-sc. Luminal 5-HT-evoked I-sc was acetazolamide sensitive and HCO3- dependent, consistent with cytosolic carbonic anhydrase-dependent electrogenic HCO3- secretion, while not affected by tetrodotoxin (TTX), atropine or indomethacin. Pretreatment with the selective 5-HT4 antagonist GR113808, but not antagonists for 5-HT3, 5-HT6 or 5-HT7, inhibited luminal 5-HT-evoked I-sc. Furthermore, luminal cisapride and tegaserod increased I-sc to the same extent as did 5-HT in the presence of indomethacin and TTX. Removal of the submucosa or pretreatment with NOS inhibitors enhanced luminal 5-HT-evoked I-sc, suggesting that NO synthesized in the submucosa suppresses mucosal anion secretion. NOS1 and NOS2 were immunostained in the submucosal neurons and glial cells respectively. Luminal 5-HT-evoked HCO3- secretion was confirmed in vivo, inhibited by co-perfusion of GR113808, but not by ondansetron.
Conclusions and ImplicationsA novel apical 5-HT4-mediated HCO3- secretory pathway and an NO-dependent inhibitory mechanism are present in the proximal colon. Luminal 5-HT-evoked HCO3- secretion may be important for the maintenance of mucosal integrity by regulating luminal pH.
C1 [Kaji, I.; Akiba, Y.; Narimatsu, K.; Kaunitz, J. D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Kaunitz, J. D.] Univ Calif Los Angeles, Dept Surg, Sch Med, Los Angeles, CA 90024 USA.
[Said, H.] Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA USA.
[Kaji, I.; Akiba, Y.; Kaunitz, J. D.] Brentwood Biomed Res Inst, Los Angeles, CA USA.
[Akiba, Y.; Kaunitz, J. D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 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, P30 DK0413]
FX The authors thank B. Palileo for preparing the manuscript. The helpful
discussion of Dr E. Engel and Dr P. H. Guth is gratefully acknowledged.
This study was supported by a Department of Veterans Affairs Merit
Review Award, NIH-NIDDK R01 DK54221 (J. D. K.), and the animal core of
NIH-NIDDK P30 DK0413 (J. E. Rozengurt).
NR 57
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD OCT
PY 2015
VL 172
IS 19
BP 4655
EP 4670
DI 10.1111/bph.13216
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CQ9FM
UT WOS:000360918200005
PM 26061462
ER
PT J
AU Cao, Y
Meyerhardt, JA
Chan, AT
Wu, K
Fuchs, CS
Giovannucci, EL
AF Cao, Yin
Meyerhardt, Jeffrey A.
Chan, Andrew T.
Wu, Kana
Fuchs, Charles S.
Giovannucci, Edward L.
TI Television watching and colorectal cancer survival in men
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Sedentary behavior; Television watching; Colorectal cancer; Survival
ID TYPE-2 DIABETES-MELLITUS; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY;
SEDENTARY BEHAVIOR; CARDIOVASCULAR-DISEASE; VIEWING TIME; RECTAL-CANCER;
COLON-CANCER; AARP DIET; RISK
AB To assess the association between pre- and postdiagnostic time spent sitting watching TV as well as other sedentary behaviors (other sitting at home and at work/driving) and mortality from colorectal cancer or other causes, and overall mortality.
We followed stage I-III colorectal cancer patients from the Health Professionals Follow-up Study (1986-2010). Cox models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs).
A total of 926 and 714 patients were included in the analysis of pre- and postdiagnostic TV watching, respectively, and 471 and 325 died during follow-up. Prolonged prediagnostic TV viewing was associated with increased risk of colorectal cancer-specific mortality independent of leisure-time physical activity. The HRs (95 % CIs) for 0-6, 7-13, 14-20, and a parts per thousand yen21 h/week were 1.00 (referent), 0.84 (0.56-1.25), 1.15 (0.75-1.78), and 2.13 (1.31-3.45) (p (trend) = 0.01). The association was observed primarily among overweight and obese individuals. Prediagnostic TV watching was also associated with overall mortality within 5 years of diagnosis, largely due to the association with colorectal cancer mortality. Other prediagnostic sitting at home or at work/driving was not associated with mortality. Postdiagnostic TV viewing was associated with a nonsignificantly increased risk of colorectal cancer-specific mortality (HR for a parts per thousand yen21 vs 0-6 h/week = 1.45; 95 % CI 0.73-2.87) adjusting for TV viewing before diagnosis.
Prolonged prediagnostic TV watching is associated with higher colorectal cancer-specific mortality independent of leisure-time physical activity among colorectal cancer patients.
C1 [Cao, Yin; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Cao, Y (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM yic576@mail.harvard.edu
FU National Institute of Health [P01 CA87969, P01 CA55075, UM1 CA167552,
R01 CA137178, K24 DK098311]
FX This work was supported by Grants from the National Institute of Health
(P01 CA87969; P01 CA55075; UM1 CA167552; R01 CA137178; K24 DK098311).
Dr. Chan is a Damon Runyon Clinical Investigator. The study sponsors had
no role in the design of the study: the collection, analysis, and
interpretation of the data; the writing of the manuscript; and the
decision to submit the manuscript for publication.
NR 40
TC 1
Z9 1
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD OCT
PY 2015
VL 26
IS 10
BP 1467
EP 1476
DI 10.1007/s10552-015-0645-x
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CR1FD
UT WOS:000361068800010
PM 26293240
ER
PT J
AU Poole, EM
Schernhammer, E
Mills, L
Hankinson, SE
Tworoger, SS
AF Poole, Elizabeth M.
Schernhammer, Eva
Mills, Leigha
Hankinson, Susan E.
Tworoger, Shelley S.
TI Urinary melatonin and risk of ovarian cancer
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Melatonin; Circadian rhythm; Ovarian cancer
ID BREAST-CANCER; SHIFT-WORK; CELL-LINES; CIRCADIAN DISRUPTION; NURSES
HEALTH; WOMEN; NIGHT; EXPRESSION; GROWTH; LIGHT
AB Melatonin has anti-carcinogenic properties, including modulation of estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary melatonin has been inversely associated with breast cancer in some studies, but the association with ovarian cancer has not been investigated.
We measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case-control studies in the Nurses' Health Study (NHS; n = 100 cases; 199 controls) and NHSII (n = 52 cases; 105 controls); samples were mainly from first morning voids. Controls were matched to cases on year of birth, menopause status, use of menopausal hormone therapy, and urine collection characteristics. We evaluated the association of tertiles of aMT6s, corrected for creatinine concentrations, with risk of ovarian cancer using conditional logistic regression. Models were adjusted for key ovarian cancer risk factors, and we additionally evaluated adjustment for usual sleep duration, snoring, and history of rotating night shift work.
aMT6s was not significantly associated with risk of ovarian cancer. In multivariable models, the odds ratio comparing the highest tertile of aMT6s to the lowest was 0.79, 95 % confidence interval (CI) 0.40-1.56 in the NHS and 2.88, and 95 % CI in the NHSII 0.97-8.52. Additional adjustment for sleep habits and night shift work had little impact on the observed results. We observed no clear association between urinary melatonin and ovarian cancer risk.
These results are consistent with our previous study in which we reported no association between night shift work and ovarian cancer; however, given the small sample size in our study, additional evaluation in larger studies is warranted.
C1 [Poole, Elizabeth M.; Schernhammer, Eva; Hankinson, Susan E.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Schernhammer, Eva; Hankinson, Susan E.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Schernhammer, Eva; Hankinson, Susan E.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mills, Leigha] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
RP Poole, EM (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA.
EM nhlip@channing.harvard.edu
FU National Cancer Institute [UM1 CA186107, P01 CA87969, R01 CA49449, UM1
CA176726, R01 CA67262]
FX We would like to thank the participants and staff of the Nurses' Health
Studies 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, and WY. This work was supported by
National Cancer Institute Grants UM1 CA186107, P01 CA87969, R01 CA49449,
UM1 CA176726, and R01 CA67262.
NR 28
TC 0
Z9 0
U1 6
U2 13
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD OCT
PY 2015
VL 26
IS 10
BP 1501
EP 1506
DI 10.1007/s10552-015-0640-2
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CR1FD
UT WOS:000361068800014
PM 26223889
ER
PT J
AU Sarma, A
Shyn, PB
Vivian, MA
Ng, JM
Tuncali, K
Lorch, JH
Zaheer, SN
Gordon, MS
Silverman, SG
AF Sarma, Asha
Shyn, Paul B.
Vivian, Mark A.
Ng, Ju-Mei
Tuncali, Kemal
Lorch, Jorchen H.
Zaheer, Sarah N.
Gordon, Michael S.
Silverman, Stuart G.
TI Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral
Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
DE Image-guided intervention; Adrenal hyperplasia; Cushing's syndrome;
Ectopic ACTH syndrome; Microwave ablation
ID RADIOFREQUENCY ABLATION; CUSHINGS-SYNDROME; CRYOABLATION; NEOPLASMS;
TUMOR
AB Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: O ne was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.
C1 [Sarma, Asha; Shyn, Paul B.; Tuncali, Kemal; Silverman, Stuart G.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Vivian, Mark A.] Univ Manitoba, Dept Radiol, Winnipeg, MB R3T 2N2, Canada.
[Ng, Ju-Mei] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Lorch, Jorchen H.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Zaheer, Sarah N.; Gordon, Michael S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
RP Shyn, PB (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
EM ashasarma@gmail.com; pshyn@partners.org
FU Canon, Inc.; Novartis
FX Dr. Tuncali receives grant support from Canon, Inc. for unrelated
projects. Dr. Lorch receives grant support from Novartis for unrelated
projects.
NR 10
TC 1
Z9 1
U1 0
U2 1
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 OCT
PY 2015
VL 38
IS 5
BP 1335
EP 1338
DI 10.1007/s00270-015-1056-9
PG 4
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CR1FH
UT WOS:000361069400039
PM 25762486
ER
PT J
AU Kaushal, V
Dye, R
Pakavathkumar, P
Foveau, B
Flores, J
Hyman, B
Ghetti, B
Koller, BH
LeBlanc, AC
AF Kaushal, V.
Dye, R.
Pakavathkumar, P.
Foveau, B.
Flores, J.
Hyman, B.
Ghetti, B.
Koller, B. H.
LeBlanc, A. C.
TI Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately
regulates inflammatory interleukin-1-beta production and axonal
degeneration-associated Caspase-6 activation
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MICROGLIAL ACTIVATION;
COGNITIVE IMPAIRMENT; MOLECULAR PLATFORM; NALP3 INFLAMMASOME;
BETA-PEPTIDE; EXPRESSION; APOPTOSIS; DEATH
AB Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation. NLRP1 and Casp1 siRNAs also abolished stress-induced Casp6 activation in neurons. The functionality of the NLRP1 inflammasome in serum-deprived neurons was also demonstrated by NLRP1 siRNA-mediated inhibition of speck formation of the apoptosis-associated speck-like protein containing a caspase recruitment domain conjugated to green fluorescent protein. These results indicated a novel stress-induced intraneuronal NLRP1/Casp1/Casp6 pathway. Lipopolysaccharide induced Casp1 and Casp6 activation in wild-type mice brain cortex, but not in that of Nlrp1(-/-) and Casp1(-/-) mice. NLRP1 immunopositive neurons were increased 25- to 30-fold in AD brains compared with non-AD brains. NLRP1 immunoreactivity in these neurons co-localized with Casp6 activity. Furthermore, the NLRP1/Casp1/Casp6 pathway increased amyloid beta peptide 42 ratio in serum-deprived neurons. Therefore, CNS human neurons express functional NLRP1 inflammasomes, which activate Casp1 and subsequently Casp6, thus revealing a fundamental mechanism linking intraneuronal inflammasome activation to Casp1-generated interleukin-1-beta-mediated neuroinflammation and Casp6-mediated axonal degeneration.
C1 [Kaushal, V.; Pakavathkumar, P.; Foveau, B.; Flores, J.; LeBlanc, A. C.] Jewish Gen Hosp, Lady Davis Inst Med Res, Bloomfield Ctr Res Aging, Montreal, PQ H3T 1E2, Canada.
[Kaushal, V.; Pakavathkumar, P.; Foveau, B.; Flores, J.; LeBlanc, A. C.] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
[Dye, R.; Koller, B. H.] Dept Genet, Chapel Hill, NC 27599 USA.
[Hyman, B.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat, Charlestown, MA USA.
[Ghetti, B.] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA.
RP LeBlanc, AC (reprint author), Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Bloomfield Ctr Res Aging, 3755 Ch Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada.
EM andrea.leblanc@mcgill.ca
FU Canadian Foundation of Innovation; Canadian Institutes of Health
Research (CIHR) [MOP-243413-BCA-CGAG-45097]; JGH Foundation; NIH [P30
AG010133]; McGill's CIHR Neuroinflammation Training Program award; Fonds
de recherche Quebec-Sante scholarship; FRSQ-Alzheimer Society of Canada
doctoral award
FX We thank Marc-Andre Dery for generating the ASC-GFP construct. The
Canadian Foundation of Innovation, Canadian Institutes of Health
Research (CIHR) MOP-243413-BCA-CGAG-45097, and the JGH Foundation (ALB),
and NIH Grant P30 AG010133 (BG) supported this work. Dr. Vikas Kaushal
was a recipient of McGill's CIHR Neuroinflammation Training Program
award (2010-2012); Prateep Pakavathkumar is the recipient of a Fonds de
recherche Quebec-Sante scholarship (2011-2013) and the FRSQ-Alzheimer
Society of Canada doctoral award (2014-2016).
NR 55
TC 15
Z9 15
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD OCT
PY 2015
VL 22
IS 10
BP 1676
EP 1686
DI 10.1038/cdd.2015.16
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CR0DV
UT WOS:000360989400010
PM 25744023
ER
PT J
AU Somanna, NK
Yariswamy, M
Garagliano, JM
Siebenlist, U
Mummidi, S
Valente, AJ
Chandrasekar, B
AF Somanna, Naveen K.
Yariswamy, Manjunath
Garagliano, Joseph M.
Siebenlist, Ulrich
Mummidi, Srinivas
Valente, Anthony J.
Chandrasekar, Bysani
TI Aldosterone-induced cardiomyocyte growth, and fibroblast migration and
proliferation are mediated by TRAF3IP2
SO CELLULAR SIGNALLING
LA English
DT Article
DE RAAS; Aldosterone; TRAF3IP2; Hypertrophy; Mitogenesis; Migration
ID KAPPA-B KINASE; HEART-FAILURE; ANGIOTENSIN-II; MYOCARDIAL FIBROSIS;
CARDIAC-HYPERTROPHY; MATRIX METALLOPROTEINASES; HYPERTENSIVE PATIENTS;
SYSTOLIC DYSFUNCTION; PRESSURE-OVERLOAD; OXIDATIVE STRESS
AB Sustained activation of the Renin-Angiotensin-Aldosterone System (RAAS) contributes to the pathogenesis of heart failure. Aldosterone (Aldo) is known to induce both myocardial hypertrophy and fibrosis through oxidative stress and proinflammatory pathways. Here we have investigated whether Aldo-mediated cardiomycocyte hypertrophy is dependent on TRAF3IP2, an upstream regulator of IKK and JNIC We also investigated whether the pro-mitogenic and pro-migratory effects of Aldo on cardiac fibroblasts are also mediated by TRAF3IP2. Aldo induced both superoxide and hydrogen peroxide in isolated adult mouse cardiomyocytes (CM), and upregulated TRAF3IP2 expression in part via the mineralocorticoid receptor and oxidative stress. Silencing TRAF3IP2 blunted Aldo-induced IKK beta, p65, JNK, and c-Jun activation, IL-18, IL-6 and CT-1 upregulation, and cardiomyocyte hypertrophy. In isolated adult mouse cardiac fibroblasts (CF), Aldo stimulated TRAF3IP2-dependent IL-18 and IL-6 production, CTGF, collagen land III expression, MMP2 activation, and proliferation and migration. These in vitro results suggest that TRAF3IP2 may play a causal role in Aldo-induced adverse cardiac remodeling in vivo, and identify TRAF3IP2 as a potential therapeutic target in hypertensive heart disease. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Somanna, Naveen K.] Tulane Univ, Sch Med, Dept Microbiol, New Orleans, LA 70112 USA.
[Yariswamy, Manjunath; Garagliano, Joseph M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Yariswamy, Manjunath; Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, New Orleans, LA 70161 USA.
[Siebenlist, Ulrich; Chandrasekar, Bysani] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Siebenlist, Ulrich; Chandrasekar, Bysani] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Mummidi, Srinivas; Valente, Anthony J.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA.
FU Department of Veterans Affairs Research Career Scientist award; U.S.
Department of Veterans Affairs, Office of Research and
Development-Biomedical Laboratory Research and Development (ORD-BLRD)
Service Award [VA-I01 BX002255]; Usha Ramadhyani Bourgeois Medical
Student Research Endowed Fund; NIH/NIAID
FX BC is a recipient of the Department of Veterans Affairs Research Career
Scientist award, and is supported by the U.S. Department of Veterans
Affairs, Office of Research and Development-Biomedical Laboratory
Research and Development (ORD-BLRD) Service Award VA-I01 BX002255. JMG
is a recipient of The Warren R Bourgeois III and Usha Ramadhyani
Bourgeois Medical Student Research Endowed Fund. US is supported by the
Intramural Research Program of the NIH/NIAID. The contents of this
report do not represent the views of the Department of Veterans Affairs
or the United States government
NR 44
TC 7
Z9 8
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD OCT
PY 2015
VL 27
IS 10
BP 1928
EP 1938
DI 10.1016/j.cellsig.2015.07.001
PG 11
WC Cell Biology
SC Cell Biology
GA CQ7ID
UT WOS:000360775300002
PM 26148936
ER
PT J
AU Siegler, JE
Samai, A
Albright, KC
Boehme, AK
Martin-Schild, S
AF Siegler, James E.
Samai, Alyana
Albright, Karen C.
Boehme, Amelia K.
Martin-Schild, Sheryl
TI Factoring in Factor VIII With Acute Ischemic Stroke
SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
LA English
DT Review
DE stroke; von Willebrand factor; thrombosis; hypercoagulability; factor
viii
ID VON-WILLEBRAND-FACTOR; ELEVATED FACTOR-VIII; CLOTTING FACTOR-VIII; HIGH
PLASMA-LEVELS; FACTOR-V-LEIDEN; RISK-FACTORS; MYOCARDIAL-INFARCTION;
VENOUS THROMBOEMBOLISM; COAGULATION-FACTORS; HIGH PREVALENCE
AB There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke.
C1 [Siegler, James E.; Samai, Alyana; Martin-Schild, Sheryl] Tulane Univ Med Ctr Hosp & Clin, Tulane Stroke Res Program, Dept Neurol, New Orleans, LA USA.
[Samai, Alyana] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Albright, Karen C.] Birmingham VA Med Ctr, GRECC, Birmingham, AL USA.
[Albright, Karen C.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Boehme, Amelia K.] Columbia Univ, Dept Neurol, Gertrude Sergievsky Ctr, New York, NY USA.
RP Martin-Schild, S (reprint author), Tulane Univ, Stroke Program, Tulane Stroke Res Program, Dept Neurol, 1440 Canal St,TB-52,Suite 1000, New Orleans, LA 70112 USA.
EM smartin2@tulane.edu
OI Siegler, James/0000-0003-0287-3967
FU NINDS NIH [T32 NS007153-31]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: Dr. Boehme
is supported by NINDS NIH T32 NS007153-31. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NINDS or the NIH.
NR 48
TC 0
Z9 0
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1076-0296
EI 1938-2723
J9 CLIN APPL THROMB-HEM
JI Clin. Appl. Thromb.-Hemost.
PD OCT
PY 2015
VL 21
IS 7
BP 597
EP 602
DI 10.1177/1076029615571630
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA CQ8AB
UT WOS:000360827200001
PM 25669199
ER
PT J
AU Marshall, AL
Campigotto, F
Neuberg, D
Rowe, B
Connors, JM
AF Marshall, Ariela L.
Campigotto, Federico
Neuberg, Donna
Rowe, Betty
Connors, Jean M.
TI Recurrence of Venous Thromboembolism in Patients With Cancer Treated
With Warfarin
SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
LA English
DT Article
DE anticoagulants; venous thromboembolism; hypercoagulability
ID MOLECULAR-WEIGHT HEPARIN; SECONDARY PREVENTION; VEIN THROMBOSIS; USUAL
CARE; RISK; COUMARIN; DISEASE; EVENTS
AB Venous thromboembolism (VTE) is a common complication in patients with cancer. Previous randomized studies have demonstrated that the rates of recurrent VTE are lower in patients treated with low-molecular-weight heparin compared to warfarin. We performed a retrospective analysis of 236 patients with cancer managed by a dedicated oncology anticoagulation management service to compare real-world rates of recurrent VTE and bleeding in patients treated with warfarin versus parenteral anticoagulants. Initial anticoagulant regimen included a parenteral agent with transition to warfarin in 132 (55.9%) patients, enoxaparin in 53 (22.5%), dalteparin in 37 (15.7%), and fondaparinux in 14 (5.9%). Taking into account the competing risk of death, cumulative incidence of VTE recurrence at 6 months was 4.0% with warfarin, 10.3% with enoxaparin, 3.0% with dalteparin, and 7.7% with fondaparinux (P = .004). Bleeding complications occurred in 10.6% of patients on warfarin, 17.0% on enoxaparin, 27.0% on dalteparin, and 14.3% on fondaparinux (P = .089). In a dedicated anticoagulation clinic, specific for patients with cancer, warfarin may be an acceptable treatment for first thrombotic events in patients with cancer.
C1 [Marshall, Ariela L.; Rowe, Betty; Connors, Jean M.] Dana Farber Canc Inst, Dept Hematol & Med Oncol, Boston, MA 02115 USA.
[Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Rowe, Betty; Connors, Jean M.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
RP Connors, JM (reprint author), Brigham & Womens Hosp, Dept Hematol, 75 Francis St,Mid Campus 3, Boston, MA 02115 USA.
EM jconnors@partners.org
FU Dana-Farber/Harvard Cancer Center Core Grant [5P30 CA-006516]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article:
Statistical analyses were supported in part by the Dana-Farber/Harvard
Cancer Center Core Grant 5P30 CA-006516.
NR 23
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 1076-0296
EI 1938-2723
J9 CLIN APPL THROMB-HEM
JI Clin. Appl. Thromb.-Hemost.
PD OCT
PY 2015
VL 21
IS 7
BP 632
EP 638
DI 10.1177/1076029615579099
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA CQ8AB
UT WOS:000360827200006
PM 25850917
ER
PT J
AU Huang, JW
Feldman, AS
Dong, L
Cornejo, K
Liu, Q
Dahl, DM
Wu, SL
Blute, ML
Huang, YR
Wu, CL
AF Huang, Jiwei
Feldman, Adam S.
Dong, Liang
Cornejo, Kristine
Liu, Qiang
Dahl, Douglas M.
Wu, Shulin
Blute, Michael L.
Huang, Yiran
Wu, Chin-Lee
TI Preoperative Anemia as an Independent Prognostic Indicator of Papillary
Renal Cell Carcinoma
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE Anemia; Kidney; Neoplasm by histologic type; Prognosis; Renal cell
carcinoma
ID CLEAR-CELL; TUMOR HYPOXIA; NEPHRECTOMY; SURVIVAL; FEATURES; CANCER
AB The role of preoperative anemia in the prognosis of patients with localized papillary renal cell carcinoma was retrospectively evaluated in 352 patients of 2 large institutions. Patients with anemia were older and more likely to have larger tumor size and higher Fuhrman grade. Anemia was an independent prognostic factor in terms of recurrence-free survival, cancer-specific survival, and overall survival. Preoperative anemia will provide urologists additional prognostic information in patients with papillary renal cell carcinoma.
Objectives: Preoperative anemia has been proposed as a prognostic factor for clear cell renal cell carcinoma. We evaluate its role in papillary renal cell carcinoma (pRCC). Methods: At 2 institutions, patients who underwent complete resection of localized (T1-3 N0/+ M0) pRCC by radical or partial nephrectomy were retrospectively reviewed in this study. Anemia was defined as hemoglobin < 13.5 g/dL in men and < 12 g/dL in women. The associations of preoperative anemia with clinical and pathologic variables were assessed using the Student t, Wilcoxon rank-sum, and chi-square tests. Univariable and multivariable analyses using the Kaplan-Meier method and the Cox regression model were performed to determine factors that were associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Our final cohort included 352 patients. Compared with patients without anemia, patients with anemia were older and more likely to have larger tumor size and higher Fuhrman grade. Kaplan-Meier curves showed that patients with preoperative anemia had significantly worse RFS, CSS, and OS than patients without anemia (log-rank test, all P<.001). Multivariable analyses revealed that anemia was an independent prognostic factor in terms of RFS, CSS, and OS (all P<.001). Conclusions: Preoperative anemia is an important independent prognostic factor associated with an increased risk of recurrence and mortality in patients after surgery with a curative intent for localized pRCC. Consideration of preoperative anemia could provide urologists additional prognostic information in patients with pRCC. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Huang, Jiwei; Dong, Liang; Huang, Yiran] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Urol, Shanghai 200127, Peoples R China.
[Feldman, Adam S.; Dahl, Douglas M.; Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Feldman, Adam S.; Cornejo, Kristine; Dahl, Douglas M.; Wu, Shulin; Blute, Michael L.; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA USA.
[Cornejo, Kristine; Wu, Shulin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Liu, Qiang; Wu, Chin-Lee] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Pathol, Shanghai 200127, Peoples R China.
RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA.
EM yrhuangrenji@163.com; cwu2@partners.org
FU National Natural Science Foundation of China [81402084]
FX This study was supported by Award Number 81402084 from National Natural
Science Foundation of China.
NR 19
TC 1
Z9 1
U1 1
U2 3
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
EI 1938-0682
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD OCT
PY 2015
VL 13
IS 5
BP E353
EP E360
DI 10.1016/j.clgc.2015.04.014
PG 8
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA CQ9EK
UT WOS:000360914600003
PM 25998556
ER
PT J
AU Ring, D
Leopold, SS
AF Ring, David
Leopold, Seth S.
TI Editorial-Measuring Satisfaction: Can It Be Done?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Editorial Material
ID PATIENT-SATISFACTION
C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Ring, David; Leopold, Seth S.] Clin Orthopaed & Related Res, Philadelphia, PA 19103 USA.
RP Leopold, SS (reprint author), Clin Orthopaed & Related Res, Philadelphia, PA 19103 USA.
EM sleopold@clinorthop.org
NR 15
TC 1
Z9 1
U1 0
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 OCT
PY 2015
VL 473
IS 10
BP 3071
EP 3073
DI 10.1007/s11999-015-4485-5
PG 3
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA CQ9FO
UT WOS:000360918400001
PM 26228896
ER
PT J
AU Janssen, SJ
van der Heijden, AS
van Dijke, M
Ready, JE
Raskin, KA
Ferrone, ML
Hornicek, FJ
Schwab, JH
AF Janssen, Stein J.
van der Heijden, Andrea S.
van Dijke, Maarten
Ready, John E.
Raskin, Kevin A.
Ferrone, Marco L.
Hornicek, Francis J.
Schwab, Joseph H.
TI 2015 Marshall Urist Young Investigator Award: Prognostication in
Patients With Long Bone Metastases: Does a Boosting Algorithm Improve
Survival Estimates?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID CHARLSON COMORBIDITY INDEX; EXTERNAL VALIDATION; SKELETAL METASTASIS;
PREDICTION MODEL; PROSTATE-CANCER; BREAST-CANCER; PROGNOSIS; NOMOGRAM;
DISEASE; SURGERY
AB Survival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms-nomograms or boosting algorithms-could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient's set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables.
We wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival.
We included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation.
The following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0-1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0-1.4; p = 0.034), BMI less than 18.5 kg/m(2) (HR, 2.0; 95% CI, 1.2-3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6-2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1-1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4-1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87-0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods.
Comorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice.
Level III, prognostic study.
C1 [Janssen, Stein J.; van der Heijden, Andrea S.; van Dijke, Maarten; Raskin, Kevin A.; Hornicek, Francis J.; Schwab, Joseph H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA USA.
[Ready, John E.; Ferrone, Marco L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA 02115 USA.
[Janssen, Stein J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Janssen, SJ (reprint author), Massachusetts Gen Hosp, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA.
EM steinjanssen@gmail.com
FU Anna Foundation (Oegstgeest, The Netherlands); De Drie Lichten
Foundation (Hilversum, The Netherlands); KWF Kankerbestrijding
(Amsterdam, The Netherlands); Michael van Vloten Foundation (Rotterdam,
The Netherlands); Stryker (Kalamazoo, MI, USA); Biom'up (Saint-Priest,
Lyon, France)
FX One author (SJ) certifies that he has received, an amount less than USD
10,000, from the Anna Foundation (Oegstgeest, The Netherlands), an
amount less than USD 10,000 from the De Drie Lichten Foundation
(Hilversum, The Netherlands), an amount less than USD 10,000 from the
KWF Kankerbestrijding (Amsterdam, The Netherlands), and an amount less
than USD 10,000, from the Michael van Vloten Foundation (Rotterdam, The
Netherlands). One author (JS) certifies that he or a member of his
family has or may receive payments or benefits, an amount less than USD
10,000, from Stryker (Kalamazoo, MI, USA), and an amount less than USD
10,000, from Biom'up (Saint-Priest, Lyon, France).
NR 38
TC 5
Z9 5
U1 1
U2 4
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 OCT
PY 2015
VL 473
IS 10
BP 3112
EP 3121
DI 10.1007/s11999-015-4446-z
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA CQ9FO
UT WOS:000360918400009
PM 26155769
ER
PT J
AU Shi, LL
Cahill, KE
Ek, ET
Tompson, JD
Higgins, LD
Warner, JJP
AF Shi, Lewis L.
Cahill, Kirk E.
Ek, Eugene T.
Tompson, Jeffrey D.
Higgins, Laurence D.
Warner, Jon J. P.
TI Latissimus Dorsi and Teres Major Transfer With Reverse Shoulder
Arthroplasty Restores Active Motion and Reduces Pain for Posterosuperior
Cuff Dysfunction
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID EXTERNAL ROTATION; TEAR ARTHROPATHY; PSEUDOPARESIS; PROSTHESIS;
ELEVATION; OUTCOMES; DEFICIT
AB In patients with rotator cuff dysfunction, reverse shoulder arthroplasty can restore active forward flexion, but it does not provide a solution for the lack of active external rotation because of infraspinatus and the teres minor dysfunction. A modified L'Episcopo procedure can be performed in the same setting wherein the latissimus dorsi and teres major tendons are transferred to the lateral aspect of proximal humerus in an attempt to restore active external rotation.
(1) Do latissimus dorsi and teres major tendon transfers with reverse shoulder arthroplasty improve external rotation function in patients with posterosuperior rotator cuff dysfunction? (2) Do patients experience less pain and have improved outcome scores after surgery? (3) What are the complications associated with reverse shoulder arthroplasty with latissimus dorsi and teres major transfer?
Between 2007 and 2010, we treated all patients undergoing shoulder arthroplasty who had a profound external rotation lag sign and advanced fatty degeneration of the posterosuperior rotator cuff (infraspinatus plus teres minor) with this approach. A total of 21 patients (mean age 66 years; range, 58-82 years) were treated this way and followed for a minimum of 2 years (range, 26-81 months); none was lost to followup, and all have been seen in the last 5 years. We compared pre- and postoperative ranges of motion, pain, and functional status; scores were drawn from chart review. We also categorized major and minor complications.
Active forward flexion improved from 56A degrees +/- 36A degrees to 120A degrees +/- 38A degrees (mean difference: 64A degrees [95% confidence interval {CI}, 45A degrees-83A degrees], p < 0.001). Active external rotation with the arm adducted improved from 6A degrees +/- 16A degrees to 38A degrees +/- 14A degrees (mean difference: 30A degrees [95% CI, 21A degrees-39A degrees], p < 0.001); active external rotation with the arm abducted improved from 19A degrees +/- 25A degrees to 74A degrees +/- 22A degrees (mean difference: 44A degrees [95% CI, 22A degrees-65A degrees], p < 0.001). Pain visual analog score improved from 8.4 +/- 2.3 to 1.7 +/- 2.1 (mean difference: -6.9 [95% CI, -8.7 to -5.2], p < 0.001), and Single Assessment Numeric Evaluation score improved from 28% +/- 21% to 80% +/- 24% (mean difference: 46% [95% CI, 28%-64%], p < 0.001). There were six major complications, five of which were treated operatively. Overall, three patients' latissimus and teres major transfer failed based on persistent lack of external rotation.
In patients with posterior and superior cuff deficiency, reverse shoulder arthroplasty combined with latissimus dorsi and teres major transfer through a single deltopectoral incision can reliably increase active forward flexion and external rotation. Patients experience pain relief and functional improvement but have a high rate of complications; therefore, we recommend the procedure be limited to patients indicated for reverse who have profound external rotation loss and a high grade of infraspinatus/teres minor fatty atrophy.
Level IV, therapeutic study.
C1 [Shi, Lewis L.; Cahill, Kirk E.] Univ Chicago Hosp, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA.
[Ek, Eugene T.] Univ Melbourne, Austin Hosp, Melbourne Orthopaed Grp, Melbourne, Vic, Australia.
[Ek, Eugene T.] Univ Melbourne, Austin Hosp, Dept Orthopaed Surg, Melbourne, Vic, Australia.
[Tompson, Jeffrey D.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA.
[Higgins, Laurence D.] Brigham & Womens Hosp, Sports Med & Shoulder Serv, Boston, MA 02115 USA.
RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, 55 Fruit St, Boston, MA 02114 USA.
EM jwarner@partners.org
FU NCATS NIH HHS [UL1 TR000430]
NR 18
TC 1
Z9 1
U1 0
U2 4
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 OCT
PY 2015
VL 473
IS 10
BP 3212
EP 3217
DI 10.1007/s11999-015-4433-4
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA CQ9FO
UT WOS:000360918400022
PM 26139622
ER
PT J
AU Graham, JR
Calloway, A
Roemer, L
AF Graham, Jessica R.
Calloway, Amber
Roemer, Lizabeth
TI The Buffering Effects of Emotion Regulation in the Relationship Between
Experiences of Racism and Anxiety in a Black American Sample
SO COGNITIVE THERAPY AND RESEARCH
LA English
DT Article
DE African American; Racism; Anxiety; Emotion regulation
ID AMBULATORY BLOOD-PRESSURE; STRESS SCALES DASS-21; DEPRESSION ANXIETY;
AFRICAN-AMERICANS; REGULATION DIFFICULTIES; ETHNIC-DIFFERENCES;
COLLEGE-STUDENTS; DISCRIMINATION; DISORDER; IDENTITY
AB The current study explores the potential moderating effect of difficulties in emotion regulation on the relationship between racist experiences and anxiety symptomology in a Black American sample. One hundred forty participants completed a questionnaire packet containing measures of anxious arousal and stress (general anxiety) symptoms, difficulties in emotion regulation, and experiences of racist events. Results indicated that difficulties in emotion regulation moderated the relationship between past week frequency of racist events and anxious arousal as well as past year frequency of racist events and anxious arousal. Specifically, these relationships were significantly positive at high levels of difficulties in emotion regulation and not significant at low levels of difficulties in emotion regulation. Emotion regulation skills may help Black Americans cope with anxious arousal related to racist experiences. The clinical implications of these findings and future research directions are discussed.
C1 [Graham, Jessica R.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA.
[Calloway, Amber; Roemer, Lizabeth] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA.
RP Graham, JR (reprint author), Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA.
EM Jessica.Rose.Graham@gmail.com
FU Craig R. Bollinger Dissertation Grant through the University of
Massachusetts Boston
FX This study was supported by the Craig R. Bollinger Dissertation Grant
through the University of Massachusetts Boston.
NR 62
TC 4
Z9 4
U1 4
U2 14
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0147-5916
EI 1573-2819
J9 COGNITIVE THER RES
JI Cogn. Ther. Res.
PD OCT
PY 2015
VL 39
IS 5
BP 553
EP 563
DI 10.1007/s10608-015-9682-8
PG 11
WC Psychology, Clinical
SC Psychology
GA CR1BP
UT WOS:000361058100001
ER
PT J
AU Magruder, K
Yeager, D
Goldberg, J
Forsberg, C
Litz, B
Vaccarino, V
Friedman, M
Gleason, T
Huang, G
Smith, N
AF Magruder, K.
Yeager, D.
Goldberg, J.
Forsberg, C.
Litz, B.
Vaccarino, V.
Friedman, M.
Gleason, T.
Huang, G.
Smith, N.
TI Diagnostic performance of the PTSD checklist and the Vietnam Era Twin
Registry PTSD scale
SO EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES
LA English
DT Article
DE Assessment; CIDI; PCL; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY-CARE; SCREENING INSTRUMENT;
TERRORIST ATTACKS; FEMALE VETERANS; COMORBIDITY; PREVALENCE; MORTALITY;
INTERVIEW; CANCER
AB Aims. Self-report questionnaires are frequently used in clinical and epidemiologic studies to assess post-traumatic stress disorder (PTSD). A number of studies have evaluated these scales relative to clinician administered structured interviews; however, there has been no formal evaluation of their performance relative to non-clinician administered epidemiologic assessments such as the Composite International Diagnostic Interview (CIDI). We examined the diagnostic performance of two self-report PTSD scales, the PTSD checklist (PCL) and the Vietnam Era Twin Registry (VET-R) PTSD scale, compared to the CIDI.
Methods. Data were derived from a large epidemiologic follow-up study of PTSD in 5141 Vietnam Era Veterans. Measures included the PCL, VET-R PTSD scale and CIDI. For both the PCL and VET-R PTSD scale, ROC curves, areas under the curve (AUC), sensitivity, specificity, % correctly classified, likelihood ratios, predictive values and quality estimates were generated based on the CIDI PTSD diagnosis.
Results. For the PCL and VET-R PTSD scale the AUCs were 89.0 and 87.7%, respectively. Optimal PCL cutpoints varied from the 31-33 range (when considering sensitivity and specificity) to the 36-56 range (when considering quality estimates). Similar variations were found for the VET-R PTSD, ranging from 31 (when considering sensitivity and specificity) to the 37-42 range (when considering quality estimates).
Conclusions. The PCL and VET-R PTSD scale performed similarly using a CIDI PTSD diagnosis as the criterion. There was a range of acceptable cutpoints, depending on the metric used, but most metrics suggested a lower PCL cutpoint than in previous studies in Veteran populations.
C1 [Magruder, K.; Yeager, D.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA.
[Magruder, K.; Yeager, D.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Goldberg, J.; Forsberg, C.; Smith, N.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Goldberg, J.; Smith, N.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Litz, B.] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr, Boston, MA USA.
[Litz, B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Vaccarino, V.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Vaccarino, V.] Emory Univ, Dept Med, Atlanta, GA 30322 USA.
[Friedman, M.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, White River Jct, VT USA.
[Friedman, M.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA.
[Friedman, M.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA.
[Gleason, T.; Huang, G.] VA Off Res & Dev, Cooperat Studies Program, Clin Sci Res & Dev, Washington, DC USA.
RP Magruder, K (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA.
EM magrudkm@musc.edu
FU Cooperative Studies Program (CSP) of the US Department of Veterans
Affairs' Office of Research and Development [569]; National Institutes
of Health award [K24 HL077506]
FX The Cooperative Studies Program (CSP) of the US Department of Veterans
Affairs' Office of Research and Development 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 36
TC 2
Z9 2
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2045-7960
EI 2045-7979
J9 EPIDEMIOL PSYCH SCI
JI Epidemiol. Psychiatr. Sci.
PD OCT
PY 2015
VL 24
IS 5
BP 415
EP 422
DI 10.1017/S2045796014000365
PG 8
WC Psychiatry
SC Psychiatry
GA CR2DN
UT WOS:000361135400010
PM 24905737
ER
PT J
AU Chaudhary, K
Speights, K
McGuire, K
White, AP
AF Chaudhary, Kshitij
Speights, Katharine
McGuire, Kevin
White, Andrew P.
TI Trans-cranial motor evoked potential detection of femoral nerve injury
in trans-psoas lateral lumbar interbody fusion
SO JOURNAL OF CLINICAL MONITORING AND COMPUTING
LA English
DT Article
DE Motor evoked potentials; Electromyography; Trans-psoas interbody fusion;
LLIF; XLIF; DLIF; Lumbar plexus
ID APPROACH CLINICAL ARTICLE; SURGERY; ELECTROMYOGRAPHY; EFFICACY
AB Trans-psoas lateral lumbar interbody fusion (LLIF) is frequently associated with neurological complications, limiting its value as a less invasive procedure. The routine use of EMG neuromonitoring has been inadequate to detect iatrogenic injuries; significant postoperative deficits have gone undetected by EMG. An effective way to monitor for these intraoperative neurological events is not yet well established. To our knowledge, detection of lumbar plexus injury during LLIF by trans-cranial motor evoked potentials (MEP) without corresponding change in EMG has not been reported in the literature. Three cases are presented to illustrate the potential utility of trans-cranial MEP monitoring during trans-psoas LLIF. We introduce a modified intraoperative neuro-monitoring (IONM) protocol for LLIF surgery, which includes MEP in addition to spontaneous and triggered EMG. Postoperative neurological outcome was correlated with the IONM findings. In each case, loss of quadriceps MEP signals occurred during LLIF at L4/L5, and after prolonged retraction (27, 25 and 61 min respectively). The EMG, however, did not show any abnormal activity. Two patients had post-operative quadriceps weakness, concordant with MEP data. The third patient, in whom the MEP signals returned to normal after expeditious removal of the retractor, did not exhibit quadriceps weakness, also concordant with MEP data. These cases contribute to the developing perception that stand-alone EMG nerve monitoring is not adequate for trans-psoas surgery. The addition of MEP may improve the sensitivity of IONM during trans-psoas surgery. Multimodality IONM may offer the opportunity to intervene on evolving iatrogenic nerve injuries, and may reduce the incidence of adverse postoperative findings.
C1 [Chaudhary, Kshitij; McGuire, Kevin; White, Andrew P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA.
[White, Andrew P.] BIDMC Orthopaed, Boston, MA 02215 USA.
[Speights, Katharine] Safe Passage Neuromonitoring, Boston, MA USA.
RP Chaudhary, K (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA.
EM chaudhary.kc@gmail.com; apwhite@bidmc.harvard.edu
NR 14
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1387-1307
EI 1573-2614
J9 J CLIN MONIT COMPUT
JI J. Clin. Monitor. Comp.
PD OCT
PY 2015
VL 29
IS 5
BP 549
EP 554
DI 10.1007/s10877-015-9713-8
PG 6
WC Anesthesiology
SC Anesthesiology
GA CR1BU
UT WOS:000361058600004
PM 26076805
ER
PT J
AU Liu, YH
Pian-Smith, MCM
Leffert, LR
Minehart, RD
Torri, A
Cote, C
Kacmarek, RM
Jiang, YD
AF Liu, Yanhong
Pian-Smith, May C. M.
Leffert, Lisa R.
Minehart, Rebecca D.
Torri, Andrea
Cote, Charles
Kacmarek, Robert M.
Jiang, Yandong
TI Continuous measurement of cardiac output with the electrical velocimetry
method in patients under spinal anesthesia for cesarean delivery
SO JOURNAL OF CLINICAL MONITORING AND COMPUTING
LA English
DT Article
DE Cardiac output; Spinal anesthesia; Electrical velocimetry; Obstetric;
Cesarean delivery
ID IMPEDANCE CARDIOGRAPHY; MATERNAL HEMODYNAMICS; STROKE VOLUME;
PHENYLEPHRINE; THERMODILUTION; PRESSURE; SURGERY; STIMULATION; OXYTOCIN;
LABOR
AB In this study, we aimed to continuously measure cardiac output (CO) with the electrical velocimetry (EV) method and characterize the hemodynamic profile of patients undergoing spinal anesthesia for elective cesarean delivery (CD), and to discuss the potential benefit of using real time CO monitoring to guide patient management. Forty-two patients scheduled for elective CD under spinal anesthesia were enrolled in this observational study. A non-invasive CO monitor incorporating the electrical velocimetry algorithm, ICONA (R) (Cardiotronic(A (R)), La Jolla, California, USA), was used to measure CO and stroke volume (SV) continuously. Peripheral venous pressure was measured intermittently at pre-defined time points. Systemic vascular resistance was calculated retrospectively after completion of the study. Hemodynamic changes at pre-defined time points and caused by phenylephrine administration were analyzed. Hypotension (MAP reduction more than 20 % from baseline values) occurred in 71.1 % of patients after spinal anesthesia, while the coinstantaneous CO was increased a parts per thousand yen20 % from baseline in the majority of patients (76.3 %) at the same time. Significant increase in CO took place at 3-2 min before the administration of phenylephrine bolus. Treatment of hypotension with phenylephrine was associated with significant decrease in CO. Continuous CO monitoring with EV enables clinicians to determine CO and SV changes prior to onset of hypotension and to better understand patients' hemodynamics. It is an important addition to the current monitoring. The benefit of routinely using this technique remains to be determined in term of the patient outcomes.
C1 [Liu, Yanhong; Pian-Smith, May C. M.; Leffert, Lisa R.; Minehart, Rebecca D.; Torri, Andrea; Cote, Charles; Kacmarek, Robert M.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA.
EM yjiang@partners.org
FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts
General Hospital
FX Authors sincerely thank Dr. Donald P. Bernstein, Cardiovascular
Engineering Sotera Wireless, Inc. San Diego, CA for his editing of this
article. This project is funded by the Department of Anesthesia,
Critical Care and Pain Medicine, Massachusetts General Hospital.
NR 30
TC 2
Z9 2
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1387-1307
EI 1573-2614
J9 J CLIN MONIT COMPUT
JI J. Clin. Monitor. Comp.
PD OCT
PY 2015
VL 29
IS 5
BP 627
EP 634
DI 10.1007/s10877-014-9645-8
PG 8
WC Anesthesiology
SC Anesthesiology
GA CR1BU
UT WOS:000361058600016
PM 25510959
ER
PT J
AU Pachankis, JE
Hatzenbuehler, ML
Rendina, HJ
Safren, SA
Parsons, JT
AF Pachankis, John E.
Hatzenbuehler, Mark L.
Rendina, H. Jonathon
Safren, Steven A.
Parsons, Jeffrey T.
TI LGB-Affirmative Cognitive-Behavioral Therapy for Young Adult Gay and
Bisexual Men: A Randomized Controlled Trial of a Transdiagnostic
Minority Stress Approach
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE minority stress; stigma; LGB-affirmative; intervention;
cognitive-behavioral therapy (CBT)
ID PSYCHOSOCIAL HEALTH-PROBLEMS; SEXUAL COMPULSIVITY SCALE; REJECTION
SENSITIVITY; EMOTIONAL DISORDERS; STRUCTURAL STIGMA; UNIFIED PROTOCOL;
IMPAIRMENT SCALE; HETEROSEXUAL ADOLESCENTS; SCREENING INSTRUMENT;
ALCOHOL-CONSUMPTION
AB Objectives: We tested the preliminary efficacy of a transdiagnostic cognitive-behavioral treatment adapted to improve depression, anxiety, and co-occurring health risks (i.e., alcohol use, sexual compulsivity, condomless sex) among young adult gay and bisexual men. Treatment adaptations focused on reducing minority stress processes that underlie sexual orientation-related mental health disparities. Method: Young gay and bisexual men (n = 63; M age = 25.94) were randomized to immediate treatment or a 3-month waitlist. At baseline, 3-month, and 6-month assessments, participants completed self-reports of mental health and minority stress and an interview of past-90-day risk behavior. Results: Compared to waitlist, treatment significantly reduced depressive symptoms (b = -2.43, 95% CI: -4.90, 0.35, p < .001), alcohol use problems (b = -3.79, 95% CI: -5.94, -1.64, p < .001), sexual compulsivity (b = -5.09, 95% CI: -8.78, -1.40, p < .001), and past-90-day condomless sex with casual partners (b = -1.09, 95% CI: -1.80, -0.37, p < .001), and improved condom use self-efficacy (b = 10.08, 95% CI: 3.86, 16.30, p < .001). The treatment yielded moderate and marginally significant greater improvements than waitlist in anxiety symptoms (b = -2.14, 95% CI: -4.61, 0.34, p = .09) and past-90-day heavy drinking (b = -0.32, 95% CI: -0.71, 0.07, p = .09). Effects were generally maintained at follow-up. Minority stress processes showed small improvements in the expected direction. Conclusion: This study demonstrated preliminary support for the first intervention adapted to address gay and bisexual men's co-occurring health problems at their source in minority stress. If found to be efficacious compared to standard evidence-based treatments, the treatment will possess substantial potential for helping clinicians translate LGB-affirmative treatment guidelines into evidence-based practice.
C1 [Pachankis, John E.] Yale Univ, Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, Social & Behav Sci Div, New Haven, CT 06520 USA.
[Hatzenbuehler, Mark L.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10027 USA.
[Rendina, H. Jonathon; Parsons, Jeffrey T.] Ctr HIV AIDS Educ Studies & Training CHEST, New York, NY USA.
[Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA.
[Parsons, Jeffrey T.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA.
RP Pachankis, JE (reprint author), Yale Univ, Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, Social & Behav Sci Div,Lab Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA.
EM john.pachankis@yale.edu
RI Rendina, H. Jonathon/M-9286-2016;
OI Rendina, H. Jonathon/0000-0002-0148-2852; Parsons,
Jeffrey/0000-0002-6875-7566
FU National Institute of Mental Health [R34-MH096607, K24 MH094214];
National Institute on Drug Abuse [K01 DA039030]
FX This project was supported by a research grant from the National
Institute of Mental Health (R34-MH096607; John E. Pachankis, Principal
Investigator). H. Jonathon Rendina's contribution to this project was
supported, in part, by a grant from the National Institute on Drug Abuse
(K01 DA039030). Steven A. Safren's contribution was supported by a grant
from the National Institute of Mental Health (K24 MH094214). The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. The
authors would like to acknowledge the contributions of the ESTEEM
research team: Evie Arroyo, Aliza Boim, Demetria Cain, Michael Castro,
Chris Cruz, Sitaji Gurung, Ethan Fusaris, Ruben Jimenez, Douglas Keeler,
Alexa Michl, Brett Millar, Chloe Mirzayi, Theresa Navalta, Luis Nobrega,
Brian Salfas, Martez Smith, Laurie Spacek, Rachel Proujansky, Anita
Viswanath, Jonathan Warren, and Thomas Whitfield.
NR 85
TC 16
Z9 16
U1 3
U2 19
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
EI 1939-2117
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD OCT
PY 2015
VL 83
IS 5
BP 875
EP 889
DI 10.1037/ccp0000037
PG 15
WC Psychology, Clinical
SC Psychology
GA CR3IS
UT WOS:000361226400004
PM 26147563
ER
PT J
AU Tothova, Z
Berliner, N
AF Tothova, Zuzana
Berliner, Nancy
TI Hemophagocytic Syndrome and Critical Illness: New Insights into
Diagnosis and Management
SO JOURNAL OF INTENSIVE CARE MEDICINE
LA English
DT Review
DE hemophagocytic lymphohistiocytosis; ferritin; hemophagocytic syndrome;
HPS
ID EPSTEIN-BARR-VIRUS; STEM-CELL TRANSPLANTATION; PERFORIN GENE-MUTATIONS;
CLINICAL-FEATURES; BONE-MARROW; SOLUBLE INTERLEUKIN-2-RECEPTOR;
LYMPHOHISTIOCYTOSIS FHL; INTERFERON-GAMMA; CYTOKINE PATTERN; XIAP
DEFICIENCY
AB Hemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous group of diseases that are characterized by a hyperinflammatory state due to uncontrolled T cell, macrophage, and histiocyte activation, accompanied by excessive cytokine production. This rare condition is almost uniformly fatal unless promptly recognized and treated. Much progress has been made in the last two decades in our understanding of the mechanisms underlying familial, and to a lesser extent, acquired cases of HLH. Recurrent mutations in more than 10 different genes have now been identified, involving biological pathways converging on intracellular vesicle trafficking and cytolytic granule exocytosis. Mechanisms underlying the majority of patients with acquired HLH, however, remain elusive, hampering both diagnostic evaluation and therapeutic management of these patients. Given that the majority of intensive care unit (ICU) patients with sepsis or multiorgan failure share many features of HLH, it is especially critical for pediatric and adult intensivists to be able to recognize patients with bona fide HLH and initiate treatment without delay. In this article, we review our current understanding of the pathophysiology, clinical testing, diagnosis, and treatment of patients with HLH, especially as it pertains to the care of critically ill patients in pediatric and medical ICUs.
C1 [Tothova, Zuzana; Berliner, Nancy] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Tothova, Zuzana; Berliner, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Berliner, N (reprint author), Brigham & Womens Hosp, Div Hematol, Mid Campus 3,75 Francis St, Boston, MA 02115 USA.
EM nancy_berliner@dfci.harvard.edu
FU NCI NIH HHS [T32 CA009172]
NR 84
TC 7
Z9 7
U1 1
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0885-0666
EI 1525-1489
J9 J INTENSIVE CARE MED
JI J. Intensive Care Med.
PD OCT
PY 2015
VL 30
IS 7
BP 401
EP 412
DI 10.1177/0885066613517076
PG 12
WC Critical Care Medicine
SC General & Internal Medicine
GA CR2FK
UT WOS:000361141400004
PM 24407034
ER
PT J
AU Feldman, S
Kimball, AB
Warren, RB
Frazier, D
Proulx, J
Marren, A
AF Feldman, Steven
Kimball, Alexandra B.
Warren, Richard B.
Frazier, Don
Proulx, James
Marren, Amy
TI Pregnancy outcomes in the tofacitinib psoriasis safety database up to
April 2014
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 4th World Psoriasis and Psoriatic Arthritis Conference on Psoriasis -
New Insights and Innovations
CY OCT, 2015
CL Stockholm, SWEDEN
C1 [Feldman, Steven] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Kimball, Alexandra B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kimball, Alexandra B.] Harvard Univ, Sch Med, Boston, MA USA.
[Warren, Richard B.] Univ Manchester, Manchester, Lancs, England.
[Frazier, Don; Proulx, James] Pfizer Inc, Groton, CT 06340 USA.
[Marren, Amy] Pfizer Inc, Collegeville, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD OCT
PY 2015
VL 135
SU 3
MA P036
BP S9
EP S9
PG 1
WC Dermatology
SC Dermatology
GA CR2LG
UT WOS:000361160500037
ER
PT J
AU Kimball, AB
Guenther, L
De Jong, E
Kalia, S
Goyal, K
Langholff, W
Fakharzadeh, S
Calabro, S
Crow, JA
Hopkins, L
Shear, NH
AF Kimball, A. B.
Guenther, L.
De Jong, E.
Kalia, S.
Goyal, K.
Langholff, W.
Fakharzadeh, S.
Calabro, S.
Crow, J. A.
Hopkins, L.
Shear, N. H.
TI Pregnancy outcomes in women with moderate to severe psoriasis: The
PSOLAR experience
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 4th World Psoriasis and Psoriatic Arthritis Conference on Psoriasis -
New Insights and Innovations
CY OCT, 2015
CL Stockholm, SWEDEN
C1 [Kimball, A. B.] Harvard Univ, Sch Med, Dermatol, Boston, MA USA.
[Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Guenther, L.] Guenther Dermatol Res Ctr, Dermatol, London, ON, Canada.
[De Jong, E.] Univ Med Ctr Nijmegen St Radboud, Dermatol, Nijmegen, Netherlands.
[Kalia, S.] UBC Dermatol, Dermatol, Vancouver, BC, Canada.
[Goyal, K.; Fakharzadeh, S.; Calabro, S.; Hopkins, L.] Janssen Sci Affairs LLC, Immunol, Horsham, PA USA.
[Langholff, W.] Janssen Res & Dev LLC, Biostat, Spring House, PA USA.
[Crow, J. A.] Janssen Sci Affairs LLC, Dermatol, Horsham, PA USA.
[Shear, N. H.] Univ Toronto, Dermatol, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD OCT
PY 2015
VL 135
SU 3
MA P056
BP S16
EP S16
PG 1
WC Dermatology
SC Dermatology
GA CR2LG
UT WOS:000361160500057
ER
PT J
AU Kimball, AB
Nikai, E
Zhu, BJ
Carlier, H
Yosipovitch, G
AF Kimball, Alexa Boer
Nikai, Enkeleida
Zhu, Baojin
Carlier, Hilde
Yosipovitch, Gil
TI Ixekizumab impact on itch severity compared to etanercept and placebo:
Results from UNCOVER-2, a phase 3 trial in patients with
moderate-to-severe plaque psoriasis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT 4th World Psoriasis and Psoriatic Arthritis Conference on Psoriasis -
New Insights and Innovations
CY OCT, 2015
CL Stockholm, SWEDEN
C1 [Kimball, Alexa Boer] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kimball, Alexa Boer] Harvard Univ, Sch Med, Boston, MA USA.
[Nikai, Enkeleida; Zhu, Baojin; Carlier, Hilde] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Yosipovitch, Gil] Temple Univ, Philadelphia, PA 19122 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 OCT
PY 2015
VL 135
SU 3
MA P066
BP S19
EP S19
PG 1
WC Dermatology
SC Dermatology
GA CR2LG
UT WOS:000361160500066
ER
PT J
AU Yeh, DD
Cropano, C
Quraishi, SA
Fuentes, E
Kaafarani, H
Lee, J
Velmahos, G
AF Yeh, Daniel Dante
Cropano, Catrina
Quraishi, Sadeq A.
Fuentes, Eva
Kaafarani, Haytham
Lee, Jarone
Velmahos, George
TI Periprocedural nutrition in the intensive care unit: a pilot study
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Compensatory feedings; Perioperative nutrition; Caloric debt;
Complications; Malnutrition; Tracheostomy
ID ENTERAL NUTRITION; MECHANICAL VENTILATION; PRACTICE GUIDELINES;
AMERICAN-SOCIETY; TUBE FEEDINGS; DELIVERY; THERAPY; PATIENT; SUPPORT
AB Background: Enteral nutrition (EN) delivery in the surgical intensive care unit (ICU) is often suboptimal as it is commonly interrupted for procedures. We hypothesized that continuing perioperative nutrition or providing compensatory nutrition would improve caloric delivery without increasing morbidity.
Materials and methods: We enrolled 10 adult surgical ICU patients receiving EN who were scheduled for elective bedside percutaneous tracheostomy. In these patients (fed group), either perioperative EN was maintained or compensatory nutrition was provided. We compared the amount of calories delivered, caloric deficits, and the rate of complications of these patients with those of 22 contemporary controls undergoing tracheostomy while adhering to the traditional American Society of Anesthesiology nil per os guidelines (unfed group). We defined caloric deficit as the difference between prescribed calories and actual delivered calories.
Results: There was no difference in demographic characteristics between the two groups. On the day of procedure, the fed group had higher median delivered calories (1706 kcal; interquartile range [IQR], 1481-2009 versus 588 kcal; IQR, 353-943; P < 0.0001) and received a higher percentage of prescribed calories (92%; IQR, 82%-97% versus 34%; IQR, 24%-51%; P < 0.0001). Median caloric deficit on the day of the procedure was significantly lower in the fed group (175 kcal; IQR, 49-340 versus 1133 kcal; IQR, 660-1365; P < 0.0001). There were no differences in total overall ICU complications per patient, gastrointestinal complications on the day of procedure, or total infectious complications per patient between the two groups.
Conclusions: In our pilot study, perioperative and compensatory nutrition resulted in higher caloric delivery and was not associated with increased morbidity. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Yeh, Daniel Dante; Cropano, Catrina; Quraishi, Sadeq A.; Fuentes, Eva; Kaafarani, Haytham; Lee, Jarone; Velmahos, George] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St 810, Boston, MA 02114 USA.
EM dyeh2@partners.org
NR 17
TC 0
Z9 0
U1 2
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD OCT
PY 2015
VL 198
IS 2
BP 346
EP 350
DI 10.1016/j.jss.2015.06.039
PG 5
WC Surgery
SC Surgery
GA CQ6IM
UT WOS:000360708000013
PM 26187187
ER
PT J
AU Albadawi, H
Oklu, R
Milner, JD
Uong, TP
Yoo, HJ
Austen, WG
Watkins, MT
AF Albadawi, Hassan
Oklu, Rahmi
Milner, John D.
Uong, Thuy P.
Yoo, Hyung-Jin
Austen, William G., Jr.
Watkins, Michael T.
TI Effect of limb demand ischemia on autophagy and morphology in mice
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Limb demand ischemia; Diet-induced obesity; Type-2 diabetes; Peripheral
arterial disease; Autophagy; Mitochondrial biogenesis; Muscle
regeneration
ID PERIPHERAL ARTERIAL-DISEASE; MUSCLE SATELLITE CELLS; SKELETAL-MUSCLE;
MITOCHONDRIAL FUSION; REPERFUSION INJURY; OXIDATIVE DAMAGE; EXERCISE;
MYOPATHY; GASTROCNEMIUS; DEGENERATION
AB Background: Obesity is a major risk factor for diabetes and peripheral arterial disease, which frequently leads to lower limb demand ischemia. Skeletal muscle autophagy and mitochondrial biogenesis are important processes for proper oxidative capacity and energy metabolism, which are compromised in diabetes. This study compares autophagy, mitochondrial biogenesis, energy metabolism, and morphology in the hind limbs of obese diabetic mice subjected to demand or sedentary ischemia.
Materials and methods: Unilateral hind limb demand ischemia was created in a group of diet-induced obese mice after femoral artery ligation and 4 wk of daily exercise. A parallel group of mice underwent femoral artery ligation but remained sedentary for 4 wk. Hind limb muscles were analyzed for markers of autophagy, mitochondrial biogenesis, adenosine triphosphate, and muscle tissue morphology.
Results: At the end of the 4-wk exercise period, demand ischemia increased the autophagy mediator Beclin-1, but it did not alter the autophagy indicator, LC3B-II/I ratio, or markers of mitochondrial biogenesis, optic atrophy/dynamin-related protein. In contrast, exercise significantly increased the level of mitochondrial protein-succinate dehydrogenase subunit-A and reduced adipocyte accumulation and the percentage of centrally nucleated myofibers in the demand ischemia limb. In addition, demand ischemia resulted in decreased uncoupling protein-3 levels without altering muscle adenosine triphosphate or pS473-Akt levels.
Conclusions: Limb demand ischemia markedly decreased adipocyte accumulation and enhanced muscle regeneration in obese mice, but it did not appear to enhance autophagy, mitochondrial biogenesis, energy metabolism, or insulin sensitivity. Future studies aimed at evaluating novel therapies that enhance autophagy and mitochondrial biogenesis in diabetes with peripheral arterial disease are warranted. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Albadawi, Hassan; Milner, John D.; Uong, Thuy P.; Yoo, Hyung-Jin; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
[Albadawi, Hassan; Oklu, Rahmi; Milner, John D.; Uong, Thuy P.; Yoo, Hyung-Jin; Austen, William G., Jr.; Watkins, Michael T.] Harvard Univ, Sch Med, Boston, MA USA.
[Oklu, Rahmi] Massachusetts Gen Hosp, Dept Imaging, Div Vasc & Intervent Radiol, Boston, MA 02114 USA.
[Austen, William G., Jr.] Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA.
RP Albadawi, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Vasc Res Lab, Div Vasc & Endovasc Surg, Edwards 301,70 Blossom St, Boston, MA 02114 USA.
EM halbadawi@mgh.harvard.edu
OI Albadawi, Hassan/0000-0001-5913-8571
FU NIH [RO1 (AR055843)]; Department of Surgery, Division of Vascular and
Endovascular Surgery, Henry & Nod Meyer Sundry Fund
FX This study was supported by NIH grant RO1 (AR055843), the Department of
Surgery, Division of Vascular and Endovascular Surgery, Henry & Nod
Meyer Sundry Fund.
NR 41
TC 1
Z9 1
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 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD OCT
PY 2015
VL 198
IS 2
BP 515
EP 524
DI 10.1016/j.jss.2015.04.008
PG 10
WC Surgery
SC Surgery
GA CQ6IM
UT WOS:000360708000040
PM 25959834
ER
PT J
AU Vargas, CR
Koolen, PGL
Ho, OA
Ricci, JA
Tobias, AM
Lin, SJ
Lee, BT
AF Vargas, Christina R.
Koolen, Pieter G. L.
Ho, Olivia A.
Ricci, Joseph A.
Tobias, Adam M.
Lin, Samuel J.
Lee, Bernard T.
TI Tumescent mastectomy technique in autologous breast reconstruction
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Tumescent technique; Mastectomy; Breast cancer; Breast reconstruction;
Microsurgery; Autologous reconstruction; Outcomes
ID IMMEDIATE RECONSTRUCTION; PERFORATOR-DISSECTION; FLAP NECROSIS; RISK;
HYDRODISSECTION; ELECTROCAUTERY; ANESTHESIA; INCREASE
AB Background: Use of the tumescent mastectomy technique has been reported to facilitate development of a hydrodissection plane, reduce blood loss, and provide adjunct analgesia. Previous studies suggest that tumescent dissection may contribute to adverse outcomes after immediate implant reconstruction; however, its effect on autologous microsurgical reconstruction has not been established.
Methods: A retrospective review was conducted of all immediate microsurgical breast reconstruction procedures at a single academic center between January 2004 and December 2013. Records were queried for age, body mass index, mastectomy weight, diabetes, hypertension, smoking, preoperative radiation, reconstruction flap type, and autologous flap weight. Outcomes of interest were mastectomy skin necrosis, complete and partial flap loss, return to the operating room, breast hematoma, seroma, and infection.
Results: There were 730 immediate autologous breast reconstructions performed during the study period; 46% with the tumescent dissection technique. Groups were similar with respect to baseline patient and procedural characteristics. Univariate analysis revealed no significant difference in the incidence of mastectomy skin necrosis, complete or partial flap loss, return to the operating room, operative time, estimated blood loss, recurrence, breast hematoma, seroma, or infection in patients undergoing tumescent mastectomy. Multivariate analysis also demonstrated no significant association between the use of tumescent technique and postoperative breast mastectomy skin necrosis (P = 0.980), hematoma (P = 0.759), or seroma (P = 0.340).
Conclusions: Use of the tumescent dissection technique during mastectomy is not significantly associated with adverse outcomes after microsurgical breast reconstruction. Despite concern for its impact on implant reconstruction, our findings suggest that this method can be used safely preceding autologous procedures. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Vargas, Christina R.; Tobias, Adam M.; Lin, Samuel J.; Lee, Bernard T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA.
[Koolen, Pieter G. L.; Ho, Olivia A.; Ricci, Joseph A.; Tobias, Adam M.; Lin, Samuel J.; Lee, Bernard T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Plast & Reconstruct Surg, Dept Surg,Med Sch, Boston, MA 02215 USA.
RP Lee, BT (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg, 110 Francis St,Suite 5A, Boston, MA 02215 USA.
EM btlee@bidmc.harvard.edu
RI Lee, Bernard/K-1106-2016
OI Lee, Bernard/0000-0002-5533-3166
NR 19
TC 1
Z9 1
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 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD OCT
PY 2015
VL 198
IS 2
BP 525
EP 529
DI 10.1016/j.jss.2015.03.050
PG 5
WC Surgery
SC Surgery
GA CQ6IM
UT WOS:000360708000041
PM 25891675
ER
PT J
AU Vargas, CR
Koolen, PG
Anderson, KE
Paul, MA
Tobias, AM
Lin, SJ
Lee, BT
AF Vargas, Christina R.
Koolen, Pieter G.
Anderson, Katarina E.
Paul, Marek A.
Tobias, Adam M.
Lin, Samuel J.
Lee, Bernard T.
TI Mastectomy skin necrosis after microsurgical breast reconstruction
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Mastectomy skin necrosis; Autologous breast reconstruction; Breast
cancer; Microsurgical breast reconstruction
ID SPARING MASTECTOMY; FLAP NECROSIS; COMPLICATIONS; METAANALYSIS;
OUTCOMES; OBESITY; RISK
AB Background: Mastectomy skin necrosis represents a significant clinical morbidity after immediate breast reconstruction. In addition to aesthetic deformity, necrosis of the native mastectomy skin may require debridement, additional reconstruction, or prolonged wound care and potentially delay oncologic treatment. This study aims to evaluate patient and procedural characteristics to identify predictors of mastectomy skin necrosis after microsurgical breast reconstruction.
Methods: A retrospective review was performed of all immediate microsurgical breast reconstructions performed at a single academic center. Patient records were queried for age, diabetes, active smoking, previous breast surgery, preoperative radiation, preoperative chemotherapy, body mass index, mastectomy type, mastectomy weight, flap type, autologous flap type, and postoperative mastectomy skin flap necrosis.
Results: There were 746 immediate autologous microsurgical flaps performed by three plastic surgeons at our institution during the study period. The incidence of mastectomy skin flap necrosis was 13.4%. Univariate analysis revealed a significantly higher incidence of mastectomy skin necrosis in patients with higher mastectomy weight (P < 0.001), higher autologous flap weight (P < 0.001), higher body mass index (0.002), and diabetes (P = 0.021). No significant association was found for age, smoking, prior breast surgery, preoperative chemotherapy or radiation, or mastectomy type. Multivariate analysis demonstrated statistically significant associations between mastectomy skin necrosis and both increasing mastectomy weight (odds ratio 1.348 per quartile increase, P = 0.009) and diabetes (odds ratio 2.356, P = 0.011).
Conclusions: Increasing mastectomy weight and coexisting diabetes are significantly associated with postoperative mastectomy skin necrosis after microsurgical reconstruction. These characteristics should be considered during patient counseling, procedure selection, operative planning, and intraoperative tissue viability assessment. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Vargas, Christina R.; Koolen, Pieter G.; Anderson, Katarina E.; Paul, Marek A.; Tobias, Adam M.; Lin, Samuel J.; Lee, Bernard T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Plast & Reconstruct Surg, Dept Surg,Med Sch, Boston, MA 02215 USA.
RP Lee, BT (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg, 110 Francis St,Suite 5A, Boston, MA 02215 USA.
EM btlee@bidmc.harvard.edu
RI Lee, Bernard/K-1106-2016;
OI Lee, Bernard/0000-0002-5533-3166; Paul, Marek/0000-0003-3474-9063
NR 17
TC 3
Z9 3
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 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD OCT
PY 2015
VL 198
IS 2
BP 530
EP 534
DI 10.1016/j.jss.2015.03.076
PG 5
WC Surgery
SC Surgery
GA CQ6IM
UT WOS:000360708000042
PM 25913487
ER
PT J
AU Enamandram, M
Rathmell, JP
Kimball, AB
AF Enamandram, Monica
Rathmell, James P.
Kimball, Alexandra B.
TI Chronic pain management in dermatology A guide to assessment and
nonopioid pharmacotherapy
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Review
DE hidradenitis suppurativa; nonsteroidal antiinflammatory drugs; opioid
analgesia; pain management; postherpetic neuralgia
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-BACK-PAIN; POSTHERPETIC
NEURALGIA; HERPES-ZOSTER; RHEUMATOID-ARTHRITIS; NEUROPATHIC PAIN;
PHARMACOLOGICAL MANAGEMENT; TOPICAL LIDOCAINE; CONTROLLED-TRIAL;
NONCANCER PAIN
AB Pain is a central component of illness and suffering, yet unfortunately it is frequently undertreated. In dermatology, many acute and chronic conditions are characterized by pain that may require therapeutic intervention in addition to medical treatment aimed at treating the primary disease. To date, however, there are limited recommendations or evidence in the published literature on pain and pain management strategies for patients with skin disease. In an effort to enable providers to more comprehensively and effectively treat chronic pain in the primary and multidisciplinary dermatologic context, these topics will be discussed in this 2-part continuing medical education article. Part I of this series will describe important mechanisms of pain and detail individualized chronic pain assessment and treatment strategies using nonopioid analgesia.
C1 [Enamandram, Monica; Kimball, Alexandra B.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Ste 240, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
NR 72
TC 2
Z9 2
U1 1
U2 6
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 OCT
PY 2015
VL 73
IS 4
BP 563
EP 573
DI 10.1016/j.jaad.2014.11.039
PG 11
WC Dermatology
SC Dermatology
GA CR2HC
UT WOS:000361146700016
PM 26369840
ER
PT J
AU Enamandram, M
Rathmell, JP
Kimball, AB
AF Enamandram, Monica
Rathmell, James P.
Kimball, Alexandra B.
TI Chronic pain management in dermatology Pharmacotherapy and therapeutic
monitoring with opioid analgesia
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Review
DE nonsteroidal antiinflammatory drugs; opioid analgesia; pain;
postherpetic neuralgia
ID CHRONIC NONCANCER PAIN; COMBINATION; GABAPENTIN; GUIDELINES; MORPHINE;
EFFICACY; SAFETY
AB A number of chronic dermatologic conditions may necessitate long-term adjunctive pain management in addition to treatment of the primary skin disease, such as hidradenitis suppurativa, lichen planus, and other systemic diseases associated with significant pain. Adequate management of chronic pain can represent a unique challenge, but remains an integral component of clinical treatment in relevant contexts. For nociceptive pain of moderate to severe intensity, opioid analgesics can be beneficial when other pain management strategies have failed to produce adequate relief. The decision to initiate long-term opioid therapy must be carefully weighed, and individualized treatment plans are often necessary to effectively treat pain while minimizing adverse effects. Part II of this 2-part continuing medical education article will describe the appropriate settings for initiation of opioid analgesia for dermatology patients and detail therapeutic strategies and patient monitoring guidelines.
C1 [Enamandram, Monica; Kimball, Alexandra B.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Ste 240, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
NR 26
TC 1
Z9 1
U1 1
U2 2
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 OCT
PY 2015
VL 73
IS 4
BP 575
EP 582
DI 10.1016/j.jaad.2014.11.038
PG 8
WC Dermatology
SC Dermatology
GA CR2HC
UT WOS:000361146700017
PM 26369841
ER
PT J
AU Tsao, H
Begolka, WS
AF Tsao, Hensin
Begolka, Wendy Smith
CA Amer Acad Dermatology Ad Hoc Task
TI Reply to: "Time to move forward after the report of the AAD Task Force
for the ABCDEs of Melanoma"
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Tsao, Hensin] Harvard Univ, Sch Med, Boston, MA USA.
[Begolka, Wendy Smith] Amer Acad Dermatol, Schaumburg, IL 60173 USA.
RP Begolka, WS (reprint author), Amer Acad Dermatol, 930 E Woodfield Rd, Schaumburg, IL 60173 USA.
EM wsmithbegolka@aad.org
NR 3
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD OCT
PY 2015
VL 73
IS 4
BP E151
EP E151
DI 10.1016/j.jaad.2015.06.044
PG 1
WC Dermatology
SC Dermatology
GA CR2HC
UT WOS:000361146700011
PM 26369859
ER
PT J
AU Acher, AW
LeCaire, TJ
Hundt, AS
Greenberg, CC
Carayon, P
Kind, AJ
Weber, SM
AF Acher, Alexandra W.
LeCaire, Tamara J.
Hundt, Ann Schoofs
Greenberg, Caprice C.
Carayon, Pascale
Kind, Amy J.
Weber, Sharon M.
TI Using Human Factors and Systems Engineering to Evaluate Readmission
after Complex Surgery
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID POSTOPERATIVE COGNITIVE DYSFUNCTION; 30-DAY HOSPITAL READMISSIONS;
QUALITATIVE CONTENT-ANALYSIS; HEALTH-CARE PROFESSIONALS;
ABDOMINAL-SURGERY; INFORMED-CONSENT; RISK-FACTORS; DELIRIUM; PATIENT;
PANCREATICODUODENECTOMY
AB BACKGROUND: Our objective was to use a human factors and systems engineering approach to understand contributors to surgical readmissions from a patient and provider perspective. Previous studies on readmission have neglected the patient perspective. To address this gap and to better inform intervention design, we evaluated how transitions of care relate to and influence readmission from the patient and clinician perspective using the Systems Engineering Initiative for Patient Safety (SEIPS) model.
STUDY DESIGN: Patients readmitted within 30 days of discharge after complex abdominal surgery were interviewed. A focus group of inpatient clinician providers was conducted. Questions were guided by the SEIPS framework and content was analyzed. Data were collected concurrently from the medical record for a mixed-methods approach.
RESULTS: Readmission occurred a median of 8 days (range 1 to 25 days) after discharge. All patients had follow-up scheduled with their surgeon, but readmission occurred before this in 72% of patients. Primary readmission diagnoses included infection, gastrointestinal complications, and dehydration. Patients (n = 18) and clinician providers (n = 6) identified a number of factors during the transition of care that may have contributed to readmission, including poor patient and caregiver understanding; inadequate discharge preparation for home care; insufficient educational process and materials, negatively affected by electronic health record design; and inadequate care team communication.
CONCLUSIONS: This is the first study to use a human factors and systems engineering approach to evaluate the impact of the quality of the transition of care and its influence on readmission from the patient and clinician perspective. Important targets for future interventions include enhancing the discharge process, improving education materials, and increasing care team coordination, with the overarching theme that improved patient and caregiver understanding and engagement are essential to decrease readmission and postdischarge health care use. (C) 2015 by the American College of Surgeons
C1 [Acher, Alexandra W.; LeCaire, Tamara J.; Greenberg, Caprice C.; Weber, Sharon M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Surg Outcomes Res Program, Madison, WI 53792 USA.
[Kind, Amy J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA.
[LeCaire, Tamara J.; Greenberg, Caprice C.; Weber, Sharon M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA.
[Hundt, Ann Schoofs; Greenberg, Caprice C.; Carayon, Pascale] Univ Wisconsin, Ctr Qual & Prod Improvement, Madison, WI 53792 USA.
[Greenberg, Caprice C.; Carayon, Pascale] Univ Wisconsin, Dept Ind & Syst Engn, Coll Engn, Madison, WI 53792 USA.
[Acher, Alexandra W.; Kind, Amy J.; Weber, Sharon M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Weber, SM (reprint author), Univ Wisconsin, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA.
EM webers@surgery.wisc.edu
FU Clinical and Translational Science Award (CTSA) program through the
National Institutes of Health (NIH) National Center for Advancing
Translational Sciences (NCATS) [UL1TR000427]; University of Wisconsin
School of Medicine and Public Health's Wisconsin Partnership Program
(WPP); Agency for Healthcare Research and Quality (AHRQ) [K18 HS022446]
FX This study was supported by the Clinical and Translational Science Award
(CTSA) program, through the National Institutes of Health (NIH) National
Center for Advancing Translational Sciences (NCATS), grant UL1TR000427;
the University of Wisconsin School of Medicine and Public Health's
Wisconsin Partnership Program (WPP); and by the Agency for Healthcare
Research and Quality (AHRQ), grant K18 HS022446.
NR 42
TC 5
Z9 5
U1 2
U2 14
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 OCT
PY 2015
VL 221
IS 4
BP 810
EP 820
DI 10.1016/j.jamcollsurg.2015.06.014
PG 11
WC Surgery
SC Surgery
GA CR1EQ
UT WOS:000361067200006
PM 26228011
ER
PT J
AU Nurudeen, SM
Kwakye, G
Berry, WR
Chaikof, EL
Lillemoe, KD
Millham, F
Rubin, M
Schwaitzberg, S
Shamberger, RC
Zinner, MJ
Sato, L
Lipsitz, S
Gawande, AA
Haynes, AB
AF Nurudeen, Suliat M.
Kwakye, Gifty
Berry, William R.
Chaikof, Elliot L.
Lillemoe, Keith D.
Millham, Frederick
Rubin, Marc
Schwaitzberg, Steven
Shamberger, Robert C.
Zinner, Michael J.
Sato, Luke
Lipsitz, Stuart
Gawande, Atul A.
Haynes, Alex B.
TI Can 360-Degree Reviews Help Surgeons? Evaluation of Multisource Feedback
for Surgeons in a Multi-Institutional Quality Improvement Project
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Review
ID PERFORMANCE; PHYSICIANS; BEHAVIOR; MANAGERS; SAFETY; TRIAL
AB BACKGROUND: Medical organizations have increased interest in identifying and improving behaviors that threaten team performance and patient safety. Three hundred and sixty degree evaluations of surgeons were performed at 8 academically affiliated hospitals with a common Code of Excellence. We evaluate participant perceptions and make recommendations for future use.
STUDY DESIGN: Three hundred and eighty-five surgeons in a variety of specialties underwent 360-degree evaluations, with a median of 29 reviewers each (interquartile range 23 to 36). Beginning 6 months after evaluation, surgeons, department heads, and reviewers completed follow-up surveys evaluating accuracy of feedback, willingness to participate in repeat evaluations, and behavior change.
RESULTS: Survey response rate was 31% for surgeons (118 of 385), 59% for department heads (10 of 17), and 36% for reviewers (1,042 of 2,928). Eighty-seven percent of surgeons (95% CI, 75%-94%) agreed that reviewers provided accurate feedback. Similarly, 80% of department heads believed the feedback accurately reflected performance of surgeons within their department. Sixty percent of surgeon respondents (95% CI, 49%-75%) reported making changes to their practice based on feedback received. Seventy percent of reviewers (95% CI, 69%-74%) believed the evaluation process was valuable, with 82% (95% CI, 79%-84%) willing to participate in future 360-degree reviews. Thirty-two percent of reviewers (95% CI, 29%-35%) reported perceiving behavior change in surgeons.
CONCLUSIONS: Three hundred and sixty degree evaluations can provide a practical, systematic, and subjectively accurate assessment of surgeon performance without undue reviewer burden. The process was found to result in beneficial behavior change, according to surgeons and their coworkers. (C) 2015 by the American College of Surgeons
C1 [Nurudeen, Suliat M.; Kwakye, Gifty; Berry, William R.; Lipsitz, Stuart; Gawande, Atul A.; Haynes, Alex B.] Ariadne Labs, Boston, MA USA.
[Nurudeen, Suliat M.; Kwakye, Gifty; Berry, William R.; Zinner, Michael J.; Lipsitz, Stuart; Gawande, Atul A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Nurudeen, Suliat M.; Berry, William R.; Lipsitz, Stuart; Gawande, Atul A.; Haynes, Alex B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Chaikof, Elliot L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Lillemoe, Keith D.; Haynes, Alex B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shamberger, Robert C.] Boston Childrens Hosp, Boston, MA USA.
[Millham, Frederick] South Shore Hosp, South Weymouth, MA USA.
[Rubin, Marc] North Shore Med Ctr, Salem, MA USA.
[Schwaitzberg, Steven] Cambridge Hlth Alliance, Cambridge, MA USA.
[Sato, Luke] Harvard Med Inst Inc, Risk Management Fdn, Cambridge, MA USA.
RP Haynes, AB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM abhaynes@mgh.harvard.edu
FU Risk Management Foundation of the Harvard Medical Institutions, Inc.
FX This study was supported by a grant from The Risk Management Foundation
of the Harvard Medical Institutions, Inc.
NR 33
TC 3
Z9 3
U1 2
U2 6
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 OCT
PY 2015
VL 221
IS 4
BP 837
EP 844
DI 10.1016/j.jamcollsurg.2015.06.017
PG 8
WC Surgery
SC Surgery
GA CR1EQ
UT WOS:000361067200009
PM 26272014
ER
PT J
AU Adler, JT
Chang, DC
Maguire, LH
AF Adler, Joel T.
Chang, David C.
Maguire, Lillias H.
TI Seasonal Variation in Diverticulitis: Evidence from Both Hemispheres
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S36
EP S37
PG 2
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700055
ER
PT J
AU Aggarwal, A
Madigan, MC
Cody, E
Tzeng, E
AF Aggarwal, Ankur
Madigan, Michael C.
Cody, Ellen
Tzeng, Edith
TI A Role for Topical Nitrite in Diabetic Wound Healing
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S176
EP S176
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700369
ER
PT J
AU Bohnen, JD
Chang, DC
George, BC
AF Bohnen, Jordan D.
Chang, David C.
George, Brian C.
TI Changing Trends in Operating Room Times Between Teaching and
Non-Teaching Cases: Less Time for Learning?
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Bohnen, Jordan D.; Chang, David C.; George, Brian C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S49
EP S49
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700085
ER
PT J
AU Chang, DC
Noorbakhsh, A
Mullen, J
AF Chang, David C.
Noorbakhsh, Abraham
Mullen, John
TI Analysis of Early and Late Readmission after Gastrectomy to Index and
Nonindex Hospitals
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S122
EP S122
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700247
ER
PT J
AU Cheng, L
Hotta, R
Graham, HK
Goldstein, AM
AF Cheng, Lily
Hotta, Ryo
Graham, Hannah K.
Goldstein, Allan M.
TI Serotonin Receptor Agonism Promotes Growth of Postnatal Enteric Neuronal
Stem Cells
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Cheng, Lily; Hotta, Ryo; Graham, Hannah K.; Goldstein, Allan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S107
EP S107
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700213
ER
PT J
AU Kinnier, CV
Ju, MH
Kmiecik, TE
Barnard, C
Halverson, T
Yang, AD
Caprini, JA
Bilimoria, KY
AF Kinnier, Christine V.
Ju, Mila H.
Kmiecik, Thomas E.
Barnard, Cynthia
Halverson, Terri
Yang, Anthony D.
Caprini, Joseph A.
Bilimoria, Karl Y.
TI Development of a Novel Composite Process Measure for Venous
Thromboembolism Prophylaxis
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Northwestern Univ, Chicago, IL 60611 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NorthShore Univ Hlth Syst, Evanston, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S123
EP S123
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700251
ER
PT J
AU Li, ZM
Anderson, J
Romano, PS
Parker, JP
Young, JN
Chang, DC
AF Li, Zhongmin
Anderson, Jamie
Romano, Patrick S.
Parker, Joseph P.
Young, J. Nilas
Chang, David C.
TI Impact of Risk Adjustment for Patient Sociodemographic Status in Public
Reporting of Cardiac Surgery Outcomes
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
Calif Off Statewide Hlth Planning & Dev, Sacramento, CA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S128
EP S128
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700261
ER
PT J
AU Liu, C
Riesel, JN
Twesigye, D
Mugyenyi, G
Ngonzi, JNJ
Sanyu, F
Ttendo, S
Musinguzi, N
Mushagara, R
Firth, PG
AF Liu, Charles
Riesel, Johanna N.
Twesigye, Deus
Mugyenyi, Godfrey
Ngonzi, Joseph N. J.
Sanyu, Frank
Ttendo, Stephen
Musinguzi, Nicholas
Mushagara, Rhina
Firth, Paul G.
TI Surgical Diagnosis and Procedure Codes for Outcomes Research in a
Ugandan Regional Referral Hospital: The Mbarara Experience
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Mbarara Reg Referral Hosp, Mbarara, Uganda.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S88
EP S89
PG 2
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700173
ER
PT J
AU Loehrer, AP
Song, ZR
Chang, DC
Hutter, MM
AF Loehrer, Andrew P.
Song, Zirui
Chang, David C.
Hutter, Matthew M.
TI Health Care Reform and Equity in Bariatric Surgery: Does Increased
Access to Care Mitigate Disparities?
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Loehrer, Andrew P.; Song, Zirui; Chang, David C.; Hutter, Matthew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S126
EP S127
PG 2
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700258
ER
PT J
AU Molina, G
Neville, BA
Lipsitz, SR
Berry, W
Gawande, AA
Haynes, AB
AF Molina, George
Neville, Bridget A.
Lipsitz, Stuart R.
Berry, William
Gawande, Atul A.
Haynes, Alex B.
TI Patterns of Postoperative Care after Surgery in Freestanding Ambulatory
Surgery Centers in South Carolina
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S130
EP S131
PG 2
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700267
ER
PT J
AU Ramly, EP
Rahbani, DDR
Khalifeh, J
Hoballah, JJ
Kaafarani, HMA
AF Ramly, Elie P.
Rahbani, David D. R.
Khalifeh, Jawad
Hoballah, Jamal J.
Kaafarani, Haytham M. A.
TI Systematic Evaluation of National Surgical Capacity in Lebanon in Times
of Crisis and Refugees
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Amer Univ Beirut, Med Ctr, Beirut, Lebanon.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S89
EP S89
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700174
ER
PT J
AU Sangji, NF
Silvestri, S
Abayaah, E
Chang, DC
Hutter, MM
O'Malley, C
AF Sangji, Naveen F.
Silvestri, Sandra
Abayaah, Evelyn
Chang, David C.
Hutter, Matthew M.
O'Malley, Catherine
TI Sharps Injuries in the Operating Room Sterile Fields of an Academic
Tertiary Care Center
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 70th Annual Sessions of the Scientific Forum and Annual Clinical
Congress of the American-College-of-Surgeons
CY OCT 04-08, 2015
CL Chicago, IL
SP Amer Coll Surg
C1 [Sangji, Naveen F.; Silvestri, Sandra; Abayaah, Evelyn; Chang, David C.; Hutter, Matthew M.; O'Malley, Catherine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD OCT
PY 2015
VL 221
IS 4
SU 1
BP S132
EP S132
PG 1
WC Surgery
SC Surgery
GA CR1XX
UT WOS:000361119700271
ER
PT J
AU Deshmukh, S
Sternberg, K
Hernandez, N
Eisner, BH
AF Deshmukh, Sameer
Sternberg, Kevan
Hernandez, Natalia
Eisner, Brian H.
TI Compliance with American Urological Association Guidelines for
Post-Percutaneous Nephrolithotomy Antibiotics Does Not Appear to
Increase Rates of Infection
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; nephrostomy, percutaneous; anti-bacterial agents; standards;
compliance
ID RISK-FACTORS; TRACT INFECTION; PROPHYLAXIS; COMPLICATIONS; SURGERY;
UROSEPSIS; SEPSIS
AB Purpose: We compared infection rates after percutaneous nephrolithotomy in a group of patients without a history of infection or struvite calculi who received 24 hours or less of antibiotics postoperatively (ie compliance with AUA guidelines) vs a group that received 5 to 7 days of antibiotics postoperatively.
Materials and Methods: We retrospectively reviewed the records of consecutive percutaneous nephrolithotomy procedures in patients without a history of urinary tract infection. Group 1 received 24 hours or less of antibiotics postoperatively and group 2 received a mean of 6 days of antibiotics postoperatively.
Results: A total of 52 patients in group 1 (24 hours or less of antibiotics) and 30 in group 2 (mean 6 days of antibiotics) met study inclusion criteria. In 5 group 1 patients (9.6%) fever developed within 72 hours of percutaneous nephrolithotomy but none demonstrated bacteriuria or bacteremia on cultures. No patient in group 1 was treated for urinary tract infection on postoperative days 3 to 14. In 4 group 2 patients (13.3%) fever developed within 72 hours of percutaneous nephrolithotomy. Asingle patient showed bacteriuria (less than 10,000 cfu mixed gram-positive bacteria) on culture while no patient demonstrated bacteremia. No patient in group 2 was treated for urinary tract infection on postoperative days 3 to 14. There was no difference in stone-free rates or the need for additional procedures between the 2 groups.
Conclusions: In this pilot series compliance with AUA guidelines for antibiotic prophylaxis did not result in higher rates of infection than in a comparable group of 30 patients who received approximately 6 days of antibiotics postoperatively.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA.
[Sternberg, Kevan] Univ Vermont, Coll Med, Div Urol, Burlington, VT USA.
RP Eisner, BH (reprint author), Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA.
EM beisner@partners.org
NR 15
TC 9
Z9 9
U1 0
U2 2
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 OCT
PY 2015
VL 194
IS 4
BP 992
EP 996
DI 10.1016/j.juro.2015.04.097
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA CR3LS
UT WOS:000361234900039
PM 25936864
ER
PT J
AU Bechis, SK
Otsetov, AG
Ge, RB
Wang, ZW
Vangel, MG
Wu, CL
Tabatabaei, S
Olumi, AF
AF Bechis, Seth K.
Otsetov, Alexander G.
Ge, Rongbin
Wang, Zongwei
Vangel, Mark G.
Wu, Chin-Lee
Tabatabaei, Shahin
Olumi, Aria F.
TI Age and Obesity Promote Methylation and Suppression of 5 alpha-Reductase
2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic hyperplasia; obesity; lower urinary tract symptoms; 5-alpha
reductase inhibitors; epigenomics
ID URINARY-TRACT SYMPTOMS; DNA METHYLATION; GASTRIC BYPASS; ADULT PROSTATE;
WEIGHT-LOSS; CANCER; RISK; FINASTERIDE; EXPRESSION; SURGERY
AB Purpose: In men with symptomatic benign prostatic hyperplasia 5 alpha-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5 alpha-reductase inhibitors. We have found that a third of adult prostate samples do not express 5 alpha-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5 alpha-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5 alpha-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen.
Materials and Methods: Prostate samples from men undergoing transurethral prostate resection were used. We determined 5 alpha-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, hypertension, hyperlipidemia, diabetes, prostate specific antigen and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling.
Results: Body mass index and age significantly correlated with methylation of the 5 alpha-reductase type 2 gene promoter (p < 0.05) whereas prostate volume, prostate specific antigen or benign prostatic hyperplasia medication did not correlate. Methylation highly correlated with 5 alpha-reductase protein expression (p < 0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p < 0.01).
Conclusions: Increasing age and body mass index correlate with increased 5 alpha-reductase type 2 gene promoter methylation and decreased protein expression in men with symptomatic benign prostatic hyperplasia. These results highlight the interplay among age, obesity and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic benign prostatic hyperplasia, which may be important to choose appropriate personalized treatment options.
C1 [Bechis, Seth K.; Otsetov, Alexander G.; Ge, Rongbin; Wang, Zongwei; Tabatabaei, Shahin; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA.
[Vangel, Mark G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
[Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
[Vangel, Mark G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA.
RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,Yawkey Bldg,Suite 7E, Boston, MA 02114 USA.
EM Olumi.Aria@mgh.harvard.edu
FU National Institutes of Health [R01 DK091353]; Harvard Catalyst\The
Harvard Clinical and Translational Science Center (NCRR); Harvard
Catalyst\The Harvard Clinical and Translational Science Center (NCATS,
National Institutes of Health) [UL1 TR001102]; Harvard University, its
affiliated academic health care centers
FX Supported by National Institutes of Health Grant R01 DK091353, Harvard
Catalyst vertical bar The Harvard Clinical and Translational Science
Center (NCRR and NCATS, National Institutes of Health Award UL1
TR001102), and financial contributions from Harvard University and its
affiliated academic health care centers.
NR 30
TC 1
Z9 1
U1 1
U2 4
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 OCT
PY 2015
VL 194
IS 4
BP 1031
EP 1037
DI 10.1016/j.juro.2015.04.079
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA CR3LS
UT WOS:000361234900067
PM 25916673
ER
PT J
AU Nalls, MA
McLean, CY
Rick, J
Eberly, S
Hutten, SJ
Gwinn, K
Sutherland, M
Martinez, M
Heutink, P
Williams, NM
Hardy, J
Gasser, T
Brice, A
Price, TR
Nicolas, A
Keller, MF
Molony, C
Gibbs, JR
Chen-Plotkin, A
Suh, E
Letson, C
Fiandaca, MS
Mapstone, M
Federoff, HJ
Noyce, AJ
Morris, H
Van Deerlin, VM
Weintraub, D
Zabetian, C
Hernandez, DG
Lesage, S
Mullins, M
Conley, ED
Northover, CAM
Frasier, M
Marek, K
Day-Williams, AG
Stone, DJ
Ioannidis, JPA
Singleton, AB
AF Nalls, Mike A.
McLean, Cory Y.
Rick, Jacqueline
Eberly, Shirley
Hutten, Samantha J.
Gwinn, Katrina
Sutherland, Margaret
Martinez, Maria
Heutink, Peter
Williams, Nigel M.
Hardy, John
Gasser, Thomas
Brice, Alexis
Price, T. Ryan
Nicolas, Aude
Keller, Margaux F.
Molony, Cliona
Gibbs, J. Raphael
Chen-Plotkin, Alice
Suh, Eunran
Letson, Christopher
Fiandaca, Massimo S.
Mapstone, Mark
Federoff, Howard J.
Noyce, Alastair J.
Morris, Huw
Van Deerlin, Vivianna M.
Weintraub, Daniel
Zabetian, Cyrus
Hernandez, Dena G.
Lesage, Suzanne
Mullins, Meghan
Conley, Emily Drabant
Northover, Carrie A. M.
Frasier, Mark
Marek, Ken
Day-Williams, Aaron G.
Stone, David J.
Ioannidis, John P. A.
Singleton, Andrew B.
CA Parkinson's Dis Biomarkers Program
TI Diagnosis of Parkinson's disease on the basis of clinical and genetic
classification: a population-based modelling study
SO LANCET NEUROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MUTATIONS; IDENTIFICATION; METAANALYSIS
AB Background Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts.
Methods We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD).
Findings In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0.923 (95% CI 0.900-0.946) with high sensitivity (0.834, 95% CI 0.711-0.883) and specificity (0.903, 95% CI 0.824-0.946) at its optimum AUC threshold (0.655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0.894 (95% CI 0.867-0.921) in the PDBP cohort, 0.998 (0.992-1.000) in PARS, 0.955 (no 95% CI available) in 23andMe, 0.929 (0.896-0.962) in LABS-PD, and 0.939 (0.891-0.986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0.003).
Interpretation Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions.
C1 [Nalls, Mike A.; Price, T. Ryan; Nicolas, Aude; Gibbs, J. Raphael; Letson, Christopher; Hernandez, Dena G.; Singleton, Andrew B.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
[McLean, Cory Y.; Mullins, Meghan; Conley, Emily Drabant; Northover, Carrie A. M.] 23andMe, Mountain View, CA USA.
[Rick, Jacqueline; Chen-Plotkin, Alice; Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA.
[Eberly, Shirley] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY 14627 USA.
[Hutten, Samantha J.; Frasier, Mark] Michael J Fox Fdn, Parkinsons Res, New York, NY USA.
[Gwinn, Katrina; Sutherland, Margaret] NINDS, NIH, Bethesda, MD 20892 USA.
[Martinez, Maria] INSERM, UMR 1043, Ctr Physiopathol Toulouse Purpan, Toulouse, France.
[Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
[Heutink, Peter] German Ctr Neurodegenerat Dis, Genome Biol Neurodegenerat Dis, Tubingen, Germany.
[Williams, Nigel M.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Gen, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
[Hardy, John; Noyce, Alastair J.; Morris, Huw] UCL, Inst Neurol, Reta Lila Weston Inst, London, England.
[Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Brice, Alexis; Lesage, Suzanne] Sorbonne Univ, UPMC Univ Paris 06, 1127, Paris, France.
[Brice, Alexis; Lesage, Suzanne] CNRS, INSERM, UMR 7225,U 1127, Inst Cerveau & Moelle Epiniere, Paris, France.
[Brice, Alexis; Lesage, Suzanne] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France.
[Keller, Margaux F.; Molony, Cliona; Stone, David J.] Merck Res Labs, Genet & Pharmacogen, West Point, PA USA.
[Keller, Margaux F.; Molony, Cliona; Stone, David J.] Merck Res Labs, Boston, MA USA.
[Suh, Eunran; Van Deerlin, Vivianna M.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
[Fiandaca, Massimo S.; Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA.
[Mapstone, Mark] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
[Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Zabetian, Cyrus] VA Puget Sound Hlth Care Syst, Div Neurogenet, Dept Neurol, Seattle, WA USA.
[Marek, Ken] Inst Neurodegenerat Disorders, New Haven, CT USA.
[Day-Williams, Aaron G.] Biogen, Precis Med, Cambridge, MA USA.
[Ioannidis, John P. A.] Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.
RP Nalls, MA (reprint author), NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Martinez,
Maria/B-3111-2013; Morris, Huw/B-8527-2008; corvol,
jean-christophe/I-6387-2012;
OI Martinez, Maria/0000-0003-2180-4537; Morris, Huw/0000-0002-5473-3774;
corvol, jean-christophe/0000-0001-7325-0199; Gwinn,
Katrina/0000-0002-8277-651X
FU National Institute on Aging, National Institute of Neurological
Disorders and Stroke; Michael J Fox Foundation
FX National Institute on Aging, National Institute of Neurological
Disorders and Stroke, and the Michael J Fox Foundation.
NR 20
TC 26
Z9 26
U1 1
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD OCT
PY 2015
VL 14
IS 10
BP 1002
EP 1009
DI 10.1016/S1474-4422(15)00178-7
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CR2VI
UT WOS:000361188400011
PM 26271532
ER
PT J
AU Gray, NE
Quinn, JF
AF Gray, Nora E.
Quinn, Joseph F.
TI Alterations in mitochondrial number and function in Alzheimer's disease
fibroblasts
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE beta-amyloid; Mitochondrial dysfunction; Alzheimer's disease
ID MAGNETIC-RESONANCE-SPECTROSCOPY; MILD COGNITIVE IMPAIRMENT; CULTURED
SKIN FIBROBLASTS; AMYLOID-BETA; MOUSE MODEL; BRAIN; PATHOLOGY; DEMENTIA;
MICE
AB Mitochondrial dysfunction is observed in brains of Alzheimer's Disease patients as well as many rodent model systems including those modeling mutations in preseinilin 1 (PSEN1). The aim of our study was to characterize mitochondrial function and number in fibroblasts from AD patients with PSEN1 mutations. We used biochemical assays, metabolic profiling and fluorescent labeling to assess mitochondrial number and function in fibroblasts from three AD patients compared to fibroblasts from three controls. The mutant AD fibroblasts had increased A beta 42 relative to controls along with reduction in ATP, basal and maximal mitochondrial respiration as well as impaired spare mitochondrial respiratory capacity. Fluorescent staining and expression of genes encoding electron transport chain enzymes showed diminished mitochondrial content in the AD fibroblasts. This study demonstrates that mitochondrial dysfunction is observable in AD fibroblasts and provides evidence that this model system could be useful as a tool to screen disease-modifying compounds.
C1 [Gray, Nora E.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Quinn, Joseph F.] Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA.
[Quinn, Joseph F.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Care Ctr PADRECC, Portland, OR 97239 USA.
RP Gray, NE (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
EM grayn@ohsu.edu
FU Department of Veterans Affairs Merit Review grant
FX This work was funded by a Department of Veterans Affairs Merit Review
grant awarded to J. Quinn.
NR 28
TC 0
Z9 0
U1 0
U2 4
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 OCT
PY 2015
VL 30
IS 5
BP 1275
EP 1278
DI 10.1007/s11011-015-9667-z
PG 4
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA CQ8TG
UT WOS:000360881400019
PM 25862550
ER
PT J
AU Poutiainen, P
Kil, KE
Zhang, ZD
Kuruppu, D
Tannous, B
Brownell, AL
AF Poutiainen, Pekka
Kil, Kun-Eek
Zhang, Zhaoda
Kuruppu, Darshini
Tannous, Bakhos
Brownell, Anna-Liisa
TI Co-operative binding assay for the characterization of mGlu(4)
allosteric modulators
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Metabotropic glutamate receptor; Parkinson disease; mGlu(4); Binding
affinity
ID METABOTROPIC GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; PET RADIOTRACER;
DRUG DISCOVERY; RADIOSYNTHESIS; INSIGHTS; FAMILY; CNS
AB The interest in the role of metabotropic glutamate receptor 4 (mGlu(4)) in CNS related disorders has increased the need for methods to investigate the binding of allosteric drug candidates. Our aim is to present the first fully characterized in vitro binding assay of mGlu(4) positive allosteric modulators (PAMs). Results suggest that mGlu(4) PAMs have characteristic co-operative binding with orthosteric glutamate, which offers a notable insight to the further development of mGlu(4) targeted therapies. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Poutiainen, Pekka; Kil, Kun-Eek; Zhang, Zhaoda; Brownell, Anna-Liisa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Biomed Imaging Ctr, Boston, MA 02115 USA.
[Kuruppu, Darshini] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA USA.
[Tannous, Bakhos] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA.
[Tannous, Bakhos] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
RP Brownell, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Biomed Imaging Ctr, Boston, MA 02115 USA.
EM abrownell@partners.org
FU Orion Farmos Research Foundation; Kuopio University Foundation;
[NIBIB-R01EB012864]; [NIMH-R01MH091684]
FX Studies were supported by the grants NIBIB-R01EB012864 and
NIMH-R01MH091684 to A-LB. PP was supported by the Orion Farmos Research
Foundation and Kuopio University Foundation. We would like also to thank
Drs. Tanabe and Shigetada Nakanishi's laboratory (Osaka Bioscience
Institute, Osaka, Japan) for providing us the vector of mGlu4
from rat as a gift. In addition, Dr. Shilpa Prabhakar and Dr. Xandra
Breakefield from Molecular Neurogenetics Unit, Massachusetts General
Hospital (Boston, MA, USA) are greatly acknowledged for helping with the
transfection of the cell line.
NR 29
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U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD OCT
PY 2015
VL 97
BP 142
EP 148
DI 10.1016/j.neuropharm.2015.05.017
PG 7
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA CQ8PC
UT WOS:000360869700015
PM 26025660
ER
PT J
AU Gomeni, R
Goyal, N
Bressolle, F
Fava, M
AF Gomeni, Roberto
Goyal, Navin
Bressolle, Francoise
Fava, Maurizio
TI A Novel Methodology to Estimate the Treatment Effect in Presence of
Highly Variable Placebo Response
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID SIGNAL-DETECTION-THEORY; CLINICAL-TRIALS; ANTIDEPRESSANT DRUGS;
ENRICHMENT STRATEGY; IMPROVE EFFICIENCY; MAJOR DEPRESSION; DISORDERS;
ESCITALOPRAM; PERFORMANCE; SEVERITY
AB One of the main reasons for the inefficiency of multicenter randomized clinical trials (RCTs) in depression is the excessively high level of placebo response. The aim of this work was to propose a novel methodology to analyze RCTs based on the assumption that centers with high placebo response are less informative than the other centers for estimating the 'true' treatment effect (TE). A linear mixed-effect modeling approach for repeated measures (MMRM) was used as a reference approach. The new method for estimating TE was based on a nonlinear longitudinal modeling of clinical scores (NLMMRM). NLMMRM estimates TE by associating a weighting factor to the data collected in each center. The weight was defined by the posterior probability of detecting a clinically relevant difference between active treatment and placebo at that center. Data from five RCTs in depression were used to compare the performance of MMRM with NLMMRM. The results of the analyses showed an average improvement of similar to 15% in the TE estimated with NLMMRM when the center effect was included in the analyses. Opposite results were observed with MMRM: TE estimate was reduced by similar to 4% when the center effect was considered as covariate in the analysis. The novel NLMMRM approach provides a tool for controlling the confounding effect of high placebo response, to increase signal detection and to provide a more reliable estimate of the 'true' TE by controlling false negative results associated with excessively high placebo response.
C1 [Gomeni, Roberto; Bressolle, Francoise] Longcol, R&D Dept, Pharmacometr, La Fouillade, France.
[Goyal, Navin] GlaxoSmithKline, Clin Pharmacol Modeling & Simulat Dept, King Of Prussia, PA USA.
[Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Gomeni, R (reprint author), Lieudit Longcol, R&D Pharmacometr, F-12270 La Fouillade, France.
EM roberto.gomeni@pharmacometrica.com
FU Pharmacometrica France; Abbot Laboratories; Alkermes; American Cyanamid;
Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals;
BioResearch; BrainCells; Bristol-Myers Squibb; CeNeRx BioPharma;
Cephalon; Clintara, LLC; Covance; Covidien; Eli Lilly and Company;
EnVivo Pharmaceuticals; Euthymics Bioscience; Forest Pharmaceuticals;
Ganeden Biotech; GlaxoSmithKline; Harvard Clinical Research Institute;
Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenix; Janssen RD,
LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research
Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck;
MedAvante; Methylation Sciences; National Alliance for Research on
Schizophrenia & Depression (NARSAD); National Center for Complementary
and Alternative Medicine (NCCAM); National Institute of Drug Abuse
(NIDA); National Institute of Mental Health (NIMH); Neuralstem, Inc.;
Novartis AG; Organon Pharmaceuticals; PamLab, LLC; Pfizer;
Pharmacia-Upjohn; Pharmaceutical Research Associates; Pharmavite LLC;
PharmoRx Therapeutics; Photothera; Reckitt Benckiser; Roche
Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay
Pharmaceuticals; Stanley Medical Research Institute (SMRI); Synthelabo;
Wyeth-Ayerst Laboratories; GSK
FX This study has been sponsored by Pharmacometrica France. The authors
declare no conflict of interest and that they did not receive any
financial support for this study. RG is a full time employee of
Pharmacometrica. NG is a full time employee of GSK. He receives salary
and stocks from GSK. FB is a consultant of Pharmacometrica. MF: Research
Support: Abbot Laboratories; Alkermes; American Cyanamid; Aspect Medical
Systems; AstraZeneca; Avanir Pharmaceuticals; BioResearch; BrainCells;
Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara, LLC;
Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals;
Euthymics Bioscience; Forest Pharmaceuticals; Ganeden Biotech;
GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche;
Icon Clinical Research; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed
Foundation; Johnson & Johnson Pharmaceutical Research & Development;
Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck; MedAvante;
Methylation Sciences; National Alliance for Research on Schizophrenia &
Depression (NARSAD); National Center for Complementary and Alternative
Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National
Institute of Mental Health (NIMH); Neuralstem, Inc.; Novartis AG;
Organon Pharmaceuticals; PamLab, LLC.; Pfizer; Pharmacia-Upjohn;
Pharmaceutical Research Associates; Pharmavite LLC; PharmoRx
Therapeutics; Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT
Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US
LLC; Shire; Solvay Pharmaceuticals; Stanley Medical Research Institute
(SMRI); Synthelabo; Wyeth-Ayerst Laboratories. Advisory/Consulting:
Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes; Amarin
Pharma; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals;
Bayer AG; Best Practice Project Management; BioMarin Pharmaceuticals;
Biovail Corporation; BrainCells; Bristol-Myers Squibb; CeNeRx BioPharma;
Cephalon; Cerecor; CNS Response; Compellis Pharmaceuticals; Cypress
Pharmaceutical; DiagnoSearch Life Sciences (P); Dinippon Sumitomo
Pharma; Dov Pharmaceuticals; Edgemont Pharmaceuticals; Eisai; Eli Lilly
and Company; EnVivo Pharmaceuticals; ePharmaSolutions; EPIX
Pharmaceuticals; Euthymics Bioscience; Fabre-Kramer Pharmaceuticals;
Forest Pharmaceuticals; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH;
i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals; Johnson
& Johnson Pharmaceutical Research & Development, LLC; Knoll
Pharmaceuticals; Labopharm; Lorex Pharmaceuticals; Lundbeck; MedAvante;
Merck; MSI Methylation Sciences; Naurex; Neuralstem; Neuronetics;
NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen
Therapeutics; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab,
LLC.; Pfizer; PharmaStar; Pharmavite LLC.; PharmoRx Therapeutics;
Precision Human Biolaboratory; Prexa Pharmaceuticals; Puretech Ventures;
PsychoGenics; Psylin Neurosciences; RCT Logic, LLC (formerly Clinical
Trials Solutions, LLC); Rexahn Pharmaceuticals; Ridge Diagnostics;
Roche; Sanofi-Aventis US LLC.; Sepracor; Servier Laboratories;
Schering-Plough Corporation; Solvay Pharmaceuticals; Somaxon
Pharmaceuticals; Somerset Pharmaceuticals; Sunovion Pharmaceuticals;
Supernus Pharmaceuticals; Synthelabo; Takeda Pharmaceutical Company
Limited; Tal Medical; Tetragenex Pharmaceuticals; TransForm
Pharmaceuticals; Transcept Pharmaceuticals; Vanda Pharmaceuticals.;
Speaking/Publishing: Adamed; Advanced Meeting Partners; American
Psychiatric Association; American Society of Clinical
Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer
Ingelheim GmbH; Bristol-Myers Squibb; Cephalon; CME Institute/Physicians
Postgraduate Press; Eli Lilly and Company; Forest Pharmaceuticals;
GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH
Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals;
Pfizer; PharmaStar; United BioSource; Wyeth-Ayerst Laboratories. Equity
Holdings: Compellis; PsyBrain. Royalty/patent, other income: Patent for
Sequential Parallel Comparison Design (SPCD), which are licensed by MGH
to Pharmaceutical Product Development, LLC (PPD); and patent application
for a combination of Ketamine plus Scopolamine in Major Depressive
Disorder (MDD). Copyright for the MGH Cognitive & Physical Functioning
Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant
Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs
& Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolkers
Kluwer; World Scientific Publishing.
NR 32
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U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD OCT
PY 2015
VL 40
IS 11
BP 2588
EP 2595
DI 10.1038/npp.2015.105
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CR2EM
UT WOS:000361138300011
PM 25895454
ER
PT J
AU Booi, AN
Menendez, J
Norton, HJ
Anderson, WE
Ellis, AC
AF Booi, Amy N.
Menendez, Jerome
Norton, H. James
Anderson, William E.
Ellis, Amy C.
TI Validation of a Screening Tool to Identify Undernutrition in Ambulatory
Patients With Liver Cirrhosis
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Article
DE liver diseases; end-stage liver disease; nutrition assessment;
malnutrition; liver cirrhosis
ID MALNUTRITION; NUTRITION; DISEASE; PREVALENCE; MANAGEMENT
AB Background: The prevalence of chronic liver disease is increasing in the United States. Malnutrition is common as liver disease progresses. However, an accepted method to screen these patients for malnutrition is lacking. The 6-question undernutrition screening tool was developed for professionals without nutrition training to identify a decline in the nutrition status of patients with liver cirrhosis. A 3-phase validation study was completed to assess face, content, and clinical validity of the screening tool in ambulatory patients with liver cirrhosis. Methods: In phase I, face validity was determined by surveying 13 liver disease professionals. In phase II, content validity was assessed by surveying 12 registered dietitians who specialize in liver disease. In phase III, a cross-sectional investigation was completed to compare the agreement between the undernutrition screening tool and nutrition assessment by a registered dietitian (RD). Results: Twenty-two patients with a diagnosis of liver cirrhosis participated in phase III of the investigation. The RD assessment identified undernutrition in 82% of patients (95% CI, 60%-95%). The statistic indicated a fair agreement between the screening tool and RD assessment. Sensitivity and specificity of the tool were 72% and 75%, respectively, and positive predictive value was 93%. Conclusions: Feedback from phase I, II, and III indicate that the undernutrition screening tool is simple, is easy to use, and measures the constructs that have the strongest link with undernutrition in liver disease. Additional minor adjustments to the screening tool and a multicenter investigation are indicated to confirm clinical effectiveness and cross-validity of the tool.
C1 [Booi, Amy N.; Menendez, Jerome; Norton, H. James; Anderson, William E.] Carolinas Healthcare Syst, Charlotte, NC USA.
[Ellis, Amy C.] Univ Alabama, Dept Human Nutr, Tuscaloosa, AL USA.
RP Booi, AN (reprint author), Nutr & Food Serv, US Dept Vet Affairs, Southern Nevada Healthcare Syst, North Las Vegas Med Ctr, 6900 North Pecos Rd, North Las Vegas, NV 89096 USA.
EM amybooi@gmail.com
NR 15
TC 1
Z9 1
U1 3
U2 4
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 OCT
PY 2015
VL 30
IS 5
BP 683
EP 689
DI 10.1177/0884533615587537
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CQ7DQ
UT WOS:000360763500009
PM 26024676
ER
PT J
AU Cunningham, SED
Verkaik, D
Gross, G
Khazim, K
Hirachan, P
Agarwal, G
Lorenzo, C
Matteucci, E
Bansal, S
Fanti, P
AF Cunningham, Sue E. D.
Verkaik, Darlene
Gross, Georgiana
Khazim, Khalid
Hirachan, Padam
Agarwal, Gurav
Lorenzo, Carlos
Matteucci, Elena
Bansal, Shweta
Fanti, Paolo
TI Comparison of Nutrition Profile and Diet Record Between Veteran and
Nonveteran End-Stage Renal Disease Patients Receiving Hemodialysis in
Veterans Affairs and Community Clinics in Metropolitan South-Central
Texas
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Article
DE wasting syndrome; inflammation; diabetes mellitus; ethnic groups;
healthcare disparities; socioeconomic factors
ID ENERGY-INTAKE; KIDNEY-DISEASE; PROTEIN-INTAKE; MUSCLE MASS; DIALYSIS;
ASSOCIATION; MORTALITY; MEMBRANES; SURVIVAL; FAILURE
AB Background: U.S. military veterans have high rates of chronic disease and social disadvantage, which are risk factors for protein-energy wasting (PEW). It is not known whether this translates into high prevalence of PEW in veterans with end-stage renal disease. Methods: We compared the clinical, socioeconomic, and nutrition status and the diet of 33 veteran and 38 nonveteran clinically stable patients receiving maintenance hemodialysis (MHD) in south-central Texas. Results: The whole cohort included 82% Mexican Americans (MAs), 72% type 2 diabetics, and 73% males. The body mass index was 28.9 +/- 6.2, while energy intake was 21.5 +/- 8.2 kcal/kg/d and protein intake was 1.0 +/- 0.4 g/kg/d. Serum albumin (bromocresol purple) was 3.5 +/- 0.4 g/dL, transferrin was 171.9 +/- 27.8 mg/d, C-reactive protein was 2.9 (1.4-6.5) mg/L, interleukin-6 (IL-6) was 8.3 (4.2-17.9) pg/mL, neutrophil gelatinase-associated lipocalin was 729 (552-1256) ng/mL, and the malnutrition-inflammation score was 8.8 +/- 3.0. In group comparison that adjusted for sex and ethnicity, the veterans had better household income, less MAs (60% vs 100%), more males (94% vs 55%), more use of a renin-angiotensin-aldosterone system blockade (66% vs 33%), and lower IL-6 levels (4.4 [3.1-5.8] vs 15.4 [8.3-20.5] pg/mL; P = .01) than nonveterans. In regression analysis, the lower serum IL-6 level in veterans was independently explained by dialysis clinic, sex, and, possibly, household income (intermediate significance). Conclusion: In a relatively small cohort of clinically stable MHD patients, the veterans showed equivalent nutrition status and dietary intake and less inflammation than the nonveterans, thus not supporting the possibility that veteran MHD patients may have worse nutrition than the nonveteran counterpart.
C1 [Cunningham, Sue E. D.; Khazim, Khalid; Hirachan, Padam; Agarwal, Gurav; Fanti, Paolo] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, San Antonio, TX 78229 USA.
[Cunningham, Sue E. D.; Gross, Georgiana] Univ Texas Hlth Sci Ctr San Antonio, Sch Hlth Profess, San Antonio, TX 78229 USA.
[Verkaik, Darlene; Bansal, Shweta; Fanti, Paolo] Audie L Murphy Vet Mem Hosp, STVHCS, San Antonio, TX USA.
[Khazim, Khalid] Western Galilee Hosp, Div Nephrol, Nahariyya, Israel.
[Lorenzo, Carlos] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Clin Epidemiol, San Antonio, TX 78229 USA.
[Matteucci, Elena] Univ Pisa, Div Endocrinol, I-56100 Pisa, Italy.
RP Fanti, P (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA.
EM fanti@uthscsa.edu
FU NIH-NCCAM [AT004490]; Veterans Administration [1I01CX000264]; CTSA
program [NIH-NCATS 1UL TR001120]
FX This work was supported by grants to PF from NIH-NCCAM (AT004490) and
from the Veterans Administration (Merit Review 1I01CX000264) and by the
CTSA program award to UTHSCSA (NIH-NCATS 1UL TR001120).
NR 51
TC 0
Z9 0
U1 0
U2 8
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 OCT
PY 2015
VL 30
IS 5
BP 698
EP 708
DI 10.1177/0884533615575046
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CQ7DQ
UT WOS:000360763500011
PM 25899538
ER
PT J
AU Yonker, LM
Pazos, MA
Hurley, BP
AF Yonker, L. M.
Pazos, M. A.
Hurley, B. P.
TI NEUTROPHIL-DERIVED CYTOSOLIC PHOSPHOLIPASE A2 IS AN IMPORTANT MEDIATOR
OF PSEUDOMONAS-MEDIATED NEUTROPHIL TRANSEPITHELIAL MIGRATION
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Yonker, L. M.; Pazos, M. A.; Hurley, B. P.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA.
[Yonker, L. M.; Pazos, M. A.; Hurley, B. P.] Harvard Univ, Sch Med, Dept Pediat, 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 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 41
MA 132
BP 239
EP 240
PG 2
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NS
UT WOS:000360791500202
ER
PT J
AU Birket, S
Tuggle, KL
Chu, KK
Harris, WT
Tearney, G
Fanucchi, MV
Sorscher, EJ
Rowe, SM
AF Birket, S.
Tuggle, K. L.
Chu, K. K.
Harris, W. T.
Tearney, G.
Fanucchi, M., V
Sorscher, E. J.
Rowe, S. M.
TI THE CFTR-/- RAT IS SUSCEPTIBLE TO PSEUDOMONAS AERUGINOSA INFECTION
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Birket, S.; Tuggle, K. L.; Sorscher, E. J.; Rowe, S. M.] Univ Alabama Birmingham, Med, Birmingham, AL USA.
[Chu, K. K.; Tearney, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Harris, W. T.; Fanucchi, M., V] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 41
MA 139
BP 242
EP 242
PG 1
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NS
UT WOS:000360791500209
ER
PT J
AU Chu, KK
Ford, TN
Mojahed, D
Fernandez, CM
Birket, S
Solomon, GM
Rowe, SM
Tearney, GJ
AF Chu, K. K.
Ford, T. N.
Mojahed, D.
Fernandez, C. M.
Birket, S.
Solomon, G. M.
Rowe, S. M.
Tearney, G. J.
TI IN SITU RHEOLOGY AND PH MEASUREMENT OF AIRWAY MUCUS WITH DUAL MODALITY
mu OCT/FLUORESCENCE IMAGING
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Chu, K. K.; Ford, T. N.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Mojahed, D.] Tufts Univ, Medford, MA 02155 USA.
[Fernandez, C. M.; Birket, S.; Solomon, G. M.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 41
MA 283
BP 298
EP 298
PG 1
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NS
UT WOS:000360791500353
ER
PT J
AU Pazos, MA
Yonker, LM
Moskowitz, SM
Hurley, BP
AF Pazos, M. A.
Yonker, L. M.
Moskowitz, S. M.
Hurley, B. P.
TI TRANSEPITHELIAL MIGRATION IS IMPAIRED IN PERIPHERAL BOOD NEUTROPHILS
ISOLATED FROM CYSTIC FIBROSIS PATIENTS
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Pazos, M. A.; Yonker, L. M.; Hurley, B. P.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA USA.
[Pazos, M. A.; Yonker, L. M.; Moskowitz, S. M.; Hurley, B. P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Moskowitz, S. M.] Massachusetts Gen Hosp, Pediat Cyst Fibrosis Ctr, 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 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 41
MA 374
BP 332
EP 332
PG 1
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NS
UT WOS:000360791500444
ER
PT J
AU Ballok, AE
Rahme, LG
AF Ballok, A. E.
Rahme, L. G.
TI PSEUDOMONAS AERUGINOSA VIRULENCE PHENOTYPES ARE IMPACTED BY
2,4-DIHYDROXYQUINOLINE (DHQ), AN ABUNDANT PRODUCT OF THE PQS OPERON
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Ballok, A. E.; Rahme, L. G.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA.
[Ballok, A. E.; Rahme, L. G.] Harvard Univ, Sch Med, Microbiol & Immunobiol, Boston, MA USA.
[Ballok, A. E.; Rahme, L. G.] Shriners Hosp Children, Boston, MA 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 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 41
MA 379
BP 334
EP 334
PG 1
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NS
UT WOS:000360791500449
ER
PT J
AU Mou, H
Brazauskas, K
Rajagopal, J
AF Mou, Hongmei
Brazauskas, Karissa
Rajagopal, Jayaraj
TI Personalized medicine for cystic fibrosis: Establishing human model
systems
SO PEDIATRIC PULMONOLOGY
LA English
DT Review
DE cystic fibrosis (CF); airway and lung cell biology; stem cells;
individualized medicine; induced pluripotent stem cells; organoids
ID PLURIPOTENT STEM-CELLS; TRANSMEMBRANE CONDUCTANCE REGULATOR; AIRWAY
EPITHELIAL-CELLS; C VIRUS-INFECTION; MOUSE MODEL; BICARBONATE SECRETION;
EFFICIENT DERIVATION; PRIMARY CULTURES; ANIMAL-MODELS; IMMUNE-SYSTEM
AB With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. Pediatr Pulmonol. 2015; 50:S14-S23. (c) 2015 Wiley Periodicals, Inc.
C1 [Mou, Hongmei; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Mou, Hongmei; Rajagopal, Jayaraj] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Mou, Hongmei; Brazauskas, Karissa] Massachusetts Gen Hosp Children, Pediat Pulm Med, Boston, MA USA.
[Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm Crit Care Unit, Internal Med & Pediat, Boston, MA 02114 USA.
RP Rajagopal, J (reprint author), 185 Cambridge St CPZN 4500, Boston, MA 02114 USA.
EM jrajagopal@mgh.harvard.edu
NR 87
TC 2
Z9 2
U1 1
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD OCT
PY 2015
VL 50
SU 40
SI SI
BP S14
EP S23
DI 10.1002/ppul.23233
PG 10
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CQ7NQ
UT WOS:000360791300004
PM 26335952
ER
PT J
AU Genewsky, A
Jost, I
Busch, C
Huber, C
Stindl, J
Skerka, C
Zipfel, PF
Rohrer, B
Strauss, O
AF Genewsky, Andreas
Jost, Ingmar
Busch, Catharina
Huber, Christian
Stindl, Julia
Skerka, Christine
Zipfel, Peter F.
Rohrer, Baerbel
Strauss, Olaf
TI Activation of endogenously expressed ion channels by active complement
in the retinal pigment epithelium
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE (4-6): complement system; Retinal pigment epithelium; RPE; L-type
channels; BK channels
ID MEMBRANE-ATTACK-COMPLEX; HUMAN POLYMORPHONUCLEAR LEUKOCYTES;
INTRACELLULAR FREE CALCIUM; MACULAR DEGENERATION; VEGF SECRETION; CA2+
CHANNELS; FACTOR-H; CELLS; FIBROBLASTS; INCREASE
AB Defective regulation of the alternative pathway of the complement system is believed to contribute to damage of retinal pigment epithelial (RPE) cells in age-related macular degeneration. Thus we investigated the effect of complement activation on the RPE cell membrane by analyzing changes in membrane conductance via patch-clamp techniques and Ca2+ imaging. Exposure of human ARPE-19 cells to complement-sufficient normal human serum (NHS) (25 %) resulted in a biphasic increase in intracellular free Ca2+ ([Ca2+](i)); an initial peak followed by sustained Ca2+ increase. C5- or C7-depleted sera did not fully reproduce the signal generated by NHS. The initial peak of the Ca2+ response was reduced by sarcoplasmic Ca2+-ATPase inhibitor thapsigargin, L-type channel blockers (R)-(+)-BayK8644 and isradipine, transient-receptor-potential (TRP) channel blocker ruthenium-red and ryanodine receptor blocker dantrolene. The sustained phase was carried by Ca(V)1.3 L-type channels via tyrosine-phosphorylation. Changes in [Ca2+](I) were accompanied by an abrupt hyperpolarization, resulting from a transient increase in membrane conductance, which was absent under extracellular Ca2+- or K+-free conditions and blocked by (R)-(+)-BayK8644 or paxilline, a maxiK channel inhibitor. Single-channel recordings confirmed the contribution of maxiK channels. Primary porcine RPE cells responded to NHS in a comparable manner. Pre-incubation with NHS reduced H2O2-induced cell death. In summary, in a concerted manner, C3a, C5a and sC5b-9 increased [Ca2+](i) by ryanodine-receptor-dependent activation of L-type channels in addition to maxi-K channels and TRP channels absent from any insertion of a lytic pore.
C1 [Genewsky, Andreas] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Genewsky, Andreas; Jost, Ingmar; Stindl, Julia; Strauss, Olaf] Univ Med Ctr Regensburg, Eye Clin, Expt Ophthalmol, Regensburg, Germany.
[Skerka, Christine; Zipfel, Peter F.] Leibniz Inst Nat Prod Res & Infect Biol, Dept Infect Biol, Jena, Germany.
[Zipfel, Peter F.] Univ Jena, Jena, Germany.
[Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
[Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA.
[Busch, Catharina; Huber, Christian; Strauss, Olaf] Charite, Dept Ophthalmol, Expt Ophthalmol, Campus Virchow Klinikum, D-13353 Berlin, Germany.
RP Strauss, O (reprint author), Charite, Dept Ophthalmol, Expt Ophthalmol, Campus Virchow Klinikum, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM olaf.strauss@charite.de
FU National Institutes of Health (NIH) [R01EY019320]; Department for
Veterans Affairs [RX000444]; Research to Prevent Blindness (RPB), New
York, NY; Deutsche Forschungsgemeinschaft (DFG) [SK46/2-1, SK46/2-2]
FX The authors thank Andrea Dannullis, Elfriede Eckert and Renate Fockler
for expert technical assistance. Financial support: OS: Novartis
Professorship; BR: in part by the National Institutes of Health (NIH)
(R01EY019320), a Department for Veterans Affairs merit award RX000444
and an unrestricted grant to MUSC from Research to Prevent Blindness
(RPB), New York, NY; CS: Deutsche Forschungsgemeinschaft (DFG) SK46/2-1,
SK46/2-2.
NR 44
TC 3
Z9 3
U1 1
U2 5
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 OCT
PY 2015
VL 467
IS 10
BP 2179
EP 2191
DI 10.1007/s00424-014-1656-2
PG 13
WC Physiology
SC Physiology
GA CR0IB
UT WOS:000361000800011
PM 25427445
ER
PT J
AU True, G
Rigg, KK
Butler, A
AF True, Gala
Rigg, Khary K.
Butler, Anneliese
TI Understanding Barriers to Mental Health Care for Recent War Veterans
Through Photovoice
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE health care; access to; health care; users' experiences; lived
experience; mental health and illness; participatory action research;
photography; photovoice; post-traumatic stress disorder; stigma; visual
methods; vulnerable populations
ID RETURNING COMBAT VETERANS; TREATMENT-SEEKING; AFGHANISTAN VETERANS;
IRAQ; SERVICES; INTERVENTIONS; DEPLOYMENT; SOLDIERS; PTSD; PERCEPTIONS
AB Despite an urgent need for mental health care among U.S. service members returning from deployments to Iraq and Afghanistan, many veterans do not receive timely or adequate treatment. We used photovoice methods to engage veterans in identifying barriers to utilizing mental health services. Veterans described how key aspects of military culture and identity, highly adaptive during deployment, can deter help-seeking behavior and hinder recovery. Veterans' photographs highlighted how mental health symptoms and self-coping strategies operated as barriers to care. Many veterans' photos and stories revealed how negative health care encounters contributed to avoidance and abandonment of treatment; some veterans described these experiences as re-traumatizing. Visual methods can be a powerful tool for engaging recent war veterans in research. In particular, community-based participatory research approaches, which have rarely been used with veterans, hold great promise for informing effective interventions to improve access and enhance provision of patient-centered care for veterans.
C1 [True, Gala] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Butler, Anneliese] Philadelphia Vet Affairs Med Ctr, VISN Ctr Evaluat Patient Aligned Care Teams 4, Philadelphia, PA 19104 USA.
[Rigg, Khary K.] Univ S Florida, Dept Mental Hlth Law & Policy, Louis de la Parte Florida Mental Hlth Inst, Tampa, FL USA.
RP True, G (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, 3900 Woodland Ave,Bldg 4100, Philadelphia, PA 19104 USA.
EM Jennifer.True2@va.gov
FU VA Health Services Research Development [PPO 10-255]; VISN 4 Center for
Evaluation of Patient Aligned Care Teams (CEPACT); Center for Health
Equity Research and Promotion (CHERP)
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 VA Health Services Research & Development grant to Gala True
(PPO 10-255), with additional support from the VISN 4 Center for
Evaluation of Patient Aligned Care Teams (CEPACT) and the Center for
Health Equity Research and Promotion (CHERP).
NR 45
TC 4
Z9 4
U1 3
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
EI 1552-7557
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD OCT
PY 2015
VL 25
IS 10
SI SI
BP 1443
EP 1455
DI 10.1177/1049732314562894
PG 13
WC Information Science & Library Science; Social Sciences,
Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
Biomedical Social Sciences
GA CR2AP
UT WOS:000361127100012
PM 25488935
ER
PT J
AU Moschovis, PP
Addo-Yobo, EOD
Banajeh, S
Chisaka, N
Christiani, DC
Hayden, D
Jeena, P
MacLeod, WB
Mino, G
Patel, A
Qazi, S
Santosham, M
Thea, DM
Hibberd, PL
AF Moschovis, Peter P.
Addo-Yobo, Emmanuel O. D.
Banajeh, Salem
Chisaka, Noel
Christiani, David C.
Hayden, Douglas
Jeena, Prakash
MacLeod, William B.
Mino, Greta
Patel, Archana
Qazi, Shamim
Santosham, Mathuram
Thea, Donald M.
Hibberd, Patricia L.
TI Stunting is associated with poor outcomes in childhood pneumonia
SO TROPICAL MEDICINE & INTERNATIONAL HEALTH
LA English
DT Article
DE pneumonia; malnutrition; treatment failure; global health
ID LUNG-FUNCTION; ECUADORIAN CHILDREN; NUTRITIONAL-STATUS; RISK-FACTORS;
MORTALITY; INFECTION; MALNUTRITION; PREDICTORS; COUNTRIES; DISEASE
AB Objective Stunting affects 26.7% of children worldwide, and little is known about its effects on the outcomes of childhood pneumonia. We evaluated the effect of stunting on the outcomes of pneumonia among children enrolled in two large clinical trials.
Methods We analysed data from two WHO and USAID-sponsored inpatient treatment trials, the Severe Pneumonia Evaluation Antimicrobial Research study (n=958) and the Amoxicillin Penicillin Pneumonia International Study (n=1702), which enrolled children aged 2-59months across 16 sites in LMICs. We assessed the effect of stunting (height-for-age Z score<-2) on treatment outcome and time to resolution of hypoxaemic pneumonia.
Results Among 2542 (96%) children with valid data for height, 28% were stunted and 12.8% failed treatment by 5days. The failure rate among stunted patients was 16.0% vs. 11.5% among non-stunted patients [unadjusted RR=1.24 (95% CI 1.08, 1.41); adjusted RR=1.28 (95% CI 1.10, 1.48)]. An inverse relationship was observed between height and failure rates, even among non-stunted children. Among 845 patients with hypoxaemic pneumonia, stunting was associated with a lower probability of normalisation of respiratory rate [HR=0.63 (95% CI 0.52, 0.75)] and oxygen saturation [HR=0.74 (95% CI 0.61, 0.89)].
Conclusions Stunting increases the risk of treatment failure and is associated with a longer course of recovery in children with pneumonia. Strategies to decrease stunting may decrease the burden of adverse outcomes in childhood pneumonia in low-resource settings.
C1 [Moschovis, Peter P.; Christiani, David C.; Hayden, Douglas; Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Addo-Yobo, Emmanuel O. D.] Kwame Nkrumah Univ Sci & Technol, Komfo Anokye Teaching Hosp, Kumasi, Ghana.
[Banajeh, Salem] Sanaa Univ, Al Sabeen Hosp Women & Children, Sanaa, Yemen.
[Chisaka, Noel] World Bank, Washington, DC 20433 USA.
[Jeena, Prakash] Univ KwaZulu Natal, Durban, South Africa.
[MacLeod, William B.; Thea, Donald M.] Boston Univ, Boston, MA 02215 USA.
[Mino, Greta] Childrens Hosp Dr Francisco de Ycaza Bustamante, Guayaquil, Ecuador.
[Patel, Archana] Lata Med Res Fdn, Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Qazi, Shamim] World Hlth Org, Geneva, Switzerland.
[Santosham, Mathuram] Johns Hopkins Univ, Baltimore, MD USA.
RP Moschovis, PP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Pulm, Sch Med, 125 Nashua St,Suite 840, Boston, MA 02114 USA.
EM pmoschovis@mgh.harvard.edu
FU Department of Child and Adolescent Health and Development, WHO; Center
for International Health and Development, Boston University; Johns
Hopkins Bloomberg School of Public Health, Baltimore; National Heart,
Lung, and Blood Institute of the National Institutes of Health
[F32HL124951]; Harvard Clinical and Translational Science Center
(National Institutes of Health) [UL1 TR001102]; Harvard University;
Harvard Catalyst
FX The SPEAR and APPIS studies were funded by the Department of Child and
Adolescent Health and Development, WHO; Center for International Health
and Development, Boston University; and Johns Hopkins Bloomberg School
of Public Health, Baltimore. This analysis was supported by the National
Heart, Lung, and Blood Institute of the National Institutes of Health
under award number F32HL124951. Statistical support was provided by
Harvard Catalyst | The Harvard Clinical and Translational Science Center
(National Center for Research Resources and the National Center for
Advancing Translational Sciences, National Institutes of Health Award
UL1 TR001102) and financial contributions from Harvard University and
its affiliated academic healthcare centers. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the World Health Organization or National Institutes
of Health. The results of this study were presented in part at the
American Thoracic Society International Conference, San Diego, USA,
16-21 May 2014.
NR 32
TC 1
Z9 1
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1360-2276
EI 1365-3156
J9 TROP MED INT HEALTH
JI Trop. Med. Int. Health
PD OCT
PY 2015
VL 20
IS 10
BP 1320
EP 1328
DI 10.1111/tmi.12557
PG 9
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CQ7DR
UT WOS:000360763600009
PM 26083963
ER
PT J
AU Wood, PL
Barnette, BL
Kaye, JA
Quinn, JF
Woltjer, RL
AF Wood, Paul L.
Barnette, Brooke L.
Kaye, Jeffrey A.
Quinn, Joseph F.
Woltjer, Randall L.
TI Non-targeted lipidomics of CSF and frontal cortex grey and white matter
in control, mild cognitive impairment, and Alzheimer's disease subjects
SO ACTA NEUROPSYCHIATRICA
LA English
DT Article
DE Alzheimer's disease; lipidomics; diacylglycerols; mild cognitive
impairment; frontal cortex
ID PLASMALOGEN DEFICIENCY; MASS-SPECTROMETRY; HUMAN BRAIN; PATHOGENESIS;
INDIVIDUALS; DEMENTIA; CERAMIDE; ENZYMES; MOUSE; AGE
AB Objective: We undertook a non-targeted lipidomics analysis of postmortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment.
Methods: Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform.
Results: Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26: 0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups.
Conclusion: The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.
C1 [Wood, Paul L.; Barnette, Brooke L.] Lincoln Mem Univ, DeBusk Coll Osteopath Med, Dept Physiol & Pharmacol, Metabol Unit, Harrogate, TN 37752 USA.
[Kaye, Jeffrey A.; Quinn, Joseph F.; Woltjer, Randall L.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Neurol, Portland, OR USA.
RP Wood, PL (reprint author), Lincoln Mem Univ, DeBusk Coll Osteopath Med, Dept Physiol & Pharmacol, Metabol Unit, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752 USA.
EM paul.wood@lmunet.edu
FU Lincoln Memorial University, DeBusk College of Osteopathic medicine;
[NIA-AG08017]
FX This research was funded by Lincoln Memorial University, DeBusk College
of Osteopathic medicine, and by NIA-AG08017.
NR 36
TC 9
Z9 9
U1 2
U2 17
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1601-5215
J9 ACTA NEUROPSYCHIATR
JI Acta Neuropsychiatr.
PD OCT
PY 2015
VL 27
IS 5
BP 270
EP 278
DI 10.1017/neu.2015.18
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CQ6CM
UT WOS:000360692000002
PM 25858158
ER
PT J
AU Safren, SA
Perry, NS
Blashill, AJ
O'Cleirigh, C
Mayer, KH
AF Safren, Steven A.
Perry, Nicholas S.
Blashill, Aaron J.
O'Cleirigh, Conall
Mayer, Kenneth H.
TI The Cost and Intensity of Behavioral Interventions to Promote HIV
Treatment for Prevention Among HIV-Positive Men Who Have Sex with Men
SO ARCHIVES OF SEXUAL BEHAVIOR
LA English
DT Article
DE HIV; Intervention; Prevention; Cost; Syndemic; Sexual orientation
ID RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY ADHERENCE;
PSYCHOSOCIAL HEALTH-PROBLEMS; INJECTION-DRUG USERS; DEPRESSION CBT-AD;
UNITED-STATES; ANAL INTERCOURSE; INFECTED ADULTS; RISK BEHAVIORS;
BISEXUAL MEN
AB Recently, behavioral prevention interventions for HIV have been criticized as being ineffective, costly, or inefficient. In this commentary, using HIV-positive men who have sex with men (MSM) as an illustrative high-risk population, we argue that the opposite is true-that behavioral interventions for HIV prevention, if implemented with the populations who need them, are affordable and critical for future prevention efforts. We base this argument on recent evidence showing that (1) adherence to antiretroviral treatment (ART) for prevention purposes is necessary to suppress HIV replication and reduce transmissibility, (2) individuals living with HIV have multiple psychosocial concerns that impact self-care and moderate the potential effectiveness of health behavior interventions, and (3) intensive interventions targeting both concerns together (psychosocial and HIV care) can show clinically significant improvement. We follow by comparing the cost of these types of interventions to the cost of standard clinical treatment for HIV with ART and demonstrate a cost-savings of potential intensive behavioral interventions for, in this case, HIV-positive MSM who have uncontrolled virus. Keeping this evidence in mind, we conclude that individual intervention must remain a mainstay of HIV prevention for certain critical populations.
C1 [Safren, Steven A.; Perry, Nicholas S.; Blashill, Aaron J.; O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA.
[Safren, Steven A.; Perry, Nicholas S.; Blashill, Aaron J.; O'Cleirigh, Conall; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA.
[Safren, Steven A.; Blashill, Aaron J.; O'Cleirigh, Conall; Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA.
[Safren, Steven A.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Perry, Nicholas S.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA.
[Blashill, Aaron J.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Dept Gen Med, Boston, MA 02215 USA.
RP Safren, SA (reprint author), Univ Miami, Dept Psychol, 5665 Ponce Leon Blvd,POB 248185, Coral Gables, FL 33124 USA.
EM ssafren@psy.miami.edu
FU National Institutes of Health [K24MH094214, P30AI060354, K23MH096647]
FX Support for author time on the article came from National Institutes of
Health Grants K24MH094214 and P30AI060354 awarded to the first author
and K23MH096647 to the third author.
NR 53
TC 1
Z9 1
U1 4
U2 10
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0004-0002
EI 1573-2800
J9 ARCH SEX BEHAV
JI Arch. Sex. Behav.
PD OCT
PY 2015
VL 44
IS 7
BP 1833
EP 1841
DI 10.1007/s10508-014-0455-3
PG 9
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA CQ5TF
UT WOS:000360667900017
PM 26223385
ER
PT J
AU Mimiaga, MJ
Biello, KB
Robertson, AM
Oldenburg, CE
Rosenberger, JG
O'Cleirigh, C
Novak, DS
Mayer, KH
Safren, SA
AF Mimiaga, Matthew J.
Biello, Katie B.
Robertson, Angela M.
Oldenburg, Catherine E.
Rosenberger, Joshua G.
O'Cleirigh, Conall
Novak, David S.
Mayer, Kenneth H.
Safren, Steven A.
TI High Prevalence of Multiple Syndemic Conditions Associated with Sexual
Risk Behavior and HIV Infection Among a Large Sample of Spanish- and
Portuguese-Speaking Men Who Have Sex with Men in Latin America
SO ARCHIVES OF SEXUAL BEHAVIOR
LA English
DT Article
DE HIV; Men who have sex with men; Sexual behavior; Syndemics; Latin
America; Internet; Sexual orientation
ID PSYCHOSOCIAL HEALTH-PROBLEMS; MULTICENTER AIDS COHORT; BASE-LINE DATA;
UNITED-STATES; SUBSTANCE USE; BISEXUAL MEN; ACTIVE MEN; DRUG-USE; GAY;
ONLINE
AB The HIV epidemic in Latin America is highly concentrated in men who have sex with men (MSM). In the United States, multiple co-occurring psychosocial conditions have been shown to act as intertwined epidemics to potentiate HIV transmission among MSM. To date, no study has examined the role of syndemics and condomless sex among MSM in Latin America. In 2012, an online survey was conducted among members of the largest social/sexual networking website for MSM in Latin America. Participants were asked about demographics, sexual behaviors, HIV/STI diagnoses, and psychosocial well-being, including depression, suicidal ideation, hazardous alcohol use, hard drug use during sex, history of childhood/adolescent sexual abuse, intimate partner violence, and sexual compulsivity. Multivariable logistic generalized estimation equations were used to assess the relationship of syndemic factors and (1) engagement in higher risk condomless anal sex and (2) self-report of prior HIV diagnosis. Among 24,274 survey respondents, 74.6 % of the sample had at least one syndemic factor. In an additive model, syndemics were associated with increased odds of higher risk condomless anal sex, ranging from adjusted odds ratio of 1.31 (95 % CI 1.20, 1.43) for one syndemic factor to 4.06 (95 % CI 3.25, 5.09) for 6/7 syndemic factors. Similarly, syndemics were associated with increased odds of HIV infection (p < .0001). This study provides initial evidence that intertwined syndemics increase HIV risk behavior and HIV infection among MSM in Latin America. In the Latin American context, comprehensive HIV prevention interventions for MSM should be developed and tested that simultaneously address co-occurring psychosocial conditions and HIV risk.
C1 [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med,Dept Psychiat, Boston, MA 02114 USA.
[Mimiaga, Matthew J.; Biello, Katie B.; Robertson, Angela M.; Oldenburg, Catherine E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mimiaga, Matthew J.; Biello, Katie B.; Robertson, Angela M.; Oldenburg, Catherine E.; O'Cleirigh, Conall; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Rosenberger, Joshua G.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA.
[Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA.
[Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Infect Dis, Boston, MA 02215 USA.
RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med,Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM mmimiaga@hsph.harvard.edu
OI Bazzi, Angela/0000-0001-6828-1919
NR 68
TC 8
Z9 9
U1 6
U2 21
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0004-0002
EI 1573-2800
J9 ARCH SEX BEHAV
JI Arch. Sex. Behav.
PD OCT
PY 2015
VL 44
IS 7
BP 1869
EP 1878
DI 10.1007/s10508-015-0488-2
PG 10
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA CQ5TF
UT WOS:000360667900020
PM 26159862
ER
PT J
AU Boroughs, MS
Valentine, SE
Ironson, GH
Shipherd, JC
Safren, SA
Taylor, SW
Dale, SK
Baker, JS
Wilner, JG
O'Cleirigh, C
AF Boroughs, Michael S.
Valentine, Sarah E.
Ironson, Gail H.
Shipherd, Jillian C.
Safren, Steven A.
Taylor, S. Wade
Dale, Sannisha K.
Baker, Joshua S.
Wilner, Julianne G.
O'Cleirigh, Conall
TI Complexity of Childhood Sexual Abuse: Predictors of Current
Post-Traumatic Stress Disorder, Mood Disorders, Substance Use, and
Sexual Risk Behavior Among Adult Men Who Have Sex with Men
SO ARCHIVES OF SEXUAL BEHAVIOR
LA English
DT Article
DE Men who have sex with men (MSM); Childhood sexual abuse (CSA); PTSD;
HIV; Sexual orientation
ID PSYCHOSOCIAL HEALTH-PROBLEMS; HIV-RISK; BISEXUAL MEN; PHYSICAL ABUSE;
GAY MEN; BAUSERMAN 1998; URBAN MEN; LIFE-SPAN; YOUNG MEN; WOMEN
AB Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46 %. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections, and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR 2.64: CI 1.24-5.63), two times higher odds of substance use disorder (OR 2.1: CI 1.02-2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04-7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56-6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16-6.36), and a greater number of casual sexual partners (p = 0.02). Both CSA with Physical Injury (OR 4.05: CI 1.9-8.7) and CSA with Intense Fear (OR 5.16: CI 2.5-10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including post-traumatic stress disorder, substance use, and sexual risk taking, and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities.
C1 [Boroughs, Michael S.; Valentine, Sarah E.; Safren, Steven A.; Dale, Sannisha K.; Wilner, Julianne G.; O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Boroughs, Michael S.; Valentine, Sarah E.; Safren, Steven A.; Dale, Sannisha K.; O'Cleirigh, Conall] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Ironson, Gail H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD Womens Hlth Sci, Boston, MA USA.
[Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Safren, Steven A.; Taylor, S. Wade; Baker, Joshua S.; O'Cleirigh, Conall] Fenway Inst, Fenway Hlth, Boston, MA USA.
[Taylor, S. Wade] Wheelock Coll, Dept Social Work, Boston, MA USA.
RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM cocleirigh@mgh.harvard.edu
FU NIMH [R01 MH095624]; [5K24MH094214]
FX This study was supported by a Grant from the NIMH (R01 MH095624) PI:
O'Cleirigh; Author time (Safren) was supported, in part, by Grant
5K24MH094214.
NR 81
TC 4
Z9 4
U1 8
U2 28
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0004-0002
EI 1573-2800
J9 ARCH SEX BEHAV
JI Arch. Sex. Behav.
PD OCT
PY 2015
VL 44
IS 7
BP 1891
EP 1902
DI 10.1007/s10508-015-0546-9
PG 12
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA CQ5TF
UT WOS:000360667900022
PM 26159863
ER
PT J
AU Mimiaga, MJ
Closson, EF
Thomas, B
Mayer, KH
Betancourt, T
Menon, S
Safren, SA
AF Mimiaga, Matthew J.
Closson, Elizabeth F.
Thomas, Beena
Mayer, Kenneth H.
Betancourt, Theresa
Menon, Sunil
Safren, Steven A.
TI Garnering an In-depth Understanding of Men Who Have Sex with Men in
Chennai, India: A Qualitative Analysis of Sexual Minority Status and
Psychological Distress
SO ARCHIVES OF SEXUAL BEHAVIOR
LA English
DT Article
DE HIV; Men who have sex with men; Gay men; Bisexual men; Sexual
orientation; Stigma
ID RISK-TAKING; HIV RISK; GENDER NONCONFORMITY; BISEXUAL YOUTHS; HEALTH;
ABUSE; GAY; PREVENTION; VICTIMIZATION; ORIENTATION
AB Men who have sex with men (MSM) in India are a hidden and largely understudied population, and have an HIV prevalence 17 times higher than that of the general Indian population. Experiences of social marginalization and negative psychosocial conditions occur concurrent to HIV risk among Indian MSM. To better understand the contextual variables driving HIV risk and inform intervention development, five focus groups (n = 46) and nine key informant interviews were conducted with 55 MSM in Chennai in 2010. NVivo software was used to code the transcripts, and data were analyzed using qualitative descriptive analysis methodology. Participants described sources of psychological distress and low self-worth related to gender non-conformity and sexual minority status. These included stigma from society, pressure to marry, lack of familial acceptance, childhood sexual abuse, and the imperative to keep sexual minority status a secret. Participants' personal evaluations revealed that self-acceptance may be an important resilience factor that can shield these psychosocial and HIV risk factors. In promoting health-seeking behavioral changes for Indian MSM at an individual level, our findings point to the potential strength of strategies that focus on self-acceptance of one's sexual minority identity to foster better psychosocial and overall health.
C1 [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Dept Psychiat, Med Sch, Massachusetts Gen Hosp,Behav Med, Boston, MA 02114 USA.
[Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mimiaga, Matthew J.; Closson, Elizabeth F.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Thomas, Beena] Natl Inst Res TB, Chennai, Tamil Nadu, India.
[Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA USA.
[Mayer, Kenneth H.; Betancourt, Theresa] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Menon, Sunil] Sahodaran, Chennai, Tamil Nadu, India.
RP Mimiaga, MJ (reprint author), Harvard Univ, Dept Psychiat, Med Sch, Massachusetts Gen Hosp,Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM mmimiaga@partners.org
FU Indo-U.S. Joint Working Group on Prevention of Sexually Transmitted
Diseases and HIV/AIDS through U.S. National Institute of Mental Health
[R21 MH085314-01]; Indian Council of Medical Research
[Indo-U.S./41/2007-ECD-II]
FX This project was supported by the Indo-U.S. Joint Working Group on
Prevention of Sexually Transmitted Diseases and HIV/AIDS through U.S.
National Institute of Mental Health grant #R21 MH085314-01 (Steven A.
Safren, PI) and Indian Council of Medical Research grant
#Indo-U.S./41/2007-ECD-II (Beena Thomas, PI).
NR 50
TC 3
Z9 3
U1 8
U2 19
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0004-0002
EI 1573-2800
J9 ARCH SEX BEHAV
JI Arch. Sex. Behav.
PD OCT
PY 2015
VL 44
IS 7
BP 2077
EP 2086
DI 10.1007/s10508-014-0369-0
PG 10
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA CQ5TF
UT WOS:000360667900037
PM 25358949
ER
PT J
AU Bellmunt, J
Orsola, A
Sonpavde, G
AF Bellmunt, Joaquim
Orsola, Anna
Sonpavde, Guru
TI Precision and Predictive Medicine in Urothelial Cancer: Are We Making
Progress?
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID BLADDER-CANCER; PHASE-I; CARCINOMA; SENSITIVITY; EVEROLIMUS; MUTATIONS
C1 [Bellmunt, Joaquim; Orsola, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bellmunt, Joaquim; Orsola, Anna] Harvard Univ, Sch Med, Boston, MA USA.
[Sonpavde, Guru] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
RP Bellmunt, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM joaquim_bellmunt@dfci.harvard.edu
NR 13
TC 2
Z9 3
U1 0
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 OCT
PY 2015
VL 68
IS 4
BP 547
EP 549
DI 10.1016/j.eururo.2015.04.025
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA CQ4KM
UT WOS:000360573600008
PM 25935702
ER
PT J
AU Saad, F
Shore, N
Van Poppel, H
Rathkopf, DE
Smith, MR
de Bono, JS
Logothetis, CJ
de Souza, P
Fizazi, K
Mulders, PFA
Mainwaring, P
Hainsworth, JD
Beer, TM
North, S
Fradet, Y
Griffin, TA
De Porre, P
Londhe, A
Kheoh, T
Small, EJ
Scher, HI
Molina, A
Ryan, CJ
AF Saad, Fred
Shore, Neal
Van Poppel, Hendrik
Rathkopf, Dana E.
Smith, Matthew R.
de Bono, Johann S.
Logothetis, Christopher J.
de Souza, Paul
Fizazi, Karim
Mulders, Peter F. A.
Mainwaring, Paul
Hainsworth, John D.
Beer, Tomasz M.
North, Scott
Fradet, Yves
Griffin, Thomas A.
De Porre, Peter
Londhe, Anil
Kheoh, Thian
Small, Eric J.
Scher, Howard I.
Molina, Arturo
Ryan, Charles J.
TI Impact of Bone-targeted Therapies in Chemotherapy-naive Metastatic
Castration-resistant Prostate Cancer Patients Treated with Abiraterone
Acetate: Post Hoc Analysis of Study COU-AA-302
SO EUROPEAN UROLOGY
LA English
DT Article
DE Abiraterone acetate; Bone-targeted therapy; Chemotherapy-naive;
Metastatic castration-resistant prostate cancer
ID ANDROGEN-DEPRIVATION THERAPY; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE;
ZOLEDRONIC ACID; SKELETAL COMPLICATIONS; SURVIVAL; MEN; RECOMMENDATIONS;
PREDNISONE; CARCINOMA
AB Background: Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.
Objective: Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naive mCRPC patients.
Design, setting, and participants: This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
Intervention: Patients were grouped by concomitant BTT use or no BTT use.
Outcome measurements and statistical analysis: Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.
Results and limitations: While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.
Conclusions: AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naive mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.
Patient summary: Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Saad, Fred] Univ Montreal, Montreal, PQ H2L 4M1, Canada.
[Shore, Neal] Atlantic Urol Clin, Carolina Urol Res Ctr, Myrtle Beach, SC USA.
[Van Poppel, Hendrik] Katholieke Univ Leuven Hosp, Leuven, Belgium.
[Rathkopf, Dana E.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Rathkopf, Dana E.; Scher, Howard I.] Weill Cornell Med Coll, New York, NY USA.
[Smith, Matthew R.] Harvard Univ, Sch Med, Boston, MA USA.
[Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[de Bono, Johann S.] Inst Canc Res, Sutton, Surrey, England.
[de Bono, Johann S.] Royal Marsden Hosp, Sutton, Surrey, England.
[Logothetis, Christopher J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[de Souza, Paul] Univ Western Sydney, Sch Med, Ingham Inst, Liverpool, Australia.
[Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Villejuif, France.
[Mulders, Peter F. A.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Mainwaring, Paul] Hematol & Oncol Clin Australia, Brisbane, Qld, Australia.
[Hainsworth, John D.] Sarah Cannon Res Inst, Nashville, TN USA.
[Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[North, Scott] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Fradet, Yves] Univ Laval, Quebec City, PQ, Canada.
[Griffin, Thomas A.] Janssen Res & Dev, Los Angeles, CA USA.
[De Porre, Peter] Janssen Res & Dev, Beerse, Belgium.
[Londhe, Anil] Janssen Res & Dev, Raritan, NJ USA.
[Kheoh, Thian] Janssen Res & Dev, San Diego, CA USA.
[Small, Eric J.; Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Molina, Arturo] Janssen Res & Dev, Menlo Pk, CA USA.
RP Saad, F (reprint author), Univ Montreal, Ctr Hlth, 560 Rue Sherbrooke E, Montreal, PQ H2L 4M1, Canada.
EM fredsaad@videotron.ca
RI Mulders, Peter/H-8076-2014;
OI Rathkopf, Dana/0000-0002-4503-7582
FU Janssen Global Services, LLC.; Janssen Research Development
FX This work was supported by Janssen Research & Development (formerly
Ortho Biotech Oncology Research & Development, unit of Cougar
Biotechnology). Writing assistance was provided by Ann P. Tighe of
PAREXEL and was funded by Janssen Global Services, LLC. The sponsor
played a role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, and approval of the manuscript.
NR 27
TC 9
Z9 9
U1 1
U2 7
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 OCT
PY 2015
VL 68
IS 4
BP 570
EP 577
DI 10.1016/j.eururo.2015.04.032
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CQ4KM
UT WOS:000360573600013
PM 25985882
ER
PT J
AU Sun, T
McKay, R
Lee, GSM
Kantoff, P
AF Sun, Tong
McKay, Rana
Lee, Gwo-Shu Mary
Kantoff, Philip
TI The Role of miRNAs in Prostate Cancer
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID MICRORNAS
C1 [Sun, Tong; McKay, Rana; Lee, Gwo-Shu Mary; Kantoff, Philip] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Kantoff, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM philip_kantoff@dfci.harvard.edu
FU NCI NIH HHS [T32 CA009172]
NR 10
TC 1
Z9 1
U1 1
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 OCT
PY 2015
VL 68
IS 4
BP 589
EP 590
DI 10.1016/j.eururo.2014.12.037
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA CQ4KM
UT WOS:000360573600016
PM 25577717
ER
PT J
AU Koontz, BF
Bossi, A
Cozzarini, C
Wiegel, T
D'Amico, A
AF Koontz, Bridget F.
Bossi, Alberto
Cozzarini, Cesare
Wiegel, Thomas
D'Amico, Anthony
TI A Systematic Review of Hypofractionation for Primary Management of
Prostate Cancer
SO EUROPEAN UROLOGY
LA English
DT Review
DE Prostate cancer; Stereotactic radiation therapy; Hypofractionation;
Prostate-specific antigen; Randomized trials; Genitourinary toxicity;
Gastrointestinal toxicity
ID BODY RADIATION-THERAPY; QUALITY-OF-LIFE; EXTERNAL-BEAM RADIOTHERAPY;
INTENSITY-MODULATED RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL;
COST-EFFECTIVENESS ANALYSIS; DOSE-ESCALATION; LATE TOXICITY; REAL-TIME;
RISK
AB Context: Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined.
Objective: To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology.
Evidence acquisition: Embase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4 Gy per fraction) and extreme hypofractionation (5-10 Gy in 4-7 fractions).
Evidence synthesis: Six relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low-and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade >= 2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015.
Conclusions: Moderate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol.
Patient summary: Hypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Koontz, Bridget F.] Duke Canc Inst, Dept Radiat Oncol, Durham, NC 27707 USA.
[Bossi, Alberto] Inst Gustave Roussy, Dept Radiat Oncol, Villejuif, France.
[Cozzarini, Cesare] Ist Sci San Raffaele, Dept Radiotherapy, I-20132 Milan, Italy.
[Wiegel, Thomas] Univ Hosp Ulm, Dept Radiat Oncol, Ulm, Germany.
[D'Amico, Anthony] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[D'Amico, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Koontz, BF (reprint author), Duke Canc Inst, Dept Radiat Oncol, Box 3085, Durham, NC 27707 USA.
EM bridget.koontz@duke.edu
NR 50
TC 24
Z9 24
U1 3
U2 9
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 OCT
PY 2015
VL 68
IS 4
BP 683
EP 691
DI 10.1016/j.eururo.2014.08.009
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CQ4KM
UT WOS:000360573600036
PM 25171903
ER
PT J
AU Hazlehurst, BL
Kurtz, SE
Masica, A
Stevens, VJ
McBurnie, MA
Puro, JE
Vijayadeva, V
Au, DH
Brannon, ED
Sittig, DF
AF Hazlehurst, Brian L.
Kurtz, Stephen E.
Masica, Andrew
Stevens, Victor J.
McBurnie, Mary Ann
Puro, Jon E.
Vijayadeva, Vinutha
Au, David H.
Brannon, Elissa D.
Sittig, Dean F.
TI CER Hub: An informatics platform for conducting comparative
effectiveness research using multi-institutional, heterogeneous,
electronic clinical data
SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
LA English
DT Article
DE Comparative effectiveness research; Natural language processing;
Electronic health records
ID MEDICAL-RECORD; RESEARCH NETWORK; SYSTEM; CARE; INFRASTRUCTURE; QUALITY;
EVENTS
AB Objectives: Comparative effectiveness research (CER) requires the capture and analysis of data from disparate sources, often from a variety of institutions with diverse electronic health record (EHR) implementations. In this paper we describe the CER Hub, a web-based informatics platform for developing and conducting research studies that combine comprehensive electronic clinical data from multiple health care organizations.
Methods: The CER Hub platform implements a data processing pipeline that employs informatics standards for data representation and web-based tools for developing study-specific data processing applications, providing standardized access to the patient-centric electronic health record (EHR) across organizations.
Results: The CER Hub is being used to conduct two CER studies utilizing data from six geographically distributed and demographically diverse health systems. These foundational studies address the effectiveness of medications for controlling asthma and the effectiveness of smoking cessation services delivered in primary care.
Discussion: The CER Hub includes four key capabilities: the ability to process and analyze both free-text and coded clinical data in the EHR; a data processing environment supported by distributed data and study governance processes; a clinical data-interchange format for facilitating standardized extraction of clinical data from EHRs; and a library of shareable clinical data processing applications.
Conclusion: CER requires coordinated and scalable methods for extracting, aggregating, and analyzing complex, multi-institutional clinical data. By offering a range of informatics tools integrated into a framework for conducting studies using EHR data, the CER Hub provides a solution to the challenges of multi-institutional research using electronic medical record data. (C) 2015 Published by Elsevier Ireland Ltd.
C1 [Hazlehurst, Brian L.; Kurtz, Stephen E.; Stevens, Victor J.; McBurnie, Mary Ann] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Masica, Andrew] Baylor Scott & White Hlth, Ctr Clin Effectiveness, Dallas, TX USA.
[Puro, Jon E.] OCHIN Inc, Portland, OR USA.
[Vijayadeva, Vinutha] Kaiser Permanente Hawaii, Ctr Hlth Res, Honolulu, HI USA.
[Au, David H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Brannon, Elissa D.] Kaiser Permanente Southeast, Atlanta, GA USA.
[Sittig, Dean F.] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA.
RP Hazlehurst, BL (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res 3800 N, Interstate Ave Portland, Hillsboro, OR 97227 USA.
EM Brian.hazlehurst@kpchr.org
FU Agency for Health Care Research and Quality (AHRQ), Department of Health
and Human Services [R01HS019828]
FX The CER Hub project (www.cerhub.org) is funded by grant R01HS019828
(Hazlehurst, PI) from the Agency for Health Care Research and Quality
(AHRQ), Department of Health and Human Services. The funders had no role
in protocol development, data collection, analysis, interpretation, or
manuscript production. The authors of this report are solely responsible
for its content.
NR 42
TC 1
Z9 1
U1 2
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1386-5056
EI 1872-8243
J9 INT J MED INFORM
JI Int. J. Med. Inform.
PD OCT
PY 2015
VL 84
IS 10
BP 763
EP 773
DI 10.1016/j.ijmedinf.2015.06.002
PG 11
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA CQ4GI
UT WOS:000360562100005
PM 26138036
ER
PT J
AU Donfrancesco, R
Innocenzi, M
Marano, A
Biederman, J
AF Donfrancesco, R.
Innocenzi, M.
Marano, A.
Biederman, J.
TI Deficient Emotional Self-Regulation in ADHD Assessed Using a Unique
Profile of the Child Behavior Checklist (CBCL): Replication in an
Italian Study
SO JOURNAL OF ATTENTION DISORDERS
LA English
DT Article
DE emotional self-regulation; ADHD; sensitivity; specificity
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC BIPOLAR DISORDER;
FAMILY RISK ANALYSIS; HYPERACTIVITY DISORDER; DIAGNOSIS; SYMPTOMS;
PREDICTS; YOUTH
AB Objective: A unique profile of the empirically derived Child Behavior Checklist-anxious/depressed, attention, and aggression-deficient emotional self-regulation (CBCL-AAA-DESR profile: 180 and 210) may be used to identify a sizable minority of children with ADHD with associated DESR. The main aim of this study was to replicate these findings in an Italian sample. Method: The sample consisted of 358 children and teenagers aged 6 to 17 years of both sexes with (n = 190) and without a diagnosis of ADHD (n = 168). Results: In all, 40.0% of children with ADHD had a positive CBCL-DESR profile compared with 3.5% of controls. Receiver-operating characteristic analysis showed that the CBCL-DESR profile cut-off (sensitivity = 97.33, specificity = 79.66, criterion 179, 210) discriminated the two subsamples. Conclusion: The findings replicate previous results highlighting the utility of the CBCL as a means of identifying DESR in children with ADHD.
C1 [Donfrancesco, R.] ASL RM B Sandro Pertini Hosp Rome, Rome, Italy.
[Innocenzi, M.] ASL RM B Rome, Rome, Italy.
[Marano, A.] Univ Roma La Sapienza, Cognit Psychol Psychophysiol & Personal, I-00185 Rome, Italy.
[Biederman, J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
RP Marano, A (reprint author), Univ Roma La Sapienza, Dept Dev & Social Psychol, I-00185 Rome, Italy.
EM assunta.marano@uniroma1.it
NR 35
TC 1
Z9 1
U1 3
U2 18
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0547
EI 1557-1246
J9 J ATTEN DISORD
JI J. Atten. Disord.
PD OCT
PY 2015
VL 19
IS 10
SI SI
BP 895
EP 900
DI 10.1177/1087054712462884
PG 6
WC Psychology, Developmental; Psychiatry
SC Psychology; Psychiatry
GA CQ8AV
UT WOS:000360829300007
PM 23212599
ER
PT J
AU Schulte, M
Hser, Y
Saxon, A
Evans, E
Li, L
Huang, D
Hillhouse, M
Thomas, C
Ling, W
AF Schulte, M.
Hser, Y.
Saxon, A.
Evans, E.
Li, L.
Huang, D.
Hillhouse, M.
Thomas, C.
Ling, W.
TI Risk Factors Associated with HCV Among Opioid-Dependent Patients in a
Multisite Study
SO JOURNAL OF COMMUNITY HEALTH
LA English
DT Article
DE Hepatitis C; Injection drug use; Buprenorphine; Methadone maintenance;
Injection risk behavior
ID HEPATITIS-C VIRUS; INJECTION-DRUG USERS; CORE ANTIGEN; GLOBAL
EPIDEMIOLOGY; UNITED-STATES; HEROIN USERS; INFECTION; PREVALENCE;
COCAINE; HEALTH
AB We examined risk factors associated with hepatitis C virus (HCV) infection among opioid-dependent patients enrolled into medication-assisted therapy (buprenorphine or methadone) to determine factors affecting chronic infection. Patients (N = 1039) were randomized as part of a larger, multisite clinical trial sponsored by the National Drug Abuse Treatment Clinical Trials Network assessing liver function. HCV status was first assessed with an antibody screen; if positive, then current infection was determined with an antigen screen testing for detectable virus. Patients were classified as HCV negative, HCV positive but have cleared the virus, or as having chronic HCV. Logistic regression analysis was used to examine demographic and behavioral correlates of the three groups. Thirty-four percent of patients were classified with chronic infection and 14 % had evidence of prior infection with apparent clearing of the virus. Chronic infection was associated with recent injection drug use and cocaine use. Chronic HCV infection was also associated with being older and Hispanic. Age, ethnicity, and current drug use increase the likelihood of being chronically infected with HCV. Strategies targeting high risk subgroups can aid in preventing further disease escalation.
C1 [Schulte, M.; Hser, Y.; Evans, E.; Li, L.; Huang, D.; Hillhouse, M.; Thomas, C.; Ling, W.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Saxon, A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA.
[Saxon, A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Schulte, M (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Integrated Subst Abuse Programs, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA 90025 USA.
EM mtschulte@ucla.edu
RI Evans, Elizabeth/C-5294-2013
OI Evans, Elizabeth/0000-0002-3478-9957
FU National Institute on Drug Abuse [U10DA013045, P30 DA016383]
FX Funding has been provided by the National Institute on Drug Abuse
through Grants U10DA013045 and P30 DA016383. Thanks to the participating
Nodes of the Clinical Trials Network: Pacific Region Node (Matrix
Institute, Los Angeles and BAART, Turk St. Clinic, San Francisco);
Western States Node (Bi-Valley Medical Clinic Inc., Sacramento and CODA
Research, Portland); Delaware Valley Node (NET Steps, Philadelphia);
Pacific Northwest Node (Evergreen Treatment Services, Seattle); and New
England Consortium (Connecticut Counseling Centers, Waterbury and
Hartford Dispensary, Hartford). NIDA had no further role in study
design; in the collection, analysis and interpretation of data; in the
writing of the report; or in the decision to submit the paper for
publication.
NR 40
TC 0
Z9 0
U1 0
U2 2
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 OCT
PY 2015
VL 40
IS 5
BP 940
EP 947
DI 10.1007/s10900-015-0016-2
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CQ5VC
UT WOS:000360672800013
PM 25814381
ER
PT J
AU Ambrus, DB
Benjamin, EJ
Bajwa, EK
Hibbert, KA
Walkey, AJ
AF Ambrus, Daniel B.
Benjamin, Emelia J.
Bajwa, Ednan K.
Hibbert, Kathryn A.
Walkey, Allan J.
TI Risk factors and outcomes associated with new-onset atrial fibrillation
during acute respiratory distress syndrome
SO JOURNAL OF CRITICAL CARE
LA English
DT Article
DE Atrial fibrillation; Acute respiratory distress syndrome; Interleukins;
Troponin; Epinephrine; Mortality; Mechanism
ID SEPTIC SHOCK; ARRHYTHMIAS; SEPSIS; COHORT; NOREPINEPHRINE; MANAGEMENT;
MORTALITY; DOPAMINE; SCORE
AB Purpose: Outcomes and risk factors associated with new-onset atrial fibrillation (AF) during acute respiratory distress syndrome (ARDS) are unclear. We investigated mortality and risk factors associated with new-onset AF during ARDS.
Materials and methods: We obtained data from the ARDS Network Albuterol for Treatment of Acute Lung Injury trial, which prospectively identified new-onset AF among patients with ARDS as an adverse event. We determined Acute Physiology and Chronic Health Evaluation III-adjusted associations between new-onset AF and 90-day mortality. We also examined associations between new-onset AF and markers of inflammation (interleukin 6 and interleukin 8), myocardial injury (troponin I), autonomic activation (epinephrine), and atrial stretch (central venous pressure) as well as other clinical characteristics.
Measurements and main results: Of 282 patients (mean age, 51.6 years; 45% women; 77% white) enrolled in Albuterol for Treatment of Acute Lung Injury, 28 (10%) developed new-onset AF during the study. We did not identify associations between new-onset AF and baseline central venous pressure, plasma levels of troponin I, epinephrine, interleukin 6, or interleukin 8. New-onset AF during ARDS was associated with increased 90-day mortality (new-onset AF, 43% vs no new-onset AF, 19%; Acute Physiology and Chronic Health Evaluation-adjusted odds ratio, 3.09 [95% confidence interval, 1.24-7.72]; P = .02).
Conclusion: New-onset AF during ARDS is associated with increased mortality; however, its mechanisms require further study. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Ambrus, Daniel B.] Umass Mem Med Ctr, Sect Hosp Med, Dept Internal Med, Worcester, MA 01566 USA.
[Ambrus, Daniel B.] Boston Univ, Sch Med, Div Gen Internal Med, Dept Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med & Prevent Med, Boston, MA 02118 USA.
[Bajwa, Ednan K.; Hibbert, Kathryn A.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Sect Pulm & Crit Care,Pulm Ctr, Boston, MA 02118 USA.
RP Walkey, AJ (reprint author), Boston Univ, Sch Med, 72 E Newton St,R 304, Boston, MA 02118 USA.
EM alwalkey@bu.edu
OI Walkey, Allan/0000-0003-4685-6894; Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health/National Heart Lung and Blood Institute
[K01HL116768-01, 2R01HL092577]
FX National Institutes of Health/National Heart Lung and Blood Institute
K01HL116768-01 (Walkey) and 2R01HL092577 (Benjamin)
NR 24
TC 2
Z9 2
U1 0
U2 6
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 OCT
PY 2015
VL 30
IS 5
BP 994
EP 997
DI 10.1016/j.jcrc.2015.06.003
PG 4
WC Critical Care Medicine
SC General & Internal Medicine
GA CQ4FA
UT WOS:000360558500022
PM 26138630
ER
PT J
AU Caya, T
Musuuza, J
Yanke, E
Schmitz, M
Anderson, B
Carayon, P
Safdar, N
AF Caya, Teresa
Musuuza, Jackson
Yanke, Eric
Schmitz, Michelle
Anderson, Brooke
Carayon, Pascale
Safdar, Nasia
TI Using a Systems Engineering Initiative for Patient Safety to Evaluate a
Hospital-wide Daily Chlorhexidine Bathing Intervention
SO JOURNAL OF NURSING CARE QUALITY
LA English
DT Article
DE chlorhexidine bathing; infection control; quality improvement; SEIPS;
systems engineering
ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE-UNIT; ACQUIRED INFECTIONS;
REDUCE; IMPACT
AB We undertook a systems engineering approach to evaluate housewide implementation of daily chlorhexidine bathing. We performed direct observations of the bathing process and conducted provider and patient surveys. The main outcome was compliance with bathing using a checklist. Fifty-seven percent of baths had full compliance with the chlorhexidine bathing protocol. Additional time was the main barrier. Institutions undertaking daily chlorhexidine bathing should perform a rigorous assessment of implementation to optimize the benefits of this intervention.
C1 [Safdar, Nasia] Univ Wisconsin Madison, Dept Med, Madison, WI 53705 USA.
[Caya, Teresa] Univ Wisconsin Madison, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Musuuza, Jackson] Univ Wisconsin Madison, Inst Clin & Translat Res, Madison, WI 53705 USA.
[Carayon, Pascale] Univ Wisconsin Madison, Dept Ind & Syst Engn, Madison, WI 53705 USA.
[Carayon, Pascale] Univ Wisconsin Madison, Ctr Qual & Prod Improvement, Madison, WI 53705 USA.
[Yanke, Eric] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA.
[Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Div Infect Dis, Madison, WI USA.
[Schmitz, Michelle; Anderson, Brooke] Univ Wisconsin Hosp & Clin, Dept Infect Control, Madison, WI 53792 USA.
[Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Infect Dis, Madison, WI 53792 USA.
RP Safdar, N (reprint author), Univ Wisconsin Madison, Dept Med, UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA.
EM ns2@medicine.wisc.edu
FU Clinical and Translational Science Award (CTSA) program, through the NIH
National Center for Advancing Translational Sciences (NCATS)
[UL1TR000427]; United States Department of Veterans Affairs MERIT award
FX The project described was supported by the Clinical and Translational
Science Award (CTSA) program, through the NIH National Center for
Advancing Translational Sciences (NCATS), grant UL1TR000427, and the
United States Department of Veterans Affairs MERIT award.
NR 17
TC 2
Z9 2
U1 3
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-3631
EI 1550-5065
J9 J NURS CARE QUAL
JI J. Nurs. Care Qual.
PD OCT-DEC
PY 2015
VL 30
IS 4
BP 337
EP 344
DI 10.1097/NCQ.0000000000000129
PG 8
WC Nursing
SC Nursing
GA CQ5RN
UT WOS:000360663300008
PM 26035708
ER
PT J
AU Elabdeen, HRZ
Mustafa, M
Hasturk, H
Klepac-Ceraj, V
Ali, RW
Paster, BJ
Van Dyke, T
Bolstad, AI
AF Elabdeen, H. R. Z.
Mustafa, M.
Hasturk, H.
Klepac-Ceraj, V.
Ali, R. W.
Paster, B. J.
Van Dyke, T.
Bolstad, A. I.
TI Subgingival microbial profiles of Sudanese patients with aggressive
periodontitis
SO JOURNAL OF PERIODONTAL RESEARCH
LA English
DT Article
DE human oral microbe identification microarrays; PCR; plaque; saliva
ID DNA-DNA HYBRIDIZATION; HUMAN ORAL MICROBIOME; LEUKOTOXIC JP2 CLONE;
ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; JUVENILE
PERIODONTITIS; AGGREGATIBACTER-ACTINOMYCETEMCOMITANS; MICROBIOLOGICAL
FEATURES; PLAQUE; IDENTIFICATION
AB Background and ObjectiveAggressive periodontitis (AgP) is prevalent and shows a rapid course in African individuals. Although a strong focus has been placed on Aggregatibacteractinomycetemcomitans, new methods support the existence of a complex subgingival microflora in AgP. The purpose of the present study was to map the subgingival microbiota as well as explore the presence of A.actinomycetemcomitans and the JP2 clone in a group of Sudanese individuals with AgP, using different analytical methods.
Material and MethodsA study population consisting of 19 patients with AgP was recruited from patients seeking treatment at University of Science and Technology (UST) in Khartoum. Fifteen healthy subjects were included as controls. Plaque samples were analyzed for 272 taxa using human oral microbe identification microarrays and for 26 periodontal taxa using DNA-DNA hybridization checkerboard. Conventional polymerase chain reaction (PCR) was applied for the detection of A.actinomycetemcomitans and the JP2 clone in plaque. Saliva from patients with AgP was analyzed using quantitative PCR (qPCR) for the detection of A.actinomycetemcomitans.
ResultsEubacteriumyurii was detected more frequently in patients with AgP than in controls, and E.nodatum was found in patients with AgP only. A.actinomycetemcomitans was found in plaque samples of two (12%) patients by human oral microbe identification microarrays and in five (29%) patients with AgP by conventional PCR, as well as in six (32%) of the AgP saliva samples by qPCR. The JP2 clone was identified in only one patient.
ConclusionThe classical periodontal pathogens were not present in high amounts in AgP in the population studied here. Species of Eubacterium, which are not typically associated with AgP, were often detected in individuals with disease. Using laboratory methods with different sensitivities and detection levels allowed identification of variances in microbial communities. The findings reported in this study provide a basis for the further understanding of AgP.
C1 [Elabdeen, H. R. Z.; Mustafa, M.; Bolstad, A. I.] Univ Bergen, Dept Clin Dent, Periodont, Bergen, Norway.
[Hasturk, H.; Van Dyke, T.] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
[Klepac-Ceraj, V.; Paster, B. J.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA.
[Klepac-Ceraj, V.] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02481 USA.
[Ali, R. W.] Univ Sci & Technol, Fac Dent, Omdurman, Sudan.
[Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
RP Bolstad, AI (reprint author), Univ Bergen, Fac Med & Dent, Dept Clin Dent, Periodont, Arstadveien 19, Bergen, Norway.
EM anne.bolstad@iko.uib.no
FU L. Meltzers hoyskolefond; University of Bergen, Bergen, Norway
FX The authors would like to thank Assoc. Professor Olav Boe, University of
Bergen, for helpful advice regarding the statistical analysis, Oyunn
Nilsen, University of Bergen, for technical assistance, and Professor
Vidar Bakken, University of Bergen, for valuable advice regarding
microbiological analysis. The technical assistance from Sean Cotton at
Forsyth Institute is highly acknowledged. This study was supported by L.
Meltzers hoyskolefond and University of Bergen, Bergen, Norway.
NR 48
TC 3
Z9 3
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3484
EI 1600-0765
J9 J PERIODONTAL RES
JI J. Periodont. Res.
PD OCT
PY 2015
VL 50
IS 5
BP 674
EP 682
DI 10.1111/jre.12250
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CQ8LP
UT WOS:000360859600013
PM 25487558
ER
PT J
AU Fontana, J
Jurado, KA
Cheng, NQ
Ly, NL
Fuchs, JR
Gorelick, RJ
Engelman, AN
Steven, AC
AF Fontana, Juan
Jurado, Kellie A.
Cheng, Naiqian
Ly, Ngoc L.
Fuchs, James R.
Gorelick, Robert J.
Engelman, Alan N.
Steven, Alasdair C.
TI Distribution and Redistribution of HIV-1 Nucleocapsid Protein in
Immature, Mature, and Integrase-Inhibited Virions: a Role for Integrase
in Maturation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITORS;
RADIATION-DAMAGE; CRYOELECTRON TOMOGRAPHY; VIRAL-REPLICATION; ELECTRON
CRYOTOMOGRAPHY; 3-DIMENSIONAL STRUCTURE; NUCLEAR-LOCALIZATION;
STRUCTURAL-ANALYSIS; IN-VITRO
AB During virion maturation, HIV-1 capsid protein assembles into a conical core containing the viral ribonucleoprotein (vRNP) complex, thought to be composed mainly of the viral RNA and nucleocapsid protein (NC). After infection, the viral RNA is reverse transcribed into double-stranded DNA, which is then incorporated into host chromosomes by integrase (IN) catalysis. Certain IN mutations (class II) and antiviral drugs (allosteric IN inhibitors [ALLINIs]) adversely affect maturation, resulting in virions that contain "eccentric condensates," electron-dense aggregates located outside seemingly empty capsids. Here we demonstrate that in addition to this mislocalization of electron density, a class II IN mutation and ALLINIs each increase the fraction of virions with malformed capsids (from similar to 12% to similar to 53%). Eccentric condensates have a high NC content, as demonstrated by "tomo-bubblegram" imaging, a novel labeling technique that exploits the susceptibility of NC to radiation damage. Tomo-bubblegrams also localized NC inside wild-type cores and lining the spherical Gag shell in immature virions. We conclude that eccentric condensates represent nonpackaged vRNPs and that either genetic or pharmacological inhibition of IN can impair vRNP incorporation into mature cores. Supplying IN in trans as part of a Vpr-IN fusion protein partially restored the formation of conical cores with internal electron density and the infectivity of a class II IN deletion mutant virus. Moreover, the ability of ALLINIs to induce eccentric condensate formation required both IN and viral RNA. Based on these observations, we propose a role for IN in initiating core morphogenesis and vRNP incorporation into the mature core during HIV-1 maturation.
IMPORTANCE
Maturation, a process essential for HIV-1 infectivity, involves core assembly, whereby the viral ribonucleoprotein (vRNP, composed of vRNA and nucleocapsid protein [NC]) is packaged into a conical capsid. Allosteric integrase inhibitors (ALLINIs) affect multiple viral processes. We have characterized ALLINIs and integrase mutants that have the same phenotype. First, by comparing the effects of ALLINIs on several steps of the viral cycle, we show that inhibition of maturation accounts for compound potency. Second, by using cryoelectron tomography, we find that ALLINIs impair conical capsid assembly. Third, by developing tomo-bubblegram imaging, which specifically labels NC protein, we find that ALLINIs block vRNP packaging; instead, vRNPs form "eccentric condensates" outside the core. Fourth, malformed cores, typical of integrase-deleted virus, are partially replaced by conical cores when integrase is supplied in trans. Fifth, vRNA is necessary for ALLINI-induced eccentric condensate formation. These observations suggest that integrase is involved in capsid morphogenesis and vRNP packaging.
C1 [Fontana, Juan; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Jurado, Kellie A.; Ly, Ngoc L.; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Fuchs, James R.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
[Gorelick, Robert J.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Engelman, AN (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM alan_engelman@dfci.harvard.edu; stevena@mail.nih.gov
RI Fontana, Juan/A-9138-2009
OI Fontana, Juan/0000-0002-9084-2927
FU Intramural Research Program of NIAMS; Intramural AIDS Targeted Antiviral
Program; NIH [AI070042, GM103368]; National Cancer Institute
[HHSN261200800001E]; Leidos Biomedical Research, Inc.
FX This work was funded in part by the Intramural Research Program of NIAMS
(A.C.S.), the Intramural AIDS Targeted Antiviral Program (A.C.S.), NIH
grants AI070042 (A.N.E.) and GM103368 (A.N.E. and J.R.F.), and funds of
the National Cancer Institute under contract HHSN261200800001E with
Leidos Biomedical Research, Inc. (R.J.G.). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 74
TC 17
Z9 17
U1 0
U2 7
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 OCT
PY 2015
VL 89
IS 19
BP 9765
EP 9780
DI 10.1128/JVI.01522-15
PG 16
WC Virology
SC Virology
GA CQ6HJ
UT WOS:000360704900009
PM 26178982
ER
PT J
AU Murphy, SA
Bell, MJ
Clark, ME
Whalen, MJ
Noviski, N
AF Murphy, Sarah A.
Bell, Michael J.
Clark, Maureen E.
Whalen, Michael J.
Noviski, Natan
TI Pediatric Neurocritical Care: A Short Survey of Current Perceptions and
Practices
SO NEUROCRITICAL CARE
LA English
DT Article
DE Pediatrics; Neurocritical care; Pediatric neurocritical care;
Sub-specialization Critical care fellowship; Practice patterns
ID TRAUMATIC BRAIN-INJURY; CARDIAC CRITICAL-CARE; INTENSIVE-CARE;
MANAGEMENT; NEUROLOGY; MEDICINE; CONDUCT
AB Although attention to neurologic injuries and illnesses in pediatric critical care is not new, a sub-specialized field of pediatric neurocritical care has only recently been recognized. Pediatric neurocritical care is an emerging area of clinical and investigative focus. Little is known about the prevalence of specialized pediatric neurocritical care services nor about perceptions regarding how it is impacting medical practice. This survey sought to capture perceptions about an emerging area of specialized pediatric neurocritical care among practitioners in intersecting disciplines, including pediatric intensivists, pediatric neurologits and pediatric neurosurgeons.
A web-based survey was distributed via email to members of relevant professional societies and groups. Survey responses were analyzed using descriptive statistics. Differences in responses between groups of respondents were analyzed using Chi-squared analysis where appropriate.
Specialized clinical PNCC programs were not uncommon among the survey respondents with 20 % currently having a PNCC service at their institution. Despite familiarity with this area of sub-specialization among the survey respondents, the survey did not find consensus regarding its value. Overall, 46 % of respondents believed that a specialized clinical PNCC service improves the quality of care of critically ill children. Support for PNCC sub-specialization was more common among pediatric neurologists and pediatric neurosurgeons than pediatric intensivists. This survey found support across specialties for creating PNCC training pathways for both pediatric intensivists and pediatric neurologists with an interest in this specialized field.
PNCC programs are not uncommon; however, there is not clear agreement on the optimal role or benefit of this area of practice sub-specialization. A broader dialog should be undertaken regarding the emerging practice of pediatric neurocritical care, the potential benefits and drawbacks of this partitioning of neurology and critical care medicine practice, economic and other practical factors, the organization of clinical support services, and the formalization of training and certification pathways for sub-specialization.
C1 [Murphy, Sarah A.; Bell, Michael J.; Clark, Maureen E.; Whalen, Michael J.; Noviski, Natan] MassGen Hosp Children, Pediat Crit Care Off, Boston, MA 02114 USA.
RP Murphy, SA (reprint author), MassGen Hosp Children, Pediat Crit Care Off, 175 Cambridge St,CPZ5,Rm 526, Boston, MA 02114 USA.
EM samurphy@partners.org
FU MGHfC Pediatric Critical Care Department
FX Departmental funds from the MGHfC Pediatric Critical Care Department
were used to pay service fees requested by professional societies to
process survey distribution.
NR 31
TC 0
Z9 0
U1 2
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 OCT
PY 2015
VL 23
IS 2
BP 149
EP 158
DI 10.1007/s12028-015-0120-2
PG 10
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA CQ6FU
UT WOS:000360700700002
PM 25693892
ER
PT J
AU Post, RM
Leverich, GS
Kupka, R
Keck, PE
McElroy, SL
Altshuler, LL
Frye, MA
Rowe, M
Grunze, H
Suppes, T
Nolen, WA
AF Post, Robert M.
Leverich, Gabriele S.
Kupka, Ralph, Jr.
Keck, Paul E.
McElroy, Susan L.
Altshuler, Lori L.
Frye, Mark A.
Rowe, Michael
Grunze, Heinz
Suppes, Trisha
Nolen, Willem A.
TI Increases in multiple psychiatric disorders in parents and grandparents
of patients with bipolar disorder from the USA compared with The
Netherlands and Germany
SO PSYCHIATRIC GENETICS
LA English
DT Article
DE alcohol abuse; depression; family history; genetics; substance abuse
ID ASTERISK-D-CHILD; MENTAL-DISORDERS; UNITED-STATES; FOLLOW-UP; MATERNAL
DEPRESSION; II DISORDER; EARLY-ONSET; HIGH-RISK; STEP-BD;
PSYCHOPATHOLOGY
AB ObjectiveWe previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations.MethodsA total of 968 outpatients (average age 41) with bipolar disorder from four sites in the USA and three in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic and family history information on a patient questionnaire. Family history of psychiatric illness (bipolar disorder, unipolar depression, suicide attempt, alcohol abuse, substance abuse, and other illness) was collected for each parent, four grandparents, siblings, and children.ResultsParents of the probands with bipolar disorder from the USA compared with Europe had a significantly higher incidence of both unipolar and bipolar mood disorders, as well as each of the other psychiatric conditions listed above. With a few exceptions, this burden of psychiatric disorders was also significantly greater in the grandparents, siblings, and children of the USA versus European patients.ConclusionThe increased complexity of psychiatric illness and its occurrence over several generations in the families of patients with bipolar disorder from the USA versus Europe could be contributing to the higher incidence of childhood onsets and greater virulence of illness in the USA compared with Europe. These data are convergent with others suggesting increased both genetic and environmental risk in the USA, but require replication in epidemiologically-derived populations with data based on interviews of the family members.
C1 [Post, Robert M.; Leverich, Gabriele S.; Rowe, Michael] Bipolar Collaborat Network, Bethesda, MD 20814 USA.
[Post, Robert M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA.
[Keck, Paul E.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
[McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Biol Psychiat Program, Cincinnati, OH USA.
[Keck, Paul E.; McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA.
[Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Altshuler, Lori L.] West Los Angeles Healthcare Ctr, Dept Psychiat, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Suppes, Trisha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Suppes, Trisha] VA Palo Alto HealthCare Syst, Palo Alto, CA USA.
[Frye, Mark A.] Mayo Clin, Dept Psychiat, Rochester, MI USA.
[Kupka, Ralph, Jr.] Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands.
[Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Grunze, Heinz] Paracelsus Med Univ Salzburg, Dept Psychiat & Psychotherapy, Christian Doppler Klink, Salzburg, Austria.
RP Post, RM (reprint author), Bipolar Collaborat Network, 5415 West Cedar Lane,Suite 201-B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
OI Grunze, Heinz/0000-0003-4712-8979
FU Stanley Foundation Bipolar Network
FX The research funding for this article was provided by the Stanley
Foundation Bipolar Network from 1995-2002.
NR 57
TC 5
Z9 5
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8829
EI 1473-5873
J9 PSYCHIAT GENET
JI Psychiatr. Genet.
PD OCT
PY 2015
VL 25
IS 5
BP 194
EP 200
DI 10.1097/YPG.0000000000000093
PG 7
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA CQ5PQ
UT WOS:000360658100002
PM 26146875
ER
PT J
AU Throckmorton, A
VanderWalde, L
Brackett, C
Dominici, L
Eisenhauer, T
Johnson, N
Kong, A
Ludwig, K
O'Neill, J
Pugliese, M
Teller, P
Sarantou, T
AF Throckmorton, Alyssa
VanderWalde, Lindi
Brackett, Craig
Dominici, Laura
Eisenhauer, Thomas
Johnson, Nathalie
Kong, Amanda
Ludwig, Kandice
O'Neill, Jennifer
Pugliese, Matthew
Teller, Paige
Sarantou, Terry
TI The Ethics of Breast Surgery
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SKIN-SPARING MASTECTOMY; MEDICAL DECISION-MAKING; CLINICAL-PRACTICE;
CONSENSUS STATEMENT; ADJUVANT TREATMENT; SYSTEMIC THERAPY;
INFORMED-CONSENT; CANCER; WOMEN; GUIDELINES
AB Breast surgery has evolved as a subspecialty of general surgery and requires a working knowledge of benign and malignant diseases, surgical techniques, shared decision-making with patients, collaboration with a multi-disciplinary team, and a basic foundation in surgical ethics. Ethics is defined as the practice of analyzing, evaluating, and promoting best conduct based upon available standards. As new information is obtained or as cultural values change, best conduct may be re-defined. In 2014, the Ethics Committee of the ASBrS acknowledged numerous ethical issues, specific to the practice of breast surgery. This independent review of ethical concerns was created by the Ethics Committee to provide a resource for ASBrS members as well as other surgeons who perform breast surgery. In this review, the professional, clinical, research and technology considerations that breast surgeons face are reviewed with guidelines for ethical physician behavior.
C1 [Throckmorton, Alyssa; VanderWalde, Lindi] Baptist Canc Ctr, Memphis, TN 38120 USA.
[Throckmorton, Alyssa] Univ Tennessee, Memphis, TN USA.
[Brackett, Craig] Coastal Carolina Breast Ctr, Murrells Inlet, SC USA.
[Dominici, Laura] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Eisenhauer, Thomas] Univ N Carolina, Chapel Hill, NC USA.
[Johnson, Nathalie] Legacy Canc Inst, Portland, OR USA.
[Kong, Amanda] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Ludwig, Kandice] Indiana Univ, Indianapolis, IN 46204 USA.
[O'Neill, Jennifer] Arizona Associated Surg, Phoenix, AZ USA.
[Pugliese, Matthew] Univ Hosp, Augusta, GA USA.
[Teller, Paige] Atirus Hlth Harvard Vanguard Med Associates, Boston, MA USA.
[Sarantou, Terry] Carolinas HealthCare Syst, Levine Canc Inst, Dept Gen Surg, Charlotte, NC USA.
RP Throckmorton, A (reprint author), Baptist Canc Ctr, Memphis, TN 38120 USA.
EM Alyssa.Throckmorton@BMHCC.org
NR 37
TC 0
Z9 0
U1 1
U2 3
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 OCT
PY 2015
VL 22
IS 10
BP 3191
EP 3196
DI 10.1245/s10434-015-4751-5
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800006
PM 26219240
ER
PT J
AU Bellon, JR
Golshan, M
Solin, LJ
AF Bellon, Jennifer R.
Golshan, Mehra
Solin, Lawrence J.
TI Controversies in Radiation Oncology for Early-Stage Breast Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID CARCINOMA IN-SITU; GENE-EXPRESSION PATTERNS; LOCAL RECURRENCE;
CONSERVING THERAPY; CONSERVATION TREATMENT; ESTROGEN-RECEPTOR;
FOLLOW-UP; WOMEN; RADIOTHERAPY; TAMOXIFEN
AB Multiple randomized trials, as well as a meta-analysis of these studies, have confirmed the equivalence of breast-conservation and mastectomy. In addition, in unselected populations, adjuvant radiation therapy following lumpectomy has been shown to decrease in-breast recurrence and improve overall survival. However, radiation has morbidity, and is costly and inconvenient. Multiple efforts to minimize treatment have been studied, including omitting radiation in low-risk populations, as well as in those with significant competing risks. Central to these efforts has been an increased awareness of the inherent biology, allowing treatment to be more precisely tailored to the risks posed by each individual patient's disease. In addition, an improved understanding of the radio-responsiveness of both tumor and adjacent normal tissue has permitted safe use of short-course (hypofractionated) radiation. Studies are ongoing to determine the most appropriate candidates for both hypofractionated treatment and omission of radiation entirely. The optimal management of ductal carcinoma in situ is also a subject of intense study. Multiple trials have attempted to identify patients who can safely forego radiation and, more recently, molecular predictors of recurrence have been developed to further fine-tune this low-risk population.
C1 [Bellon, Jennifer R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Bellon, Jennifer R.; Golshan, Mehra] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Golshan, Mehra] Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA.
[Solin, Lawrence J.] Albert Einstein Healthcare Network, Dept Radiat Oncol, Philadelphia, PA USA.
RP Bellon, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
EM jbellon@lroc.harvard.edu
NR 33
TC 2
Z9 2
U1 0
U2 8
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 OCT
PY 2015
VL 22
IS 10
BP 3213
EP 3218
DI 10.1245/s10434-015-4713-y
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800010
PM 26202560
ER
PT J
AU Dietz, JR
Partridge, AH
Gemignani, ML
Javid, SH
Kuerer, HM
AF Dietz, Jill R.
Partridge, Ann H.
Gemignani, Mary L.
Javid, Sara H.
Kuerer, Henry M.
TI Breast Cancer Management Updates: Young and Older, Pregnant, or Male
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID LYMPH-NODE BIOPSY; FERTILITY PRESERVATION; AMERICAN SOCIETY;
UNITED-STATES; FOLLOW-UP; WOMEN; DIAGNOSIS; AGE; BRCA2; MAMMOGRAPHY
AB Every year, more and more patients fall into rare or extreme categories of breast cancer-young, elderly, pregnant, or male. Contributing factors may be improved risk assessment and screening techniques (especially of dense breast tissue), delayed childbearing, and the aging population. These patients can challenge usual medical decision making because of their unique situation. There might be a concern for the fetus, worry about future fertility, a question of local control in a man, or concern for overdiagnosis or overtreatment in an older patient. Because these populations are seldom included in the large breast cancer trials from which standard treatment recommendations are made, an update on management for young, elderly, pregnant, and male breast cancer patients may be helpful.
C1 [Dietz, Jill R.] Case Western Reserve Sch Med, Cleveland, OH 44106 USA.
[Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gemignani, Mary L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Javid, Sara H.] Univ Washington, Seattle, WA 98195 USA.
[Kuerer, Henry M.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Dietz, JR (reprint author), Case Western Reserve Sch Med, Cleveland, OH 44106 USA.
EM jill.dietz@uhhospitals.org
NR 53
TC 1
Z9 1
U1 1
U2 7
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 OCT
PY 2015
VL 22
IS 10
BP 3219
EP 3224
DI 10.1245/s10434-015-4755-1
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800011
PM 26265366
ER
PT J
AU Wong, SM
Freedman, RA
Stamell, E
Sagara, Y
Mbbs, JEB
Desantis, SD
Golshan, M
AF Wong, Stephanie M.
Freedman, Rachel A.
Stamell, Emily
Sagara, Yasuaki
Mbbs, Jane E. Brock
Desantis, Stephen D.
Golshan, Mehra
TI Modern Trends in the Surgical Management of Paget's Disease
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID BREAST-CONSERVING THERAPY; LYMPH-NODE BIOPSY; PROSPECTIVE
EUROPEAN-ORGANIZATION; CONSERVATIVE MANAGEMENT; CANCER; NIPPLE;
RADIOTHERAPY; DISPARITIES; EXPERIENCE; RECEIPT
AB Purpose. We examined the incidence and modern national trends in the management of Paget's disease (PD), including the use of breast-conserving surgery (BCS), mastectomy, axillary surgery, and receipt of radiotherapy.
Methods. Using surveillance, epidemiology and end results (SEER) data, we identified 2631 patients diagnosed with PD during 2000-2011. Of these patients, 185 (7 %) had PD of the nipple only, 953 (36.2 %) had PD with ductal carcinoma in situ (PD-DCIS), and 1493 (56.7 %) had PD with invasive ductal carcinoma (PD-IDC). Trends in age-adjusted incidence, primary surgery, sentinel lymph node biopsy (SLNB), and axillary lymph node dissection were examined. Multivariable logistic regression was used to evaluate factors associated with receipt of BCS and radiotherapy.
Results. A decrease in the age-adjusted incidence of PD occurred from 2000 to 2011 (-4.3 % per year, p < 0.05). The overall rates of mastectomy in the PD only, PD-DCIS, and PD-IDC groups were 47, 69, and 88.9 %, respectively. Only in the PD-IDC group did the proportion of patients undergoing BCS increase significantly, from 8.5 % in 2000 to 15.7 % in 2011 (p = 0.01). Of those who underwent axillary surgery, the proportion of patients undergoing SLNB increased from 2000 to 2011. In adjusted analyses, Paget's subgroup, older age, central tumor location, low/intermediate grade, tumor size < 2.0 cm, SEER region, and year of diagnosis after 2006 were significantly associated with receipt of BCS.
Conclusions. The incidence of Paget's disease has decreased over time while modern trends in local therapy suggest that BCS, SLNB, and adjuvant radiotherapy remain underutilized.
C1 [Wong, Stephanie M.; Stamell, Emily] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Wong, Stephanie M.] McGill Univ, Dept Surg, Ctr Hlth, Montreal, PQ H3A 2T5, Canada.
[Freedman, Rachel A.; Stamell, Emily; Desantis, Stephen D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Mbbs, Jane E. Brock] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Sagara, Yasuaki; Desantis, Stephen D.; Golshan, Mehra] Dana Farber Canc Inst, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Wong, SM (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM mgolshan@partners.org
NR 28
TC 1
Z9 1
U1 0
U2 4
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 OCT
PY 2015
VL 22
IS 10
BP 3308
EP 3316
DI 10.1245/s10434-015-4664-3
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800024
PM 26202552
ER
PT J
AU Tang, R
Coopey, SB
Colwell, AS
Specht, MC
Gadd, MA
Kansal, K
McEvoy, MP
Merrill, AL
Rai, U
Taghian, A
Austen, WG
Smith, BL
AF Tang, Rong
Coopey, Suzanne B.
Colwell, Amy S.
Specht, Michelle C.
Gadd, Michele A.
Kansal, Kari
McEvoy, Maureen P.
Merrill, Andrea L.
Rai, Upahvan
Taghian, Alphonse
Austen, William G.
Smith, Barbara L.
TI Nipple-Sparing Mastectomy in Irradiated Breasts: Selecting Patients to
Minimize Complications
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID RADIATION-THERAPY; RECONSTRUCTION; IMPLANTS; OUTCOMES
AB Background. Nipple-sparing mastectomies (NSM) are increasingly common because of their cosmetic advantage. Radiotherapy (RT) has been a relative contraindication to immediate reconstruction because of concerns about increased complications. We aimed to evaluate outcomes of NSM plus immediate reconstruction in irradiated breasts and to determine additional risk factors for complications.
Methods. We retrospectively reviewed NSM with immediate reconstruction from 2007 to 2013 at our institution. Complications were broken down into several categories. Potential risk factors for complications were evaluated.
Results. There were 982 NSM: 816 had no RT, 67 had prior RT, and 97 had postmastectomy radiotherapy (PMRT). Compared to breasts with no RT, both prior RT and PMRT increased overall complications (10.2 vs. 21.7 and 17.5 %, p = 0.003, 0.03, respectively) and nipple loss (0.9 vs. 4.3 and 4.1 %, p = 0.04, 0.02, respectively), while PMRT increased rate of reconstruction failure (2.2 vs. 8.2 %, p = 0.003). On multivariate regression analysis, prior RT [odds ratio (OR) 2.53, p = 0.006], PMRT (OR 2.29, p = 0.015), age > 55 years (OR 2.03, p = 0.04), breast volume >= 800 cm(3) (OR 1.96, p = 0.04), smoking (OR 2.62, p = 0.001), and periareolar incision (OR 1.74, p = 0.03) were independent risk factors for complications requiring surgical revision. In irradiated breasts, complication rates were 13.4 % without further risk factors and 17.5, 50, and 66.7 % when 1, 2, and >= 3 additional independent risk factors were present, respectively (p < 0.001).
Conclusions. Although complication rates were higher in irradiated breasts, reconstruction failure and nipple/areola necrosis was infrequent. RT should not be a contraindication to NSM. Preoperative identification of risk factors and appropriate patient selection may reduce complication rates.
C1 [Tang, Rong; Coopey, Suzanne B.; Specht, Michelle C.; Gadd, Michele A.; Kansal, Kari; McEvoy, Maureen P.; Merrill, Andrea L.; Rai, Upahvan; Smith, Barbara L.] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Surg Oncol, Boston, MA 02114 USA.
[Tang, Rong] Cent S Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Div Breast Surg,Hunan Canc Hosp, Changsha, Hunan, Peoples R China.
[Colwell, Amy S.; Austen, William G.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA.
[Taghian, Alphonse] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Tang, R (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Surg Oncol, Boston, MA 02114 USA.
EM blsmith1@partners.org
NR 15
TC 12
Z9 12
U1 0
U2 1
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 OCT
PY 2015
VL 22
IS 10
BP 3331
EP 3337
DI 10.1245/s10434-015-4669-y
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800027
PM 26202557
ER
PT J
AU McEvoy, MP
Coopey, SB
Mazzola, E
Buckley, J
Belli, A
Polubriaginof, F
Merrill, AL
Tang, R
Garber, JE
Smith, BL
Gadd, MA
Specht, MC
Guidi, AJ
Roche, CA
Hughes, KS
AF McEvoy, Maureen P.
Coopey, Suzanne B.
Mazzola, Emanuele
Buckley, Julliette
Belli, Ahmet
Polubriaginof, Fernanda
Merrill, Andrea L.
Tang, Rong
Garber, Judy E.
Smith, Barbara L.
Gadd, Michele A.
Specht, Michelle C.
Guidi, Anthony J.
Roche, Constance A.
Hughes, Keven S.
TI Breast Cancer Risk and Follow-up Recommendations for Young Women
Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS)
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID DISEASE; MAMMOGRAPHY; TAMOXIFEN; ULTRASOUND; MRI
AB Background. The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.
Methods. A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.
Results. We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19-34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH.
7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1-298). Median time to cancer diagnosis was 90 months (range 37-231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS.
Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.
Conclusion. Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.
C1 [McEvoy, Maureen P.; Coopey, Suzanne B.; Mazzola, Emanuele; Buckley, Julliette; Belli, Ahmet; Polubriaginof, Fernanda; Merrill, Andrea L.; Tang, Rong; Garber, Judy E.; Smith, Barbara L.; Gadd, Michele A.; Specht, Michelle C.; Guidi, Anthony J.; Roche, Constance A.; Hughes, Keven S.] Massachusetts Gen Hosp, Dept Surg Oncol, Breast Surg Div, Boston, MA 02114 USA.
RP McEvoy, MP (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Breast Surg Div, Boston, MA 02114 USA.
EM mcevoy.maureen@gmail.com
NR 20
TC 3
Z9 3
U1 1
U2 10
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 OCT
PY 2015
VL 22
IS 10
BP 3346
EP 3349
DI 10.1245/s10434-015-4747-1
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800029
PM 26242364
ER
PT J
AU Mallory, MA
Losk, K
Lin, NU
Sagara, Y
Birdwell, RL
Cutone, L
Camuso, K
Bunnell, C
Aydogan, F
Golshan, M
AF Mallory, Melissa Anne
Losk, Katya
Lin, Nancy U.
Sagara, Yasuaki
Birdwell, Robyn L.
Cutone, Linda
Camuso, Kristen
Bunnell, Craig
Aydogan, Fatih
Golshan, Mehra
TI The Influence of Radiology Image Consultation in the Surgical Management
of Breast Cancer Patients
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID DIAGNOSTIC MAMMOGRAPHY; 2ND OPINIONS; VARIABILITY; IMPACT
AB Patients referred to comprehensive cancer centers arrive with clinical data requiring review. Radiology consultation for second opinions often generates additional imaging requests; however, the impact of this service on breast cancer management remains unclear. We sought to identify the incidence of additional imaging requests and the effect additional imaging has on patients' ultimate surgical management.
Between November 2013 and March 2014, 153 consecutive patients with breast cancer received second opinion imaging reviews and definitive surgery at our cancer center. We identified the number of additional imaging requests, the number of fulfilled requests, the modality of additional imaging completed, the number of biopsies performed, and the number of patients whose management was altered due to additional imaging results.
Of 153 patients, the mean age was 55 years; 98.9 % were female; 23.5 % (36) had in situ carcinoma (35 DCIS/1 LCIS), and 76.5 % (117) had invasive carcinoma. Additional imaging was suggested for 47.7 % (73/153) of patients. After multidisciplinary consultation, 65.8 % (48/73) of patients underwent additional imaging. Imaging review resulted in biopsy in 43.7 % (21/48) of patients and ultimately altered preliminary treatment plans in 37.5 % (18/48) of patients (Fig. 1). Changes in management included: conversion to mastectomy or breast conservation, neoadjuvant therapy, additional wire placement, and need for contralateral breast surgery.
Our analysis of second opinion imaging consultation demonstrates the significant value that this service has on breast cancer management. Overall, 11.7 % (18/153) of patients who underwent breast surgery had management changes as a consequence of radiologic imaging review.
C1 [Mallory, Melissa Anne; Sagara, Yasuaki; Cutone, Linda; Aydogan, Fatih; Golshan, Mehra] Dana Farber Brigham & Womens Canc Ctr, Dept Surg, Boston, MA 02115 USA.
[Losk, Katya; Camuso, Kristen] Dana Farber Canc Inst, Dept Qual & Patient Safety, Boston, MA 02115 USA.
[Lin, Nancy U.; Bunnell, Craig] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Birdwell, Robyn L.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Mallory, MA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Surg, Boston, MA 02115 USA.
EM mgolshan@partners.org
FU NIH [R25CA089017]; National Comprehensive Cancer Network (NCCN)
FX This study was funded in part by the NIH Grant R25CA089017 and by the
National Comprehensive Cancer Network (NCCN) Opportunities for
Improvement grant.
NR 14
TC 3
Z9 3
U1 0
U2 2
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 OCT
PY 2015
VL 22
IS 10
BP 3383
EP 3388
DI 10.1245/s10434-015-4663-4
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ0RF
UT WOS:000360303800035
PM 26202551
ER
PT J
AU Bolon-Canedo, V
Ataer-Cansizoglu, E
Erdogmus, D
Kalpathy-Cramer, J
Fontenla-Romero, O
Alonso-Betanzos, A
Chiang, MF
AF Bolon-Canedo, V.
Ataer-Cansizoglu, E.
Erdogmus, D.
Kalpathy-Cramer, J.
Fontenla-Romero, O.
Alonso-Betanzos, A.
Chiang, M. F.
TI Dealing with inter-expert variability in retinopathy of prematurity: A
machine learning approach
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Inter-expert variability; Clinical decision-making; Feature selection;
Machine learning; Classification; Retinopathy of prematurity
ID PLUS DISEASE; INTRAOBSERVER VARIABILITY; FEATURE-SELECTION; DIAGNOSIS;
INTEROBSERVER; AGREEMENT; CLASSIFICATION; PATHOLOGISTS
AB Background and objective: Understanding the causes of disagreement among experts in clinical decision making has been a challenge for decades. In particular, a high amount of variability exists in diagnosis of retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and a major cause of childhood blindness. A possible cause of variability, that has been mostly neglected in the literature, is related to discrepancies in the sets of important features considered by different experts. In this paper we propose a methodology which makes use of machine learning techniques to understand the underlying causes of inter-expert variability.
Methods: The experiments are carried out on a dataset consisting of 34 retinal images, each with diagnoses provided by 22 independent experts. Feature selection techniques are applied to discover the most important features considered by a given expert. Those features selected by each expert are then compared to the features selected by other experts by applying similarity measures. Finally, an automated diagnosis system is built in order to check if this approach can be helpful in solving the problem of understanding high inter-rater variability.
Results: The experimental results reveal that some features are mostly selected by the feature selection methods regardless the considered expert. Moreover, for pairs of experts with high percentage agreement among them, the feature selection algorithms also select similar features. By using the relevant selected features, the classification performance of the automatic system was improved or maintained.
Conclusions: The proposed methodology provides a handy framework to identify important features for experts and check whether the selected features reflect the pairwise agreements/disagreements. These findings may lead to improved diagnostic accuracy and standardization among clinicians, and pave the way for the application of this methodology to other problems which present inter-expert variability. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Bolon-Canedo, V.; Fontenla-Romero, O.; Alonso-Betanzos, A.] Univ A Coruna, Dept Comp Sci, La Coruna, Spain.
[Ataer-Cansizoglu, E.; Erdogmus, D.] Northeastern Univ, Cognit Syst Lab, Boston, MA USA.
[Kalpathy-Cramer, J.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Ophthalmol & Med Informat, Portland, OR 97201 USA.
[Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Clin Epidemiol, Portland, OR 97201 USA.
RP Bolon-Canedo, V (reprint author), Univ A Coruna, Dept Comp Sci, La Coruna, Spain.
EM vbolon@udc.es
RI Alonso-Betanzos, Amparo/K-5057-2014; Fontenla-Romero, Oscar/A-1142-2015;
Bolon-Canedo, Veronica/A-5573-2015;
OI Alonso-Betanzos, Amparo/0000-0003-0950-0012; Fontenla-Romero,
Oscar/0000-0003-4203-8720; Bolon-Canedo, Veronica/0000-0002-0524-6427;
Kalpathy-Cramer, Jayashree/0000-0001-8906-9618
FU Secretaria de Estado de Investigacion of the Spanish Government - FEDER
funds of the European Union [TIN 2012-37954]; Xunta de Galicia - FEDER
funds of the European Union [GRC 2014/035]; NSF [IIS-1118061,
IIS-1149570, SMA-0835976, CNS-1136027]; NLM/NIH [R00LM009889]; NIH
[EY19474, 1R21EY022387-01A1]; Research to Prevent Blindness; Xunta de
Galicia [POS-A/2014/164]
FX This research has been financially supported in part by the Secretaria
de Estado de Investigacion of the Spanish Government through the
research project TIN 2012-37954, and by the Xunta de Galicia through the
research project GRC 2014/035, both of them partially funded by FEDER
funds of the European Union. Also supported by grants IIS-1118061,
IIS-1149570, SMA-0835976, CNS-1136027 from NSF, grant R00LM009889 from
the NLM/NIH; by grants EY19474 and 1R21EY022387-01A1 from the NIH, and
by unrestricted departmental funding from Research to Prevent Blindness.
V. Bolon-Canedo acknowledges the support of Xunta de Galicia under
posdoctoral Grant code POS-A/2014/164. M.F. Chiang is an unpaid member
of the Scientific Advisory Board for Clarity Medical Systems
(Pleasanton, CA).
NR 50
TC 4
Z9 4
U1 1
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-2607
EI 1872-7565
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD OCT
PY 2015
VL 122
IS 1
BP 1
EP 15
DI 10.1016/j.cmpb.2015.06.004
PG 15
WC Computer Science, Interdisciplinary Applications; Computer Science,
Theory & Methods; Engineering, Biomedical; Medical Informatics
SC Computer Science; Engineering; Medical Informatics
GA CP7ZV
UT WOS:000360110100001
PM 26120072
ER
PT J
AU Bowen, ME
Ruch, A
AF Bowen, Mary Elizabeth
Ruch, Alexandra
TI Depressive Symptoms and Disability Risk Among Older White and Latino
Adults by Nativity Status
SO JOURNAL OF AGING AND HEALTH
LA English
DT Article
DE minority health; depression; activities of daily living (ADL);
instrumental activities of daily living (IADL); health paradox
ID MEXICAN-AMERICANS; RACIAL/ETHNIC DIFFERENCES; FUNCTIONAL LIMITATIONS;
PHYSICAL-DISABILITY; HISPANIC IMMIGRANTS; HEALTH; US; COMMUNITY;
ACCULTURATION; PREVALENCE
AB Objective: To examine how the relationship between depressive symptoms and disability may vary by nativity status in later life. Method: This nationally representative prospective study of community-dwelling adults age 51 years and older in the Health and Retirement Study (1998-2010) used hierarchical linear modeling to examine how depressive symptoms (Center for Epidemiological Symptoms of Depression) and disability (instrumental activities of daily living [IADL]; activities of daily living [ADL]) vary by nativity status (U.S.- vs. foreign-born), accounting for changes in social support, health behaviors, and health conditions. Results: Depressive symptoms were associated with increased IADL and ADL disability among Latinos compared with Whites; foreign-born Latinos had lower than expected depressive symptom-related IADL and ADL (0.82; p .001) disability. Discussion: Given that U.S.-born Latinos had similar or poorer depressive symptom-related disability outcomes than Whites, interventions focused on early detection and treatment of depressive symptoms for this group are warranted and may improve disablement outcomes.
C1 [Bowen, Mary Elizabeth] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Bowen, Mary Elizabeth; Ruch, Alexandra] West Chester Univ Penn, W Chester, PA USA.
RP Bowen, ME (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM Mary.Bowen3@va.gov
FU Department of Veterans Affairs, Rehabilitation Research and Development
[RRD CDA E7503W]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Dr. Bowen is
supported by the Department of Veterans Affairs, Rehabilitation Research
and Development (RR&D CDA E7503W).
NR 41
TC 1
Z9 1
U1 3
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0898-2643
EI 1552-6887
J9 J AGING HEALTH
JI J. Aging Health
PD OCT
PY 2015
VL 27
IS 7
BP 1286
EP 1305
DI 10.1177/0898264315580121
PG 20
WC Gerontology; Health Policy & Services
SC Geriatrics & Gerontology; Health Care Sciences & Services
GA CQ2CI
UT WOS:000360406600008
PM 25953809
ER
PT J
AU Liu, WH
Ren, LN
Wang, X
Wang, T
Zhang, N
Gao, Y
Luo, H
Navarro-Alvarez, N
Tang, LJ
AF Liu, Wei-hui
Ren, Li-na
Wang, Xing
Wang, Tao
Zhang, Ning
Gao, Yuan
Luo, Hao
Navarro-Alvarez, Nalu
Tang, Li-jun
TI Combination of exosomes and circulating microRNAs may serve as a
promising tumor marker complementary to alpha-fetoprotein for
early-stage hepatocellular carcinoma diagnosis in rats
SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
LA English
DT Article
DE Hepatocellular carcinoma (HCC); Alpha-fetoprotein (AFP); Circulating
miRNAs; Exosomes; Molecular diagnosis
ID STEM/PROGENITOR CELLS DIFFERENTIATION; EXPRESSION; HEPATITIS; BIOMARKER;
HEPATOCYTES; PROGRESSION; PROGNOSIS; TISSUES; NOTCH; GENE
AB Due to unsatisfying prognosis of AFP for hepatocellular carcinoma (HCC), we aim to evaluate the prognostic value of combination of exosomes and miRNAs in detecting HCC.
HCC was induced with diethylnitrosamine in rats and using a scoring system based on histological examination six different stages (normal liver, degeneration, fibrosis, cirrhosis, early HCC and late HCC) were identified in the development of HCC. The expression levels of AFP, exosomes and miRNAs (miRNA-10b, miRNA-21, miRNA-122 and miRNA-200a) were detected in both tissue and blood samples from those six stages. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the power of each parameter and their different combinations in diagnosing HCC or cirrhosis.
A change in the expression of both exosomes and miRNAs was observed during cirrhosis, which in contrast with AFP starts showing up until the early HCC stage. Interestingly, the expressions of exosomes and the selected four miRNAs at early HCC stage obtained more remarkably alterations than the level of AFP (P < 0.05). On correlation analysis, four selected miRNAs had a significant closer relationship with exosomes when compared with AFP. The different combinations of AFP, exosomes, serous miRNAs and exosomal miRNAs had stronger power in predicting HCC than AFP (area under the curve of ROC, 0.943 vs 0.826).
To conclude, the combination of circulating miRNAs and exosomes might serve as promising biomarkers for non-virus infected HCC screening and cirrhosis discrimination.
C1 [Liu, Wei-hui; Ren, Li-na; Wang, Tao; Luo, Hao; Tang, Li-jun] Chengdu Mil Gen Hosp, Gen Surg Ctr PLA, Chengdu 610083, Sichuan Provinc, Peoples R China.
[Wang, Xing; Zhang, Ning; Gao, Yuan] Xijing Hosp, Gen Surg Ctr, Xian 710032, Shanxi Province, Peoples R China.
[Navarro-Alvarez, Nalu] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Liu, WH (reprint author), Chengdu Mil Gen Hosp, Gen Surg Ctr PLA, Chengdu 610083, Sichuan Provinc, Peoples R China.
EM audiliu12@163.com; whjtlj1251@163.com
NR 41
TC 8
Z9 10
U1 0
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-5216
EI 1432-1335
J9 J CANCER RES CLIN
JI J. Cancer Res. Clin. Oncol.
PD OCT
PY 2015
VL 141
IS 10
BP 1767
EP 1778
DI 10.1007/s00432-015-1943-0
PG 12
WC Oncology
SC Oncology
GA CP7QS
UT WOS:000360083600007
PM 25724413
ER
PT J
AU Zemer-Wassercug, N
Haim, M
Leshem-Lev, D
Orvin, KL
Vaduganathan, M
Gutstein, A
Kadmon, E
Mager, A
Kornowski, R
Lev, EL
AF Zemer-Wassercug, Noa
Haim, Moti
Leshem-Lev, Dorit
Orvin, Katia L.
Vaduganathan, Muthiah
Gutstein, Ariel
Kadmon, Ehud
Mager, Aviv
Kornowski, Ran
Lev, Eli L.
TI The effect of dabigatran and rivaroxaban on platelet reactivity and
inflammatory markers
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Anticoagulation; Atrial fibrillation; Platelet reactivity
ID NONVALVULAR ATRIAL-FIBRILLATION; UNFRACTIONATED HEPARIN; STROKE
PREVENTION; REPERFUSION INJURY; RISK-FACTORS; P-SELECTIN; WARFARIN;
THROMBIN; BIVALIRUDIN; INHIBITION
AB The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 +/- A 7 years, 35 % women, mean CHADS2 score 2.6 +/- A 1.2), and ten patients treated with rivaroxaban (mean age 73 +/- A 9 years, 20 % women, mean CHADS2 score 2.7 +/- A 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.
C1 [Zemer-Wassercug, Noa; Orvin, Katia L.; Gutstein, Ariel; Kadmon, Ehud; Mager, Aviv; Kornowski, Ran; Lev, Eli L.] Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel.
[Zemer-Wassercug, Noa; Haim, Moti; Leshem-Lev, Dorit; Orvin, Katia L.; Gutstein, Ariel; Kadmon, Ehud; Mager, Aviv; Kornowski, Ran; Lev, Eli L.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Haim, Moti] Meir Med Ctr, Dept Cardiol, Kefar Sava, Israel.
[Leshem-Lev, Dorit] Rabin Med Ctr, Felsenstein Med Res Ctr, Petah Tiqwa, Israel.
[Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
RP Lev, EL (reprint author), Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel.
EM elil@clalit.org.il
RI Haim, Moti/K-7381-2014
FU Rabin Medical Center
FX Rabin Medical Center.
NR 37
TC 6
Z9 6
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
EI 1573-742X
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD OCT
PY 2015
VL 40
IS 3
BP 340
EP 346
DI 10.1007/s11239-015-1245-z
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA CP9DF
UT WOS:000360193200013
PM 26184605
ER
PT J
AU Suchomelova, L
Lopez-Meraz, ML
Niquet, J
Kubova, H
Wasterlain, CG
AF Suchomelova, L.
Lopez-Meraz, M. L.
Niquet, J.
Kubova, H.
Wasterlain, C. G.
TI HYPERTHERMIA AGGRAVATES STATUS EPILEPTICUS-INDUCED EPILEPTOGENESIS AND
NEURONAL LOSS IN IMMATURE RATS
SO NEUROSCIENCE
LA English
DT Article
DE neuronal injury; temperature; immature brain; lithium/pilocarpine model;
EEG monitoring
ID TEMPORAL-LOBE EPILEPSY; PROLONGED FEBRILE SEIZURES; UNBIASED
STEREOLOGICAL ESTIMATION; HYPOXIC-ISCHEMIC ENCEPHALOPATHY;
LITHIUM-PILOCARPINE MODEL; ACID-INDUCED SEIZURES; NEONATAL
ENCEPHALOPATHY; BRAIN-DAMAGE; LONG-TERM; HIPPOCAMPAL EXCITABILITY
AB This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 +/- 1 degrees C in hyperthermic SE rats (HT + SE) or at 35 +/- 1 degrees C in normothermic SE animals (NT + SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT + SE and NT + SE pups. At 24 h, neuronal injury was present in the amygdala in the HT + SE group only, and was far more severe in the hippocampus in HT + SE than NT + SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT + SE animals developed convulsive SRS. Both HT + SE and NT + SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 +/- 3.5 vs. 4.2 +/- 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT + SE over NT + SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Suchomelova, L.; Niquet, J.] Vet Adm Greater Los Angeles Healthcare Syst, Epilepsy Res 151, Los Angeles, CA 90073 USA.
[Lopez-Meraz, M. L.] Univ Veracruzana, Ctr Invest Cerebrales, Xalapa 91190, Veracruz, Mexico.
[Kubova, H.] Acad Sci Czech Republic, Inst Physiol, Dept Dev Epileptol, CR-14220 Prague, Czech Republic.
[Wasterlain, C. G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, VA Med Ctr 127, Los Angeles, CA 90073 USA.
RP Suchomelova, L (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, 11 301 Wilshire Blvd,Bldg 114,Room 139, Los Angeles, CA 90073 USA.
EM lsuchomelova@yahoo.com
RI Kubova, Hana/C-4210-2012
OI Kubova, Hana/0000-0002-2016-7428
FU VHA Research Service; National Institute of Health [NS13515, NS059704,
NS074926]; Grant Agency of the Czech Republic [P302/10/0971]; Ministry
of Education of the Czech Republic [ME08045, LC554]; [AV0Z50110509];
[RVO 67985823]
FX This work was supported by VHA Research Service, National Institute of
Health [NS13515, NS059704, NS074926 to C.W.]; Grant Agency of the Czech
Republic [P302/10/0971 to H.K.]; Ministry of Education of the Czech
Republic [ME08045, LC554 to H.K.], and Research Project [AV0Z50110509
and RVO 67985823 to H.K.].
NR 88
TC 2
Z9 2
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD OCT 1
PY 2015
VL 305
BP 209
EP 224
DI 10.1016/j.neuroscience.2015.08.006
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CQ4AT
UT WOS:000360547100019
PM 26259902
ER
PT J
AU Brunetto, AL
Castillo, LA
Petrilli, AS
Macedo, CD
Boldrini, E
Costa, C
Almeida, MT
Kirst, D
Rodriguez-Galindo, C
Pereira, WV
Watanabe, FM
Pizza, M
Benites, E
Morais, V
Gadelha, A
Nakasato, A
Abujamra, AL
Gregianin, LJ
AF Brunetto, Algemir L.
Castillo, Luis A.
Petrilli, Antonio S.
Macedo, Carla D.
Boldrini, Erica
Costa, Cecilia
Almeida, Maria T.
Kirst, Daniela
Rodriguez-Galindo, Carlos
Pereira, Waldir V.
Watanabe, Flora M.
Pizza, Maria
Benites, Eliana
Morais, Vera
Gadelha, Andrea
Nakasato, Antonio
Abujamra, Ana L.
Gregianin, Lauro J.
CA Brazilian Collaborative
Brazilian Collaborative Study Grp
Brazilian Soc Pediat Oncol-SOBOPE
TI Carboplatin in the treatment of Ewing sarcoma: Results of the first
Brazilian collaborative study group for Ewing sarcoma family
tumors-EWING1
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE Ewing/PNET; metastatic disease; VDC/ICE
ID CHILDRENS ONCOLOGY GROUP; PRIMITIVE NEUROECTODERMAL TUMOR;
PROGNOSTIC-FACTORS; STANDARD CHEMOTHERAPY; HOSPITAL EXPERIENCE; SOLID
TUMORS; BONE; CONTROVERSIES; IFOSFAMIDE; GUIDELINES
AB BackgroundLarge cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group.
ProcedurePatients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given.
ResultsOne-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P<0.01).
ConclusionThe VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required. Pediatr Blood Cancer 2015;62:1747-1753. (c) 2015 Wiley Periodicals, Inc.
C1 [Brunetto, Algemir L.; Abujamra, Ana L.] Childrens Canc Inst, Porto Alegre, RS, Brazil.
[Castillo, Luis A.] Hosp Pereira Rossell, Montevideo, Uruguay.
[Petrilli, Antonio S.; Macedo, Carla D.] Univ Fed Sao Paulo, Dept Pediat, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, SP, Brazil.
[Boldrini, Erica] Fundacao Pio XII Hosp Infantojuvenil, Barretos, SP, Brazil.
[Costa, Cecilia] Hosp Canc AC Camargo, Sao Paulo, SP, Brazil.
[Almeida, Maria T.] Hosp Clin Sao Paulo ITACI, Sao Paulo, SP, Brazil.
[Kirst, Daniela] Hosp Crianca Santo Antonio, Porto Alegre, RS, Brazil.
[Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pereira, Waldir V.] Hosp Univ Santa Maria, Santa Maria, RS, Brazil.
[Watanabe, Flora M.] Hosp Infantil Pequeno Principe, Curitiba, PR, Brazil.
[Pizza, Maria] Santa Casa Misercordia Sao Paulo, Sao Paulo, SP, Brazil.
[Benites, Eliana] Inst Clin Pediat Bolivar Risso, Jundia, SP, Brazil.
[Morais, Vera] Hosp Univ Oswaldo Cruz, Recife, PE, Brazil.
[Gadelha, Andrea] Hosp Napoleao Laureano, Joao Pessoa, Paraiba, Brazil.
[Nakasato, Antonio] Univ Fed Rio de Janeiro, Inst Pediat, Rio de Janeiro, RJ, Brazil.
[Gregianin, Lauro J.] Hosp Sao Lucas PUC RS, Porto Alegre, RS, Brazil.
[Gregianin, Lauro J.] Univ Fed Rio Grande do Sul, Dept Pediat, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
RP Gregianin, LJ (reprint author), Hosp Clin Porto Alegre, Rua Ramiro Barcelos 2350,3 Leste Pediat Oncol, Porto Alegre, RS, Brazil.
EM Igregianin@hcpa.ufrgs.br
FU Children's Cancer Institute
FX Grant sponsor: The Children's Cancer Institute
NR 29
TC 2
Z9 2
U1 0
U2 4
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 OCT
PY 2015
VL 62
IS 10
BP 1747
EP 1753
DI 10.1002/pbc.25562
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CP9PY
UT WOS:000360228000011
PM 25917418
ER
PT J
AU Meyersohn, NM
Walker, TG
Oliveira, GR
AF Meyersohn, Nandini M.
Walker, T. Gregory
Oliveira, George R.
TI Advances in Axial Imaging of Peripheral Vascular Disease
SO CURRENT CARDIOLOGY REPORTS
LA English
DT Review
DE Peripheral artery disease; Peripheral vascular disease; Atherosclerosis;
Arterial stenosis; Computed tomography angiography; Magnetic resonance
angiography; Non-contrast angiography
ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ROW CT ANGIOGRAPHY; ENHANCED
MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; MAGNETIC-RESONANCE
ANGIOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; ARTERIAL-DISEASE;
LOWER-EXTREMITY; DIAGNOSTIC PERFORMANCE; OCCLUSIVE DISEASE
AB Peripheral artery disease (PAD) has become increasingly common in the US patient population and can be a highly symptomatic and significant source of morbidity. When PAD is suspected, the first-line screening study that is obtained is typically a noninvasive evaluation that includes the ankle brachial index (ABI). Following a positive screening study, invasive catheter digital subtraction angiography (DSA) has been historically used to image the peripheral artery system and still remains the gold standard. However, newer developments in axial imaging including computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have in large part supplanted DSA for imaging the peripheral artery system in clinical practice. Benefits of CTA include rapid noninvasive acquisition, wide availability, high spatial resolution, and the ability to generate isotropic datasets on 64-detector row and higher CT scanners, thereby allowing for multiplanar 3D reformatting. Drawbacks of CTA include the exposure to both iodinated contrast and ionizing radiation, although the radiation dose exposure is lower than for DSA, and newer techniques such as using low tube voltage and rapid acquisition times allow for lower contrast doses. The presence of vascular calcification also limits the evaluation of small distal arteries using CTA, although the development of dual-energy CT techniques has significantly addressed this issue. Benefits of MRA include the avoidance of exposure to ionizing radiation and high diagnostic accuracy, while drawbacks include limited availability and increased cost along with the risk of nephrogenic systemic fibrosis that is associated with gadolinium-based contrast agents, although the latter can be mitigated by using newer non-contrast MR angiography techniques. Future technical advances in CT and MR hardware and software and MR pulse sequences will likely lead to the broader applicability and increased accuracy of noninvasive axial imaging in the evaluation of patients with peripheral artery disease.
C1 [Meyersohn, Nandini M.; Oliveira, George R.] Massachusetts Gen Hosp, Div Cardiovasc Imaging, Boston, MA 02114 USA.
[Walker, T. Gregory; Oliveira, George R.] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA.
RP Meyersohn, NM (reprint author), Massachusetts Gen Hosp, Div Cardiovasc Imaging, Boston, MA 02114 USA.
EM nmeyersohn@mgh.harvard.edu; tgwalker@mgh.harvard.edu;
groliveira@mgh.harvard.edu
NR 28
TC 0
Z9 0
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3782
EI 1534-3170
J9 CURR CARDIOL REP
JI Curr. Cardiol. Rep.
PD OCT
PY 2015
VL 17
IS 10
AR 87
DI 10.1007/s11886-015-0644-2
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP4OV
UT WOS:000359862800009
PM 26285590
ER
PT J
AU Takatani, R
Minagawa, M
Molinaro, A
Reyes, M
Kinoshita, K
Takatani, T
Kazukawa, I
Nagatsuma, M
Kashimada, K
Sato, K
Matsushita, K
Nomura, F
Shimojo, N
Juppner, H
AF Takatani, Rieko
Minagawa, Masanori
Molinaro, Angelo
Reyes, Monica
Kinoshita, Kaori
Takatani, Tomozumi
Kazukawa, Itsuro
Nagatsuma, Misako
Kashimada, Kenichi
Sato, Kenichi
Matsushita, Kazuyuki
Nomura, Fumio
Shimojo, Naoki
Jueppner, Harald
TI Similar frequency of paternal uniparental disomy involving chromosome
20q (patUPD20q) in Japanese and Caucasian patients affected by sporadic
pseudohypoparathyroidism type Ib (sporPHP1B)
SO BONE
LA English
DT Article
DE Pseudohypoparathyroidism; Parathyroid hormone; Epigenetic; GNAS;
Uniparental disomy
ID BECKWITH-WIEDEMANN-SYNDROME; IMPRINTING CONTROL ELEMENT;
SILVER-RUSSELL-SYNDROME; AUTOSOMAL-DOMINANT; HEREDITARY OSTEODYSTROPHY;
EPIGENETIC DEFECTS; GNAS LOCUS; NEURONATIN; DELETION; GENE
AB Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone that occurs in most cases in the absence of Albright's Hereditary Osteodystrophy (AHO). Familial forms of PHP1B are caused by maternally inherited microdeletions within STX16, the gene encoding syntaxin 16, or within GNAS, a complex genetic locus on chromosome 20q133 encoding Gs alpha and several splice variants thereof. These deletions lead either to a loss-of-methylation affecting GNAS exon A/B alone or to epigenetic changes involving multiple differentially methylated regions (DMRs) within GNAS. Broad GNAS methylation abnormalities are also observed in most sporadic PHP1B (sporPHP1B) cases. However, with the exception of paternal uniparental disomy involving chromosome 20q (patUPD20q), the molecular mechanism leading to this disease variant remains unknown. We now investigated 23 Japanese sporPHP1B cases, who presented with hypocalcemia, hyperphosphatemia, elevated PTH levels, and occasionally with TSH elevations and mild AHO features. Age at diagnosis was 10.6 +/- 1.45 years. Calcium, phosphate, and PTH were 63 +/- 023 mg/dL, 7.7 +/- 0.33 mg/dL, and 305 +/- 34.5 pg/mL, respectively, i.e. laboratory findings that are indistinguishable from those previously observed for Caucasian sporPHP1B cases. All investigated patients showed broad GNAS methylation changes. Eleven individuals were homozygous for SNPs within exon NESP and a pentanucleotide repeat in exon A/B. Two of these patients furthermore revealed homozygosity for numerous microsatellite markers on chromosome 20q raising the possibility of patUPD20q, which was confirmed through the analysis of parental DNA. Based on this and our previous reports, paternal duplication of the chromosomal region comprising the GNAS locus appears to be a fairly common cause of sporPHP1B that is likely to occur with equal frequency in Caucasians and Asians. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Takatani, Rieko; Molinaro, Angelo; Reyes, Monica; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Takatani, Rieko; Molinaro, Angelo; Reyes, Monica; Jueppner, Harald] Harvard Univ, Sch Med, Endocrine Unit, Boston, MA USA.
[Takatani, Rieko; Minagawa, Masanori; Takatani, Tomozumi; Kazukawa, Itsuro; Shimojo, Naoki] Chiba Univ, Grad Sch Med, Dept Pediat, Chiba, Japan.
[Minagawa, Masanori; Kazukawa, Itsuro] Chiba Childrens Hosp, Dept Endocrinol, Chiba, Japan.
[Molinaro, Angelo] Univ Pisa, Univ Hosp Pisa, Dept Clin & Expt Med, Endocrinol Unit, Pisa, Italy.
[Kinoshita, Kaori] Cimitsu Chuo Hosp, Dept Pediat, Kisarazu, Japan.
[Nagatsuma, Misako; Kashimada, Kenichi] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, Japan.
[Sato, Kenichi] Int Univ Hlth & Welf, Dept Med Technol & Sci, Fukuoka, Japan.
[Matsushita, Kazuyuki; Nomura, Fumio] Chiba Univ, Grad Sch Med, Dept Mol Diag, Chiba, Japan.
[Matsushita, Kazuyuki; Nomura, Fumio] Chiba Univ, Grad Sch Med, Div Clin Genet & Prote, Chiba, Japan.
RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA.
EM hjueppner@partners.org
OI Matsushita, Kazuyuki/0000-0001-6742-0761; Molinaro,
Angelo/0000-0002-8539-4429; Kashimada, Kenichi/0000-0003-2505-5932
FU National Institutes of Health [R01 DK46718-22]; Ministry of Health,
Labor and Welfare, Japan
FX We thank Drs. Kenji Fujieda, Shoko Ikema, Tomohiro Ishii, Hiroshi
Mochizuki, Fumio Morohashi, Ayuko Narita, Shinichi Niijima, Hisayuki
Oda, Masaya Osaki, Akira Otake, Tatsuya Shiina, Yoshihito Takahashi,
Tomoyuki Takagi, Seiki Wada, Hiroyuki Yamaoka, Kazuko Yonamine, and
Masanori Yoshida for their help in obtaining blood samples and
laboratory results. Furthermore, we are grateful for continuous support
and interest of all families for participation in this study. This work
was supported by the National Institutes of Health (R01 DK46718-22 to
H.J.) This study was also supported in part by grants from Ministry of
Health, Labor and Welfare, Japan.
NR 44
TC 5
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD OCT
PY 2015
VL 79
BP 15
EP 20
DI 10.1016/j.bone.2015.05.011
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CO9QF
UT WOS:000359509700003
PM 25997889
ER
PT J
AU Crago, AM
Chmielecki, J
Rosenberg, M
O'Connor, R
Byrne, C
Wilder, FG
Thorn, K
Agius, P
Kuk, D
Socci, ND
Qin, LX
Meyerson, M
Hameed, M
Singer, S
AF Crago, Aimee M.
Chmielecki, Juliann
Rosenberg, Mara
O'Connor, Rachael
Byrne, Caitlin
Wilder, Fatima G.
Thorn, Katherine
Agius, Phaedra
Kuk, Deborah
Socci, Nicholas D.
Qin, Li-Xuan
Meyerson, Matthew
Hameed, Meera
Singer, Samuel
TI Near universal detection of alterations in CTNNB1 and Wnt pathway
regulators in desmoid-type fibromatosis by whole-exome sequencing and
genomic analysis
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID BETA-CATENIN; AGGRESSIVE FIBROMATOSES; TUMORS; MUTATIONS; CANCER;
RECURRENCE; MANAGEMENT; PROTEIN; SAMPLES; SINGLE
AB CTNNB1 mutations or APC abnormalities have been observed in approximate to 85% of desmoids examined by Sanger sequencing and are associated with Wnt/-catenin activation. We sought to identify molecular aberrations in wild-type tumors (those without CTNNB1 or APC alteration) and to determine their prognostic relevance. CTNNB1 was examined by Sanger sequencing in 117 desmoids; a mutation was observed in 101 (86%) and 16 were wild type. Wild-type status did not associate with tumor recurrence. Moreover, in unsupervised clustering based on U133A-derived gene expression profiles, wild-type and mutated tumors clustered together. Whole-exome sequencing of eight of the wild-type desmoids revealed that three had a CTNNB1 mutation that had been undetected by Sanger sequencing. The mutation was found in a mean 16% of reads (vs. 37% for mutations identified by Sanger). Of the other five wild-type tumors sequenced, two had APC loss, two had chromosome 6 loss, and one had mutation of BMI1. The finding of low-frequency CTNNB1 mutation or APC loss in wild-type desmoids was validated in the remaining eight wild-type desmoids; directed miSeq identified low-frequency CTNNB1 mutation in four and comparative genomic hybridization identified APC loss in one. These results demonstrate that mutations affecting CTNNB1 or APC occur more frequently in desmoids than previously recognized (111 of 117; 95%), and designation of wild-type genotype is largely determined by sensitivity of detection methods. Even true CTNNB1 wild-type tumors (determined by next-generation sequencing) may have genomic alterations associated with Wnt activation (chromosome 6 loss/BMI1 mutation), supporting Wnt/-catenin activation as the common pathway governing desmoid initiation. (c) 2015 Wiley Periodicals, Inc.
C1 [Crago, Aimee M.; O'Connor, Rachael; Wilder, Fatima G.; Thorn, Katherine; Singer, Samuel] Mem Sloan Kettering Canc Ctr, Sarcoma Biol Lab, Dept Surg, New York, NY 10065 USA.
[Crago, Aimee M.; O'Connor, Rachael; Wilder, Fatima G.; Thorn, Katherine; Singer, Samuel] Mem Sloan Kettering Canc Ctr, Sarcoma Dis Management Program, Dept Surg, New York, NY 10065 USA.
[Crago, Aimee M.; Singer, Samuel] Weill Cornell Med Coll, Dept Surg, New York, NY USA.
[Chmielecki, Juliann; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chmielecki, Juliann; Rosenberg, Mara; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA.
[Byrne, Caitlin; Agius, Phaedra; Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Bioinformat Core, New York, NY 10065 USA.
[Kuk, Deborah; Qin, Li-Xuan] Mem Sloan Kettering Canc Ctr, Biostat & Epidemiol, New York, NY 10065 USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Hameed, Meera] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
RP Crago, AM (reprint author), Mem Sloan Kettering Canc Ctr, Sarcoma Dis Management Program, Dept Surg, 1275 York Ave, New York, NY 10065 USA.
EM cragoa@mskcc.org
OI Kuk, Deborah/0000-0003-1477-3170; Crago, Aimee/0000-0002-2965-752X;
O'Connor, Rachael/0000-0002-6869-7954
FU National Cancer Institute (through the SPORE in Soft Tissue Sarcoma)
[P50-CA140146]; MSKCC Institutional Cancer Center Core [P30-CA008748];
American Cancer Society (Mentored Research Scholar Grant in Applied and
Clinical Research) [MRSG-15-064-01-TBG]; AstraZeneca Postdoctoral
Fellowship (American Cancer Society); Kristen Ann Carr Foundation;
Alicia and Corey Pinkston; Cycle for Survival; Carlos Slim Foundation,
Mexico
FX Supported by: National Cancer Institute (through the SPORE in Soft
Tissue Sarcoma), Grant number: P50-CA140146; MSKCC Institutional Cancer
Center Core, Grant number: P30-CA008748; American Cancer Society
(Mentored Research Scholar Grant in Applied and Clinical Research),
Grant number: MRSG-15-064-01-TBG; AstraZeneca Postdoctoral Fellowship
(American Cancer Society), Kristen Ann Carr Foundation, Alicia and Corey
Pinkston, and Cycle for Survival and the Carlos Slim Foundation, Mexico.
NR 37
TC 8
Z9 8
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-2257
EI 1098-2264
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD OCT
PY 2015
VL 54
IS 10
BP 606
EP 615
DI 10.1002/gcc.22272
PG 10
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA CP3MH
UT WOS:000359783100002
PM 26171757
ER
PT J
AU Yoo, I
Woo, JM
Lee, SH
Fava, M
Mischoulon, D
Papakostas, GI
Kim, EJ
Chung, S
Ha, JH
Jeon, HJ
AF Yoo, Ikki
Woo, Jong-Min
Lee, Seung-Hwan
Fava, Maurizio
Mischoulon, David
Papakostas, George I.
Kim, Eui-Joong
Chung, Seockhoon
Ha, Jee Hyun
Jeon, Hong Jin
TI Influence of anxiety symptoms on improvement of neurocognitive functions
in patients with major depressive disorder: A 12-week, multicenter,
randomized trial of tianeptine versus escitalopram, the CAMPION study
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Major depressive disorder; Neurocognition; Anxiety; Antidepressant trial
ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE DEFICITS; MEMORY DYSFUNCTION;
PANIC DISORDER; PERFORMANCE; ADULTS; ANTIDEPRESSANT; QUESTIONNAIRE;
COMPLAINTS; MORBIDITY
AB Background: Previous research has reported evidence that patients with major depressive disorder (MDD) show anxiety symptoms and neurocognitive impairments. However, the influence of anxiety on neurocognitive function in MDD patients during antidepressant treatment is unclear.
Method: MDD patients (n=164) completed a 12-week, multicenter, randomized trial assigned in a 1:1 ratio to either tianeptine or escitalopram. Changes of anxiety symptoms were assessed by the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D), self-rated subjective cognitive impairment on memory and concentration, the Mini-Mental Status Examination (MMSE), Continuous Performance Test (CPT), Verbal Learning Test (VLT), and Raven's Progressive Matrices (RPM) were assessed every 4 weeks.
Results: During 12 weeks of treatment, decrease in the HAM-A score was significantly associated with improvement of subjective cognitive impairments on memory (p < 0.001) and concentration (p < 0.001), and objective measures on delayed memory (p =0.006) ancl reasoning ability (p-0.002), after adjusting for covariates such as baseline HAM-A scores, time, sex, age, education years and assigned medication using the Mixed effects and Generalized Estimated Equation model analysis. However, the other cognitive outcome variables, immediate memory, commission error, and MMSE, which showed significant improvement through 12-week study period, showed no significant association with improvement of anxiety.
Conclusion: Improvement of anxiety symptoms was significantly associated with improvement in subjective and objective neurocognitive functions such as delayed memory and reasoning ability in elderly MDD patients during antidepressant treatment, but not significantly associated with improvement of immediate memory and commission error. Trial registration: ClinicalTrials.gov identifier NC101309776 (C) 2015 Elsevier B.V. All rights reserved.
C1 [Yoo, Ikki; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea.
[Jeon, Hong Jin] SAIHST, Dept Clin Res Design, Seoul, South Korea.
[Jeon, Hong Jin] SAIHST, Dept Med Device Management & Res, Seoul, South Korea.
[Fava, Maurizio; Mischoulon, David; Papakostas, George I.; Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA.
[Woo, Jong-Min] Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea.
[Lee, Seung-Hwan] Inje Univ, Sch Med, Ilsan Paik Hosp, Dept Psychiat, Seoul, South Korea.
[Kim, Eui-Joong] Eulji Univ, Sch Med, Eulji Gen Hosp, Dept Psychiat, Seoul, South Korea.
[Chung, Seockhoon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Seoul, South Korea.
[Ha, Jee Hyun] Konkuk Univ, Sch Med, Dept Psychiat, Seoul, South Korea.
RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, 50 Irwon Dong, Seoul, South Korea.
EM jeonhj@skku.edu
OI yoo, ikki/0000-0003-4474-4522
FU Jeil Pharmaceutical Co., LTD; Basic Science Research Program through the
National Research Foundation of Korea (NRF) - Ministry of Education,
Science and Technology [2011-0013064]; Samsung Medical Center Clinical
Research Development Program (CRDP) [SMO1131461]
FX Financial support for this research was in the form of an unrestricted
grant front the Jeil Pharmaceutical Co., LTD, the Basic Science Research
Program through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (No. 2011-0013064),
and the Samsung Medical Center Clinical Research Development Program
(CRDP) Grant SMO1131461. The authors thank the 164 patients for their
voluntary participation and our research team. The authors thank the
Biostatistics team, Samsung Biomedical Research Institute, Chief Dr.
Seon-Woo Kim and MS. Sook-Young Woo for statistical analysis.
NR 47
TC 1
Z9 1
U1 3
U2 18
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 OCT 1
PY 2015
VL 185
BP 24
EP 30
DI 10.1016/j.jad.2015.06.038
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CP2RS
UT WOS:000359725400005
PM 26142691
ER
PT J
AU Van Horn, DHA
Drapkin, M
Lynch, KG
Rennert, L
Goodman, JD
Thomas, T
Ivey, M
McKay, JR
AF Van Horn, Deborah H. A.
Drapkin, Michelle
Lynch, Kevin G.
Rennert, Lior
Goodman, Jessica D.
Thomas, Tyrone
Ivey, Megan
McKay, James R.
TI Treatment choices and subsequent attendance by substance-dependent
patients who disengage from intensive outpatient treatment
SO ADDICTION RESEARCH & THEORY
LA English
DT Article
DE Adaptive treatment; intensive outpatient programmes; treatment choice;
treatment disengagement
ID CONTINUING CARE; ALCOHOL DEPENDENCE; COCAINE DEPENDENCE;
RANDOMIZED-TRIAL; USE DISORDERS; ENGAGEMENT; RETENTION; RELAPSE;
COMMITMENT; ABSTINENCE
AB In an effort to increase engagement in effective treatment, we offered a choice of alternate evidence-based treatments to 137 alcohol- or cocaine-dependent adults (110 males, 27 females), who entered an intensive outpatient programme (IOP) but disengaged within the first 8 weeks. We hypothesised that disengaged patients would choose and subsequently attend alternatives to IOP when given the chance, that their choices would be consistent with their previously-stated preferences, and that demographic and clinical characteristics would be predictive of alternatives chosen. Of 96 participants reached by phone, 19% chose no treatment; 49% chose to return to IOP; 24% chose individual psychotherapy; 6% chose telephone counselling; 2% chose naltrexone with medication management. There were few relationships between participant characteristics and choices made upon disengagement. Participants who chose alternative treatments were equally likely to attend their chosen treatment as those who chose IOP. Limited interest in alternative treatments may reflect allegiance to IOP, which was initially chosen by all participants. Implications for implementation of patient-centred adaptive treatment are discussed.
C1 [Van Horn, Deborah H. A.; Drapkin, Michelle; Lynch, Kevin G.; Rennert, Lior; Goodman, Jessica D.; Thomas, Tyrone; Ivey, Megan; McKay, James R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Drapkin, Michelle; Goodman, Jessica D.] Vet Affairs Med Ctr, Philadelphia, PA USA.
[McKay, James R.] Philadelphia VA Med Ctr, CESATE, Philadelphia, PA USA.
RP Van Horn, DHA (reprint author), Univ Penn, Dept Psychiat, 3440 Market St, Philadelphia, PA 19104 USA.
EM dvh@mail.med.upenn.edu
FU NIDA [P60-DA-05186, K24 DA029062]; NIAAA [P01-AA016821]; Department of
Veterans Affairs
FX The authors report no conflicts of interest. This research was supported
by NIDA grants P60-DA-05186 and K24 DA029062, NIAAA grant P01-AA016821,
and by the Department of Veterans Affairs. There was no involvement of a
pharmaceutical company in funding this research. The sponsors played no
role in preparation of this article.
NR 42
TC 1
Z9 1
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1606-6359
EI 1476-7392
J9 ADDICT RES THEORY
JI Addict. Res. Theory
PD OCT
PY 2015
VL 23
IS 5
BP 391
EP 403
DI 10.3109/16066359.2015.1017570
PG 13
WC Substance Abuse; Social Issues
SC Substance Abuse; Social Issues
GA CO0EZ
UT WOS:000358824200006
PM 27667970
ER
PT J
AU Li, W
Reategui, E
Park, MH
Castleberry, S
Deng, JZ
Hsu, B
Mayner, S
Jensen, AE
Sequist, LV
Maheswaran, S
Haber, DA
Toner, M
Stott, SL
Hammond, PT
AF Li, Wei
Reategui, Eduardo
Park, Myoung-Hwan
Castleberry, Steven
Deng, Jason Z.
Hsu, Bryan
Mayner, Sarah
Jensen, Anne E.
Sequist, Lecia V.
Maheswaran, Shyamala
Haber, Daniel A.
Toner, Mehmet
Stott, Shannon L.
Hammond, Paula T.
TI Biodegradable nano-films for capture and non-invasive release of
circulating tumor cells
SO BIOMATERIALS
LA English
DT Article
DE Biodegradable; Nano-film; Alginate; Circulating tumor cells;
Layer-by-layer; Surface modification
ID LAYER-BY-LAYER; PROSTATE-CANCER; BLOOD; LYMPHOCYTES; FLUORESCENT;
CHALLENGES; SEPARATION; MARKER; DNA
AB Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips. Published by Elsevier Ltd.
C1 [Li, Wei; Park, Myoung-Hwan; Castleberry, Steven; Deng, Jason Z.; Hsu, Bryan; Mayner, Sarah; Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Li, Wei] Texas Tech Univ, Dept Chem Engn, Lubbock, TX 79409 USA.
[Reategui, Eduardo; Maheswaran, Shyamala; Toner, Mehmet] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Reategui, Eduardo; Jensen, Anne E.; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA USA.
[Deng, Jason Z.; Hammond, Paula T.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Sequist, Lecia V.; Maheswaran, Shyamala; Haber, Daniel A.; Stott, Shannon L.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Sequist, Lecia V.; Haber, Daniel A.; Stott, Shannon L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Hammond, PT (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM sstott@mgh.harvard.edu; hammond@mit.edu
RI Li, Wei/P-3546-2016;
OI Li, Wei/0000-0002-4738-1475; Park, Myoung-Hwan/0000-0003-3095-3016
FU Stand Up to Cancer, a joint program of the Entertainment Industry
Foundation (EIF); American Association for Cancer Research (AACR);
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
[EB008047]; NIH [P41 EB002503-11]
FX We express our gratitude to the all patients who participated in this
study and the healthy volunteers who contributed blood samples. We are
also grateful to Dr. Ajay Shah for initial critical discussions. We
would like to acknowledge Octavio Hurtado and Laura Libby for their
expert technical support. This work was supported by a grant from Stand
Up to Cancer, a joint program of the Entertainment Industry Foundation
(EIF) and the American Association for Cancer Research (AACR). We
acknowledge support from: National Institute for Biomedical Imaging and
Bioengineering (NIBIB) EB008047 (M. T., and D.A.H.), and NIH P41
EB002503-11 (M. T.).
NR 44
TC 11
Z9 11
U1 16
U2 141
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD OCT
PY 2015
VL 65
BP 93
EP 102
DI 10.1016/j.biomaterials.2015.06.036
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA CN9YH
UT WOS:000358806600010
PM 26142780
ER
PT J
AU Cao, Y
Rosner, BA
Ma, J
Tamimi, RM
Chan, AT
Fuchs, CS
Wu, KN
Giovannucci, EL
AF Cao, Yin
Rosner, Bernard A.
Ma, Jing
Tamimi, Rulla M.
Chan, Andrew T.
Fuchs, Charles S.
Wu, Kana
Giovannucci, Edward L.
TI Assessing individual risk for high-risk colorectal adenoma at first-time
screening colonoscopy
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE risk prediction; colorectal adenoma; colonoscopy; screening
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; FOOD FREQUENCY QUESTIONNAIRE; MALE
HEALTH-PROFESSIONALS; SOCIETY-TASK-FORCE; AGE 70 YEARS; CANCER-RISK;
UNITED-STATES; COLON-CANCER; BREAST-CANCER; ADVANCED NEOPLASIA
AB Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma 1 cm, or with advanced histology, or 3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR]=9.41), and 6.6% vs. 2.1% for women (OR=3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening.
What's New? Population screening has dramatically reduced mortality rates for colorectal cancer (CRC) in the U.S. However, colonoscopy is expensive, and healthcare resources need to be more efficiently allocated. In this study, the authors developed and validated a comprehensive risk-assessment tool for high-risk colorectal adenoma. This tool, which includes a list of risk factors, may allow first-line colorectal cancer screening to identify people who are at increased risk. These people could then be encouraged to undergo colonoscopy, and to alter their behavior and lifestyle factors to lower their risk.
C1 [Cao, Yin; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Cao, Yin; Ma, Jing; Tamimi, Rulla M.; Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Rosner, Bernard A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Giovannucci, EL (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA.
EM egiovann@hsph.harvard.edu
RI Dey, Kamalesh/E-6568-2017
FU NIH [P01 CA87969, P01 CA55075, 1UM1 CA167552, R01 CA137178, K24
DK098311]; Entertainment Industry Foundation through the National
Colorectal Cancer Research Alliance
FX Grant sponsor: NIH; Grant number: P01 CA87969, P01 CA55075, 1UM1
CA167552, R01 CA137178, K24 DK098311; Grant sponsor: Entertainment
Industry Foundation through the National Colorectal Cancer Research
Alliance. A.T.C. is a Damon Runyon Clinical Investigator.
NR 59
TC 3
Z9 3
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 1
PY 2015
VL 137
IS 7
BP 1719
EP 1728
DI 10.1002/ijc.29533
PG 10
WC Oncology
SC Oncology
GA CM9FK
UT WOS:000358012600020
PM 25820865
ER
PT J
AU Salma, N
Song, JS
Arany, Z
Fisher, DE
AF Salma, Nunciada
Song, Jun S.
Arany, Zoltan
Fisher, David E.
TI Transcription Factor Tfe3 Directly Regulates Pgc-1alpha in Muscle
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID ACTIVATED RECEPTOR-GAMMA; SKELETAL-MUSCLE; OXIDATIVE-METABOLISM; INSULIN
SENSITIVITY; LIPID-METABOLISM; GENE-EXPRESSION; PGC-1-ALPHA;
COACTIVATOR; MICROPHTHALMIA; FAMILY
AB The microphthalmia (MiT) family of transcription factors is an important mediator of metabolism. Family members Mitf and Tfeb directly regulate the expression of the master regulator of metabolism, peroxisome-proliferator activated receptor gamma coactivator-1 alpha (Pgc-1alpha), in melanomas and in the liver, respectively. Pgc-1alpha is enriched in tissues with high oxidative capacity and plays an important role in the regulation of mitochondrial biogenesis and cellular metabolism. In skeletal muscle, Pgc-1alpha affects many aspects of muscle functionally such as endurance, fiber-type switching, and insulin sensitivity. Tfe3 also regulates muscle metabolic genes that enhance insulin sensitivity in skeletal muscle. Tfe3 has not yet been shown to regulate Pgc-1alpha expression. Our results reported here show that Tfe3 directly regulates Pgc-1alpha expression in myotubes. Tfe3 ectopic expression induces Pgc-1alpha, and Tfe3 silencing suppresses Pgc-1alpha expression. This regulation is direct, as shown by Tfe3's binding to E-boxes on the Pgc-1alpha proximal promoter. We conclude that Tfe3 is a critical transcription factor that regulates Pgc-1alpha gene expression in myotubes. Since Pgc-1alpha coactivates numerous biological programs in diverse tissues, the regulation of its expression by upstream transcription factors such Tfe3 implies potential opportunities for the treatment of diseases where modulation of Pgc-1alpha expression may have important clinical outcomes. (C) 2015 Wiley Periodicals, Inc.
C1 [Salma, Nunciada; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC,Dept Dermatol, Boston, MA 02114 USA.
[Song, Jun S.] CDMC Theme, Inst Genom Biol, Urbana, IL USA.
[Song, Jun S.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
[Song, Jun S.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
[Arany, Zoltan] Univ Penn, Smilow Ctr Translat Res, Sch Med, Cardiovasc Inst Perelman, Philadelphia, PA 19104 USA.
RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bartlett 6,55 Fruit St, Boston, MA 02114 USA.
EM dfisher3@partners.org
FU The American Heart Association Fellowship (AHA) [AHA-0726015T, R01
CA163336, RO1-AR043369, P01 CA163222, R01 HL094499]; PhRMA Foundation;
National Cancer Institute; Melanoma Research Alliance; Dr. Miriam and
Sheldon G. Adelson Medical Research Foundation; National Institutes of
Health; US-Israel Binational Science Foundation; Doris Duke Medical
Research Foundation
FX Contract grant sponsor: The American Heart Association Fellowship
(AHA);; Contract grant numbers: AHA-0726015T, R01 CA163336,
RO1-AR043369, P01 CA163222, R01 HL094499.; Contract grant sponsor: PhRMA
Foundation.; Contract grant sponsor: National Cancer Institute.;
Contract grant sponsor: Melanoma Research Alliance.; Contract grant
sponsor: Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.;
Contract grant sponsor: National Institutes of Health.; Contract grant
sponsor: US-Israel Binational Science Foundation.; Contract grant
sponsor: Doris Duke Medical Research Foundation.
NR 47
TC 4
Z9 5
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD OCT
PY 2015
VL 230
IS 10
BP 2330
EP 2336
DI 10.1002/jcp.24978
PG 7
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA CM6RA
UT WOS:000357815600006
PM 25736533
ER
PT J
AU Ahonkhai, AA
Banigbe, B
Adeola, J
Onwuatuelo, I
Bassett, IV
Losina, E
Freedberg, KA
Okonkwo, P
Regan, S
AF Ahonkhai, Aimalohi A.
Banigbe, Bolanle
Adeola, Juliet
Onwuatuelo, Ifeyinwa
Bassett, Ingrid V.
Losina, Elena
Freedberg, Kenneth A.
Okonkwo, Prosper
Regan, Susan
TI High rates of unplanned interruptions from HIV care early after
antiretroviral therapy initiation in Nigeria
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE Retention; Unplanned care interruption; Gaps in care; Resource-limited
setting; HIV
ID SUB-SAHARAN AFRICA; SOUTH-AFRICA; FOLLOW-UP; INFECTED ADOLESCENTS;
TREATMENT PROGRAMS; PATIENT RETENTION; PATIENTS LOST; PRE-ART;
MORTALITY; ADHERENCE
AB Background: Unplanned care interruption (UCI) challenges effective HIV treatment. We determined the frequency and risk factors for UCI in Nigeria.
Methods: We conducted a retrospective-cohort study of adults initiating antiretroviral therapy (ART) between January 2009 and December 2011. At censor, patients were defined as in care, UCI, or inactive. Associations between baseline factors and UCI rates were quantified using Poisson regression.
Results: Among 2,496 patients, 44 % remained in care, 35 % had >= 1 UCI, and 21 % became inactive. UCI rates were higher in the first year on ART (39/100PY), than the second (19/100PY), third (16/100PY), and fourth (14/100PY) years (p < 0.001). In multivariate analysis, baseline CD4 > 350/uL (IRR 3.21, p < 0.0001), being a student (IRR 1.95, p < 0.0001), and less education (IRR 1.58, p = 0.001) increased risk for UCI. Fifty-five percent of patients with UCI and viral load data had HIV viral load > 1,000 copies/ml upon return to care.
Discussion: UCI were observed in over one-third of patients treated, and were most common in the first year on ART. High baseline CD4 count at ART initiation was the greatest predictor of subsequent UCI.
Conclusions: Interventions focused on the first year on ART are needed to improve continuity of HIV care.
C1 [Ahonkhai, Aimalohi A.; Bassett, Ingrid V.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Ahonkhai, Aimalohi A.; Bassett, Ingrid V.; Losina, Elena; Freedberg, Kenneth A.; Regan, Susan] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Banigbe, Bolanle; Adeola, Juliet; Onwuatuelo, Ifeyinwa; Okonkwo, Prosper] APIN, Abuja, Nigeria.
[Bassett, Ingrid V.; Freedberg, Kenneth A.; Regan, Susan] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Bassett, Ingrid V.; Freedberg, Kenneth A.; Regan, Susan] Harvard Univ, Ctr AIDS Res CFAR, Boston, MA 02115 USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Freedberg, Kenneth A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Ahonkhai, AA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM aahonkhai@mgh.harvard.edu
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [K23 AI106406-02, R01 AI058736-09S1, R01 MH090326,
2P30AI060354]; Centers for Disease Control and Prevention [5U2GPS001058]
FX Research reported in this publication was supported by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health under Award Numbers: K23 AI106406-02, R01 AI058736-09S1, R01
MH090326, 2P30AI060354. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health. This study was also supported in part by
cooperative agreement number 5U2GPS001058 from the Centers for Disease
Control and Prevention.
NR 54
TC 3
Z9 3
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD SEP 30
PY 2015
VL 15
AR 397
DI 10.1186/s12879-015-1137-z
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA CS7GN
UT WOS:000362252200006
PM 26424505
ER
PT J
AU Dossett, ML
Mu, L
Davis, RB
Bell, IR
Lembo, AJ
Kaptchuk, TJ
Yeh, GY
AF Dossett, Michelle L.
Mu, Lin
Davis, Roger B.
Bell, Iris R.
Lembo, Anthony J.
Kaptchuk, Ted J.
Yeh, Gloria Y.
TI Patient-Provider Interactions Affect Symptoms in Gastroesophageal Reflux
Disease: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial
SO PLOS ONE
LA English
DT Article
ID ALTERNATIVE MEDICINE; CONVENTIONAL MEDICINE; RELATIONAL EMPATHY; CARE;
COMPLEMENTARY; CONSULTATION; QUALITY; RELIABILITY; SEVERITY; OUTCOMES
AB Background
It is unclear whether the benefits that some patients derive from complementary and integrative medicine (CIM) are related to the therapies recommended or to the consultation process as some CIM provider visits are more involved than conventional medical visits. Many patients with gastrointestinal conditions seek out CIM therapies, and prior work has demonstrated that the quality of the patient-provider interaction can improve health outcomes in irritable bowel syndrome, however, the impact of this interaction on gastroesophageal reflux disease (GERD) is unknown. We aimed to assess the safety and feasibility of conducting a 2x2 factorial design study preliminarily exploring the impact of the patient-provider interaction, and the effect of an over-the-counter homeopathic product, Acidil, on symptoms and health-related quality of life in subjects with GERD.
Methods
24 subjects with GERD-related symptoms were randomized in a 2x2 factorial design to receive 1) either a standard visit based on an empathic conventional primary care evaluation or an expanded visit with questions modeled after a CIM consultation and 2) either Acidil or placebo for two weeks. Subjects completed a daily GERD symptom diary and additional measures of symptom severity and health-related quality of life.
Results
There was no significant difference in GERD symptom severity between the Acidil and placebo groups from baseline to follow-up (p = 0.41), however, subjects who received the expanded visit were significantly more likely to report a 50% or greater improvement in symptom severity compared to subjects who received the standard visit (p = 0.01). Total consultation length, perceived empathy, and baseline beliefs in CIM were not associated with treatment outcomes.
Conclusion
An expanded patient-provider visit resulted in greater GERD symptom improvement than a standard empathic medical visit. CIM consultations may have enhanced placebo effects, and further studies to assess the active components of this visit-based intervention are warranted.
C1 [Dossett, Michelle L.; Mu, Lin; Davis, Roger B.; Kaptchuk, Ted J.; Yeh, Gloria Y.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Mu, Lin] Beth Israel Deaconess Med Ctr, Clin Res Ctr, Boston, MA 02215 USA.
[Davis, Roger B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Bell, Iris R.] Univ Arizona, Coll Med, Dept Family & Community Med, Tucson, AZ USA.
[Lembo, Anthony J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA.
[Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA.
[Kaptchuk, Ted J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Dossett, ML (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA.
EM mdossett@mgh.harvard.edu
FU National Center for Complementary and Integrative Health (NCCIH) at the
NIH [T32 AT000051]; Division of General Medicine and Primary Care at
Beth Israel Deaconess Medical Center (BIDMC); NCCIH [K24 AT004095];
BIDMC Research Pharmacy and Clinical Research Center, Harvard Catalyst;
Harvard Clinical and Translational Science Center (NIH) [1UL1
TR001102-01]; Harvard University
FX MLD was supported by an institutional National Research Service Award
T32 AT000051 from the National Center for Complementary and Integrative
Health (NCCIH) at the NIH and by the Division of General Medicine and
Primary Care at Beth Israel Deaconess Medical Center (BIDMC). TJK was
supported by a K24 AT004095 (NCCIH). This work was conducted with
support from the BIDMC Research Pharmacy and Clinical Research Center,
Harvard Catalyst, The Harvard Clinical and Translational Science Center
(NIH Award 1UL1 TR001102-01 and financial contributions from Harvard
University and its affiliated academic health care centers). 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 National Institutes
of Health. No funding or support was received from Boiron. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 35
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U1 1
U2 4
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 SEP 30
PY 2015
VL 10
IS 9
AR e0136855
DI 10.1371/journal.pone.0136855
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS6GF
UT WOS:000362175700007
PM 26422466
ER
PT J
AU Wang, LX
Mogami, S
Yakabi, S
Karasawa, H
Yamada, C
Yakabi, K
Hattori, T
Tache, Y
AF Wang, Lixin
Mogami, Sachiko
Yakabi, Seiichi
Karasawa, Hiroshi
Yamada, Chihiro
Yakabi, Koji
Hattori, Tomohisa
Tache, Yvette
TI Patterns of Brain Activation and Meal Reduction Induced by Abdominal
Surgery in Mice and Modulation by Rikkunshito
SO PLOS ONE
LA English
DT Article
ID CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC ARCUATE NUCLEUS;
STRESS-RELATED ALTERATIONS; POSTOPERATIVE GASTRIC ILEUS;
CISPLATIN-INDUCED ANOREXIA; GHRELIN RECEPTOR AGONIST; COLONIC MOTOR
FUNCTION; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; PARABRACHIAL NUCLEUS
AB Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.
C1 [Wang, Lixin; Yakabi, Seiichi; Karasawa, Hiroshi; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Ctr, Los Angeles, CA 90089 USA.
[Wang, Lixin; Yakabi, Seiichi; Karasawa, Hiroshi; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA.
[Wang, Lixin; Yakabi, Seiichi; Karasawa, Hiroshi; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Mogami, Sachiko; Yamada, Chihiro; Hattori, Tomohisa] Tsumura & Co, Kampo Sci Strategies Div, Tsumura Res Labs, Tsukuba, Ibaraki, Japan.
[Yakabi, Koji] Saitama Med Univ, Saitama Med Ctr, Dept Gastroenterol & Hepatol, Saitama, Japan.
RP Wang, LX (reprint author), Univ Calif Los Angeles, CURE Digest Dis Ctr, Los Angeles, CA 90089 USA.
EM lixinw@ucla.edu
RI Xu, Meiqu/C-5311-2016
FU Veterans Administration Research Career Scientist Award; VA Merit Award;
Tsumura Co.; [NIHDDK-41303]
FX The work was supported by NIHDDK-41303 (Animal core, YT, LW), Veterans
Administration Research Career Scientist Award (YT), VA Merit Award (YT)
and Tsumura & Co. Drs. SM, CY and TH are employees of Tsumura & Co. The
funders of Tsumura & Co. had no role in study design, data collection
and analysis, decision topublish, or preparation of the manuscript.
NR 85
TC 1
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 30
PY 2015
VL 10
IS 9
AR e0139325
DI 10.1371/journal.pone.0139325
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS6GF
UT WOS:000362175700094
PM 26421719
ER
PT J
AU Ladha, K
Kurth, T
Eikermann, M
AF Ladha, Karim
Kurth, Tobias
Eikermann, Matthias
TI INTRAOPERATIVE PROTECTIVE MECHANICAL VENTILATION Authors' reply to
Whitlock and Saied and colleagues
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Letter
C1 [Ladha, Karim; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care Pain Med, Boston, MA 02114 USA.
[Kurth, Tobias] INSERM, Res Ctr Epidemiol & Biostat, U897, Team Neuroepidemiol, Bordeaux, France.
RP Ladha, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Pain Med, Boston, MA 02114 USA.
EM meikermann@partners.org
NR 6
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD SEP 30
PY 2015
VL 351
AR h5143
DI 10.1136/bmj.h5143
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS9ZE
UT WOS:000362452200014
PM 26424610
ER
PT J
AU Flanagan, JC
Baker, NL
McRae-Clark, AL
Brady, KT
Maria, MMMS
AF Flanagan, Julianne C.
Baker, Nathaniel L.
McRae-Clark, Aimee L.
Brady, Kathleen T.
Maria, Margaret M. Moran-Santa
TI Effects of adverse childhood experiences on the association between
intranasal oxytocin and social stress reactivity among individuals with
cocaine dependence
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Oxytocin; Drug dependence; Social stress reactivity; HPA
ID SUBSTANCE USE; PSYCHOLOGICAL DISTRESS; HOUSEHOLD DYSFUNCTION;
MENTAL-HEALTH; AXIS ACTIVITY; DRUG-USE; RISK; ALCOHOL; ABUSE; ADDICTION
AB Background: Drug dependence and adverse childhood experiences (ACE) are commonly reflected by dysregulation of the hypothalamic-pituitary-adrenal axis (HPA). Accumulating research indicates that the neuropeptide oxytocin may regulate HPA function, resulting in reductions in neuroendocrine reactivity to social stress among individuals with drug dependence. However, emerging literature suggests that individual differences may differentially impact intranasal oxytbcin's effects on human social behaviors.
Methods: This study employed a double-blind, placebo-controlled design to examine the extent to which ACE influenced the effects of intranasal oxytocin (40 IU) on neuroendocrine reactivity to a laboratory social stress paradigm in a sample of 31 cocaine-dependent individuals.
Results: ACE scores modified the relationship between intranasal oxytocin and cortisol reactivity. While ACE modified the relationship between intranasal oxytocin and DHEA response in a similar direction to what was seen in cortisol, it did not reach statistical significance.
Conclusions: Findings are congruent with the emerging hypothesis that intranasal oxytocin may differentially attenuate social stress reactivity among individuals with specific vulnerabilities. Future research examining the nuances of intranasal oxytocin's therapeutic potential is necessary. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Flanagan, Julianne C.; McRae-Clark, Aimee L.; Brady, Kathleen T.; Maria, Margaret M. Moran-Santa] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29401 USA.
[Brady, Kathleen T.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Baker, Nathaniel L.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
RP Flanagan, JC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 5 Charleston Ctr Dr,Suite 151, Charleston, SC 29401 USA.
EM hellmuth@musc.edu
FU National Institute on Child Health and Human Development and the Office
of Research on Women's Health [K12HD055885]; National Institute on Drug
Abuse [P50DA016511]; National Center for Advancing Translational
Sciences [UL1TR000062]
FX This manuscript is the result of work supported, in part, by resources
from the National Institute on Child Health and Human Development and
the Office of Research on Women's Health (K12HD055885), the National
Institute on Drug Abuse (P50DA016511), and the National Center for
Advancing Translational Sciences (UL1TR000062).
NR 60
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U1 4
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2015
VL 229
IS 1-2
BP 94
EP 100
DI 10.1016/j.psychres.2015.07.064
PG 7
WC Psychiatry
SC Psychiatry
GA CQ7HC
UT WOS:000360772600013
PM 26231584
ER
PT J
AU Silverstein, SM
Elliott, CM
Feusner, JD
Keane, BP
Mikkilineni, D
Hansen, N
Hartmann, A
Wilhelm, S
AF Silverstein, Steven M.
Elliott, Corinna M.
Feusner, Jamie D.
Keane, Brian P.
Mikkilineni, Deepthi
Hansen, Natasha
Hartmann, Andrea
Wilhelm, Sabine
TI Comparison of visual perceptual organization in schizophrenia and body
dysmorphic disorder
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Schizophrenia; Body dysmorphic disorder; Perception; Vision; Perceptual
organization; Obsessive-Compulsive Disorder; RDoC
ID OBSESSIVE-COMPULSIVE SCALE; FACIAL EMOTION RECOGNITION; TOP-DOWN
CONTROL; 5 FACTOR MODEL; CONTOUR INTEGRATION; EBBINGHAUS ILLUSION;
SPECTRUM DISORDERS; SPATIAL-FREQUENCY; FACE RECOGNITION; CONFIGURAL
INFORMATION
AB People with schizophrenia are impaired at organizing potentially ambiguous visual information into well-formed shape and object representations. This perceptual organization (PO) impairment has not been found in other psychiatric disorders. However, recent data on body dysmorphic disorder (BDD), suggest that BDD may also be characterized by reduced PO. Similarities between these groups could have implications for understanding the RDoC dimension of visual perception in psychopathology, and for modeling symptom formation across these two conditions. We compared patients with SCZ (n=24) to those with BDD (n=20), as well as control groups of obsessive compulsive disorder (OCD) patients (n=20) and healthy controls (n=20), on two measures of PO that have been reliably associated with schizophrenia-related performance impairment. On both the contour integration and Ebbinghaus illusion tests, only the SCZ group demonstrated abnormal performance relative to controls; the BDD group performed similarly to the OCD and CON groups. In addition, on both tasks, the SCZ group performed more abnormally than the BDD group. Overall, these data suggest that PO reductions observed in SCZ are not present in BDD. Visual processing impairments in BDD may arise instead from other perceptual disturbances or attentional biases related to emotional factors. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Silverstein, Steven M.; Keane, Brian P.; Mikkilineni, Deepthi] Rutgers State Univ, Dept Psychiat, Piscataway, NJ 08854 USA.
[Silverstein, Steven M.; Keane, Brian P.; Mikkilineni, Deepthi] Rutgers State Univ, Univ Behav Hlth Care, Piscataway, NJ 08854 USA.
[Elliott, Corinna M.; Hansen, Natasha; Hartmann, Andrea; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Feusner, Jamie D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Silverstein, SM (reprint author), Rutgers State Univ, Dept Psychiat, 151 Centennial Ave, Piscataway, NJ 08854 USA.
EM steven.silverstein@rutgers.edu
RI Feusner, Jamie/K-2312-2012
OI Feusner, Jamie/0000-0002-0391-345X
FU Fonds de Recherche du Que-bec-Sante (FRQS); NIMH [R01MH093439]; NIH
IRACDA Postdoctoral Training Grant [1K12GM093854-05]; Neil and Anna
Rasmussen Foundation
FX We would like to thank Amanda Calkins, Lillian Reuman, Yushi Wang, and
Danielle Paterno for their help with recruitment and testing. This
research was supported in part by fellowship support awarded to Corinna
Elliott from the Fonds de Recherche du Que-bec-Sante (FRQS), by NIMH
Grant R01MH093439 to the first author, by NIH IRACDA Postdoctoral
Training Grant 1K12GM093854-05 to M. W. Roche, and by funding from The
Neil and Anna Rasmussen Foundation to the last author.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2015
VL 229
IS 1-2
BP 426
EP 433
DI 10.1016/j.psychres.2015.05.107
PG 8
WC Psychiatry
SC Psychiatry
GA CQ7HC
UT WOS:000360772600061
PM 26184989
ER
PT J
AU Caqueo-Urizar, A
Boyer, L
Baumstarck, K
Gilman, SE
AF Caqueo-Urizar, Alejandra
Boyer, Laurent
Baumstarck, Karine
Gilman, Stephen E.
TI The relationships between patients' and caregivers' beliefs about the
causes of schizophrenia and clinical outcomes in Latin American
countries
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Schizophrenia; Causal beliefs; Caregivers; Health outcomes; Symptoms;
Attitudes towards medication
ID SERIOUS MENTAL ILLNESSES; MIDDLE-INCOME COUNTRIES; NEGATIVE SYNDROME
SCALE; EXPRESSED EMOTION; FAMILY-MEMBERS; HEALTH; POVERTY; RELATIVES;
MODELS; HELP
AB Beliefs about the causes of schizophrenia are thought to impact treatment outcomes. We investigated 3 theoretically opposing belief systems (biological, psychosocial, magical-religious) in relation to the severity of positive and negative symptoms and to attitudes towards medications. We recruited 253 patients with schizophrenia and their primary caregivers from public mental health clinics in Bolivia, Chile, and Peru. We assessed patients' and caregivers' beliefs about the causes of schizophrenia, which were used as predictors of symptom severity and medication attitudes in linear regression analyses. Patients' scores on biological, psychosocial, and magical-religious beliefs were positively correlated with one another, indicating that these domains were not, as anticipated, "opposing". Patients with higher levels of biological and psychosocial beliefs had significantly lower levels of positive and negative symptoms; in contrast, higher levels of magical-religious beliefs were associated with increased positive symptoms and less favorable attitudes towards medications. Patients' belief systems are significant predictors of symptom severity and medication attitudes. Research is needed on the extent to which psychotherapeutic treatments for schizophrenia should bolster patients' beliefs in the biological and psychosocial domains and weaken beliefs in the magical-religious domain; this research should also attend to the ethical considerations involved in intervening on belief systems cross-culturally. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Caqueo-Urizar, Alejandra] Univ Tarapaca, Arica, Chile.
[Caqueo-Urizar, Alejandra; Gilman, Stephen E.] Harvard Univ, Dept Social & Behav Sci, Sch Publ Hlth, Boston, MA 02115 USA.
[Boyer, Laurent; Baumstarck, Karine] Aix Marseille Univ, Chron Dis & Qual Life Res Unit, EA Publ Hlth 3279, F-13005 Marseille, France.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Gilman, Stephen E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
RP Caqueo-Urizar, A (reprint author), Univ Tarapaca, Dept Filosofia & Psicol, Ave 18 Septiembre 2222, Arica, Chile.
EM acaqueo@uta.cl; Laurent.BOYER@ap-hm.fr; karine.baumstarck@univ-amu.fr;
stephen.gilman@nih.gov
RI Gilman, Stephen/E-7632-2010; Boyer, Laurent/E-5728-2016
OI Gilman, Stephen/0000-0002-8331-6419; Boyer, Laurent/0000-0003-1229-6622
FU CONICYT; BECAS-CHILE Postdoctorado en el Extranjero [74140004]; Convenio
de De-sempenio UTA-MINEDUC; Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This research was funded in part by CONICYT and BECAS-CHILE
Postdoctorado en el Extranjero (74140004), the Convenio de De-sempenio
UTA-MINEDUC, and by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2015
VL 229
IS 1-2
BP 440
EP 446
DI 10.1016/j.psychres.2015.06.033
PG 7
WC Psychiatry
SC Psychiatry
GA CQ7HC
UT WOS:000360772600063
PM 26188641
ER
PT J
AU Thomas, JJ
Eddy, KT
Murray, HB
Tromp, MDP
Hartmann, AS
Stone, MT
Levendusky, PG
Becker, AE
AF Thomas, Jennifer J.
Eddy, Kamryn T.
Murray, Helen B.
Tromp, Marilou D. P.
Hartmann, Andrea S.
Stone, Melissa T.
Levendusky, Philip G.
Becker, Anne E.
TI The impact of revised DSM-5 criteria on the relative distribution and
inter-rater reliability of eating disorder diagnoses in a residential
treatment setting
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE DSM-5; Eating disorder; Diagnostic reliability; Other specified feeding
or eating disorder (OSFED); Eating disorder not otherwise specified
(EDNOS)
ID CLINICAL UTILITY; IV; ADOLESCENTS; COMMUNITY; SEVERITY; METAANALYSIS;
PREVALENCE; AGREEMENT; EDNOS
AB This study evaluated the relative distribution and inter-rater reliability of revised DSM-5 criteria for eating disorders in a residential treatment program. Consecutive adolescent and young adult females (N=150) admitted to a residential eating disorder treatment facility were assigned both DSM-IV and DSM-5 diagnoses by a clinician (n=14) via routine clinical interview and a research assessor (n=4) via structured interview. We compared the frequency of diagnostic assignments under each taxonomy and by type of assessor. We evaluated concordance between clinician and researcher assignment through inter-rater reliability kappa and percent agreement. Significantly fewer patients received either clinician or researcher diagnoses of a residual eating disorder under DSM-5 (clinician-12.0%; researcher-31.3%) versus DSM-IV (clinician-28.7%; researcher-59.3%), with the majority of reassigned DSM-IV residual cases reclassified as DSM-5 anorexia nervosa. Researcher and clinician diagnoses showed moderate inter-rater reliability under DSM-IV (kappa= .48) and DSM-5 (kappa= .57), though agreement for specific DSM-5 other specified feeding or eating disorder (OSFED) presentations was poor (kappa=.05). DSM-5 revisions were associated with significantly less frequent residual eating disorder diagnoses, but not with reduced inter-rater reliability. Findings support specific dimensions of clinical utility for revised DSM-5 criteria for eating disorders. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Thomas, Jennifer J.; Eddy, Kamryn T.; Murray, Helen B.; Tromp, Marilou D. P.; Becker, Anne E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA.
[Thomas, Jennifer J.; Eddy, Kamryn T.; Stone, Melissa T.; Levendusky, Philip G.; Becker, Anne E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Hartmann, Andrea S.] Univ Osnabruck, Inst Psychol, D-49074 Osnabruck, Germany.
[Levendusky, Philip G.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA.
[Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA.
EM jjthomas@mgh.harvard.edu
FU Hilda and Preston Davis Foundation; Klarman Family Foundation
FX Funded by Hilda and Preston Davis Foundation, Klarman Family Foundation,
Mr. and Mrs. Samuel Martini.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2015
VL 229
IS 1-2
BP 517
EP 523
DI 10.1016/j.psychres.2015.06.017
PG 7
WC Psychiatry
SC Psychiatry
GA CQ7HC
UT WOS:000360772600074
PM 26160205
ER
PT J
AU De Nadai, A
Nagpal, PS
Piacentini, J
Penis, TS
Geftken, GR
Geller, DA
Murphy, TK
Storch, EA
Lewin, AB
AF De Nadai, Alessandro
Nagpal, Prianka S.
Piacentini, John
Penis, Tara S.
Geftken, Gary R.
Geller, Daniel A.
Murphy, Tanya K.
Storch, Eric A.
Lewin, Adam B.
TI Contemporary models of pediatric obsessive-compulsive disorder: An
evaluation with a large clinical sample
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Obsessive-compulsive disorder; Pediatric; Assessment
ID SCALE
AB We evaluated the construct validity of the Child Yale-Brofwn Obsessive-Compulsive Scale (CYBOCS) in a large clinical sample (N=730) using confirmatory factor analysis. Results found inadequate fit for a priori models, though a model accounting for overlapping item content displayed good fit. Parallel obsessions/compulsions items may provide largely redundant information on the CYBOCS. Findings suggest modifying the CYBOCS to reduce burden on researchers, patients, and clinicians, and to more accurately measure pediatric obsessive-compulsive disorder (OCD). (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [De Nadai, Alessandro; Storch, Eric A.; Lewin, Adam B.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA.
[De Nadai, Alessandro; Nagpal, Prianka S.; Murphy, Tanya K.; Storch, Eric A.; Lewin, Adam B.] Univ S Florida, Coll Med, Rothman Ctr Neuropsychiat, Dept Pediat, St Petersburg, FL 33701 USA.
[De Nadai, Alessandro; Nagpal, Prianka S.; Murphy, Tanya K.; Storch, Eric A.; Lewin, Adam B.] Univ S Florida, Coll Med, Rothman Ctr Neuropsychiat, Dept Psychiat, St Petersburg, FL 33701 USA.
[Piacentini, John; Penis, Tara S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Geftken, Gary R.] Univ Florida, Dept Psychiat, Gainesville, FL 32606 USA.
[Geftken, Gary R.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA.
[Geller, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Storch, Eric A.] Rogers Behav Hlth Tampa Bay, Tampa, FL 33629 USA.
[Storch, Eric A.] All Childrens Hosp Johns Hopkins Med, St Petersburg, FL 33701 USA.
RP De Nadai, A (reprint author), Univ S Florida, Coll Med, Rothman Ctr Neuropsychiat, 880 6th St South,Suite 460 Box 7523, St Petersburg, FL 33701 USA.
EM denadai@mail.usf.edu
RI Murphy, Tanya/J-7079-2013
FU National Institutes of Health under National Institute of Mental Health
[F31 MH094095, R01 MH058549, K23 MH085058, R01 MH093402, R01 MH063914,
R01 MH093381, R03 MH076775]; International OCD Foundation; University of
South Florida Research Council
FX This research was supported by the National Institutes of Health under
National Institute of Mental Health Grants F31 MH094095 (De Nadai), R01
MH058549 (Piacentini), K23 MH085058 (Peris), R01 MH093402 (Geller), R01
MH063914 (Murphy), R01 MH093381 (Storch), R03 MH076775 (Storch), as well
as from the International OCD Foundation (Lewin and Murphy) and the
University of South Florida Research Council (Lewin). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2015
VL 229
IS 1-2
BP 620
EP 622
DI 10.1016/j.psychres.2015.03.034
PG 3
WC Psychiatry
SC Psychiatry
GA CQ7HC
UT WOS:000360772600096
PM 26003507
ER
PT J
AU Bohula, EA
Giugliano, RP
Cannon, CP
Zhou, J
Murphy, SA
White, JA
Tershakovec, AM
Blazing, MA
Braunwald, E
AF Bohula, Erin A.
Giugliano, Robert P.
Cannon, Christopher P.
Zhou, Jing
Murphy, Sabina A.
White, Jennifer A.
Tershakovec, Andrew M.
Blazing, Michael A.
Braunwald, Eugene
TI Achievement of Dual Low-Density Lipoprotein Cholesterol and
High-Sensitivity C-Reactive Protein Targets More Frequent With the
Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes
in IMPROVE-IT
SO CIRCULATION
LA English
DT Article
DE acute coronary syndrome; cholesterol, LDL; C-reactive protein;
ezetimibe; hydroxymethylglutaryl-CoA reductase inhibitors; secondary
prevention
ID ACUTE CORONARY SYNDROMES; STATIN THERAPY; HEART-DISEASE;
MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; CLINICAL-TRIALS; EFFICACY;
INFLAMMATION; SAFETY; RISK
AB Background-Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP); addition of ezetimibe to statins further reduces LDL-C and hs-CRP. An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).
Methods and Results-The IMPROVE-IT trial randomly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin. LDL-C and hs-CRP were measured at baseline and 1 month after randomization. Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target, adjusting for differences in baseline characteristics. An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline, with no 1-month values, or with end points before 1 month were excluded. Of 15 179 patients, 39% achieved the dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) targets at 1 month, 14% met neither target, 14% met only the hs-CRP target, and 33% met only the LDL-C target. Those achieving dual targets had lower primary end point rates than those meeting neither target (cardiovascular death, major coronary event, or stroke; 38.9% versus 28.0%; adjusted hazard ratio, 0.73; 0.66-0.81; P<0.001). More patients treated with ezetimibe/simvastatin met dual targets than those treated with simvastatin alone (50% versus 29%, P<0.001). The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment (P-interaction=0.65). Similar findings were observed using the exploratory targets.
Conclusions-Significantly more patients treated with ezetimibe/simvastatin met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone. Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment.
C1 [Bohula, Erin A.; Giugliano, Robert P.; Cannon, Christopher P.; Zhou, Jing; Murphy, Sabina A.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA.
[White, Jennifer A.; Blazing, Michael A.] Duke Clin Res Inst, Durham, NC USA.
[Tershakovec, Andrew M.] Merck, Kenilworth, NJ USA.
RP Bohula, EA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,First Off Floor, Boston, MA 02115 USA.
EM ebohula@partners.org
FU Merck and Co, Inc.
FX The IMPROVE-IT Trial was sponsored by Merck and Co, Inc.
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD SEP 29
PY 2015
VL 132
IS 13
BP 1224
EP 1233
DI 10.1161/CIRCULATIONAHA.115.018381
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DC5IP
UT WOS:000369255000013
PM 26330412
ER
PT J
AU Shi, P
Goodson, JM
Hartman, ML
Hasturk, H
Yaskell, T
Vargas, J
Cugini, M
Barake, R
Alsmadi, O
Al-Mutawa, S
Ariga, J
Soparkar, P
Behbehani, J
Behbehani, K
Welty, F
AF Shi, Ping
Goodson, J. Max
Hartman, Mor-Li
Hasturk, Hatice
Yaskell, Tina
Vargas, Jorel
Cugini, Maryann
Barake, Roula
Alsmadi, Osama
Al-Mutawa, Sabiha
Ariga, Jitendra
Soparkar, Pramod
Behbehani, Jawad
Behbehani, Kazem
Welty, Francine
TI Continuous Metabolic Syndrome Scores for Children Using Salivary
Biomarkers
SO PLOS ONE
LA English
DT Article
ID PHYSICAL-ACTIVITY; RISK SCORE; ADOLESCENTS; ADIPONECTIN; LEPTIN; YOUTH;
ADIPOCYTOKINES; PREVALENCE; PREDICTORS; CHILDHOOD
AB Background
Binary definitions of the metabolic syndrome based on the presence of a particular number of individual risk factors are limited, particularly in the pediatric population. To address this limitation, we aimed at constructing composite and continuous metabolic syndrome scores (cmetS) to represent an overall measure of metabolic syndrome (MetS) in a large cohort of metabolically at-risk children, focusing on the use of the usual clinical parameters (waist circumference (WC) and systolic blood pressure (SBP), supplemented with two salivary surrogate variables (glucose and high density lipoprotein cholesterol (HDLC). Two different approaches used to create the scores were evaluated in comparison.
Methods
Data from 8,112 Kuwaiti children (10.00 +/- 0.67 years) were used to construct two cmetS for each subject. The first cmetS (cmetS-Z) was created by summing standardized residuals of each variable regressed on age and gender; and the second cmetS (cmetS-PCA) was defined as the first principal component from gender-specific principal component analysis based on the four variables.
Results
There was a graded relationship between both scores and the number of adverse risk factors. The areas under the curve using cmetS-Z and cmetS-PCA as predictors for severe metabolic syndrome (defined as the presence of >= 3 metabolic risk factors) were 0.935 and 0.912, respectively. cmetS-Z was positively associated with WC, SBP, and glucose, but inversely associated with HDLC. Except for the lack of association with glucose, cmetS-PCA was similar to cmetS-Z in boys, but had minimum loading on HDLC in girls. Analysis using quantile regression showed an inverse association of fitness level with cmetS-PCA (p = 0.001 for boys; p = 0.002 for girls), and comparison of cmetS-Z and cmetS-PCA suggested that WC and SBP were main contributory components. Significant alterations in the relationship between cmetS and salivary adipocytokines were demonstrated in overweight and obese children as compared to underweight and normal-weight children.
Conclusion
We have derived continuous summary scores for MetS from a large-scale pediatric study using two different approaches, incorporating salivary measures as surrogate for plasma measures. The derived scores were viable expressions of metabolic risk, and can be utilized to study the relationships of MetS with various aspects of the metabolic disease process.
C1 [Shi, Ping; Goodson, J. Max; Hartman, Mor-Li; Hasturk, Hatice; Yaskell, Tina; Vargas, Jorel; Cugini, Maryann; Soparkar, Pramod] Forsyth Res Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
[Barake, Roula; Alsmadi, Osama; Behbehani, Kazem] Dasman Diabet Inst, Kuwait, Kuwait.
[Al-Mutawa, Sabiha; Ariga, Jitendra] Minist Hlth, Kuwait, Kuwait.
[Behbehani, Jawad] Kuwait Univ, Fac Dent, Kuwait, Kuwait.
[Welty, Francine] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
RP Shi, P (reprint author), Forsyth Res Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
EM pscshi@gmail.com; mgoodson@forsyth.org
FU Dasman Diabetes Institute in Kuwait; [P30 DK46200]
FX This project was funded by a grant from the Dasman Diabetes Institute in
Kuwait. The authors also received a consultation service from Boston
Nutrition and Obesity Research Center, supported by grant P30 DK46200.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 29
PY 2015
VL 10
IS 9
AR e0138979
DI 10.1371/journal.pone.0138979
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS6EV
UT WOS:000362171400030
PM 26418011
ER
PT J
AU Anderson, TS
Good, CB
Gellad, WF
AF Anderson, Timothy S.
Good, Chester B.
Gellad, Walid F.
TI Prevalence and compensation of academic leaders, professors, and
trustees on publicly traded US healthcare company boards of directors:
cross sectional study
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID CONFLICTS-OF-INTEREST; MEDICAL-CENTERS
AB OBJECTIVE
To identify the prevalence, characteristics, and compensation of members of the boards of directors of healthcare industry companies who hold academic appointments as leaders, professors, or trustees.
DESIGN
Cross sectional study.
SETTING
US healthcare companies publicly traded on the NASDAQ or New York Stock Exchange in 2013.
PARTICIPANTS
3434 directors of pharmaceutical, biotechnology, medical equipment and supply, and healthcare provider companies.
MAIN OUTCOME MEASURES
Prevalence, annual compensation, and beneficial stock ownership of directors with affiliations as leaders, professors, or trustees of academic medical and research institutions.
RESULTS
446 healthcare companies met the study search criteria, of which 442 (99%) had publicly accessible disclosures on boards of directors. 180 companies (41%) had one or more academically affiliated directors. Directors were affiliated with 85 geographically diverse non-profit academic institutions, including 19 of the top 20 National Institute of Health funded medical schools and all of the 17 US News honor roll hospitals. Overall, these 279 academically affiliated directors included 73 leaders, 121 professors, and 85 trustees. Leaders included 17 chief executive officers and 11 vice presidents or executive officers of health systems and hospitals; 15 university presidents, provosts, and chancellors; and eight medical school deans or presidents. The total annual compensation to academically affiliated directors for their services to companies was $54 995 786 (35 pound 836 000; (sic)49 185 900) (median individual compensation $193 000) and directors beneficially owned 59 831 477 shares of company stock (median 50 699 shares).
CONCLUSIONS
A substantial number and diversity of academic leaders, professors, and trustees hold directorships at US healthcare companies, with compensation often approaching or surpassing common academic clinical salaries. Dual obligations to for profit company shareholders and non-profit clinical and educational institutions pose considerable personal, financial, and institutional conflicts of interest beyond that of simple consulting relationships. These conflicts have not been fully addressed by professional societies or academic institutions and deserve additional review, regulation, and, in some cases, prohibition when conflicts cannot be reconciled.
C1 [Anderson, Timothy S.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA USA.
[Good, Chester B.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA.
[Good, Chester B.] Univ Pittsburgh, VA Ctr Medicat Safety, Dept Vet Affairs, Sch Med, Pittsburgh, PA 15260 USA.
[Gellad, Walid F.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA 15240 USA.
[Gellad, Walid F.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15240 USA.
RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
EM wfg3@pitt.edu
FU VA Health Services Research and Development award [CDA 09-207]
FX WFG was supported by a VA Health Services Research and Development award
CDA 09-207. The funder had no role in the design and conduct of the
study, collection, management, analysis, and interpretation of data, or
preparation of the manuscript.
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD SEP 29
PY 2015
VL 351
AR h4826
DI 10.1136/bmj.h4826
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS9YU
UT WOS:000362450900005
PM 26420786
ER
PT J
AU Otipoby, KL
Waisman, A
Derudder, E
Srinivasan, L
Franklin, A
Rajewsky, K
AF Otipoby, Kevin L.
Waisman, Ari
Derudder, Emmanuel
Srinivasan, Lakshmi
Franklin, Andrew
Rajewsky, Klaus
TI The B-cell antigen receptor integrates adaptive and innate immune
signals
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE BCR; B-cell proliferation; PI-3K; GSK3 beta; Foxo1
ID MOUSE IMMUNOGLOBULIN ANTIBODIES; LYMPHOCYTE DEVELOPMENT; KAPPA-B; GENE;
ACTIVATION; KINASE; EXPRESSION; RESPONSES; SURVIVAL; PATHWAY
AB B cells respond to antigens by engagement of their B-cell antigen receptor (BCR) and of coreceptors through which signals from helper T cells or pathogen-associated molecular patterns are delivered. We show that the proliferative response of B cells to the latter stimuli is controlled by BCR-dependent activation of phosphoinositidyl 3-kinase (PI-3K) signaling. Glycogen synthase kinase 3 beta and Foxo1 are two PI-3K-regulated targets that play important roles, but to different extents, depending on the specific mitogen. These results suggest a model for integrating signals from the innate and the adaptive immune systems in the control of the B-cell immune response.
C1 [Otipoby, Kevin L.; Derudder, Emmanuel; Srinivasan, Lakshmi; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Waisman, Ari; Rajewsky, Klaus] Univ Cologne, Inst Genet, D-50674 Cologne, Germany.
[Derudder, Emmanuel; Franklin, Andrew; Rajewsky, Klaus] Max Delbruck Ctr Mol Med, Lab Immune Regulat & Canc, D-13125 Berlin, Germany.
RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM kevin.otipoby@biogen.com; Klaus.Rajewsky@mdc-berlin.de
RI Waisman, Ari/C-7383-2015
OI Waisman, Ari/0000-0003-4304-8234
FU National Institutes of Health [AI057947, AI054636]; European Research
Council [ERC-2010-AdG_20100317, 268921]; European Commission
[H2020-MSCA-IF-2014_ST, 660883]
FX We thank Stefano Casola, Marc Schmidt-Supprian, Dinis P. Calado, Jane
Seagal, Sergei B. Koralov, and Michael Reth for helpful discussions. We
thank Joanne L. Viney for critically reading the finished manuscript. We
are grateful to Junrong Xia, Dvora Ghitza, Anthony Monti, Alex Pellerin,
and Jackie Grundy for technical support. We thank Riikka Lauhkonen-Seitz
for administrative assistance. This work was supported by National
Institutes of Health Grants AI057947 and AI054636. K.R. is supported by
an Advanced Grant from the European Research Council
(ERC-2010-AdG_20100317 Grant 268921). A.F. is supported by a Marie
Sklodowska-Curie Actions Individual Fellowship from the European
Commission (H2020-MSCA-IF-2014_ST Grant 660883).
NR 30
TC 1
Z9 1
U1 6
U2 11
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 SEP 29
PY 2015
VL 112
IS 39
BP 12145
EP 12150
DI 10.1073/pnas.1516428112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS2ZU
UT WOS:000361941600045
PM 26371314
ER
PT J
AU Kamat, NP
Tobe, S
Hill, IT
Szostak, JW
AF Kamat, Neha P.
Tobe, Sylvia
Hill, Ian T.
Szostak, Jack W.
TI Electrostatic Localization of RNA to Protocell Membranes by Cationic
Hydrophobic Peptides
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE origin of life; peptides; protocells; RNA; vesicles
ID CELL-PENETRATING PEPTIDES; ANTIMICROBIAL PEPTIDES;
PHOSPHOLIPID-BILAYERS; VESICLES; MECHANISM; COMPLEXES; KINETICS; ORIGIN
AB Cooperative interactions between RNA and vesicle membranes on the prebiotic earth may have led to the emergence of primitive cells. The membrane surface offers a potential platform for the catalysis of reactions involving RNA, but this scenario relies upon the existence of a simple mechanism by which RNA could become associated with protocell membranes. Here, we show that electrostatic interactions provided by short, basic, amphipathic peptides can be harnessed to drive RNA binding to both zwitterionic phospholipid and anionic fatty acid membranes. We show that the association of cationic molecules with phospholipid vesicles can enhance the local positive charge on a membrane and attract RNA polynucleotides. This phenomenon can be reproduced with amphipathic peptides as short as three amino acids. Finally, we show that peptides can cross bilayer membranes to localize encapsulated RNA. This mechanism of polynucleotide confinement could have been important for primitive cellular evolution.
C1 [Kamat, Neha P.; Tobe, Sylvia; Hill, Ian T.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
[Kamat, Neha P.; Tobe, Sylvia; Hill, Ian T.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Tobe, Sylvia] Ra Pharmaceut, Cambridge, MA 02139 USA.
[Hill, Ian T.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Hill, Ian T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
RI Kamat, Neha/L-2799-2016
FU NASA Exobiology Program [NNX07AJ09G]; Simons Foundation [290363]; NASA
Postdoctoral Program; NSF Graduate Fellowship; NASA
FX This work was supported in part by grants from the NASA Exobiology
Program (grnat number NNX07AJ09G) and from the Simons Foundation (grant
number 290363) to J.W.S. J.W.S. is an Investigator of the Howard Hughes
Medical Institute (HHMI). N.P.K. is supported by an appointment to the
NASA Postdoctoral Program, administered by Oak Ridge Associated
Universities through a contract with NASA. I.T.H. is supported by an NSF
Graduate Fellowship. We thank Albert Fahrenbach, Victor Lelyveld, Tony
Jia, and all other members of the Szostak lab for helpful comments on
the manuscript.
NR 26
TC 7
Z9 7
U1 9
U2 35
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD SEP 28
PY 2015
VL 54
IS 40
BP 11735
EP 11739
DI 10.1002/anie.201505742
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA CU3AF
UT WOS:000363394800023
PM 26223820
ER
PT J
AU Maesako, M
Uemura, M
Tashiro, Y
Sasaki, K
Watanabe, K
Noda, Y
Ueda, K
Asada-Utsugi, M
Kubota, M
Okawa, K
Ihara, M
Shimohama, S
Uemura, K
Kinoshita, A
AF Maesako, Masato
Uemura, Maiko
Tashiro, Yoshitaka
Sasaki, Kazuki
Watanabe, Kiwamu
Noda, Yasuha
Ueda, Karin
Asada-Utsugi, Megumi
Kubota, Masakazu
Okawa, Katsuya
Ihara, Masafumi
Shimohama, Shun
Uemura, Kengo
Kinoshita, Ayae
TI High Fat Diet Enhances beta-Site Cleavage of Amyloid Precursor Protein
(APP) via Promoting beta-Site APP Cleaving Enzyme 1/Adaptor Protein
2/Clathrin Complex Formation
SO PLOS ONE
LA English
DT Article
ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; CELL-SURFACE; SECRETASE
PROTEIN; MEMORY DEFICITS; MICE; DEMENTIA; ENDOCYTOSIS; RISK; GENERATION
AB Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We reported that a high fat diet (HFD) promotes amyloid precursor protein (APP) cleavage by beta-site APP cleaving enzyme 1 (BACE1) without increasing BACE1 levels in APP transgenic mice. However, the detailed mechanism had remained unclear. Here we demonstrate that HFD promotes BACE1/Adaptor protein-2 (AP-2)/clathrin complex formation by increasing AP-2 levels in APP transgenic mice. In Swedish APP overexpressing Chinese hamster ovary (CHO) cells as well as in SH-SY5Y cells, overexpression of AP-2 promoted the formation of BACE1/AP2/ clathrin complex, increasing the level of the soluble form of APP beta (sAPP beta). On the other hand, mutant D495R BACE1, which inhibits formation of this trimeric complex, was shown to decrease the level of sAPP beta. Overexpression of AP-2 promoted the internalization of BACE1 from the cell surface, thus reducing the cell surface BACE1 level. As such, we concluded that HFD may induce the formation of the BACE1/AP-2/clathrin complex, which is followed by its transport of BACE1 from the cell surface to the intracellular compartments. These events might be associated with the enhancement of beta-site cleavage of APP in APP transgenic mice. Here we present evidence that HFD, by regulation of subcellular trafficking of BACE1, promotes APP cleavage.
C1 [Maesako, Masato; Sasaki, Kazuki; Noda, Yasuha; Ueda, Karin; Asada-Utsugi, Megumi; Kubota, Masakazu; Kinoshita, Ayae] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Kyoto, Japan.
[Uemura, Maiko; Watanabe, Kiwamu; Uemura, Kengo] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan.
[Tashiro, Yoshitaka] Kyoto Univ, Grad Sch Med, SK Project Med Innovat Ctr, Kyoto, Japan.
[Okawa, Katsuya] Kyowa Hakko Kirin Co Ltd, Shizuoka, Japan.
[Ihara, Masafumi] Natl Cerebral & Cardiovasc Ctr, Dept Neurol, Osaka, Japan.
[Shimohama, Shun] Sapporo Med Univ, Dept Neurol, Sapporo, Hokkaido, Japan.
[Uemura, Kengo] Ishiki Hosp, Kagoshima, Japan.
RP Kinoshita, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Alzheimers Dis Re, Charlestown, MA 02129 USA.
EM kinoshita.ayae.6v@kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
[24111524, 23591243, 13J00221]; Japan Society for the Promotion of
Science [820130600001]; Kyowa Hakko Kirin Co., Ltd
FX AK, K. Uemura and MM are funded with Grant-in-Aid from the Ministry of
Education, Culture, Sports, Science and Technology, Japan (AK: 24111524,
K. Uemura: 23591243, MM: 13J00221, URL:
http://www.mext.go.jp/a_menu/shinkou/hojyo/main5_a5.htm). MM is funded
with Japan Society for the Promotion of Science research fellowship
(820130600001, URL: http://www.jsps.go.jp/). Kyowa Hakko Kirin Co., Ltd
provided support in the form of salary for author KO, but did not have
any additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific role
of this author is articulated in the 'author contributions' section.
NR 47
TC 6
Z9 6
U1 0
U2 3
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 SEP 28
PY 2015
VL 10
IS 9
AR e0131199
DI 10.1371/journal.pone.0131199
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS6EO
UT WOS:000362170700001
PM 26414661
ER
PT J
AU Namjou, B
Marsolo, K
Lingren, T
Ritchie, MD
Verma, SS
Cobb, BL
Perry, C
Kitchner, TE
Brilliant, MH
Peissig, PL
Borthwick, KM
Williams, MS
Grafton, J
Jarvik, GP
Holm, IA
Harley, JB
AF Namjou, Bahram
Marsolo, Keith
Lingren, Todd
Ritchie, Marylyn D.
Verma, Shefali S.
Cobb, Beth L.
Perry, Cassandra
Kitchner, Terrie E.
Brilliant, Murray H.
Peissig, Peggy L.
Borthwick, Kenneth M.
Williams, Marc S.
Grafton, Jane
Jarvik, Gail P.
Holm, Ingrid A.
Harley, John B.
TI A GWAS Study on Liver Function Test Using eMERGE Network Participants
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SERUM BILIRUBIN LEVELS; CORONARY-HEART-DISEASE;
SYNDROME TYPE-II; 7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38;
ALKALINE-PHOSPHATASE; ACTIVE METABOLITE; GILBERTS-SYNDROME; UGT1A1 GENE;
POPULATION
AB Introduction
Liver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations.
Methods
The process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously. After removing missing data and outliers based on principal components (PC) analyses, 3294 samples from European ancestry were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and total serum bilirubin and other liver function tests was tested using linear regression, adjusting for age, gender, site, platform and ancestry principal components (PC).
Results
Consistent with previous results, a strong association signal has been detected for UGT1A gene cluster (best SNP rs887829, beta = 0.15, p = 1.30x10(-118)) for total serum bilirubin level. Indeed, in this region more than 176 SNPs (or indels) had p<10(-8) spanning 150Kb on the long arm of chromosome 2q37.1. In addition, we found a similar level of magnitude in a pediatric group (p = 8.26x10(-47), beta = 0.17). Further imputation using sequencing data as a reference panel revealed association of other markers including known TA7 repeat indels (rs8175347) (p = 9.78x10(-117)) and rs111741722 (p = 5.41x10(-119)) which were in proxy (r2 = 0.99) with rs887829. Among rare variants, two Asian subjects homozygous for coding SNP rs4148323 (G71R) were identified. Additional known effects for total serum bilirubin were also confirmed including organic anion transporters SLCO1B1-SLCO1B3, TDRP and ZMYND8 at FDR<0.05 with no gene-gene interaction effects. Phenome-wide association studies (PheWAS) suggest a protective effect of TA7 repeat against cerebrovascular disease in an adult cohort (OR = 0.75, p = 0.0008). Among other liver function tests, we also confirmed the previous effect of the ABO blood group locus for variation in serum alkaline phosphatase (rs579459, p = 9.44x10(-15)).
Conclusions
Taken together, our data present interesting findings with strong confirmation of previous effects by simply using the eMERGE electronic health record phenotyping. In addition, our findings indicate that similar to the adult population, the UGT1A1 is the main locus responsible for normal variation of serum bilirubin in pediatric populations.
C1 [Namjou, Bahram; Cobb, Beth L.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr CCHMC, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA.
[Namjou, Bahram; Marsolo, Keith; Lingren, Todd; Harley, John B.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Marsolo, Keith; Lingren, Todd] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
[Ritchie, Marylyn D.; Verma, Shefali S.] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA.
[Perry, Cassandra] Boston Childrens Hosp BCH, Div Genet & Genom, Boston, MA USA.
[Kitchner, Terrie E.; Brilliant, Murray H.; Peissig, Peggy L.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI USA.
[Borthwick, Kenneth M.; Williams, Marc S.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA.
[Grafton, Jane] Grp Hlth Res Inst, Seattle, WA USA.
[Jarvik, Gail P.] Univ Washington, Dept Med, Seattle, WA USA.
[Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Holm, Ingrid A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA.
[Holm, Ingrid A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA.
[Holm, Ingrid A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
RP Namjou, B (reprint author), Cincinnati Childrens Hosp Med Ctr CCHMC, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA.
EM Bahram.namjou@cchmc.org
FU National Institutes of Health [U01HG006828, U01HG006389, U01HG006382,
U01HG006375, U01HG006385, U01HG004438]
FX This study was supported by the National Institutes of Health
(http://www.nih.gov/) grants: U01HG006828-NHGRI-Cincinnati Children's
Hospital Medical Center/Boston Children's Hospital (to JBH, IAH, BN,
BLC, KM, TL, CP); U01HG006389-NHGRI-Essentia Institute of Rural Health,
Marshfield Clinic Research Foundation and Pennsylvania State University
(to PLP, MHB, TEK, MDR, SSV); U01HG006382-NHGRI-Geisinger Clinic (to
MSW, KMB); U01HG006375-NHGRI-Group Health Cooperative/University of
Washington (to GPJ, JG); U01HG006385-NHGRI-Vanderbilt University Medical
Center serving as the Coordinating Center and the PGRNSeq dataset
(eMERGE PGx); U01HG004438-NHGRI- The Center for Inherited Disease
Research (CIDR) serving as a Sequencing Center for eMERGE. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 43
TC 6
Z9 6
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 28
PY 2015
VL 10
IS 9
AR e0138677
DI 10.1371/journal.pone.0138677
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS6EO
UT WOS:000362170700020
PM 26413716
ER
PT J
AU Garland, A
Rolfson, O
Garellick, G
Karrholm, J
Hailer, NP
AF Garland, Anne
Rolfson, Ola
Garellick, Goran
Karrholm, Johan
Hailer, Nils P.
TI Early postoperative mortality after simultaneous or staged bilateral
primary total hip arthroplasty: an observational register study from the
Swedish Hip Arthroplasty Register (vol 16, 77, 2015)
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Correction
C1 [Garland, Anne] Visby Hosp, Dept Orthopaed, Visby, Sweden.
[Garland, Anne; Rolfson, Ola; Garellick, Goran; Karrholm, Johan; Hailer, Nils P.] Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
[Rolfson, Ola; Garellick, Goran; Karrholm, Johan] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
[Garland, Anne; Hailer, Nils P.] Univ Uppsala Hosp, Inst Surg Sci, Dept Orthopaed, Uppsala, Sweden.
[Rolfson, Ola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, Boston, MA USA.
RP Garland, A (reprint author), Visby Hosp, Dept Orthopaed, Visby, Sweden.
EM anne.garland@gotland.se
NR 2
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD SEP 28
PY 2015
VL 16
AR 263
DI 10.1186/s12891-015-0717-9
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA CS1BJ
UT WOS:000361796700001
PM 26415948
ER
PT J
AU von Keudell, AG
Weaver, MJ
Appelton, PT
Bae, DS
Dyer, GSM
Heng, M
Jupiter, JB
Vrahas, MS
AF von Keudell, Arvind G.
Weaver, Michael J.
Appelton, Paul T.
Bae, Donald S.
Dyer, George S. M.
Heng, Marilyn
Jupiter, Jesse B.
Vrahas, Mark S.
TI Diagnosis and treatment of acute extremity compartment syndrome
SO LANCET
LA English
DT Article
ID NEAR-INFRARED SPECTROSCOPY; QUALITY-OF-LIFE; TIBIAL FRACTURES; LOWER
LEG; TISSUE PRESSURE; LOWER-LIMB; INTRACOMPARTMENTAL PRESSURE; ISCHEMIC
CONTRACTURE; MUSCLE ISCHEMIA; SKELETAL-MUSCLE
AB Acute compartment syndrome of the extremities is well known, but diagnosis can be challenging. Ineffective treatment can have devastating consequences, such as permanent dysaesthesia, ischaemic contractures, muscle dysfunction, loss of limb, and even loss of life. Despite many studies, there is no consensus about the way in which acute extremity compartment syndromes should be diagnosed. Many surgeons suggest continuous monitoring of intracompartmental pressure for all patients who have high-risk extremity injuries, whereas others suggest aggressive surgical intervention if acute compartment syndrome is even suspected. Although surgical fasciotomy might reduce intracompartmental pressure, this procedure also carries the risk of long-term complications. In this paper in The Lancet Series about emergency surgery we summarise the available data on acute extremity compartment syndrome of the upper and lower extremities in adults and children, discuss the underlying pathophysiology, and propose a clinical guideline based on the available data.
C1 [von Keudell, Arvind G.; Weaver, Michael J.; Appelton, Paul T.; Dyer, George S. M.; Jupiter, Jesse B.; Vrahas, Mark S.] Harvard Univ, Sch Med, Orthoped Trauma Initiat, Boston, MA 02114 USA.
[Dyer, George S. M.; Heng, Marilyn; Jupiter, Jesse B.; Vrahas, Mark S.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weaver, Michael J.; Dyer, George S. M.; Vrahas, Mark S.] Harvard Univ, Sch Med, Dept Orthoped Surg, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Bae, Donald S.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston Childrens Hosp, Boston, MA 02114 USA.
[Appelton, Paul T.] Harvard Univ, Sch Med, Dept Orthoped Surg, Beth Israel Deaconess Hosp, Boston, MA 02114 USA.
RP von Keudell, AG (reprint author), Harvard Univ, Sch Med, Orthoped Trauma Initiat, Boston, MA 02114 USA.
EM avonkeudell@mgh.harvard.edu
NR 104
TC 4
Z9 4
U1 3
U2 15
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 SEP 26
PY 2015
VL 386
IS 10000
BP 1299
EP 1310
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR9TQ
UT WOS:000361700100039
PM 26460664
ER
PT J
AU Anderson, JC
Willey, CD
Mehta, A
Welaya, K
Chen, DQ
Duarte, CW
Ghatalia, P
Arafat, W
Madan, A
Sudarshan, S
Naik, G
Grizzle, WE
Choueiri, TK
Sonpavde, G
AF Anderson, Joshua C.
Willey, Christopher D.
Mehta, Amitkumar
Welaya, Karim
Chen, Dongquan
Duarte, Christine W.
Ghatalia, Pooja
Arafat, Waleed
Madan, Ankit
Sudarshan, Sunil
Naik, Gurudatta
Grizzle, William E.
Choueiri, Toni K.
Sonpavde, Guru
TI High Throughput Kinomic Profiling of Human Clear Cell Renal Cell
Carcinoma Identifies Kinase Activity Dependent Molecular Subtypes
SO PLOS ONE
LA English
DT Article
ID BIOMARKERS; EVOLUTION; TUMORS; EXOME
AB Despite the widespread use of kinase-targeted agents in clear cell renal cell carcinoma (CC-RCC), comprehensive kinase activity evaluation (kinomic profiling) of these tumors is lacking. Thus, kinomic profiling of CC-RCC may assist in devising a classification system associated with clinical outcomes, and help identify potential therapeutic targets. Fresh frozen CC-RCC tumor lysates from 41 clinically annotated patients who had localized disease at diagnosis were kinomically profiled using the PamStation (R) 12 high-content phospho-peptide substrate microarray system (PamGene International). Twelve of these patients also had matched normal kidneys available that were also profiled. Unsupervised hierarchical clustering and supervised comparisons based on tumor vs. normal kidney and clinical outcome (tumor recurrence) were performed and coupled with advanced network modeling and upstream kinase prediction methods. Unsupervised clustering analysis of localized CC-RCC tumors identified 3 major kinomic groups associated with inflammation (A), translation initiation (B), and immune response and cell adhesions (C) processes. Potential driver kinases implicated include PFTAIRE (PFTK1), PKG1, and SRC, which were identified in groups A, B, and C, respectively. Of the 9 patients who had tumor recurrence, only one was found in Group B. Supervised analysis showed decreased kinase activity of CDK1 and RSK1-4 substrates in those which progressed compared to others. Twelve tumors with matching normal renal tissue implicated increased PIM's and MAPKAPK's in tumors compared to adjacent normal renal tissue. As such, comprehensive kinase profiling of CC-RCC tumors could provide a functional classification strategy for patients with localized disease and identify potential therapeutic targets.
C1 [Anderson, Joshua C.; Willey, Christopher D.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL 35294 USA.
[Mehta, Amitkumar; Ghatalia, Pooja; Madan, Ankit; Naik, Gurudatta; Sonpavde, Guru] Univ Alabama Birmingham, Div Hematol & Oncol, Birmingham, AL 35294 USA.
[Chen, Dongquan] Univ Alabama Birmingham, Div Preventat Med, Birmingham, AL USA.
[Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL USA.
[Grizzle, William E.] Univ Alabama Birmingham, Div Anat Pathol, Birmingham, AL USA.
[Welaya, Karim; Arafat, Waleed] Univ Alexandria, Dept Clin Oncol, Alexandria, Egypt.
[Duarte, Christine W.] MMCRI, CORE, Portland, ME USA.
[Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA.
[Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Div Hematol & Oncol, Birmingham, AL 35294 USA.
EM gsonpavde@uabmc.edu
OI Anderson, Joshua/0000-0002-6977-9054
FU Egyptian Partnership & Ownership Initiative Fellowship Grant;
Comprehensive Cancer Center Pilot Grant Program [P30CA013148]
FX Egyptian Partnership & Ownership Initiative Fellowship Grant provided
the stipend support for UAB Kinome Core Fellow (KW). The UAB
Comprehensive Cancer Center Pilot Grant Program (P30CA013148) provided
funding for the experimental work (to GS). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 33
TC 8
Z9 8
U1 0
U2 5
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 SEP 25
PY 2015
VL 10
IS 9
AR e0139267
DI 10.1371/journal.pone.0139267
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1CR
UT WOS:000361800700201
PM 26406598
ER
PT J
AU Koh, SH
Liang, AC
Takahashi, Y
Maki, T
Shindo, A
Osumi, N
Zhao, J
Lin, H
Holder, JC
Chuang, TT
McNeish, JD
Arai, K
Lo, EH
AF Koh, Seong-Ho
Liang, Anna C.
Takahashi, Yoko
Maki, Takakuni
Shindo, Akihiro
Osumi, Noriko
Zhao, Jing
Lin, Hong
Holder, Julie C.
Chuang, Tsu Tshen
McNeish, John D.
Arai, Ken
Lo, Eng H.
TI Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells,
Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells
SO PLOS ONE
LA English
DT Article
ID STROKE RECOVERY; SMALL-MOLECULE; STEM-CELLS; BRAIN; ANGIOGENESIS;
NEUROGENESIS; PROLIFERATION; TRANSLATION; THERAPY; FATE
AB Adult mammalian brain can be plastic after injury and disease. Therefore, boosting endogenous repair mechanisms would be a useful therapeutic approach for neurological disorders. Isoxazole-9 (Isx-9) has been reported to enhance neurogenesis from neural stem/progenitor cells (NSPCs). However, the effects of Isx-9 on other types of progenitor/precursor cells remain mostly unknown. In this study, we investigated the effects of Isx-9 on the three major populations of progenitor/precursor cells in brain: NSPCs, oligodendrocyte precursor cells (OPCs), and endothelial progenitor cells (EPCs). Cultured primary NSPCs, OPCs, or EPCs were treated with various concentrations of Isx-9 (6.25, 12.5, 25, 50 mu M), and their cell numbers were counted in a blinded manner. Isx-9 slightly increased the number of NSPCs and effectively induced neuronal differentiation of NSPCs. However, Isx-9 significantly decreased OPC number in a concentration-dependent manner, suggesting cytotoxicity. Isx-9 did not affect EPC cell number. But in a matrigel assay of angiogenesis, Isx-9 significantly inhibited tube formation in outgrowth endothelial cells derived from EPCs. This potential anti-tube-formation effect of Isx-9 was confirmed in a brain endothelial cell line. Taken together, our data suggest that mechanisms and targets for promoting stem/progenitor cells in the central nervous system may significantly differ between cell types.
C1 [Koh, Seong-Ho; Liang, Anna C.; Takahashi, Yoko; Maki, Takakuni; Shindo, Akihiro; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol & Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
[Koh, Seong-Ho; Liang, Anna C.; Takahashi, Yoko; Maki, Takakuni; Shindo, Akihiro; Arai, Ken; Lo, Eng H.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Koh, Seong-Ho] Hanyang Univ, Coll Med, Dept Neurol, Seoul 133791, South Korea.
[Takahashi, Yoko; Osumi, Noriko] Tohoku Univ, Grad Sch Med, United Ctr Adv Res & Translat Med, Dept Dev Neurosci, Sendai, Miyagi 980, Japan.
[Zhao, Jing; Lin, Hong; Holder, Julie C.; Chuang, Tsu Tshen; McNeish, John D.] GlaxoSmithKline, Regenerat Med Discovery Performance Unit, Cambridge, MA USA.
RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Radiol & Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
EM Lo@helix.mgh.harvard.edu
FU National Institutes of Health [P01-NS55104]; Uehara Memorial Foundation;
Glaxo-Smith-Kline-Harvard-Stem-Cell-Institute consortium;
Glaxo-Smith-Kline
FX Work was supported in part by grants from the National Institutes of
Health (P01-NS55104), the Uehara Memorial Foundation, and the
Glaxo-Smith-Kline-Harvard-Stem-Cell-Institute consortium. Salaries for
authors with primary appointments with Glaxo-Smith-Kline (JZ, HL, JCH,
TTC, and JDM) were paid by Glaxo-Smith-Kline. JZ, HL, JCH, TTC, and JDM
participated in study design and data analysis.
NR 25
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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 SEP 25
PY 2015
VL 10
IS 9
AR e0138724
DI 10.1371/journal.pone.0138724
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS1CR
UT WOS:000361800700076
PM 26407349
ER
PT J
AU Byun, S
Lim, S
Mun, JY
Kim, KH
Ramadhar, TR
Farrand, L
Shin, SH
Thimmegowda, NR
Lee, HJ
Frank, DA
Clardy, J
Lee, SW
Lee, KW
AF Byun, Sanguine
Lim, Semi
Mun, Ji Young
Kim, Ki Hyun
Ramadhar, Timothy R.
Farrand, Lee
Shin, Seung Ho
Thimmegowda, N. R.
Lee, Hyong Joo
Frank, David A.
Clardy, Jon
Lee, Sam W.
Lee, Ki Won
TI Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70
Ribosomal S6 Kinase1 (S6K1) Pathways
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OVARIAN-CANCER CELLS; ZINGIBER-OFFICINALE; NATURAL-PRODUCTS;
PROSTATE-CANCER; GINGER EXTRACT; BREAST-CANCER; GROWTH-FACTOR;
APOPTOSIS; EXPRESSION; ACTIVATION
AB Bioactive phytochemicals can suppress the growth of malignant cells, and investigation of the mechanisms responsible can assist in the identification of novel therapeutic strategies for cancer therapy. Ginger has been reported to exhibit potent anticancer effects, although previous reports have often focused on a narrow range of specific compounds. Through a direct comparison of various ginger compounds, we determined that gingerenone A selectively kills cancer cells while exhibiting minimal toxicity toward normal cells. Kinase array screening revealed JAK2 and S6K1 as the molecular targets primarily responsible for gingerenone A-induced cancer cell death. The effect of gingerenone A was strongly associated with relative phosphorylation levels of JAK2 and S6K1, and administration of gingerenone A significantly suppressed tumor growth in vivo. More importantly, the combined inhibition of JAK2 and S6K1 by commercial inhibitors selectively induced apoptosis in cancer cells, whereas treatment with either agent alone did not. These findings provide rationale for dual targeting of JAK2 and S6K1 in cancer for a combinatorial therapeutic approach.
C1 [Byun, Sanguine; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Byun, Sanguine; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Byun, Sanguine; Lee, Ki Won] Seoul Natl Univ, Adv Inst Convergence Technol, Suwon 443270, South Korea.
[Lim, Semi; Lee, Hyong Joo; Lee, Ki Won] Seoul Natl Univ, Dept Agr Biotechnol, WCU Biomodulat Major, Seoul 151742, South Korea.
[Mun, Ji Young] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Songnam 461463, South Korea.
[Kim, Ki Hyun; Ramadhar, Timothy R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Kim, Ki Hyun] Sungkyunkwan Univ, Sch Pharm, Suwon 440746, South Korea.
[Farrand, Lee] Yuhan Corp, Yuhan Res Inst, Yongin 446902, South Korea.
[Shin, Seung Ho] Univ Minnesota, Program Biomed Informat & Computat Biol, Minneapolis, MN 55455 USA.
[Thimmegowda, N. R.] Govt Sri Krishnarajendra Silver Jubilee Technol I, Dept Chem, Bangalore 560001, Karnataka, India.
[Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Thimmegowda, N. R.] Korea Res Inst Biosci & Biotechnol, World Class Inst, Ochang 363883, South Korea.
RP Clardy, J (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA.
EM jon_clardy@hms.harvard.edu; swlee@mgh.harvard.edu; kiwon@snu.ac.kr
RI Regan, Clinton/E-6250-2012;
OI Ramadhar, Timothy/0000-0002-7063-5445
FU National Institutes of Health [1RO1CA142805, 1RO1CA149477]; National
Leap Research Program through National Research Foundation of Korea -
Ministry of Science, ICT, and Future Planning (MSIP) of Korea, Republic
of Korea [2010-0029233]; F32 postdoctoral fellowship from the National
Institutes of Health [GM108415]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 1RO1CA142805 and 1RO1CA149477 (NCI). This work was also
supported by the National Leap Research Program (2010-0029233) through
the National Research Foundation of Korea funded by the Ministry of
Science, ICT, and Future Planning (MSIP) of Korea, Republic of Korea.
The authors declare that they have no conflicts of interest with the
contents of this article.; Supported by an F32 postdoctoral fellowship
from the National Institutes of Health (GM108415).
NR 60
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U1 0
U2 5
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 SEP 25
PY 2015
VL 290
IS 39
BP 23553
EP 23562
DI 10.1074/jbc.M115.662445
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS1IF
UT WOS:000361816500008
PM 26242912
ER
PT J
AU Wheeler, TM
Baker, JN
Chad, DA
Zilinski, JL
Verzosa, S
Mordes, DA
AF Wheeler, Thurman M.
Baker, Joshua N.
Chad, David A.
Zilinski, Jodi L.
Verzosa, Stacey
Mordes, Daniel A.
TI Case 30-2015: A 50-Year-Old Man with Cardiogenic Shock
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID EXTRACORPOREAL MEMBRANE-OXYGENATION; MYOTONIC-DYSTROPHY TYPE-1;
EFFECTIVE ANTIMYOTONIA TREATMENT; ADULT PATIENTS; ABNORMALITIES;
EXPERIENCE; MEXILETINE; EXPANSION; SUPPORT; MUSCLE
C1 [Wheeler, Thurman M.; Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Verzosa, Stacey] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mordes, Daniel A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Baker, Joshua N.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA.
[Zilinski, Jodi L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Wheeler, Thurman M.; Chad, David A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Baker, Joshua N.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Zilinski, Jodi L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Verzosa, Stacey] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mordes, Daniel A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Wheeler, TM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 23
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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 SEP 24
PY 2015
VL 373
IS 13
BP 1251
EP 1261
DI 10.1056/NEJMcpc1415169
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200012
PM 26398074
ER
PT J
AU Kassim, AA
Payne, AB
Rodeghier, M
Macklin, EA
Strunk, RC
DeBaun, MR
AF Kassim, Adetola A.
Payne, Amanda B.
Rodeghier, Mark
Macklin, Eric A.
Strunk, Robert C.
DeBaun, Michael R.
TI Low forced expiratory volume is associated with earlier death in sickle
cell anemia
SO BLOOD
LA English
DT Article
ID LUNG-FUNCTION; PULMONARY-FUNCTION; CYSTIC-FIBROSIS; REFERENCE VALUES;
FUNCTION TESTS; FOLLOW-UP; DISEASE; MORTALITY; RISK; ADULTS
AB Pulmonary complications result in mortality in adults with sickle cell anemia (SCA). We tested the hypothesis that abnormal pulmonary function was associated with earlier death. A prospective cohort of adults with SCA, followed in the Cooperative Study for Sickle Cell Disease, was constructed using the first pulmonary function test at >21 years of age. Spirometry measures: forced expiratory volume in 1 second (FEV1), forced vital capacity, and total lung capacity were categorized based on age, gender, height, and race. Pulmonary function patterns were categorized based on the American Thoracic Society guidelines using both spirometry and lung volumes. A cohort of 430 adults with SCA, mean age 32.6 +/- 9.5 (range, 21.0-67.8) years at time of first pulmonary function test, and a median follow-up of 5.5 years, was evaluated. A total of 63 deaths occurred. At baseline, 47% had normal, 29% restrictive, 8% obstructive, 2% mixed, and 14% nonspecific lung function patterns. In the final multivariable model, lower FEV1 percent predicted was associated with increased hazard ratio of death (HRper% predicted 1.02; 95% confidence interval [CI] 1.00-1.04; P=.037), as was older age(HR 1.07; 95% CI 1.04-1.10; P<.001), male sex (HR 2.09; 95% CI 1.20-3.65; P=.010), higher lactate dehydrogenase levels (HR per mg/dL 1.002; 95% CI 1.00-1.003; P=.015), and higher acute chest syndrome incidence rate (HR per event/year 10.4; 95% CI 3.11-34.8; P < .001). Presence of obstructive (HR 1.18; 95% CI: 0.44-3.20; P=.740) and restrictive (HR 1.31; 95% CI: 0.64-2.32; P = .557) pulmonary function patterns were not associated with earlier death. Understanding the pathophysiology of a low FEV1 percent predicted in individuals with SCA is warranted, enabling early intervention for those at risk.
C1 [Kassim, Adetola A.] Vanderbilt Univ, Sch Med, Dept Med, Div Hematol Oncol, Nashville, TN 37232 USA.
[Kassim, Adetola A.; DeBaun, Michael R.] Vanderbilt Univ, Sch Med, Vanderbilt Meharry Ctr Excellence Sickle Cell Dis, Nashville, TN 37232 USA.
[Payne, Amanda B.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
[Rodeghier, Mark] Rodeghier Consultants, Chicago, IL USA.
[Macklin, Eric A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Strunk, Robert C.] Washington Univ, Sch Med, Dept Pediat, Div Allergy Immunol & Pulm Med, St Louis, MO 63110 USA.
[DeBaun, Michael R.] Vanderbilt Univ, Sch Med, Dept Pediat & Med, Div Hematol Oncol, Nashville, TN 37232 USA.
RP DeBaun, MR (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Meharry Ctr Excellence Sickle Cell Dis, Dept Pediat, 2200 Childrens Way,11206DOT, Nashville, TN 37232 USA.
EM m.debaun@vanderbilt.edu
OI Macklin, Eric/0000-0003-1618-3502
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[5R01-HL079937-07]; Burroughs Wellcome Foundation
FX This work was supported in part by the National Institutes of Health,
National Heart, Lung, and Blood Institute (grant 5R01-HL079937-07)
(R.C.S. and M.R.D.) and the Burroughs Wellcome Foundation (M.R.D.). The
funding sources provided the financial resources to conduct the
research. M.R.D. confirms that he had full access to all of the data in
this study and had the final responsibility for the decision to submit
for publication.
NR 33
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U1 0
U2 2
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 SEP 24
PY 2015
VL 126
IS 13
BP 1544
EP 1550
DI 10.1182/blood-2015-05-644435
PG 7
WC Hematology
SC Hematology
GA CU4EX
UT WOS:000363481000008
PM 26261241
ER
PT J
AU Bhatt, S
Matthews, J
Parvin, S
Sarosiek, KA
Zhao, DK
Jiang, XY
Isik, E
Letai, A
Lossos, IS
AF Bhatt, Shruti
Matthews, Julie
Parvin, Salma
Sarosiek, Kristopher A.
Zhao, Dekuang
Jiang, Xiaoyu
Isik, Elif
Letai, Anthony
Lossos, Izidore S.
TI Direct and immune-mediated cytotoxicity of interleukin-21 contributes to
antitumor effects in mantle cell lymphoma
SO BLOOD
LA English
DT Article
ID RECOMBINANT HUMAN INTERLEUKIN-21; LYMPHOCYTIC-LEUKEMIA CELLS;
PROGRESSION-FREE SURVIVAL; MYC-INDUCED APOPTOSIS; C-MYC; B-CELLS;
PHASE-I; METASTATIC MELANOMA; GROWTH ARREST; BCL-2 FAMILY
AB Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin D1 in 95% of patients. MCL patients experience frequent relapses resulting in median survival of 3 to 5 years, requiring more efficient therapeutic regimens. Interleukin (IL)-21, a member of the IL-2 cytokine family, possesses potent antitumor activity against a variety of cancers not expressing the IL-21 receptor (IL-21R) through immune activation. Previously, we established that IL-21 exerts direct cytotoxicity on IL-21R-expressing diffuse large B-cell lymphoma cells. Herein, we demonstrate that IL-21 possesses potent cytotoxicity against MCL cell lines and primary tumors. We identify that IL-21-induced direct cytotoxicity is mediated through signal transducer and activator of transcription 3-dependent cMyc upregulation, resulting in activation of Bax and inhibition of Bcl-2 and Bcl-XL. IL-21-mediated cMyc upregulation is only observed in IL-21-sensitive cells. Further, we demonstrate that IL-21 leads to natural killer (NK)-cell-dependent lysis of MCL cell lines that were resistant to direct cytotoxicity. In vivo treatment with IL-21 results in complete FC-muMCL1 tumor regression in syngeneicmice via NK- and T-cell-dependent mechanisms. Together, these data indicate that IL-21 has potent antitumor activity against MCL cells via direct cytotoxic and indirect, immune-mediated effects.
C1 [Bhatt, Shruti; Matthews, Julie; Sarosiek, Kristopher A.; Lossos, Izidore S.] Sylvester Comprehens Canc Ctr, Dept Mol & Cellular Pharmacol, Miami, FL USA.
[Bhatt, Shruti; Matthews, Julie; Parvin, Salma; Sarosiek, Kristopher A.; Zhao, Dekuang; Jiang, Xiaoyu; Lossos, Izidore S.] Sylvester Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Miami, FL USA.
[Parvin, Salma; Zhao, Dekuang] Univ Miami, Miller Sch Med, Sheila & David Fuente Grad Program Canc Biol, Miami, FL 33136 USA.
[Isik, Elif; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Letai, Anthony] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Lossos, IS (reprint author), Univ Miami, Sylvester Comprehens Canc Ctr, Div Hematol & Oncol, 1475 NW 12th Ave D8-4, Miami, FL 33136 USA.
EM ilossos@med.miami.edu
RI Zhao, Dekuang/H-5671-2015
OI Zhao, Dekuang/0000-0002-7251-2481
FU Lymphoma Research Foundation; National Institutes of Health National
Cancer Institute [CA109335]; Dwoskin Family Foundation; Recio Family
Foundation; Antony Rizzo Foundation
FX This study was supported by the Lymphoma Research Foundation ( I.S.L.).
I.S.L. was also supported by a grant from the National Institutes of
Health National Cancer Institute (CA109335) and the Dwoskin Family,
Recio Family, and Antony Rizzo Foundations.
NR 50
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U1 0
U2 5
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 SEP 24
PY 2015
VL 126
IS 13
BP 1555
EP 1564
DI 10.1182/blood-2015-01-624585
PG 10
WC Hematology
SC Hematology
GA CU4EX
UT WOS:000363481000010
PM 26194763
ER
PT J
AU Sun, BH
Shah, B
Fiskus, W
Qi, J
Rajapakshe, K
Coarfa, C
Li, L
Devaraj, SGT
Sharma, S
Zhang, L
Wang, ML
Saenz, DT
Krieger, S
Bradner, JE
Bhalla, KN
AF Sun, Baohua
Shah, Bhavin
Fiskus, Warren
Qi, Jun
Rajapakshe, Kimal
Coarfa, Cristian
Li, Li
Devaraj, Santhana G. T.
Sharma, Sunil
Zhang, Liang
Wang, Michael L.
Saenz, Dyana T.
Krieger, Stephanie
Bradner, James E.
Bhalla, Kapil N.
TI Synergistic activity of BET protein antagonist-based combinations in
mantle cell lymphoma cells sensitive or resistant to ibrutinib
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; BRUTONS TYROSINE KINASE; SELECTIVE-INHIBITION; EMERGING
ROLES; P-TEFB; BRD4; CANCER; LEUKEMIA; BROMODOMAIN; MECHANISMS
AB Mantle cell lymphoma (MCL) cells exhibit increased B-cell receptor and nuclear factor (NF)-kappa B activities. The bromodomain and extra-terminal (BET) protein bromodomain 4 is essential for the transcriptional activity of NF-kappa B. Here, we demonstrate that treatment with the BET protein bromodomain antagonist (BA) JQ1 attenuates MYC and cyclin-dependent kinase (CDK) 4/6, inhibits the nuclear RelA levels and the expression of NF-kappa B target genes, including Bruton tyrosine kinase (BTK) in MCL cells. Although lowering the levels of the antiapoptotic B-cell lymphoma (BCL) 2 family proteins, BA treatment induces the proapoptotic protein BIM and exerts dose-dependent lethality against cultured and primary MCL cells. Cotreatment with BA and the BTK inhibitor ibrutinib synergistically induces apoptosis of MCL cells. Compared with each agent alone, cotreatment with BA and ibrutinib markedly improved the median survival of mice engrafted with the MCL cells. BA treatment also induced apoptosis of the in vitro isolated, ibrutinib-resistant MCL cells, which overexpress CDK6, BCL2, Bcl-xL, XIAP, and AKT, but lack ibrutinib resistance-conferring BTK mutation. Cotreatment with BA and panobinostat (pan-histone deacetylase inhibitor) or palbociclib (CDK4/6 inhibitor) or ABT-199 (BCL2 antagonist) synergistically induced apoptosis of the ibrutinib-resistant MCL cells. These findings highlight and support further in vivo evaluation of the efficacy of the BA-based combinations with these agents against MCL, including ibrutinib-resistant MCL.
C1 [Sun, Baohua; Fiskus, Warren; Zhang, Liang; Wang, Michael L.; Saenz, Dyana T.; Krieger, Stephanie; Bhalla, Kapil N.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Sun, Baohua; Fiskus, Warren; Zhang, Liang; Wang, Michael L.; Saenz, Dyana T.; Krieger, Stephanie; Bhalla, Kapil N.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
[Shah, Bhavin; Devaraj, Santhana G. T.] Houston Methodist Res Inst, Canc Res, Houston, TX USA.
[Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rajapakshe, Kimal; Coarfa, Cristian] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Li, Li] Tom & Gayle Benson Canc Ctr, Lab Translat Canc Res, New Orleans, LA USA.
[Sharma, Sunil] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
RP Bhalla, KN (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Leukemia Dept, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA.
EM kbhalla@mdanderson.org
RI Rajapakshe, Kimal/P-1592-2015
FU National Institutes of Health, National Cancer Institute, through the MD
Anderson Cancer Center Support grant [P30 CA016672]; National Institutes
of Health, National Cancer Institute, through the MD Anderson Cancer
Center Leukemia Specialized Program of Research Excellence grant [CA
100632]
FX This research was supported in part by the National Institutes of
Health, National Cancer Institute, through the MD Anderson Cancer Center
Support grant (P30 CA016672), and through the MD Anderson Cancer Center
Leukemia Specialized Program of Research Excellence grant (CA 100632).
NR 50
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U2 8
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 SEP 24
PY 2015
VL 126
IS 13
BP 1565
EP 1574
DI 10.1182/blood-2015-04-639542
PG 10
WC Hematology
SC Hematology
GA CU4EX
UT WOS:000363481000011
PM 26254443
ER
PT J
AU Wang, YB
Zhang, TH
Kwiatkowski, N
Abraham, BJ
Lee, TI
Xie, SZ
Yuzugullu, H
Von, T
Li, HY
Lin, Z
Stover, DG
Lim, E
Wang, ZGC
Iglehart, JD
Young, RA
Gray, NS
Zhao, JJ
AF Wang, Yubao
Zhang, Tinghu
Kwiatkowski, Nicholas
Abraham, Brian J.
Lee, Tong Ihn
Xie, Shaozhen
Yuzugullu, Haluk
Thanh Von
Li, Heyuan
Lin, Ziao
Stover, Daniel G.
Lim, Elgene
Wang, Zhigang C.
Iglehart, J. Dirk
Young, Richard A.
Gray, Nathanael S.
Zhao, Jean J.
TI CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast
Cancer
SO CELL
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; RNA-POLYMERASE-II; COVALENT CDK7 INHIBITOR;
THERAPEUTIC TARGET; SUPER-ENHANCERS; MOLECULAR PORTRAITS;
TUMOR-SUPPRESSOR; FACTOR RECEPTOR; CELL IDENTITY; CLAUDIN-LOW
AB Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing kinase inhibitors and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not hormone receptor-positive breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBCcells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An "Achilles cluster'' of TNBC-specific genes is especially sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be a useful therapy for this challenging cancer.
C1 [Wang, Yubao; Zhang, Tinghu; Xie, Shaozhen; Yuzugullu, Haluk; Thanh Von; Li, Heyuan; Lin, Ziao; Wang, Zhigang C.; Iglehart, J. Dirk; Gray, Nathanael S.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Wang, Yubao; Zhang, Tinghu; Xie, Shaozhen; Yuzugullu, Haluk; Thanh Von; Gray, Nathanael S.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Kwiatkowski, Nicholas; Abraham, Brian J.; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
[Stover, Daniel G.; Lim, Elgene] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wang, Zhigang C.; Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM nathanael_gray@dfci.harvard.edu; jean_zhao@dfci.harvard.edu
RI Young, Richard/F-6495-2012; Wang, Yubao/L-3912-2014;
OI Young, Richard/0000-0001-8855-8647; Stover, Daniel/0000-0001-9003-8165
FU NIH [R01CA179483-01]; MIT-DFCI Bridge grant; NIH/NCI [P50 CA168504]
FX We thank D. Wiederschain and F. Zhang for sharing the plasmids. We thank
the Nikon Imaging Center at Harvard Medical School, DFCI Flow Cytometry
Core Facility, and Dana-Farber/Harvard Cancer Center Rodent
Histopathology Core for technical assistance and the use of instruments.
This study was supported by NIH R01CA179483-01 (N.S.G.), a MIT-DFCI
Bridge grant (N.S.G. and R.A.Y.), and NIH/NCI P50 CA168504 (J.Z.).
N.S.G., T.Z., and N.K. are inventors on a patent application covering
THZ1 and THZ2. N.S.G. and R.A.Y. are scientific founders of Syros
Pharmaceuticals, a company that has licensed THZ1 and THZ2 from the
Dana-Farber Cancer Institute.
NR 55
TC 22
Z9 23
U1 4
U2 42
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 SEP 24
PY 2015
VL 163
IS 1
BP 174
EP 186
DI 10.1016/j.cell.2015.08.063
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS1RX
UT WOS:000361846500030
PM 26406377
ER
PT J
AU Yang, BX
El Farran, CA
Guo, HC
Yu, T
Fang, HT
Wang, HF
Schlesinger, S
Seah, YFS
Goh, GYL
Neo, SP
Li, YH
Lorincz, MC
Tergaonkar, V
Lim, TM
Chen, LY
Gunaratne, J
Collins, JJ
Goff, SP
Daley, GQ
Li, H
Bard, FA
Loh, YH
AF Yang, Bin Xia
El Farran, Chadi A.
Guo, Hong Chao
Yu, Tao
Fang, Hai Tong
Wang, Hao Fei
Schlesinger, Sharon
Seah, Yu Fen Samantha
Goh, Germaine Yen Lin
Neo, Suat Peng
Li, Yinghui
Lorincz, Matthew C.
Tergaonkar, Vinay
Lim, Tit-Meng
Chen, Lingyi
Gunaratne, Jayantha
Collins, James J.
Goff, Stephen P.
Daley, George Q.
Li, Hu
Bard, Frederic A.
Loh, Yuin-Han
TI Systematic Identification of Factors for Provirus Silencing in Embryonic
Stem Cells
SO CELL
LA English
DT Article
ID PRIMER-BINDING SITE; MURINE LEUKEMIA-VIRUS; CHROMATIN ASSEMBLY FACTOR-1;
LONG TERMINAL REPEAT; DNA-REPLICATION; ENDOGENOUS RETROVIRUSES;
DEPENDENT RESTRICTION; CARCINOMA-CELLS; HISTONE H3.3; ES CELLS
AB Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/At-f7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome.
C1 [Yang, Bin Xia; El Farran, Chadi A.; Yu, Tao; Fang, Hai Tong; Wang, Hao Fei; Seah, Yu Fen Samantha; Loh, Yuin-Han] A STAR Inst Mol & Cell Biol, Epigenet & Cell Fates Lab, Singapore 138673, Singapore.
[El Farran, Chadi A.; Yu, Tao; Wang, Hao Fei; Lim, Tit-Meng; Loh, Yuin-Han] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
[Guo, Hong Chao; Chen, Lingyi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
[Schlesinger, Sharon; Goff, Stephen P.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Schlesinger, Sharon; Goff, Stephen P.] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Goh, Germaine Yen Lin; Bard, Frederic A.] A STAR Inst Mol & Cell Biol, Membrane Traff Lab, Singapore 138673, Singapore.
[Neo, Suat Peng; Gunaratne, Jayantha] A STAR Inst Mol & Cell Biol, Quantitat Prote Grp, Singapore 138673, Singapore.
[Gunaratne, Jayantha] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117597, Singapore.
[Li, Yinghui; Tergaonkar, Vinay] A STAR Inst Mol & Cell Biol, Lab NF KB Signaling, Div Canc Genet & Therapeut, Singapore 138673, Singapore.
[Lorincz, Matthew C.] Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
[Collins, James J.] MIT, Inst Med Engn & Sci, Dept Biol Engn, Synthet Biol Ctr, Cambridge, MA 02139 USA.
[Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.
[Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Collins, James J.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Goff, Stephen P.] Howard Hughes Med Inst, New York, NY 10032 USA.
[Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
[Li, Hu] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Ctr Individualized Med, Rochester, MN 55905 USA.
[Tergaonkar, Vinay; Bard, Frederic A.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 119077, Singapore.
RP Loh, YH (reprint author), A STAR Inst Mol & Cell Biol, Epigenet & Cell Fates Lab, 61 Biopolis Dr Proteos, Singapore 138673, Singapore.
EM yhloh@imcb.a-star.edu.sg
RI ASTAR, IMCB/E-2320-2012; Schlesinger, Sharon/A-5283-2016;
OI Schlesinger, Sharon/0000-0001-9549-2383; Li, Yinghui/0000-0002-9023-9466
FU Mayo Clinic Center for Individualized Medicine; NIH [R01 CA30488];
A*Star Investigatorship research award; Biomedical Research Council,
Agency for Science, Technology and Research, Singapore
FX We are grateful to Yang Lin for helpful discussion. We thank Wong Chee
Wai for technical assistance. H.L. is supported by Mayo Clinic Center
for Individualized Medicine. S.P.G. is supported by NIH grant R01
CA30488. Y.-H.L. is supported by the A*Star Investigatorship research
award. We are grateful to the Biomedical Research Council, Agency for
Science, Technology and Research, Singapore for research funding.
NR 57
TC 17
Z9 17
U1 5
U2 21
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 SEP 24
PY 2015
VL 163
IS 1
BP 230
EP 245
DI 10.1016/j.cell.2015.08.037
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS1RX
UT WOS:000361846500034
PM 26365490
ER
PT J
AU Mata, IF
Jang, Y
Kim, CH
Hanna, DS
Dorschner, MO
Samii, A
Agarwal, P
Roberts, JW
Klepitskaya, O
Shprecher, DR
Chung, KA
Factor, SA
Espay, AJ
Revilla, FJ
Higgins, DS
Litvan, I
Leverenz, JB
Yearout, D
Inca-Martinez, M
Martinez, E
Thompson, TR
Cholerton, BA
Hu, SC
Edwards, KL
Kim, KS
Zabetian, CP
AF Mata, Ignacio F.
Jang, Yongwoo
Kim, Chun-Hyung
Hanna, David S.
Dorschner, Michael O.
Samii, Ali
Agarwal, Pinky
Roberts, John W.
Klepitskaya, Olga
Shprecher, David R.
Chung, Kathryn A.
Factor, Stewart A.
Espay, Alberto J.
Revilla, Fredy J.
Higgins, Donald S.
Litvan, Irene
Leverenz, James B.
Yearout, Dora
Inca-Martinez, Miguel
Martinez, Erica
Thompson, Tiffany R.
Cholerton, Brenna A.
Hu, Shu-Ching
Edwards, Karen L.
Kim, Kwang-Soo
Zabetian, Cyrus P.
TI The RAB39B p.G192R mutation causes X-linked dominant Parkinson's disease
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID LEWY BODY; PATHOLOGY; VARIANTS; GTPASES; RISK
AB Objective: To identify the causal gene in a multi-incident U.S. kindred with Parkinson's disease (PD).
Methods: We characterized a family with a classical PD phenotype in which 7 individuals (5 males and 2 females) were affected with a mean age at onset of 46.1 years (range, 29-57 years). We performed whole exome sequencing on 4 affected and 1 unaffected family members. Sanger-sequencing was then used to verify and genotype all candidate variants in the remainder of the pedigree. Cultured cells transfected with wild-type or mutant constructs were used to characterize proteins of interest.
Results: We identified a missense mutation (c.574G > A; p.G192R) in the RAB39B gene that closely segregated with disease and exhibited X-linked dominant inheritance with reduced penetrance in females. The mutation occurred in a highly conserved amino acid residue and was not observed among 87,725 X chromosomes in the Exome Aggregation Consortium dataset. Sequencing of the RAB39B coding region in 587 familial PD cases yielded two additional mutations (c.428C > G [p.A143G] and c.624_626delGAG [p.R209del]) that were predicted to be deleterious in silico but occurred in families that were not sufficiently informative to assess segregation with disease. Experiments in PC12 and SK-N-BE(2) C cells demonstrated that p.G192R resulted in mislocalization of the mutant protein, possibly by altering the structure of the hypervariable C-terminal domain which mediates intracellular targeting.
Conclusions: Our findings implicate RAB39B, an essential regulator of vesicular-trafficking, in clinically typical PD. Further characterization of normal and aberrant RAB39B function might elucidate important mechanisms underlying neurodegeneration in PD and related disorders.
C1 [Mata, Ignacio F.; Samii, Ali; Yearout, Dora; Martinez, Erica; Thompson, Tiffany R.; Cholerton, Brenna A.; Hu, Shu-Ching; Edwards, Karen L.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Mata, Ignacio F.; Samii, Ali; Yearout, Dora; Martinez, Erica; Hu, Shu-Ching; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Jang, Yongwoo; Kim, Chun-Hyung; Kim, Kwang-Soo] McLean Hosp, Dept Psychiat, Mol Neurobiol Lab, Belmont, MA 02178 USA.
[Jang, Yongwoo; Kim, Chun-Hyung; Kim, Kwang-Soo] McLean Hosp, Program Neurosci, Belmont, MA 02178 USA.
[Jang, Yongwoo; Kim, Chun-Hyung; Kim, Kwang-Soo] Harvard Univ, Sch Med, Belmont, MA 02178 USA.
[Hanna, David S.; Dorschner, Michael O.; Cholerton, Brenna A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Hanna, David S.; Dorschner, Michael O.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Agarwal, Pinky] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Klepitskaya, Olga] Univ Colorado, Dept Neurol, Denver, CO 80202 USA.
[Shprecher, David R.] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Chung, Kathryn A.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA.
[Chung, Kathryn A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Espay, Alberto J.] Univ Cincinnati, Dept Neurol Rehabil Med, Cincinnati, OH USA.
[Revilla, Fredy J.] Div Neurol Greenville Hlth Syst, Greenville, SC USA.
[Higgins, Donald S.] Univ S Carolina, Med Sch Greenville, Greenville, SC USA.
[Higgins, Donald S.] Samuel Stratton Vet Affairs Med Ctr, Albany, NY USA.
[Litvan, Irene] Univ Calif San Diego, Dept Neurosci, Movement Disorder Ctr, San Diego, CA 92103 USA.
[Leverenz, James B.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA.
[Inca-Martinez, Miguel] Inst Nacl Ciencias Neurolog, Neurogenet Res Ctr, Lima, Peru.
[Edwards, Karen L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
RP Zabetian, CP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
EM zabetian@u.washington.edu
OI Litvan, Irene/0000-0002-3485-3445
FU National Institutes of Health [P50 NS062684, R01 NS065070, R01
NS084869]; Department of Veterans Affairs [1I01BX000531]
FX This work was supported by grants from the National Institutes of Health
(P50 NS062684, R01 NS065070, R01 NS084869) and the Department of
Veterans Affairs (1I01BX000531), and by a gift from the Dolsen
Foundation. We thanks all of the individuals who participated in the
study and Drs. Jennifer Witt and Rosalind Chuang for assistance with
patient recruitment.
NR 23
TC 15
Z9 15
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD SEP 24
PY 2015
VL 10
AR 50
DI 10.1186/s13024-015-0045-4
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CR8FE
UT WOS:000361585700001
PM 26399558
ER
PT J
AU Gupta, V
Kerry, VB
Goosby, E
Yates, R
AF Gupta, Vin
Kerry, Vanessa B.
Goosby, Eric
Yates, Robert
TI Politics and Universal Health Coverage - The Post-2015 Global Health
Agenda
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Gupta, Vin] Univ Cambridge, Dept Polit & Int Studies, Cambridge, England.
[Yates, Robert] Royal Inst Int Affairs, London, England.
[Gupta, Vin; Kerry, Vanessa B.] Brigham & Womens Hosp, Dept Pulm & Crit Care Med, Boston, MA 02115 USA.
[Kerry, Vanessa B.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Kerry, Vanessa B.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Kerry, Vanessa B.] Seed Global Hlth, Boston, MA USA.
[Goosby, Eric] Univ Calif San Francisco, Ctr Implementat Sci, San Francisco, CA 94143 USA.
RP Gupta, V (reprint author), Univ Cambridge, Dept Polit & Int Studies, Cambridge, England.
NR 5
TC 3
Z9 3
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 SEP 24
PY 2015
VL 373
IS 13
BP 1189
EP 1192
DI 10.1056/NEJMp1508807
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200003
PM 26376044
ER
PT J
AU Lokhorst, HM
Plesner, T
Laubach, JP
Nahi, H
Gimsing, P
Hansson, M
Minnema, MC
Lassen, U
Krejcik, J
Palumbo, A
van de Donk, NWCJ
Ahmadi, T
Khan, I
Uhlar, CM
Wang, J
Sasser, AK
Losic, N
Lisby, S
Basse, L
Brun, N
Richardson, PG
AF Lokhorst, H. M.
Plesner, T.
Laubach, J. P.
Nahi, H.
Gimsing, P.
Hansson, M.
Minnema, M. C.
Lassen, U.
Krejcik, J.
Palumbo, A.
van de Donk, N. W. C. J.
Ahmadi, T.
Khan, I.
Uhlar, C. M.
Wang, J.
Sasser, A. K.
Losic, N.
Lisby, S.
Basse, L.
Brun, N.
Richardson, P. G.
TI Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; MULTICENTER; BORTEZOMIB;
ELOTUZUMAB; SAR650984; THERAPIES; SURVIVAL; PROTEIN; CELLS
AB BACKGROUND
Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1 kappa monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.
METHODS
In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics.
RESULTS
No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in >= 5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months.
CONCLUSIONS
Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.)
C1 [Lokhorst, H. M.; Minnema, M. C.; van de Donk, N. W. C. J.] Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands.
[Lokhorst, H. M.; van de Donk, N. W. C. J.] Vrije Univ Amsterdam Med Ctr, Dept Hematol, NL-1081 HV Amsterdam, Netherlands.
[Plesner, T.; Krejcik, J.] Vejle Hosp, Vejle, Denmark.
[Plesner, T.; Krejcik, J.] Univ Southern Denmark, Vejle, Denmark.
[Gimsing, P.; Lassen, U.] Rigshosp, DK-2100 Copenhagen, Denmark.
[Gimsing, P.; Lassen, U.] Univ Copenhagen, Copenhagen, Denmark.
[Losic, N.; Lisby, S.; Basse, L.; Brun, N.] Genmab, Copenhagen, Denmark.
[Laubach, J. P.; Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Nahi, H.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Stockholm, Sweden.
[Nahi, H.] Karolinska Univ Hosp Huddinge, Dept Med, Div Hematol, Stockholm, Sweden.
[Hansson, M.] Skane Univ Hosp, Lund, Sweden.
[Hansson, M.] Lund Univ, Lund, Sweden.
[Palumbo, A.] Univ Turin, Div Hematol, Myeloma Unit, Turin, Italy.
[Ahmadi, T.; Uhlar, C. M.; Sasser, A. K.] Janssen Res & Dev, Spring House, PA USA.
[Khan, I.; Wang, J.] Janssen Res & Dev, Raritan, NJ USA.
RP Lokhorst, HM (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Hematol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM h.lokhorst@vumc.nl
OI Lassen, Ulrik/0000-0002-3865-4574; Krejcik, Jakub/0000-0003-1833-583X;
nahi, hareth/0000-0003-4711-5094
FU Janssen Research and Development; Genmab
FX Funded by Janssen Research and Development and Genmab
NR 24
TC 137
Z9 139
U1 7
U2 17
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 SEP 24
PY 2015
VL 373
IS 13
BP 1207
EP 1219
DI 10.1056/NEJMoa1506348
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200006
PM 26308596
ER
PT J
AU Raje, N
Longo, DL
AF Raje, Noopur
Longo, Dan L.
TI Monoclonal Antibodies in Multiple Myeloma Come of Age
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID THERAPY
C1 [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Raje, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 10
TC 9
Z9 10
U1 0
U2 4
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 SEP 24
PY 2015
VL 373
IS 13
BP 1264
EP 1266
DI 10.1056/NEJMe1509419
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200014
PM 26308594
ER
PT J
AU Larkin, J
Hodi, FS
Wolchok, JD
AF Larkin, James
Hodi, F. Stephen
Wolchok, Jedd D.
TI Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England.
[Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Larkin, J (reprint author), Royal Marsden Hosp, London SW3 6JJ, England.
EM wolchokj@mskcc.org
NR 1
TC 34
Z9 36
U1 5
U2 17
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 SEP 24
PY 2015
VL 373
IS 13
BP 1270
EP 1271
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR8WP
UT WOS:000361635200017
PM 26398076
ER
PT J
AU De Los Angeles, A
Ferrari, F
Xi, RB
Fujiwara, Y
Benvenisty, N
Deng, HK
Hochedlinger, K
Jaenisch, R
Lee, S
Leitch, HG
Lensch, MW
Lujan, E
Pei, DQ
Rossant, J
Wernig, M
Park, PJ
Daley, GQ
AF De Los Angeles, Alejandro
Ferrari, Francesco
Xi, Ruibin
Fujiwara, Yuko
Benvenisty, Nissim
Deng, Hongkui
Hochedlinger, Konrad
Jaenisch, Rudolf
Lee, Soohyun
Leitch, Harry G.
Lensch, M. William
Lujan, Ernesto
Pei, Duanqing
Rossant, Janet
Wernig, Marius
Park, Peter J.
Daley, George Q.
TI Hallmarks of pluripotency
SO NATURE
LA English
DT Review
ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; GROUND-STATE PLURIPOTENCY;
X-CHROMOSOME INACTIVATION; DNA METHYLATION; TRANSCRIPTIONAL NETWORK;
REGULATORY CIRCUITRY; ISOLATED BLASTOMERES; NAIVE PLURIPOTENCY;
CULTURE-CONDITIONS
AB Stem cells self-renew and generate specialized progeny through differentiation, but vary in the range of cells and tissues they generate, a property called developmental potency. Pluripotent stem cells produce all cells of an organism, while multipotent or unipotent stem cells regenerate only specific lineages or tissues. Defining stem-cell potency relies upon functional assays and diagnostic transcriptional, epigenetic and metabolic states. Here we describe functional and molecular hallmarks of pluripotent stem cells, propose a checklist for their evaluation, and illustrate how forensic genomics can validate their provenance.
C1 [De Los Angeles, Alejandro; Fujiwara, Yuko; Lensch, M. William; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Lensch, M. William; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Lensch, M. William; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Hochedlinger, Konrad; Lensch, M. William; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Hochedlinger, Konrad; Lensch, M. William; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Ferrari, Francesco; Xi, Ruibin; Hochedlinger, Konrad; Lee, Soohyun; Park, Peter J.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02115 USA.
[Xi, Ruibin] Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China.
[Xi, Ruibin] Peking Univ, Ctr Stat Sci, Beijing 100871, Peoples R China.
[Benvenisty, Nissim] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, Stem Cell Unit, IL-91904 Jerusalem, Israel.
[Deng, Hongkui] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
[Deng, Hongkui] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
[Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA.
[Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Leitch, Harry G.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England.
[Lujan, Ernesto; Wernig, Marius] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Pei, Duanqing] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China.
[Rossant, Janet] Hosp Sick Children, Res Inst, Toronto, ON M5G 0A4, Canada.
RP Daley, GQ (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
RI Ferrari, Francesco/H-5007-2012;
OI Ferrari, Francesco/0000-0002-9811-3753; Rossant,
Janet/0000-0002-3731-5466
FU Howard Hughes Medical Institute
NR 112
TC 43
Z9 43
U1 9
U2 68
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 SEP 24
PY 2015
VL 525
IS 7570
BP 469
EP 478
DI 10.1038/nature15515
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KI
UT WOS:000361599900041
PM 26399828
ER
PT J
AU De Los Angeles, A
Ferrari, F
Fujiwara, Y
Mathieu, R
Lee, S
Lee, S
Tu, HC
Ross, S
Chou, S
Nguyen, M
Wu, ZT
Theunissen, TW
Powell, BE
Imsoonthornruksa, S
Chen, JK
Borkent, M
Krupalnik, V
Lujan, E
Wernig, M
Hanna, JH
Hochedlinger, K
Pei, DQ
Jaenisch, R
Deng, HK
Orkin, SH
Park, PJ
Daley, GQ
AF De Los Angeles, Alejandro
Ferrari, Francesco
Fujiwara, Yuko
Mathieu, Ronald
Lee, Soohyun
Lee, Semin
Tu, Ho-Chou
Ross, Samantha
Chou, Stephanie
Minh Nguyen
Wu, Zhaoting
Theunissen, Thorold W.
Powell, Benjamin E.
Imsoonthornruksa, Sumeth
Chen, Jiekai
Borkent, Marti
Krupalnik, Vladislav
Lujan, Ernesto
Wernig, Marius
Hanna, Jacob H.
Hochedlinger, Konrad
Pei, Duanqing
Jaenisch, Rudolf
Deng, Hongkui
Orkin, Stuart H.
Park, Peter J.
Daley, George Q.
TI Failure to replicate the STAP cell phenomenon
SO NATURE
LA English
DT Letter
ID PLURIPOTENT STEM-CELLS; SEE VOL. 511; SOMATIC-CELLS; PG. 112
C1 [De Los Angeles, Alejandro; Fujiwara, Yuko; Tu, Ho-Chou; Ross, Samantha; Chou, Stephanie; Minh Nguyen; Wu, Zhaoting; Orkin, Stuart H.; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Tu, Ho-Chou; Ross, Samantha; Chou, Stephanie; Minh Nguyen; Wu, Zhaoting; Orkin, Stuart H.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Tu, Ho-Chou; Ross, Samantha; Chou, Stephanie; Minh Nguyen; Wu, Zhaoting; Borkent, Marti; Hochedlinger, Konrad; Orkin, Stuart H.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[De Los Angeles, Alejandro; Fujiwara, Yuko; Tu, Ho-Chou; Ross, Samantha; Chou, Stephanie; Minh Nguyen; Wu, Zhaoting; Borkent, Marti; Hochedlinger, Konrad; Orkin, Stuart H.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Ferrari, Francesco; Lee, Soohyun; Lee, Semin; Park, Peter J.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02115 USA.
[Mathieu, Ronald] Childrens Hosp Boston, Childrens Hosp, Boston, MA 02115 USA.
[Mathieu, Ronald] Childrens Hosp Boston, Harvard Stem Cell Inst Flow Cytometry Res Facil, Boston, MA 02115 USA.
[Theunissen, Thorold W.; Powell, Benjamin E.; Imsoonthornruksa, Sumeth; Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Chen, Jiekai] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China.
[Borkent, Marti; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Borkent, Marti; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA.
[Borkent, Marti] Erasmus MC, Dept Dev & Reprod, NL-3015 CN Rotterdam, Netherlands.
[Krupalnik, Vladislav; Hanna, Jacob H.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
[Lujan, Ernesto; Wernig, Marius] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Deng, Hongkui] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
[Deng, Hongkui] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
RP De Los Angeles, A (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
EM peter_park@hms.harvard.edu
RI Ferrari, Francesco/H-5007-2012; HANNA, JACOB/K-1339-2012; Lee,
Semin/S-2629-2016
OI Ferrari, Francesco/0000-0002-9811-3753; HANNA,
JACOB/0000-0003-2042-9974; Lee, Semin/0000-0002-9015-6046
FU Howard Hughes Medical Institute
NR 14
TC 11
Z9 11
U1 2
U2 43
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 SEP 24
PY 2015
VL 525
IS 7570
BP E6
EP +
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8KI
UT WOS:000361599900009
PM 26399835
ER
PT J
AU Mesgari, M
Ghaffarian, N
Ghadiri, MK
Sadeghian, H
Speckmann, EJ
Stummer, W
Gorji, A
AF Mesgari, M.
Ghaffarian, N.
Ghadiri, M. Khaleghi
Sadeghian, H.
Speckmann, E. -J.
Stummer, W.
Gorji, A.
TI ALTERED INHIBITION IN THE HIPPOCAMPAL NEURAL NETWORKS AFTER SPREADING
DEPRESSION
SO NEUROSCIENCE
LA English
DT Article
DE spreading depolarization; epilepsy; migraine; stroke; hippocampus;
disinhibition
ID CEREBRAL-CORTEX; SYNAPTIC-TRANSMISSION; GABAERGIC NEURONS; PYRAMIDAL
NEURONS; RAT NEOCORTEX; TISSUE-SLICES; IN-VITRO; GABA; CA1; GABAPENTIN
AB Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra-and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of c-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. The results revealed that SD decreased the degree of PPD, enhanced the number and duration of bicuculline-induced afterdischarges, and reduced the amplitude and duration of IPSPs. Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Mesgari, M.; Ghaffarian, N.; Speckmann, E. -J.; Gorji, A.] Univ Munster, Epilepsy Res Ctr, D-48149 Munster, Germany.
[Ghadiri, M. Khaleghi; Stummer, W.] Univ Munster, Dept Neurosurg, D-48149 Munster, Germany.
[Sadeghian, H.] Harvard Univ, Massachusetts Gen Hosp, Neurovasc Res Lab, Dept Radiol,Med Sch, Charlestown, MA USA.
[Gorji, A.] Univ Munster, Dept Neurol, D-48149 Munster, Germany.
[Gorji, A.] Univ Munster, Inst Neurophysiol, D-48149 Munster, Germany.
[Gorji, A.] Khatam Alanbia Hosp, Shefa Neurosci Res Ctr, Tehran, Iran.
[Gorji, A.] Razavi Hosp, Razavi Neurosci Ctr, Mashhad, Iran.
RP Gorji, A (reprint author), Univ Munster, Epilepsy Res Ctr, Robert Koch Str 27a, D-48149 Munster, Germany.
EM gorjial@uni-muenster.de
OI Gorji, Ali/0000-0002-4557-3270
FU Iran National Science Foundation (INSF); Shefa Neuroscience Research
Center [267201]
FX This article was part of PhD thesis supported by Iran National Science
Foundation (INSF) and the Shefa Neuroscience Research Center Grant
related to Dr Thesis 267201.
NR 48
TC 2
Z9 2
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 24
PY 2015
VL 304
BP 190
EP 197
DI 10.1016/j.neuroscience.2015.07.035
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CP6PD
UT WOS:000360008800017
PM 26210578
ER
PT J
AU Sanders, SJ
Xin, H
Willsey, AJ
Ercan-Sencicek, AG
Samocha, KE
Cicek, AE
Murtha, MT
Bal, VH
Bishop, SL
Shan, D
Goldberg, AP
Cai, JL
Keaney, JF
Klei, L
Mandell, JD
Moreno-De-Luca, D
Poultney, CS
Robinson, EB
Smith, L
Solli-Nowlan, T
Su, MY
Teran, NA
Walker, MF
Werling, DM
Beaudet, AL
Cantor, RM
Fombonne, E
Geschwind, DH
Grice, DE
Lord, C
Lowe, JK
Mane, SM
Martin, DM
Morrow, EM
Talkowski, ME
Sutcliffe, JS
Walsh, CA
Yu, TW
Ledbetter, DH
Martin, CL
Cook, EH
Buxbaum, JD
Daly, MJ
Devlin, B
Roeder, K
State, MW
AF Sanders, Stephan J.
Xin He
Willsey, A. Jeremy
Ercan-Sencicek, A. Gulhan
Samocha, Kaitlin E.
Cicek, A. Ercument
Murtha, Michael T.
Bal, Vanessa H.
Bishop, Somer L.
Shan Dong
Goldberg, Arthur P.
Cai Jinlu
Keaney, John F., III
Klei, Lambertus
Mandell, Jeffrey D.
Moreno-De-Luca, Daniel
Poultney, Christopher S.
Robinson, Elise B.
Smith, Louw
Solli-Nowlan, Tor
Su, Mack Y.
Teran, Nicole A.
Walker, Michael F.
Werling, Donna M.
Beaudet, Arthur L.
Cantor, Rita M.
Fombonne, Eric
Geschwind, Daniel H.
Grice, Dorothy E.
Lord, Catherine
Lowe, Jennifer K.
Mane, Shrikant M.
Martin, Donna M.
Morrow, Eric M.
Talkowski, Michael E.
Sutcliffe, James S.
Walsh, Christopher A.
Yu, Timothy W.
Ledbetter, David H.
Martin, Christa Lese
Cook, Edwin H.
Buxbaum, Joseph D.
Daly, Mark J.
Devlin, Bernie
Roeder, Kathryn
State, Matthew W.
CA Autism Sequencing Consortium
TI Insights into Autism Spectrum Disorder Genomic Architecture and Biology
from 71 Risk Loci
SO NEURON
LA English
DT Article
ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; HIDDEN-MARKOV MODEL; SNP
GENOTYPING DATA; TRUNCATING MUTATIONS; STRUCTURAL VARIATION;
WILLIAMS-SYNDROME; SIMPLEX AUTISM; GENE; RARE
AB Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR <= 0.1).
C1 [Sanders, Stephan J.; Willsey, A. Jeremy; Bal, Vanessa H.; Bishop, Somer L.; Mandell, Jeffrey D.; Smith, Louw; Walker, Michael F.; Werling, Donna M.; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Xin He] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Ercan-Sencicek, A. Gulhan; Murtha, Michael T.] Yale Univ, Program Neurogenet, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA.
[Samocha, Kaitlin E.; Robinson, Elise B.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Samocha, Kaitlin E.; Robinson, Elise B.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Samocha, Kaitlin E.; Robinson, Elise B.; Daly, Mark J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Samocha, Kaitlin E.; Robinson, Elise B.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Genet & Genom, Biol & Biomed Sci, Boston, MA 02114 USA.
[Cicek, A. Ercument] Carnegie Mellon Univ, Computat Biol Dept, Pittsburgh, PA 15213 USA.
[Cicek, A. Ercument] Bilkent Univ, Dept Comp Engn, TR-0680 Ankara, Turkey.
[Shan Dong] Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
[Goldberg, Arthur P.; Cai Jinlu; Poultney, Christopher S.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
[Goldberg, Arthur P.; Cai Jinlu; Poultney, Christopher S.; Grice, Dorothy E.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Keaney, John F., III] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA.
[Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Moreno-De-Luca, Daniel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA.
[Solli-Nowlan, Tor] TheLab Inc, Los Angeles, CA 90068 USA.
[Su, Mack Y.] Harvard Univ, Program Biophys, Boston, MA 02115 USA.
[Teran, Nicole A.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Beaudet, Arthur L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA.
[Geschwind, Daniel H.; Lowe, Jennifer K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Semel Inst,Neurogenet Program, Los Angeles, CA 90095 USA.
[Geschwind, Daniel H.; Lowe, Jennifer K.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst, Los Angeles, CA 90095 USA.
[Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Dev Brain, White Plains, NY 10605 USA.
[Mane, Shrikant M.] Yale Univ, Sch Med, Yale Ctr Genom Anal, New Haven, CT 06520 USA.
[Martin, Donna M.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Martin, Donna M.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA.
[Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Mol Neurosci, Nashville, TN 37232 USA.
[Walsh, Christopher A.; Yu, Timothy W.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Walsh, Christopher A.; Yu, Timothy W.] Childrens Hosp Boston, Div Genet & Genom, Boston, MA 02115 USA.
[Walsh, Christopher A.; Yu, Timothy W.] Harvard Univ, Sch Med, Ctr Life Sci, Neurol & Pediat, Boston, MA 02115 USA.
[Ledbetter, David H.; Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA 17822 USA.
[Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60637 USA.
[Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
RP Sanders, SJ (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM stephan.sanders@ucsf.edu; matthew.state@ucsf.edu
OI Robinson, Elise/0000-0003-2314-2792; Sutcliffe,
James/0000-0001-5200-6007; Sanders, Stephan/0000-0001-9112-5148;
Buxbaum, Joseph/0000-0001-8898-8313; Yu, Timothy/0000-0003-2988-7701
FU Simons Foundation (SFARI) [124827, 307705]; National Institute for
Health/National Institute for Mental Health [MH100233, MH100229,
MH100239, MH057881, MH100209, DC009410, MH074090, MH071584-07,
MH19961-14]; Donita B. Sullivan MD Research Professorship funds; Howard
Hughes Medical Institute (International Student Research Fellowship);
Canadian Institutes of Health Research (Doctoral Foreign Study Award);
ADOS; ADI-R from Western Psychological Services
FX We are grateful to all the families participating in this research,
including the Simons Foundation Autism Research Initiative (SFARI)
Simplex Collection (SSC), the Autism Sequencing Consortium (ASC), and
the Autism Genome Project (AGP). This work was supported by grants from
the Simons Foundation (SFARI # 124827 to M.W.S. and SFARI #307705 to
S.J.S.), the National Institute for Health/National Institute for Mental
Health (MH100233 to J.D.B., MH100229 to M.J.D., MH100239 to M.W.S.,
MH057881 and MH100209 to B.D., DC009410 to D.M.M., MH074090 to D.H.L.
and C.L.M., and MH071584-07 and MH19961-14 supporting D.M.M.), Donita B.
Sullivan MD Research Professorship funds to D.M.M., the Howard Hughes
Medical Institute (International Student Research Fellowship to S.J.S.),
and the Canadian Institutes of Health Research (Doctoral Foreign Study
Award to A.J.W.). C.L. receives royalties for the ADOS and ADI-R from
Western Psychological Services; royalties related to this project are
donated to charities. We would like to thank the SSC principal
investigators (A.L. Beaudet, R. Bernier, J. Constantino, E.H. Cook, Jr,
E. Fombonne, D. Geschwind, D. E. Grice, A. Klin, D.H. Ledbetter, C.
Lord, C.L. Martin, D.M. Martin, R. Maxim, J. Miles, O. Ousley, B.
Peterson, J. Piggot, C. Saulnier, M.W. State, W. Stone, J.S. Sutcliffe,
C. A. Walsh, and E. Wijsman) and the coordinators and staff at the SSC
clinical sites; the SFARI staff, in particular M. Benedetti; the Rutgers
University Cell and DNA repository for accessing biomaterials; the Yale
Center of Genomic Analysis for SNP genotyping data; and I. Hart and X.
Sanders for their unwavering support. D.H.L. acts as a consultant to
Natera, Inc.
NR 65
TC 86
Z9 86
U1 8
U2 34
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD SEP 23
PY 2015
VL 87
IS 6
BP 1215
EP 1233
DI 10.1016/j.neuron.2015.09.016
PG 19
WC Neurosciences
SC Neurosciences & Neurology
GA CU8HJ
UT WOS:000363782200012
PM 26402605
ER
PT J
AU Buckholtz, JW
Martin, JW
Treadway, MT
Jan, K
Zald, DH
Jones, O
Marois, R
AF Buckholtz, Joshua W.
Martin, Justin W.
Treadway, Michael T.
Jan, Katherine
Zald, David H.
Jones, Owen
Marois, Rene
TI From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals
Norm Enforcement Mechanisms
SO NEURON
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; WORKING-MEMORY; MORAL JUDGMENT;
ULTIMATUM GAME; 3RD-PARTY PUNISHMENT; COSTLY PUNISHMENT; HUMAN
COOPERATION; NEURAL CIRCUITRY; DECISION-MAKING; SOCIAL NORMS
AB The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and fMRI to determine the specific role of DLPFC function in norm-enforcement behavior. DLPFC rTMS reduced punishment for wrongful acts without affecting blameworthiness ratings, and fMRI revealed punishment-selective DLPFC recruitment, suggesting that these two facets of norm-based decision making are neurobiologically dissociable. Finally, we show that DLPFC rTMS affects punishment decision making by altering the integration of information about culpability and harm. Together, these findings reveal a selective, causal role for DLPFC in norm enforcement: representational integration of the distinct information streams used to make punishment decisions.
C1 [Buckholtz, Joshua W.; Martin, Justin W.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Buckholtz, Joshua W.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Martin, Justin W.; Jan, Katherine; Zald, David H.; Marois, Rene] Vanderbilt Univ, Dept Psychol, Nashville, TN 37235 USA.
[Zald, David H.; Jones, Owen; Marois, Rene] Vanderbilt Univ, Ctr Integrat & Cognit Neurosci, Nashville, TN 37235 USA.
[Jones, Owen] Vanderbilt Univ, Sch Law, Nashville, TN 37235 USA.
[Jones, Owen] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
[Treadway, Michael T.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Buckholtz, Joshua W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Buckholtz, JW (reprint author), Harvard Univ, Dept Psychol, 52 Oxford St, Cambridge, MA 02138 USA.
EM joshua_buckholtz@harvard.edu; rene.marois@vanderbilt.edu
FU John D. and Catherine T. MacArthur Foundation; University of California
at Santa Barbara; Vanderbilt's Center for Integrative and Cognitive
Neuroscience; NIMH [T32MH018921, T32MH064913]; National Institute on
Drug Abuse [1R03DA034126-01]; Sloan Foundation; Brain and Behavior
Research Foundation; MGH Center for Law, Brain, and Behavior
FX We wish to thank Brian Essex for assistance with the rTMS localization
protocol, Randolph Blake for kindly making available TMS equipment, and
Ashley Schwartzman for assistance with rTMS sessions. We are grateful to
Fiery Cushman, Liane Young, and Joshua Green for comments on this
manuscript. This study was supported by a grant from the John D. and
Catherine T. MacArthur Foundation to Vanderbilt University and the
University of California at Santa Barbara and by Vanderbilt's Center for
Integrative and Cognitive Neuroscience. Its contents do not necessarily
represent the official views of either the John D. and Catherine T.
MacArthur Foundation or the MacArthur Foundation Research Network on Law
and Neuroscience (http://www.lawneuro.org). J.W.B. was supported by the
NIMH (T32MH018921 and T32MH064913), the National Institute on Drug Abuse
(1R03DA034126-01), the Sloan Foundation, the Brain and Behavior Research
Foundation, and the MGH Center for Law, Brain, and Behavior.
NR 72
TC 7
Z9 7
U1 7
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD SEP 23
PY 2015
VL 87
IS 6
BP 1369
EP 1380
DI 10.1016/j.neuron.2015.08.023
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA CU8HJ
UT WOS:000363782200023
PM 26386518
ER
PT J
AU Baca, CB
Barkley, GL
AF Baca, Christine B.
Barkley, Gregory L.
TI Can big data help us close an epilepsy care gap?
SO NEUROLOGY
LA English
DT Editorial Material
ID DISPARITIES; OUTCOMES; PEOPLE
AB Epilepsy has been termed an ambulatory care sensitive condition, meaning that high-quality outpatient epilepsy care can reduce unnecessary emergency department (ED) visits and hospitalizations. Using this framework, high ED use is a marker of poor disease control or limited access to care.(1) Do all people with epilepsy (PWE) with poorly controlled disease or limited access frequent the ED? Are other factors at play? In this changing health care landscape, with accountable care organizations and a need to reduce costs, can we predict PWE who are at high risk of frequent ED use?
C1 [Baca, Christine B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Baca, Christine B.] Vet Adm Greater Los Angeles, Dept Neurol, Los Angeles, CA USA.
[Barkley, Gregory L.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA.
[Barkley, Gregory L.] Wayne State Univ, Sch Med, Detroit, MI USA.
RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
EM cbower@mednet.ucla.edu
NR 8
TC 0
Z9 0
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD SEP 22
PY 2015
VL 85
IS 12
BP 1014
EP 1015
DI 10.1212/WNL.0000000000001961
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CX3CG
UT WOS:000365572500002
PM 26311744
ER
PT J
AU Ott, PA
Hodi, FS
Buchbinder, EI
AF Ott, Patrick A.
Hodi, F. Stephen
Buchbinder, Elizabeth I.
TI Inhibition of immune checkpoints and vascular endothelial growth factor
as combination therapy for metastatic melanoma: an overview of
rationale, preclinical evidence, and initial clinical data
SO FRONTIERS IN ONCOLOGY
LA English
DT Review
DE PD-1 :PD-1L blockade; angiogenesis inhibitors; VEGF; melanoma;
immunotherapy
ID REGULATORY T-CELLS; STAGE IV MELANOMA; DENDRITIC CELLS;
CANCER-IMMUNOTHERAPY; UNTREATED MELANOMA; ANGIOGENIC FACTORS; FACTOR
RECEPTOR-1; PLUS IPILIMUMAB; FACTOR-TRAP; TUMOR
AB The role of angiogenesis as a mediator of immune regulation in the tumor microenvironment has recently come into focus. Furthermore, emerging evidence indicates that immunotherapy can lead to immune-mediated vasculopathy in the tumor, suggesting that the tumor vasculature may be an important interface between the tumor-directed immune response and the cancer itself. The advent of immune checkpoint inhibition as an effective immunotherapeutic strategy for many cancers has led to a better understanding of this interface. While the inhibition of angiogenesis through targeting of vascular endothelial growth factor (VEGF) has been used successfully for the treatment of cancer for many years, the mechanisms of its anti-tumor activity remain poorly understood. Initial studies of the complex relationship between angiogenesis, VEGF signaling and the immune system suggest that the combination of immune checkpoint blockade with angiogenesis inhibition has potential. While the majority of this work has been performed in metastatic melanoma, immunotherapy is rapidly showing promise in a broad range of malignancies and efforts to enhance immunotherapy will broadly impact the future of oncology. Here, we review the preclinical rationale and clinical investigations of combined angiogenesis inhibition and immunotherapy/immune checkpoint inhibition as a potentially promising combinatorial approach for cancer treatment.
C1 [Ott, Patrick A.; Hodi, F. Stephen; Buchbinder, Elizabeth I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr,Ctr Immunooncol,Dept Med Oncol, Boston, MA 02215 USA.
[Ott, Patrick A.; Hodi, F. Stephen; Buchbinder, Elizabeth I.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
RP Ott, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr,Ctr Immunooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM patrick_ott@dfci.harvard.edu
NR 55
TC 16
Z9 16
U1 1
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD SEP 22
PY 2015
VL 5
AR 202
DI 10.3389/fonc.2015.00202
PG 7
WC Oncology
SC Oncology
GA CW6UL
UT WOS:000365133400001
PM 26442214
ER
PT J
AU Yuan, KY
Yong, S
Xu, F
Zhou, T
McDonald, JM
Chen, YB
AF Yuan, Kaiyu
Yong, Sun
Xu, Fei
Zhou, Tong
McDonald, Jay M.
Chen, Yabing
TI Calmodulin antagonists promote TRA-8 therapy of resistant pancreatic
cancer
SO ONCOTARGET
LA English
DT Article
DE death receptor 5; apoptosis; resistance; calmodulin antagonists;
pancreatic cancer
ID APOPTOSIS-INDUCING LIGAND; TUMOR-NECROSIS-FACTOR; TRAIL-INDUCED
APOPTOSIS; DEATH RECEPTOR EXPRESSION; MEDIATED APOPTOSIS;
MONOCLONAL-ANTIBODY; SIGNALING COMPLEX; HEPATOMA-CELLS; IN-VITRO;
ACTIVATION
AB Pancreatic cancer is highly malignant with limited therapy and a poor prognosis. TRAIL-activating therapy has been promising, however, clinical trials have shown resistance and limited responses of pancreatic cancers. We investigated the effects of calmodulin(CaM) antagonists, trifluoperazine(TFP) and tamoxifen(TMX), on TRA-8-induced apoptosis and tumorigenesis of TRA-8-resistant pancreatic cancer cells, and underlying mechanisms. TFP or TMX alone did not induce apoptosis of resistant PANC-1 cells, while they dose-dependently enhanced TRA-8-induced apoptosis. TMX treatment enhanced efficacy of TRA-8 therapy on tumorigenesis in vivo. Analysis of TRA-8-induced death-inducing-signaling-complex (DISC) identified recruitment of survival signals, CaM/Src, into DR5-associated DISC, which was inhibited by TMX/TFP. In contrast, TMX/TFP increased TRA-8-induced DISC recruitment/activation of caspase-8. Consistently, caspase-8 inhibition blocked the effects of TFP/TMX on TRA-8-induced apoptosis. Moreover, TFP/TMX induced DR5 expression. With a series of deletion/point mutants, we identified CaM antagonist-responsive region in the putative Sp1-binding domain between -295 to -300 base pairs of DR5 gene. Altogether, we have demonstrated that CaM antagonists enhance TRA-8-induced apoptosis of TRA-8-resistant pancreatic cancer cells by increasing DR5 expression and enhancing recruitment of apoptotic signal while decreasing survival signals in DR5-associated DISC. Our studies support the use of these readily available CaM antagonists combined with TRAIL-activating agents for pancreatic cancer therapy.
C1 [Yuan, Kaiyu; Yong, Sun; Xu, Fei; McDonald, Jay M.; Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Zhou, Tong] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[McDonald, Jay M.; Chen, Yabing] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA.
RP Chen, YB (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
EM ybchen@uab.edu
FU VA Merit Review Awards [BX000311, BX002296]
FX This work was supported by VA Merit Review Awards BX000311 (JMM) and
BX002296 (YC).
NR 50
TC 0
Z9 0
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP 22
PY 2015
VL 6
IS 28
BP 25308
EP 25319
DI 10.18632/oncotarget.4490
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT9TS
UT WOS:000363160100062
PM 26320171
ER
PT J
AU Boros, K
Puissant, A
Back, M
Alexe, G
Bassil, CF
Sinha, P
Tholouli, E
Stegmaier, K
Byers, RJ
Rodig, SJ
AF Boros, Katalin
Puissant, Alexandre
Back, Morgan
Alexe, Gabriela
Bassil, Christopher F.
Sinha, Papiya
Tholouli, Eleni
Stegmaier, Kimberly
Byers, Richard J.
Rodig, Scott J.
TI Increased SYK activity is associated with unfavorable outcome among
patients with acute myeloid leukemia
SO ONCOTARGET
LA English
DT Article
DE SYK tyrosine kinase; AML; poor prognosis; tissue microarray; clinical
trials
ID ACTIVATION LOOP TYROSINES; IN-VIVO; KINASE INHIBITOR; MUTATIONS;
NETWORKS
AB Recent discoveries have led to the testing of novel targeted therapies for the treatment of acute myeloid leukemia (AML). To better inform the results of clinical trials, there is a need to identify and systematically assess biomarkers of response and pharmacodynamic markers of successful target engagement. Spleen tyrosine kinase (SYK) is a candidate therapeutic target in AML. Small-molecule inhibitors of SYK induce AML differentiation and impair leukemia progression in preclinical studies. However, tools to predict response to SYK inhibition and to routinely evaluate SYK activation in primary patient samples have been lacking. In this study we quantified phosphorylated SYK (P-SYK) in AML cell lines and establish that increasing levels of baseline P-SYK are correlated with an increasing sensitivity to small-molecule inhibitors targeting SYK. In addition, we found that pharmacological inhibition of SYK activity extinguishes P-SYK expression as detected by an immunohistochemical (IHC) test. Quantitative analysis of P-SYK expression by the IHC test in a series of 70 primary bone marrow biopsy specimens revealed a spectrum of P-SYK expression across AML cases and that high P-SYK expression is associated with unfavourable outcome independent of age, cytogenetics, and white blood cell count. This study thus establishes P-SYK as a critical biomarker in AML that identifies tumors sensitive to SYK inhibition, identifies an at-risk patient population, and allows for the monitoring of target inhibition during treatment.
C1 [Boros, Katalin] Manchester Royal Infirm, Dept Histopathol, Manchester M13 9WL, Lancs, England.
[Puissant, Alexandre; Alexe, Gabriela; Bassil, Christopher F.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Puissant, Alexandre; Alexe, Gabriela; Bassil, Christopher F.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA.
[Puissant, Alexandre] Fac Med Nice, INSERM, U1065, C3M,Team 2, F-06034 Nice, France.
[Back, Morgan] Univ Manchester, Sch Med, Manchester, Lancs, England.
[Sinha, Papiya; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Tholouli, Eleni] Manchester Royal Infirm, Dept Haematol, Manchester M13 9WL, Lancs, England.
[Byers, Richard J.] Univ Manchester, Inst Canc Sci, Manchester, Lancs, England.
RP Byers, RJ (reprint author), Univ Manchester, Inst Canc Sci, Manchester, Lancs, England.
EM richard.byers@cmft.nhs.uk
RI PUISSANT, ALEXANDRE/O-9575-2016;
OI PUISSANT, ALEXANDRE/0000-0002-3997-9282; Byers,
Richard/0000-0003-0796-0365
FU National Cancer Institute [R01 CA140292]; American Cancer Society; Starr
Cancer Consortium
FX This research was supported with grants from the National Cancer
Institute (R01 CA140292), the American Cancer Society and the Starr
Cancer Consortium (KS). KS is a Leukemia and Lymphoma Society Scholar
and AP is a Leukemia and Lymphoma Society Fellow. AP received the "Prix
Jeune Chercheur" of the Bettencourt foundation.
NR 23
TC 2
Z9 2
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP 22
PY 2015
VL 6
IS 28
BP 25575
EP 25587
DI 10.18632/oncotarget.4669
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT9TS
UT WOS:000363160100080
PM 26315286
ER
PT J
AU Balasubramanian, K
Maeda, A
Lee, JS
Mohammadyani, D
Dar, HH
Jiang, JF
Croix, CMS
Watkins, S
Tyurin, VA
Tyurina, YY
Kloditz, K
Polimova, A
Kapralova, VI
Xiong, ZY
Ray, P
Klein-Seetharaman, J
Mallampalli, RK
Bayir, H
Fadeel, B
Kagan, VE
AF Balasubramanian, Krishnakumar
Maeda, Akihiro
Lee, Janet S.
Mohammadyani, Dariush
Dar, Haider Hussain
Jiang, Jian Fei
Croix, Claudette M. St.
Watkins, Simon
Tyurin, Vladimir A.
Tyurina, Yulia Y.
Kloeditz, Katharina
Polimova, Anastassia
Kapralova, Valentyna I.
Xiong, Zeyu
Ray, Prabir
Klein-Seetharaman, Judith
Mallampalli, Rama K.
Bayir, Huelya
Fadeel, Bengt
Kagan, Valerian E.
TI Dichotomous roles for externalized cardiolipin in extracellular
signaling: Promotion of phagocytosis and attenuation of innate immunity
SO SCIENCE SIGNALING
LA English
DT Article
ID APOPTOTIC CELLS; BACTERIAL LIPOPOLYSACCHARIDE; MACROPHAGE ACTIVATION;
SCAVENGER RECEPTORS; MEDIATED APOPTOSIS; CELLULAR MEMBRANES;
MOLECULAR-PATTERNS; ESCHERICHIA-COLI; MANNOSE RECEPTOR; STRUCTURAL BASIS
AB Among the distinct molecular signatures present in the mitochondrion is the tetra-acylated anionic phospholipid cardiolipin, a lipid also present in primordial, single-cell bacterial ancestors of mitochondria and multiple bacterial species today. Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy. Given the immunogenicity of mitochondrial and bacterial membranes that are released during sterile and pathogen-induced trauma, we hypothesized that cardiolipins might function as "eat me" signals for professional phagocytes. In experiments with macrophage cell lines and primary macrophages, we found that membranes with mitochondrial or bacterial cardiolipins on their surface were engulfed through phagocytosis, which depended on the scavenger receptor CD36. Distinct from this process, the copresentation of cardiolipin with the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide dampened TLR4-stimulated production of cytokines. These data suggest that externalized, extracellular cardiolipins play a dual role in host-host and host-pathogen interactions by promoting phagocytosis and attenuating inflammatory immune responses.
C1 [Balasubramanian, Krishnakumar; Mohammadyani, Dariush; Dar, Haider Hussain; Jiang, Jian Fei; Tyurin, Vladimir A.; Tyurina, Yulia Y.; Polimova, Anastassia; Kapralova, Valentyna I.; Bayir, Huelya; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Ctr Free Radical & Antioxidant Hlth, Pittsburgh, PA 15219 USA.
[Maeda, Akihiro; Kloeditz, Katharina; Fadeel, Bengt] Karolinska Inst, Inst Environm Med, Div Mol Toxicol, S-17177 Stockholm, Sweden.
[Lee, Janet S.; Xiong, Zeyu; Ray, Prabir] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Croix, Claudette M. St.; Watkins, Simon] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15261 USA.
[Klein-Seetharaman, Judith] Univ Warwick, Div Metab & Vasc Hlth, Coventry CV4 7AL, W Midlands, England.
[Mallampalli, Rama K.] Univ Pittsburgh, Dept Internal Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA.
[Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15215 USA.
[Bayir, Huelya] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA.
RP Balasubramanian, K (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, Ctr Free Radical & Antioxidant Hlth, Pittsburgh, PA 15219 USA.
EM kris.balasub@gmail.com; bengt.fadeel@ki.se; kagan@pitt.edu
OI Tyurin, Vladimir/0000-0002-3474-1697
FU NIH [PO1 HL114453, HL086884, U19AIO68021, ES020693, NS076511, NS061817,
CA165065]; Human Frontier Science Program [HFSP-RGP0013/2014]; Swedish
Research Council; NIH (NIOSH) [OH008282]; [P30CA047904]
FX This study was supported by grants from the NIH (PO1 HL114453, HL086884,
U19AIO68021, ES020693; NS076511, NS061817, CA165065; NIOSH OH008282),
the Human Frontier Science Program (HFSP-RGP0013/2014), the Swedish
Research Council, and a Core grant to the UPCI Cancer Biomarkers
Facility/Luminex Core Laboratory (P30CA047904).
NR 81
TC 11
Z9 11
U1 0
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD SEP 22
PY 2015
VL 8
IS 395
AR ra95
DI 10.1126/scisignal.aaa6179
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CU1YJ
UT WOS:000363318000002
PM 26396268
ER
PT J
AU Cummings, JL
Lyketsos, CG
Peskind, ER
Porsteinsson, AP
Mintzer, JE
Scharre, D
De La Gandara, JE
Agronin, M
Davis, CS
Nguyen, U
Shin, P
Tariot, PN
Siffert, J
AF Cummings, Jeffrey L.
Lyketsos, Constantine G.
Peskind, Elaine R.
Porsteinsson, Anton P.
Mintzer, Jacobo E.
Scharre, DouglasW.
De La Gandara, Jose E.
Agronin, Marc
Davis, Charles S.
Uyen Nguyen
Shin, Paul
Tariot, Pierre N.
Siffert, Joao
TI Effect of Dextromethorphan-Quinidine on Agitation in Patients With
Alzheimer Disease Dementia A Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PSEUDOBULBAR AFFECT; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL SYMPTOMS;
PLACEBO-RESPONSE; IN-VITRO; AGGRESSION; DESIGN; RECOMMENDATIONS;
PROGRESSION; MANAGEMENT
AB IMPORTANCE Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking.
OBJECTIVE To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation.
DESIGN, SETTING, AND PARTICIPANTS Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score >= 4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed.
INTERVENTIONS In stage 1, 220 patients were randomized in a 3: 4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1: 1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60).
MAIN OUTCOMES AND MEASURES The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]).
RESULTS A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo( ordinaryleastsquareszstatistic,-3.95; P < .001). In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. Between-groupt reatment differences were significantin stage 1(leasts quaresmean, -1.5; 95% CI, -2.3 to -0.7; P <. 001). In stage 2, NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. Between-group treatment differences were also significant in stage 2(least squares mean,-1.6; 95% CI,-2.9 to -0.3; P=.02). Adverseevents included falls (8.6% for dextromethorphan-quinidine vs3.9% for placebo), diarrhea (5.9% vs 3.1% respectively), and urinary tract infection (5.3% vs 3.9% respectively). Serious adverse events occurred in 7.9% with dextromethorphan-quinidine vs 4.7% with placebo. Dextromethorphan-quinidinewas not associated with cognitive impairment, sedation, or clinically significant QTc prolongation.
CONCLUSIONS AND RELEVANCE In this preliminary 10-week phase 2 randomized clinical trial of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated.
C1 [Cummings, Jeffrey L.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV 89106 USA.
[Lyketsos, Constantine G.] Johns Hopkins Bayview, Johns Hopkins Memory & Alzheimers Treatment Ctr, Baltimore, MD USA.
[Peskind, Elaine R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Mintzer, Jacobo E.] Roper St Francis Hosp, Clin Biotechnol Res Inst, Charleston, SC USA.
[Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Scharre, DouglasW.] Ohio State Univ, Columbus, OH 43210 USA.
[De La Gandara, Jose E.] Quantum Labs Inc, W Palm Beach, FL USA.
[Agronin, Marc] Miami Jewish Hlth Syst, Miami, FL USA.
[Davis, Charles S.] CSD Biostat Inc, Tucson, AZ USA.
[Uyen Nguyen; Shin, Paul; Siffert, Joao] Avanir Pharmaceut Inc, Aliso Viejo, CA USA.
[Tariot, Pierre N.] Banner Alzheimers Inst, Phoenix, AZ USA.
RP Cummings, JL (reprint author), Cleveland Clin, Lou Ruvo Ctr Brain Hlth, 888 W Bonneville Ave, Las Vegas, NV 89106 USA.
EM cumminj@ccf.org
FU Avanir Pharmaceuticals Inc.
FX This study was funded by Avanir Pharmaceuticals Inc.
NR 34
TC 16
Z9 16
U1 1
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 SEP 22
PY 2015
VL 314
IS 12
BP 1242
EP 1254
DI 10.1001/jama.2015.10214
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS5IE
UT WOS:000362110700013
PM 26393847
ER
PT J
AU D'Amico, AV
Chen, MH
Renshaw, A
Loffredo, M
Kantoff, PW
AF D'Amico, Anthony V.
Chen, Ming-Hui
Renshaw, Andrew
Loffredo, Marian
Kantoff, Philip W.
TI Long-term Follow-up of a Randomized Trial of Radiation With or Without
Androgen Deprivation Therapy for Localized Prostate Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [D'Amico, Anthony V.; Loffredo, Marian] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Renshaw, Andrew] Miami Baptist Hosp, Dept Pathol, Miami, FL USA.
[Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM adamico@partners.org
NR 6
TC 19
Z9 19
U1 0
U2 1
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 SEP 22
PY 2015
VL 314
IS 12
BP 1291
EP 1293
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS5IE
UT WOS:000362110700020
PM 26393854
ER
PT J
AU Huybrechts, KF
Bateman, BT
Hernandez-Diaz, S
AF Huybrechts, Krista F.
Bateman, Brian T.
Hernandez-Diaz, Sonia
TI Maternal Antidepressant Use and Persistent Pulmonary Hypertension of the
Newborn Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Hernandez-Diaz, Sonia] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
RP Huybrechts, KF (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA.
EM khuybrechts@partners.org
NR 2
TC 3
Z9 3
U1 0
U2 0
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 SEP 22
PY 2015
VL 314
IS 12
BP 1294
EP 1294
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS5IE
UT WOS:000362110700022
PM 26393857
ER
PT J
AU Fisichella, PM
AF Fisichella, P. Marco
TI Treating Hoarseness With Proton Pump Inhibitors Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID REFLUX
C1 [Fisichella, P. Marco] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA.
RP Fisichella, PM (reprint author), Harvard Med Sch, Boston VA Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM piero.fisichella@va.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD SEP 22
PY 2015
VL 314
IS 12
BP 1295
EP 1296
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CS5IE
UT WOS:000362110700024
PM 26393858
ER
PT J
AU Lee, S
Lee, MJ
Kim, BW
Gilman, JM
Kuster, JK
Blood, AJ
Kuhnen, CM
Breiter, HC
AF Lee, Sang
Lee, Myung J.
Kim, Byoung W.
Gilman, Jodi M.
Kuster, John K.
Blood, Anne J.
Kuhnen, Camelia M.
Breiter, Hans C.
TI The Commonality of Loss Aversion across Procedures and Stimuli
SO PLOS ONE
LA English
DT Article
ID DECISION-MAKING; PROSPECT-THEORY; RISK-AVERSION; RESPONSES; AMYGDALA;
UTILITY; CHOICE; MODEL
AB Individuals tend to give losses approximately 2-fold the weight that they give gains. Such approximations of loss aversion (LA) are almost always measured in the stimulus domain of money, rather than objects or pictures. Recent work on preference-based decision-making with a schedule-less keypress task (relative preference theory, RPT) has provided a mathematical formulation for LA similar to that in prospect theory (PT), but makes no parametric assumptions in the computation of LA, uses a variable tied to communication theory (i.e., the Shannon entropy or information), and works readily with non-monetary stimuli. We evaluated if these distinct frameworks described similar LA in healthy subjects, and found that LA during the anticipation phase of the PT-based task correlated significantly with LA related to the RPT-based task. Given the ease with which non-monetary stimuli can be used on the Internet, or in animal studies, these findings open an extensive range of applications for the study of loss aversion. Furthermore, the emergence of methodology that can be used to measure preference for both social stimuli and money brings a common framework to the evaluation of preference in both social psychology and behavioral economics.
C1 [Lee, Sang; Lee, Myung J.; Kim, Byoung W.; Breiter, Hans C.] Northwestern Univ, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lee, Sang; Lee, Myung J.; Kim, Byoung W.; Gilman, Jodi M.; Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Boston, MA 02114 USA.
[Lee, Sang; Lee, Myung J.; Kim, Byoung W.; Gilman, Jodi M.; Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] Harvard Univ, Sch Med, Boston, MA USA.
[Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] MGH & HMS, Mood & Motor Control Lab, Boston, MA USA.
[Kuhnen, Camelia M.] Univ N Carolina, Kenan Flagler Business Sch, Chapel Hill, NC USA.
[Lee, Sang; Lee, Myung J.; Kim, Byoung W.; Gilman, Jodi M.; Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, Sang; Lee, Myung J.; Kim, Byoung W.; Gilman, Jodi M.; Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] Northwestern Univ, Phenotype Genotype Project Addict & Mood Disorder, Chicago, IL 60611 USA.
RP Breiter, HC (reprint author), Northwestern Univ, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
EM h-breiter@northwestern.edu
FU NIDA, Bethesda, MD [14118, 026002, 026104, 027804]; Office of National
Drug Control Policy - Counterdrug Technology Assessment Center,
Washington, D.C. [DABK39-03-0098, DABK39-03-C-0098]; Warren Wright
Adolescent Center at Northwestern Memorial Hospital & Northwestern
University, Chicago Il; NINDS, Washington, D.C. [052368]
FX Funding: This work was supported by grants to H.C. B. (#14118, 026002,
026104, 027804) from the NIDA, Bethesda, MD, and grants (DABK39-03-0098
& DABK39-03-C-0098; The Phenotype Genotype Project in Addiction and Mood
Disorder) from the Office of National Drug Control Policy - Counterdrug
Technology Assessment Center, Washington, D.C. Further support was
provided to H.C.B. by the Warren Wright Adolescent Center at
Northwestern Memorial Hospital & Northwestern University, Chicago Il.
Also, support was provided by a grant to A.J.B. (#052368) from NINDS,
Washington, D.C. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 1
Z9 1
U1 1
U2 5
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 SEP 22
PY 2015
VL 10
IS 9
AR e0135216
DI 10.1371/journal.pone.0135216
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0ZW
UT WOS:000361792100004
ER
PT J
AU Shoda, H
Yanai, R
Yoshimura, T
Nagai, T
Kimura, K
Sobrin, L
Connor, KM
Sakoda, Y
Tamada, K
Ikeda, T
Sonoda, KH
AF Shoda, Hiromi
Yanai, Ryoji
Yoshimura, Takeru
Nagai, Tomohiko
Kimura, Kazuhiro
Sobrin, Lucia
Connor, Kip M.
Sakoda, Yukimi
Tamada, Koji
Ikeda, Tsunehiko
Sonoda, Koh-Hei
TI Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in
Association with Inhibition of Th1 and Th17 Cell Function
SO PLOS ONE
LA English
DT Article
ID KOYANAGI-HARADA-DISEASE; FATTY-ACIDS; CARDIOVASCULAR-DISEASE;
EICOSAPENTAENOIC ACID; N-3 PUFA; MICE; UVEORETINITIS;
NEOVASCULARIZATION; INFLAMMATION; MACROPHAGES
AB Omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of omega-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with omega-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing omega-3 LCPU-FAs or omega-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund's adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed omega-3 LCPUFAs than for those fed omega-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-gamma and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed omega-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and ROR gamma t, respectively, were reduced both in the retina and in lymph node cells of mice fed omega-3 LCPUFAs. Our results thus show that a diet enriched in omega-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function.
C1 [Shoda, Hiromi; Yanai, Ryoji; Nagai, Tomohiko; Kimura, Kazuhiro; Sonoda, Koh-Hei] Yamaguchi Univ, Grad Sch Med, Dept Ophthalmol, Ube, Yamaguchi 755, Japan.
[Yoshimura, Takeru; Sobrin, Lucia; Connor, Kip M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Dept Ophthalmol, Cambridge, MA 02138 USA.
[Sakoda, Yukimi; Tamada, Koji] Yamaguchi Univ, Grad Sch Med, Dept Immunol, Ube, Yamaguchi 755, Japan.
[Shoda, Hiromi; Ikeda, Tsunehiko] Osaka Med Coll, Dept Ophthalmol, Osaka, Japan.
RP Yanai, R (reprint author), Yamaguchi Univ, Grad Sch Med, Dept Ophthalmol, Ube, Yamaguchi 755, Japan.
EM yanai@yamaguchi-u.ac.jp
OI Connor, Kip/0000-0002-2048-9080
NR 43
TC 0
Z9 0
U1 0
U2 7
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 SEP 22
PY 2015
VL 10
IS 9
AR e0138241
DI 10.1371/journal.pone.0138241
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0ZW
UT WOS:000361792100042
PM 26393358
ER
PT J
AU Waldo, SW
Secemsky, EA
O'Brien, C
Kennedy, KF
Pomerantsev, E
Sundt, TM
McNulty, EJ
Scirica, BM
Yeh, RW
AF Waldo, Stephen W.
Secemsky, Eric A.
O'Brien, Cashel
Kennedy, Kevin F.
Pomerantsev, Eugene
Sundt, Thoralf M., III
McNulty, Edward J.
Scirica, Benjamin M.
Yeh, Robert W.
TI Response to Letter Regarding Article, "Surgical Ineligibility and
Mortality Among Patients With Unprotected Left Main or Multivessel
Coronary Artery Disease Undergoing Percutaneous Coronary Intervention"
SO CIRCULATION
LA English
DT Letter
C1 [Waldo, Stephen W.; Secemsky, Eric A.; O'Brien, Cashel; Pomerantsev, Eugene; Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
[Kennedy, Kevin F.] St Lukes Midamer Heart Inst, Kansas City, MO USA.
[Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA.
[McNulty, Edward J.] Kaiser Permanente Med Ctr, Div Cardiol, San Francisco, CA USA.
[Scirica, Benjamin M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
RP Waldo, SW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
NR 4
TC 0
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD SEP 22
PY 2015
VL 132
IS 12
BP E156
EP E156
DI 10.1161/CIRCULATIONAHA.115.016777
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR6VD
UT WOS:000361485100006
PM 26391303
ER
PT J
AU Jack, DW
Asante, KP
Wylie, BJ
Chillrud, SN
Whyatt, RM
Ae-Ngibise, KA
Quinn, AK
Yawson, AK
Boamah, EA
Agyei, O
Mujtaba, M
Kaali, S
Kinney, P
Owusu-Agyei, S
AF Jack, Darby W.
Asante, Kwaku Poku
Wylie, Blair J.
Chillrud, Steve N.
Whyatt, Robin M.
Ae-Ngibise, Kenneth A.
Quinn, Ashlinn K.
Yawson, Abena Konadu
Boamah, Ellen Abrafi
Agyei, Oscar
Mujtaba, Mohammed
Kaali, Seyram
Kinney, Patrick
Owusu-Agyei, Seth
TI Ghana randomized air pollution and health study (GRAPHS): study protocol
for a randomized controlled trial
SO TRIALS
LA English
DT Article
DE Household air pollution; LPG; Cookstove; Ghana; Pneumonia; Birth weight
ID COMPARATIVE RISK-ASSESSMENT; SOLID-FUEL USE; PARTICULATE MATTER;
CARBON-MONOXIDE; DEVELOPING-COUNTRIES; HIGHLAND GUATEMALA; KINTAMPO
HEALTH; BIOMASS FUELS; BIRTH-WEIGHT; INDOOR
AB Background: Household air pollution exposure is a major health risk, but validated interventions remain elusive.
Methods/Design: The Ghana Randomized Air Pollution and Health Study (GRAPHS) is a cluster-randomized trial that evaluates the efficacy of clean fuels (liquefied petroleum gas, or LPG) and efficient biomass cookstoves in the Brong-Ahafo region of central Ghana. We recruit pregnant women into LPG, efficient cookstove, and control arms and track birth weight and physician-assessed severe pneumonia incidence in the first year of life. A woman is eligible to participate if she is in the first or second trimester of pregnancy and carrying a live singleton fetus, if she is the primary cook, and if she does not smoke. We hypothesize that babies born to intervention mothers will weigh more and will have fewer cases of physician-assessed severe pneumonia in the first year of life. Additionally, an extensive personal air pollution exposure monitoring effort opens the way for exposure-response analyses, which we will present alongside intention-to-treat analyses. Major funding was provided by the National Institute of Environmental Health Sciences, The Thrasher Research Fund, and the Global Alliance for Clean Cookstoves.
Discussion: Household air pollution exposure is a major health risk that requires well-tested interventions. GRAPHS will provide important new evidence on the efficacy of both efficient biomass cookstoves and LPG, and will thus help inform health and energy policies in developing countries.
C1 [Jack, Darby W.; Whyatt, Robin M.; Quinn, Ashlinn K.; Kinney, Patrick] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10027 USA.
[Asante, Kwaku Poku; Ae-Ngibise, Kenneth A.; Yawson, Abena Konadu; Boamah, Ellen Abrafi; Agyei, Oscar; Mujtaba, Mohammed; Kaali, Seyram; Owusu-Agyei, Seth] Kintampo Hlth Res Ctr, Ghana Hlth Serv, Kintampo, Ghana.
[Chillrud, Steve N.] Columbia Univ, Lamont Doherty Earth Observ, New York, NY USA.
[Wylie, Blair J.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA.
[Wylie, Blair J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Jack, DW (reprint author), Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10027 USA.
EM dj2183@cumc.columbia.edu
FU NIEHS NIH HHS [1R01ES019547, ES009089, K23 ES021471, P30 ES009089, R01
ES019547, T32 ES023770]
NR 37
TC 3
Z9 3
U1 4
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD SEP 22
PY 2015
VL 16
AR 420
DI 10.1186/s13063-015-0930-8
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CR8FX
UT WOS:000361587600001
PM 26395578
ER
PT J
AU Foldes, ST
Weber, DJ
Collinger, JL
AF Foldes, Stephen T.
Weber, Douglas J.
Collinger, Jennifer L.
TI MEG-based neurofeedback for hand rehabilitation
SO JOURNAL OF NEUROENGINEERING AND REHABILITATION
LA English
DT Article
DE Brain-Computer Interface; Neurofeedback; Spinal Cord Injury;
Magnetoencephalography; Neuroplasticity; Rehabilitation
ID BRAIN-COMPUTER INTERFACE; MIRROR NEURON SYSTEM; MOTOR IMAGERY; STROKE
REHABILITATION; PLASTICITY; FEEDBACK; SUPPRESSION; MODULATION;
ARTIFACTS; RECOVERY
AB Background: Providing neurofeedback (NF) of motor-related brain activity in a biologically-relevant and intuitive way could maximize the utility of a brain-computer interface (BCI) for promoting therapeutic plasticity. We present a BCI capable of providing intuitive and direct control of a video-based grasp.
Methods: Utilizing magnetoencephalography's (MEG) high temporal and spatial resolution, we recorded sensorimotor rhythms (SMR) that were modulated by grasp or rest intentions. SMR modulation controlled the grasp aperture of a stop motion video of a human hand. The displayed hand grasp position was driven incrementally towards a closed or opened state and subjects were required to hold the targeted position for a time that was adjusted to change the task difficulty.
Results: We demonstrated that three individuals with complete hand paralysis due to spinal cord injury (SCI) were able to maintain brain-control of closing and opening a virtual hand with an average of 63 % success which was significantly above the average chance rate of 19 %. This level of performance was achieved without pre-training and less than 4 min of calibration. In addition, successful grasp targets were reached in 1.96 +/- 0.15 s. Subjects performed 200 brain-controlled trials in approximately 30 min excluding breaks. Two of the three participants showed a significant improvement in SMR indicating that they had learned to change their brain activity within a single session of NF.
Conclusions: This study demonstrated the utility of a MEG-based BCI system to provide realistic, efficient, and focused NF to individuals with paralysis with the goal of using NF to induce neuroplasticity.
C1 [Foldes, Stephen T.; Weber, Douglas J.; Collinger, Jennifer L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA.
[Foldes, Stephen T.; Weber, Douglas J.; Collinger, Jennifer L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
[Foldes, Stephen T.; Weber, Douglas J.; Collinger, Jennifer L.] Univ Pittsburgh, Ctr Neural Basis Cognit, Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Weber, Douglas J.; Collinger, Jennifer L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA.
RP Collinger, JL (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA.
EM collingr@pitt.edu
FU Department of Veterans Affairs, Office of Research and Development,
Rehabilitation Research & Development Service [B7143R]; VISN 4
Competitive Pilot Project Fund
FX The authors would like to express gratitude to Betsy Harchick, Debbie
Harrington, and Michael Randazzo for assistance with the experiments and
Emily Grattan and Juleen Rodakowski for assistance with the functional
assessments. This work was supported by the Department of Veterans
Affairs, Office of Research and Development, Rehabilitation Research &
Development Service (Grants #B7143R) and the VISN 4 Competitive Pilot
Project Fund. Its contents are solely the responsibility of the authors
and do not necessarily represent the official view of the Department of
Veterans Affairs or the United States Government.
NR 47
TC 3
Z9 4
U1 2
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-0003
J9 J NEUROENG REHABIL
JI J. NeuroEng. Rehabil.
PD SEP 22
PY 2015
VL 12
AR 85
DI 10.1186/s12984-015-0076-7
PG 9
WC Engineering, Biomedical; Neurosciences; Rehabilitation
SC Engineering; Neurosciences & Neurology; Rehabilitation
GA CR6AS
UT WOS:000361426100001
PM 26392353
ER
PT J
AU Dec, GW
Arbustini, E
AF Dec, G. William
Arbustini, Eloisa
TI Utilizing the MOGE(S) Classification for Predicting Prognosis in Dilated
Cardiomyopathy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE dilated cardiomyopathy; MOGE(S) classification; prognosis
ID CARDIOLOGY; ASSOCIATION; STATEMENT; SOCIETY
C1 [Dec, G. William] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Arbustini, Eloisa] Policlin San Matteo, I-27100 Pavia, Italy.
RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA.
EM gdec@partners.org
NR 9
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD SEP 22
PY 2015
VL 66
IS 12
BP 1324
EP 1326
DI 10.1016/j.jacc.2015.06.1335
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR6KV
UT WOS:000361456600002
PM 26383717
ER
PT J
AU Zhu, L
Zhong, MH
Elder, GA
Sano, M
Holtzman, DM
Gandy, S
Cardozo, C
Haroutunian, V
Robakis, NK
Cai, DM
AF Zhu, Li
Zhong, Minghao
Elder, Gregory A.
Sano, Mary
Holtzman, David M.
Gandy, Sam
Cardozo, Christopher
Haroutunian, Vahram
Robakis, Nikolaos K.
Cai, Dongming
TI Phospholipid dysregulation contributes to ApoE4-associated cognitive
deficits in Alzheimer's disease pathogenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Alzheimer's disease; apolipoprotein E4; phospholipid; dysregulation;
cognitive deficits
ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; MOUSE MODEL; EPSILON-4
HOMOZYGOTES; ENDOCYTIC TRAFFICKING; BRAIN; METABOLISM; MEMORY;
PHOSPHORYLATION; PERFORMANCE
AB The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.
C1 [Zhu, Li; Elder, Gregory A.; Sano, Mary; Gandy, Sam; Cai, Dongming] James J Peters VA Med Ctr, Res & Dev, Bronx, NY 10468 USA.
[Zhu, Li; Sano, Mary; Gandy, Sam; Haroutunian, Vahram; Cai, Dongming] Icahn Sch Med Mt Sinai, Alzheimer Dis Res Ctr, Dept Neurol, New York, NY 10029 USA.
[Zhong, Minghao] New York Med Coll, Dept Pathol, Westchester Med Ctr, Valhalla, NY 10595 USA.
[Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63100 USA.
[Cardozo, Christopher] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA.
[Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
[Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA.
[Haroutunian, Vahram; Robakis, Nikolaos K.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
RP Cai, DM (reprint author), James J Peters VA Med Ctr, Res & Dev, Bronx, NY 10468 USA.
EM dongming.cai@mssm.edu
OI Cai, Dongming/0000-0002-0601-6826
FU Department of Veteran Affairs Basic Life Science Research & Development
CDA; Alzheimer Association [NIRP14-304720]; Department of Veteran
Affairs Rehabilitation Research & Development Small Projects in
Rehabilitation Research [1I21RX001558-01A1]; NIH R01 [1R01AG048923-01,
2R01AG008200]; NIH R37 [AG017926]; NIH UO1 [AG046170]; NIH P50
[AG005138]; NIH R34 [AG049649]; NIH RO1 [NS075685]; Department of
Veterans Affairs RR&D National Center for Excellence for the Medical
Consequences of Spinal Cord Injury; James J. Peters VA Medical Center
Research Core Facility
FX We thank Dr. Pietro De Camilli (Yale School of Medicine) for providing
synj1 haploinsufficiency mice. Antibody p369 was generously provided by
Dr. Paul Greengard. We also thank Dr. William Netzer (The Rockefeller
University) and Dr. Michaela Kiernan (Stanford University) for critical
reading of the manuscript. This work was supported in whole or in part
by funding from the Department of Veteran Affairs Basic Life Science
Research & Development CDA (Award CAI-spring 2010); Alzheimer
Association (Award NIRP14-304720); Department of Veteran Affairs
Rehabilitation Research & Development Small Projects in Rehabilitation
Research (Grant 1I21RX001558-01A1); and NIH R01 (Grant 1R01AG048923-01)
(to D.C.), NIH R37 (Grant AG017926) and R01 (Grant 2R01AG008200) (to
N.K.R.), NIH UO1 (Grant AG046170), P50 (Grant AG005138), R34 (Grant
AG049649), and RO1 (Grant NS075685) (to S.G.); as well as Department of
Veterans Affairs RR&D National Center for Excellence for the Medical
Consequences of Spinal Cord Injury (Grant B9212C) (to C.C.). Confocal
microscopy studies were supported by the James J. Peters VA Medical
Center Research Core Facility.
NR 47
TC 11
Z9 11
U1 2
U2 13
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 SEP 22
PY 2015
VL 112
IS 38
BP 11965
EP 11970
DI 10.1073/pnas.1510011112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7JH
UT WOS:000361525100066
PM 26372964
ER
PT J
AU Prusiner, SB
Woerman, AL
Mordes, DA
Watts, JC
Rampersaud, R
Berry, DB
Patel, S
Oehler, A
Lowe, JK
Kravitz, SN
Geschwind, DH
Glidden, DV
Halliday, GM
Middleton, LT
Gentleman, SM
Grinberg, LT
Giles, K
AF Prusiner, Stanley B.
Woerman, Amanda L.
Mordes, Daniel A.
Watts, Joel C.
Rampersaud, Ryan
Berry, David B.
Patel, Smita
Oehler, Abby
Lowe, Jennifer K.
Kravitz, Stephanie N.
Geschwind, Daniel H.
Glidden, David V.
Halliday, Glenda M.
Middleton, Lefkos T.
Gentleman, Steve M.
Grinberg, Lea T.
Giles, Kurt
TI Evidence for alpha-synuclein prions causing multiple system atrophy in
humans with parkinsonism
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurodegeneration; Parkinson's disease; synucleinopathies; strains
ID PROGRESSIVE SUPRANUCLEAR PALSY; GLIAL CYTOPLASMIC INCLUSIONS;
CREUTZFELDT-JAKOB-DISEASE; TRANSGENIC MICE; LEWY BODIES; CONSENSUS
STATEMENT; TRANSMISSION; MUTATIONS; SCRAPIE; NEURODEGENERATION
AB Prions are proteins that adopt alternative conformations that become self-propagating; the PrPSc prion causes the rare human disorder Creutzfeldt-Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the alpha-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of alpha-synuclein. To determine whether human alpha-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human alpha-synuclein fused to yellow fluorescent protein (alpha-syn140*A53T-YFP) and TgM83(+/-) mice expressing alpha-synuclein (A53T). The TgM83(+/-) mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83(+/+) mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83(+/-) mice after incubation periods of similar to 120 d, which was accompanied by deposition of alpha-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of alpha-syn*A53T-YFP in cultured cells, whereas none of six Parkinson's disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of alpha-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83(+/+) mice. Remarkably, alpha-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible.
C1 [Prusiner, Stanley B.; Woerman, Amanda L.; Watts, Joel C.; Rampersaud, Ryan; Berry, David B.; Patel, Smita; Giles, Kurt] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
[Prusiner, Stanley B.; Watts, Joel C.; Grinberg, Lea T.; Giles, Kurt] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Prusiner, Stanley B.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[Mordes, Daniel A.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Oehler, Abby] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Lowe, Jennifer K.; Kravitz, Stephanie N.; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.
[Lowe, Jennifer K.; Kravitz, Stephanie N.; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
[Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
[Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Halliday, Glenda M.] Univ New S Wales, Fac Med, Sch Med Sci, Randwick, NSW 2031, Australia.
[Middleton, Lefkos T.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ageing Res Unit, London SW7 2AZ, England.
[Gentleman, Steve M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Neuroinflammat & Neurodegenerat, London SW7 2AZ, England.
[Grinberg, Lea T.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA.
RP Prusiner, SB (reprint author), Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
EM stanley@ind.ucsf.edu
RI Halliday, Glenda/E-8555-2011
OI Halliday, Glenda/0000-0003-0422-8398
FU National Institutes of Health [AG021601, AG002132, AG010770, AG031220];
Sherman Fairchild Foundation; Rainwater Charitable Foundation; Mary Jane
Brinton Fund; Parkinson's UK, a charity registered in England and Wales
[948776]; Parkinson's UK, a charity registered in Scotland [SC037554];
Sydney Brain Bank; Neuroscience Research Australia; University of New
South Wales; National Health and Medical Research Council of Australia
FX This work was supported by grants from the National Institutes of Health
(AG021601, AG002132, AG010770, and AG031220) as well as the Sherman
Fairchild Foundation, the Rainwater Charitable Foundation, and the Mary
Jane Brinton Fund. Synucleinopathy tissue samples were supplied by the
neuropathology core of the Massachusetts Alzheimer's Disease Research
Center (AG005134); the Parkinson's UK Brain Bank at Imperial College
London, funded by Parkinson's UK, a charity registered in England and
Wales (948776) and in Scotland (SC037554); and the Sydney Brain Bank,
which is supported by Neuroscience Research Australia, the University of
New South Wales, and the National Health and Medical Research Council of
Australia. Glenda M. Halliday is a National Health and Medical Research
Council of Australia Senior Principal Research Fellow (1079679). We
thank Robert L. Nussbaum for his gift of the alpha-synuclein-knockout
and transgenic mice, and Eric Huang for providing the control brain
sample.
NR 63
TC 78
Z9 80
U1 3
U2 29
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 SEP 22
PY 2015
VL 112
IS 38
BP E5308
EP E5317
DI 10.1073/pnas.1514475112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7JH
UT WOS:000361525100014
PM 26324905
ER
PT J
AU Paterson, AM
Lovitch, SB
Sage, PT
Juneja, VR
Lee, Y
Trombley, JD
Arancibia-Carcamo, CV
Sobel, RA
Rudensky, AY
Kuchroo, VK
Freeman, GJ
Sharpe, AH
AF Paterson, Alison M.
Lovitch, Scott B.
Sage, Peter T.
Juneja, Vikram R.
Lee, Youjin
Trombley, Justin D.
Arancibia-Carcamo, Carolina V.
Sobel, Raymond A.
Rudensky, Alexander Y.
Kuchroo, Vijay K.
Freeman, Gordon J.
Sharpe, Arlene H.
TI Deletion of CTLA-4 on regulatory T cells during adulthood leads to
resistance to autoimmunity
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IN-VIVO; NEGATIVE SELECTION;
CUTTING EDGE; ANTIGEN 4; CD4(+)CD8(+) THYMOCYTES; PERIPHERAL
HOMEOSTASIS; ACTIVATION ANTIGEN-B7; CTLA-4-DEFICIENT MICE; CD28
COSTIMULATION
AB Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4(+)Foxp3(-) (T conv) and regulatory Foxp3(+) (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells.
C1 [Paterson, Alison M.; Lovitch, Scott B.; Sage, Peter T.; Juneja, Vikram R.; Trombley, Justin D.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Paterson, Alison M.; Lovitch, Scott B.; Sage, Peter T.; Juneja, Vikram R.; Lee, Youjin; Trombley, Justin D.; Kuchroo, Vijay K.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA.
[Paterson, Alison M.; Lovitch, Scott B.; Sage, Peter T.; Juneja, Vikram R.; Lee, Youjin; Trombley, Justin D.; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lovitch, Scott B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Arancibia-Carcamo, Carolina V.] Univ Oxford, Nuffield Dept Clin Med, Div Expt Med, Translat Gastroenterol Unit, Oxford OX3 9DU, England.
[Sobel, Raymond A.] Stanford Univ, Dept Pathol, Stanford, CA 94304 USA.
[Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
[Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, Sloan Kettering Inst Canc Res, Program Immunol, New York, NY 10065 USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
EM arlene_sharpe@hms.harvard.edu
OI Lovitch, Scott/0000-0001-9013-0105
FU National Institutes of Health [AI38310, AI40614, P01 AI39671, PO1
AI56299]; National Multiple Sclerosis Society [FG-1916-A-1]
FX This work was supported by grants from the National Institutes of Health
(AI38310 and AI40614 to A.H. Sharpe; P01 AI39671 to A.H. Sharpe and V.K.
Kuchroo; PO1 AI56299 to A.H. Sharpe, G.J. Freeman, and V.K. Kuchroo) and
the National Multiple Sclerosis Society (FG-1916-A-1 to S.B. Lovitch).
NR 81
TC 18
Z9 19
U1 2
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD SEP 21
PY 2015
VL 212
IS 10
BP 1603
EP 1621
DI 10.1084/jem.20141030
PG 19
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CW6VB
UT WOS:000365135200012
PM 26371185
ER
PT J
AU Hao, Y
Altundal, Y
Moreau, M
Sajo, E
Kumar, R
Ngwa, W
AF Hao, Yao
Altundal, Yucel
Moreau, Michele
Sajo, Erno
Kumar, Rajiv
Ngwa, Wilfred
TI Potential for enhancing external beam radiotherapy for lung cancer using
high-Z nanoparticles administered via inhalation
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE inhalation; cisplatin nanoparticles; carboplatin nanoparticles;
radiotherapy; dose Enhancement; chemoradiotherapy
ID BODY RADIATION-THERAPY; GOLD NANOPARTICLES; ANTICANCER DRUGS; DOSE
ENHANCEMENT; PHOTON BEAMS; CO-DELIVERY; SIRNA
AB Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs).
Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV.
For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected.
The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.
C1 [Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Ngwa, Wilfred] Univ Massachusetts, Lowell, MA 01854 USA.
[Moreau, Michele; Kumar, Rajiv; Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Moreau, Michele; Kumar, Rajiv; Ngwa, Wilfred] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kumar, Rajiv] North Eastern Univ, Boston, MA 02115 USA.
RP Hao, Y (reprint author), Univ Massachusetts, Lowell, MA 01854 USA.
EM Yao_hao@uml.edu
FU National Institutes of Health NationalCancer Institute [1 K01
CA172478-01]
FX This study was supported by National Institutes of Health NationalCancer
Institute grant 1 K01 CA172478-01.
NR 24
TC 3
Z9 3
U1 4
U2 12
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD SEP 21
PY 2015
VL 60
IS 18
BP 7035
EP 7043
DI 10.1088/0031-9155/60/18/7035
PG 9
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA CR1ZL
UT WOS:000361124000002
PM 26309064
ER
PT J
AU Pui, CH
Yang, JJ
Hunger, SP
Pieters, R
Schrappe, M
Biondi, A
Vora, A
Baruchel, A
Silverman, LB
Schmiegelow, K
Escherich, G
Horibe, K
Benoit, YCM
Izraeli, S
Yeoh, AEJ
Liang, DC
Downing, JR
Evans, WE
Relling, MV
Mullighan, CG
AF Pui, Ching-Hon
Yang, Jun J.
Hunger, Stephen P.
Pieters, Rob
Schrappe, Martin
Biondi, Andrea
Vora, Ajay
Baruchel, Andre
Silverman, Lewis B.
Schmiegelow, Kjeld
Escherich, Gabriele
Horibe, Keizo
Benoit, Yves C. M.
Izraeli, Shai
Yeoh, Allen Eng Juh
Liang, Der-Cherng
Downing, James R.
Evans, William E.
Relling, Mary V.
Mullighan, Charles G.
TI Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID MINIMAL RESIDUAL DISEASE; B-CELL PRECURSOR; CHILDRENS ONCOLOGY GROUP;
KINASE INHIBITOR THERAPY; BFM STUDY-GROUP; T-CELL; TREATMENT RESPONSE;
DOWN-SYNDROME; GENOME-WIDE; ASPARAGINASE ANTIBODIES
AB Purpose
To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.
Methods
A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.
Results
With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL.
Conclusion
The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. (C) 2015 by American Society of Clinical Oncology
C1 [Pui, Ching-Hon; Yang, Jun J.; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Pui, Ching-Hon; Yang, Jun J.; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA.
[Hunger, Stephen P.] Univ Colorado, Ctr Canc, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO USA.
[Pieters, Rob] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
[Schrappe, Martin] Univ Kiel, Univ Med Ctr Schleswig Holstein, Kiel, Germany.
[Escherich, Gabriele] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Hamburg, Germany.
[Biondi, Andrea] Univ Milano Bicocca, Clin Pediat, Monza, Italy.
[Biondi, Andrea] Univ Milano Bicocca, Ctr Ric Tettamanti, Monza, Italy.
[Vora, Ajay] Univ Manchester, Manchester Acad Hlth Sci Ctr, Sch Canc, Childrens Canc Grp, Manchester, Lancs, England.
[Baruchel, Andre] Hop Robert Debre, F-75019 Paris, France.
[Baruchel, Andre] Univ Paris Diderot, Paris, France.
[Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA.
[Schmiegelow, Kjeld] Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark.
[Schmiegelow, Kjeld] Univ Hosp Rigshosp, Juliane Marie Ctr, Copenhagen, Denmark.
[Horibe, Keizo] Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan.
[Benoit, Yves C. M.] Univ Ghent, Ghent, Belgium.
[Izraeli, Shai] Tel Aviv Univ, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel.
[Izraeli, Shai] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Yeoh, Allen Eng Juh] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
[Yeoh, Allen Eng Juh] Natl Univ Singapore, Canc Sci Inst, Singapore 117595, Singapore.
[Yeoh, Allen Eng Juh] Natl Univ Singapore Hosp, Viva Univ Childrens Canc Ctr, Singapore, Singapore.
[Liang, Der-Cherng] Mackay Mem Hosp, Taipei, Taiwan.
RP Pui, CH (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM ching-hon.pui@stjude.org
FU National Institutes of Health [CA21765, CA36401, U01 GM92666, U10
CA98543, U10 CA98413]; United Kingdom Medical Research Council,
Leukaemia and Lymphoma Research and National Cancer Research Institute
(United Kingdom Childhood Acute Lymphoblastic Leukemia trials); Stand Up
to Cancer Innovative Research Grant; Singapore VIVA Foundation; American
Lebanese Syrian Associated Charities
FX Supported in part by Grants No. CA21765, CA36401, U01 GM92666, U10
CA98543 (to the Children's Oncology Group [COG] Chair), and U10 CA98413
(to the COG Statistical Center) from the National Institutes of Health;
by the United Kingdom Medical Research Council, Leukaemia and Lymphoma
Research and National Cancer Research Institute (United Kingdom
Childhood Acute Lymphoblastic Leukemia trials); by a Stand Up to Cancer
Innovative Research Grant (C.G.M.); by the Singapore VIVA Foundation;
and by the American Lebanese Syrian Associated Charities. S.P.H. is the
Ergen Family Chair in Pediatric Cancer, C.G.M. is a St Baldrick's
Scholar and Pew Scholar in the Biomedical Sciences, and C.-H.P. is an
American Cancer Society professor.
NR 101
TC 42
Z9 44
U1 3
U2 12
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 2938
EP U24
DI 10.1200/JCO.2014.59.1636
PG 12
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800002
PM 26304874
ER
PT J
AU Dome, JS
Graf, N
Geller, JI
Fernandez, CV
Mullen, EA
Spreafico, F
Van den Heuvel-Eibrink, M
Pritchard-Jones, K
AF Dome, Jeffrey S.
Graf, Norbert
Geller, James I.
Fernandez, Conrad V.
Mullen, Elizabeth A.
Spreafico, Filippo
Van den Heuvel-Eibrink, Marry
Pritchard-Jones, Kathy
TI Advances in Wilms Tumor Treatment and Biology: Progress Through
International Collaboration
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID STEM-CELL RESCUE; CHILDRENS ONCOLOGY GROUP; P53 GENE-MUTATIONS;
FAVORABLE-HISTOLOGY; POOR-PROGNOSIS; RENAL TUMORS; PEDIATRIC-HEMATOLOGY;
ITALIAN-ASSOCIATION; INITIAL TREATMENT; ACTINOMYCIN-D
AB Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. (C) 2015 by American Society of Clinical Oncology
C1 [Dome, Jeffrey S.] Childrens Natl Hlth Syst, Washington, DC 20010 USA.
[Geller, James I.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Mullen, Elizabeth A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Graf, Norbert] Univ Saarland, Homburg, Germany.
[Fernandez, Conrad V.] IWK Hlth Ctr, Halifax, NS, Canada.
[Spreafico, Filippo] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy.
[Van den Heuvel-Eibrink, Marry] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
[Pritchard-Jones, Kathy] UCL, Inst Child Hlth, London, England.
RP Dome, JS (reprint author), Childrens Natl Hlth Syst, Div Hematol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM jdome@childrensnational.org
RI Spreafico, Filippo/K-7813-2016
OI Spreafico, Filippo/0000-0002-5587-3509
FU National Institutes of Health [U10CA098543]; Children's Oncology Group
[U10CA098543, U10CA180886, U10CA180899, U10CA098413]; European Union
[261474, 270089]; P-Medicine: From Data Sharing and Integration via VPH
Models [270089]; Cancer Research United Kingdom [C1188/A4614]; Great
Ormond Street Hospital Children's Charity; Children with Cancer;
National Institutes of Health Research Great Ormond Street
Hospital-University College London Biomedical Research Centre; German
Cancer Aid for International Society of Pediatric Oncology Gesellschaft
fur Padiatrische Onkologie und Hamatologie [50-2709-Gr2]
FX Supported by grants from the National Institutes of Health to the
National Wilms Tumor Study Group (Grant No. U10CA098543) and the
Children's Oncology Group (Grants No. U10CA180886, U10CA180899,
U10CA098543, and U10CA098413). K.P.-J.'s renal tumors research receives
support from the following European Union Framework Programme 7 grants:
European Network for Cancer Research in Children and Adolescents (Grant
No. 261474) and P-Medicine: From Data Sharing and Integration via VPH
Models to Personalised Medicine (Grant No. 270089); Cancer Research
United Kingdom (Grant No. C1188/A4614); Great Ormond Street Hospital
Children's Charity; and Children with Cancer and the National Institutes
of Health Research Great Ormond Street Hospital-University College
London Biomedical Research Centre. N.G.'s renal tumor research receives
funding from the German Cancer Aid for International Society of
Pediatric Oncology 2001/Gesellschaft fur Padiatrische Onkologie und
Hamatologie (Grant No. 50-2709-Gr2) and from the European Union
Framework Programme 7 P-Medicine Grant No. 270089.
NR 77
TC 11
Z9 13
U1 2
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 2999
EP U94
DI 10.1200/JCO.2015.62.1888
PG 11
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800007
PM 26304882
ER
PT J
AU Olson, TA
Murray, MJ
Rodriguez-Galindo, C
Nicholson, JC
Billmore, DF
Krailo, MD
Dang, HM
Amatruda, JF
Thornton, CM
Arul, GS
Stoneham, SJ
Pashankar, F
Stark, D
Shaikh, F
Gershenson, DM
Covens, A
Hurteau, J
Stenning, SP
Feldman, DR
Grimison, PS
Huddart, RA
Sweeney, C
Powles, T
Lopes, LF
Agular, SD
Chinnaswamy, G
Khaleel, S
Abouelnaga, S
Hale, JP
Frazier, AL
AF Olson, Thomas A.
Murray, Matthew J.
Rodriguez-Galindo, Carlos
Nicholson, James C.
Billmore, Deborah F.
Krailo, Mark D.
Dang, Ha M.
Amatruda, James F.
Thornton, Claire M.
Arul, G. Suren
Stoneham, Sara J.
Pashankar, Farzana
Stark, Daniel
Shaikh, Furqan
Gershenson, David M.
Covens, Allan
Hurteau, Jean
Stenning, Sally P.
Feldman, Darren R.
Grimison, Peter S.
Huddart, Robert A.
Sweeney, Christopher
Powles, Thomas
Lopes, Luiz Fernando
Agular, Simone dos Santos
Chinnaswamy, Girish
Khaleel, Sahar
Abouelnaga, Sherif
Hale, Juliet P.
Frazier, A. Lindsay
TI Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to
Collaboration
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID CHILDRENS ONCOLOGY GROUP; HIGH-DOSE CHEMOTHERAPY; INTENSIVE INDUCTION
CHEMOTHERAPY; COUNCIL EUROPEAN ORGANIZATION; RANDOMIZED PHASE-III;
STAGE-I; TESTICULAR CANCER; UNITED-KINGDOM; COMBINATION CHEMOTHERAPY;
YOUNG-ADULTS
AB During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges. (C) 2015 by American Society of Clinical Oncology
C1 [Olson, Thomas A.] Emory Univ, Atlanta, GA 30322 USA.
[Murray, Matthew J.; Nicholson, James C.] Cambridge Univ Hosp Natl Hlth Serv NHS Fdn Trust, Cambridge, England.
[Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, Boston, MA USA.
[Rodriguez-Galindo, Carlos; Sweeney, Christopher; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Billmore, Deborah F.] Riley Hosp Sick Children, Indianapolis, IN USA.
[Krailo, Mark D.; Dang, Ha M.] Univ So Calif, Los Angeles, CA USA.
[Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Amatruda, James F.] Childrens Med Ctr, Dallas, TX 75235 USA.
[Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Thornton, Claire M.] Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland.
[Arul, G. Suren] Birmingham Childrens Hosp NHS Fdn Trust, Birmingham, W Midlands, England.
[Stoneham, Sara J.] Univ Coll London Hosp NHS Fdn Trust, London, England.
[Pashankar, Farzana] Yale Univ, Sch Med, New Haven, CT USA.
[Stark, Daniel] Univ Leeds, Leeds, W Yorkshire, England.
[Shaikh, Furqan] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Covens, Allan] Univ Toronto, Toronto, ON, Canada.
[Hurteau, Jean] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[Stenning, Sally P.] MRC, London, England.
[Feldman, Darren R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Grimison, Peter S.] Sydney Canc Ctr, Sydney, NSW, Australia.
[Huddart, Robert A.] Inst Canc Res, Surrey, England.
[Huddart, Robert A.] Royal Marsden Hosp, Surrey, England.
[Powles, Thomas] Barts Canc Inst, London, England.
[Lopes, Luiz Fernando] Barretos Pediat Canc Ctr, Sao Paulo, Brazil.
[Agular, Simone dos Santos] Ctr Infantil Boldrini, Campinas, SP, Brazil.
[Chinnaswamy, Girish] Tata Mem Hosp, Bombay 400012, Maharashtra, India.
[Khaleel, Sahar; Abouelnaga, Sherif] Childrens Canc Hosp, Cairo, Egypt.
[Hale, Juliet P.] Royal Victoria Infirm NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England.
RP Olson, TA (reprint author), Emory Univ, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Div Pediat Hematol Oncol, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA.
EM Thomas.Olson@choa.org
RI Lopes, Luiz Fernando/L-5513-2016;
OI Feldman, Darren/0000-0003-2424-4635
FU Medical Research Council [MC_U122861331]; NCI NIH HHS [U10 CA180899, U10
CA098543]
NR 66
TC 6
Z9 6
U1 2
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 3018
EP U119
DI 10.1200/JCO.2014.60.5337
PG 14
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800009
PM 26304902
ER
PT J
AU Rodriguez-Galindo, C
Friedrich, P
Alcasabas, P
Antillon, F
Banavali, S
Castillo, L
Israels, T
Jeha, S
Harif, M
Sullivan, MJ
Quah, TC
Patte, C
Pui, CH
Barr, R
Gross, T
AF Rodriguez-Galindo, Carlos
Friedrich, Paola
Alcasabas, Patricia
Antillon, Federico
Banavali, Shripad
Castillo, Luis
Israels, Trijn
Jeha, Sima
Harif, Mhammed
Sullivan, Michael J.
Thuan Chong Quah
Patte, Catherine
Pui, Ching-Hon
Barr, Ronald
Gross, Thomas
TI Toward the Cure of All Children With Cancer Through Collaborative
Efforts: Pediatric Oncology As a Global Challenge
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; RESOURCE-STRATIFIED GUIDELINES; ENDEMIC
BURKITT-LYMPHOMA; MIDDLE-INCOME COUNTRIES; CHILDHOOD-CANCER;
CLINICAL-TRIALS; GRADUATED-INTENSITY; ESSENTIAL DRUGS; AFRICA;
MANAGEMENT
AB Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported. (C) 2015 by American Society of Clinical Oncology
C1 [Rodriguez-Galindo, Carlos; Friedrich, Paola] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
[Rodriguez-Galindo, Carlos; Friedrich, Paola] Harvard Univ, Sch Med, Boston, MA USA.
[Alcasabas, Patricia] Philippines Gen Hosp, Manila, Philippines.
[Antillon, Federico] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala.
[Antillon, Federico] Francisco Marroquin Med Sch, Guatemala City, Guatemala.
[Banavali, Shripad] Tata Mem Hosp, Bombay 400012, Maharashtra, India.
[Castillo, Luis] Hosp Pereira Rossell, Montevideo, Uruguay.
[Israels, Trijn] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Jeha, Sima; Pui, Ching-Hon] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Harif, Mhammed] Ctr Hosp Univ Mohammed VI, Marrakech, Morocco.
[Sullivan, Michael J.] Royal Childrens Hosp, Melbourne, Vic, Australia.
[Thuan Chong Quah] Natl Univ Hlth Syst, Singapore, Singapore.
[Patte, Catherine] Inst Gustave Roussy, Villejuif, France.
[Barr, Ronald] McMaster Univ, Hamilton, ON, Canada.
[Barr, Ronald] McMaster Childrens Hosp, Hamilton, ON, Canada.
[Gross, Thomas] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D3-133, Boston, MA 02215 USA.
EM carlos_rodriguez-galindo@dfci.harvard.edu
NR 62
TC 16
Z9 16
U1 4
U2 10
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2015
VL 33
IS 27
BP 3065
EP U175
DI 10.1200/JCO.2014.60.6376
PG 12
WC Oncology
SC Oncology
GA CX9IL
UT WOS:000366018800014
PM 26304881
ER
PT J
AU Leder, BZ
Tsai, JN
Uihlein, AV
Wallace, PM
Lee, H
Neer, RM
Burnett-Bowie, SAM
AF Leder, Benjamin Z.
Tsai, Joy N.
Uihlein, Alexander V.
Wallace, Paul M.
Lee, Hang
Neer, Robert M.
Burnett-Bowie, Sherri-Ann M.
TI Denosumab and teriparatide transitions in postmenopausal osteoporosis
(the DATA-Switch study): extension of a randomised controlled trial
SO LANCET
LA English
DT Article
ID PARATHYROID-HORMONE; FRACTURE RISK; BONE MASS; WORLDWIDE PREVALENCE; HIP
FRACTURE; WOMEN; ALENDRONATE; BMD; THERAPY; DENSITY
AB Background Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments.
Methods This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00926380.
Findings Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18.3% (95% CI 14.9-21.8) in 27 women in the teriparatide to denosumab group, 14.0% (10.9-17.2) in 27 women the denosumab to teriparatide group, and 16.0% (14.0-18.0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparisons, p=0.13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0.30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0.41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6.6% [95% CI 5.3-7.9]) than in the denosumab to teriparatide group (2.8% [1.3-4.2], p=0.0002), but had the greatest increase in the combination to denosumab group (8.6% [7.1-10.0]; p=0.0446 vs the teriparatide to denosumab group, p<0.0001 vs the denosumab to teriparatide group). Similarly, femoral neck bone mineral density increased more in the teriparatide to denosumab group (8.3% [95% CI 6.1-10.5]) and the combination to denosumab group (9.1% [6.1-12.0]) than in the denosumab to teriparatide group (4.9% [2.2-7.5]; p=0.0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0.0336 for combination to denosumab vs denosumab to teriparatide). Differences between the combination to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0.67). After 48 months, radius bone mineral density was unchanged in the teriparatide to denosumab group (0.0% [95% CI -1.3 to 1.4]), whereas it decreased by -1.8% (-5.0 to 1.3) in the denosumab to teriparatide group, and increased by 2.8% (1.2-4.4) in the combination to denosumab group (p=0.0075 for the teriparatide to denosumab group vs the combination to denosumab group; p=0.0099 for the denosumab to teriparatide group vs the combination to denosumab group). One participant in the denosumab to teriparatide group had nephrolithiasis, classified as being possibly related to treatment.
Interpretation In postmenopausal osteoporotic women switching from teriparatide to denosumab, bone mineral density continued to increase, whereas switching from denosumab to teriparatide results in progressive or transient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients.
C1 [Leder, Benjamin Z.; Tsai, Joy N.; Uihlein, Alexander V.; Wallace, Paul M.; Neer, Robert M.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051, Boston, MA 02114 USA.
EM bzleder@partners.org
FU Amgen; Eli Lilly; National Institutes of Health; National Institutes of
Health from the National Center for Research Resources [ULI RR025758]
FX Funding Amgen, Eli Lilly, and National Institutes of Health.; This study
was funded by investigator-initiated grants from Amgen and Eli Lilly and
by National Institutes of Health Grant ULI RR025758 from the National
Center for Research Resources.
NR 36
TC 26
Z9 26
U1 1
U2 8
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 SEP 19
PY 2015
VL 386
IS 9999
BP 1147
EP 1155
DI 10.1016/S0140-6736(15)61120-5
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR5GE
UT WOS:000361368000029
PM 26144908
ER
PT J
AU Santos, SA
Lukens, AK
Coelho, L
Nogueira, F
Wirth, DF
Mazitschek, R
Moreira, R
Paulo, A
AF Santos, Sofia A.
Lukens, Amanda K.
Coelho, Lis
Nogueira, Fatima
Wirth, Dyann F.
Mazitschek, Ralph
Moreira, Rui
Paulo, Alexandra
TI Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel
antimalarial chemotype
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Antimalarial; Drug lead; Indole; Reagent-based diversity
ID ANTIPLASMODIAL ACTIVITY; PLASMODIUM-FALCIPARUM; DRUG DISCOVERY;
BIS-ALKYLAMINE; MALARIA; POTENT; SPIROINDOLONES; DERIVATIVES; PROGRESS
AB A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity. The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, we were able to identify a new compound (10d) with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC50 values similar to 3 mu M), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.
C1 [Santos, Sofia A.; Moreira, Rui; Paulo, Alexandra] Univ Nova Lisboa, Fac Farm, Res Inst Med IMed ULisboa, P-1640003 Lisbon, Portugal.
[Santos, Sofia A.; Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Lukens, Amanda K.; Wirth, Dyann F.; Mazitschek, Ralph] Infect Dis Initiat, Broad Inst, Cambridge, MA 02142 USA.
[Lukens, Amanda K.; Wirth, Dyann F.; Mazitschek, Ralph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Coelho, Lis; Nogueira, Fatima] Univ Nova Lisboa, IHMT, Ctr Malaria & Doencas Trop, UEI Malaria, P-1349008 Lisbon, Portugal.
RP Paulo, A (reprint author), Univ Nova Lisboa, Fac Farm, Res Inst Med IMed ULisboa, Av Prof Gama Pinto, P-1640003 Lisbon, Portugal.
EM mapaulo@ff.ulisboa.pt
RI Moreira, Rui/G-7485-2011; Paulo, Alexandra/M-6683-2013; PTMS,
RNEM/C-1589-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa,
MedChem /B-4834-2014
OI Moreira, Rui/0000-0003-0727-9852; Paulo, Alexandra/0000-0003-1433-5402;
FU Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-FAR/114864/2009,
PEst-OE/SAU/UI4013/2014, SFRH/BD/80162/2011]
FX This work was supported by Fundacao para a Ciencia e Tecnologia (FCT)
project grants: PTDC/SAU-FAR/114864/2009 and PEst-OE/SAU/UI4013/2014. S.
A. Santos thanks FCT for a PhD grant (SFRH/BD/80162/2011). R. Mazitschek
thanks ChemAxon for Instant JChem 5.9.3, 2012.
NR 37
TC 1
Z9 1
U1 2
U2 13
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD SEP 18
PY 2015
VL 102
BP 320
EP 333
DI 10.1016/j.ejmech.2015.07.047
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CS2SS
UT WOS:000361922600029
PM 26295174
ER
PT J
AU Larsen, AT
Fahrenbach, AC
Sheng, J
Pian, JL
Szostak, JW
AF Larsen, Aaron T.
Fahrenbach, Albert C.
Sheng, Jia
Pian, Julia
Szostak, Jack W.
TI Thermodynamic insights into 2-thiouridine-enhanced RNA hybridization
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DOT-U PAIR; BASE-PAIRS; MOLECULAR-DYNAMICS; PRIMER EXTENSION; WOBBLE
POSITION; RECOGNITION; RIBOZYME; BINDING; DNA; URIDINE
AB Nucleobase modifications dramatically alter nucleic acid structure and thermodynamics. 2-thiouridine (s(2)U) is a modified nucleobase found in tRNAs and known to stabilize U:A base pairs and destabilize U:G wobble pairs. The recently reported crystal structures of s(2)U-containing RNA duplexes do not entirely explain the mechanisms responsible for the stabilizing effect of s(2)U or whether this effect is entropic or enthalpic in origin. We present here thermodynamic evaluations of duplex formation using ITC and UV thermal denaturation with RNA duplexes containing internal s(2)U:A and s(2)U:U pairs and their native counterparts. These results indicate that s(2)U stabilizes both duplexes. The stabilizing effect is entropic in origin and likely results from the s(2)U-induced preorganization of the single-stranded RNA prior to hybridization. The same preorganizing effect is likely responsible for structurally resolving the s(2)U:U pair-containing duplex into a single conformation with a well-defined H-bond geometry. We also evaluate the effect of s(2)U on single strand conformation using UV- and CD-monitored thermal denaturation and on nucleoside conformation using H-1 NMR spectroscopy, MD and umbrella sampling. These results provide insights into the effects that nucleobase modification has on RNA structure and thermodynamics and inform efforts toward improving both ribozyme-catalyzed and nonenzymatic RNA copying.
C1 [Larsen, Aaron T.; Fahrenbach, Albert C.; Pian, Julia; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Larsen, Aaron T.; Fahrenbach, Albert C.; Pian, Julia; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Ctr, Boston, MA 02114 USA.
[Fahrenbach, Albert C.; Szostak, Jack W.] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, Tokyo 1528550, Japan.
[Sheng, Jia] SUNY Albany, Dept Chem, RNA Inst, Albany, NY 12222 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU Fonds de recherche du Quebec-Nature et technologies; ELSI; Autonomous
Province of Trento, Call 'Grandi Progetti', project 'Characterizing and
improving brain mechanisms of attention-ATTEND [CHE-0809413]; Simons
Foundation [290363]
FX The Autonomous Province of Trento, Call 'Grandi Progetti 2012', project
'Characterizing and improving brain mechanisms of attention-ATTEND
[CHE-0809413]; Simons Foundation [290363 to J.W.S.]. A.T.L. is partially
supported by a fellowship from Fonds de recherche du Quebec-Nature et
technologies. A.C.F. would like to thank ELSI for a postdoctoral
fellowship award. J.W.S. is an Investigator of the Howard Hughes Medical
Institute. Funding for open access charge: Simons Collaboration on the
Origins of Life.
NR 55
TC 5
Z9 6
U1 7
U2 27
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP 18
PY 2015
VL 43
IS 16
BP 7675
EP 7687
DI 10.1093/nar/gkv761
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS4WW
UT WOS:000362077900009
PM 26240387
ER
PT J
AU Hu, YJ
Belaghzal, H
Hsiao, WY
Qi, J
Bradner, JE
Guertin, DA
Sif, S
Imbalzano, AN
AF Hu, Yu-Jie
Belaghzal, Houda
Hsiao, Wen-Yu
Qi, Jun
Bradner, James E.
Guertin, David A.
Sif, Said
Imbalzano, Anthony N.
TI Transcriptional and post-transcriptional control of adipocyte
differentiation by Jumonji domain-containing protein 6
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PHOSPHATIDYLSERINE RECEPTOR; ENHANCER RNAS; PPAR-GAMMA;
SELECTIVE-INHIBITION; SUPER-ENHANCERS; GENE-EXPRESSION; PAUSE RELEASE;
JMJD6; BRD4; CHROMATIN
AB Jumonji domain-containing protein 6 ( JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/ EBP beta and C/ EBP delta protein expression without affectingmRNA levels in the early phase of differentiation. However, ectopic expression of C/ EBP beta and C/ EBP delta did not rescue differentiation. Further analysis demonstrated that JMJD6 was associated with the Ppar.2 and Cebp alpha loci and putative enhancers. JMJD6 was previously found associated with bromodomain and extra-terminal domain ( BET) proteins, which can be targeted by the bromodomain inhibitor JQ1. JQ1 treatment prevented chromatin binding of JMJD6, Ppar.2 and Cebpa expression, and adipogenic differentiation, yet had no effect on C/ EBP beta and C/ EBP delta expression or chromatin binding. These results indicate dual roles for JMJD6 in promoting adipogenic gene expression program by post-transcriptional regulation of C/ EBP beta and C/ EBP delta and direct transcriptional activation of Ppar.2 and Cebpa during adipocyte differentiation.
C1 [Hu, Yu-Jie; Belaghzal, Houda; Imbalzano, Anthony N.] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA.
[Hsiao, Wen-Yu; Guertin, David A.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Sif, Said] Ohio State Univ, Coll Med, Dept Internal Med, Columbus, OH 43210 USA.
[Sif, Said] Qatar Univ, Coll Arts & Sci, Dept Biol & Environm Sci, Doha, Qatar.
RP Imbalzano, AN (reprint author), Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA.
EM anthony.imbalzano@umassmed.edu
FU National Institutes of Health (NIH) [DK084278, GM56244, DK32520]
FX National Institutes of Health (NIH) [DK084278 to S.S. and A.N.I.,
GM56244 to A.N.I., DK32520 to UMass Medical School Diabetes and
Endocrine Research Center].
NR 66
TC 6
Z9 6
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP 18
PY 2015
VL 43
IS 16
BP 7790
EP 7804
DI 10.1093/nar/gkv645
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CS4WW
UT WOS:000362077900018
PM 26117538
ER
PT J
AU Teshome, BF
Lee, GC
Reveles, KR
Attridge, RT
Koeller, J
Wang, CP
Mortensen, EM
Frei, CR
AF Teshome, Besu F.
Lee, Grace C.
Reveles, Kelly R.
Attridge, Russell T.
Koeller, Jim
Wang, Chen-pin
Mortensen, Eric M.
Frei, Christopher R.
TI Application of a methicillin-resistant Staphylococcus aureus risk score
for community-onset pneumonia patients and outcomes with initial
treatment
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID CARE-ASSOCIATED PNEUMONIA; INFECTIOUS-DISEASES-SOCIETY; ACQUIRED
PNEUMONIA; NOSOCOMIAL PNEUMONIA; ANTIBIOTIC-THERAPY; INFLUENZA SEASON;
PATHOGENS; ADULTS; COHORT; EPIDEMIOLOGY
AB Background: Community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an evolving problem, and there is a great need for a reliable method to assess MRSA risk at hospital admission. A new MRSA prediction score classifies CO-pneumonia patients into low, medium, and high-risk groups based on objective criteria available at baseline. Our objective was to assess the effect of initial MRSA therapy on mortality in these three risk groups.
Methods: We conducted a retrospective cohort study using data from the Veterans Health Administration (VHA). Patients were included if they were hospitalized with pneumonia and received antibiotics within the first 48 h of admission. They were stratified into MRSA therapy and no MRSA therapy treatment arms based on antibiotics received in the first 48 h. Multivariable logistic regression was used to adjust for potential confounders.
Results: A total of 80,330 patients met inclusion criteria, of which 36 % received MRSA therapy and 64 % did not receive MRSA therapy. The majority of patients were classified as either low (51 %) or medium (47 %) risk, with only 2 % classified as high-risk. Multivariable logistic regression analysis demonstrated that initial MRSA therapy was associated with a lower 30-day mortality in the high-risk group (adjusted odds ratio 0.57; 95 % confidence interval 0.42-0.77). Initial MRSA therapy was not beneficial in the low or medium-risk groups.
Conclusions: This study demonstrated improved survival with initial MRSA therapy in high-risk CO-pneumonia patients. The MRSA risk score might help spare MRSA therapy for only those patients who are likely to benefit.
C1 [Teshome, Besu F.] St Louis Coll Pharm, St Louis, MO USA.
[Teshome, Besu F.; Lee, Grace C.; Reveles, Kelly R.; Koeller, Jim; Frei, Christopher R.] Univ Texas Austin, Coll Pharm, Pharmacotherapy Div, Austin, TX 78712 USA.
[Teshome, Besu F.; Lee, Grace C.; Reveles, Kelly R.; Koeller, Jim; Frei, Christopher R.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA.
[Attridge, Russell T.] Univ Incarnate Word, Feik Sch Pharm, San Antonio, TX USA.
[Attridge, Russell T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Wang, Chen-pin] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA.
[Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Frei, CR (reprint author), Univ Texas Austin, Coll Pharm, Pharmacotherapy Div, Austin, TX 78712 USA.
EM freic@uthscsa.edu
OI Mortensen, Eric/0000-0002-3880-5563
FU National Institutes of Health (NIH)/National Institute of Nursing
Research [R01NR010828]; NIH Clinical Research Scholar (KL2) career
development award (National Center for Research Resources) [5KL2
RR025766]; NIH Clinical Research Scholar (KL2) career development award
(National Center for Advancing Translational Sciences) [8KL2 TR000118];
Agency for Healthcare Research and Quality [R24 HS022418]; University of
Texas Southwestern Center for Patient-Centered Outcomes Research
FX This study was supported by a grant from the National Institutes of
Health (NIH)/National Institute of Nursing Research (R01NR010828). Dr.
Frei was supported in part by a NIH Clinical Research Scholar (KL2)
career development award (National Center for Research Resources 5KL2
RR025766 [2010-2012] and National Center for Advancing Translational
Sciences 8KL2 TR000118 [2013]). Dr. Mortensen was supported in part by a
grant from the Agency for Healthcare Research and Quality (R24 HS022418)
and the University of Texas Southwestern Center for Patient-Centered
Outcomes Research. This material is the result of work supported with
resources and the use of facilities at the South Texas Veterans Health
Care System. The funding sources had no role in the design and conduct
of the study; collection, management, analysis, and interpretation of
the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication. The views expressed
in this article are those of the authors and do not necessarily
represent the views of the Department of Veterans Affairs or the
National Institutes of Health. Finally, the co-authors would like to
acknowledge the assistance of Stefan Allen and Ashley Pechal (pharmacy
students at The University of Texas at Austin College of Pharmacy, who
assisted the co-authors with literature searches during part of the peer
review process).
NR 40
TC 3
Z9 3
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD SEP 18
PY 2015
VL 15
AR 380
DI 10.1186/s12879-015-1119-1
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA CR5BV
UT WOS:000361355200001
PM 26385225
ER
PT J
AU Miyamoto, DT
Zheng, Y
Wittner, BS
Lee, RJ
Zhu, HL
Broderick, KT
Desai, R
Fox, DB
Brannigan, BW
Trautwein, J
Arora, KS
Desai, N
Dahl, DM
Sequist, LV
Smith, MR
Kapur, R
Wu, CL
Shioda, T
Ramaswamy, S
Ting, DT
Toner, M
Maheswaran, S
Haber, DA
AF Miyamoto, David T.
Zheng, Yu
Wittner, Ben S.
Lee, Richard J.
Zhu, Huili
Broderick, Katherine T.
Desai, Rushil
Fox, Douglas B.
Brannigan, Brian W.
Trautwein, Julie
Arora, Kshitij S.
Desai, Niyati
Dahl, Douglas M.
Sequist, Lecia V.
Smith, Matthew R.
Kapur, Ravi
Wu, Chin-Lee
Shioda, Toshi
Ramaswamy, Sridhar
Ting, David T.
Toner, Mehmet
Maheswaran, Shyamala
Haber, Daniel A.
TI RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in
antiandrogen resistance
SO SCIENCE
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; CANCER; PATHWAY; ENZALUTAMIDE; METASTASIS;
DATABASE
AB Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging; hence, sampling circulating tumor cells (CTCs) may reveal drug-resistance mechanisms. We established single-cell RNA-sequencing (RNA-Seq) profiles of 77 intact CTCs isolated from 13 patients (mean six CTCs per patient), by using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing under treatment with an AR inhibitor, compared with untreated cases, indicates activation of noncanonical Wnt signaling (P = 0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, whereas its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single-cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.
C1 [Miyamoto, David T.; Zheng, Yu; Wittner, Ben S.; Lee, Richard J.; Zhu, Huili; Broderick, Katherine T.; Desai, Rushil; Fox, Douglas B.; Brannigan, Brian W.; Trautwein, Julie; Arora, Kshitij S.; Desai, Niyati; Dahl, Douglas M.; Sequist, Lecia V.; Smith, Matthew R.; Wu, Chin-Lee; Shioda, Toshi; Ramaswamy, Sridhar; Ting, David T.; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Canc Ctr, Charlestown, MA 02129 USA.
[Miyamoto, David T.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Charlestown, MA 02129 USA.
[Zheng, Yu; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Wittner, Ben S.; Lee, Richard J.; Sequist, Lecia V.; Smith, Matthew R.; Ramaswamy, Sridhar; Ting, David T.; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Charlestown, MA 02129 USA.
[Arora, Kshitij S.; Desai, Niyati; Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Charlestown, MA 02129 USA.
[Dahl, Douglas M.] Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, Charlestown, MA 02129 USA.
[Kapur, Ravi; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Ctr Bioengn Med, Sch Med, Charlestown, MA 02129 USA.
[Maheswaran, Shyamala] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Charlestown, MA 02129 USA.
RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Canc Ctr, Charlestown, MA 02129 USA.
EM haber@helix.mgh.harvard.edu; smaheswaran@mgh.harvard.edu
RI bebarta, vikhyat/K-3476-2015;
OI Ting, David/0000-0002-3261-2322
FU Prostate Cancer Foundation; Charles Evans Foundation; Department of
Defense; Stand Up to Cancer; Howard Hughes Medical Institute; National
Institute of Biomedical Imaging and Bioengineering (NIBIB); NIH
[EB008047]; NCI [2RO1CA129933]; National Cancer Institute, NCI; Federal
Share Program and Income; Affymetrix, Inc.; Mazzone Program-Dana-Farber
Harvard Cancer Center; Burroughs Wellcome Fund; Massachusetts General
Hospital-Johnson & Johnson Center for Excellence in CTC Technologies;
Janssen LLC.
FX We thank C. Sawyers for helpful discussions; A. McGovern, E.
Stadtmueller, and B. Abebe for clinical trial support; and L. Libby and
L. Nieman for technical assistance. This work was supported by grants
from the Prostate Cancer Foundation (D.A.H., S.M., M.T., M.R.S., and
R.J.L.), Charles Evans Foundation (D.A.H.), Department of Defense
(D.T.M., R.J.L., and D.T.T.), Stand Up to Cancer (D.A.H., M.T., S.M.,
and L.V.S.), Howard Hughes Medical Institute (D.A.H.), National
Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH,
EB008047 (M.T.), NCI 2RO1CA129933 (D.A.H.), National Cancer Institute,
NCI, Federal Share Program and Income (S.M. and D.T.M.), Affymetrix,
Inc. (D.T.T., K.A., and N.D.), Mazzone Program-Dana-Farber Harvard
Cancer Center (D.T.M.), Burroughs Wellcome Fund (D.T.T.), and the
Massachusetts General Hospital-Johnson & Johnson Center for Excellence
in CTC Technologies (D.A.H., M.T., and S.M.). D.T.T. is a paid
consultant for Affymetrix, Inc.; R.J.L. is a paid consultant for Janssen
LLC. The Massachusetts General Hospital has filed for patent protection
for the CTC-iChip technology. RNA-sequencing data have been deposited in
GEO under accession number GSE67980.
NR 30
TC 78
Z9 81
U1 10
U2 60
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD SEP 18
PY 2015
VL 349
IS 6254
BP 1351
EP 1356
DI 10.1126/science.aab0917
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5CR
UT WOS:000361357700052
PM 26383955
ER
PT J
AU Feske, SK
Goldberg, M
Dudzinski, DM
Gonzalez, RG
Kovach, AE
AF Feske, Steven K.
Goldberg, Marcia
Dudzinski, David M.
Gonzalez, Ramon Gilberto
Kovach, Alexandra E.
TI Case 29-2015: A 38-Year-Old Pregnant Woman with Headache and Visual
Symptoms
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ENDOMYOCARDIAL FIBROSIS; HYPEREOSINOPHILIC SYNDROME; EPIDEMIOLOGY;
MYOCARDITIS; STROKE; SYSTEM; WOMEN; PICA; RISK
C1 [Feske, Steven K.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Goldberg, Marcia] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Dudzinski, David M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Gonzalez, Ramon Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kovach, Alexandra E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Feske, Steven K.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Goldberg, Marcia; Dudzinski, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gonzalez, Ramon Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Kovach, Alexandra E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Feske, SK (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
NR 23
TC 0
Z9 0
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 SEP 17
PY 2015
VL 373
IS 12
BP 1154
EP 1164
DI 10.1056/NEJMcpc1404335
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR7UG
UT WOS:000361556400012
PM 26376139
ER
PT J
AU Brook, K
Camargo, CA
Christopher, KB
Quraishi, SA
AF Brook, Karolina
Camargo, Carlos A.
Christopher, Kenneth B.
Quraishi, Sadeq A.
TI Admission vitamin D status is associated with discharge destination in
critically ill surgical patients
SO ANNALS OF INTENSIVE CARE
LA English
DT Article
DE Vitamin D; 25-hydroxyvitamin D; Critical illness; Discharge destination;
Patient-centered outcome
ID INTENSIVE-CARE-UNIT; LOCALLY WEIGHTED REGRESSION; CHRONIC CRITICAL
ILLNESS; SKELETAL-MUSCLE CELLS; LENGTH-OF-STAY; D DEFICIENCY; SEVERE
SEPSIS; 25-HYDROXYVITAMIN D-1-ALPHA-HYDROXYLASE;
1,25-DIHYDROXYVITAMIN-D3 RECEPTORS; HOSPITAL DISCHARGE
AB Background: Discharge destination after critical illness is increasingly recognized as a valuable patient-centered outcome. Recently, vitamin D status has been shown to be associated with important outcomes such as length of stay (LOS) and mortality in intensive care unit (ICU) patients. Our goal was to investigate whether vitamin D status on ICU admission is associated with discharge destination.
Methods: We performed a retrospective analysis from an ongoing prospective cohort study of vitamin D status in critical illness. Patients were recruited from two surgical ICUs at a single teaching hospital in Boston, Massachusetts. All patients had 25-hydroxyvitamin D (25OHD) levels measured within 24 h of ICU admission. Discharge destination was dichotomized as non-home or home. Locally weighted scatterplot smoothing (LOWESS) was used to graph the relationship between 25OHD levels and discharge destination. To investigate the association between 25OHD level and discharge destination, we performed logistic regression analyses, controlling for age, sex, race, body mass index, socioeconomic status, acute physiology and chronic health evaluation II score, need for emergent vs. non-emergent surgery, vitamin D supplementation status, and hospital LOS.
Results: 300 patients comprised the analytic cohort. Mean 25OHD level was 19 (standard deviation 8) ng/mL and 41 % of patients had a non-home discharge destination. LOWESS analysis demonstrated a near-inverse linear relationship between vitamin D status and non-home discharge destination to 25OHD levels around 10 ng/mL, with rapid flattening of the curve between levels of 10 and 20 ng/mL. Overall, 25OHD level at the outset of critical illness was inversely associated with non-home discharge destination (adjusted OR, 0.88; 95 % CI 0.82-0.95). When vitamin D status was dichotomized, patients with 25OHD levels < 20 ng/mL had an almost 3-fold risk of a non-home discharge destination (adjusted OR, 2.74; 95 % CI 1.23-6.14) compared to patients with 25OHD levels >= 20 ng/mL.
Conclusions: Our results suggest that vitamin D status may be a modifiable risk factor for non-home discharge destination in surgical ICU patients. Future randomized, controlled trials are needed to determine whether vitamin D supplementation in surgical ICU patients can improve clinical outcomes such as the successful rate of discharge to home after critical illness
C1 [Brook, Karolina; Quraishi, Sadeq A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Camargo, Carlos A.; Christopher, Kenneth B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Camargo, Carlos A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Quraishi, Sadeq A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
RP Quraishi, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA.
EM squraishi@mgh.harvard.edu
FU United States National Institutes of Health [R01 AI093723, U01 AI087881,
T32 GM007592, UL1 RR025758, L30 TR001257]; Harvard Medical School
FX CAC received support from the United States National Institutes of
Health grants R01 AI093723 and U01 AI087881. SAQ received support from
the United States National Institutes of Health grants T32 GM007592, UL1
RR025758, and L30 TR001257 as well as from Harvard Medical School.
NR 82
TC 0
Z9 0
U1 1
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 2110-5820
J9 ANN INTENSIVE CARE
JI Ann. Intensive Care
PD SEP 17
PY 2015
VL 5
AR 23
DI 10.1186/s13613-015-0065-9
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA CZ9AY
UT WOS:000367391400002
PM 26380991
ER
PT J
AU Buisson, R
Boisvert, JL
Benes, CH
Zou, L
AF Buisson, Remi
Boisvert, Jessica L.
Benes, Cyril H.
Zou, Lee
TI Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering
Replication Stress during S Phase
SO MOLECULAR CELL
LA English
DT Article
ID RIBONUCLEOTIDE REDUCTASE R2; ADVANCED SOLID TUMORS; DAMAGE CHECKPOINT;
CANCER-CELLS; GENOMIC INSTABILITY; FORK PROGRESSION; DOSE-ESCALATION;
DEFICIENT CELLS; BETA-TRCP; ACTIVATION
AB The ATR-Chk1 pathway is critical for DNA damage responses and cell-cycle progression. Chk1 inhibition is more deleterious to cycling cells than ATR inhibition, raising questions about ATR and Chk1 functions in the absence of extrinsic replication stress. Here we show that a key role of ATR in S phase is to coordinate RRM2 accumulation and origin firing. ATR inhibitor (ATRi) induces massive ssDNA accumulation and replication catastrophe in a fraction of early S-phase cells. In other S-phase cells, however, ATRi induces moderate ssDNA and triggers a DNA-PK and Chk1-mediated backup pathway to suppress origin firing. The backup pathway creates a threshold such that ATRi selectively kills cells under high replication stress, whereas Chk1 inhibitor induces cell death at a lower threshold. The levels of ATRi-induced ssDNA correlate with ATRi sensitivity in a panel of cell lines, suggesting that ATRi-induced ssDNA could be predictive of ATRi sensitivity in cancer cells.
C1 [Buisson, Remi; Boisvert, Jessica L.; Benes, Cyril H.; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
EM zou.lee@mgh.harvard.edu
FU NIH [GM076388]; Federal Share of the MGH Proton Program; Wellcome Trust
[102696]
FX We thank J. Bartek, C. Bakkenist, B. Chen, N. Dyson, M. Lopes, S.
Maheswaran, M. Pagano, and W. Wei for reagents; S. Yazinski and V.
Comaills for advice on DNA fiber and qRT-PCR assays; E. Hardy for
technical assistance; and members of the L.Z. lab for helpful
discussions. R.B. is partly supported by a Tosteson Postdoctoral Award,
a Marsha Rivkin Scientific Scholar Award, and a fellowship from the
Phillips Foundation. L.Z. is a Jim & Ann Orr Massachusetts General
Hospital (MGH) Research Scholar. This work was supported by grants from
the NIH (GM076388) and the Federal Share of the MGH Proton Program to
L.Z. and a grant from the Wellcome Trust (102696) to C.H.B.
NR 70
TC 19
Z9 19
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD SEP 17
PY 2015
VL 59
IS 6
BP 1011
EP 1024
DI 10.1016/j.molcel.2015.07.029
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CW7GQ
UT WOS:000365166500013
PM 26365377
ER
PT J
AU Hiraki, M
Hwang, SY
Cao, SG
Ramadhar, TR
Byun, S
Yoon, KW
Lee, JH
Chu, K
Gurkar, AU
Kolev, V
Zhang, JM
Namba, T
Murphy, ME
Newman, DJ
Mandinova, A
Clardy, J
Lee, SW
AF Hiraki, Masatsugu
Hwang, So-Young
Cao, Shugeng
Ramadhar, Timothy R.
Byun, Sanguine
Yoon, Kyoung Wan
Lee, Jung Hyun
Chu, Kiki
Gurkar, Aditi U.
Kolev, Vihren
Zhang, Jianming
Namba, Takushi
Murphy, Maureen E.
Newman, David J.
Mandinova, Anna
Clardy, Jon
Lee, Sam W.
TI Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through
the p53-Hsp40 Regulatory Axis
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR P53; CANCER-CELLS; BREAST-CANCER; COMPLEX; STRESS;
TARGET; IDENTIFICATION; TRANSCRIPTION; INHIBITION; EXPRESSION
AB TP53 is the most frequently mutated gene in human cancer, and small-molecule reactivation of mutant p53 function represents an important anticancer strategy. A cell-based, high-throughput small-molecule screen identified chetomin (CTM) as a mutant p53 R175H reactivator. CTM enabled p53 to transac-tivate target genes, restored MDM2 negative regulation, and selectively inhibited the growth of cancer cells harboring mutant p53 R175H in vitro and in vivo. We found that CTM binds to Hsp40 and increases the binding capacity of Hsp40 to the p53 R175H mutant protein, causing a potential conformational change to a wild-type-like p53. Thus, CTM acts as a specific reactivator of the p53 R175H mutant form through Hsp40. These results provide new insights into the mechanism of reactivation of this specific p53 mutant.
C1 [Hiraki, Masatsugu; Hwang, So-Young; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; Chu, Kiki; Gurkar, Aditi U.; Kolev, Vihren; Zhang, Jianming; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Hiraki, Masatsugu; Hwang, So-Young; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; Chu, Kiki; Gurkar, Aditi U.; Kolev, Vihren; Zhang, Jianming; Namba, Takushi; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Cao, Shugeng] Univ Hawaii, Dept Pharmaceut Sci, Daniel K Inouye Coll Pharm, Hilo, HI 96720 USA.
[Cao, Shugeng; Ramadhar, Timothy R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Murphy, Maureen E.] Wistar Inst Anat & Biol, Program Mol & Cellular Oncogenesis, Philadelphia, PA 19104 USA.
[Newman, David J.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[Mandinova, Anna; Lee, Sam W.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Clardy, J (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM jon_clardy@hms.harvard.edu; swlee@mgh.harvard.edu
OI Ramadhar, Timothy/0000-0002-7063-5445
FU postdoctoral fellowships for research abroad from the Japan Society for
the Promotion of Science; research fellowship for research abroad from
the Uehara Memorial Foundation; F32 postdoctoral fellowship from the NIH
[GM108415]; NIH [CA142805, CA149477, CA80058, GM086258]; FAS Division of
Science, Research Computing group at Harvard University
FX We thank Z. Yuan for MEF cells, X. Chen and J. Manfredi for mutant p53
plasmids and tet-inducible cell lines, J. Manfredi for p53 binding site
of PUMA promoter plasmid, M. Taipale and S. Lindquist for materials and
help on some heat-shock protein activity experiments, H. Li and S. J.
Lee for help on Biacore studies, and W. Gu for in vitro gel-shift
experiments. M. H. and T.N. were supported by postdoctoral fellowships
for research abroad from the Japan Society for the Promotion of Science.
M. H. was also supported by a research fellowship for research abroad
from the Uehara Memorial Foundation. T.R.R. was supported by an F32
postdoctoral fellowship from the NIH (GM108415). The research was
supported by NIH grants CA142805, CA149477, CA80058, and GM086258.
Quantum-chemical calculations were run on the Odyssey cluster supported
by the FAS Division of Science, Research Computing group at Harvard
University.
NR 46
TC 7
Z9 7
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD SEP 17
PY 2015
VL 22
IS 9
BP 1206
EP 1216
DI 10.1016/j.chembiol.2015.07.016
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CV1JT
UT WOS:000364012100006
PM 26320861
ER
PT J
AU Rook, AH
Gelfand, JC
Wysocka, M
Troxel, AB
Benoit, B
Surber, C
Elenitsas, R
Buchanan, MA
Leahy, DS
Watanabe, R
Kirsch, IR
Kim, EJ
Clark, RA
AF Rook, Alain H.
Gelfand, Joel C.
Wysocka, Maria
Troxel, Andrea B.
Benoit, Bernice
Surber, Christian
Elenitsas, Rosalie
Buchanan, Marie A.
Leahy, Deborah S.
Watanabe, Rei
Kirsch, Ilan R.
Kim, Ellen J.
Clark, Rachael A.
TI Topical resiquimod can induce disease regression and enhance T-cell
effector functions in cutaneous T-cell lymphoma
SO BLOOD
LA English
DT Article
ID IMMUNE-RESPONSE MODIFIER; MYCOSIS-FUNGOIDES; DENDRITIC CELLS;
SEZARY-SYNDROME; SKIN-CANCER; IMIQUIMOD; CLASSIFICATION; INTERLEUKIN-12;
RESIDENT; AGONISTS
AB Early-stage cutaneous T-cell lymphoma (CTCL) is a skin-limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T-cell clones in treated skin, increased skin T-cell effector functions, and a trend toward increased natural killer cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. Fifty percent of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early-stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients. This trial was registered at www.clinicaltrials.gov as #NCT813320.
C1 [Rook, Alain H.; Gelfand, Joel C.; Wysocka, Maria; Troxel, Andrea B.; Benoit, Bernice; Elenitsas, Rosalie; Buchanan, Marie A.; Leahy, Deborah S.; Kim, Ellen J.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
[Rook, Alain H.; Gelfand, Joel C.; Wysocka, Maria; Troxel, Andrea B.; Benoit, Bernice; Elenitsas, Rosalie; Buchanan, Marie A.; Leahy, Deborah S.; Kim, Ellen J.] Univ Penn, Perelman Sch Med, Ctr Clin Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Surber, Christian] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Surber, Christian] Univ Basel Hosp, Dept Dermatol, CH-4031 Basel, Switzerland.
[Watanabe, Rei] Univ Tokyo, Dept Dermatol, Tokyo 113, Japan.
[Watanabe, Rei; Clark, Rachael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Kirsch, Ilan R.] Adapt Biotechnol, Seattle, WA USA.
[Clark, Rachael A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
RP Rook, AH (reprint author), Perelman Sch Med, Dept Dermatol, 3600 Spruce St, Philadelphia, PA 19104 USA.
EM arook@mail.med.upenn.edu; rclark1@partners.org
OI Troxel, Andrea/0000-0002-1393-3075
FU National Institutes of Health (NIH)/National Cancer Institute [R01
CA122569, R21 CA178424, FD-RO1-04092]; NIH/National Institute of
Arthritis and Musculoskeletal and Skin Diseases [R01 AR056720, R01
AR063962]; NIH [R01 AI097128]; CLARIONS from the Cutaneous Lymphoma
Foundation; Leukemia and Lymphoma Society; Leukemia & Lymphoma Society
FX This work was supported by the National Institutes of Health
(NIH)/National Cancer Institute grant R01 CA122569 (to A.H.R.), grant
R21 CA178424 (to A.H.R. and M.W.), and grant FD-RO1-04092 (to A.H.R.);
NIH/National Institute of Arthritis and Musculoskeletal and Skin
Diseases (grants R01 AR056720 and R01 AR063962) (to R.A.C.); and NIH
(R01 AI097128) (to Thomas S. Kupper and R.A.C.). This work was also
supported by a CLARIONS grant from the Cutaneous Lymphoma Foundation (to
R.A.C.), a Translational Research grant from the Leukemia and Lymphoma
Society (to A.H.R.), and a Special Fellow grant from the Leukemia &
Lymphoma Society (to R.W.).
NR 24
TC 10
Z9 10
U1 1
U2 4
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 SEP 17
PY 2015
VL 126
IS 12
BP 1452
EP 1461
DI 10.1182/blood-2015-02-630335
PG 10
WC Hematology
SC Hematology
GA CU4ET
UT WOS:000363480500011
PM 26228486
ER
PT J
AU Black, JC
Whetstine, JR
AF Black, Joshua C.
Whetstine, Johnathan R.
TI Too little O-2 Too much gain
SO CELL CYCLE
LA English
DT Editorial Material
ID COPY GAIN; EXPRESSION; CANCER
C1 [Whetstine, Johnathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA.
RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM jwhetstine@hms.harvard.edu
RI Black, Joshua/Q-2484-2015
NR 6
TC 2
Z9 2
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD SEP 17
PY 2015
VL 14
IS 18
BP 2869
EP 2870
DI 10.1080/15384101.2015.1076659
PG 2
WC Cell Biology
SC Cell Biology
GA CR7KE
UT WOS:000361527600004
PM 26221746
ER
PT J
AU Xiong, ML
Ferder, IC
Ohguchi, Y
Wang, N
AF Xiong, Mulin
Ferder, Ianina C.
Ohguchi, Yasuyo
Wang, Ning
TI Quantitative analysis of male germline stem cell differentiation reveals
a role for the p53-mTORC1 pathway in spermatogonial maintenance
SO CELL CYCLE
LA English
DT Article
DE differentiation; germline stem cell; mTORC1; p53; spermatogonia
ID SELF-RENEWAL; UNDIFFERENTIATED SPERMATOGONIA; TUMOR SUPPRESSION;
GENE-EXPRESSION; RETINOIC ACID; MTOR PATHWAY; MOUSE TESTES; P53; MICE;
QUIESCENCE
AB p53 protects cells from DNA damage by inducing cell-cycle arrest upon encountering genomic stress. Among other pathways, p53 elicits such an effect by inhibiting mammalian target of rapamycin complex 1 (mTORC1), the master regulator of cell proliferation and growth. Although recent studies have indicated roles for both p53 and mTORC1 in stem cell maintenance, it remains unclear whether the p53-mTORC1 pathway is conserved to mediate this process under normal physiological conditions. Spermatogenesis is a classic stem cell-dependent process in which undifferentiated spermatogonia undergo self-renewal and differentiation to maintain the lifelong production of spermatozoa. To better understand this process, we have developed a novel flow cytometry (FACS)-based approach that isolates spermatogonia at consecutive differentiation stages. By using this as a tool, we show that genetic loss of p53 augments mTORC1 activity during early spermatogonial differentiation. Functionally, loss of p53 drives spermatogonia out of the undifferentiated state and causes a consistent expansion of early differentiating spermatogonia until the stage of preleptotene (premeiotic) spermatocyte. The frequency of early meiotic spermatocytes is, however, dramatically decreased. Thus, these data suggest that p53-mTORC1 pathway plays a critical role in maintaining the homeostasis of early spermatogonial differentiation. Moreover, our FACS approach could be a valuable tool in understanding spermatogonial differentiation.
C1 [Xiong, Mulin; Ferder, Ianina C.; Ohguchi, Yasuyo; Wang, Ning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Dept Obstet & Gyn, Boston, MA 02138 USA.
RP Wang, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Dept Obstet & Gyn, Boston, MA 02138 USA.
EM nwang3@mgh.harvard.edu
FU NIA [R00-AG-039512]; Vincent Department of Obstetrics and Gynecology at
Massachusetts General Hospital
FX This work was supported by NIA (R00-AG-039512) and the Vincent
Department of Obstetrics and Gynecology at Massachusetts General
Hospital to N.W.
NR 51
TC 2
Z9 2
U1 0
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD SEP 17
PY 2015
VL 14
IS 18
BP 2905
EP 2913
DI 10.1080/15384101.2015.1069928
PG 9
WC Cell Biology
SC Cell Biology
GA CR7KE
UT WOS:000361527600014
PM 26177380
ER
PT J
AU Lammers, KM
Chieppa, M
Liu, L
Liu, S
Omatsu, T
Janka-Junttila, M
Casolaro, V
Reinecker, HC
Parent, CA
Fasano, A
AF Lammers, Karen M.
Chieppa, Marcello
Liu, Lunhua
Liu, Song
Omatsu, Tatsushi
Janka-Junttila, Mirkka
Casolaro, Vincenzo
Reinecker, Hans-Christian
Parent, Carole A.
Fasano, Alessio
TI Gliadin Induces Neutrophil Migration via Engagement of the Formyl
Peptide Receptor, FPR1
SO PLOS ONE
LA English
DT Article
ID MUCOSAL GRANULOCYTE ACTIVATION; CELIAC-DISEASE; INTESTINAL PERMEABILITY;
BARRIER FUNCTION; GUT PERMEABILITY; CONTROLLED-TRIAL; GENE-EXPRESSION;
GLUTEN; ZONULIN; CHEMOTAXIS
AB Background
Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-activating and chemoattractant chemokine. We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure.
Methods
Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control.
Results
Redistribution of ZO-1 and an influx of CD11b(+)Lys6G(+) cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP(+) cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe. We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu-Phe-, gliadin- and synthetic peptide-induced migration.
Conclusions
Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process.
C1 [Lammers, Karen M.; Fasano, Alessio] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA.
[Chieppa, Marcello] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Lunhua; Janka-Junttila, Mirkka; Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Song; Omatsu, Tatsushi; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
RP Lammers, KM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA.
EM klammers@mgh.harvard.edu
RI Casolaro, Vincenzo/E-9144-2010;
OI Casolaro, Vincenzo/0000-0001-9810-0488; Chieppa,
Marcello/0000-0001-9819-0823
FU National Institutes of Health [DK-078699, DK-48373, DK068181, AI113333,
DK033506, DK043351, MFAG 10684]; Center for Cancer Research, NCI, NIH;
Associazione Italiana per la Ricerca sul Cancro
FX This research was supported in part by the National Institutes of Health
Grants DK-078699 and DK-48373 to AF, DK068181, AI113333, DK033506 and
DK043351 to HCR, MFAG 10684 (AIRC) to MC, and the Intramural Research
Program of the Center for Cancer Research, NCI, NIH to CAP. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 41
TC 2
Z9 2
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 17
PY 2015
VL 10
IS 9
AR e0138338
DI 10.1371/journal.pone.0138338
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CS0RH
UT WOS:000361769400084
PM 26378785
ER
PT J
AU Elsarraj, HS
Hong, Y
Valdez, KE
Michaels, W
Hook, M
Smith, WP
Chien, J
Herschkowitz, JI
Troester, MA
Beck, M
Inciardi, M
Gatewood, J
May, L
Cusick, T
McGinness, M
Ricci, L
Fan, F
Tawfik, O
Marks, JR
Knapp, JR
Yeh, HW
Thomas, P
Carrasco, DR
Fields, TA
Godwin, AK
Behbod, F
AF Elsarraj, Hanan S.
Hong, Yan
Valdez, Kelli E.
Michaels, Whitney
Hook, Marcus
Smith, William P.
Chien, Jeremy
Herschkowitz, Jason I.
Troester, Melissa A.
Beck, Moriah
Inciardi, Marc
Gatewood, Jason
May, Lisa
Cusick, Therese
McGinness, Marilee
Ricci, Lawrence
Fan, Fang
Tawfik, Ossama
Marks, Jeffrey R.
Knapp, Jennifer R.
Yeh, Hung-Wen
Thomas, Patricia
Carrasco, D. R.
Fields, Timothy A.
Godwin, Andrew K.
Behbod, Fariba
TI Expression profiling of in vivo ductal carcinoma in situ progression
models identified B cell lymphoma-9 as a molecular driver of breast
cancer invasion
SO BREAST CANCER RESEARCH
LA English
DT Article
ID WNT SIGNALING PATHWAY; CANDIDATE GENES; RNA-SEQ; ACTIVATION; MARKERS;
COMPLEX; TARGET; COLON; NOTCH; DCIS
AB Introduction: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated beta-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized.
Methods: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers.
Results: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification.
Conclusion: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.
C1 [Elsarraj, Hanan S.; Hong, Yan; Valdez, Kelli E.; Fan, Fang; Tawfik, Ossama; Thomas, Patricia; Fields, Timothy A.; Godwin, Andrew K.; Behbod, Fariba] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66160 USA.
[Michaels, Whitney; Hook, Marcus] Univ Kansas, Med Ctr, Sch Med, Kansas City, KS 66160 USA.
[Smith, William P.; Inciardi, Marc; Gatewood, Jason] Univ Kansas, Med Ctr, Dept Radiol, Kansas City, KS 66160 USA.
[Chien, Jeremy] Univ Kansas, Med Ctr, Dept Canc Biol, Kansas City, KS 66160 USA.
[Herschkowitz, Jason I.] SUNY Albany, Dept Biomed Sci, Rensselaer, NY 12144 USA.
[Troester, Melissa A.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA.
[Beck, Moriah] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA.
[May, Lisa; Cusick, Therese] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[McGinness, Marilee] Univ Kansas, Med Ctr, Dept Med, Kansas City, KS 66160 USA.
[Ricci, Lawrence] Univ Missouri, Truman Med Ctr, Dept Radiol, Kansas City, MO 64108 USA.
[Marks, Jeffrey R.] Duke Univ, Dept Surg, Durham, NC 27710 USA.
[Yeh, Hung-Wen] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA.
[Knapp, Jennifer R.] Univ Kansas, Med Ctr, Kansas Intellectual & Dev Disabil Res Ctr, Kansas City, KS 66160 USA.
[Carrasco, D. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA.
RP Behbod, F (reprint author), Univ Kansas, Med Ctr, Dept Pathol, 3901 Rainbow Blvd,Mail Stop 3003, Kansas City, KS 66160 USA.
EM fbehbod@kumc.edu
OI Knapp, Jennifer R./0000-0003-4342-5378; Chien,
Jeremy/0000-0003-4744-8374
FU Breast Cancer Research Foundation-AACR; NIH/NCI [1R21CA185460-01];
Institutional Development Award (IDeA) from the National Institute of
General Medical Sciences of the National Institutes of Health [P20
GM103418]; NCI Early Detection Research Network [U01 CA084955,
U01CA113916]; Komen Foundation [BCTR0603000]; University of Kansas
Cancer Center [P30 CA168524]; Chancellors Distinguished Chair in
Biomedical Sciences Professorship; Libyan-North American Scholarship
program; Kansas University-School of Medicine; Smith Intellectual and
Developmental Disabilities Research Center [HD02528]; K-INBRE
Bioinformatics Core, NIH [P20 RR016475]
FX This study was supported in part by grants from 2014 Breast Cancer
Research Foundation-AACR, NIH/NCI 1R21CA185460-01 and Institutional
Development Award (IDeA) from the National Institute of General Medical
Sciences of the National Institutes of Health P20 GM103418 (FB); by the
NCI Early Detection Research Network (U01 CA084955 to JRM and
U01CA113916 to AKG), and by the Komen Foundation (BCTR0603000) to TAF.
The authors also acknowledge support from The University of Kansas
Cancer Center (P30 CA168524). AKG was funded by the Chancellors
Distinguished Chair in Biomedical Sciences Professorship. HE was
supported by the Libyan-North American Scholarship program. We would
like to acknowledge the University of Kansas Cancer Center Biospecimen
Repository Core Facility staff for helping obtain human specimens. We
thank the Kansas University Medical Center-Genomics Core for generating
the array and sequencing data sets. The Genomics Core is supported by
the Kansas University-School of Medicine and the Smith Intellectual and
Developmental Disabilities Research Center (HD02528). Data analysis is
supported by the K-INBRE Bioinformatics Core, NIH grant number P20
RR016475.
NR 41
TC 4
Z9 5
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD SEP 17
PY 2015
VL 17
AR 128
DI 10.1186/s13058-015-0630-z
PG 21
WC Oncology
SC Oncology
GA CR4EF
UT WOS:000361283900002
PM 26384318
ER
PT J
AU Chen, P
Guven, S
Usta, OB
Yarmush, ML
Demirci, U
AF Chen, Pu
Gueven, Sinan
Usta, Osman Berk
Yarmush, Martin L.
Demirci, Utkan
TI Biotunable Acoustic Node Assembly of Organoids
SO ADVANCED HEALTHCARE MATERIALS
LA English
DT Article
ID FARADAY WAVES; REGENERATIVE MEDICINE; MICROSCALE HYDROGELS; BONE
REGENERATION; HEPATOCYTES; CHALLENGES; PATTERNS; LIVER; FILMS
C1 [Chen, Pu; Gueven, Sinan; Demirci, Utkan] Stanford Univ, Bioacoust MEMS Med BAMM Lab, Canary Ctr Stanford Early Canc Detect, Dept Radiol,Sch Med, Palo Alto, CA 94304 USA.
[Usta, Osman Berk; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
[Usta, Osman Berk; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA.
[Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
RP Demirci, U (reprint author), Stanford Univ, Bioacoust MEMS Med BAMM Lab, Canary Ctr Stanford Early Canc Detect, Dept Radiol,Sch Med, Palo Alto, CA 94304 USA.
EM utkan@stanford.edu
RI Chen, Pu/B-9795-2011
OI Chen, Pu/0000-0002-6857-2211
FU NIH [R21-HL112114, 1R01EB015776, R15HL115556, 4UH3TR000503-03,
2P41EB002503-11, NS069375]; National Science Foundation under NSF
[1150733]; Shrine Fellowship from Shriners Hospitals for Children
[84202]
FX P.C. and S.G. contributed equally to this work. The authors would like
to acknowledge NIH R21-HL112114, 1R01EB015776, R15HL115556,
4UH3TR000503-03, and 2P41EB002503-11. This material is based in part
upon work supported by the National Science Foundation under NSF CAREER
Award No. 1150733 and Shrine Fellowship #84202 (for O.B.U.) from the
Shriners Hospitals for Children. Any opinions, findings, and conclusions
or recommendations expressed in this material are those of the author(s)
and do not necessarily reflect the views of the National Science
Foundation. Authors acknowledge Stanford Neuroscience Microscopy Service
facility, which is supported by NIH NS069375. U.D. is a founder of, and
has an equity interest in: i) DxNow Inc., a company that is developing
microfluidic and imaging technologies for point-of-care diagnostic
solutions, and ii) Koek Biotech, a company that is developing
microfluidic IVF technologies for clinical solutions. U.D.'s interests
were viewed and managed by the Brigham and Women's Hospital and Partners
HealthCare in accordance with their conflict-of-interest policies.
Correspondence and requests for materials should be addressed to U.D.
NR 38
TC 5
Z9 5
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2192-2640
EI 2192-2659
J9 ADV HEALTHC MATER
JI Adv. Healthc. Mater.
PD SEP 16
PY 2015
VL 4
IS 13
BP 1937
EP 1943
DI 10.1002/adhm.201500279
PG 7
WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials
Science, Biomaterials
SC Engineering; Science & Technology - Other Topics; Materials Science
GA DA4EG
UT WOS:000367752300003
PM 26149464
ER
PT J
AU Si, Y
Kim, S
Cui, XQ
Zheng, L
Oh, SJ
Anderson, T
AlSharabati, M
Kazamel, M
Volpicelli-Daley, L
Bamman, MM
Yu, SH
King, PH
AF Si, Ying
Kim, Soojin
Cui, Xiangqin
Zheng, Lei
Oh, Shin J.
Anderson, Tina
AlSharabati, Mohammad
Kazamel, Mohamed
Volpicelli-Daley, Laura
Bamman, Marcas M.
Yu, Shaohua
King, Peter H.
TI Transforming Growth Factor Beta (TGF-beta) Is a Muscle Biomarker of
Disease Progression in ALS and Correlates with Smad Expression
SO PLOS ONE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SKELETAL-MUSCLE; TRANSCRIPTION FACTORS;
SIGNALING PATHWAY; MOTONEURONS; REGENERATION; ACTIVATION; CELLS; BONE;
MASS
AB We recently identified Smads1, 5 and 8 as muscle biomarkers in human ALS. In the ALS mouse, these markers are elevated and track disease progression. Smads are signal transducers and become activated upon receptor engagement of ligands from the TGF-beta superfamily. Here, we sought to characterize ligands linked to activation of Smads in ALS muscle and their role as biomarkers of disease progression. RNA sequencing data of ALS muscle samples were mined for TGF-beta superfamily ligands. Candidate targets were validated by qRT-PCR in a large cohort of human ALS muscle biopsy samples and in the G93A SOD1 mouse. Protein expression was evaluated by Western blot, ELISA and immunohistochemistry. C2C12 muscle cells were used to assess Smad activation and induction. TGF-beta 1, 2 and 3 mRNAs were increased in ALS muscle samples compared to controls and correlated with muscle strength and Smads1, 2, 5 and 8. In the G93A SOD1 mouse, the temporal pattern of TGF-beta expression paralleled the Smads and increased with disease progression. TGF-beta 1 immunoreactivity was detected in mononuclear cells surrounding muscle fibers in ALS samples. In muscle cells, TGF-beta ligands were capable of activating Smads. In conclusion, TGF-beta 1, 2 and 3 are novel biomarkers of ALS in skeletal muscle. Their correlation with weakness in human ALS and their progressive increase with advancing disease in the ALS mouse suggest that they, as with the Smads, can track disease progression. These ligands are capable of upregulating and activating Smads and thus may contribute to the Smad signaling pathway in ALS muscle.
C1 [Si, Ying; Kim, Soojin; Zheng, Lei; Oh, Shin J.; Anderson, Tina; AlSharabati, Mohammad; Kazamel, Mohamed; Volpicelli-Daley, Laura; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Si, Ying; Zheng, Lei; King, Peter H.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Cui, Xiangqin; Yu, Shaohua] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Bamman, Marcas M.; King, Peter H.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA.
[King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
RP King, PH (reprint author), Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA.
EM phking@uabmc.edu
OI Cui, Xiangqin/0000-0003-0621-9313
FU United States Department of Veterans Affairs Biomedical Laboratory
Research and Development Program Merit Review [BX001148]; National
Institute of Neurological Disorders [NS064133, R21NS081743,
R21NS085497]; National Center for Medical Rehabilitation Research
[R01HD084124]
FX Funded by the United States Department of Veterans Affairs Biomedical
Laboratory Research and Development Program Merit Review BX001148
(http://www.research.va.gov/services/blrd/), National Institute of
Neurological Disorders NS064133, R21NS081743, R21NS085497
(http://www.ninds.nih.gov/), and National Center for Medical
Rehabilitation Research R01HD084124
(https://www.nichd.nih.gov/about/org/ncmrr/Pages/overview.aspx). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 38
TC 1
Z9 2
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 16
PY 2015
VL 10
IS 9
AR e0138425
DI 10.1371/journal.pone.0138425
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8NH
UT WOS:000361610200106
PM 26375954
ER
PT J
AU Garay, CD
Dreyfuss, JM
Galagan, JE
AF Garay, Christopher D.
Dreyfuss, Jonathan M.
Galagan, James E.
TI Metabolic modeling predicts metabolite changes in Mycobacterium
tuberculosis
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID DRUG-RESISTANT TUBERCULOSIS; FLUX-BALANCE ANALYSIS; CONSTRAINT-BASED
ANALYSIS; ESCHERICHIA-COLI; HYPOXIC RESPONSE; CHOLESTEROL-METABOLISM;
TRANSCRIPTION FACTOR; 2-COMPONENT SYSTEM; REGULATORY NETWORK;
FATTY-ACIDS
AB Background: Mycobacterium tuberculosis (MTB) is the causal agent of the disease tuberculosis (TB). Metabolic adaptations are thought to be critical to the survival of MTB during pathogenesis. Computational tools that can be used to study MTB metabolism in silico and prioritize resource-intensive experimental work could significantly accelerate research.
Results: We have developed E-Flux-MFC, an enhancement of our original E-Flux method that enables the prediction of changes in the production of external and internal metabolites corresponding to gene expression measurements. We have used this method to simulate the changes in the metabolic state of Mycobacterium tuberculosis (MTB). We have validated the accuracy of E-Flux-MFC for predicting changes in lipids and metabolites during a hypoxia time course using previously published metabolomics and transcriptomics data. We have further validated the accuracy of the method for predicting changes in MTB lipids following the deletion and induction of two well-studied transcription factors (TFs). We have applied the method to predict the metabolic impact of the induction of each of the approximately 180 MTB TFs using a previously generated and publically available expression data set.
Conclusions: E-flux-MFC can be used to study global changes in MTB metabolites from gene expression data associated with environmental and genetic perturbations. The application of this method to a data set of MTB TF perturbations provides a resource for studying the large number of TFs whose functions remain unknown. Most TFs impact metabolites indirectly through the propagation of gene expression changes through the regulatory network rather than through their direct regulons. E-Flux-MFC is also applicable to any organism for which accurate metabolic models are available.
C1 [Garay, Christopher D.; Dreyfuss, Jonathan M.; Galagan, James E.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Dreyfuss, Jonathan M.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Galagan, James E.] Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.
[Galagan, James E.] Natl Emerging Infect Dis Labs, Boston, MA 02118 USA.
RP Galagan, JE (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
EM jgalag@bu.edu
OI Dreyfuss, Jonathan/0000-0001-7242-3991
FU Federal funds from the National Institute of Allergy and Infectious
Diseases National Institute of Health, Department of Health and Human
Services [HHSN272200800059C]
FX The authors gratefully acknowledge Jeremy Zucker, Matthew Peterson,
Elham Azizi and Ed Reznik for help in discussing this project. This work
was supported in whole or in part with Federal funds from the National
Institute of Allergy and Infectious Diseases National Institute of
Health, Department of Health and Human Services, under Contract No.
HHSN272200800059C.
NR 112
TC 0
Z9 0
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD SEP 16
PY 2015
VL 9
AR 57
DI 10.1186/s12918-015-0206-7
PG 16
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA CR4EB
UT WOS:000361283500002
PM 26377923
ER
PT J
AU Schendan, HE
Ganis, G
AF Schendan, Haline E.
Ganis, Giorgio
TI Top-down modulation of visual processing and knowledge after 250 ms
supports object constancy of category decisions
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE category decision; categorization; identification; recognition; object
constancy; visual perception; event-related potentials; knowledge memory
ID INFERIOR TEMPORAL CORTEX; EVENT-RELATED POTENTIALS; OSCILLATORY BRAIN
ACTIVITY; PRIMATE PREFRONTAL CORTEX; HUMAN FACE PERCEPTION;
NEUROPHYSIOLOGICAL EVIDENCE; SPATIOTEMPORAL DYNAMICS; RAPID
CATEGORIZATION; NATURAL SCENES; RECOGNITION MEMORY
AB People categorize objects more slowly when visual input is highly impoverished instead of optimal. While bottom-up models may explain a decision with optimal input, perceptual hypothesis testing (PHI) theories implicate top-down processes with impoverished input. Brain mechanisms and the time course of PHI are largely unknown. This event-related potential study used a neuroimaging paradigm that implicated prefrontal cortex in top down modulation of occipitotemporal cortex. Subjects categorized more impoverished and less impoverished real and pseudo objects. PHI theories predict larger impoverishment effects for real than pseudo objects because top-down processes modulate knowledge only for real objects, but different PHI variants predict different timing. Consistent with parietal prefrontal PHI variants, around 250 ms, the earliest impoverished real object interaction started on an N3 complex, which reflects interactive cortical activity for object cognition. N3 impoverishment effects localized to both prefrontal and occipitotemporal cortex for real objects only. The N3 also showed knowledge effects by 230 ms that localized to occipitotemporal cortex. Later effects reflected (a) word meaning in temporal cortex during the N400, (b) internal evaluation of prior decision and memory processes and secondary higher-order memory involving anterotemporal parts of a default mode network during posterior positivity (P600), and (c) response related activity in posterior cingulate during an anterior slow wave (SW) after 700 ms. Finally, response activity in supplementary motor area during a posterior SW after 900 ms showed impoverishment effects that correlated with RTs. Convergent evidence from studies of vision, memory, and mental imagery which reflects purely top-down inputs, indicates that the N3 reflects the critical top-down processes of PHI. A hybrid multiple-state interactive, PHI and decision theory best explains the visual constancy of object cognition.
C1 [Schendan, Haline E.; Ganis, Giorgio] Univ Plymouth, Cognit Inst, Sch Psychol, Plymouth PL4 8AA, Devon, England.
[Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Schendan, HE (reprint author), Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England.
EM halina.schendan@plymouth.aa.uk
OI Ganis, Giorgio/0000-0001-6175-2618
FU Tufts University
FX This project was completed in the School of Psychology at the University
of Plymouth. Additional research support from Tufts University. HS and
GG designed and set-up the experiment. HS assisted with testing and
directed the plan for data acquisition and analyses, supervised data
collection, analyzed some data, prepared tables and figures, and wrote
the manuscript. GG contributed to manuscript preparation. Emily A.
Slocombe (ES) collected the data. The authors are grateful to ES also
for assisting with some data analyses, Emily Newman for assisting ES
with analyses, and Lisa C. Lucia and Stephen M. Maher for assistance
with data collection.
NR 156
TC 2
Z9 2
U1 2
U2 11
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD SEP 16
PY 2015
VL 6
AR 1289
DI 10.3389/fpsyg.2015.01289
PG 34
WC Psychology, Multidisciplinary
SC Psychology
GA CR7WB
UT WOS:000361561400001
PM 26441701
ER
PT J
AU Lee, S
Allendorfer, JB
Gaston, TE
Griffis, JC
Hernando, KA
Knowlton, RC
Szaflarski, JP
Hoef, LWV
AF Lee, Seongtaek
Allendorfer, Jane B.
Gaston, Tyler E.
Griffis, Joseph C.
Hernando, Kathleen A.
Knowlton, Robert C.
Szaflarski, Jerzy P.
Hoef, Lawrence W. Ver
TI White matter diffusion abnormalities in patients with psychogenic
non-epileptic seizures
SO BRAIN RESEARCH
LA English
DT Article
DE Psychogenic non-epileptic seizures (PNES); Diffusion tensor imaging
(DTI); Tract-based spatial statistics (TBSS); Uncinate fasciculus (UF);
Superior temporal gyrus (STG)
ID UNCINATE FASCICULUS; FRACTIONAL ANISOTROPY; ICTAL SPECT; VIDEO-EEG;
EPILEPSY; DISCONNECTION; CONNECTIVITY; DISSOCIATION; INTEGRITY;
DIAGNOSIS
AB The purpose of this study was to conduct a preliminary investigation of the white matter characteristics in patients with psychogenic non-epileptic seizures (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3 T in 16 patients with PNES and 16 age- and sex-matched healthy controls (HC). All patients with PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid neurological or psychiatric conditions. DTI indices including fractional anisotropy (FA), and mean diffusivity (MD) were calculated and compared between patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS). Significantly higher FA values were observed in patients with PNES in the left corona radiata, left internal and external capsules, left superior temporal gyms, as well as left uncinate fasciculus (UP) (P < 0.05; corrected for multiple comparisons). There was no significant change in other indices between patients with PNES and HCs. These findings suggest that patients with PNES have significantly altered white matter structural connectivity when compared to age- and sex-matched HCs. These abnormalities are present in left hemispheric regions associated with emotion regulation and motor pathways. While the relationship between the pathophysiology of PNES and these abnormalities is not entirely clear, this work provides an initial basis to guide future prospective studies. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Lee, Seongtaek; Hoef, Lawrence W. Ver] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA.
[Allendorfer, Jane B.; Gaston, Tyler E.; Szaflarski, Jerzy P.; Hoef, Lawrence W. Ver] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Griffis, Joseph C.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
[Hernando, Kathleen A.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Knowlton, Robert C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Hoef, Lawrence W. Ver] Birmingham VA Med Ctr, Neurol Serv, Birmingham, AL 35294 USA.
RP Hoef, LWV (reprint author), Univ Alabama Birmingham, Dept Biomed Engn, Suite 312,1719 6th Ave South, Birmingham, AL 35294 USA.
EM lverhoef@uab.edu
OI Lee, Seongtaek/0000-0001-8954-6103
NR 49
TC 10
Z9 10
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD SEP 16
PY 2015
VL 1620
BP 169
EP 176
DI 10.1016/j.brainres.2015.04.050
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CR2LZ
UT WOS:000361162800014
PM 25979311
ER
PT J
AU Goldman, JG
Weintraub, D
AF Goldman, Jennifer G.
Weintraub, Daniel
TI Advances in the Treatment of Cognitive Impairment in Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Review
DE cholinesterase inhibitor; clinical trials; dementia; executive function;
mild cognitive impairment
ID TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIAL; DEEP
BRAIN-STIMULATION; ALZHEIMERS ASSOCIATION WORKGROUPS; PLACEBO-CONTROLLED
TRIAL; LONG-TERM SAFETY; PHASE-III TRIAL; LEWY BODIES; NEUROPSYCHIATRIC
SYMPTOMS; DOUBLE-BLIND
AB Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges. (c) 2015 International Parkinson and Movement Disorder Society
C1 [Goldman, Jennifer G.] Rush Univ, Med Ctr, Dept Neurol Sci, Sect Parkinson Dis & Movement Disorders, Chicago, IL 60612 USA.
[Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Goldman, JG (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1725 West Harrison St,Suite 755, Chicago, IL 60612 USA.
EM Jennifer_Goldman@rush.edu
NR 95
TC 10
Z9 12
U1 11
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD SEP 15
PY 2015
VL 30
IS 11
SI SI
BP 1471
EP 1489
DI 10.1002/mds.26352
PG 19
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW0AX
UT WOS:000364652400005
PM 26297863
ER
PT J
AU Shoamanesh, A
Yan, SQ
Charidimou, A
AF Shoamanesh, Ashkan
Yan, Shenqiang
Charidimou, Andreas
TI New cerebral microbleeds and mechanism of post-thrombolysis remote
intracerebral hemorrhage: "red meets white" revisited
SO FRONTIERS IN NEUROLOGY
LA English
DT Editorial Material
DE acute stroke; cerebral microbleeds; cerebral small vessel disease;
cerebral amyloid angiopathy; intracerebral hemorrhage; thrombolysis
ID METAANALYSIS; STROKE; RISK
C1 [Shoamanesh, Ashkan] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Yan, Shenqiang] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurol, Hangzhou 310003, Zhejiang, Peoples R China.
[Charidimou, Andreas] UCL Inst Neurol, London, England.
[Charidimou, Andreas] Harvard Univ, Ctr Stroke Res, Massachusetts Gen Hosp, Sch Med,Hemorrhag Stroke Res Program,Dept Neurol, Boston, MA 02115 USA.
RP Shoamanesh, A (reprint author), McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
EM Ashkan.Shoamanesh@phri.ca; andreas.charidimou.09@ucl.ac.uk
OI Yan, Shenqiang/0000-0001-6425-0672
NR 15
TC 3
Z9 3
U1 0
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-2295
J9 FRONT NEUROL
JI Front. Neurol.
PD SEP 15
PY 2015
VL 6
AR 203
DI 10.3389/fneur.2015.00203
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CV0HO
UT WOS:000363931400001
PM 26441822
ER
PT J
AU Haas, NB
Manola, J
Ky, B
Flaherty, KT
Uzzo, RG
Kane, CJ
Jewett, M
Wood, L
Wood, CG
Atkins, MB
Dutcher, JJ
Wilding, G
DiPaola, RS
AF Haas, Naomi B.
Manola, Judith
Ky, Bonnie
Flaherty, Keith T.
Uzzo, Robert G.
Kane, Christopher J.
Jewett, Michael
Wood, Lori
Wood, Christopher G.
Atkins, Michael B.
Dutcher, Janice J.
Wilding, George
DiPaola, Robert S.
TI Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal
Cell Carcinoma Patients without Overt Metastases: Results from ASSURE,
ECOG 2805
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; HEART-FAILURE; DOUBLE-BLIND; TRASTUZUMAB; CARDIOTOXICITY;
TRIAL; BEVACIZUMAB; CHEMOTHERAPY; INHIBITION; RISK
AB Purpose: Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown. We prospectively defined the incidence of cardiotoxicity among resected, high-risk RCC patients treated with these agents.
Experimental Design: Sunitinib, sorafenib, or placebo was administered for up to 12 months in patients with high-risk, resected RCC. LVEF was measured by multigated acquisition (MUGA) scans at standard intervals. Additional CV adverse events were reported according to NCI Common Terminology Criteria for Adverse Events (CTCAE).
Results: Among 1,943 patients randomized, 1,599 had at least 1 post-baseline MUGA. Within 6 months, 21 patients (1.3%) experienced a cardiac event, defined as an LVEF decline from baseline that was >15% and below the institutional lower limit of normal. Nine of 513 patients (1.8%) were on sunitinib, 7 of 508 (1.4%) on sorafenib, and 5 of 578 (0.9%) on placebo (P = 0.28 and 0.56 comparing sunitinib and sorafenib to placebo, respectively). With dose interruption or adjustment, 16 of the 21 recovered their LVEF to >50%. The incidence of symptomatic heart failure, arrhythmia, or myocardial ischemia did not differ among groups.
Conclusions: In the adjuvant setting, we prospectively define low incidence of cardiotoxicity with sunitinib and sorafenib. These findings may be related to close CV monitoring, or potentially to fewer CV comorbidities in our nonmetastatic population. (C)2015 AACR.
C1 [Haas, Naomi B.; Ky, Bonnie; Flaherty, Keith T.] Univ Penn, Philadelphia, PA 19104 USA.
[Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Uzzo, Robert G.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Kane, Christopher J.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Jewett, Michael] Univ Toronto, Toronto, ON, Canada.
[Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
[Wood, Lori] Dalhousie Univ, Halifax, NS, Canada.
[Wood, Christopher G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Dutcher, Janice J.] New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA.
[Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[DiPaola, Robert S.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
RP Haas, NB (reprint author), Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM Naomi.haas@uphs.upenn.edu
FU Public Health Service Grants [CA180820, CA180794, CA180867, CA180821,
CA31946, CA077202, CA180863, CCSRI021039, CA32102, CA105409]; National
Cancer Institute, National Institutes of Health; Department of Health
and Human Services; Pfizer
FX This study was coordinated by the ECOG-ACRIN Cancer Research Group
(Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs)
and supported in part by Public Health Service Grants CA180820,
CA180794, CA180867, CA180821, CA31946, CA077202, CA180863, CCSRI021039,
CA32102, CA105409, and from the National Cancer Institute, National
Institutes of Health, and the Department of Health and Human Services.
Its content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Cancer
Institute. The cardiac substudy was supported by Pfizer.
NR 22
TC 7
Z9 7
U1 2
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2015
VL 21
IS 18
BP 4048
EP 4054
DI 10.1158/1078-0432.CCR-15-0215
PG 7
WC Oncology
SC Oncology
GA CU2CN
UT WOS:000363329900006
PM 25967143
ER
PT J
AU Benson, DM
Cohen, AD
Jagannath, S
Munshi, NC
Spitzer, G
Hofmeister, CC
Efebera, YA
Andre, P
Zerbib, R
Caligiuri, MA
AF Benson, Don M., Jr.
Cohen, Adam D.
Jagannath, Sundar
Munshi, Nikhil C.
Spitzer, Gary
Hofmeister, Craig C.
Efebera, Yvonne A.
Andre, Pascale
Zerbib, Robert
Caligiuri, Michael A.
TI A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in
Patients with Relapsed/Refractory Multiple Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NATURAL-KILLER-CELL; MONOCLONAL GAMMOPATHIES; PLUS DEXAMETHASONE;
TUMOR-CELLS; BONE-MARROW; CYTOTOXICITY; ACTIVATION; RECEPTORS; THERAPY;
ENHANCE
AB Purpose: Natural killer (NK) cells may play an important role in the immune response to multiple myeloma; however, multiple myeloma cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against multiple myeloma; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR antibody, has acceptable safety and tolerability in multiple myeloma as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for multiple myeloma.
Experimental Design: A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to 21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No corticosteroids were utilized. The primary endpoint was safety, and secondary endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD).
Results: The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single-agent IPH2101 trial. Five serious adverse events (SAE) were reported. Five objective responses occurred. No autoimmunity was seen.
Conclusions: These findings suggest that lenalidomide in combination with antiinhibitory KIR therapy warrants further investigation in multiple myeloma as a steroid-sparing, dual immune therapy. (C)2015 AACR.
C1 [Benson, Don M., Jr.; Hofmeister, Craig C.; Efebera, Yvonne A.; Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Cohen, Adam D.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Jagannath, Sundar] Mt Sinai Sch Med, New York, NY USA.
[Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA.
[Spitzer, Gary] St Francis Hosp, Greenville, SC USA.
[Andre, Pascale; Zerbib, Robert] Innate Pharma, Marseille, France.
RP Benson, DM (reprint author), Ohio State Univ, Div Hematol, Ctr Comprehens Canc, B310 Starling Loving Hall,320 West 10th Ave, Columbus, OH 43210 USA.
EM Don.benson@osumc.edu
RI Hofmeister, Craig/E-3256-2011; Efebera, Yvonne/E-3012-2011
OI Hofmeister, Craig/0000-0003-4816-1607;
FU National Cancer Institute [P01 CA095426]
FX This study was supported by the National Cancer Institute grant P01
CA095426 (to D.M. Benson Jr and M.A. Caligiuri).
NR 32
TC 22
Z9 23
U1 2
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2015
VL 21
IS 18
BP 4055
EP 4061
DI 10.1158/1078-0432.CCR-15-0304
PG 7
WC Oncology
SC Oncology
GA CU2CN
UT WOS:000363329900007
PM 25999435
ER
PT J
AU Metelo, AM
Noonan, H
Iliopoulos, O
AF Metelo, Ana Martins
Noonan, Haley
Iliopoulos, Othon
TI HIF2a inhibitors for the treatment of VHL disease
SO ONCOTARGET
LA English
DT Editorial Material
DE hypoxia; VHL; HIF2a inhibitors; renal cancer
ID CANCER; GENE
C1 [Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Iliopoulos, Othon] Harvard Univ, Sch Med, Charlestown, MA USA.
RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM oiliopoulos@partners.org
FU NCI NIH HHS [R01 CA160458]
NR 7
TC 3
Z9 3
U1 1
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP 15
PY 2015
VL 6
IS 27
BP 23036
EP 23037
DI 10.18632/oncotarget.4564
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CT9SU
UT WOS:000363157700001
PM 26325097
ER
PT J
AU Ecker, BL
Paulson, EC
Datta, J
Jeganathan, AN
Aarons, C
Kelz, RR
Mahmoud, NN
AF Ecker, Brett L.
Paulson, Emily C.
Datta, Jashodeep
Jeganathan, Arjun N.
Aarons, Cary
Kelz, Rachel R.
Mahmoud, Najjia N.
TI Lymph Node Identification Following Neoadjuvant Therapy in Rectal
Cancer: A Stage-Stratified Analysis using the Surveillance,
Epidemiology, and End Results (SEER)-Medicare Database
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE rectal cancer; lymph node staging; neoadjuvant therapy; survival; SEER
ID PREOPERATIVE CHEMORADIOTHERAPY; COLORECTAL-CANCER; GASTRIC-CANCER;
IMPACT; RADIOTHERAPY; SURVIVAL; RADIOCHEMOTHERAPY; CHEMOTHERAPY;
GUIDELINES; RADIATION
AB Background and Objectives: Neoadjuvant chemoradiation (nCRT) for rectal adenocarcinoma reduces lymph node (LN) identification following surgical resection. We sought to evaluate the relationship between LN identification following nCRT and disease-specific survival (DSS), stratified by pathologic stage.
Methods: The SEER-Medicare database (2000-2009) was queried for 1,216 pathologic stage I-III rectal cancer patients who underwent nCRT followed by curative-intent resection. Cox regressions evaluated the association between pathologic stage and DSS for LN cut-points from >= 2 up to >= 12 LNs.
Results: Extent of LN identification did not influence DSS in ypStage I or ypStage III disease; in particular, the 12 LN cut-point was not associated with DSS for ypStage I (HR 1.29, P = 0.51) or ypStage III (HR 1.08, P = 0.42) patients. In ypStage II patients, actuarial survival improved continually with increasing lymph node identification up to >= 12 LNs. The 5 LN cut-point was associated with the greatest reduction of risk of cancer death (HR 0.56, P = 0.006), with decreasing magnitudes of survival benefit associated with nodal counts beyond 5 LN. The 12 LN cut-point was not associated with DSS in ypStage II patients (HR 0.67, P = 0.07).
Conclusion: The association between DSS and LN identification is a dynamic outcome that varies by pathologic stage, with unique prognostic significance for ypStage II patients. (c) 2015 Wiley Periodicals, Inc.
C1 [Ecker, Brett L.; Paulson, Emily C.; Datta, Jashodeep; Jeganathan, Arjun N.; Aarons, Cary; Kelz, Rachel R.; Mahmoud, Najjia N.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Paulson, Emily C.] Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA.
RP Mahmoud, NN (reprint author), Hosp Univ Penn, 3400 Spruce St,4 Silverstein, Philadelphia, PA 19104 USA.
EM Najjia.Mahmoud@uphs.upenn.edu
NR 24
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
EI 1096-9098
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD SEP 15
PY 2015
VL 112
IS 4
BP 415
EP 420
DI 10.1002/jso.23991
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CT2VN
UT WOS:000362662900014
PM 26250884
ER
PT J
AU Aydogan, F
Mallory, MA
Tukenmez, M
Sagara, Y
Ozturk, E
Ince, Y
Celik, V
Akca, T
Golshan, M
AF Aydogan, Fatih
Mallory, Melissa Anne
Tukenmez, Mustafa
Sagara, Yasuaki
Ozturk, Erkan
Ince, Yavuz
Celik, Varol
Akca, Tamer
Golshan, Mehra
TI A Low Cost Training Phantom Model for Radio-Guided Localization
Techniques in Occult Breast Lesions
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE breast; radio-guided localization; training; phantom model
ID WIRE LOCALIZATION; CANCER; BIOPSY; ROLL; METAANALYSIS; SIMULATOR;
SURGERY
AB Radio-guided localization (RGL) for identifying occult breast lesions has been widely accepted as an alternative technique to other localization methods, including those using wire guidance. An appropriate phantom model would be an invaluable tool for practitioners interested in learning the technique of RGL prior to clinical application. The aim of this study was to devise an inexpensive and reproducible training phantom model for RGL. We developed a simple RGL phantom model imitating an occult breast lesion from inexpensive supplies including a pimento olive, a green pea and a turkey breast. The phantom was constructed for a total cost of less than $20 and prepared in approximately 10 min. After the first model's construction, we constructed approximately 25 additional models and demonstrated that the model design was easily reproducible. The RGL phantom is a time-and cost-effective model that accurately simulates the RGL technique for non-palpable breast lesions. Future studies are warranted to further validate this model as an effective teaching tool. (c) 2015 Wiley Periodicals, Inc.
C1 [Aydogan, Fatih; Mallory, Melissa Anne; Tukenmez, Mustafa; Sagara, Yasuaki; Golshan, Mehra] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp, Womens Canc Ctr, Boston, MA 02215 USA.
[Aydogan, Fatih; Celik, Varol] Istanbul Univ, Cerrahpasa Med Sch, Dept Surg, Breast Div, Istanbul, Turkey.
[Tukenmez, Mustafa] Istanbul Univ, Istanbul Med Sch, Dept Surg, Istanbul, Turkey.
[Ozturk, Erkan] Gulhane Mil Med Acad, Dept Surg, Ankara, Turkey.
[Ozturk, Erkan] Sch Med, Ankara, Turkey.
[Ince, Yavuz] Koc Med Sch, Istanbul, Turkey.
[Akca, Tamer] Mersin Univ, Fac Med, Dept Gen Surg, Mersin, Turkey.
RP Aydogan, F (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp, Womens Canc Ctr, 450 Brookline Ave,Yawkey 1441, Boston, MA 02215 USA.
EM faydoganmd@gmail.com
FU NIH [R25CA089017]; Turkish Anti-Cancer Foundation
FX Grant sponsor: NIH; Grant number: R25CA089017; Grant sponsor: Turkish
Anti-Cancer Foundation.
NR 19
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
EI 1096-9098
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD SEP 15
PY 2015
VL 112
IS 4
BP 449
EP 451
DI 10.1002/jso.23984
PG 3
WC Oncology; Surgery
SC Oncology; Surgery
GA CT2VN
UT WOS:000362662900020
PM 26250621
ER
PT J
AU Ye, SQ
Cheng, B
Lip, GYH
Buchsbaum, R
Sacco, RL
Levin, B
Di Tullio, MR
Qian, M
Mann, DL
Pullicino, PM
Freudenberger, RS
Teerlink, JR
Mohr, JP
Graham, S
Labovitz, AJ
Estol, CJ
Lok, DJ
Ponikowski, P
Anker, SD
Thompson, JLP
Homma, S
AF Ye, Siqin
Cheng, Bin
Lip, Gregory Y. H.
Buchsbaum, Richard
Sacco, Ralph L.
Levin, Bruce
Di Tullio, Marco R.
Qian, Mm
Mann, Douglas L.
Pullicino, Patrick M.
Freudenberger, Ronald S.
Teerlink, John R.
Mohr, J. P.
Graham, Susan
Labovitz, Arthur J.
Estol, Conrado J.
Lok, Dirk J.
Ponikowski, Piotr
Anker, Stefan D.
Thompson, John L. P.
Homma, Shunichi
CA WARCEF Investigators
TI Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm
and Heart Failure With Reduced Ejection Fraction Treated With Warfarin
or Aspirin
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ATRIAL-FIBRILLATION; ANTICOAGULATED PATIENTS; SUBGROUP ANALYSIS; SCORES;
TRIAL; RECLASSIFICATION; CHA(2)DS(2)-VASC; PERFORMANCE; HEMORRHAGE;
CHADS(2)
AB We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for (the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12),"but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk, scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Ye, Siqin; Di Tullio, Marco R.; Homma, Shunichi] Columbia Univ, Dept Med, Med Ctr, Div Cardiol, New York, NY 10027 USA.
[Mohr, J. P.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Cheng, Bin; Buchsbaum, Richard; Levin, Bruce; Qian, Mm; Thompson, John L. P.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Mann, Douglas L.] Washington Univ, Dept Med, St Louis, MO USA.
[Pullicino, Patrick M.] Univ Kent, Kent Inst Med & Hlth Sci, Canterbury, Kent, England.
[Freudenberger, Ronald S.] Lehigh Valley Hosp, Dept Med, Div Cardiol, Allentown, PA USA.
[Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA.
[Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Graham, Susan] SUNY Upstate Med Univ, Dept Med, Div Cardiol, Buffalo, NY USA.
[Labovitz, Arthur J.] Univ S Florida, Dept Cardiovasc Med, Tampa, FL USA.
[Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina.
[Lok, Dirk J.] Deventer Hosp, Dept Cardiol, Deventer, Netherlands.
[Ponikowski, Piotr] Wroclaw Med Univ, Mil Hosp, Dept Heart Dis, Wroclaw, Poland.
[Anker, Stefan D.] Univ Med Ctr Gottingen, Dept Innovat Clin Trials, Gottingen, Germany.
RP Ye, SQ (reprint author), Columbia Univ, Dept Med, Med Ctr, Div Cardiol, New York, NY 10027 USA.
EM sy2357@cumc.columbia.edu
RI Ponikowski, Piotr/O-6454-2015;
OI Ponikowski, Piotr/0000-0002-3391-7064; Ye, Siqin/0000-0002-5229-9775
FU National Institute of Neurological Diseases and Stroke [U01-NS-043975,
U01-NS-039143]
FX The WARCEF trial was supported by Grant U01-NS-043975 (SH) and
U01-NS-039143 (JLPT) from the National Institute of Neurological
Diseases and Stroke. Warfarin and warfarin placebo were provided by Taro
Pharmaceuticals USA, and aspirin and aspirin placebo by Bayer
HealthCare.
NR 23
TC 4
Z9 4
U1 1
U2 13
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 15
PY 2015
VL 116
IS 6
BP 904
EP 912
DI 10.1016/j.amjcard.2015.06.016
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR8ZU
UT WOS:000361643800013
PM 26189039
ER
PT J
AU Pierre, JF
Neuman, JC
Brill, AL
Brar, HK
Thompson, MF
Cadena, MT
Connors, KM
Busch, RA
Heneghan, AF
Cham, CM
Jones, EK
Kibbe, CR
Davis, DB
Groblewski, GE
Kudsk, KA
Kimple, ME
AF Pierre, Joseph F.
Neuman, Joshua C.
Brill, Allison L.
Brar, Harpreet K.
Thompson, Mary F.
Cadena, Mark T.
Connors, Kelsey M.
Busch, Rebecca A.
Heneghan, Aaron F.
Cham, Candace M.
Jones, Elaina K.
Kibbe, Carly R.
Davis, Dawn B.
Groblewski, Guy E.
Kudsk, Kenneth A.
Kimple, Michelle E.
TI The gastrin-releasing peptide analog bombesin preserves exocrine and
endocrine pancreas morphology and function during parenteral nutrition
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE bombesin; gut hormones; pancreas; parenteral nutrition; adjuvant therapy
ID DIGESTIVE ENZYME EXPRESSION; PROTEIN-COUPLED RECEPTORS; GLUCAGON-LIKE
PEPTIDE-1; GLUCOSE-INTOLERANCE; INSULIN-SECRETION; LYMPHOID-TISSUE;
ACINAR-CELLS; RAT PANCREAS; AMINO-ACIDS; BETA-CELLS
AB Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.
C1 [Davis, Dawn B.; Kudsk, Kenneth A.; Kimple, Michelle E.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Pierre, Joseph F.; Busch, Rebecca A.; Heneghan, Aaron F.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA.
[Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Kibbe, Carly R.; Davis, Dawn B.; Kimple, Michelle E.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Endocrinol, Madison, WI USA.
[Neuman, Joshua C.; Jones, Elaina K.; Davis, Dawn B.; Groblewski, Guy E.; Kimple, Michelle E.] Univ Wisconsin, Coll Agr & Life Sci, Interdisciplinary Grad Program Nutr Sci, Madison, WI 53706 USA.
[Pierre, Joseph F.; Cham, Candace M.] Univ Chicago, Dept Med, Div Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA.
RP Kimple, ME (reprint author), 4148 UW Med Fdn Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA.
EM mkimple@medicine.wisc.edu
OI Brill, Allison/0000-0002-5046-3578
FU Biomedical Laboratory Research and Development Service of the VA Office
of Research and Development Award [I01BX001672]; American Diabetes
Association [1-14-BS-115]; National Institutes of Health (NIH)
[DK-102598, DK-070888]; Wisconsin Partnership Program Grant; US
Department of Agriculture/HATCH [WIS01583]; University of Chicago
Training Grant in Digestive Diseases and Nutrition (NIH) [T32
DK-007074]; University of Wisconsin Institute on Aging (NIH) [T32
AG-000213]; University of Wisconsin Surgical Oncology Research Training
Program (NIH) [T32 CA-090217]
FX This research is supported by Biomedical Laboratory Research and
Development Service of the VA Office of Research and Development Award
I01BX001672 (to K. A. Kudsk) and also by American Diabetes Association
Grant 1-14-BS-115 (to M. E. Kimple), National Institutes of Health (NIH)
Grant DK-102598 (to M. E. Kudsk), a Wisconsin Partnership Program Grant
(to D. B. Davis), NIH Grant DK-070888 (to G. E. Groblewski), and US
Department of Agriculture/HATCH Grant WIS01583 (to G. E. Groblewski). J.
F. Pierre is supported in part by a University of Chicago Training Grant
in Digestive Diseases and Nutrition (NIH Grant T32 DK-007074). J. C.
Neuman and C. R. Kibbe are supported in part by a training grant from
the University of Wisconsin Institute on Aging (NIH Grant T32
AG-000213). R. A. Busch is supported in part by a training grant from
the University of Wisconsin Surgical Oncology Research Training Program
(NIH Grant T32 CA-090217).
NR 63
TC 1
Z9 1
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
EI 1522-1547
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD SEP 15
PY 2015
VL 309
IS 6
BP G431
EP G442
DI 10.1152/ajpgi.00072.2015
PG 12
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA CS1IO
UT WOS:000361817700004
PM 26185331
ER
PT J
AU Hwang, VJ
Kim, J
Rand, A
Yang, CZ
Sturdivant, S
Hammock, B
Bell, PD
Guay-Woodford, LM
Weiss, RH
AF Hwang, Vicki J.
Kim, Jeffrey
Rand, Amy
Yang, Chaozhe
Sturdivant, Steve
Hammock, Bruce
Bell, P. Darwin
Guay-Woodford, Lisa M.
Weiss, Robert H.
TI The cpk model of recessive PKD shows glutamine dependence associated
with the production of the oncometabolite 2-hydroxyglutarate
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE ARPKD; glutamine; metabolomics; oncometabolite; reprogramming
ID POLYCYSTIC KIDNEY-DISEASE; REDUCTIVE CARBOXYLATION; ALPHA-KETOGLUTARATE;
IDH2 MUTATIONS; CANCER; CELLS; METABOLISM; D-2-HYDROXYGLUTARATE;
HYPOXIA; GROWTH
AB Since polycystic kidney disease (PKD) was first noted over 30 years ago to have neoplastic parallels, there has been a resurgent interest in elucidating neoplasia-relevant pathways in PKD. Taking a nontargeted metabolomics approach in the B6(Cg)-Cys1(cpk/)J (cpk) mouse model of recessive PKD, we have now characterized metabolic reprogramming in these tissues, leading to a glutamine-dependent TCA cycle shunt toward total 2-hydroxyglutarate (2-HG) production in cpk compared with B6 wild-type kidney tissue. After confirmation of increased 2-HG expression in immortalized collecting duct cpk cells as well as in human autosomal recessive PKD tissue using targeted analysis, we show that the increase in 2-HG is likely due to glutamine-sourced alpha-ketoglutarate. In addition, cpk cells require exogenous glutamine for growth such that inhibition of glutaminase-1 decreases cell viability as well as proliferation. This study is a demonstration of the striking parallels between recessive PKD and cancer metabolism. Our data, once confirmed in other PKD models, suggest that future therapeutic approaches targeting this pathway, such as using glutaminase inhibitors, have the potential to open novel treatment options for renal cystic disease.
C1 [Hwang, Vicki J.; Weiss, Robert H.] Univ Calif Davis, Grad Grp Integrat Genet & Genom, Davis, CA 95616 USA.
[Hwang, Vicki J.; Kim, Jeffrey; Weiss, Robert H.] Univ Calif Davis, Dept Internal Med, Div Nephrol, Davis, CA 95616 USA.
[Rand, Amy; Hammock, Bruce] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Hammock, Bruce; Weiss, Robert H.] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA.
[Yang, Chaozhe; Guay-Woodford, Lisa M.] Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA.
[Sturdivant, Steve] Metabolon, Durham, NC USA.
[Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
[Bell, P. Darwin] Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Weiss, Robert H.] Sacramento Vet Affairs Med Ctr, Med Serv, Sacramento, CA USA.
RP Weiss, RH (reprint author), Univ Calif Davis, Dept Internal Med, Div Nephrol, Genome & Biomed Sci Bldg,Rm 6312,451 Hlth Sci Dr, Davis, CA 95616 USA.
EM rhweiss@ucdavis.edu
FU National Institutes of Health (NIH) [1R01CA135401-01A1, 1R03CA181837-01,
1R01DK082690-01A1]; Medical Service of the US Department of Veterans
Affairs, and Dialysis Clinics; NIEHS [R01 ES002710, P42 ES004699]; UAB
Hepato-Renal Fibrocystic Diseases Core Center [P30 DK074038]
FX This work was supported by National Institutes of Health (NIH) Grants
1R01CA135401-01A1, 1R03CA181837-01, and 1R01DK082690-01A1, the Medical
Service of the US Department of Veterans Affairs, and Dialysis Clinics
(all to R. H. Weiss). Partial support was provided by NIEHS R01 ES002710
and NIEHS Superfund Program P42 ES004699 (to. B. D. Hammock), and the
UAB Hepato-Renal Fibrocystic Diseases Core Center, P30 DK074038 (to L.
Guay-Woodford and P. D. Bell). A. Rand is a fellow of NIH/NIEHS T32
CA108459.
NR 34
TC 3
Z9 3
U1 2
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD SEP 15
PY 2015
VL 309
IS 6
BP F492
EP F498
DI 10.1152/ajprenal.00238.2015
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA CS1KD
UT WOS:000361822100003
PM 26155843
ER
PT J
AU Takaya, S
Kuperberg, GR
Liu, HS
Greve, DN
Makris, N
Stufflebeam, SM
AF Takaya, Shigetoshi
Kuperberg, Gina R.
Liu, Hesheng
Greve, Douglas N.
Makris, Nikos
Stufflebeam, Steven M.
TI Asymmetric projections of the arcuate fasciculus to the temporal cortex
underlie lateralized language function in the human brain
SO FRONTIERS IN NEUROANATOMY
LA English
DT Article
DE language pathway; cortical projection; structure-function;
surface-based; structural connectivity; functional connectivity; MRI;
semantic decision
ID PROBABILISTIC DIFFUSION TRACTOGRAPHY; SURFACE-BASED ANALYSIS; CORTICAL
SURFACE; LOBE EPILEPSY; RESTING BRAIN; CONNECTIVITY; PATHWAYS;
ORGANIZATION; NETWORK; MRI
AB The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting state functional MRI (fMRI) and task related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyms to the mid part of the superior temporal sulcus and the middle temporal gyms, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyms. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language.
C1 [Takaya, Shigetoshi; Kuperberg, Gina R.; Liu, Hesheng; Greve, Douglas N.; Makris, Nikos; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Takaya, Shigetoshi; Kuperberg, Gina R.; Liu, Hesheng; Greve, Douglas N.; Makris, Nikos; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA.
[Stufflebeam, Steven M.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA.
RP Takaya, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St, Charlestown, MA 02129 USA.
EM shige@nmr.mgh.harvard.edu
FU National Institute of Health [R01NS069696, R41EB015896, S10ODRR031599,
S10RR021110]; National Science Foundation [NPS-DMS-1042134]; Hehara
Memorial Foundation; SNMMI (Wagner-Torizuka Fellowship); department of
energy [DE-SC0008430]
FX This work was supported by grants from the National Institute of Health
(R01NS069696, R41EB015896, S100DRR031599, S10RR021110) and National
Science Foundation grant (NPS-DMS-1042134). This study was also partly
supported by fellowships from the Hehara Memorial Foundation, the SNMMI
(Wagner-Torizuka Fellowship) and a grant from the department of energy
(DE-SC0008430).
NR 68
TC 2
Z9 2
U1 5
U2 10
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD SEP 15
PY 2015
VL 9
AR 119
DI 10.3389/fnana.2015.00119
PG 12
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA CR8XA
UT WOS:000361636400001
PM 26441551
ER
PT J
AU Hodkinson, DJ
Veggeberg, R
Wilcox, SL
Scrivani, S
Burstein, R
Becerra, L
Borsook, D
AF Hodkinson, Duncan J.
Veggeberg, Rosanna
Wilcox, Sophie L.
Scrivani, Steven
Burstein, Rami
Becerra, Lino
Borsook, David
TI Primary Somatosensory Cortices Contain Altered Patterns of Regional
Cerebral Blood Flow in the Interictal Phase of Migraine
SO PLOS ONE
LA English
DT Article
ID HUMAN BRAIN; ARTERIAL; CORTEX; ALLODYNIA; PAIN; PATHOPHYSIOLOGY;
QUESTIONNAIRE; SENSITIZATION; POPULATION; MECHANISMS
AB The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique-arterial spin labeling (ASL)-to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks.
C1 [Hodkinson, Duncan J.; Veggeberg, Rosanna; Wilcox, Sophie L.; Scrivani, Steven; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA 02163 USA.
[Scrivani, Steven] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Burstein, Rami] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Anesthesia & Crit Care, Boston, MA 02215 USA.
[Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Boston, MA 02115 USA.
RP Hodkinson, DJ (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Ctr Pain & Brain,Dept Anesthesiol Perioperat & Pa, Boston, MA 02163 USA.
EM duncan.hodkinson@childrens.harvard.edu
FU National Institutes of Health [RO1 NS073977, K24 NS064050]
FX This study was funded by National Institutes of Health (RO1 NS073977 and
K24 NS064050).
NR 59
TC 2
Z9 2
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 SEP 15
PY 2015
VL 10
IS 9
AR e0137971
DI 10.1371/journal.pone.0137971
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8LR
UT WOS:000361604400042
PM 26372461
ER
PT J
AU Smith, D
Aherrera, A
Lopez, A
Neptune, E
Winickoff, JP
Klein, JD
Chen, G
Lazarus, P
Collaco, JM
McGrath-Morrow, SA
AF Smith, Dani
Aherrera, Angela
Lopez, Armando
Neptune, Enid
Winickoff, Jonathan P.
Klein, Jonathan D.
Chen, Gang
Lazarus, Philip
Collaco, Joseph M.
McGrath-Morrow, Sharon A.
TI Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors
during Late Prenatal and Early Postnatal Life
SO PLOS ONE
LA English
DT Article
ID C57BL/6J MICE; SMOKE EXPOSURE; TERATOGENICITY; HYPERACTIVITY;
PERFORMANCE; COTININE; ANXIETY; BRAIN; RISK; TIME
AB Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice.
Methods
Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine/PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.
Results
Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/ PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/ PG mice spent more than 25% of time in the new location whereas the other groups did not.
Conclusion
Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.
C1 [Smith, Dani] Johns Hopkins Univ, Dept Psychol & Brain Sci, Neurogenet & Behav Ctr, Baltimore, MD USA.
[Aherrera, Angela; Lopez, Armando; Collaco, Joseph M.; McGrath-Morrow, Sharon A.] Johns Hopkins Univ, Sch Med, Eudowood Div Pediat Resp Sci, Baltimore, MD 21218 USA.
[Lopez, Armando; Neptune, Enid] Johns Hopkins Med Inst, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
[Winickoff, Jonathan P.; Klein, Jonathan D.; Collaco, Joseph M.; McGrath-Morrow, Sharon A.] Amer Acad Pediat, Julius B Richmond Ctr Excellence, Elk Grove Village, IL USA.
[Winickoff, Jonathan P.] Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA.
[Winickoff, Jonathan P.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Gang; Lazarus, Philip] Washington State Univ, Dept Pharmacol, Pullman, WA 99164 USA.
RP McGrath-Morrow, SA (reprint author), Johns Hopkins Univ, Sch Med, Eudowood Div Pediat Resp Sci, Baltimore, MD 21218 USA.
EM smcgrath@jhmi.edu
FU Flight Attendant Medical Research Institute; National Institutes of
Health, NIH [RHL114800A]
FX This work was funded by a Center of Excellence Grant to the American
Academy of Pediatrics from the Flight Attendant Medical Research
Institute (SAM, JMC, JDK, JPW); and National Institutes of Health, NIH
RHL114800A (SAM).
NR 29
TC 8
Z9 8
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 15
PY 2015
VL 10
IS 9
AR e0137953
DI 10.1371/journal.pone.0137953
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR8LR
UT WOS:000361604400038
PM 26372012
ER
PT J
AU Lu, FK
Basu, S
Igras, V
Hoang, MP
Ji, MB
Fu, D
Holtom, GR
Neel, VA
Freudiger, CW
Fisher, DE
Xie, XS
AF Lu, Fa-Ke
Basu, Srinjan
Igras, Vivien
Hoang, Mai P.
Ji, Minbiao
Fu, Dan
Holtom, Gary R.
Neel, Victor A.
Freudiger, Christian W.
Fisher, David E.
Xie, X. Sunney
TI Label-free DNA imaging in vivo with stimulated Raman scattering
microscopy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE stimulated Raman scattering microscopy; skin cancer; label-free
histology; cell division; mitotic rate
ID NONMELANOMA SKIN-CANCER; SQUAMOUS-CELL CARCINOMA; LIVING CELLS;
WAVELENGTH SELECTION; TUMOR XENOGRAFTS; MOUSE SKIN; SPECTROSCOPY;
PROTEIN; MICE; MICROSPECTROSCOPY
AB Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.
C1 [Lu, Fa-Ke; Ji, Minbiao; Fu, Dan; Holtom, Gary R.; Freudiger, Christian W.; Xie, X. Sunney] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Basu, Srinjan] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Igras, Vivien; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Charlestown, MA 02129 USA.
[Hoang, Mai P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Neel, Victor A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Charlestown, MA 02129 USA.
EM dfisher3@mgh.harvard.edu; xie@chemistry.harvard.edu
RI Ji, Minbiao/C-7793-2011; Basu, Srinjan/M-7835-2016
OI Ji, Minbiao/0000-0002-9066-4008; Basu, Srinjan/0000-0002-1080-979X
FU US Department of Energy's Basic Energy Sciences Program
[DE-FG02-09ER16104]; National Institutes of Health (NIH)
[1R01EB010244-01]; Dr. Miriam and Sheldon G. Adelson Medical Research
Foundation; NIH [P01 CA163222, R01 AR043369, R21 CA175907]
FX We thank Dr. X. Ni, Dr. X. Zhang, and Dr. J. Yong for help on the animal
experiments; W. Yang for technical assistance on the photo detector; Dr.
L. Sang, Dr. L. Kong, Dr. A. J. Golby, and Dr. N. Y. Agar for helpful
discussions; and Dr. D. Lando and Dr. P. Purcell for critical reading
and editing of the manuscript. This work was supported by grants to
X.S.X. from the US Department of Energy's Basic Energy Sciences
Program(DE-FG02-09ER16104) and National Institutes of Health (NIH) T-R01
(1R01EB010244-01) and to D.E.F. from the Dr. Miriam and Sheldon G.
Adelson Medical Research Foundation and the NIH (P01 CA163222, R01
AR043369, and R21 CA175907).
NR 60
TC 21
Z9 21
U1 22
U2 67
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 SEP 15
PY 2015
VL 112
IS 37
BP 11624
EP 11629
DI 10.1073/pnas.1515121112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5OW
UT WOS:000361393700058
PM 26324899
ER
PT J
AU Suhara, T
Hishiki, T
Kasahara, M
Hayakawa, N
Oyaizu, T
Nakanishi, T
Kubo, A
Morisaki, H
Kaelin, WG
Suematsu, M
Minamishima, YA
AF Suhara, Tomohiro
Hishiki, Takako
Kasahara, Masataka
Hayakawa, Noriyo
Oyaizu, Tomoko
Nakanishi, Tsuyoshi
Kubo, Akiko
Morisaki, Hiroshi
Kaelin, William G., Jr.
Suematsu, Makoto
Minamishima, Yoji Andrew
TI Inhibition of the oxygen sensor PHD2 in the liver improves survival in
lactic acidosis by activating the Cori cycle
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hypoxic response; PHD inhibitor; hyperlactatemia; gluconeogenesis;
sepsis
ID MYOCARDIAL-INFARCTION; SEPTIC SHOCK; HYPOXIA; METABOLISM; LACTATE;
INACTIVATION; DISEASE; FAMILY; MOUSE; HIF
AB Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyper-lacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate-glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo C-13-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from C-13-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.
C1 [Suhara, Tomohiro; Hishiki, Takako; Kasahara, Masataka; Hayakawa, Noriyo; Oyaizu, Tomoko; Nakanishi, Tsuyoshi; Kubo, Akiko; Suematsu, Makoto; Minamishima, Yoji Andrew] Keio Univ, Sch Med, Dept Biochem, Tokyo 1608582, Japan.
[Suhara, Tomohiro; Oyaizu, Tomoko; Morisaki, Hiroshi] Keio Univ, Sch Med, Dept Anesthesiol, Tokyo 1608582, Japan.
[Hishiki, Takako; Hayakawa, Noriyo] Keio Univ, Sch Med, Translat Res Ctr, Tokyo 1608582, Japan.
[Hishiki, Takako; Hayakawa, Noriyo; Nakanishi, Tsuyoshi; Suematsu, Makoto; Minamishima, Yoji Andrew] Japan Sci & Technol Agcy, Exploratory Res Adv Technol, Suematsu Gas Biol Project, Core Res Evolut Sci & Technol, Tokyo 1608582, Japan.
[Hishiki, Takako] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo 1608582, Japan.
[Kasahara, Masataka] Tokyo Dent Coll, Dept Pharmacol, Tokyo 1010061, Japan.
[Nakanishi, Tsuyoshi] Shimadzu Co Ltd, MS Business Unit, Kyoto 6048511, Japan.
[Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM william_kaelin@dfci.harvard.edu; gasbiology@keio.jp;
yoji_andrew_minamishima@keio.jp
RI Suematsu, Makoto/I-8135-2013; Minamishima, Yoji/E-5380-2010
OI Suematsu, Makoto/0000-0002-7165-6336; Minamishima,
Yoji/0000-0001-7995-9318
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
[23310136, 23659175, 20593966, 24659154, 26111006]; Takeda Science
Foundation, Japan
FX This study was supported in part by Grants-in-Aid for Scientific
Research (B) (23310136 to Y.A.M.), Grant-in-Aid for Exploratory Research
(23659175 and 20593966 to Y.A.M., and 24659154 to M.K.), Grant-in-Aid
for Scientific Research on Innovative Areas "Oxygen Biology: a new
criterion for integrated understanding of life" (26111006 to Y.A.M.)
from the Ministry of Education, Culture, Sports, Science and Technology,
Japan, and a research grant from Takeda Science Foundation, Japan (to
Y.A.M.). M.S. was a leader of the Japan Science and Technology Agency,
Exploratory Research for Advanced Technology, Suematsu Gas Biology
Project until March 31, 2015. LC/MS-based metabolome analysis was
supported by Biobank Japan Project in the Ministry of Education,
Culture, Sports, Science and Technology, Japan, under the supervision of
T.H., and capillary electrophoresis-mass spectrometry (CE/MS)-based
metabolome analysis was supported by the Japan Science and Technology
Agency, Core Research for Evolutional Science and Technology, under the
supervision of T.H. and Dr. Yasuaki Kabe.
NR 33
TC 5
Z9 5
U1 2
U2 11
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 SEP 15
PY 2015
VL 112
IS 37
BP 11642
EP 11647
DI 10.1073/pnas.1515872112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR5OW
UT WOS:000361393700061
PM 26324945
ER
PT J
AU Soeda, T
Uemura, S
Park, SJ
Jang, Y
Lee, S
Cho, JM
Kim, SJ
Vergallo, R
Minami, Y
Ong, DS
Gao, L
Lee, H
Zhang, SS
Yu, B
Saito, Y
Jang, IK
AF Soeda, Tsunenari
Uemura, Shiro
Park, Seung-Jung
Jang, Yangsoo
Lee, Stephen
Cho, Jin-Man
Kim, Soo-Joong
Vergallo, Rocco
Minami, Yoshiyasu
Ong, Daniel S.
Gao, Lei
Lee, Hang
Zhang, Shaosong
Yu, Bo
Saito, Yoshihiko
Jang, Ik-Kyung
TI Incidence and Clinical Significance of Poststent Optical Coherence
Tomography Findings One-Year Follow-Up Study From a Multicenter Registry
SO CIRCULATION
LA English
DT Article
DE diagnostic imaging; optical coherence tomography; stents
ID ELUTING STENT IMPLANTATION; INTRAVASCULAR ULTRASOUND ANALYSIS;
MYOCARDIAL-INFARCTION; NATURAL-HISTORY; TISSUE PROLAPSE; HUMAN AUTOPSY;
PREDICTORS; RESTENOSIS; PLAQUE; INTERVENTION
AB Background Optical coherence tomography (OCT) was recently introduced to optimize percutaneous coronary intervention. However, the exact incidence and significance of poststent OCT findings are unknown.
Methods and Results A total of 900 lesions treated with 1001 stents in 786 patients who had postprocedure OCT imaging were analyzed to evaluate the incidence of poststent OCT findings and to identify the OCT predictors for device-oriented clinical end points, including cardiac death, target vessel-related myocardial infarction, target lesion revascularization, and stent thrombosis. Patients were followed up to 1 year. Stent edge dissection was detected in 28.7% of lesions, and incomplete stent apposition was detected in 39.1% of lesions. The incidences of smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion were 92.9%, 61.0%, and 53.8%, respectively. Small minimal stent area, defined as a lesion with minimal stent area <5.0 mm(2) in a drug-eluting stent or <5.6 mm(2) in a bare metal stent, was observed in 40.4% of lesions. One-year device-oriented clinical end points occurred in 33 patients (4.5%). Following adjustment, irregular protrusion and small minimal stent area were independent OCT predictors of 1-year device-oriented clinical end points (P=0.003 and P=0.012, respectively).
Conclusions Abnormal poststent OCT findings were frequent. Irregular protrusion and small minimal stent area were independent predictors of 1-year device-oriented clinical end points, which were primarily driven by target lesion revascularization.
C1 [Soeda, Tsunenari; Vergallo, Rocco; Minami, Yoshiyasu; Ong, Daniel S.; Gao, Lei; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Soeda, Tsunenari; Uemura, Shiro; Saito, Yoshihiko] Nara Med Univ, Dept Med 1, Kashihara, Nara 634, Japan.
[Park, Seung-Jung] Univ Ulsan, Coll Med, Asan Med Ctr, Div Cardiol, Seoul, South Korea.
[Jang, Yangsoo] Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea.
[Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China.
[Cho, Jin-Man; Kim, Soo-Joong; Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea.
[Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA.
[Zhang, Shaosong; Yu, Bo] Harbin Med Univ, Chinese Minist Educ, Key Lab Myocardial Ischemia, Dept Cardiol,Affiliated Hosp 2, Harbin, Peoples R China.
RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM yubodr@163.com; ijang@mgh.harvard.edu
FU Mr and Mrs Michael Park and Dr John Nam Research Fellowship; Italian
Society of Cardiology Award for Research Abroad
FX This study was supported by a Mr and Mrs Michael Park and Dr John Nam
Research Fellowship grant. Dr Vergallo was funded in part by the 2013
Italian Society of Cardiology Award for Research Abroad.
NR 33
TC 11
Z9 12
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD SEP 15
PY 2015
VL 132
IS 11
BP 1020
EP 1029
DI 10.1161/CIRCULATIONAHA.114.014704
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CR4HW
UT WOS:000361293800007
PM 26162917
ER
PT J
AU Zhang, CA
Doherty, JA
Burgess, S
Hung, RJ
Lindstrom, S
Kraft, P
Gong, J
Amos, CI
Sellers, TA
Monteiro, ANA
Chenevix-Trench, G
Bickeboller, H
Risch, A
Brennan, P
Mckay, JD
Houlston, RS
Landi, MT
Timofeeva, MN
Wang, YF
Heinrich, J
Kote-Jarai, Z
Eeles, RA
Muir, K
Wiklund, F
Gronberg, H
Berndt, SI
Chanock, SJ
Schumacher, F
Haiman, CA
Henderson, BE
Al Olama, AA
Andrulis, IL
Hopper, JL
Chang-Claude, J
John, EM
Malone, KE
Gammon, MD
Ursin, G
Whittemore, AS
Hunter, DJ
Gruber, SB
Knight, JA
Hou, LF
Le Marchand, L
Newcomb, PA
Hudson, TJ
Chan, AT
Li, L
Woods, MO
Ahsan, H
Pierce, BL
AF Zhang, Chenan
Doherty, Jennifer A.
Burgess, Stephen
Hung, Rayjean J.
Lindstroem, Sara
Kraft, Peter
Gong, Jian
Amos, Christopher I.
Sellers, Thomas A.
Monteiro, Alvaro N. A.
Chenevix-Trench, Georgia
Bickeboeller, Heike
Risch, Angela
Brennan, Paul
Mckay, James D.
Houlston, Richard S.
Landi, Maria Teresa
Timofeeva, Maria N.
Wang, Yufei
Heinrich, Joachim
Kote-Jarai, Zsofia
Eeles, Rosalind A.
Muir, Ken
Wiklund, Fredrik
Gronberg, Henrik
Berndt, Sonja I.
Chanock, Stephen J.
Schumacher, Fredrick
Haiman, Christopher A.
Henderson, Brian E.
Al Olama, Ali Amin
Andrulis, Irene L.
Hopper, John L.
Chang-Claude, Jenny
John, Esther M.
Malone, Kathleen E.
Gammon, Marilie D.
Ursin, Giske
Whittemore, Alice S.
Hunter, David J.
Gruber, Stephen B.
Knight, Julia A.
Hou, Lifang
Le Marchand, Loic
Newcomb, Polly A.
Hudson, Thomas J.
Chan, Andrew T.
Li, Li
Woods, Michael O.
Ahsan, Habibul
Pierce, Brandon L.
CA GECCO
GAME-ON Network
CORECT
DRIVE
ELLIPSE
FOCI
TRICL
TI Genetic determinants of telomere length and risk of common cancers: a
Mendelian randomization study
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE METAANALYSIS; SHANGHAI WOMENS HEALTH; LUNG-CANCER;
PROSTATE-CANCER; OVARIAN-CANCER; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER;
CIGARETTE-SMOKING; DNA-DAMAGE; ASSOCIATION
AB Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 x 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 x 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk.
C1 [Zhang, Chenan; Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA.
[Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Ctr Canc Epidemiol & Prevent, Chicago, IL 60637 USA.
[Ahsan, Habibul] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Ahsan, Habibul; Pierce, Brandon L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Doherty, Jennifer A.] Dartmouth Coll, Epidemiol & Biostat Sect, Geisel Sch Med, Lebanon, NH 03756 USA.
[Amos, Christopher I.] Dartmouth Coll, Dept Community & Family Med, Ctr Genom Med, Geisel Sch Med, Lebanon, NH 03756 USA.
[Burgess, Stephen] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Al Olama, Ali Amin] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Hung, Rayjean J.] Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Toronto, ON, Canada.
[Lindstroem, Sara; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gong, Jian; Malone, Kathleen E.; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Sellers, Thomas A.; Monteiro, Alvaro N. A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Bickeboeller, Heike] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, D-37073 Gottingen, Germany.
[Risch, Angela] DKFZ, German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany.
[Risch, Angela] TLRC H, Heidelberg, Germany.
[Brennan, Paul; Mckay, James D.; Timofeeva, Maria N.] Int Agcy Res Canc, F-69372 Lyon, France.
[Houlston, Richard S.; Wang, Yufei; Kote-Jarai, Zsofia; Eeles, Rosalind A.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Landi, Maria Teresa; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Publ Hlth Serv, NIH, Bethesda, MD 20892 USA.
[Heinrich, Joachim] Helmholtz Zentrum Munchen, Inst Epidemiol 1, German Res Ctr Environm Hlth, Neuherberg, Germany.
[Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England.
[Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England.
[Muir, Ken] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Muir, Ken] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Andrulis, Irene L.] Univ Toronto, Mt Sinai Hosp, Mol Genet Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada.
[Hopper, John L.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne Sch Populat & Global Hlth, Parkville, Vic 3052, Australia.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Ursin, Giske] Kreftregisteret, Canc Registry Norway, Oslo, Norway.
[John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Gruber, Stephen B.] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Hou, Lifang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI USA.
[Newcomb, Polly A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Zhang, Chenan; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada.
[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.
[Li, Li] Case Western Reserve Univ, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA.
[Woods, Michael O.] Mem Univ St Johns, Fac Med, Discipline Genet, St Johns, NF, Canada.
RP Pierce, BL (reprint author), Univ Chicago, Dept Publ Hlth Sci, 5841 S Maryland Ave MC2000, Chicago, IL 60637 USA.
EM brandonpierce@uchicago.edu
RI Knight, Julia/A-6843-2012; Hung, Rayjean/A-7439-2013; Andrulis,
Irene/E-7267-2013; Risch, Angela/H-2669-2013;
OI Eeles, Rosalind/0000-0002-3698-6241; Risch, Angela/0000-0002-8026-5505;
Pierce, Brandon/0000-0002-7829-952X; Burgess,
Stephen/0000-0001-5365-8760; Houlston, Richard/0000-0002-5268-0242
FU Genetic Associations and Mechanisms in Oncology Network, GAME-ON:
Discovery, Biology, and Risk of Inherited Variants in Breast Cancer,
DRIVE [U19 CA148065]; Colorectal Transdisciplinary Study, CORECT [U19
CA148107]; Transdisciplinary Research in Cancer of the Lung, TRICL [U19
CA148127]; Follow-up of ovarian cancer genetic association and
interaction studies, FOCI [U19 CA148112]; Elucidating Loci Involved in
Prostate Cancer Susceptibility, ELLIPSE [U19 CA148537]; Genetics and
Epidemiology of Colorectal Cancer Consortium, GECCO: National Cancer
Institute, National Institutes of Health, US Department of Health and
Human Services [U01 CA137088, R01 CA059045]; National Institute of
Health, National Institute on Aging [T32AG000243, P30AG012857]; Cancer
Research Foundation Young Investigator Award [R01 ES020506, U01
HG007601]; Wellcome Trust [100114]; NHMRC; University of Cambridge (COAF
Open Access block grant)
FX This work was supported by the Genetic Associations and Mechanisms in
Oncology Network, GAME-ON: Discovery, Biology, and Risk of Inherited
Variants in Breast Cancer, DRIVE, PI: D.J.H. (U19 CA148065); Colorectal
Transdisciplinary Study, CORECT, PI: S.B.G. (U19 CA148107);
Transdisciplinary Research in Cancer of the Lung, TRICL, PI: C.A. (U19
CA148127); Follow-up of ovarian cancer genetic association and
interaction studies, FOCI, PI: T.A. S. (U19 CA148112); Elucidating Loci
Involved in Prostate Cancer Susceptibility, ELLIPSE, PI: B.E.H. (U19
CA148537); Genetics and Epidemiology of Colorectal Cancer Consortium,
GECCO: National Cancer Institute, National Institutes of Health, US
Department of Health and Human Services (U01 CA137088, R01 CA059045);
National Institute of Health, National Institute on Aging (T32AG000243;
P30AG012857) to C.Z.; Cancer Research Foundation Young Investigator
Award, R01 ES020506, and U01 HG007601 to BLP; The Wellcome Trust
(100114) to S.B.; The NHMRC Senior Principal Research Fellow to G.C.T.
Funding to pay the Open Access publication charges for this article was
provided by the University of Cambridge (COAF Open Access block grant).
NR 69
TC 20
Z9 20
U1 2
U2 16
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 SEP 15
PY 2015
VL 24
IS 18
BP 5356
EP 5366
DI 10.1093/hmg/ddv252
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CR4PE
UT WOS:000361317200024
PM 26138067
ER
PT J
AU Ndhlovu, ZM
Kamya, P
Mewalal, N
Kloverpris, HN
Nkosi, T
Pretorius, K
Laher, F
Ogunshola, F
Chopera, D
Shekhar, K
Ghebremichael, M
Ismail, N
Moodley, A
Malik, A
Leslie, A
Goulder, PJR
Buus, S
Chakraborty, A
Dong, K
Ndung'u, T
Walker, BD
AF Ndhlovu, Zaza M.
Kamya, Philomena
Mewalal, Nikoshia
Kloverpris, Henrik N.
Nkosi, Thandeka
Pretorius, Karyn
Laher, Faatima
Ogunshola, Funsho
Chopera, Denis
Shekhar, Karthik
Ghebremichael, Musie
Ismail, Nasreen
Moodley, Amber
Malik, Amna
Leslie, Alasdair
Goulder, Philip J. R.
Buus, Soren
Chakraborty, Arup
Dong, Krista
Ndung'u, Thumbi
Walker, Bruce D.
TI Magnitude and Kinetics of CD8(+) T Cell Activation during Hyperacute HIV
Infection Impact Viral Set Point
SO IMMUNITY
LA English
DT Article
ID IMMUNODEFICIENCY VIRUS-INFECTION; ANTIRETROVIRAL THERAPY;
IMMUNE-RESPONSES; VIREMIA; EXPRESSION; EXPANSION; ANTIBODY; ESCAPE;
AIDS; SEROCONVERSION
AB CD8(+) T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV-specific CD8(+) T cells secreted little interferon-gamma, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8(+) T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.
C1 [Ndhlovu, Zaza M.; Kamya, Philomena; Mewalal, Nikoshia; Nkosi, Thandeka; Pretorius, Karyn; Laher, Faatima; Ogunshola, Funsho; Ismail, Nasreen; Moodley, Amber; Goulder, Philip J. R.; Ndung'u, Thumbi; Walker, Bruce D.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa.
[Ndhlovu, Zaza M.; Kamya, Philomena; Ghebremichael, Musie; Moodley, Amber; Leslie, Alasdair; Chakraborty, Arup; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
[Kloverpris, Henrik N.; Chopera, Denis; Leslie, Alasdair; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV K RITH, ZA-4001 Durban, South Africa.
[Ndung'u, Thumbi] Max Planck Inst Infect Biol, D-10117 Berlin, Germany.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Chakraborty, Arup] MIT, Dept Chem Engn, Cambridge, MA 02142 USA.
[Malik, Amna; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England.
[Kloverpris, Henrik N.; Buus, Soren] Univ Copenhagen, Dept Immunol & Microbiol, DK-2200 Copenhagen N, Denmark.
RP Walker, BD (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa.
EM bwalker@mgh.harvard.edu
FU Bill and Melinda Gates Foundation; Witten Family Foundation; Mark and
Lisa Schwartz Foundation; International AIDS Vaccine Initiative (IAVI)
[UKZNRSA1001]; NIAID [R37AI067073]; NIH [P30 AI060354]; NIAID, NIH; NCI,
NIH; NICHD, NIH; NHLBI, NIH; NIDA, NIH; NIMH, NIH; NIA, NIH; FIC, NIH;
OAR, NIH; Howard Hughes Medical Institute; South African Research Chairs
Initiative; Collaboration for AIDS Vaccine Discovery
FX We would like to thank the FRESH participants, as well as the FRESH and
HIV Pathogenesis Programme (HPP) laboratory staff. This work was
supported by the Bill and Melinda Gates Foundation and the Collaboration
for AIDS Vaccine Discovery, the Witten Family Foundation, Dan and
Marjorie Sullivan, the Mark and Lisa Schwartz Foundation, Ursula
Brunner, Gary and Loren Cohen, the International AIDS Vaccine Initiative
(IAVI) (UKZNRSA1001), the NIAID (R37AI067073), and an NIH funded Center
for AIDS Research (P30 AI060354), which is supported by the following
NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI,
NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR, and the Howard Hughes
Medical Institute. Additional funding was received from the South
African Research Chairs Initiative. We would like to thank Drs. Alan S.
Perelson and Ruy M. Rubeiro for their expert advice on viral growth
kinetics calculations, and Dr. Daniel E. Kaufmann, MD for critical
reading of the manuscript.
NR 50
TC 25
Z9 26
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD SEP 15
PY 2015
VL 43
IS 3
BP 591
EP 604
DI 10.1016/j.immuni.2015.08.012
PG 14
WC Immunology
SC Immunology
GA CR8BE
UT WOS:000361575300011
PM 26362266
ER
PT J
AU Anzueto, A
Wise, R
Calverley, P
Dusser, D
Tang, WB
Metzdorf, N
Dahl, R
AF Anzueto, Antonio
Wise, Robert
Calverley, Peter
Dusser, Daniel
Tang, Wenbo
Metzdorf, Norbert
Dahl, Ronald
TI The Tiotropium Safety and Performance in Respimat (R) (TIOSPIR (R))
Trial: Spirometry Outcomes
SO RESPIRATORY RESEARCH
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION; COPD
AB Background: Tiotropium Safety and Performance in Respimat (R) (TIOSPIR (R)) compared the safety and efficacy of tiotropium Respimat (R) and tiotropium HandiHaler (R) in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups.
Methods: TIOSPIR (R) was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial.
Results: The substudy included 1370 patients who received once-daily tiotropium Respimat (R) 5 mu g (n = 461), 2.5 mu g (n = 464), or tiotropium HandiHaler (R) 18 mu g (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat (R) 5 mu g, 2.5 mu g, and HandiHaler (R) 18 mu g groups (difference versus HandiHaler (R) [95 % CI]: -10 [-38, 18] mL for Respimat (R) 5 mu g and, -37 [-65, -9] mL for Respimat (R) 2.5 mu g); achieving noninferiority to tiotropium HandiHaler (R) 18 mu g for tiotropium Respimat (R) 5 but not for 2.5 mu g (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat (R) 5 mu g, 2.5 mu g, and HandiHaler (R) 18 mu g groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat (R) 5-mu g, 2.5-mu g, and HandiHaler (R) 18-mu g groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not.
Conclusions: The TIOSPIR (R) spirometry substudy showed that tiotropium Respimat (R) 5 mu g was noninferior to tiotropium HandiHaler (R) 18 mu g for trough FEV1, but Respimat (R) 2.5 mu g was not. Tiotropium Respimat (R) 5 mu g provides similar bronchodilator efficacy to tiotropium HandiHaler (R) 18 mu g with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.
C1 [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Pulm Crit Care, San Antonio, TX 78229 USA.
[Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Wise, Robert] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Calverley, Peter] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool L69 3BX, Merseyside, England.
[Dusser, Daniel] Hop Cochin, Serv Pneumol, F-75674 Paris, France.
[Tang, Wenbo] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
[Metzdorf, Norbert] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
[Dahl, Ronald] Odense Univ Hosp, DK-5000 Odense, Denmark.
RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pulm Crit Care, 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA.
EM anzueto@uthscsa.edu
FU Boehringer Ingelheim
FX This study was funded by Boehringer Ingelheim. Writing assistance was
provided by Sarah J. Petit of PAREXEL, funded by Boehringer Ingelheim.
Data have been reported in part in the primary data publication [7] and
at the CHEST/ACCP congress 2013 [21].
NR 19
TC 3
Z9 4
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-993X
EI 1465-9921
J9 RESP RES
JI Respir. Res.
PD SEP 15
PY 2015
VL 16
AR 107
DI 10.1186/s12931-015-0269-4
PG 9
WC Respiratory System
SC Respiratory System
GA CR5EH
UT WOS:000361362500001
PM 26369563
ER
PT J
AU Rigotti, NA
Wallace, RB
AF Rigotti, Nancy A.
Wallace, Robert B.
TI Using Agent-Based Models to Address "Wicked Problems" Like Tobacco Use:
A Report From the Institute of Medicine
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,Room 914, Boston, MA 02114 USA.
EM nrigotti@partners.org
NR 9
TC 3
Z9 3
U1 2
U2 7
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD SEP 15
PY 2015
VL 163
IS 6
BP 469
EP +
DI 10.7326/M15-1567
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR5FL
UT WOS:000361365900022
PM 26216183
ER
PT J
AU Moin, T
Duru, OK
Mangione, CM
AF Moin, Tannaz
Duru, O. Kenrik
Mangione, Carol M.
TI Metformin Prescription for Insured Adults With Prediabetes From 2010 to
2012 RESPONSE
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID DIABETES PREVENTION PROGRAM
C1 [Moin, Tannaz] Vet Affairs Greater Los Angeles Hlth Syst, Vet Affairs Hlth Serv Res & Dev Serv, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA.
[Moin, Tannaz; Duru, O. Kenrik; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Mangione, Carol M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA USA.
RP Moin, T (reprint author), Vet Affairs Greater Los Angeles Hlth Syst, Vet Affairs Hlth Serv Res & Dev Serv, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA.
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD SEP 15
PY 2015
VL 163
IS 6
BP 483
EP 483
DI 10.7326/L15-5136-2
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR5FL
UT WOS:000361365900031
PM 26370017
ER
PT J
AU Hunter, JE
Zepp, JM
Gilmore, MJ
Davis, JV
Esterberg, EJ
Muessig, KR
Peterson, SK
Syngal, S
Acheson, LS
Wiesner, GL
Reiss, JA
Goddard, KAB
AF Hunter, Jessica Ezzell
Zepp, Jamilyn M.
Gilmore, Mari J.
Davis, James V.
Esterberg, Elizabeth J.
Muessig, Kristin R.
Peterson, Susan K.
Syngal, Sapna
Acheson, Louise S.
Wiesner, Georgia L.
Reiss, Jacob A.
Goddard, Katrina A. B.
TI Universal tumor screening for Lynch syndrome: Assessment of the
perspectives of patients with colorectal cancer regarding benefits and
barriers
SO CANCER
LA English
DT Article
DE hereditary nonpolyposis colorectal cancer (HNPCC); Lynch syndrome;
genetic screening; genetic counseling; colorectal neoplasms
ID REVISED BETHESDA GUIDELINES; GENETIC TESTING STRATEGIES; REDUCING
MORBIDITY; COST-EFFECTIVENESS; HNPCC; RISK; IDENTIFICATION; INDIVIDUALS;
MOTIVATIONS; MORTALITY
AB BACKGROUNDUniversal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria.
METHODSA total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed.
RESULTSThe majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing 6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing 4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage.
CONCLUSIONSThe results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs. Cancer 2015;121:3281-3289. (c) 2015 American Cancer Society.
In the current study, perspectives among patients newly diagnosed with colorectal cancer are assessed regarding universal tumor screening for Lynch syndrome. The majority of patients appear to have a positive attitude toward screening and endorse the benefits for themselves and their families, whereas potential barriers include concerns over the cost of additional genetic counseling and testing.
C1 [Hunter, Jessica Ezzell; Zepp, Jamilyn M.; Gilmore, Mari J.; Davis, James V.; Esterberg, Elizabeth J.; Muessig, Kristin R.; Reiss, Jacob A.; Goddard, Katrina A. B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97229 USA.
[Peterson, Susan K.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA.
[Syngal, Sapna] Harvard Univ, Sch Med, Div Med Oncol, Dept Med,Dana Farber Canc Inst,Brigham & Womens H, Boston, MA USA.
[Acheson, Louise S.] Case Western Reserve Univ, Dept Reprod Biol, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA.
[Acheson, Louise S.] Univ Hosp Case, Med Ctr, Cleveland, OH USA.
[Wiesner, Georgia L.] Vanderbilt Univ, Vanderbilt Hereditary Canc Program, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA.
RP Hunter, JE (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97229 USA.
EM Jessica.E.Hunter@kpchr.org
FU National Cancer Institute of the National Institutes of Health
[5R01CA140377]
FX Supported through a grant from the National Cancer Institute of the
National Institutes of Health (grant 5R01CA140377 to Dr. Goddard).
NR 41
TC 0
Z9 0
U1 1
U2 6
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 SEP 15
PY 2015
VL 121
IS 18
BP 3281
EP 3289
DI 10.1002/cncr.29470
PG 9
WC Oncology
SC Oncology
GA CQ7DN
UT WOS:000360763200016
PM 26036338
ER
PT J
AU Derwall, M
Ebeling, A
Nolte, KW
Weis, J
Rossaint, R
Ichinose, F
Nix, C
Fries, M
Brucken, A
AF Derwall, Matthias
Ebeling, Andreas
Nolte, Kay Wilhelm
Weis, Joachim
Rossaint, Rolf
Ichinose, Fumito
Nix, Christoph
Fries, Michael
Bruecken, Anne
TI Inhaled nitric oxide improves transpulmonary blood flow and clinical
outcomes after prolonged cardiac arrest: a large animal study
SO CRITICAL CARE
LA English
DT Article
ID MILD THERAPEUTIC HYPOTHERMIA; ISCHEMIA-REPERFUSION INJURY; DECREASES
INFARCTION SIZE; VENTRICULAR ASSIST DEVICE;
CARDIOPULMONARY-RESUSCITATION; MYOCARDIAL-ISCHEMIA; STROKE MODEL;
BRAIN-DAMAGE; GLUCOSE; PIGS
AB Introduction: The probability to achieve a return of spontaneous circulation (ROSC) after cardiac arrest can be improved by optimizing circulation during cardiopulomonary resuscitation using a percutaneous left ventricular assist device (iCPR). Inhaled nitric oxide may facilitate transpulmonary blood flow during iCPR and may therefore improve organ perfusion and outcome.
Methods: Ventricular fibrillation was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20 ppm of inhaled nitric oxide (iNO, n = 10) or 0 ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following ROSC. Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains were harvested for neurohistopathologic evaluation.
Results: All animals in both groups achieved ROSC. Administration of iNO markedly increased iCPR flow during CPR (iNO: 1.81 +/- 0.30 vs Control: 1.64 +/- 0.51 L/min, p < 0.001), leading to significantly higher coronary perfusion pressure (CPP) during the 6 minutes of CPR (25 +/- 13 vs 16 +/- 6 mmHg, p = 0.002). iNO-treated animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 +/- 0.09 vs 0.38 +/- 0.15 ng/mL, p = 0.048), as well as lower blood glucose levels 120-360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO-treated animals as estimated with OPC (3 +/- 2 vs. 5 +/- 1, p = 0.036 on days 3 to 5). Three out of ten iNO-treated, but none of the Control animals were able to successfully participate in the spatial memory task. Neurohistopathological examination of vulnerable cerebral structures revealed a trend towards less cerebral lesions in neocortex, archicortex, and striatum in iNO-treated animals compared to Controls.
Conclusions: In pigs resuscitated with mechanically-assisted CPR from prolonged cardiac arrest, the administration of 20 ppm iNO during and following iCPR improved transpulmonary blood flow, leading to improved clinical neurological outcomes.
C1 [Derwall, Matthias; Ebeling, Andreas; Rossaint, Rolf; Bruecken, Anne] Univ Hosp RWTH Aachen, Dept Anesthesiol, D-52074 Aachen, Germany.
[Nolte, Kay Wilhelm; Weis, Joachim] Univ Hosp RWTH Aachen, Inst Neuropathol, D-52074 Aachen, Germany.
[Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Nix, Christoph] Abiomed Europe GmbH, D-52074 Aachen, Germany.
[Fries, Michael] St Vincenz Hosp Limburg, Dept Anesthesiol, D-65549 Limburg, Germany.
RP Derwall, M (reprint author), Univ Hosp RWTH Aachen, Dept Anesthesiol, Pauwelsstr 30, D-52074 Aachen, Germany.
EM mderwall@ukaachen.de
RI Weis, Joachim/G-1984-2014
OI Weis, Joachim/0000-0003-3280-6773
FU German Research Foundation (Deutsche Forschungsgemeinschaft) [DE
1685/3-1]; Else Kroner-Fresenius-Foundation [EKFS: 2014_A119]; National
Institutes of Health [NIH R01 110378]
FX This work was made possible by a grant by the German Research Foundation
(Deutsche Forschungsgemeinschaft: DE 1685/3-1) to Matthias Derwall and a
grant to Michael Fries by the Else Kroner-Fresenius-Foundation (EKFS:
2014_A119). Fumito Ichinose was supported by the National Institutes of
Health grant NIH R01 110378 (Matthias Derwall, Andreas Ebeling, Rolf
Rossaint, and Anne Brucken).
NR 33
TC 1
Z9 1
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD SEP 15
PY 2015
VL 19
AR 328
DI 10.1186/s13054-015-1050-2
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA CR1PM
UT WOS:000361097300001
PM 26369409
ER
PT J
AU Jena, AB
Khullar, D
Ho, O
Olenski, AR
Blumenthal, DM
AF Jena, Anupam B.
Khullar, Dhruv
Ho, Oliver
Olenski, Andrew R.
Blumenthal, Daniel M.
TI Sex Differences in Academic Rank in US Medical Schools in 2014
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GENDER-DIFFERENCES; PHYSICIAN-RESEARCHERS; CAREER SATISFACTION; WOMEN
PHYSICIANS; FACULTY; PRODUCTIVITY; TRENDS; MEN; RESPONSIBILITIES;
ADVANCEMENT
AB IMPORTANCE The proportion of women at the rank of full professor in US medical schools has not increased since 1980 and remains below that of men. Whether differences in age, experience, specialty, and research productivity between sexes explain persistent disparities in faculty rank has not been studied.
OBJECTIVE To analyze sex differences in faculty rank among US academic physicians.
DESIGN, SETTING, AND PARTICIPANTS We analyzed sex differences in faculty rank using a cross-sectional comprehensive database of US physicians with medical school faculty appointments in 2014 (91 073 physicians; 9.1% of all US physicians), linked to information on physician sex, age, years since residency, specialty, authored publications, National Institutes of Health (NIH) funding, and clinical trial investigation. We estimated sex differences in full professorship, as well as a combined outcome of associate or full professorship, adjusting for these factors in a multilevel (hierarchical) model. We also analyzed how sex differences varied with specialty and whether differences were more prevalent at schools ranked highly in research.
EXPOSURES Physician sex.
MAIN OUTCOMES AND MEASURES Academic faculty rank.
RESULTS In all, there were 30 464 women who were medical faculty vs 60 609 men. Of those, 3623 women (11.9%) vs 17 354 men (28.6%) had full-professor appointments, for an absolute difference of -16.7%(95% CI, -17.3% to -16.2%). Women faculty were younger and disproportionately represented in internal medicine and pediatrics. The mean total number of publications for women was 11.6 vs 24.8 for men, for a difference of -13.2 (95% CI, -13.6 to -12.7); the mean first-or last-author publications for women was 5.9 vs 13.7 for men, for a difference of -7.8 (95% CI, -8.1 to -7.5). Among 9.1% of medical faculty with an NIH grant, 6.8%(2059 of 30 464) were women and 10.3%(6237 of 60 609) were men, for a difference of -3.5%(95% CI, -3.9% to -3.1%). In all, 6.4% of women vs 8.8% of men had a trial registered on ClinicalTrials.gov, for a difference of -2.4%(95% CI, -2.8% to -2.0%). After multivariable adjustment, women were less likely than men to have achieved full-professor status (absolute adjusted difference in proportion, -3.8%; 95% CI, -4.4% to -3.3%). Sex-differences in full professorship were present across all specialties and did not vary according to whether a physician's medical school was ranked highly in terms of research funding.
CONCLUSIONS AND RELEVANCE Among physicians with faculty appointments at US medical schools, there were sex differences in academic faculty rank, with women substantially less likely than men to be full professors, after accounting for age, experience, specialty, and measures of research productivity.
C1 [Jena, Anupam B.; Ho, Oliver; Olenski, Andrew R.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA.
[Khullar, Dhruv] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Khullar, Dhruv; Blumenthal, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA.
[Blumenthal, Daniel M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM jena@hcp.med.harvard.edu
FU Office of the Director, National Institutes of Health [1DP5OD017897-01]
FX The authors report funding grant 1DP5OD017897-01 Early Independence
Award from the Office of the Director, National Institutes of Health (Dr
Jena).
NR 33
TC 22
Z9 22
U1 0
U2 6
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 SEP 15
PY 2015
VL 314
IS 11
BP 1149
EP 1158
DI 10.1001/jama.2015.10680
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA CR4EL
UT WOS:000361284500026
PM 26372584
ER
PT J
AU Cox, A
Varma, A
Barry, J
Vertegel, A
Banik, N
AF Cox, April
Varma, Abhay
Barry, John
Vertegel, Alexey
Banik, Naren
TI Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid
Anti-Inflammatory Effects in Plasma, Cerebrospinal Fluid, and Tissue
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE spinal cord injury; MCP-1; IL-6; GRO-KC; S100 beta; nanoparticle;
estrogen; CSF
ID TRAUMATIC BRAIN-INJURY; RANDOMIZED CONTROLLED-TRIAL; APOPTOTIC
CELL-DEATH; INFLAMMATORY CYTOKINES; CLINICAL-TRIALS; POSTMENOPAUSAL
WOMEN; FUNCTIONAL RECOVERY; LOCOMOTOR FUNCTION; RECEPTOR-ALPHA; SEX
STEROIDS
AB Persons with spinal cord injury (SCI) are in need of effective therapeutics. Estrogen (E2), as a steroid hormone, is a highly pleiotropic agent; with anti-inflammatory, anti-apoptotic, and neurotrophic properties, it is ideal for use in treatment of patients with SCI. Safety concerns around the use of high doses of E2 have limited clinical application, however. To address these concerns, low doses of E2 (25 mu g and 2.5 mu g) were focally delivered to the injured spinal cord using nanoparticles. A per-acute model (6 h after injury) was used to assess nanoparticle release of E2 into damaged spinal cord tissue; in addition, E2 was evaluated as a rapid anti-inflammatory. To assess inflammation, 27-plex cytokine/chemokine arrays were conducted in plasma, cerebrospinal fluid (CSF), and spinal cord tissue. A particular focus was placed on IL-6, GRO-KC, and MCP-1 as these have been identified from CSF in human studies as potential biomarkers in SCI. S100 beta, an additional proposed biomarker, was also assessed in spinal cord tissue only. Tissue concentrations of E2 were double those found in the plasma, indicating focal release. E2 showed rapid anti-inflammatory effects, significantly reducing interleukin (IL)-6, GRO-KC, MCP-1, and S100 beta in one or all compartments. Numerous additional targets of rapid E2 modulation were identified including: leptin, MIP-1 alpha, IL-4, IL-2, IL-10, IFN gamma, tumor necrosis factor-alpha, etc. These data further elucidate the rapid anti-inflammatory effects E2 exerts in an acute rat SCI model, have identified additional targets of estrogen efficacy, and suggest nanoparticle delivered estrogen may provide a safe and efficacious treatment option in persons with acute SCI.
C1 [Cox, April; Varma, Abhay; Banik, Naren] Med Univ S Carolina, Dept Neurol & Neurosurg, Charleston, SC 29425 USA.
[Barry, John; Vertegel, Alexey] Clemson Univ, Dept Bioengn, Clemson, SC USA.
[Banik, Naren] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Cox, A (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St,MSC 606, Charleston, SC 29412 USA.
EM coxaa@musc.edu
FU NIH [NINDS-RO1 NS-31622, NS-45967]; Office of Research and Development,
Medical Research Service, Department of Veterans Affairs, at Ralph H.
Johnson VA Medical Center, Charleston, SC, the Department of
Neurosurgery, MUSC [1IOBX001262]; South Carolina Spinal Cord Injury
Research Fund; National Institutes of Health from the Extramural
Research Facilities Program of the National Center for Research
Resources [C06 RR015455]
FX The funding for this project was provided in part by NIH, NINDS-RO1
NS-31622 and NS-45967; also by 1IOBX001262 from the Office of Research
and Development, Medical Research Service, Department of Veterans
Affairs, at Ralph H. Johnson VA Medical Center, Charleston, SC, the
Department of Neurosurgery, MUSC, and South Carolina Spinal Cord Injury
Research Fund. This work was conducted in a facility constructed with
support from the National Institutes of Health, Grant Number C06
RR015455 from the Extramural Research Facilities Program of the National
Center for Research Resources. We would like to acknowledge Dr. Supriti
Samantaray and Nakul Thakore for help in organizing this article.
NR 67
TC 5
Z9 5
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD SEP 15
PY 2015
VL 32
IS 18
BP 1413
EP 1421
DI 10.1089/neu.2014.3730
PG 9
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA CQ8AR
UT WOS:000360828900004
PM 25845398
ER
PT J
AU Bell, SP
Orr, NM
Dodson, JA
Rich, MW
Wenger, NK
Blum, K
Harold, JG
Tinetti, ME
Maurer, MS
Forman, DE
AF Bell, Susan P.
Orr, Nicole M.
Dodson, John A.
Rich, Michael W.
Wenger, Nanette K.
Blum, Kay
Harold, John Gordon
Tinetti, Mary E.
Maurer, Mathew S.
Forman, Daniel E.
TI What to Expect From the Evolving Field of Geriatric Cardiology
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE aging; cardiovascular disease; geriatrics; quality; training
ID AMERICAN-HEART-ASSOCIATION; OLDER-ADULTS; MYOCARDIAL-INFARCTION;
PHYSICAL-ACTIVITY; COGNITIVE IMPAIRMENT; HEALTH-BENEFITS; GAIT SPEED;
MINI-COG; CARE; FAILURE
AB The population of older adults is expanding rapidly, and aging predisposes to cardiovascular disease. The principle of patient-centered care must respond to the preponderance of cardiac disease that now occurs in combination with the complexities of old age. Geriatric cardiology melds cardiovascular perspectives with multimorbidity, polypharmacy, frailty, cognitive decline, and other clinical, social, financial, and psychological dimensions of aging. Although some assume that a cardiologist may instinctively cultivate some of these skills over the course of a career, we assert that the volume and complexity of older cardiovascular patients in contemporary practice warrants a more direct approach to achieve suitable training and a more reliable process of care. We present a rationale and vision for geriatric cardiology as a melding of primary cardiovascular and geriatrics skills, thereby infusing cardiology practice with expanded proficiencies in diagnosis, risks, care coordination, communications, end-of-life, and other competences required to best manage older cardiovascular patients. (C) 2015 by the American College of Cardiology Foundation.
C1 [Bell, Susan P.] Vanderbilt Univ, Sch Med, Dept Med, Div Cardiovasc Med, Nashville, TN 37212 USA.
[Bell, Susan P.] Vanderbilt Univ, Sch Med, Div Geriatr Med, Ctr Qual Aging, Nashville, TN 37212 USA.
[Orr, Nicole M.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
[Orr, Nicole M.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA.
[Dodson, John A.] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY USA.
[Rich, Michael W.] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA.
[Wenger, Nanette K.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[Blum, Kay] Amer Coll Cardiol, Geriatr Cardiol Sect, Washington, DC USA.
[Harold, John Gordon] Univ Calif Los Angeles, Cedars Sinai Heart Inst, Los Angeles, CA USA.
[Harold, John Gordon] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Tinetti, Mary E.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Tinetti, Mary E.] Yale Univ, Sch Med, Dept Publ Hlth & Epidemiol, New Haven, CT USA.
[Maurer, Mathew S.] Columbia Univ, Dept Med, Med Ctr, Div Cardiol, New York, NY USA.
[Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Dept Med, Geriatr Cardiol Sect, Pittsburgh, PA USA.
[Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Forman, DE (reprint author), Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA.
EM formand@pitt.edu
FU National Institute of Child Health and Human Development
[2K12HD043483-11]; Eisenstein's Women's Heart Fund; National Institute
on Aging (NIA) grant [U13 AG047008]; John A. Hartford Foundation; NIA
[AG045148, AG036778, P30 AG024827]; VA Office of Rehabilitation Research
and Development grant [F0834-R]
FX Dr. Bell is supported by a grant from the National Institute of Child
Health and Human Development (2K12HD043483-11) and the Eisenstein's
Women's Heart Fund. Dr. Rich is supported by National Institute on Aging
(NIA) grant U13 AG047008. Dr. Tinetti receives funding from the John A.
Hartford Foundation for work related to developing a patient
goals-directed approach to the care of older adults with multiple
chronic conditions; and is supported by an NIA R21 grant (AG045148). Dr.
Maurer receives funding from an NIA K24 award (AG036778). Dr. Forman is
supported in part by NIA grant P30 AG024827 and VA Office of
Rehabilitation Research and Development grant F0834-R. All other authors
have reported that they have no relationships relevant to the contents
of this paper to disclose.
NR 47
TC 13
Z9 14
U1 4
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD SEP 15
PY 2015
VL 66
IS 11
BP 1286
EP 1299
DI 10.1016/j.jacc.2015.07.048
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CQ7XV
UT WOS:000360820800012
PM 26361161
ER
PT J
AU Oleson, BJ
McGraw, JA
Broniowska, KA
Annamalai, M
Chen, J
Bushkofsky, JR
Davis, DB
Corbett, JA
Mathews, CE
AF Oleson, Bryndon J.
McGraw, Jennifer A.
Broniowska, Katarzyna A.
Annamalai, Mani
Chen, Jing
Bushkofsky, Justin R.
Davis, Dawn B.
Corbett, John A.
Mathews, Clayton E.
TI Distinct differences in the responses of the human pancreatic beta-cell
line EndoC-beta H1 and human islets to proinflammatory cytokines
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE insulinoma; islet; diabetes; nitric oxide; cytokine
ID NITRIC-OXIDE SYNTHASE; INSULIN-SECRETING CELLS; CONFERS RESISTANCE;
INDUCED INHIBITION; S-NITROSATION; DNA-DAMAGE; RAT ISLETS; ER STRESS;
APOPTOSIS; LANGERHANS
AB While insulinoma cells have been developed and proven to be extremely useful in studies focused on mechanisms controlling beta-cell function and viability, translating findings to human beta-cells has proven difficult because of the limited access to human islets and the absence of suitable insulinoma cell lines of human origin. Recently, a human beta-cell line, EndoC-beta H1, has been derived from human fetal pancreatic buds. The purpose of this study was to determine whether human EndoC-beta H1 cells respond to cytokines in a fashion comparable to human islets. Unlike most rodent-derived insulinoma cell lines that respond to cytokines in a manner consistent with rodent islets, EndoC-beta H1 cells fail to respond to a combination of cytokines (IL-1, IFN-gamma, and TNF) in a manner consistent with human islets. Nitric oxide, produced following inducible nitric oxide synthase (iNOS) expression, is a major mediator of cytokine-induced human islet cell damage. We show that EndoC-beta H1 cells fail to express iNOS or produce nitric oxide in response to this combination of cytokines. Inhibitors of iNOS prevent cytokine-induced loss of human islet cell viability; however, they do not prevent cytokine-induced EndoC-beta H1 cell death. Stressed human islets or human islets expressing heat shock protein 70 (HSP70) are resistant to cytokines, and, much like stressed human islets, EndoC-beta H1 cells express HSP70 under basal conditions. Elevated basal expression of HSP70 in EndoC-beta H1 cells is consistent with the lack of iNOS expression in response to cytokine treatment. While expressing HSP70, EndoC-beta H1 cells fail to respond to endoplasmic reticulum stress activators, such as thapsigargin. These findings indicate that EndoC-beta H1 cells do not faithfully recapitulate the response of human islets to cytokines. Therefore, caution should be exercised when making conclusions regarding the actions of cytokines on human islets when using this human-derived insulinoma cell line.
C1 [Oleson, Bryndon J.; McGraw, Jennifer A.; Broniowska, Katarzyna A.; Corbett, John A.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
[Annamalai, Mani; Chen, Jing; Mathews, Clayton E.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA.
[Bushkofsky, Justin R.; Davis, Dawn B.] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI USA.
[Davis, Dawn B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Corbett, JA (reprint author), Med Coll Wisconsin, Dept Biochem, 8701 W Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM jcorbett@mcw.edu
OI Broniowska, Katarzyna/0000-0002-8000-9093
FU National Institutes of Health [DK-083442, DK-074656, UC4 DK-104194, UC4
DK-104167, P01 AI-042288, DK-052194, AI-44458]; United States Department
of Veterans Affairs [1101BX001880]; American Diabetes Association (ADA)
[1-11-BS-104]; American Health Association [13POST16940076,
14PRE20380585]; University of Wisconsin; Integrated Islet Distribution
Program
FX This work was supported by grants from the National Institutes of Health
(DK-083442 to D. B. Davis; DK-074656, UC4 DK-104194, UC4 DK-104167, and
P01 AI-042288 to C. E. Matthews; and DK-052194 and AI-44458 to J. A.
Corbett), United States Department of Veterans Affairs (1101BX001880 to
D. B. Davis), American Diabetes Association (ADA 1-11-BS-104 to C. E.
Mathews), American Health Association 13POST16940076 (to K. A.
Broniowska) and 14PRE20380585 (B. J. Oleson), and by support from the
University of Wisconsin. Human pancreatic islets were provided by the
National Institute of Diabetes and Digestive and Kidney Diseases funded
Integrated Islet Distribution Program. This work was performed, in part,
using facilities and resources from the William S. Middleton Memorial
Veterans Hospital.
NR 65
TC 6
Z9 6
U1 2
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
EI 1522-1490
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD SEP 15
PY 2015
VL 309
IS 5
BP R525
EP R534
DI 10.1152/ajpregu.00544.2014
PG 10
WC Physiology
SC Physiology
GA CQ4BE
UT WOS:000360548300010
PM 26084699
ER
PT J
AU Ikeda, K
Marutani, E
Hirai, S
Wood, ME
Whiteman, M
Ichinose, F
AF Ikeda, Kohei
Marutani, Eizo
Hirai, Shuichi
Wood, Mark E.
Whiteman, Matthew
Ichinose, Fumito
TI Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological
outcomes after cardiac arrest in mice
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Cardiac arrest; Resuscitation; Hydrogen sulfide; Mitochondria
ID CARDIOPULMONARY-RESUSCITATION; ISCHEMIA-REPERFUSION; PROTECTS; SURVIVAL;
BRAIN; PRESERVATION; HYPOTHERMIA; INJURY; MODEL; DEATH
AB Aims: Mitochondria-targeted hydrogen sulfide donor AP39, [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl) phenoxy)decyl) triphenylphosphonium bromide], exhibits cytoprotective effects against oxidative stress in vitro. We examined whether or not AP39 improves the neurological function and long term survival in mice subjected to cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).
Methods: Adult C57BL/6 male mice were subjected to 8 min of CA and subsequent CPR. We examined the effects of AP39 (10, 100, 1000 nmol kg(-1)) or vehicle administered intravenously at 2 min before CPR (Experiment 1). Systemic oxidative stress levels, mitochondrial permeability transition, and histological brain injury were assessed. We also examined the effects of AP39 (10, 1000 nmol kg(-1)) or vehicle administered intravenously at 1 min after return of spontaneous circulation (ROSC) (Experiment 2). ROSC was defined as the return of sinus rhythm with a mean arterial pressure >40 mm Hg lasting at least 10 seconds.
Results: Vehicle treated mice subjected to CA/CPR had poor neurological function and 10-day survival rate (Experiment 1; 15%, Experiment 2; 23%). Administration of AP39 (100 and 1000 nmol kg-1) 2 min before CPR significantly improved the neurological function and 10-day survival rate (54% and 62%, respectively) after CA/CPR. Administration of AP39 before CPR attenuated mitochondria] permeability transition pore opening, reactive oxygen species generation, and neuronal degeneration after CA/CPR. Administration of AP39 1 min after ROSC at 10 nmol kg(-1), but not at 1000 nmol kg(-1), significantly improved the neurological function and 10-day survival rate (69%) after CA/CPR.
Conclusion: The current results suggest that administration of mitochondria-targeted sulfide donor AP39 at the time of CPR or after ROSC improves the neurological function and long term survival rates after CA/CPR by maintaining mitochondrial integrity and reducing oxidative stress. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Ikeda, Kohei; Marutani, Eizo; Hirai, Shuichi; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Ikeda, Kohei; Marutani, Eizo; Hirai, Shuichi; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA.
[Wood, Mark E.] Univ Exeter, Dept Biosci, Coll Life & Environm Sci, Exeter EX4 4QJ, Devon, England.
[Whiteman, Matthew] Univ Exeter, Sch Med, Exeter, Devon, England.
RP Whiteman, M (reprint author), Univ Exeter, Sch Med, St Lukes Campus,Magdalen Rd, Exeter EX1 2LU, Devon, England.
EM m.whiteman@exeter.ac.uk; fichinose@mgh.harvard.edu
RI Whiteman, Matthew/C-6079-2009;
OI Whiteman, Matthew/0000-0002-6583-6779; IKEDA, KOHEI/0000-0002-0961-1532;
Wood, Mark/0000-0002-2674-6981
FU National Institutes of Health [HL101930]
FX This work was supported by a grant from National Institutes of Health
(HL101930 to FI).
NR 34
TC 6
Z9 6
U1 2
U2 21
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 SEP 15
PY 2015
VL 49
BP 90
EP 96
DI 10.1016/j.niox.2015.05.001
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CP9AY
UT WOS:000360187300010
PM 25960429
ER
PT J
AU Shelton, MA
Newman, JT
Gu, H
Sampson, AR
Fish, KN
MacDonald, ML
Moyer, CE
DiBitetto, JV
Dorph-Petersen, KA
Penzes, P
Lewis, DA
Sweet, RA
AF Shelton, Micah A.
Newman, Jason T.
Gu, Hong
Sampson, Allan R.
Fish, Kenneth N.
MacDonald, Matthew L.
Moyer, Caitlin E.
DiBitetto, James V.
Dorph-Petersen, Karl-Anton
Penzes, Peter
Lewis, David A.
Sweet, Robert A.
TI Loss of Microtubule-Associated Protein 2 Immunoreactivity Linked to
Dendritic Spine Loss in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Schizophrenia; Microtubule-Associated Protein 2; Dendritic spines;
Auditory cortex; Postmortem human tissue; Confocal microscopy
ID PRIMARY AUDITORY-CORTEX; MISMATCH NEGATIVITY GENERATION; SUPERIOR
TEMPORAL GYRUS; PREFRONTAL CORTEX; PYRAMIDAL NEURONS;
HIPPOCAMPAL-FORMATION; PLANUM TEMPORALE; MOOD DISORDERS; HESCHL GYRUS;
MAP2
AB BACKGROUND: Microtubule-associated protein 2 (MAP2) is a neuronal protein that plays a role in maintaining dendritic structure through its interaction with microtubules. In schizophrenia (Sz), numerous studies have revealed that the typically robust immunoreactivity (IR) of MAP2 is significantly reduced across several cortical regions. The relationship between MAP2-IR reduction and lower dendritic spine density, which is frequently reported in Sz, has not been explored in previous studies, and MAP2-IR loss has not been investigated in the primary auditory cortex (Brodmann area 41), a site of conserved pathology in Sz.
METHODS: Using quantitative spinning disk confocal microscopy in two cohorts of subjects with Sz and matched control subjects (Sz subjects, n = 20; control subjects, n = 20), we measured MAP2-IR and dendritic spine density and spine number in deep layer 3 of BA41.
RESULTS: Subjects with Sz exhibited a significant reduction in MAP2-IR. The reductions in MAP2-IR were not associated with neuron loss, loss of MAP2 protein, clinical confounders, or technical factors. Dendritic spine density and number also were reduced in Sz and correlated with MAP2-IR. In 12 (60%) subjects with Sz, MAP2-IR values were lower than the lowest values in control subjects; only in this group were spine density and number significantly reduced.
CONCLUSIONS: These findings demonstrate that MAP2-IR loss is closely linked to dendritic spine pathology in Sz. Because MAP2 shares substantial sequence, regulatory, and functional homology with MAP tau, the wealth of knowledge regarding tau biology and the rapidly expanding field of tau therapeutics provide resources for identifying how MAP2 is altered in Sz and possible leads to novel therapeutics. Keywords: Schizophrenia, Microtubule-Associated Protein 2, Dendritic spines, Auditory cortex, Postmortem human tissue, Confocal microscopy
C1 [Shelton, Micah A.; Newman, Jason T.; Fish, Kenneth N.; MacDonald, Matthew L.; Moyer, Caitlin E.; DiBitetto, James V.; Dorph-Petersen, Karl-Anton; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Translat Neurosci Program, Pittsburgh, PA USA.
[Shelton, Micah A.; Newman, Jason T.; Fish, Kenneth N.; MacDonald, Matthew L.; Moyer, Caitlin E.; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Gu, Hong; Sampson, Allan R.] Univ Pittsburgh, Sch Med, Dept Stat, Pittsburgh, PA USA.
[Dorph-Petersen, Karl-Anton] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, Aarhus, Denmark.
[Dorph-Petersen, Karl-Anton] Aarhus Univ, Ctr Stochast Geometry & Adv Bioimaging, Aarhus, Denmark.
[Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA.
[Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA.
[Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Sweet, RA (reprint author), Biomed Sci Tower,Room W-1645,3811 OHara St, Pittsburgh, PA 15213 USA.
EM sweetra@upmc.edu
RI Dorph-Petersen, Karl-Anton/A-9039-2015; Penzes, Peter/L-3987-2016
OI Dorph-Petersen, Karl-Anton/0000-0002-6676-034X; Penzes,
Peter/0000-0001-5449-1640
FU National Institutes of Health [DC011499-03, MH16804, MH096985, MH071316,
MH097216, MH071533]; University of Pittsburgh Cancer Institute Cancer
Biomarker Facility [P30CA047904]; Biomedical Mass Spectrometry Center;
Bristol-Myers Squibb; Pfizer
FX This work was supported by National Institutes of Health Grant Nos.
DC011499-03 (MAS), MH16804 (MLM), MH096985 (KNF), MH071316 and MH097216
(PP), and MH071533 (RAS). The Biomedical Mass Spectrometry Center and
University of Pittsburgh Cancer Institute Cancer Biomarker Facility are
supported in part by award P30CA047904.; ARS is a statistical consultant
to Janssen Pharmaceutical Research and Development LLC. DAL currently
receives investigator-initiated research support from Bristol-Myers
Squibb and Pfizer and in 2012-2014 served as a consultant in the areas
of target identification and validation and new compound development to
Autifony, Bristol-Myers Squibb, Concert Pharmaceuticals, and Sunovion.
MAS, JTN, HG, KNF, MLM, CEM, JVD, K-AD-P, PP, and RAS report no
biomedical financial interests or potential conflicts of interest.
NR 68
TC 13
Z9 14
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 15
PY 2015
VL 78
IS 6
BP 374
EP 385
DI 10.1016/j.biopsych.2014.12.029
PG 12
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CP5SR
UT WOS:000359945000005
PM 25818630
ER
PT J
AU Zhang, ZD
Kil, KE
Poutiainen, P
Choi, JK
Kang, HJ
Huang, XP
Roth, BL
Brownell, AL
AF Zhang, Zhaoda
Kil, Kun-Eek
Poutiainen, Pekka
Choi, Ji-Kyung
Kang, Hye-Jin
Huang, Xi-Ping
Roth, Bryan L.
Brownell, Anna-Liisa
TI Re-exploring the N-phenylpicolinamide derivatives to develop mGlu(4)
ligands with improved affinity and in vitro microsomal stability
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Metabotropic glutamate receptor subtype 4; (mGlu(4)); Positive
allosteric modulator (PAM); Positron emission tomography (PET);
Affinity; Metabolic stability; Structure-affinity relationship (SAR)
ID METABOTROPIC GLUTAMATE RECEPTORS; POSITIVE ALLOSTERIC MODULATOR;
POSITRON-EMISSION-TOMOGRAPHY; SUBTYPE 4 MGLU(4); PARKINSONS-DISEASE;
GROUP-III; MEDIATED MODULATION; PET RADIOTRACER; RODENT MODELS;
DISCOVERY
AB In recent years, mGlu(4) has received great attention and research effort because of the potential benefits of mGlu(4) activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu(4) have been developed. To better understand the role of mGlu(4) in healthy and disease conditions, we are interested in developing an mGlu(4) selective radioligand for in vivo studies. Thus, we had synthesized and studied [C-11]2 as a PET tracer for mGlu(4), which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu(4) ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu(4). The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu(4) ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Zhang, Zhaoda; Kil, Kun-Eek; Poutiainen, Pekka; Choi, Ji-Kyung; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Kang, Hye-Jin; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149,13th St,Suite 2301, Charlestown, MA 02129 USA.
EM abrownell@partners.org
RI Roth, Bryan/F-3928-2010
FU National Institute of Mental Health's Psychoactive Drug Screening
Program [HHSN-271-2013-00017-C]; Orion Farmos Research Foundation;
Kuopio University Foundation; Sigrid Juselius Foundation, Finland;
[NIBIB-R01EB012864]; [NIMH-R01MH91684]; [1S10RR029495-01];
[1S10RR026666-01]; [1S10RR023452-01]
FX Funding was provided by NIBIB-R01EB012864 and NIMH-R01MH91684 to A.-L.B.
Authors would like to acknowledge Supporting Grants for the
instrumentation 1S10RR029495-01, 1S10RR026666-01, and 1S10RR023452-01.
The mGlu functional data was generously provided by the National
Institute of Mental Health's Psychoactive Drug Screening Program,
Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is Directed
by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel
Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA.
Financial support for PP from The Orion Farmos Research Foundation,
Kuopio University Foundation, and Sigrid Juselius Foundation, Finland is
gratefully acknowledged.
NR 34
TC 1
Z9 1
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD SEP 15
PY 2015
VL 25
IS 18
BP 3956
EP 3960
DI 10.1016/j.bmcl.2015.07.031
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CP2ZX
UT WOS:000359747700039
PM 26231155
ER
PT J
AU Kantor, ED
Lipworth, L
Fowke, JH
Giovannucci, EL
Mucci, LA
Signorello, LB
AF Kantor, Elizabeth D.
Lipworth, Loren
Fowke, Jay H.
Giovannucci, Edward L.
Mucci, Lorelei A.
Signorello, Lisa B.
TI Statin Use and Risk of Prostate Cancer: Results From the Southern
Community Cohort Study
SO PROSTATE
LA English
DT Article
DE African Americans; chemoprevention; epidemiologic studies; prostate
cancer; statins
ID REDUCED RISK; HEALTH DISPARITIES; BARRETTS-ESOPHAGUS; SERUM-CHOLESTEROL;
COLORECTAL-CANCER; FOLLOW-UP; METAANALYSIS; TRIAL; MEN; ASSOCIATION
AB BACKGROUND. Epidemiologic studies suggest that statin use may be inversely associated with risk of prostate cancer, but prior studies have focused predominantly on non-Hispanic white populations.
METHODS. We evaluated the association between statin use and prostate cancer risk in the Southern Community Cohort Study (SCCS). Study participants were 32,091 men aged 40-79 at baseline, 67% of whom were non-Hispanic black. Between study enrollment (2002-2009) and December 31, 2010, 570 prostate cancer cases were diagnosed, including 324 low-grade cancers (Gleason score <7 or Gleason pattern 3+4) and 107 high-grade cancers (Gleason score >7 or Gleason pattern 4+3). Analyses of overall prostate cancer were conducted using Cox regression and analyses of grade-specific cancer were conducted using competing risks models.
RESULTS. Ten percent of non-Hispanic black men and 22% of non-Hispanic white men reported use of statins at study enrollment. As compared to non-use, statin use was associated with a non-significant 14% lower risk of prostate cancer in multivariable models (Hazard Ratio [HR]:0.86; 95% Confidence Interval [CI]: 0.63-1.18). This association was stronger for high-grade cancer (HR: 0.62; 95%CI: 0.30, 1.28) than low-grade cancer (HR:0.98; 95%CI: 0.65-1.48). Results were similar by race/ethnicity (p-interaction: 0.41) and did not vary by history of prostate-specific antigen [PSA] screening (p-interaction: 0.65).
CONCLUSIONS. Results suggest no strong association between statin use and prostate cancer risk overall, and further suggest that if a modest protective effect does exist, it does not vary by race/ethnicity and may be restricted to high-grade tumors, although power to detect differences by subgroup was limited. (c) 2015 Wiley Periodicals, Inc.
C1 [Kantor, Elizabeth D.; Giovannucci, Edward L.; Mucci, Lorelei A.; Signorello, Lisa B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lipworth, Loren; Fowke, Jay H.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Mucci, Lorelei A.; Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
RP Kantor, ED (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM ekantor@hsph.harvard.edu
FU Prostate Cancer Foundation; National Cancer Institute [R01CA092447,
T32CA009001]
FX Grant sponsor: National Cancer Institute; Grant numbers: R01CA092447;
T32CA009001; Grant sponsor: Prostate Cancer Foundation.
NR 46
TC 4
Z9 4
U1 1
U2 10
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 SEP 15
PY 2015
VL 75
IS 13
BP 1384
EP 1393
DI 10.1002/pros.23019
PG 10
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CP2MN
UT WOS:000359711300005
PM 26012482
ER
EF