FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Salari, B Hernandez, N Song, Y Eisner, BH Forcione, DG AF Salari, Behzad Hernandez, Natalia Song, Yan Eisner, Brian H. Forcione, David G. TI Evaluation of Patients With Large Pancreatic Duct Stones Treated by Extracorporeal Shock Wave Lithotripsy and Endoscopic Retrograde Cholangiopancreatography SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 [Salari, Behzad; Forcione, David G.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hernandez, Natalia; Song, Yan; Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, 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 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2015 VL 81 IS 5 SU S MA Mo1387 BP AB402 EP AB402 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V47DC UT WOS:000209931500146 ER PT J AU Salari, B Pitman, MB Chebib, I Albanese, E Forcione, DG AF Salari, Behzad Pitman, Martha B. Chebib, Ivan Albanese, Emily Forcione, David G. TI Review of Diagnostic Yield of FNA and Procore Biopsy in 100 Consecutive Cases of Solid Pancreatic Masses SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 [Salari, Behzad; Forcione, David G.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Pitman, Martha B.; Chebib, Ivan; Albanese, Emily] Massachusetts Gen Hosp, Dept Pathol, 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 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2015 VL 81 IS 5 SU S MA Tu1657 BP AB547 EP AB548 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V47DD UT WOS:000209931600219 ER PT J AU Sharaiha, RZ Tyberg, A Khashab, M Karia, K Siddiqui, UD Waxman, I Joshi, V Benias, PC Darwin, P Dimaio, CJ Mulder, C Friedland, S Forcione, DG Sejpal, DV Gonda, TA Gress, FG Gaidhane, M Koons, A Defilippis, EM Salgado, S Weaver, KR Poneros, JM Sethi, A Ho, S Kumbhari, V Singh, VK Tieu, AH Likhitsup, A Womeldorph, C Casey, B Jonnalagadda, SS Desai, AP Carr-Locke, DL Kahaleh, M Siddiqui, A AF Sharaiha, Reem Z. Tyberg, Amy Khashab, Mouen Karia, Kunal Siddiqui, Uzma D. Waxman, Irving Joshi, Virendra Benias, Petros C. Darwin, Peter Dimaio, Christopher J. Mulder, Christopher Friedland, Shai Forcione, David G. Sejpal, Divyesh V. Gonda, Tamas A. Gress, Frank G. Gaidhane, Monica Koons, Ann Defilippis, Ersilia M. Salgado, Sanjay Weaver, Kristen R. Poneros, John M. Sethi, Amrita Ho, Sammy Kumbhari, Vivek Singh, Vikesh K. Tieu, Alan H. Likhitsup, Alisa Womeldorph, Craig Casey, Brenna Jonnalagadda, Sreeni S. Desai, Amit P. Carr-Locke, David L. Kahaleh, Michel Siddiqui, Ali TI Multicenter Experience With a Lumen Apposing Stent for Walled-Off Pancreatic Necrosis (WOPN): the US Experience SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 46th Annual Digestive Diseases Week (DDW) / Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy (ASGE) CY MAY 16-19, 2015 CL Washington, DC SP Amer Assoc Study Liver Dis, Amer Gastroenterol Assoc, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract C1 [Sharaiha, Reem Z.; Tyberg, Amy; Karia, Kunal; Gaidhane, Monica; Defilippis, Ersilia M.; Salgado, Sanjay; Weaver, Kristen R.; Desai, Amit P.; Kahaleh, Michel] Weill Cornell Med Ctr, Gastroenterol & Hepatol, New York, NY USA. [Khashab, Mouen; Kumbhari, Vivek; Singh, Vikesh K.; Tieu, Alan H.] Johns Hopkins Med Inst, Gastroenterol & Hepatol, Baltimore, MD 21205 USA. [Siddiqui, Uzma D.; Waxman, Irving; Koons, Ann] Univ Chicago, Gastroenterol & Hepatol, Chicago, IL 60637 USA. [Gonda, Tamas A.; Gress, Frank G.; Poneros, John M.; Sethi, Amrita] Columbia Univ, Med Ctr, Gastroenterol & Hepatol, New York, NY USA. [Friedland, Shai] Stanford Hosp & Clin, Gastroenterol & Hepatol, Palo Alto, CA USA. [Joshi, Virendra] Ochsner Hlth Syst, Gastroenterol & Hepatol, New Orleans, LA USA. [Benias, Petros C.; Carr-Locke, David L.] Beth Israel Mt Sinai, Gastroenterol & Hepatol, New York, NY USA. [Darwin, Peter] Univ Maryland, Gastroenterol & Hepatol, Baltimore, MD 21201 USA. [Siddiqui, Ali] Jefferson Univ, Gastroenterol & Hepatol, Philadelphia, PA USA. [Dimaio, Christopher J.] Mt Sinai Med Ctr, Gastroenterol & Hepatol, New York, NY 10029 USA. [Ho, Sammy] Montifiore, Gastroenterol & Hepatol, New York, NY USA. [Forcione, David G.; Casey, Brenna] Harvard Med Sch, Massachusetts Gen Hosp, Gastorenterol & Hepatol, Boston, MA USA. [Mulder, Christopher; Womeldorph, Craig] Brooke Army Med Ctr, Gastroenterol & Hepatol, Ft Sam Houston, TX 78234 USA. [Sejpal, Divyesh V.] Long Isl Jewish North Shore, Gastroenterol & Hepatol, New York, NY USA. [Likhitsup, Alisa; Jonnalagadda, Sreeni S.] Univ Missouri, Gastroenterol & Hepatol, Kansas City, MO 64110 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 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2015 VL 81 IS 5 SU S MA 708 BP AB161 EP AB162 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DS4PS UT WOS:000380763600112 ER PT J AU Simmons, LH Gora, MJ Tiernan, AR Grant, CN Soomro, AR Walker-Corkery, ES Rosenberg, M Joshua, M Tearney, GJ AF Simmons, Leigh H. Gora, Michalina J. Tiernan, Aubrey R. Grant, Catriona N. Soomro, Amna R. Walker-Corkery, Elizabeth S. Rosenberg, Mireille Joshua, Metlay Tearney, Guillermo J. TI Screening for Upper GI Disease in the Primary Care Office With Tethered Capsule OCT Endomicroscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 [Gora, Michalina J.; Tiernan, Aubrey R.; Grant, Catriona N.; Soomro, Amna R.; Rosenberg, Mireille; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gora, Michalina J.; Tiernan, Aubrey R.; Tearney, Guillermo J.] Harvard Med Sch, Boston, MA USA. [Walker-Corkery, Elizabeth S.; Joshua, Metlay] Massachusetts Gen Hosp, Primary Care Dept Med, 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 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2015 VL 81 IS 5 SU S MA Su1717 BP AB389 EP AB390 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V47DC UT WOS:000209931500111 ER PT J AU Tabatabaei, N Kang, D Lu, WN Wu, T Kim, M Carruth, RW Soomro, A Grant, C Tiernan, AR Rosenberg, M Sauk, J Hesterberg, PE Nishioka, NS Yuan, Q Garber, J Katz, AJ Tearney, GJ AF Tabatabaei, Nima Kang, Dongkyun Lu, Weina Wu, Tao Kim, Minkyu Carruth, Robert W. Soomro, Amnar. Grant, CatrionaN. Tiernan, Aubrey R. Rosenberg, Mireille Sauk, Jenny Hesterberg, Paul E. Nishioka, Norman S. Yuan, Qian Garber, John Katz, Aubrey J. Tearney, Guillermo J. TI In Vivo Imaging of Eosinophils With a Tethered Confocal Endomicroscopy Capsule SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 46th Annual Digestive Diseases Week (DDW) / Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy (ASGE) CY MAY 16-19, 2015 CL Washington, DC SP Amer Assoc Study Liver Dis, Amer Gastroenterol Assoc, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract C1 [Tabatabaei, Nima; Kang, Dongkyun; Lu, Weina; Wu, Tao; Kim, Minkyu; Carruth, Robert W.; Soomro, Amnar.; Grant, CatrionaN.; Tiernan, Aubrey R.; Rosenberg, Mireille; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sauk, Jenny; Hesterberg, Paul E.; Nishioka, Norman S.; Yuan, Qian; Garber, John; Katz, Aubrey J.] Massachusetts Gen Hosp, Gastrointestinal Unit, 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 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2015 VL 81 IS 5 SU S MA 628 BP AB158 EP AB159 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DS4PS UT WOS:000380763600106 ER PT J AU Makarov, DV Soulos, PR Gold, HT Yu, JB Sen, S Ross, JS Gross, CP AF Makarov, Danil V. Soulos, Pamela R. Gold, Heather T. Yu, James B. Sen, Sounok Ross, Joseph S. Gross, Cary P. TI Regional-Level Correlations in Inappropriate Imaging Rates for Prostate and Breast Cancers Potential Implications for the Choosing Wisely Campaign SO JAMA ONCOLOGY LA English DT Article ID TOP 5 LIST; MEDICARE POPULATION; CARE; TRENDS; VISUALIZATION; APPROPRIATE; PROGRESS; OVERUSE; COSTS; RISK AB IMPORTANCE The association between regional norms of clinical practice and appropriateness of care is incompletely understood. Understanding regional patterns of care across diseases might optimize implementation of programs like Choosing Wisely, an ongoing campaign to decrease wasteful medical expenditures. OBJECTIVE To determine whether regional rates of inappropriate prostate and breast cancer imaging were associated. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using the the Surveillance, Epidemiology, and End Results-Medicare linked database. We identified patients diagnosed from 2004 to 2007 with low-risk prostate (clinical stage T1c/T2a; Gleason score, <= 6; and prostate-specific antigen level, <10 ng/mL) or breast cancer (in situ, stage I, or stage II disease), based on Choosing Wisely definitions. MAIN OUTCOMES AND MEASURES In a hospital referral region (HRR)-level analysis, our dependent variable was HRR-level imaging rate among patients with low-risk prostate cancer. Our independent variable was HRR-level imaging rate among patients with low-risk breast cancer. In a subsequent patient-level analysis we used multivariable logistic regression to model prostate cancer imaging as a function of regional breast cancer imaging and vice versa. RESULTS We identified 9219 men with prostate cancer and 30 398 women with breast cancer residing in 84 HRRs. We found high rates of inappropriate imaging for both prostate cancer (44.4%) and breast cancer (41.8%). In the first, second, third, and fourth quartiles of breast cancer imaging, inappropriate prostate cancer imaging was 34.2%, 44.6%, 41.1%, and 56.4%, respectively. In the first, second, third, and fourth quartiles of prostate cancer imaging, inappropriate breast cancer imaging was 38.1%, 38.4%, 43.8%, and 45.7%, respectively. At the HRR level, inappropriate prostate cancer imaging rates were associated with inappropriate breast cancer imaging rates (rho=0.35; P<.01). At the patient level, a man with low-risk prostate cancer had odds ratios (95% CIs) of 1.72 (1.12-2.65), 1.19 (0.78-1.81), or 1.76 (1.15-2.70) for undergoing inappropriate prostate imaging if he lived in an HRR in the fourth, third, or second quartiles, respectively, of inappropriate breast cancer imaging, compared with the lowest quartile. CONCLUSIONS AND RELEVANCE At a regional level, there is an association between inappropriate prostate and breast cancer imaging rates. This finding suggests the existence of a regional-level propensity for inappropriate imaging utilization, which may be considered by policymakers seeking to improve quality of care and reduce health care spending in high-utilization areas. C1 [Makarov, Danil V.] US Dept Vet Affairs, Washington, DC USA. [Makarov, Danil V.] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Makarov, Danil V.; Gold, Heather T.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Makarov, Danil V.; Gold, Heather T.] NYU, Inst Canc, New York, NY USA. [Soulos, Pamela R.; Yu, James B.; Sen, Sounok; Gross, Cary P.] Yale Univ, Canc Outcomes Publ Policy & Effectiveness Res COP, New Haven, CT USA. [Soulos, Pamela R.; Gold, Heather T.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Gold, Heather T.] NYU, Sch Med, Dept Med, New York, NY USA. [Yu, James B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale Univ, Dept Hlth Policy & Management, Sch Publ Hlth, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Makarov, DV (reprint author), NYU, Sch Med, 550 First Ave,VZ30 Sixth Floor,Off 613, New York, NY 10016 USA. EM danil.makarov@nyumc.org OI Makarov, Danil/0000-0002-0565-9272 FU Robert Wood Johnson Foundation; Louis Feil Charitable Lead Trust; US Department of Veterans Affairs (VA); Veterans Health Administration; Health Services Research & Development Service (HSRDS); VA HSR&DS Career Development awardee at the Manhattan VA; California Department of Public Health [103885]; National Cancer Institute (NCI) SEER Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries [U55/CCR921930-02]; Centers for Medicare & Medicaid Services; National Institute on Aging [K08 AG032886]; American Federation for Aging Research through the Paul B. Beeson Career Development Award Program FX This research was supported by the Robert Wood Johnson Foundation, The Louis Feil Charitable Lead Trust, and the US Department of Veterans Affairs (VA), Veterans Health Administration, Health Services Research & Development Service (HSR&DS). Dr Makarov is a VA HSR&DS Career Development awardee at the Manhattan VA. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute (NCI) SEER Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries, under agreement U55/CCR921930-02 awarded to the Public Health Institute. Dr Ross receives research support from the Centers for Medicare & Medicaid Services, to develop and maintain performance measures that are used for public reporting, and from the US Food and Drug Administration, to develop methods for postmarket surveillance of medical devices. Dr Ross is also supported by grant K08 AG032886 from the National Institute on Aging and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program. NR 32 TC 10 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 185 EP 194 DI 10.1001/jamaoncol.2015.37 PG 10 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400012 PM 26181021 ER PT J AU Yurgelun, MB Masciari, S Joshi, VA Mercado, RC Lindor, NM Gallinger, S Hopper, JL Jenkins, MA Buchanan, DD Newcomb, PA Potter, JD Haile, RW Kucherlapati, R Syngal, S AF Yurgelun, Matthew B. Masciari, Serena Joshi, Victoria A. Mercado, Rowena C. Lindor, Noralane M. Gallinger, Steven Hopper, John L. Jenkins, Mark A. Buchanan, Daniel D. Newcomb, Polly A. Potter, John D. Haile, Robert W. Kucherlapati, Raju Syngal, Sapna CA Colon Canc Family Registry TI Germline TP53 Mutations in Patients With Early-Onset Colorectal Cancer in the Colon Cancer Family Registry SO JAMA ONCOLOGY LA English DT Article ID LI-FRAUMENI-SYNDROME; BREAST-CANCER; GASTRIC-CANCER; HIGH-FREQUENCY; P53 MUTATIONS; BRCA2; PREVALENCE; GENES; FEATURES; CRITERIA AB IMPORTANCE Li-Fraumeni syndrome, usually characterized by germline TP53 mutations, is associated with markedly elevated lifetime risks of multiple cancers, and has been linked to an increased risk of early-onset colorectal cancer. OBJECTIVE To examine the frequency of germline TP53 alterations in patients with early-onset colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter cross-sectional cohort study of individuals recruited to the Colon Cancer Family Registry (CCFR) from 1998 through 2007 (genetic testing data updated as of January 2015). Both population-based and clinic-based patients in the United States, Canada, Australia, and New Zealand were recruited to the CCFR. Demographic information, clinical history, and family history data were obtained at enrollment. Biospecimens were collected from consenting probands and families, including microsatellite instability and DNA mismatch repair immunohistochemistry results. A total of a 510 individuals diagnosed as having colorectal cancer at age 40 years or younger and lacking a known hereditary cancer syndrome were identified from the CCFR as being potentially eligible. Fifty-three participants were excluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47) or biallelic MUTYH mutations (n = 6). INTERVENTIONS Germline sequencing of the TP53 gene was performed. Identified TP53 alterations were assessed for pathogenicity using literature and international mutation database searches and in silico prediction models. MAIN OUTCOMES AND MEASURES Frequency of nonsynonymous germline TP53 alterations. RESULTS Among 457 eligible participants (314, population-based; 143, clinic-based; median age at diagnosis, 36 years [range, 15-40 years]), 6 (1.3%; 95% CI, 0.5%-2.8%) carried germline missense TP53 alterations, none of whom met clinical criteria for Li-Fraumeni syndrome. Four of the identified TP53 alterations have been previously described in the literature in probands with clinical features of Li-Fraumeni syndrome, and 2 were novel alterations. CONCLUSIONS AND RELEVANCE In a large cohort of patients with early-onset colorectal cancer, germline TP53 mutations were detected at a frequency comparable with the published prevalence of germline APC mutations in colorectal cancer. With the increasing use of multigene next-generation sequencing panels in hereditary cancer risk assessment, clinicians will be faced with the challenge of interpreting the biologic and clinical significance of germline TP53 mutations in families whose phenotypes are atypical for Li-Fraumeni syndrome. C1 [Yurgelun, Matthew B.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yurgelun, Matthew B.; Masciari, Serena; Mercado, Rowena C.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Yurgelun, Matthew B.; Kucherlapati, Raju; Syngal, Sapna] Harvard Med Sch, Boston, MA USA. [Joshi, Victoria A.; Kucherlapati, Raju] Partners Ctr Personalized Genet Med, Cambridge, MA USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Gallinger, Steven] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Hopper, John L.; Jenkins, Mark A.; Buchanan, Daniel D.] Univ Melbourne, Ctr Biostat & Epidemiol, Carlton, Vic, Australia. [Buchanan, Daniel D.] Univ Melbourne, Dept Pathol, Oncogen Grp, Genet Epidemiol Lab, Carlton, Vic, Australia. [Newcomb, Polly A.; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Potter, John D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Haile, Robert W.] Dept Med, Stanford, CA USA. [Haile, Robert W.] Stanford Canc Inst, Stanford, CA USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM ssyngal@partners.org RI Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013 OI Jenkins, Mark/0000-0002-8964-6160; FU National Institutes of Health (NIH) (National Cancer Institute [NCI]) [K24CA113433, UM1CA167551]; American Gastroenterological Association (AGA) Translational Research Award; NCI, NIH, of Health under RFA [CA-95-011] FX This study was funded by the National Institutes of Health (NIH) (National Cancer Institute [NCI]) K24CA113433 (Dr Syngal) and UM1CA167551 (Dr Haile), as well as an American Gastroenterological Association (AGA) Translational Research Award (Drs Syngal and Kucherlapati). The Colon Cancer Family Registry (CCFR) was supported by the NCI, NIH, of Health under RFA No. CA-95-011 and through cooperative agreements with members of the CCFR and Principal Investigators. Collaborating centers include the Australasian Colorectal Cancer Family Registry, Colon Cancer Family Registry: USC Consortium, Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, Ontario Registry for Studies of Familial Colorectal Cancer, and Seattle Colorectal Cancer Family Registry. NR 48 TC 9 Z9 9 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 214 EP 221 DI 10.1001/jamaoncol.2015.0197 PG 8 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400018 PM 26086041 ER PT J AU Freedman, RA Kouri, EM West, DW Keating, NL AF Freedman, Rachel A. Kouri, Elena M. West, Dee W. Keating, Nancy L. TI Racial/Ethnic Differences in Patients' Selection of Surgeons and Hospitals for Breast Cancer Surgery SO JAMA ONCOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PRIMARY-CARE PHYSICIANS; RACIAL DISPARITIES; BLACK PATIENTS; DECISION-MAKING; UNDERGO-SURGERY; MAJOR SURGERY; OLDER WOMEN; QUALITY; MORTALITY AB IMPORTANCE Racial differences in breast cancer treatment may result in part from differences in the surgeons and hospitals from whom patients receive their care. However, little is known about differences in patients' selection of surgeons and hospitals. OBJECTIVE To examine racial/ethnic differences in how women selected their surgeons and hospitals for breast cancer surgery. DESIGN, SETTING, AND PARTICIPANTS We surveyed 500 women (222 non-Hispanic white, 142 non-Hispanic black, 89 English-speaking Hispanic, and 47 Spanish-speaking Hispanic) from northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010 through 2011. We used multivariable logistic regression to assess the reasons for surgeon and hospital selection by race/ethnicity, adjusting for other patient characteristics. We also assessed the association between reasons for physician selection and patients' ratings of their surgeon and hospital. MAIN OUTCOMES AND MEASURES Reasons for surgeon and hospital selection and ratings of surgeon and hospital. RESULTS The 500 participants represented a response rate of 47.8% and a participation rate of 69%. The most frequently reported reason for surgeon selection was referral by another physician (78%); the most frequently reported reason for hospital selection was because it was a part of a patient's health plan (58%). After adjustment, 79% to 87% of black and Spanish-speaking Hispanic women reported selecting their surgeon based on a physician's referral vs 76% of white women (P=.007). Black and Hispanic patients were less likely than white patients to report selecting their surgeon based on reputation (adjusted rates, 18% and 22% of black and Hispanic women, respectively, vs 32% of white women; P=.02). Black and Hispanic women were also less likely than white women to select their hospital based on reputation (adjusted rates, 7% and 15% vs 23%, respectively; P=.003). Women who selected their surgeon based on reputation more often rated the care from their surgeon as excellent (adjusted odds ratio, 2.21; 95% CI, 1.24-3.93); those reporting their surgeon was one of the only surgeons available through the health plan less often reported excellent quality of surgical care (adjusted odds ratio, 0.56; 95% CI, 0.34-0.91). CONCLUSIONS AND RELEVANCE Compared with white patients with breast cancer, minority patients were less actively involved in physician and hospital selection, relying more on physician referral and health plans rather than on reputation. Interventions to promote involvement in surgeon and hospital selection may have potential for addressing disparities related to lower-quality care from surgeons and hospitals. C1 [Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kouri, Elena M.; Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [West, Dee W.] Inst Publ Hlth, Canc Registry Greater Calif, Sacramento, CA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU Komen for the Cure Foundation; National Cancer Institute [K24CA181510]; California Department of Public Health [103885]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01] FX This study was sponsored by the Komen for the Cure Foundation. Dr Keating is also supported by K24CA181510 from the National Cancer Institute. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement U58DP003862-01 awarded to the California Department of Public Health. NR 36 TC 4 Z9 4 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 222 EP 230 DI 10.1001/jamaoncol.2015.20 PG 9 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400019 PM 26181027 ER PT J AU Van Allen, EM Lui, VWY Egloff, AM Goetz, EM Li, H Johnson, JT Duvvuri, U Bauman, JE Stransky, N Zeng, Y Gilbert, BR Pendleton, KP Wang, L Chiosea, S Sougnez, C Wagle, N Zhang, F Du, Y Close, D Johnston, PA McKenna, A Carter, SL Golub, TR Getz, G Mills, GB Garraway, LA Grandis, JR AF Van Allen, Eliezer M. Lui, Vivian W. Y. Egloff, Ann Marie Goetz, Eva M. Li, Hua Johnson, Jonas T. Duvvuri, Umamaheswar Bauman, Julie E. Stransky, Nicolas Zeng, Yan Gilbert, Breean R. Pendleton, Kelsey P. Wang, Lin Chiosea, Simion Sougnez, Carrie Wagle, Nikhil Zhang, Fan Du, Yu Close, David Johnston, Paul A. McKenna, Aaron Carter, Scott L. Golub, Todd R. Getz, Gad Mills, Gordon B. Garraway, Levi A. Grandis, Jennifer R. TI Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma SO JAMA ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; TYROSINE KINASE INHIBITORS; COMMON DOCKING DOMAIN; LUNG-CANCER; PREDICTS SENSITIVITY; METASTATIC HEAD; EGFR; MUTATIONS; GEFITINIB AB IMPORTANCE Randomized clinical trials demonstrate no benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in unselected patients with head and neck squamous cell carcinoma (HNSCC). However, a patient with stage IVA HNSCC received 13 days of neoadjuvant erlotinib and experienced a near-complete histologic response. OBJECTIVE To determine a mechanism of exceptional response to erlotinib therapy in HNSCC. DESIGN, SETTING, AND PARTICIPANTS Single patient with locally advanced HNSCC who received erlotinib monotherapy in a window-of-opportunity clinical trial (patients scheduled to undergo primary cancer surgery are treated briefly with an investigational agent). Whole-exome sequencing of pretreatment tumor and germline patient samples was performed at a quaternary care academic medical center, and a candidate somatic variant was experimentally investigated for mediating erlotinib response. INTERVENTION A brief course of erlotinib monotherapy followed by surgical resection. MAIN OUTCOMES AND MEASURES Identification of pretreatment tumor somatic alterations that may contribute to the exceptional response to erlotinib. Hypotheses were formulated regarding enhanced erlotinib response in preclinical models harboring the patient tumor somatic variant MAPK1 E322K following the identification of tumor somatic variants. RESULTS No EGFR alterations were observed in the pretreatment tumor DNA. Paradoxically, the tumor harbored an activating MAPK1 E322K mutation (allelic fraction 0.13), which predicts ERK activation and erlotinib resistance in EGFR-mutant lung cancer. The HNSCC cells with MAPK1 E322K exhibited enhanced EGFR phosphorylation and erlotinib sensitivity compared with wild-type MAPK1 cells. CONCLUSIONS AND RELEVANCE Selective erlotinib use in HNSCC may be informed by precision oncology approaches. C1 [Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, 200 Lothrop St,Ste 500, Pittsburgh, PA 15213 USA. [Van Allen, Eliezer M.; Goetz, Eva M.; Wagle, Nikhil; Golub, Todd R.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Van Allen, Eliezer M.; Sougnez, Carrie; Wagle, Nikhil; Carter, Scott L.; Golub, Todd R.; Getz, Gad; Garraway, Levi A.] MIT, Canc Program, Broad Inst, Cambridge, MA 02139 USA. [Van Allen, Eliezer M.; Sougnez, Carrie; Wagle, Nikhil; Carter, Scott L.; Golub, Todd R.; Getz, Gad; Garraway, Levi A.] Harvard Univ, Cambridge, MA 02138 USA. [Lui, Vivian W. Y.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China. [Lui, Vivian W. Y.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [Lui, Vivian W. Y.; Egloff, Ann Marie; Li, Hua; Johnson, Jonas T.; Duvvuri, Umamaheswar; Zeng, Yan; Gilbert, Breean R.; Pendleton, Kelsey P.; Wang, Lin; Du, Yu; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. [Egloff, Ann Marie] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Bauman, Julie E.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Stransky, Nicolas] Blueprint Med, Cambridge, MA USA. [Chiosea, Simion] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Zhang, Fan; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Close, David; Johnston, Paul A.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [McKenna, Aaron] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, Inst Eye & Ear, Dept Otolaryngol, 200 Lothrop St,Ste 500, Pittsburgh, PA 15213 USA.; Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, 200 Lothrop St,Ste 500, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu FU American Cancer Society; Patricia L. Knebel Fund of the Pittsburgh Foundation; National Cancer Institute [K07 CA137140]; Sheikh Khalifa bin Zayed Al Nahyan Institute for Personalized Cancer Therapy; Slim Initiative for Genomic Medicine; US-Mexico project - Carlos Slim Health Institute; National Cancer Institute Head and Neck Cancer Specialized Program of Research Excellence [P50 CA097190]; OSI Pharmaceuticals; Bristol-Myers Squibb; US Department of Veterans Affairs Career Development Award, Biomedical Laboratory Research and Development FX The study was supported by the American Cancer Society (Drs Van Allen and Grandis), the Patricia L. Knebel Fund of the Pittsburgh Foundation (Dr Lui), the National Cancer Institute K07 CA137140 (Dr Egloff), the Sheikh Khalifa bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (Drs Zhang and Mills), the Slim Initiative for Genomic Medicine, a joint US-Mexico project funded by the Carlos Slim Health Institute (Drs Golub and Garraway), the National Cancer Institute Head and Neck Cancer Specialized Program of Research Excellence P50 CA097190 (Dr Grandis), OSI Pharmaceuticals (Dr Grandis), and Bristol-Myers Squibb (Dr Grandis). This work was supported in part by the US Department of Veterans Affairs Career Development Award, Biomedical Laboratory Research and Development (Dr Duvvuri). NR 34 TC 10 Z9 10 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 238 EP 244 DI 10.1001/jamaoncol.2015.34 PG 7 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400021 PM 26181029 ER PT J AU Shalowitz, DI Schorge, JO AF Shalowitz, David I. Schorge, John O. TI Suggestibility of Oncologists' Clinical Estimates SO JAMA ONCOLOGY LA English DT Letter C1 [Shalowitz, David I.] Univ Penn, Div Gynecol Oncol, Dept Obstet & Gynecol, Med Ctr, Philadelphia, PA 19104 USA. [Schorge, John O.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP Shalowitz, DI (reprint author), Perelman Ctr Adv Med, 3400 Civ Ctr Blvd,Third Floor W, Philadelphia, PA 19104 USA. EM david.shalowitz@uphs.upenn.edu OI Shalowitz, David/0000-0002-5189-4687 NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 251 EP 253 DI 10.1001/jamaoncol.2015.62 PG 5 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400025 PM 26181033 ER PT J AU Bryce, S Asquith, D Bromley, S Luster, A Graham, G Nibbs, R AF Bryce, Steven Asquith, Darren Bromley, Shannon Luster, Andrew Graham, Gerard Nibbs, Robert TI The atypical chemokine receptor ACKR4 facilitates dendritic cell migration during inflammation by scavenging CCL19 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Bromley, Shannon; Luster, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bryce, Steven; Asquith, Darren; Graham, Gerard; Nibbs, Robert] Univ Glasgow, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR3P.205 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502299 ER PT J AU Chang, DK Sun, JS Zhu, Q Drapkin, R Matulonis, U Marasco, W AF Chang, DeKuan Sun, Jiusong Zhu, Quan Drapkin, Ronny Matulonis, Ursula Marasco, Wayne TI Anti-CCR4 antibody enhances anti-tumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft animal model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Chang, DeKuan; Sun, Jiusong; Zhu, Quan; Drapkin, Ronny; Matulonis, Ursula; Marasco, Wayne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chang, DeKuan; Zhu, Quan; Marasco, Wayne] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC12P1121 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501025 ER PT J AU Cherayil, B Shanmugam, N AF Cherayil, Bobby Shanmugam, Nanda TI IL-1 beta secreted by macrophages in response to commensal bacteria acts together with bone morphogenetic protein signals to increase hepcidin expression in hepatocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Cherayil, Bobby; Shanmugam, Nanda] Massachusetts Gen Hosp, Pediat, Boston, MA 02114 USA. [Cherayil, Bobby] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC5P.758 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501222 ER PT J AU Fu, Y Zhang, Z Sun, JS Zhu, Q AF Fu, Ying Zhang, Zhen Sun, Jiusong Zhu, Quan TI Isolation of broadly neutralizing antibodies from single human memory B cell against human influenza A viruses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Fu, Ying; Zhang, Zhen; Sun, Jiusong; Zhu, Quan] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TECH2P.922 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504196 ER PT J AU Hamilton, J Li, J Wu, Q Yang, PA Luo, B Li, H Bradley, J Taylor, J Randall, T Mountz, J Hsu, HC AF Hamilton, Jennie Li, Jun Wu, Qi Yang, PingAr Luo, Bao Li, Hao Bradley, John Taylor, Justin Randall, Troy Mountz, John Hsu, Hui-Chen TI Increased PKC signaling in lupus La reactive B cells promotes development of the transitional T3 population and memory B cells in autoimmune BXD2 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Hamilton, Jennie; Li, Jun; Wu, Qi; Yang, PingAr; Luo, Bao; Li, Hao; Bradley, John; Randall, Troy; Mountz, John; Hsu, Hui-Chen] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Taylor, Justin] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Mountz, John] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA3P.108 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500233 ER PT J AU Kang, YJ AF Kang, Yoon Joong TI Generation of knock-in mouse model expressing functional CD8ab without an active CD8aa SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kang, Yoon Joong] Jungwon Univ, Chungcheongbuk Do, South Korea. [Kang, Yoon Joong] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC5P.634 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502060 ER PT J AU Kannan, L Tsokos, M Lucca, JD Tsokos, G AF Kannan, Lakshmi Tsokos, Maria Lucca, Jurandir Daile Tsokos, George TI Intracellular activation of complement 3 mediates intestinal tissue damage during mesenteric ischemia SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kannan, Lakshmi; Tsokos, Maria; Tsokos, George] Harvard Med Sch, BIDMC, Boston, MA USA. [Lucca, Jurandir Daile] US Army Inst Surg Res, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC1P.356 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503143 ER PT J AU Kaplan, D Chang, LY Tanoue, S Li, YH AF Kaplan, David Chang, Li-Yuan Tanoue, Shiroh Li, Yonghai TI Increased sensitivity of peripheral CD27(+) memory B cells to Fas-induced apoptosis contributes to their disappearance in cirrhosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kaplan, David] Philadelphia Vet Affairs Med Ctr, Med, Philadelphia, PA USA. [Kaplan, David; Chang, Li-Yuan; Tanoue, Shiroh; Li, Yonghai] Univ Penn, Gastroenterol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.309 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500309 ER PT J AU Kim, M Miller, C Shadrach, J Wagers, A Serwold, T AF Kim, Mijeong Miller, Christine Shadrach, Jennifer Wagers, Amy Serwold, Thomas TI Intrathymic transplantation of young, engraftable thymic epithelial cells promotes the growth and regeneration of the aging thymus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kim, Mijeong; Miller, Christine; Shadrach, Jennifer; Wagers, Amy; Serwold, Thomas] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kim, Mijeong; Miller, Christine; Shadrach, Jennifer; Wagers, Amy; Serwold, Thomas] Harvard Med Sch, Boston, MA USA. [Wagers, Amy] Howard Hughes Med Inst, Cambridge, MA USA. [Wagers, Amy] Harvard Stem Cell Inst, Cambridge, MA USA. [Wagers, Amy] Paul F Glenn Labs Biol Mech Aging, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TRAN1P.932 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504251 ER PT J AU Kim, Y Zhang, AH Wucherpfennig, K Scott, D AF Kim, Yong Zhang, Ai-Hong Wucherpfennig, Kai Scott, David TI Engineered MBP antigen-specific human regulatory T cells: direct and bystander immunosuppressive function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kim, Yong; Zhang, Ai-Hong; Scott, David] Uniformed Serv Univ Hlth Sci, Med, Bethesda, MD 20814 USA. [Wucherpfennig, Kai] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA THER7P.954 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501109 ER PT J AU Klein, S Gokhale, P Jones, K Saur, A Rodig, S Liao, XY Kohl, N Reardon, D Freeman, G AF Klein, Sarah Gokhale, Praful Jones, Kristen Saur, Amy Rodig, Scott Liao, Xiaoyun Kohl, Nancy Reardon, David Freeman, Gordon TI Immune checkpoint blockade activates effective anti-tumor immunity in an orthotopic model of glioblastoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Klein, Sarah; Gokhale, Praful; Jones, Kristen; Saur, Amy; Reardon, David; Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. [Klein, Sarah] Harvard Med Sch, Med Brigham & Womens, Boston, MA USA. [Rodig, Scott; Liao, Xiaoyun] Brigham & Womens Hosp, Pathol, Boston, MA 02115 USA. [Kohl, Nancy] Blueprint Med, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC12P1119 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501024 ER PT J AU LeGuern, C Germana, S AF LeGuern, Christian Germana, Sharon TI Insights into MHC class II regulation of T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [LeGuern, Christian; Germana, Sharon] Harvard Med Sch, Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRM15P.463 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502274 ER PT J AU Meissner, T Strominger, J Cowan, C AF Meissner, Torsten Strominger, Jack Cowan, Chad TI The universal donor stem cell: removing the immune barrier to transplantation using CRISPR/Cas9 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Meissner, Torsten; Strominger, Jack; Cowan, Chad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Cowan, Chad] Harvard Stem Cell Inst, Cambridge, MA USA. [Cowan, Chad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TRAN1P.946 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504249 ER PT J AU Morales, EC Song, Y Marin, R Khor, B Nguyen, D AF Morales, Elisa Cruz Song, Yan Marin, Romela Khor, Bernard Nguyen, Deanna TI Rac GTPases have opposite roles in T cells and dendritic cells in mucosal immune function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Morales, Elisa Cruz; Song, Yan; Marin, Romela; Khor, Bernard; Nguyen, Deanna] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. [Morales, Elisa Cruz; Song, Yan; Marin, Romela; Khor, Bernard; Nguyen, Deanna] Harvard Med Sch, Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC8P.730 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501180 ER PT J AU Mountz, J Li, H Hsu, HC Zhou, Y Wu, Q Yang, PA Li, J Luo, B Morel, L Ware, C Fu, Y Yagita, H AF Mountz, John Li, Hao Hsu, Hui-Chen Zhou, Yong Wu, Qi Yang, PingAr Li, Jun Luo, Bao Morel, Laurence Ware, Carl Fu, Yang Yagita, Hideo TI Type I interferons promote lupus through disruption of the lymphotoxin receptor mediated mechanosensing MKL1 pathway in marginal zone macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Mountz, John; Li, Hao; Hsu, Hui-Chen; Zhou, Yong; Wu, Qi; Yang, PingAr; Li, Jun; Luo, Bao] Univ Alabama Birmingham, Birmingham, AL USA. [Morel, Laurence] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Fu, Yang] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Ware, Carl] Sanford Burnham Med Res Inst La Jolla, Infect & Inflammatory Dis Ctr, La Jolla, CA USA. [Mountz, John] Birmingham VAMC, Birmingham, AL USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA4P.124 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503081 ER PT J AU Narang, A Qiao, F Atkinson, C Kulik, L Holers, V Yang, XF Tomlinson, S AF Narang, Aarti Qiao, Fei Atkinson, Carl Kulik, Liudmila Holers, V. Yang, Xiaofeng Tomlinson, Stephen TI Targeted complement inhibition improves recovery in murine spinal cord injury model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Narang, Aarti; Qiao, Fei; Atkinson, Carl; Yang, Xiaofeng; Tomlinson, Stephen] Med Univ S Carolina, Microbiol & Immunol, Charleston, SC 29425 USA. [Kulik, Liudmila; Holers, V.] Univ Colorado, SOM MED, Denver, CO 80202 USA. [Tomlinson, Stephen] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA THER2P.956 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500016 ER PT J AU Penaloza-MacMaster, P Barber, D Wherry, E Provine, N Teigler, JE Parenteau, L Blackmore, S Borducchi, E Larocca, R Yates, K Shen, H Haining, W Sommerstein, R Pinschewer, D Ahmed, R Barouch, D AF Penaloza-MacMaster, Pablo Barber, Daniel Wherry, E. Provine, Nicholas Teigler, Jeffrey E. Parenteau, Lily Blackmore, Stephen Borducchi, Erica Larocca, Rafael Yates, Kathleen Shen, Hao Haining, W. Sommerstein, Rami Pinschewer, Daniel Ahmed, Rafi Barouch, Dan TI LCMV-specific CD4 T cells induce immunopathology and impair immune protection following chronic LCMV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Penaloza-MacMaster, Pablo; Provine, Nicholas; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica; Larocca, Rafael; Barouch, Dan] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA. [Barber, Daniel] NIAID, Parasit Dis Lab, Bethesda, MD USA. [Wherry, E.; Shen, Hao] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wherry, E.; Shen, Hao] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yates, Kathleen; Haining, W.] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Sommerstein, Rami; Pinschewer, Daniel] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. [Sommerstein, Rami; Pinschewer, Daniel] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Geneva, Switzerland. [Pinschewer, Daniel] Univ Basel, Dept Biomed Haus Peterspl, Div Expt Virol, Basel, Switzerland. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Barouch, Dan] Ragon Inst MGH MIT & Harvard, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR1P.1132 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500022 ER PT J AU Richard, ML Brandon, D Sato, S Zhang, X AF Richard, Mara Lennard Brandon, Danielle Sato, Shuzo Zhang, Xian TI Regulation of granulocyte colony stimulating factor by Fli-1, a novel transcriptional activator of inflammatory mediators SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Richard, Mara Lennard; Brandon, Danielle; Sato, Shuzo; Zhang, Xian] Med Univ South Carolina, Charleston, SC USA. [Zhang, Xian] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR3P.213 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502297 ER PT J AU Serwold, T Vroegindeweij, E Kim, M Vazguez, S AF Serwold, Thomas Vroegindeweij, Eric Kim, MiJeong Vazguez, Sara TI Homeostatic proliferation of thymocytes is controlled through dynamic regulation of delta like 4 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Serwold, Thomas; Vroegindeweij, Eric; Kim, MiJeong; Vazguez, Sara] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM7P.229 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504201 ER PT J AU Singarapu, N Xie, HF Orkin, S Richie, E AF Singarapu, Nandini Xie, Huafeng Orkin, Stuart Richie, Ellen TI Targeted deletion of Eed arrests thymus development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Xie, Huafeng; Orkin, Stuart] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart] Harvard Med Sch, Boston Childrens Hosp, Harvard Stem Cell Inst, Div Hematol Oncol, Boston, MA USA. [Singarapu, Nandini; Richie, Ellen] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Div Sci Pk Res, Smithville, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM7P.225 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504210 ER PT J AU Singh, R Hui, T Matsui, A Rittling, S AF Singh, Rani Hui, Tommy Matsui, Aritsune Rittling, Susan TI Osteopontin regulates Cxcr2 expression and neutrophil recruitment in endodontic infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Singh, Rani; Hui, Tommy; Matsui, Aritsune; Rittling, Susan] Forsyth Inst, Immunol & Infect Dis, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC6P.302 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501315 ER PT J AU Sukumaran, B Bist, P Ng, A Kim, BH Pulloor, NK Khameneh, H Hedi, M Dikshit, N Shenoy, A Balamuralidhar, V Hong, M Neutzner, A Chin, KC Kobayashi, K Bertoletti, A Mortellaro, A Abraham, C MacMicking, J Xavier, R AF Sukumaran, Bindu Bist, Pradeep Ng, Aywin Kim, Bae Hoon Pulloor, Niyas Kudukkil Khameneh, Hanif Hedi, Matija Dikshit, Neha Shenoy, Avinash Balamuralidhar, Vanniarajan Hong, Michelle Neutzner, Albert Chin, Keh-Chuang Kobayashi, Koichi Bertoletti, Antonio Mortellaro, Alessandra Abraham, Clara MacMicking, John Xavier, Ramnik TI Ubiquitination-mediated regulation of RIP2 in NOD2 signaling and MDP tolerance induction SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Sukumaran, Bindu; Bist, Pradeep; Pulloor, Niyas Kudukkil; Dikshit, Neha; Balamuralidhar, Vanniarajan; Hong, Michelle; Bertoletti, Antonio] DUKE NUS Grad Med Sch, Singapore, Singapore. [Ng, Aywin; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aywin; Xavier, Ramnik] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aywin; Xavier, Ramnik] Harvard Med Sch, Boston, MA 02114 USA. [Ng, Aywin; Xavier, Ramnik] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Kim, Bae Hoon; Shenoy, Avinash; MacMicking, John] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT 06520 USA. [Khameneh, Hanif; Chin, Keh-Chuang; Mortellaro, Alessandra] ASTAR, Singapore Immunol Network SIgN, Singapore 138648, Singapore. [Hedi, Matija; Abraham, Clara] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Neutzner, Albert] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Kobayashi, Koichi] Texas A&M Hlth Sci Ctr, Dept Microbial Pathogenesis & Immunol, College Stn, TX 77843 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INM2P.354 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501060 ER PT J AU Urso, K Alvarez, D Cremasco, V Tsang, K Lafyatis, R von Andrian, U Aliprantis, A AF Urso, Katia Alvarez, David Cremasco, Viviana Tsang, Kelly Lafyatis, Robert von Andrian, Ulrich Aliprantis, Antonios TI IL4RA regulates lymphocytes trafficking in sclerodermatous graft-versus-host disease. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Urso, Katia; Alvarez, David; Tsang, Kelly; von Andrian, Ulrich; Aliprantis, Antonios] Harvard Med Sch, Boston, MA USA. [Urso, Katia; Tsang, Kelly; Aliprantis, Antonios] Brigham & Womens Hosp, Med, Boston, MA 02115 USA. [Cremasco, Viviana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lafyatis, Robert] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CAM4P.154 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502210 ER PT J AU Young, J Chen, JJ Miller, M Yin, DP Vu, V Moon, J Alegre, ML Chong, A AF Young, James Chen, Jianjun Miller, Michelle Yin, Dengping Vu, Vinh Moon, James Alegre, Maria-Luisa Chong, Anita TI Endogenous graft-specific Tregs expand and differentiate into effector Tregs during the induction of tolerance to allografts SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Young, James; Chen, Jianjun; Miller, Michelle; Yin, Dengping; Vu, Vinh; Alegre, Maria-Luisa; Chong, Anita] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Young, James; Chen, Jianjun; Miller, Michelle; Yin, Dengping; Vu, Vinh; Alegre, Maria-Luisa; Chong, Anita] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Moon, James] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TRAN1P.949 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504253 ER PT J AU Zhou, J Jin, JO Du, J Yu, Q AF Zhou, Jing Jin, Jun-O Du, Juan Yu, Qing TI Blockade of PD-L1 accelerates the development of Sjogren's syndrome in non-obese diabetic mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Zhou, Jing; Jin, Jun-O; Du, Juan; Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Zhou, Jing; Yu, Qing] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM3P.256 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500158 ER PT J AU Haynes, AB Berry, WR Gawande, AA AF Haynes, Alex B. Berry, William R. Gawande, Atul A. TI What Do We Know About the Safe Surgery Checklist Now? SO ANNALS OF SURGERY LA English DT Editorial Material ID MORTALITY; IMPLEMENTATION C1 [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Haynes, Alex B.; Berry, William R.] Ariadne Labs, Boston, MA USA. [Haynes, Alex B.; Berry, William R.] Brigham & Womens Hosp, Boston, MA USA. [Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Haynes, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM abhaynes@partners.org NR 9 TC 9 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2015 VL 261 IS 5 BP 829 EP 830 DI 10.1097/SLA.0000000000001144 PG 2 WC Surgery SC Surgery GA CF1RZ UT WOS:000352326900025 PM 25647061 ER PT J AU Stock, CT Sundt, T AF Stock, Cameron T. Sundt, Thoralf TI Timeout for Checklists? SO ANNALS OF SURGERY LA English DT Editorial Material ID SAFETY CHECKLISTS C1 [Stock, Cameron T.] Massachusetts Gen Hosp, Div Surg Thorac, Boston, MA 02114 USA. [Sundt, Thoralf] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Stock, CT (reprint author), Massachusetts Gen Hosp, Div Surg Thorac, 55 Fruit St,Blake Bldg 1570, Boston, MA 02114 USA. EM cstock@partners.org NR 8 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2015 VL 261 IS 5 BP 841 EP 842 DI 10.1097/SLA.0000000000001141 PG 2 WC Surgery SC Surgery GA CF1RZ UT WOS:000352326900028 PM 25607765 ER PT J AU Marchegiani, G Mino-Kenudson, M Sahora, K Morales-Oyarvide, V Thayer, S Ferrone, C Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Marchegiani, Giovanni Mino-Kenudson, Mari Sahora, Klaus Morales-Oyarvide, Vicente Thayer, Sarah Ferrone, Cristina Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI IPMN Involving the Main Pancreatic Duct Biology, Epidemiology, and Long-term Outcomes Following Resection SO ANNALS OF SURGERY LA English DT Article DE cystic neoplasm; IPMN; intraductal papillary mucinous neoplasm; MD-IPMN; pancreas ID PAPILLARY-MUCINOUS NEOPLASMS; INTERNATIONAL-CONSENSUS-GUIDELINES; INVASIVE-CARCINOMA; CYSTIC NEOPLASMS; REMNANT PANCREAS; MANAGEMENT; SUBTYPES; ADENOCARCINOMA; CONCOMITANT; PREDICTORS AB Objectives: To describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) with predominant involvement of the main pancreatic duct (MPD), analyzing predictors for survival and recurrence. Background: IPMNs involving the MPD harbor a high likelihood of malignancy and different biological features. The appropriateness of including cases with minimal noncircumferential MPD involvement has been challenged because these show clinicopathological features that are similar to branch duct IPMN. Accordingly, their exclusion has led to a redefinition of MPD IPMN (MD-IPMN). Methods: Retrospective review of resected MD-IPMN from 1990 to 2013. All slides were reviewed by a single pancreatic pathologist and classified on the basis of epithelial type and invasive component. Results: A total of 223 patients underwent resection for IPMN involving the MPD. Of these, 50 were excluded because of minimal MPD involvement. Among the 173 patients analyzed, median age was 68 years and 55% were males. Predominant epithelial phenotype was intestinal (50%). Forty-eight patients (28%) had low-or intermediate-grade dysplasia, whereas 125 (72%) had either high-grade dysplasia (33%) or invasive carcinoma (39%). Of the 67 invasive IPMNs, 39 were tubular carcinomas (58%) and invasion was minimal (< 5 mm) in 28 (42%). The 5-year overall survival rate was 69% and the disease-specific survival rate was 83%. The estimated recurrence rate at 10 years was 25%. Size and type of the invasive component, lymph node positivity, and a positive resection margin were predictors for both survival and recurrence (P < 0.05). Conclusions: MD-IPMN is mainly intestinal-type and malignant. After resection, it has a very favorable prognosis, especially in the absence of macroscopic invasive carcinoma. C1 [Marchegiani, Giovanni; Sahora, Klaus; Thayer, Sarah; Ferrone, Cristina; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Morales-Oyarvide, Vicente] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernan-dez@partners.org FU National Institutes of Health/National Cancer Institute [R01CA169086, P01CA117969] FX Supported by National Institutes of Health/National Cancer Institute grants R01CA169086 and P01CA117969 (to S.T.). The other authors declare no conflict of interest. NR 45 TC 18 Z9 19 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2015 VL 261 IS 5 BP 976 EP 983 DI 10.1097/SLA.0000000000000813 PG 8 WC Surgery SC Surgery GA CF1RZ UT WOS:000352326900049 PM 24979607 ER PT J AU Zhao, GF Yu, YM Kaneki, M Bonab, AA Tompkins, RG Fischman, AJ AF Zhao, Gaofeng Yu, Yong-Ming Kaneki, Masao Bonab, Ali A. Tompkins, Ronald G. Fischman, Alan J. TI Simvastatin Reduces Burn Injury-induced Splenic Apoptosis via Downregulation of the TNF-alpha/NF-kappa B Pathway SO ANNALS OF SURGERY LA English DT Article DE apoptosis; burn; NF-kappa B; simvastatin; TNF-alpha ID SIGNALING PATHWAYS; THERMAL-INJURY; CELLS; ACTIVATION; INFLAMMATION; NECROSIS; MICE; RECRUITMENT; INHIBITION; SPLEEN AB Objective: Recent studies have suggested that epidermal burn injuries are associated with inflammation and immune dysfunction. Simvastatin has been shown to possess potent anti-inflammatory properties. Thus, we hypothesized that simvastatin protects against burn-induced apoptosis in the spleen via its anti-inflammatory activity. Methods: Wild-type, tumor necrosis factor alpha knockout (TNF-alpha KO) and NF-kappa B KO mice were subjected to full-thickness burn injury or sham treatment. The mice then were treated with or without simvastatin, and the spleen was harvested to measure the extent of apoptosis. Expression levels of TNF-alpha and NF-kappa B were also determined in spleen tissue and serum. Results: Burn injury induced significant splenic apoptosis and systemic cytokine production. Simvastatin protected the spleen from apoptosis, reduced cytokine production in the serum, and increased the survival rate. Simvastatin decreased burn-induced TNF-alpha and NF-kappa B expression in the spleen and serum. TNF-alpha and NF-kappa B KO mice demonstrated lower levels of apoptosis in spleen in response to burn injury. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice. Conclusions: Simvastatin reduces burn-induced splenic apoptosis via down-regulation of the TNF-alpha/NF-kappa B pathway. C1 [Fischman, Alan J.] Shriners Hosp Children, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Fischman, Alan J.] Harvard Univ, Sch Med, Boston, MA USA. RP Fischman, AJ (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM aajjff@gmail.com FU Shriners Hospitals for Children [87100]; National Institute of Health [P50 21700] FX Supported by Shriners Hospitals for Children (grant 87100) and National Institute of Health (P50 21700). The authors declare that they have no competing interests. NR 25 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2015 VL 261 IS 5 BP 1006 EP 1012 DI 10.1097/SLA.0000000000000764 PG 7 WC Surgery SC Surgery GA CF1RZ UT WOS:000352326900053 PM 24950285 ER PT J AU Sylla, P AF Sylla, Patricia TI Robotically Assisted Transanal Total Mesorectal Excision: An Exciting New Trend in Rectal Cancer Surgery SO ANNALS OF SURGERY LA English DT Editorial Material ID RESECTION C1 Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Sylla, P (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. EM psylla@mgh.harvard.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2015 VL 261 IS 5 BP E122 EP E122 DI 10.1097/SLA.0000000000001090 PG 1 WC Surgery SC Surgery GA CF1RZ UT WOS:000352326900002 PM 25563874 ER PT J AU Fairweather, M Wang, JP Devlin, PM Hansen, J Baldini, EH Ready, JE Sugarbaker, DJ Bertagnolli, MM Raut, CP AF Fairweather, Mark Wang, Jiping Devlin, Phillip M. Hansen, Jorgen Baldini, Elizabeth H. Ready, John E. Sugarbaker, David J. Bertagnolli, Monica M. Raut, Chandrajit P. TI Safety and Efficacy of Radiation Dose Delivered via Iodine-125 Brachytherapy Mesh Implantation for Deep Cavity Sarcomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMAS; CELL LUNG-CANCER; PROSPECTIVE RANDOMIZED-TRIAL; HIGH-RISK PATIENTS; RETROPERITONEAL SARCOMA; SUBLOBAR RESECTION; ADJUVANT BRACHYTHERAPY; PROGNOSTIC-FACTORS; POSTOPERATIVE RADIOTHERAPY; SUPERFICIAL TRUNK AB Radiation delivered as brachytherapy (BRT) via catheters placed during extremity soft tissue sarcoma (STS) resection results in acceptable local control rates; however, there are limitations in deep cavities. I-125 seeds embedded in mesh provide a flexible BRT platform that may be contoured to irregular deep cavities surfaces, but the risks and benefits are unknown. Patients with thoracic, abdominal, pelvic, retroperitoneal, and deep truncal STS undergoing resection and implantation of permanent I-125 mesh BRT at our institution were reviewed. Local recurrence rates within the tumor bed covered by mesh (in field) and postoperative complications were analyzed. Between 2000 and 2010, a total of 46 patients were treated for primary (n = 8, 17 %) or recurrent (n = 38, 83 %) deep cavity STS (median follow-up 34.8 months); 74 % received external-beam radiotherapy for this or a prior presentation. In-field recurrences were observed in 9 patients (19.5 %). Crude cumulative incidences of in-field, regional, and distant recurrences at 5 years were 26.3, 54.2, and 54.1 %, respectively. 5-year overall survival rate was 47.2 %; median survival was 44.0 months. Twenty-two patients (48 %) experienced complications, half of whom (24 %) developed grade III/IV complications requiring percutaneous intervention (n = 6) or reoperation (n = 5) at a median of 35.5 days. There were no postoperative deaths. To our knowledge, this is the first study to report safety and efficacy for permanent I-125 mesh BRT implantation after resection of deep cavity STS. Local in-field recurrence rates were relatively low in this high-risk population. However, 24 % developed complications requiring intervention. I-125 mesh BRT appears effective, but it should be used with caution. C1 [Fairweather, Mark; Wang, Jiping; Bertagnolli, Monica M.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02115 USA. [Devlin, Phillip M.; Hansen, Jorgen; Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Ready, John E.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Sugarbaker, David J.] Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. [Devlin, Phillip M.; Baldini, Elizabeth H.; Bertagnolli, Monica M.; Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Fairweather, M (reprint author), Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM mfairweather@partners.org NR 42 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2015 VL 22 IS 5 BP 1455 EP 1463 DI 10.1245/s10434-014-4171-y PG 9 WC Oncology; Surgery SC Oncology; Surgery GA CF0JN UT WOS:000352229800010 PM 25341749 ER PT J AU Kitzbichler, MG Khan, S Ganesan, S Vangel, MG Herbert, MR Hamalainen, MS Kenet, T AF Kitzbichler, Manfred G. Khan, Sheraz Ganesan, Santosh Vangel, Mark G. Herbert, Martha R. Haemaelaeinen, Matti S. Kenet, Tal TI Altered Development and Multifaceted Band-Specific Abnormalities of Resting State Networks in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; Connectivity; Cortex; Development; MEG activity; Resting state ID FUNCTIONAL CONNECTIVITY MRI; SPACE SEPARATION METHOD; SPECTRUM DISORDERS; DEFAULT-MODE; HUMAN BRAIN; CORTICAL ACTIVITY; MEG MEASUREMENTS; WORKING-MEMORY; FRONTAL-CORTEX; GAMMA AB BACKGROUND: Extensive evidence indicates that cortical connectivity patterns are abnormal in autism spectrum disorders (ASD), showing both overconnectivity and underconnectivity. Since, however, studies to date have focused on either spatial or spectral dimensions, but not both simultaneously, much remains unknown about the nature of these abnormalities. In particular, it remains unknown whether abnormal connectivity patterns in ASD are driven by specific frequency bands, by spatial network properties, or by some combination of these factors. METHODS: Magnetoencephalography recordings (15 ASD, 15 control subjects) mapped back onto cortical space were used to study resting state networks in ASD with both spatial and spectral specificity. The data were quantified using graph theoretic metrics. RESULTS: The two major factors that drove the nature of connectivity abnormalities in ASD were the mediating frequency band and whether the network included frontal nodes. These factors determined whether clustering and integration were increased or decreased in cortical resting state networks in ASD. These measures also correlated with abnormalities in the developmental trajectory of resting state networks in ASD. Lastly, these measures correlated with ASD severity in some frequency bands and spatially specific subnetworks. CONCLUSIONS: Our findings suggest that network abnormalities in ASD are widespread, are more likely in subnetworks that include the frontal lobe, and can be opposite in nature depending on the frequency band. These findings thus elucidate seemingly contradictory prior findings of both overconnectivity and underconnectivity in ASD. C1 [Kitzbichler, Manfred G.; Khan, Sheraz; Ganesan, Santosh; Vangel, Mark G.; Herbert, Martha R.; Haemaelaeinen, Matti S.; Kenet, Tal] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kitzbichler, Manfred G.; Khan, Sheraz; Ganesan, Santosh; Herbert, Martha R.; Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Vangel, Mark G.; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Kenet, T (reprint author), Massachusetts Gen Hosp, 149 Thirteenth St,Room 2275, Charlestown, MA 02129 USA. EM tal@nmr.mgh.harvard.edu OI Khan, Sheraz/0000-0002-6792-3577 FU Nancy Lurie Marks Foundation; Nancy Lurie Marks Family Foundation; Autism Speaks; National Center for Research Resources [P41RR14075]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; Cognitive Rhythms Collaborative: A Discovery Network [NFS 1042134] FX We gratefully acknowledge the financial support from the Nancy Lurie Marks Foundation without which this work would not have been possible. Authors received research funding from the following organizations and funding bodies: The Nancy Lurie Marks Family Foundation (TK, MGK, SK), Autism Speaks (TK), The National Center for Research Resources (P41RR14075, MSH), National Institute for Biomedical Imaging and Bioengineering (5R01EB009048, MSH), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, MSH). MGK is currently affiliated with the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom. NR 75 TC 14 Z9 14 U1 4 U2 13 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 MAY 1 PY 2015 VL 77 IS 9 BP 794 EP 804 DI 10.1016/j.biopsych.2014.05.012 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800006 PM 25064418 ER PT J AU Karakis, I Leeman-Markowski, BA Leveroni, CL Kilbride, RD Cash, SS Eskandar, EN Simon, MV AF Karakis, Ioannis Leeman-Markowski, Beth A. Leveroni, Catherine L. Kilbride, Ronan D. Cash, Sydney S. Eskandar, Emad N. Simon, Mirela V. TI Intra-stimulation discharges: An overlooked cortical electrographic entity triggered by direct electrical stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Functional brain mapping; Electrical cortical stimulation; After-discharges; Intra-stimulation discharges ID CEREBRAL-CORTEX; AFTERDISCHARGE; AREA AB Objective: Intra-stimulation discharges (IDs) can occur during language mapping, are largely unrecognized, and may precede the occurrence of after-discharges (ADs) and seizures. This study aimed to identify predictors of ID occurrence and determine whether IDs increase the probability of triggered ADs. Methods: A total of 332 stimulation events performed during language mapping were analyzed in 3 patients who underwent intracranial EEG recordings during evaluations for epilepsy surgery. IDs were identified in 76 stimulation events. The relationships between IDs and the stimulus current intensity, stimulation duration, and proximity to regions of abnormal cortical excitability [characterized by the presence of baseline epileptiform discharges (BEDs)] were determined using regression analysis. Results: The presence of BEDs in close proximity to stimulation, an increase in stimulus intensity by 1 mA, and an increase in stimulation duration by 1 s independently increased the odds of triggering IDs by 7.40, 1.37, and 1.39 times, respectively. All IDs were triggered during stimulations in the temporal lobe. The occurrence of IDs increased the odds of triggering ADs 5-fold. Conclusions: Longer stimulations, higher currents, and the presence of BEDs at the stimulation site increase the probability of ID occurrence, which in turn increases the probability of triggering ADs. Significance: Attention to IDs may improve the safety and precision of neurophysiologic mapping. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Karakis, Ioannis; Leeman-Markowski, Beth A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30303 USA. [Leveroni, Catherine L.; Kilbride, Ronan D.; Cash, Sydney S.; Simon, Mirela V.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Karakis, I (reprint author), Emory Univ, Sch Med, Fac Off Bldg Grady Campus,49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 USA. EM ioannis.karakis@emory.edu NR 20 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2015 VL 126 IS 5 BP 882 EP 888 DI 10.1016/j.clinph.2014.08.011 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF0KT UT WOS:000352233500007 PM 25266305 ER PT J AU Rubinfeld, RS Trattler, WB Talamo, J Majmudar, P Lindstrom, RL AF Rubinfeld, Roy S. Trattler, William B. Talamo, Jonathan Majmudar, Parag Lindstrom, Richard L. TI Screening of Refractive Surgery Candidates for LASIK and PRK SO CORNEA LA English DT Letter ID KERATOCONUS C1 [Rubinfeld, Roy S.] Georgetown Univ, Sch Med, Washington Hosp Ctr, Washington, DC 20057 USA. [Rubinfeld, Roy S.] Georgetown Univ, Sch Med, Washington Hosp Ctr, Dept Ophthalmol, Washington, DC USA. [Trattler, William B.] Ctr Excellence Eye Care, Miami, FL USA. [Talamo, Jonathan] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Talamo, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Majmudar, Parag] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago Cornea Consultants Ltd, Chicago, IL 60612 USA. [Lindstrom, Richard L.] Univ Minnesota, Minnesota Eye Consultants, Minneapolis, MN USA. [Lindstrom, Richard L.] Univ Calif Irvine, Gavin Herbert Eye Inst, Minneapolis, MN USA. RP Rubinfeld, RS (reprint author), Georgetown Univ, Sch Med, Washington Hosp Ctr, Washington, DC 20057 USA. NR 7 TC 0 Z9 0 U1 0 U2 8 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 MAY PY 2015 VL 34 IS 5 BP E13 EP E14 PG 2 WC Ophthalmology SC Ophthalmology GA CF0BZ UT WOS:000352208800002 PM 25782402 ER PT J AU Lim, SY Bolster, MB AF Lim, Sian Yik Bolster, Marcy B. TI Current approaches to osteoporosis treatment SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE bisphosphonate drug holiday; denosumab; osteoporosis; romosozumab; teriparatide ID BONE-MINERAL DENSITY; ATYPICAL FEMORAL FRACTURES; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; ZOLEDRONIC ACID; HIP FRACTURE; BISPHOSPHONATE THERAPY; INTERVENTION TRIAL; DRUG-HOLIDAYS AB Purpose of review Osteoporosis is a skeletal disorder in which bone strength is decreased leading to an increased risk of fracture. In line with advances in knowledge of bone biology, the past several years have held major therapeutic advances in osteoporosis treatment. In this article, we review the current approaches to osteoporosis treatment with a focus on issues of interest to the practicing rheumatologist. Recent findings In addition to the bisphosphonates, the introduction of denosumab, teriparatide and selective oestrogen-receptor modulators, as well as the development of new therapeutic agents (romosozumab and odanacatib) has opened the door to new approaches, including individualization of treatment in different clinical circumstances based on patient comorbidities and preference; combination therapy to optimize treatment effect; and consideration of goal-based treatment. Postmarketing surveillance of bisphosphonates has revealed several safety concerns including osteonecrosis of the jaw and atypical femoral fractures. Bisphosphonate drug holidays should be considered in patients on bisphosphonate therapy because prolonged treatment may be associated with adverse events. Summary Substantial progress has been made in the past several years in the understanding and modification of osteoporosis management. Many conditions encountered by rheumatologists are associated with bone loss; therefore, the rheumatologist needs to be aware of the current approaches in osteoporosis management. C1 [Lim, Sian Yik; Bolster, Marcy B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Lim, SY (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St Bulfinch 165, Boston, MA 02114 USA. EM sylim@partners.org FU Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital FX We wish to thank the Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital for providing assistance and support during preparation of this manuscript. NR 64 TC 12 Z9 12 U1 6 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD MAY PY 2015 VL 27 IS 3 BP 216 EP 224 DI 10.1097/BOR.0000000000000169 PG 9 WC Rheumatology SC Rheumatology GA CE5YQ UT WOS:000351912700002 PM 25760281 ER PT J AU Daniels, GH Hegedus, L Marso, SP Nauck, MA Zinman, B Bergenstal, RM Mann, JFE Karsbol, JD Moses, AC Buse, JB Tuttle, M AF Daniels, G. H. Hegedus, L. Marso, S. P. Nauck, M. A. Zinman, B. Bergenstal, R. M. Mann, J. F. E. Karsbol, J. Derving Moses, A. C. Buse, J. B. Tuttle, M. CA LEADER Trial Investigators TI LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations SO DIABETES OBESITY & METABOLISM LA English DT Article DE calcitonin; c-cell disease; diabetes; incretins ID MEDULLARY-THYROID CARCINOMA; SERUM CALCITONIN; RECEPTOR AGONISTS; UNITED-STATES; NODULES; PREVALENCE; SMOKING; SEX AB Aims: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization. Methods: The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high risk of cardiovascular disease at 410 centres worldwide. People with baseline serum calcitonin <= 50 ng/l were randomized to liraglutide once daily or placebo and will be followed for up to 5 years. Serum calcitonin was measured at baseline and will be measured annually thereafter. An independent committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations >= 20 ng/l. Results: The mean age of participants was 64.3 +/- 7.2 years, 64.3% were men, and mean the body mass index was 32.5 +/- 6.3 kg/m(2). The median (interquartile range) baseline serum calcitonin values were 3.9 (1.0 to >7.6) ng/l in men and 1.0 (1.0 to >1) ng/l in women. Serum calcitonin was >10 ng/l in 14.6% of men and in 0.96% of women. In sex-specific multivariable linear analysis of covariance models, a reduced glomerular filtration rate (GFR) was associated with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73m(2) decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men. Conclusions: In the LEADER population, the prevalence of elevated serum calcitonin concentrations at baseline was high, and there was an inverse association between eGFR and serum calcitonin concentrations. C1 [Daniels, G. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA USA. [Daniels, G. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Hegedus, L.] Univ Southern Denmark, Odense Univ Hosp, Dept Endocrinol & Metab, Odense, Denmark. [Marso, S. P.] Univ Texas Southwestern, Dept Internal Med, Div Cardiol, Dallas, TX USA. [Nauck, M. A.] Diabet Zentrum, Bad Lauterberg im Harz, Germany. [Zinman, B.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Bergenstal, R. M.] Int Diabet Ctr Pk Nicollet, Minneapolis, MN USA. [Mann, J. F. E.] Univ Erlangen Nurnberg, Dept Nephrol Hypertens & Rheumatol, Munich, Germany. [Karsbol, J. Derving; Moses, A. C.] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. [Buse, J. B.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Tuttle, M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. EM Daniels.Gilbert@mgh.harvard.edu RI Zinman, Bernard/E-7266-2013; BALCI, Mustafa Kemal/C-2979-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249 FU Novo Nordisk FX The LEADER trial is funded by Novo Nordisk. We would like to thank Henrik Wachmann, an employee of Novo Nordisk, for statistical analysis and support. Writing assistance was provided by Joseph Murphy, with funding provided by Novo Nordisk. NR 26 TC 5 Z9 5 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD MAY PY 2015 VL 17 IS 5 BP 477 EP 486 DI 10.1111/dom.12444 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF0SR UT WOS:000352255000006 PM 25656058 ER PT J AU Leibowitz, G Cahn, A Bhatt, DL Hirshberg, B Mosenzon, O Wei, C Jermendy, G Sheu, WHH Sendon, JL Im, K Braunwald, E Scirica, BM Raz, I AF Leibowitz, G. Cahn, A. Bhatt, D. L. Hirshberg, B. Mosenzon, O. Wei, C. Jermendy, G. Sheu, W. H. -H. Sendon, J. L. Im, K. Braunwald, E. Scirica, B. M. Raz, I. TI Impact of treatment with saxagliptin on glycaemic stability and beta-cell function in the SAVOR-TIMI 53 study SO DIABETES OBESITY & METABOLISM LA English DT Article DE clinical trial; dipeptidyl peptidase-4 inhibitor; glycaemic control; type 2 diabetes; beta cell ID GLUCAGON-LIKE PEPTIDE-1; DIABETES-MELLITUS; ANTIDIABETIC ACTIONS; FOLLOW-UP; TYPE-2; THERAPY; FAILURE; GLUCOSE; PROGRESSION; POPULATION AB Aims: To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and beta-cell function in the SAVOR-TIMI 53 trial. Methods: We randomized 16 492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of >= 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for >= 3 months; or (iii) an increase in dose of oral antidiabetic medication or >= 25% increase in insulin dose for >= 3 months. beta-cell function was assessed according to fasting homeostatic model 2 assessment of beta-cell function (HOMA-2 beta) values at baseline and at year 2 in patients not treated with insulin. Results: Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of >= 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2 beta values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001). Conclusions: Saxagliptin improved glycaemia and prevented the reduction in HOMA-2 beta values. Saxagliptin may reduce the usual decline in beta-cell function in T2D, thereby slowing diabetes progression. C1 [Leibowitz, G.; Cahn, A.; Mosenzon, O.; Raz, I.] Hadassah Univ Hosp, Diabet Unit, IL-91120 Jerusalem, Israel. [Leibowitz, G.] Hadassah Univ Hosp, Endocrine Serv, IL-91120 Jerusalem, Israel. [Bhatt, D. L.; Im, K.; Braunwald, E.; Scirica, B. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Hirshberg, B.; Wei, C.] AstraZeneca Res & Dev, Wilmington, DE USA. [Jermendy, G.] Bajcsy Zsilinszky Hosp, Dept Med, Budapest, Hungary. [Sheu, W. H. -H.] Taichung Vet Gen Hosp, Div Endocrinol & Metab, Taichung, Taiwan. [Sendon, J. L.] Hosp Univ La Paz, Inst Invest IdiPaz, Madrid, Spain. RP Leibowitz, G (reprint author), Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Dept Med, POB 12000, IL-91120 Jerusalem, Israel. EM gleib@hadassah.org.il FU AstraZeneca; Bristol-Myers Squibb; Novo Nordisk; Amarin; Eisai; Ethicon; Medtronic; Roche; Sanofi Aventis; The Medicines Company; TIMI Study and Brigham and Women's Hospital from AstraZeneca; Daiichi-Sankyo; GlaxoSmithKline; Johnson and Johnson; Bayer Healthcare; Gilead; Merck; Boehringer Ingelheim; Lexicon; Arena; St. Jude's Medical; Forest Pharmaceuticals; Boston Clinical Research Institute; Covance; University of Calgary; Elsevier Practice Update Cardiology; Sanofi FX This study was funded by AstraZeneca and Bristol-Myers Squibb.; O. M. has received research grant support from Novo Nordisk and is on the Speaker's Bureau for Astra Zeneca and Bristol-Myers Squibb, Novo Nordisk, Eli Lilly, Sanofi, Novartis, MSD and the Advisory Board for Astra Zeneca and Bristol-Myers Squibb, Novo Nordisk, Eli Lilly, Sanofi, Novartis. Grants were also paid to O. M.'s institution as study physician by Astra Zeneca and Bristol-Myers Squibb. D. L. B. discloses the following relationships: Advisory Board: Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); Other: Clinical Cardiology (Associate Editor), Journal of the American College of Cardiology (Section Editor, Pharmacology); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. B. M. S. reports research grants via the TIMI Study and Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson and Johnson, Bayer Healthcare, Gilead, Eisai, Merck. Consulting fees from AstraZeneca, Merck, GlaxoSmithKline, Boehringer Ingelheim, Gilead, Lexicon, Arena, Eisai, St. Jude's Medical, Forest Pharmaceuticals, Bristol-Myers Squibb, Boston Clinical Research Institute, Covance, University of Calgary, Elsevier Practice Update Cardiology. W. H.-H. S. has received speaker honoraria from Astra-Zeneca, MSD, Bayer's, Eli Lilly, Novo Nordisk, Sanofi and Pfizer companies and has served as member of advisory committees for Astra-Zeneca, MSD, Bayer's, Eli Lilly, Novo Nordisk, Sanofi and Pfizer companies. J. L. S. has received research grants from AstraZeneca, Bristol Myers Squibb and Sanofi and speaking or consultation honoraria from AstraZeneca and Bristol Myers Squibb. G. J. has served as a national lead co-investigator for the SAVOR-TIMI53 study and received honoraria from AstraZeneca and Bristol-Myers Squibb. I. R. discloses the following relationships: Advisory Board: Novo Nordisk, Astra Zeneca/BMS, MSD, Eli Lilly, Sanofi, Medscape Cardiology. Consultant: AstraZeneca/BMS, Andromeda, Insuline. Speaker's Bureau: Eli Lilly, Novo Nordisk, AstraZeneca/BMS, J&J, Sanofi, MSD, Novartis, Teva. Shareholder: Insuline, Labstyle. NR 30 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD MAY PY 2015 VL 17 IS 5 BP 487 EP 494 DI 10.1111/dom.12445 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF0SR UT WOS:000352255000007 PM 25656169 ER PT J AU Raiko, J Holstila, M Virtanen, KA Orava, J Saunavaara, V Niemi, T Laine, J Taittonen, M Borra, RJH Nuutila, P Parkkola, R AF Raiko, J. Holstila, M. Virtanen, K. A. Orava, J. Saunavaara, V. Niemi, T. Laine, J. Taittonen, M. Borra, R. J. H. Nuutila, P. Parkkola, R. TI Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity SO DIABETES OBESITY & METABOLISM LA English DT Article DE adipose tissue; body composition; H-1-MRS; MRI ID HUMANS; MRI AB The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy (H-1-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using F-18-fluorodeoxyglucose positron emission tomography (PET) and O-15-H2O PET perfusion during cold exposure, and H-1-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by H-1-MRS varied between 60 and 91% [mean +/- standard deviation (s.d.) 77 +/- 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean +/- s.d. 87 +/- 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by H-1-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation. C1 [Raiko, J.; Holstila, M.; Virtanen, K. A.; Orava, J.; Saunavaara, V.; Nuutila, P.; Parkkola, R.] Univ Turku, Turku Univ Hosp, Turku PET Ctr, Turku, Finland. [Holstila, M.; Borra, R. J. H.; Parkkola, R.] Turku Univ Hosp, Med Imaging Ctr Southwest Finland, FIN-20520 Turku, Finland. [Niemi, T.] Univ Turku, Turku Univ Hosp, Dept Plast & Gen Surg, Turku, Finland. [Laine, J.] Univ Turku, Dept Pathol, Turku Univ Hosp, Turku, Finland. [Taittonen, M.] Univ Turku, Dept Anesthesiol, Turku Univ Hosp, Turku, Finland. [Borra, R. J. H.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Parkkola, R (reprint author), Turku Univ Hosp, Dept Radiol, POB 52, FI-20521 Turku, Finland. EM riitta.parkkola@tyks.fi RI Saunavaara, Virva/M-5594-2016 OI Saunavaara, Virva/0000-0001-7858-5924 FU Academy of Finland; University of Turku; Turku University Hospital; Abo Akademi University; European Union (EU FP7 project) [278373]; National Graduate School of Clinical Investigation FX We thank the staff of the Turku PET Centre for their outstanding technical assistance. Robert M. Badeau, Ph.D. (robert.badeau@gmx.com) performed the scientific language editing of this manuscript. The study was conducted within the Finnish Centre of Excellence in Cardiovascular and Metabolic Diseases supported by the Academy of Finland, University of Turku, Turku University Hospital and Abo Akademi University. The work was also supported by the European Union (EU FP7 project 278373; DIABAT), as well as grants from Turku University Hospital and The National Graduate School of Clinical Investigation. NR 12 TC 6 Z9 7 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD MAY PY 2015 VL 17 IS 5 BP 516 EP 519 DI 10.1111/dom.12433 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF0SR UT WOS:000352255000011 PM 25586670 ER PT J AU Marx, N Rosenstock, J Kahn, SE Zinman, B Kastelein, JJ Lachin, JM Espeland, MA Bluhmki, E Mattheus, M Ryckaert, B Patel, S Johansen, OE Woerle, HJ AF Marx, Nikolaus Rosenstock, Julio Kahn, Steven E. Zinman, Bernard Kastelein, John J. Lachin, John M. Espeland, Mark A. Bluhmki, Erich Mattheus, Michaela Ryckaert, Bart Patel, Sanjay Johansen, Odd Erik Woerle, Hans-Juergen TI Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA (R)) SO DIABETES & VASCULAR DISEASE RESEARCH LA English DT Article DE Type 2 diabetes; cardiovascular complications; macrovascular; dipeptidyl-peptidase-4 inhibitor; sulphonylurea ID DPP-4 INHIBITION; CLINICAL-TRIALS; IV INHIBITORS; DOUBLE-BLIND; COMPLICATIONS; METAANALYSIS; RATIONALE; SAFETY; DRUGS AB CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (NCT01243424) is an ongoing, randomized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride. Eligible patients were sulphonylurea-naive with HbA(1c) 6.5%-8.5% or previously exposed to sulphonylurea (in monotherapy or in a combination regimen <5years) with HbA(1c) 6.5%-7.5%. Primary outcome is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina. A total of 631 patients with primary outcome events will be required to provide 91% power to demonstrate non-inferiority in cardiovascular safety by comparing the upper limit of the two-sided 95% confidence interval as being below 1.3 for a given hazard ratio. Hierarchical testing for superiority will follow, and the trial has 80% power to demonstrate a 20% relative cardiovascular risk reduction. A total of 6041 patients were treated with median type 2 diabetes duration 6.2years, 40.0% female, mean HbA1c 7.2%, 66% on 1 and 24% on 2 glucose-lowering agents and 34.5% had previous cardiovascular complications. The results of CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the decision-making process for selecting a second glucose-lowering agent after metformin in type 2 diabetes. C1 [Marx, Nikolaus] Univ Hosp Aachen, Dept Internal Med 1, D-52074 Aachen, Germany. [Rosenstock, Julio] Dallas Diabet & Endocrine Ctr Med City, Dallas, TX USA. [Rosenstock, Julio] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Zinman, Bernard] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, Bernard] Univ Toronto, Toronto, ON, Canada. [Kastelein, John J.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Lachin, John M.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Espeland, Mark A.] Wake Forest Baptist Med Ctr, Dept Biostat, Winston Salem, NC USA. [Bluhmki, Erich] Boehringer Ingelheim GmbH & Co KG, Biberach, Germany. [Mattheus, Michaela; Woerle, Hans-Juergen] Boehringer Ingelheim KG, Ingelheim, Germany. [Ryckaert, Bart] Boehringer Ingelheim GmbH & Co KG, Brussels, Belgium. [Patel, Sanjay] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. [Johansen, Odd Erik] Boehringer Ingelheim GmbH & Co KG, Asker, Norway. RP Marx, N (reprint author), Univ Hosp Aachen, Dept Internal Med 1, D-52074 Aachen, Germany. EM nmarx@ukaachen.de RI Zinman, Bernard/E-7266-2013 FU Boehringer Ingelheim; Eli Lilly FX The CAROLINA trial is sponsored by Boehringer Ingelheim and Eli Lilly. NR 23 TC 31 Z9 31 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1479-1641 EI 1752-8984 J9 DIABETES VASC DIS RE JI Diabetes Vasc. Dis. Res. PD MAY PY 2015 VL 12 IS 3 BP 164 EP 174 DI 10.1177/1479164115570301 PG 11 WC Endocrinology & Metabolism; Peripheral Vascular Disease SC Endocrinology & Metabolism; Cardiovascular System & Cardiology GA CF6EM UT WOS:000352649600002 PM 25780262 ER PT J AU Ioannou, GN Bryson, CL Weiss, NS Boyko, EJ AF Ioannou, George N. Bryson, Christopher L. Weiss, Noel S. Boyko, Edward J. TI Associations between lipodystrophy or antiretroviral medications and cirrhosis in patients with HIV infection or HIV/HCV coinfection SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE adverse effect; AIDS; drug; fibrosis; side effect ID HEPATITIS-C VIRUS; THERAPY-ASSOCIATED LIPODYSTROPHY; HEPATOCELLULAR-CARCINOMA; RISK-FACTORS; FAT LOSS; LIVER; INDIVIDUALS; LIPOATROPHY; PROGRESSION; METABOLISM AB Background Many HIV antiretroviral medications have been associated with chronic liver injury. HIV-infected patients frequently develop HIV and highly active antiretroviral treatment-associated lipodystrophy syndrome (HALS), characterized by accumulation of intra-abdominal fat, insulin resistance, and hepatic steatosis. We sought to determine whether long-term exposure to specific antiretroviral medications or the presence of HALS predispose HIV-infected patients to the development of cirrhosis. Methods HIV-infected patients with cirrhosis who received care in the Veterans Affairs Healthcare System nationally in 2009 were matched by hepatitis C virus (HCV) coinfection status and year of first visit for HIV to the Veterans Affairs Healthcare System with HIV-infected patients without cirrhosis in a 1 : 3 ratio. Results Among HIV/HCV coinfected patients (593 with cirrhosis and 1591 matched controls), HALS was associated with a significantly increased risk for cirrhosis (adjusted odds ratio 1.6, 95% confidence interval 1.1-2.3), especially among Black patients (adjusted odds ratio 2.9, 95% confidence interval 1.6-5.2). In addition, among HIV/HCV coinfected patients, longer cumulative exposures to all antiretroviral medications, all nucleoside reverse transcriptase inhibitors, all protease inhibitors, and selected individual medications (didanosine, stavudine, and nelfinavir) were found to be significantly associated with cirrhosis. In contrast, among HIV-infected patients not coinfected with HCV (245 with cirrhosis and 658 matched controls), HALS or exposure to antiretroviral medications was found not to be significantly associated with cirrhosis, with the exception of didanosine. Conclusion HALS and cumulative exposure to nucleoside reverse transcriptase inhibitors and protease inhibitors, especially stavudine, didanosine, and nelfinavir, were found to be associated with the development of cirrhosis in HIV/HCV coinfected patients, but not in HIV-monoinfected patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Bryson, Christopher L.; Boyko, Edward J.] Vet Affairs Puget Sound Healthcare Syst, Div Internal Med, Seattle, WA 98108 USA. [Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Healthcare Syst, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Merit Review grant, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [I01CX000320] FX The study was funded by a Merit Review grant (I01CX000320), Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (G.N.I.). NR 28 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-691X EI 1473-5687 J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD MAY PY 2015 VL 27 IS 5 BP 577 EP 584 DI 10.1097/MEG.0000000000000290 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE9KK UT WOS:000352162600015 PM 25769096 ER PT J AU Nishino, M Cardarella, S Dahlberg, SE Araki, T Lydon, C Jackman, DM Rabin, MS Hatabu, H Johnson, BE AF Nishino, Mizuki Cardarella, Stephanie Dahlberg, Suzanne E. Araki, Tetsuro Lydon, Christine Jackman, David M. Rabin, Michael S. Hatabu, Hiroto Johnson, Bruce E. TI Interstitial lung abnormalities in treatment-naive advanced non-small-cell lung cancer patients are associated with shorter survival SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Interstitial lung disease; Lung cancer; Computed tomography; Advanced non-small-cell lung cancer; Survival ID IDIOPATHIC PULMONARY-FIBROSIS; DISEASE; IMPACT; SMOKING; RISK; EXACERBATION; CHEMOTHERAPY; GROWTH AB Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naive stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9-9.4] compared to 14.8 months [95%CI: 11.1-18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naive advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Nishino, Mizuki; Araki, Tetsuro; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Cardarella, Stephanie; Lydon, Christine; Jackman, David M.; Rabin, Michael S.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU National Institutes of Health [1K23CA157631, 1RO1CA114465-07, 5R21CA11627-02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578-10]; Genentech Inc; Doris and William Krupp Research Fund in Thoracic Oncology; Gallup Fund in Thoracic Oncology; American Society of Clinical Oncology Translational Research Professorship FX The investigators were supported by 1K23CA157631 (NCI) (M.N.), grants 1RO1CA114465-07 (B.E.J.) and 5R21CA11627-02 (H.H.) from the National Institutes of Health, 2P50CA090578-10 (B.E.J.) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology, the Gallup Fund in Thoracic Oncology, and American Society of Clinical Oncology Translational Research Professorship. NR 27 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD MAY PY 2015 VL 84 IS 5 BP 998 EP 1004 DI 10.1016/j.ejrad.2015.01.021 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF6ZI UT WOS:000352705200039 PM 25726730 ER PT J AU Nguyen, PL Alibhai, SMH Basaria, S D'Amico, AV Kantoff, PW Keating, NL Penson, DF Rosario, DJ Tombal, B Smith, MR AF Nguyen, Paul L. Alibhai, Shabbir M. H. Basaria, Shehzad D'Amico, Anthony V. Kantoff, Philip W. Keating, Nancy L. Penson, David F. Rosario, Derek J. Tombal, Bertrand Smith, Matthew R. TI Adverse Effects of Androgen Deprivation Therapy and Strategies to Mitigate Them SO EUROPEAN UROLOGY LA English DT Review DE Androgen deprivation therapy; Prostate cancer ID ADVANCED PROSTATE-CANCER; RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; PROPHYLACTIC BREAST IRRADIATION; SUPPRESSION PLUS RADIATION; CARDIOVASCULAR-DISEASE; LONG-TERM; HORMONE AGONIST; PHYSICAL-ACTIVITY AB Context: Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. Objective: To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. Evidence acquisition: The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. Evidence synthesis: Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). Conclusions: ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. Patient summary: Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Nguyen, Paul L.; D'Amico, Anthony V.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Alibhai, Shabbir M. H.] Univ Hlth Network, Dept Med, Toronto, ON, Canada. [Basaria, Shehzad] Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Mens Hlth Aging & Metab, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Internal Med,Dept Med, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Penson, David F.] Vanderbilt Univ, Dept Urol Surg, Nashville, TN 37235 USA. [Penson, David F.] Vanderbilt Univ, Ctr Surg Qual & Outcomes Res, Nashville, TN 37235 USA. [Penson, David F.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Rosario, Derek J.] Univ Sheffield, Royal Hallamshire Hosp, Dept Oncol, Acad Urol Unit, Sheffield S10 2JF, S Yorkshire, England. [Tombal, Bertrand] Catholic Univ Louvain, Clin Univ St Luc, Div Urol, B-1200 Brussels, Belgium. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA 02114 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Prostate Cancer Foundation; Fitz's Cancer Warriors FX This study was supported by the Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. NR 107 TC 62 Z9 62 U1 9 U2 35 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 MAY PY 2015 VL 67 IS 5 BP 825 EP 836 DI 10.1016/j.eururo.2014.07.010 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CE9DF UT WOS:000352143100006 PM 25097095 ER PT J AU Montgomery, B Kheoh, T Molina, A Li, JH Bellmunt, J Tran, NP Loriot, YH Efstathiou, E Ryan, CJ Scher, HI de Bono, JS AF Montgomery, Bruce Kheoh, Thian Molina, Arturo Li, Jinhui Bellmunt, Joaquim Tran, NamPhuong Loriot, Yohann Efstathiou, Eleni Ryan, Charles J. Scher, Howard I. de Bono, Johann S. TI Impact of Baseline Corticosteroids on Survival and Steroid Androgens in Metastatic Castration-resistant Prostate Cancer: Exploratory Analysis from COU-AA-301 SO EUROPEAN UROLOGY LA English DT Article DE Abiraterone; Corticosteroids; Prostate cancer; Survival; Testosterone ID LOW-DOSE DEXAMETHASONE; ABIRATERONE ACETATE; END-POINTS; PHASE-III; RECEPTOR; CHEMOTHERAPY; PREDNISONE; CARCINOMA; EFFICACY; CELLS AB Background: Corticosteroids have been used to mitigate mineralocorticoid-related effects and restore sensitivity to abiraterone acetate. Corticosteroids may also mediate glucocorticoid receptor or mutated androgen receptor activation and adversely influence outcome. Objective: This post hoc exploratory analysis investigated whether baseline corticosteroids were an independent prognostic factor and its level of contribution in the presence of other prognostic factors for overall survival (OS) in study COU-AA-301. Design, setting, and participants: COU-AA-301 was a randomised study of abiraterone plus prednisone versus prednisone in metastatic castration-resistant prostate cancer patients after docetaxel. Intervention: Patients were randomised 2: 1 to abiraterone 1000 mg plus prednisone 5 mg by mouth twice daily versus prednisone. Outcome measurements and statistical analysis: Association of OS with baseline corticosteroids was determined by univariate and multivariate Cox models. Results and limitations: At study entry, 33% of patients received corticosteroids, had worse disease characteristics (p < 0.05 except liver metastases), and were more likely to have testosterone levels below the median (odds ratio: 2.92; chi-square p < 0.0001). Associations between prostate-specific antigen response as well as circulating tumour cell decline and higher baseline androgen levels were demonstrated. Patients taking baseline corticosteroids had inferior OS in univariate analysis (hazard ratio: 1.48; p < 0.0001); however, in multivariate stepwise selection modelling, baseline corticosteroids did not add substantially to the model. This analysis is limited as a retrospective analysis and restricted to patients after docetaxel. Conclusions: In the COU-AA-301 study, baseline corticosteroids were associated with adverse prognostic features, inferior OS, and lower baseline androgen levels but did not add substantial information to the final prognostic model. Thus in these data from study COU-AA-301, concurrent baseline corticosteroids did not have an independent impact on OS. Patient summary: Baseline corticosteroids did not adversely affect abiraterone clinical benefit in metastatic castration-resistant prostate cancer. Their use was associated with patients having worse disease characteristics. Published by Elsevier B.V. on behalf of European Association of Urology. C1 [Montgomery, Bruce] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kheoh, Thian; Tran, NamPhuong] Janssen Res & Dev, Los Angeles, CA USA. [Molina, Arturo] Janssen Res & Dev, Menlo Pk, CA USA. [Li, Jinhui] Janssen Res & Dev, Raritan, NJ USA. [Bellmunt, Joaquim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loriot, Yohann] Inst Gustave Roussy, Villejuif, France. [Efstathiou, Eleni] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Scher, Howard I.] Weill Cornell Med Coll, New York, NY 10021 USA. [de Bono, Johann S.] Inst Canc Res, Sutton, Surrey, England. [de Bono, Johann S.] Royal Marsden Hosp, Sutton, Surrey, England. RP Montgomery, B (reprint author), 1959 NE Pacific,Box 356158, Seattle, WA 98195 USA. EM rbmontgo@uw.edu FU Janssen Research Development; National Institutes of Health (Pacific Northwest Prostate Cancer SPORE) [2 P50 CA097186-11A1]; Cancer Research UK; Prostate Cancer Foundation; Experimental Cancer Medicine Centre (ECMC) grant; Biomedical Research Centre Award; Prostate Cancer UK FX This clinical trial was supported by Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology (now Janssen Research & Development). Research support was provided by National Institutes of Health (Pacific Northwest Prostate Cancer SPORE - 2 P50 CA097186-11A1). The sponsors helped design and conduct the study; collect, manage, analyse, and interpret the data; and prepare and review the manuscript. Johann de Bono's group is supported by Cancer Research UK; the Prostate Cancer Foundation; Prostate Cancer UK; an Experimental Cancer Medicine Centre (ECMC) grant as well as a Biomedical Research Centre Award. NR 24 TC 14 Z9 14 U1 1 U2 6 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 MAY PY 2015 VL 67 IS 5 BP 866 EP 873 DI 10.1016/j.eururo.2014.06.042 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CE9DF UT WOS:000352143100012 PM 25018037 ER PT J AU Grunwald, V McKay, RR Krajewski, KM Kalanovic, D Lin, X Perkins, JJ Simantov, R Choueiri, TK AF Gruenwald, Viktor McKay, Rana R. Krajewski, Katherine M. Kalanovic, Daniel Lin, Xun Perkins, Julia J. Simantov, Ronit Choueiri, Toni K. TI Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma SO EUROPEAN UROLOGY LA English DT Article DE Imaging Prognosis; Renal cell carcinoma; Targeted therapy; Tumor response; Tumor shrinkage ID PROGRESSION-FREE SURVIVAL; CLINICAL-TRIALS; TARGETED THERAPY; TUMOR SHRINKAGE; SOLID TUMORS; EVEROLIMUS; SORAFENIB; SUNITINIB; VARIABLES; CRITERIA AB Background: Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague. Objective: To define the prognostic relevance of the depth of remission in mRCC. Design, setting, and participants: Pooled data from the Pfizer database for 2749 patients from phase 2 and 3 clinical trials in mRCC were analyzed. Tumor shrinkage was categorized according to the best percentage change in the sum of the largest diameter of target lesions. Outcome was computed using Kaplan-Meier curves and correlation was assessed via Cox regression, including a 6-mo landmark. Intervention: Sunitinib, sorafenib, axitinib, temsirolimus, or temsirolimus and interferon-alpha. Outcome measurements and statistical analysis: Categorized tumor shrinkage, overall survival (OS), progression free survival (PFS). Results and limitations: Major tumor shrinkage of 60% or more occurred in approximately 10% of patients and was associated with median OS of 54.5 mo. OS expectations steadily decreased with depth of remission (26.4, 16.6, 10.4, and 7.3 mo). The association was maintained when stratified by type of therapy, line of therapy, and performance status. Cox proportional regression analyses for the 6-mo landmark confirmed the prognostic relevance of major tumor shrinkage (hazard ratio 0.29, 95% confidence interval 0.22-0.39; p < 0.001). The major limitation of our study is the variability of imaging intervals among studies. Conclusions: This is the first and largest analysis of best tumor response in mRCC. We demonstrate that depth of remission is an independent prognostic factor in mRCC. Patient summary: It remains unknown whether tumor shrinkage during therapy is needed to achieve clinical activity in metastatic renal cell carcinoma. Our analysis shows that the magnitude of tumor shrinkage correlates with better survival in patients. This observation may be used as a clinical research tool in future trials. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Gruenwald, Viktor] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [McKay, Rana R.; Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Krajewski, Katherine M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Krajewski, Katherine M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Kalanovic, Daniel; Lin, Xun; Perkins, Julia J.; Simantov, Ronit] Pfizer Inc, Pfizer Oncol, La Jolla, CA USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu FU Pfizer, Inc.; Dana-Farber/Harvard Cancer Center Kidney SPORE; Loker Pinard Fund for Kidney Cancer Research at Dana-Farber Cancer Institute; Trust Family Fund for Kidney Cancer Research at Dana-Farber Cancer Institute; Michael Brigham Fund for Kidney Cancer Research at Dana-Farber Cancer Institute FX This study was supported by Pfizer, Inc. The sponsor was involved in data management and analysis, and approval of the manuscript. Additional research support was received from the Dana-Farber/Harvard Cancer Center Kidney SPORE, and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. NR 19 TC 19 Z9 20 U1 0 U2 0 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 MAY PY 2015 VL 67 IS 5 BP 952 EP 958 DI 10.1016/j.eururo.2014.12.036 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CE9DF UT WOS:000352143100024 PM 25577718 ER PT J AU Buchwald, ZS Efstathiou, JA AF Buchwald, Zachary S. Efstathiou, Jason A. TI Re: MPDL3280A (Anti-PD-L1) Treatment Leads to Clinical Activity in Metastatic Bladder Cancer SO EUROPEAN UROLOGY LA English DT Letter C1 [Buchwald, Zachary S.] St Louis Univ, St Louis, MO 63103 USA. [Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 4 TC 1 Z9 1 U1 0 U2 5 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 MAY PY 2015 VL 67 IS 5 BP 975 EP 975 DI 10.1016/j.eururo.2014.12.065 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CE9DF UT WOS:000352143100031 PM 25845961 ER PT J AU Khalili, H Chan, AT AF Khalili, Hamed Chan, Andrew T. TI Author response: oral contraceptives and Crohn's disease SO GUT LA English DT Letter ID BARRIER FUNCTION; SEX-DIFFERENCES C1 [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM hkhalili@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD MAY PY 2015 VL 64 IS 5 DI 10.1136/gutjnl-2014-308509 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CF1GD UT WOS:000352291200024 ER PT J AU Murray, SS Wang, JC Duarte, MEL Zhao, KW Tian, HJ Francis, T Murray, EJB AF Murray, Samuel S. Wang, Jeffrey C. Leite Duarte, Maria Eugenia Zhao, Ke-Wei Tian, Haijun Francis, Timothy Murray, Elsa J. Brochmann TI The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE Secreted phosphoprotein 24 kD; Spp24; SPP2; Bone morphogenetic protein; Bone matrix proteins ID GROWTH-FACTOR-BETA; HORMONE GH ACTION; BINDING PEPTIDE; RODENT MODEL; CYSTATIN SUPERFAMILY; RESPONSE GENE; EXPRESSION; SEQUENCE; REVEALS; COMPLEX AB Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that appears to be derived primarily from the liver and delivered to other tissues in a protective complex. A significant role in bone growth and turnover is suggested by genetic studies that associate the gene locus (SPP2) with bone mineral density and bone quality. The function of this protein in the normal bone environment is unknown but clues are given by the fact that Spp24, or proteolytic products of Spp24, bind cytokines of the TGF-beta superfamily and also activate intracellular signaling pathways. Several potential biotherapeutics have been engineered from this protein including materials that enhance BMP-induced bone healing and, on the other hand, materials that inhibit BMPs in clinical situations where this is called for such as reducing BMP-induced inflammation and inhibiting tumors dependent on BMP autocrine systems. As understanding of the structure and function of this protein increases, more opportunities for rationally developed therapeutics will become apparent. C1 [Murray, Samuel S.; Murray, Elsa J. Brochmann] VA Greater Los Angeles, Sepulveda Ambulatory Care Ctr, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Murray, Samuel S.; Murray, Elsa J. Brochmann] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Wang, Jeffrey C.] Univ So Calif, Dept Orthopaed Surg, Los Angeles, CA USA. [Leite Duarte, Maria Eugenia] Natl Inst Traumatol & Orthopaed INTO, Rio De Janeiro, Brazil. [Leite Duarte, Maria Eugenia] Fed Univ Rio Janeiro UFRJ, Rio De Janeiro, Brazil. [Zhao, Ke-Wei] VA Greater Los Angeles, Res Serv, Los Angeles, CA USA. [Tian, Haijun] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, Shanghai, Peoples R China. [Francis, Timothy] Coventry Univ, Business Dev Grp, Coventry, W Midlands, England. RP Murray, SS (reprint author), VA Med Ctr, GRECC 11-E,16111 Plummer St, Sepulveda, CA 91343 USA. EM samuel.murray@va.gov FU Research Service of the Department of Veterans Affairs, USA FX Supported by the Research Service of the Department of Veterans Affairs, USA NR 37 TC 4 Z9 4 U1 0 U2 5 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 EI 1699-5848 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD MAY PY 2015 VL 30 IS 5 BP 531 EP 537 DI 10.14670/HH-30.531 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA CF4EA UT WOS:000352500300003 PM 25339413 ER PT J AU Zeinali-Davarani, S Wang, YJ Chow, MJ Turcotte, R Zhang, YH AF Zeinali-Davarani, Shahrokh Wang, Yunjie Chow, Ming-Jay Turcotte, Raphael Zhang, Yanhang TI Contribution of Collagen Fiber Undulation to Regional Biomechanical Properties Along Porcine Thoracic Aorta SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE regional variation; recruitment-based constitutive models; collagen undulation; multiphoton microscopy; biaxial tensile test; parameter sensitivity analysis ID STRUCTURAL CONSTITUTIVE MODEL; ARTERIAL-WALL MECHANICS; STRAIN-ENERGY FUNCTION; CAROTID ARTERIES; FLUORESCENCE MICROSCOPY; EXTRACELLULAR-MATRIX; ELASTIN DEGRADATION; MARFAN-SYNDROME; TISSUES; ANEURYSMS AB As major extracellular matrix components, elastin, and collagen play crucial roles in regulating the mechanical properties of the aortic wall and, thus, the normal cardiovascular function. The mechanical properties of aorta, known to vary with age and multitude of diseases as well as the proximity to the heart, have been attributed to the variations in the content and architecture of wall constituents. This study is focused on the role of layer-specific collagen undulation in the variation of mechanical properties along the porcine descending thoracic aorta. Planar biaxial tensile tests are performed to characterize the hyperelastic anisotropic mechanical behavior of tissues dissected from four locations along the thoracic aorta. Multiphoton microscopy is used to image the associated regional microstructure. Exponential-based and recruitment-based constitutive models are used to account for the observed mechanical behavior while considering the aortic wall as a composite of two layers with independent properties. An elevated stiffness is observed in distal regions compared to proximal regions of thoracic aorta, consistent with sharper and earlier collagen recruitment estimated for medial and adventitial layers in the models. Multiphoton images further support our prediction that higher stiffness in distal regions is associated with less undulation in collagen fibers. Recruitment-based models further reveal that regardless of the location, collagen in the media is recruited from the onset of stretching, whereas adventitial collagen starts to engage with a delay. A parameter sensitivity analysis is performed to discriminate between the models in terms of the confidence in the estimated model parameters. C1 [Zeinali-Davarani, Shahrokh; Wang, Yunjie; Chow, Ming-Jay; Zhang, Yanhang] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Turcotte, Raphael; Zhang, Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Turcotte, Raphael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol, Boston, MA 02114 USA. [Turcotte, Raphael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Zhang, YH (reprint author), Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. EM yanhang@bu.edu FU National Heart, Lung, and Blood Institute [R01 HL-098028] FX This work has been supported by the National Heart, Lung, and Blood Institute Grant No. R01 HL-098028. The authors would like to thank Professor Charles P. Lin from the Center for Systems Biology and Wellman Center for Photomedicine, Harvard Medical School, for providing access to the multiphoton microscope. NR 85 TC 4 Z9 4 U1 1 U2 12 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 2015 VL 137 IS 5 AR 051001 DI 10.1115/1.4029637 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA CF0YQ UT WOS:000352271000001 PM 25612301 ER PT J AU Offodile, AC Tsai, TC Wenger, JB Guo, LF AF Offodile, Anaeze C., II Tsai, Thomas C. Wenger, Julia B. Guo, Lifei TI Racial disparities in the type of postmastectomy reconstruction chosen SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Racial disparities; Immediate breast reconstruction; Health policy; Mastectomy; Race; Breast cancer ID IMMEDIATE BREAST RECONSTRUCTION; SURGICAL-TREATMENT; MASTECTOMY; CANCER; POPULATION; IMPACT; WOMEN; RATES; RACE; ETHNICITY AB Background: Racial disparities remain for women undergoing immediate breast reconstruction (IBR) after mastectomy. Understanding patterns of racial disparities in IBR utilization may present opportunities to tailor policies aimed at optimizing care across racial groups. The aim of this study was to determine if racial disparities exist for types of IBR chosen. Methods: A national, retrospective cohort study used the 2005-2011 American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression models were created to detect the odds by race for receiving each subtype of IBR after mastectomy-prosthetic, pedicled-transfer autologous tissue, or free-transfer autologous tissue. Secondary outcome was trends in IBR rates over time. Results: There were 44,597 women identified in the data set who underwent mastectomy. Thirty-seven percent of women (N = 16, 642) were noted to undergo IBR after mastectomy. Prosthetic reconstruction (84.4%, n = 37, 640) was the most common form of IBR compared with pedicled-autologous reconstruction (15.4%, n = 6868) and free transfer autologous reconstruction (4.9%, n = 2185), P < 0.001. In multivariate analysis, minorities had lower odds of undergoing IBR compared with whites (odds ratio [OR] 0.37 and 95% confidence interval [CI] 0.33-0.42 for Asians, OR 0.57 and 95% CI 0.52-0.61 for blacks, and OR 0.64 and 95% CI 0.58-0.71 for Hispanics, all P < 0.001). Compared with whites, Hispanics (OR 0.70, 95% CI 0.58-0.83) and blacks (OR 0.53, 95% CI 0.46-0.60) were less likely to use prosthetic reconstruction and more likely to use free-transfer autologous reconstruction (OR 1.66, 95% CI 1.26-2.18 for Hispanics, OR 2.13, 95% CI 1.73-2.63 for blacks), all P < 0.001. Racial disparities persisted from 2005-2011; as minority patients were less likely to undergo IBR than whites (P < 0.001). Conclusions: Utilization of IBR may be a sensitive measure of disparities in access to highquality care and underlying cultures. Strategies aimed at reducing racial disparities in IBR should be tailored to specific patterns of disparities among Asian, black, and Hispanic women. (C) 2015 Elsevier Inc. All rights reserved. C1 [Offodile, Anaeze C., II; Guo, Lifei] Lahey Hosp & Med Ctr, Dept Plast Surg, Burlington, MA 01805 USA. [Tsai, Thomas C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Tsai, Thomas C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Wenger, Julia B.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Guo, LF (reprint author), Lahey Hosp & Med Ctr, Dept Plast Surg, 41 Mall Rd, Burlington, MA 01805 USA. EM Lifei.guo@lahey.org FU National Cancer Institute (NCI) [R25CA92203] FX This study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. The American College of Surgeons National Surgical Quality Improvement Program and the hospitals participating in the ACS NSQIP are the source of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors. T.C.T. was also supported by grant R25CA92203 from the National Cancer Institute (NCI). NR 29 TC 5 Z9 5 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 MAY 1 PY 2015 VL 195 IS 1 BP 368 EP 376 DI 10.1016/j.jss.2015.01.013 PG 9 WC Surgery SC Surgery GA CE9CA UT WOS:000352139900047 PM 25676466 ER PT J AU Shi, YX Lo, CS Padda, R Abdo, S Chenier, I Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Shi, Yixuan Lo, Chao-Sheng Padda, Ranjit Abdo, Shaaban Chenier, Isabelle Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao-Ling Chan, John S. D. TI Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice SO CLINICAL SCIENCE LA English DT Article DE angiotensin-(1-7); diabetic mouse; kidney injury; oxidative stress ID CARBOXYPEPTIDASE; HOMOLOG; ACE2 AB We investigated the relationship between Ang-(1-7) [angiotensin-(1-7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1-7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1-7) was administered daily [500 mu g/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1-7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1-7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-beta 1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1-7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression. C1 [Shi, Yixuan; Lo, Chao-Sheng; Padda, Ranjit; Abdo, Shaaban; Chenier, Isabelle; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, CRCHUM, Montreal, PQ H2X 0A9, Canada. [Filep, Janos G.] Univ Montreal, Maisonneuve Rosemont Hosp, Ctr Rech, Montreal, PQ H1T 2M4, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, CRCHUM, 900 St Denis St, Montreal, PQ H2X 0A9, Canada. EM john.chan@umontreal.ca FU Kidney Foundation of Canada [KFOC120008]; Canadian Institutes of Health Research [MOP-93650, MOP-106688, MOP-86450, MOP-97742]; National Institutes of Health (NIH) of the U.S.A [HL-48455]; Foundation of the CHUM (Centre hospitalier de l'Universite de Montreal) FX This work was supported in part by the Kidney Foundation of Canada [grant number KFOC120008 (to J.S.D.C.)], the Canadian Institutes of Health Research [grant numbers MOP-93650 and MOP-106688 (to J.S.D.C.), MOP-86450 (to S.L.Z.) and MOP-97742 (to J.G.F.)], the National Institutes of Health (NIH) of the U.S.A. [grant number HL-48455 (to J.R.I.)] and the Foundation of the CHUM (Centre hospitalier de l'Universite de Montreal). NR 7 TC 12 Z9 13 U1 1 U2 11 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0143-5221 EI 1470-8736 J9 CLIN SCI JI Clin. Sci. PD MAY PY 2015 VL 128 IS 10 BP 649 EP 663 DI 10.1042/CS20140329 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CE2CF UT WOS:000351619900003 PM 25495544 ER PT J AU Mayer, EL AF Mayer, Erica L. TI Targeting Breast Cancer with CDK Inhibitors SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Breast cancer; Hormone-receptor positive; Cell cycle; CDK inhibition; Palbociclib; Abemaciclib; LEE011 ID DEPENDENT KINASE INHIBITOR; HUMAN TUMOR XENOGRAFTS; PD 0332991; ANTITUMOR-ACTIVITY; ESTROGEN-RECEPTOR; PHASE-I; CYCLIN; THERAPY; EXPRESSION; LY2835219 AB Dysregulation of the cell cycle is a classic hallmark of cancer growth and metastatic potential. Re-establishing cell cycle control through CDK inhibition has emerged as an attractive option in the development of targeted cancer therapy. Three oral agents selectively targeting CDK4/6 have been developed: palbociclib, abemaciclib, and LEE011. Preclinical models show optimal activity in hormone receptor positive breast cancer, which may display biologic features suggesting particular dependence on the CDK4/cyclin D1/Rb interaction. Palbociclib has been studied in a randomized phase 2 clinical trial in metastatic hormone receptor positive breast cancer in which the combination of palbociclib and endocrine therapy significantly prolonged progression-free survival over endocrine therapy alone. The toxicity profile of palbociclib and the other CDK 4/6 inhibitors in early phase I and II trials has been predominantly hematologic, characterized by limited neutropenia, as well as variable gastrointestinal toxicity. Multiple phase II and III studies are ongoing with all three agents, and are designed to explore the role of CDK 4/6 inhibition in metastatic hormone receptor positive breast cancer. The next wave of studies will examine further clinical and scientific topics, including the role of CDK 4/6 inhibition in the neo/adjuvant setting, the combination of CDK 4/6 inhibitors with other targeted therapies, and the activity of CDK 4/6 inhibitors in the HER2 positive subset of breast cancer, as well as in other cancer subtypes. Should ongoing study confirm benefits and tolerability of CDK 4/6 inhibition, combination therapy with endocrine agents may become a new standard of care for hormone receptor positive breast cancer. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Susan F Smith Ctr Womens Canc, Boston, MA 02215 USA. RP Mayer, EL (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Susan F Smith Ctr Womens Canc, Boston, MA 02215 USA. EM erica_mayer@dfci.harvard.edu NR 32 TC 8 Z9 9 U1 1 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD MAY PY 2015 VL 17 IS 5 AR 20 DI 10.1007/s11912-015-0443-3 PG 5 WC Oncology SC Oncology GA CE8QK UT WOS:000352108600002 ER PT J AU DeLisi, LE Fleischhacker, WW AF DeLisi, Lynn E. Fleischhacker, W. Wolfgang TI The problem of substance abuse in people with schizophrenia SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material ID CANNABIS USE; FOLLOW-UP; PSYCHOSIS; BRAIN; ONSET; AGE; COHORT; USERS; RISK C1 [DeLisi, Lynn E.; Fleischhacker, W. Wolfgang] Harvard Univ, Sch Med, Brockton, MA 02301 USA. RP DeLisi, LE (reprint author), VA Boston Healthcare Syst, 940 Belmont Ave, Brockton, MA 02301 USA. EM Lynn_DeLisi@hms.harvard.edu; wolfgang.fleischhacker@i-med.ac.at NR 22 TC 1 Z9 1 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0951-7367 EI 1473-6578 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2015 VL 28 IS 3 BP 199 EP 200 DI 10.1097/YCO.0000000000000150 PG 2 WC Psychiatry SC Psychiatry GA CE4AB UT WOS:000351771300001 PM 25714896 ER PT J AU OConghaile, A DeLisi, LE AF OConghaile, Aengus DeLisi, Lynn E. TI Distinguishing schizophrenia from posttraumatic stress disorder with psychosis SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE posttraumatic stress disorder; psychosis; schizophrenia; trauma ID SEVERE MENTAL-ILLNESS; 1ST-EPISODE PSYCHOSIS; CHILDHOOD TRAUMA; ATYPICAL ANTIPSYCHOTICS; AUDITORY HALLUCINATIONS; NEGATIVE SYMPTOMS; COMBAT VETERANS; PTSD SYMPTOMS; DOUBLE-BLIND; ASSOCIATION AB Purpose of review Co-occurrence of psychotic symptoms with symptoms typically thought of as posttraumatic stress disorder (PTSD) is well known, and there has been considerable debate whether this represents a psychotic subtype or a comorbid psychotic disorder. Recent findings Psychotic symptoms typical of schizophrenia occur with a higher than expected frequency in PTSD. A large genome-wide association study (GWAS) has identified a collection of genes associated with PTSD, and these genes overlap with those identified as increasing the risk of developing schizophrenia. Summary Up to 70% of returning veterans experience symptoms of PTSD. These individuals also fall within the peak age range for the onset of schizophrenia. PTSD with psychosis may occur for several reasons: trauma increases one's risk for schizophrenia and PTSD; patients with schizophrenia have a higher incidence of PTSD and may present with characteristic psychotic symptoms overlapping with psychosis in schizophrenia. Secondary to symptom overlap, there may be substantial misdiagnosis of psychotic disorders as PTSD, or nonidentification of a comorbid psychotic disorder. This overlap calls into question traditional diagnostic boundaries with implications for initial and long-term treatment of PTSD and psychosis. This review will discuss the recent literature relating to the association of PTSD with schizophrenia. C1 [OConghaile, Aengus; DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA USA. [OConghaile, Aengus] Harvard Southshore Residency Training Program, Brockton, MA USA. [OConghaile, Aengus; DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. RP OConghaile, A (reprint author), VA Med Ctr, Bldg 5,940 Belmont St, Brockton, MA 02301 USA. EM Aengus.oconghaile@gmail.com FU AMGEN, a biopharmaceutical company FX L.D. is in receipt of a research grant to complete a study on the genetics of schizophrenia, sponsored by AMGEN, a biopharmaceutical company. There are no conflicts of interest. NR 75 TC 6 Z9 6 U1 12 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0951-7367 EI 1473-6578 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2015 VL 28 IS 3 BP 249 EP 255 DI 10.1097/YCO.0000000000000158 PG 7 WC Psychiatry SC Psychiatry GA CE4AB UT WOS:000351771300009 PM 25785709 ER PT J AU Drozdovitch, V Brill, AB Callahan, RJ Clanton, JA DePietro, A Goldsmith, SJ Greenspan, BS Gross, MD Hays, MT Moore, SC Ponto, JA Shreeve, WW Melo, DR Linet, MS Simon, SL AF Drozdovitch, Vladimir Brill, Aaron B. Callahan, Ronald J. Clanton, Jeffrey A. DePietro, Allegra Goldsmith, Stanley J. Greenspan, Bennett S. Gross, Milton D. Hays, Marguerite T. Moore, Stephen C. Ponto, James A. Shreeve, Walton W. Melo, Dunstana R. Linet, Martha S. Simon, Steven L. TI USE OF RADIOPHARMACEUTICALS IN DIAGNOSTIC NUCLEAR MEDICINE IN THE UNITED STATES: 1960-2010 SO HEALTH PHYSICS LA English DT Article DE diagnostic imaging; nuclear medicine; radiation, medical; radiopharmaceuticals ID LOWER GASTROINTESTINAL HEMORRHAGE; RED-BLOOD-CELLS; IN-111 CAPROMAB PENDETIDE; RADIOLOGIC TECHNOLOGISTS; TC-99M PYROPHOSPHATE; COMPUTED-TOMOGRAPHY; PULMONARY EMBOLISM; TECHNETIUM TC-99M; PROSTATE-CANCER; SCANNING AGENT AB To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations. C1 [Drozdovitch, Vladimir; Linet, Martha S.; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Brill, Aaron B.] Vanderbilt Univ, Radiol & Radiol Sci, Nashville, TN 37235 USA. [Callahan, Ronald J.; DePietro, Allegra] Massachusetts Gen Hosp, Boston, MA USA. [Clanton, Jeffrey A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Goldsmith, Stanley J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA. [Greenspan, Bennett S.] Univ Missouri, Columbia Nucl Med Program, Columbia, MO USA. [Gross, Milton D.] Dept Vet Affairs Hlth Syst, Nucl Med & Radiat Serv, Ann Arbor, MI USA. [Hays, Marguerite T.] Dept Vet Affairs Hlth Syst, Palo Alto, CA USA. [Moore, Stephen C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ponto, James A.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Shreeve, Walton W.] Vet Affairs Northport, Long Isl City, NY USA. [Melo, Dunstana R.] Lovelace Resp Res Inst, Ctr Countermeasures Radiat, Albuquerque, NM USA. RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 9609 Med Ctr Dr,Room 7E548 MSC 9778, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. Special thanks to Fred A. Mettler Jr. (New Mexico VA Health Care System, Albuquerque, NM) for his participation in the survey and for comments on our manuscript. NR 126 TC 3 Z9 3 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2015 VL 108 IS 5 BP 520 EP 537 DI 10.1097/HP.0000000000000261 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CE5PP UT WOS:000351887900005 PM 25811150 ER PT J AU Pantalone, DW Horvath, KJ Hart, TA Valentine, SE Kaysen, DL AF Pantalone, David W. Horvath, Keith J. Hart, Trevor A. Valentine, Sarah E. Kaysen, Debra L. TI Traumatic Revictimization of Men Who Have Sex With Men Living With HIV/AIDS SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE revictimization; HIV; AIDS; men who have sex with men; childhood abuse; adult abuse ID BISEXUAL MEN; PHYSICAL ABUSE; DRUG-USE; RISK BEHAVIORS; SUBSTANCE USE; HEALTH; VICTIMIZATION; GAY; EXPERIENCES; HIV AB Abuse in childhood has been established as a predictor of adult abuse, with the strongest associations found between childhood sexual abuse (CSA) and adult sexual victimization. Revictimization has been demonstrated among women, and there is a growing literature on revictimization experiences among men who have sex with men (MSM). No studies have assessed revictimization among MSM living with HIV, despite strong evidence for disproportionately high rates of life span abuse among this group, along with the added vulnerability of living with HIV and sexual minority stress. In this study, we contribute to the literature by exploring associations between multiple types of childhood and adult abuse experiences (physical, sexual, and psychological; perpetrated by partners and non-partner), rather than examining sexual victimization alone. A sample of 166 HIV-positive MSM attending primary HIV health care clinics in Seattle, Washington, completed a one-time questionnaire. Results of regression analyses revealed associations between experiencing CSA and adult sexual abuse, and experiencing childhood physical abuse and adult physical and sexual abuse. Childhood psychological abuse was associated with adult physical and psychological abuse and partner psychological abuse. At higher frequencies, childhood psychological abuse was associated with all forms of adult abuse. These findings suggest that various forms of childhood abuse experiences confer broad vulnerability to adult abuse experiences and point to potentially different pathways to revictimization based on childhood abuse type. C1 [Pantalone, David W.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Pantalone, David W.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Horvath, Keith J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Hart, Trevor A.] Ryerson Univ, Appl HIV Res, Toronto, ON, Canada. [Hart, Trevor A.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Hart, Trevor A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Valentine, Sarah E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kaysen, Debra L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Pantalone, DW (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM david.pantalone@umb.edu OI Hart, Trevor/0000-0001-5107-7452 FU National Institute of Mental Health [F31 MH71179]; Robert C. Bolles Research Fund of the University of Washington; Ontario HIV Treatment Network FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by a National Institute of Mental Health award (F31 MH71179) and a small grant from the Robert C. Bolles Research Fund of the University of Washington, both awarded to the first author under the mentorship of Dr. Jane Simoni. T. A. Hart is funded by a Career Scientist Award from the Ontario HIV Treatment Network. NR 47 TC 1 Z9 1 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 EI 1552-6518 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD MAY PY 2015 VL 30 IS 9 BP 1459 EP 1477 DI 10.1177/0886260514540802 PG 19 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA CE7FR UT WOS:000352003900001 PM 24989040 ER PT J AU Abla, O Weitzman, S Chellapandian, D Abuhadra, N Carret, AS Astigarraga, I Jubran, R Chang, T Degar, B Mandel, K van den Bos, C Belletrutti, M Dix, D Visser, J Whitlock, J Shaikh, F AF Abla, Oussama Weitzman, Sheila Chellapandian, Deepakbabu Abuhadra, Nour Carret, Anne-Sophie Astigarraga, Itziar Jubran, Rima Chang, Tiffany Degar, Barbara Mandel, Karen van den Bos, Cor Belletrutti, Mark Dix, David Visser, Johann Whitlock, James Shaikh, Furqan TI MANAGEMENT AND OUTCOME OF PATIENTS WITH LANGERHANS CELL HISTIOCYTOSIS AND SINGLE-BONE CNS-RISK LESIONS: A MULTI-INSTITUTIONAL RETROSPECTIVE DESCRIPTIVE STUDY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Abla, Oussama; Weitzman, Sheila; Chellapandian, Deepakbabu; Abuhadra, Nour; Whitlock, James; Shaikh, Furqan] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Carret, Anne-Sophie] Univ Montreal, CHU St Justine, Montreal, PQ, Canada. [Astigarraga, Itziar] Hosp Univ Cruces, Baracaldo, Bizkaia, Spain. [Jubran, Rima; Chang, Tiffany] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Degar, Barbara] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mandel, Karen] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [van den Bos, Cor] Emma Childrens Hosp, Acad Med Ctr, Amsterdam, Netherlands. [Belletrutti, Mark] Stollery Childrens Hosp, Edmonton, AB, Canada. [Dix, David] British Columbia Childrens Hosp, Vancouver, BC, Canada. [Visser, Johann] Leicester Childrens Hosp, Leicester, Leics, England. RI Chellapandian, Deepak/F-6225-2017 OI Chellapandian, Deepak/0000-0003-3518-9790 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2015 VL 62 SU 1 BP S1 EP S1 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CE2VZ UT WOS:000351680100002 ER PT J AU Perez, HCS Ikram, MA Direk, N Prigerson, HG Freak-Poli, R Verhaaren, BFJ Hofman, A Vernooij, M Tiemeier, H AF Perez, H. C. Saavedra Ikram, M. A. Direk, N. Prigerson, H. G. Freak-Poli, R. Verhaaren, B. F. J. Hofman, A. Vernooij, M. Tiemeier, H. TI Cognition, structural brain changes and complicated grief. A population-based study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Brain lesions; cognitive performance; cognitive tests; complicated grief; normal grief; structural brain volumes ID GENERAL ELDERLY POPULATION; OLDER-ADULTS; BEREAVED PARENTS; PHYSICAL HEALTH; ROTTERDAM SCAN; LATE-LIFE; DEPRESSION; DISORDER; SAMPLE; ATTENTION AB Background. Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. Method. The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. Results. Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). Conclusions. Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population. C1 [Perez, H. C. Saavedra; Ikram, M. A.; Direk, N.; Freak-Poli, R.; Verhaaren, B. F. J.; Hofman, A.; Vernooij, M.; Tiemeier, H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. A.; Verhaaren, B. F. J.; Vernooij, M.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Prigerson, H. G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, H. G.] Harvard Univ, Sch Med, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA USA. [Prigerson, H. G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care, Boston, MA 02115 USA. [Freak-Poli, R.] Monash Univ, Dept Epidemiol & Prevent Med, Fac Med Nursing & Hlth Sci, Melbourne, Vic 3004, Australia. [Tiemeier, H.] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Tiemeier, H.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. RP Tiemeier, H (reprint author), Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. EM h.tiemeier@erasmusmc.nl OI Freak-Poli, Rosanne/0000-0003-4072-8699; Tiemeier, Henning/0000-0002-4395-1397 FU Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Netherlands Genomics Initiative; Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission (DGXII); Erasmus Columbus (ERACOL) grant; National Health and Medical Research Council (NHMRC) [1053666]; ZonMw [2009-017.106.370] FX The Rotterdam Study is supported by: the Erasmus Medical Center and the Erasmus University Rotterdam; The Netherlands Organization for Scientific Research (NWO); The Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; and the European Commission (DGXII). H.C.S.P was supported by an Erasmus Columbus (ERACOL) grant. R.F.-P. is supported by a National Health and Medical Research Council (NHMRC) Early Career (ECR) Fellowship (1053666). H.T. was supported by the Vidi grant of ZonMw (2009-017.106.370). The funders had no role in the study design or data collection and analysis. The authors report no competing interests. We want to thank all the persons who contributed to this paper. NR 49 TC 2 Z9 2 U1 3 U2 18 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2015 VL 45 IS 7 BP 1389 EP 1399 DI 10.1017/S0033291714002499 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CE6BF UT WOS:000351920000004 ER PT J AU Colson, K AF Colson, Kathleen TI Treatment-related symptom management in patients with multiple myeloma: a review SO SUPPORTIVE CARE IN CANCER LA English DT Review DE Multiple myeloma; Symptom management; Supportive care; Quality of life; Proteasome inhibitors; Immunomodulatory agents ID STEM-CELL TRANSPLANTATION; NURSE LEADERSHIP BOARD; LOW-DOSE DEXAMETHASONE; PERIPHERAL NEUROPATHY; PROTEASOME INHIBITORS; BORTEZOMIB RETREATMENT; DEACETYLASE INHIBITORS; RISK REDUCTION; VANTAGE 088; LENALIDOMIDE AB Recent therapeutic advancements have significantly improved overall survival of patients with multiple myeloma (MM). As a result, the impact of disease- and treatment-related symptoms must be managed effectively to improve patient quality of life, given prolonged survival after diagnosis. This review discusses current MM treatment options, effective symptom management approaches, and practical strategies for supportive care. A literature search was performed using MEDLINE/PubMed and scientific congress databases, focusing on clinical trials, review articles, clinical practice guidelines, and other guidance documents on treatment paradigms and supportive care strategies in MM. Additionally, clinical practice worksheets were developed from published sources, and nursing "pearls of wisdom" were gathered from practical experience in the clinic. Current therapeutic regimens for relapsed/refractory MM include proteasome inhibitors (i.e., bortezomib, carfilzomib) and immunomodulatory agents (i.e., thalidomide, lenalidomide, pomalidomide), alone or in combination with chemotherapy or corticosteroids. Toxicities associated with agents and combination regimens used in the treatment of MM include myelosuppression, venous thromboembolism, peripheral neuropathy, infections, fatigue, gastrointestinal disorders, and/or cardiac events. Treatment-specific tools and clinical assessments can be useful for optimizing dosing and schedule adjustments to increase therapy duration, and implementing supportive care strategies (e.g., growth factors, transfusional support, intravenous hydration, bisphosphonates, antiviral therapies) to manage treatment-related symptoms. Improved survival after MM diagnosis has led to increased patient susceptibility to other diseases and comorbidities due to advanced age. In addition to appropriate drug dosing and administration, effective supportive care and health maintenance are crucial for maximizing quality of life and disease control. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Colson, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 216, Boston, MA 02215 USA. EM Kathleen_Colson@dfci.harvard.edu FU Novartis Pharmaceuticals Corporation FX William H. Fazzone, PhD, Amanda L. Kauffman, PhD, and Peter J. Simon, PhD, provided medical editorial assistance with this manuscript that was financially supported by Novartis Pharmaceuticals Corporation. NR 97 TC 5 Z9 5 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 2015 VL 23 IS 5 BP 1431 EP 1445 DI 10.1007/s00520-014-2552-1 PG 15 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA CE9CJ UT WOS:000352140900027 PM 25646616 ER PT J AU Desai, RM Koshy, ST Hilderbrand, SA Mooney, DJ Joshi, NS AF Desai, Rajiv M. Koshy, Sandeep T. Hilderbrand, Scott A. Mooney, David J. Joshi, Neel S. TI Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry SO BIOMATERIALS LA English DT Article DE Alginate; Hydrogel; Click chemistry; Cell adhesion; Cell encapsulation; Tissue engineering ID POLY(ALDEHYDE GULURONATE) HYDROGELS; MESENCHYMAL STEM-CELLS; IN-VITRO; MECHANICAL-PROPERTIES; DELIVERY-SYSTEMS; DEGRADATION; ENCAPSULATION; LINKING; GELS; MICROENVIRONMENTS AB Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedical applications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinked alginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lack of chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymer chains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulating cells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible and allows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanical properties of the click alginate hydrogel can be tuned via the total polymer concentration and the stoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can be modified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry. Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity over several months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogels combine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistry for use in tissue engineering applications involving the stable encapsulation or delivery of cells or bioactive molecules. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Desai, Rajiv M.; Koshy, Sandeep T.; Mooney, David J.; Joshi, Neel S.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Desai, Rajiv M.; Koshy, Sandeep T.; Mooney, David J.; Joshi, Neel S.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Koshy, Sandeep T.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hilderbrand, Scott A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Hilderbrand, Scott A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu; njoshi@seas.harvard.edu OI Koshy, Sandeep/0000-0003-2836-5813; Joshi, Neel/0000-0001-8236-3566 FU Army Research Office [W911NF-13-1-0242]; NIH [R01 DE013349] FX This work was supported by the Army Research Office (W911NF-13-1-0242) and the NIH (R01 DE013349). This work was performed in part at the MGH Center for Systems Biology. The authors would like to acknowledge the help of Olivier Kister, Kaixiang Lin, and Chris Johnson for material synthesis and troubleshooting. The authors would also like to thank Dr. Luo Gu, Dr. Ovijit Chaudhuri, Daniel Rubin, Alexander Cheung, Dr. Catia Verbeke, Zsofia Botiyanski, Ajay Parmar, and Max Darnell for scientific discussions. NR 55 TC 26 Z9 27 U1 23 U2 242 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 MAY PY 2015 VL 50 BP 30 EP 37 DI 10.1016/j.biomaterials.2015.01.048 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CE2OX UT WOS:000351656000004 PM 25736493 ER PT J AU Ren, X Bischoff, D Weisgerber, DW Lewis, MS Tu, V Yamaguchi, DT Miller, TA Harley, BAC Lee, JC AF Ren, Xiaoyan Bischoff, David Weisgerber, Daniel W. Lewis, Michael S. Tu, Victor Yamaguchi, Dean T. Miller, Timothy A. Harley, Brendan A. C. Lee, Justine C. TI Osteogenesis on nanoparticulate mineralized collagen scaffolds via autogenous activation of the canonical BMP receptor signaling pathway SO BIOMATERIALS LA English DT Article DE Osteogenesis; Biomimetic material; Nanoparticulate mineralization; BMP ID BONE MORPHOGENETIC PROTEIN-2; MESENCHYMAL STEM-CELLS; CALCIUM-PHOSPHATE; CRANIAL DEFECTS; COMPOSITE; DIFFERENTIATION; COMPLICATIONS; CRANIOPLASTY; FUSION; FAMILY AB Skeletal regenerative medicine frequently incorporates deliverable growth factors to stimulate osteogenesis. However, the cost and side effects secondary to supraphysiologic dosages of growth factors warrant investigation of alternative methods of stimulating osteogenesis for clinical utilization. In this work, we describe growth factor independent osteogenic induction of human mesenchymal stem cells (hMSCs) on a novel nanoparticulate mineralized collagen glycosaminoglycan scaffold (MC-GAG). hMSCs demonstrated elevated osteogenic gene expression and mineralization on MC-GAG with minimal to no effect upon addition of BMP-2 when compared to non-mineralized scaffolds (Col-GAG). To investigate the intracellular pathways responsible for the increase in osteogenesis, we examined the canonical and non-canonical pathways downstream from BMP receptor activation. Constitutive Smad1/5 phosphorylation with nuclear translocation occurred on MC-GAG independent of BMP-2, whereas Smad1/5 phosphorylation depended on BMP-2 stimulation on Col-GAG. When non-canonical BMPR signaling molecules were examined, ERK1/2 phosphorylation was found to be decreased in MC-GAG but elevated in Col-GAG. No differences in Smad2/3 or p38 activation were detected. Collectively, these results demonstrated that MC-GAG scaffolds induce osteogenesis without exogenous BMP-2 addition via endogenous activation of the canonical BMP receptor signaling pathway. Published by Elsevier Ltd. C1 [Ren, Xiaoyan; Tu, Victor; Miller, Timothy A.; Lee, Justine C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, Los Angeles, CA 90095 USA. [Ren, Xiaoyan; Tu, Victor; Miller, Timothy A.; Lee, Justine C.] Greater Angeles VA Healthcare Syst, Div Plast & Reconstruct Surg, Los Angeles, CA 90073 USA. [Bischoff, David; Yamaguchi, Dean T.] Greater Angeles VA Healthcare Syst, Res Serv, Los Angeles, CA USA. [Weisgerber, Daniel W.; Harley, Brendan A. C.] Univ Illinois, Inst Genom Biol, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Lewis, Michael S.] Greater Los Angeles VA Healthcare Syst, Dept Pathol, Los Angeles, CA USA. RP Lee, JC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, 200 UCLA Med Plaza,Suite 465, Los Angeles, CA 90095 USA. EM justine@ucla.edu OI Harley, Brendan/0000-0001-5458-154X FU Merit Review Grant - U.S. Department of Veterans Affairs [1I01BX001367-01A2]; Jean Perkins Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R21 AR063331]; National Science Foundation (NSF) [0965918] FX This work was supported by a Merit Review Grant (1I01BX001367-01A2) awarded by the U.S. Department of Veterans Affairs (TAM) and the Jean Perkins Foundation (JCL). Research reported in this publication was also supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R21 AR063331 (BACH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. DWW was funded at UIUC from National Science Foundation (NSF) Grant 0965918 IGERT: Training the Next Generation of Researchers in Cellular & Molecular Mechanics and BioNanotechnology. NR 43 TC 11 Z9 12 U1 5 U2 38 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 MAY PY 2015 VL 50 BP 107 EP 114 DI 10.1016/j.biomaterials.2015.01.059 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CE2OX UT WOS:000351656000012 PM 25736501 ER PT J AU Schafer, AL Li, X Schwartz, AV Tufts, LS Wheeler, AL Grunfeld, C Stewart, L Rogers, SJ Carter, JT Posselt, AM Black, DM Shoback, DM AF Schafer, A. L. Li, X. Schwartz, A. V. Tufts, L. S. Wheeler, A. L. Grunfeld, C. Stewart, L. Rogers, S. J. Carter, J. T. Posselt, A. M. Black, D. M. Shoback, D. M. TI Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study SO BONE LA English DT Article DE Bone marrow fat; Bariatric surgery; Gastric bypass surgery; Diabetes ID ADIPOSE-TISSUE; MINERAL DENSITY; WEIGHT-LOSS; CALORIC RESTRICTION; BARIATRIC SURGERY; ANOREXIA-NERVOSA; FRACTURE RISK; OLDER-ADULTS; WOMEN; DXA AB Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean +/- SD decline 19.1 +/- 6.1 kg or 36.5% +/- 10.9%, p <0.001), Areal bone mineral density (BMD) decreased by 5.2% +/- 3.5% and 4.1% +/- 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% +/- 2.8% (p <0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p = 0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% Cl - 10.0 to + 11.7%, p = 0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% Cl - 152 to +0.1%, p = 0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r = -0.96, p = 0.01) but not diabetic (r = 0.52, p = 0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. Published by Elsevier Inc. C1 [Schafer, A. L.; Wheeler, A. L.; Grunfeld, C.; Shoback, D. M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Li, X.; Tufts, L. S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Schwartz, A. V.; Black, D. M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Stewart, L.; Rogers, S. J.; Carter, J. T.; Posselt, A. M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Schafer, A. L.; Wheeler, A. L.; Grunfeld, C.; Shoback, D. M.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Stewart, L.] San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. RP Schafer, AL (reprint author), 1700 Owens St,Room 367, San Francisco, CA 94158 USA. EM anne.schafer@ucsf.edu OI Wheeler, Amber/0000-0002-9926-1301 FU Department of Veterans Affairs, VHA, CSRD Service [CDA-2 5 IK2 CX000549-04]; UCSF Diabetes Center; National Center for Advancing Translational Science of the National Institutes of Health through UCSF-CTSI [UL1 TR000004]; NIH [5 K12 HD052163-15] FX Grant support: The research described here was supported by the Department of Veterans Affairs, VHA, CSR&D Service (CDA-2 5 IK2 CX000549-04, to ALS, SFVAMC) and by a pilot and feasibility grant with funds provided by the UCSF Diabetes Center. Additional support was provided by the National Center for Advancing Translational Science of the National Institutes of Health through UCSF-CTSI Grant UL1 TR000004, and by NIH grant 5 K12 HD052163-15. Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Calcium citrate supplements were supplied by Bariatric Advantage. NR 36 TC 17 Z9 17 U1 1 U2 2 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 MAY PY 2015 VL 74 BP 140 EP 145 DI 10.1016/j.bone.2015.01.010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD6HE UT WOS:000351189400017 PM 25603463 ER PT J AU Joseph, J Loscalzo, J AF Joseph, Jacob Loscalzo, Joseph TI Nutri(meta)genetics and Cardiovascular Disease: Novel Concepts in the Interaction of Diet and Genomic Variation SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Genetic variation; Genome; Microbiome; Metagenome; Nutrition; Trimethylamine oxide; Choline; Phosphatidyl choline; Betaine; Flavin monooxygenase; Cardiovascular risk; Obesity; Diabetes; Atherosclerosis; Homocysteine; B vitamins ID INFLAMMATORY-BOWEL-DISEASE; TRIMETHYLAMINE-N-OXIDE; HUMAN GUT MICROBIOTA; GERM-FREE MICE; INTESTINAL MICROBIOTA; SYSTEMS BIOLOGY; OXYGEN-CONSUMPTION; WIDE ASSOCIATION; L-CARNITINE; FOLIC-ACID AB In addition to the interaction of nutrition and genetic variation on the genesis and natural history of cardiovascular disease, recent studies have revealed an entire new genome that resides in the trillions of microbes that exist in various human habitats, predominantly in the gut, that may also contribute to the pathogenesis of cardiovascular disease. This microbial genome and the proteins for which it codes have important functions in homeostatic adaptations to the past and present changes in diet and environment accompanying human civilization. Both preclinical and clinical investigations suggest the role of commensal microbiota in promoting adverse cardiovascular risk. Specifically, microbial metabolism of methylated amines leads to direct pro-atherogenic effects in humans. Further investigations are needed to understand the complex relationships among nutritional status, genetic variation, and the microbial genome, which may explain the recent negative results of clinical trials of nutritional interventions such as B vitamin therapy to lower plasma homocysteine levels. The results of such contemporary genomic investigations would allow us to utilize personalized nutritional interventions to reduce cardiovascular risk. C1 [Joseph, Jacob; Loscalzo, Joseph] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Joseph, Jacob] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Joseph, Jacob] Brigham & Womens Hosp, NRB, Boston, MA 02115 USA. RP Loscalzo, J (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM jjoseph16@partners.org; jloscalzo@partners.org FU NIH [R37 HL 061795, U01 HG007690, HL048743] FX This work was supported by NIH grants R37 HL 061795, U01 HG007690, and HL048743. NR 59 TC 2 Z9 2 U1 2 U2 21 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD MAY PY 2015 VL 17 IS 5 AR 29 DI 10.1007/s11883-015-0505-x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE0BR UT WOS:000351468300007 PM 25782777 ER PT J AU Man, LC Kelly, E Duffy, D AF Man, Lillian C. Kelly, Erik Duffy, Danielle TI Targeting Lipoprotein (a): an Evolving Therapeutic Landscape SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Lipoprotein (a); Cardiovascular disease; Apolipoprotein (a); Nicotinic acid; Apheresis; Antisense oligonucleotides ID CORONARY-HEART-DISEASE; TRIGLYCERIDE TRANSFER PROTEIN; LOW-DENSITY-LIPOPROTEIN; HORMONE REPLACEMENT THERAPY; ELEVATED LDL CHOLESTEROL; ESTROGEN PLUS PROGESTIN; SUBTILISIN/KEXIN TYPE 9; CARDIOVASCULAR-DISEASE; OXIDIZED PHOSPHOLIPIDS; LP(A) LIPOPROTEIN AB Robust epidemiologic and genetic studies have solidified the role of lipoprotein (a) [Lp(a)] as an independent and causal risk factor for cardiovascular disease. The increased cardiovascular risk of Lp(a) is mediated through both proatherogenic and prothrombotic/antifibrinolytic mechanisms. Several societies recommend Lp(a) screening for patients with high cardiovascular risk, although no consensus exists on the management of patients with elevated Lp(a). However, numerous pharmacologic approaches are being evaluated that have the potential to reduce Lp(a) and will be the focus of this review. The majority of these interventions have been developed for other lipid-lowering indications, but also lower Lp(a). There are also novel therapies in development that specifically target Lp(a). The efficacy of these therapies varies, and their role in the evolving lipoprotein therapeutic landscape has yet to be determined. Nevertheless, targeted Lp(a) reduction is certainly intriguing and will likely continue to be an active area of investigation in the future. C1 [Man, Lillian C.] Thomas Jefferson Univ Hosp, Dept Med, Philadelphia, PA 19107 USA. [Kelly, Erik] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Duffy, Danielle] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Div Cardiol, Philadelphia, PA 19107 USA. RP Duffy, D (reprint author), Thomas Jefferson Univ, Sidney Kimmel Med Coll, Div Cardiol, 925 Chestnut St, Philadelphia, PA 19107 USA. EM Danielle.duffy@jefferson.edu FU Amgen; Forest Laboratories; Regeneron Pharmaceuticals; Aegerion Pharmaceuticals; Roche/Genentech; AstraZeneca; Genzyme FX Danielle Duffy received grants from Amgen, Forest Laboratories, Regeneron Pharmaceuticals, Aegerion Pharmaceuticals and Roche/Genentech; personal fees from AstraZeneca and Genzyme; and serves on the Board of Directors for Northeast Lipid Association and Southeastern Pennsylvania Chapter of the American Heart Association. NR 86 TC 1 Z9 1 U1 0 U2 6 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD MAY PY 2015 VL 17 IS 5 AR 25 DI 10.1007/s11883-015-0502-0 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CE0BR UT WOS:000351468300003 ER PT J AU Martin, D Nakagawa, T Siebelink, M Bramstedt, K Brierley, J Dobbels, F Rodrigue, J Sarwal, M Shapiro, R Dominguez-Gil, B Bos, M Delmonico, F AF Martin, D. Nakagawa, T. Siebelink, M. Bramstedt, K. Brierley, J. Dobbels, F. Rodrigue, J. Sarwal, M. Shapiro, R. Dominguez-Gil, B. Bos, M. Delmonico, F. TI RECOMMENDATIONS ON PAEDIATRIC DECEASED DONATION: A REPORT OF THE TRANSPLANTATION SOCIETY GENEVA MEETING SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 [Martin, D.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Nakagawa, T.] Wake Forest Sch Med, Winston Salem, NC USA. [Siebelink, M.] Univ Groningen, Groningen, Netherlands. [Bramstedt, K.] Bond Univ, Gold Coast, Australia. [Brierley, J.] Greater Ormond St Hosp, London, England. [Dobbels, F.] Univ Leuven, Leuven, Belgium. [Rodrigue, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sarwal, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shapiro, R.] Univ Pittsburgh, Pittsburgh, PA USA. [Dominguez-Gil, B.] Org Nacl Trasplantes, Madrid, Spain. [Bos, M.] Transplantat Soc, Montreal, PQ, Canada. [Delmonico, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 1397-3142 EI 1399-3046 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD MAY PY 2015 VL 19 SU 1 SI SI MA P15 BP 106 EP 106 PG 1 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA CE2GP UT WOS:000351633200125 ER PT J AU Uchida, M Serra, G Zayas, L Kenworthy, T Faraone, SV Biederman, J AF Uchida, Mai Serra, Giulia Zayas, Lazaro Kenworthy, Tara Faraone, Stephen V. Biederman, Joseph TI Can unipolar and bipolar pediatric major depression be differentiated from each other? A systematic review of cross-sectional studies examining differences in unipolar and bipolar depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Bipolar disorder; Major depressive disorder; Pediatric ID CONDUCT DISORDER; CLINICAL CHARACTERISTICS; MOOD DISORDERS; FOLLOW-UP; ADOLESCENTS; CHILDREN; PREDICTORS; MANIA; RISK; HETEROGENEITY AB Introduction: While pediatric mania and depression can be distinguished from each other, differentiating between unipolar major depressive disorder (unipolar MDD) and bipolar major depression (bipolar MDD) poses unique clinical and therapeutic challenges. Our aim was to examine the current body of knowledge on whether unipolar MDD and bipolar MDD in youth could be distinguished from one another in terms of clinical features and correlates. Methods: A systematic literature search was conducted on studies assessing the clinical characteristics and correlates of unipolar MDD and bipolar MDD in youth. Results: Four scientific papers that met our priori inclusion and exclusion criteria were identified. These papers reported that bipolar MDD is distinct from unipolar MDD in its higher levels of depression severity, associated impairment, psychiatric co-morbidity with oppositional defiant disorder, conduct disorder and anxiety disorders, and family history of mood and disruptive behavior disorders in first-degree relatives. Limitations: Though we examined a sizeable and diverse sample, we were only able to identify four cross sectional informative studies in our review. Therefore, our conclusions should be viewed as preliminary. Conclusions: These findings can aid clinicians in differentiating the two forms of MDD in youth. (C) 2015 Elsevier B.V. All rights reserved. C1 [Uchida, Mai; Kenworthy, Tara; Biederman, Joseph] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. [Zayas, Lazaro] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Serra, Giulia] Univ Roma La Sapienza, St Andrea Hosp, NESMOS Dept, I-00185 Rome, Italy. [Uchida, Mai; Serra, Giulia; Zayas, Lazaro; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Uchida, M (reprint author), Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, 55 Fruit St Warren 625, Boston, MA 02114 USA. EM muchida@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Pediatric Psychopharmacology Council Fund FX This work was supported in part by the Pediatric Psychopharmacology Council Fund. The funding source had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 30 TC 3 Z9 3 U1 3 U2 12 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 MAY 1 PY 2015 VL 176 BP 1 EP 7 DI 10.1016/j.jad.2015.01.037 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD3JV UT WOS:000350975500001 PM 25682377 ER PT J AU Steenkamp, MM Boasso, AM Nash, WP Larson, JL Lubin, RE Litz, BT AF Steenkamp, Maria M. Boasso, Alyssa M. Nash, William P. Larson, Jonathan L. Lubin, Rebecca E. Litz, Brett T. TI PTSD symptom presentation across the deployment cycle SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Afghanistan; PTSD; Latent class; Symptoms; Combat; Military ID POSTTRAUMATIC-STRESS-DISORDER; LATENT CLASS ANALYSIS; VETERANS; MILITARY; IRAQ; CHECKLIST; PERSONNEL; COMBAT; WAR AB Background: Symptom-level variation in posttraumatic stress disorder (PTSD) has not yet been examined in the early post-deployment phase, but may be meaningful etiologically, prognostically, and clinically. Methods: Using latent class analysis ([CA), we examined PTSD symptom heterogeneity in a cohort of participants from the Marine Resiliency Study (MRS), a longitudinal study of combat Marines deployed to Iraq and Afghanistan (N=892). Typologies of PTSD symptom presentation were examined at one month pre-deployment and again one, five, and eight months post-deployment. Results: Heterogeneity in PTSD symptom presentation was evident at each assessment point, and the degree of symptom heterogeneity (i.e., the number of classes identified) differed by time point. Symptom patterns stabilized over time from notable symptom fluctuations during the early post-deployment period to high, medium, and low symptom severity by eight months post-deployment. Hypervigilance and exaggerated startle were frequently endorsed by participants in the initial month post-deployment. Flashbacks, amnesia, and foreshortened future were infrequently endorsed. Greater combat exposure, lifespan trauma, and avoidant coping generally predicted worse outcomes. Limitations: Data were self-report and may have limited generalizability due to our lack of women and inclusion of only combat Marines. Attrition and re-ranging of data resulted in significant missing data and affected the representativeness of the sample. Conclusions: Symptom-level variability is highest in the month following deployment and then stabilizes over time. Should post-deployment assessments occur too soon, they may capture common and transient early post-deployment reactions, particularly anxious arousal. Published by Elsevier B.V. C1 [Steenkamp, Maria M.] NYU, Sch Med, New York, NY 10003 USA. [Boasso, Alyssa M.; Larson, Jonathan L.; Lubin, Rebecca E.; Litz, Brett T.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA 02215 USA. [Nash, William P.] Boston VA Res Inst BVARI, Boston, MA USA. RP Litz, BT (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,13-B71, Jamaica Plain, MA 02130 USA. EM Brett.Litz@va.gov FU VA Health Service Research and Development, the Navy Bureau of Medicine and Surgery, and Headquarters, U.S. Marine Corps [SDR 09-0128] FX This study was funded by VA Health Service Research and Development (SDR 09-0128), the Navy Bureau of Medicine and Surgery, and Headquarters, U.S. Marine Corps. The funding source was involved in study design and data collection and was not involved in analysis and interpretation of the data, in writing the report and in the decision to submit the article for publication. NR 23 TC 4 Z9 4 U1 0 U2 13 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 MAY 1 PY 2015 VL 176 BP 87 EP 94 DI 10.1016/j.jad.2015.01.043 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CD3JV UT WOS:000350975500013 PM 25702604 ER PT J AU Lee, DH Qi, J Bradner, JE Said, JW Doan, NB Forscher, C Yang, H Koeffler, HP AF Lee, Dhong Hyun Qi, Jun Bradner, James E. Said, Jonathan W. Doan, Ngan B. Forscher, Charles Yang, Henry Koeffler, H. Phillip TI Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE osteosarcoma; JQ1; rapamycin; synergism; RUNX2 ID BET BROMODOMAIN INHIBITION; CELL-LINES; SELECTIVE-INHIBITION; C-MYC; SUPER-ENHANCERS; EXPRESSION; CANCER; LEUKEMIA; TARGETS; CYCLE AB Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mammalian target of rapamycin (mTOR) inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of bromodomain-containing protein 4 (BRD4) inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains the antiproliferative activity of JQ1 in OS cells. What's new? Gene expression can be effectively turned on or off by addition or removal of acetyl groups. Reader proteins, such as the BET family of proteins, respond to these acetylation cues by recruiting transcription machinery. In this paper, the authors show that a BET protein inhibitor, JQ1, slows the growth of osteosarcoma cells in vitro, but wasn't too effective against tumors in vivo. That is, until they tried it in combination with rapamycin: in conjunction with that drug, JQ1 killed off OS cells both in vitro and in vivo, making it potentially useful as a treatment. C1 [Lee, Dhong Hyun; Forscher, Charles; Koeffler, H. Phillip] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol & Oncol, Los Angeles, CA 90048 USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Said, Jonathan W.; Doan, Ngan B.] Santa Monica Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA USA. [Yang, Henry; Koeffler, H. Phillip] Natl Univ Singapore, Natl Canc Inst, Singapore 117548, Singapore. [Yang, Henry; Koeffler, H. Phillip] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore. RP Lee, DH (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol & Oncol, 8700 Beverly Blvd,D5022, Los Angeles, CA 90048 USA. EM hiromasa@ucla.edu FU National Research Foundation Singapore; Singapore Ministry of Education under the Research Centers of Excellence initiative; Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award; US National Institutes of Health [R01CA026038-35] FX Grant sponsors: National Research Foundation Singapore and the Singapore Ministry of Education under the Research Centers of Excellence initiative, Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award, and US National Institutes of Health (to H.P.K.); Grant number: R01CA026038-35 NR 31 TC 18 Z9 18 U1 4 U2 27 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 MAY 1 PY 2015 VL 136 IS 9 BP 2055 EP 2064 DI 10.1002/ijc.29269 PG 10 WC Oncology SC Oncology GA CB9SI UT WOS:000349972300007 PM 25307878 ER PT J AU Wang, HF Zang, CZ Liu, XS Aster, JC AF Wang, Hongfang Zang, Chongzhi Liu, X. Shirley Aster, Jon C. TI The Role of Notch Receptors in Transcriptional Regulation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID ADENOID CYSTIC CARCINOMA; TARGET GENE-EXPRESSION; T-CELL DEVELOPMENT; LYMPHOBLASTIC-LEUKEMIA; COREPRESSOR COMPLEX; SUPER-ENHANCERS; RBP-J; ACTIVATION; BINDING; PROTEIN AB Notch signaling has pleiotropic context-specific functions that have essential roles in many processes, including embryonic development and maintenance and homeostasis of adult tissues. Aberrant Notch signaling (both hyper- and hypoactive) is implicated in a number of human developmental disorders and many cancers. Notch receptor signaling is mediated by tightly regulated proteolytic cleavages that lead to the assembly of a nuclear Notch transcription complex, which drives the expression of downstream target genes and thereby executes Notch's functions. Thus, understanding regulation of gene expression by Notch is central to deciphering how Notch carries out its many activities. Here, we summarize the recent findings pertaining to the complex interplay between the Notch transcriptional complex and interacting factors involved in transcriptional regulation, including co-activators, cooperating transcription factors, and chromatin regulators, and discuss emerging data pertaining to the role of Notch-regulated noncoding RNAs in transcription. J. Cell. Physiol. 230: 982-988, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company C1 [Wang, Hongfang; Aster, Jon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zang, Chongzhi; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Zang, Chongzhi; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. RP Aster, JC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 652E New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jaster@partners.org RI Zang, Chongzhi/D-1445-2011 FU National Institutes of Health [P01 CA119070] FX Contract grant sponsor: National Institutes of Health;; Contract grant number: P01 CA119070. NR 49 TC 10 Z9 11 U1 1 U2 21 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 MAY PY 2015 VL 230 IS 5 BP 982 EP 988 DI 10.1002/jcp.24872 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CB0FL UT WOS:000349301000003 PM 25418913 ER PT J AU Wang, B Li, DP Sidler, C Rodriguez-Juarez, R Singh, N Heyns, M Ilnytskyy, Y Bronson, RT Kovalchuk, O AF Wang, Bo Li, Dongping Sidler, Corinne Rodriguez-Juarez, Rocio Singh, Natasha Heyns, Mieke Ilnytskyy, Yaroslav Bronson, Roderick T. Kovalchuk, Olga TI A suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1 SO ONCOTARGET LA English DT Article DE ionizing radiation; miR-29c; hepatocellular carcinoma; WIP1 ID LOW-DOSE HYPERSENSITIVITY; CELL-CYCLE ARREST; HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; DOWN-REGULATION; NASOPHARYNGEAL CARCINOMA; MESSENGER-RNAS; IN-VIVO; EXPRESSION; CANCER AB Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, and it has been linked to radiation exposure. As a well-defined oncogene, wild-type p53-induced phosphatase 1 (WIP1) plays an inhibitory role in several tumor suppressor pathways, including p53. WIP1 is amplified and overexpressed in many malignancies, including HCC. However, the underlying mechanisms remain largely unknown. Here, we show that low-dose ionizing radiation (IR) induces miR-29c expression in female mouse liver, while inhibiting its expression in HepG2, a human hepatocellular carcinoma cell line which is used as a model system in this study. miR-29c expression is downregulated in human hepatocellular carcinoma cells, which is inversely correlated with WIP1 expression. miR-29c attenuates luciferase activity of a reporter harboring the 3'UTR binding motif of WIP1 mRNA. Ectopic expression of miR-29c significantly represses cell proliferation and induces apoptosis and G1 arrest in HepG2. In contrast, the knockdown of miR-29c greatly enhances HepG2 cell proliferation and suppresses apoptosis. The biological effects of miR-29c may be mediated by its target WIP1 which regulates p53 activity via dephosphorylation at Ser-15. Finally, fluorescence in situ hybridization (FISH) and immunohistochemical analyses indicate that miR-29c is downregulated in 50.6% of liver carcinoma tissues examined, whereas WIP1 is upregulated in 45.4% of these tissues. The expression of miR-29c inversely correlates with that of WIP1 in HCC. Our results suggest that the IR-responsive miR-29c may function as a tumor suppressor that plays a crucial role in the development of liver carcinoma via targeting WIP1, therefore possibly representing a target molecule for therapeutic intervention for this disease. C1 [Wang, Bo; Li, Dongping; Sidler, Corinne; Rodriguez-Juarez, Rocio; Singh, Natasha; Heyns, Mieke; Ilnytskyy, Yaroslav; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Wang, Bo; Li, Dongping] Qiqihar Med Univ, Dept Biochem, Qiqihar, Peoples R China. [Bronson, Roderick T.] Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU Canadian Institutes for Health Research; Department of Energy Low Dose Radiation program; NSERC FX This study was supported by the Canadian Institutes for Health Research and the Department of Energy Low Dose Radiation program grants to Dr. Olga Kovalchuk. Mieke Heyns was supported by the NSERC Undergraduate Student Research Award. We thank Dr. Valentina Titova for proof-reading the manuscript. NR 61 TC 1 Z9 2 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 30 PY 2015 VL 6 IS 12 BP 9937 EP 9950 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO0WO UT WOS:000358874600025 PM 25888625 ER PT J AU Viswanathan, V Lee, S Gilman, JM Kim, BW Lee, N Chamberlain, L Livengood, SL Raman, K Lee, MJ Kuster, J Stern, DB Calder, B Mulhern, FJ Blood, AJ Breiter, HC AF Viswanathan, Vijay Lee, Sang Gilman, Jodi M. Kim, Byoung Woo Lee, Nick Chamberlain, Laura Livengood, Sherri L. Raman, Kalyan Lee, Myung Joo Kuster, Jake Stern, Daniel B. Calder, Bobby Mulhern, Frank J. Blood, Anne J. Breiter, Hans C. TI Age-related striatal BOLD changes without changes in behavioral loss aversion SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE loss aversion; aging; nucleus accumbens; reward; fMRI; neurocompensation ID PERFORMING OLDER-ADULTS; DECISION-MAKING; INDIVIDUAL-DIFFERENCES; REWARD CIRCUITRY; ADOLESCENT BRAIN; PROSPECT-THEORY; PARKINSONS-DISEASE; RECOGNITION MEMORY; GENDER-DIFFERENCES; NEURAL ACTIVITY AB Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task. C1 [Viswanathan, Vijay; Raman, Kalyan; Mulhern, Frank J.] Northwestern Univ, Medill Integrated Mkt Commun, Evanston, IL USA. [Viswanathan, Vijay; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.] Northwestern Univ, Appl Neuromkt Consortium, Evanston, IL 60208 USA. [Viswanathan, Vijay; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.] Wayne State Univ, Detroit, MI 48202 USA. [Viswanathan, Vijay; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Viswanathan, Vijay; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.] Univ Loughborough, Sch Business & Econ, Loughborough, Leics, England. [Viswanathan, Vijay; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.] Harvard Univ, Massachusetts Gen Hosp, Chicago, IL USA. [Lee, Sang; Gilman, Jodi M.; Kim, Byoung Woo; Lee, Myung Joo; Kuster, Jake; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Mood & Motor Control Lab Neuroimaging & Genet, Boston, MA 02114 USA. [Lee, Sang; Kim, Byoung Woo; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Stern, Daniel B.; Breiter, Hans C.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Warren Wright Adolescent Ctr, Chicago, IL 60611 USA. [Lee, Sang; Kim, Byoung Woo; Lee, Myung Joo; Kuster, Jake; Blood, Anne J.; Breiter, Hans C.] Northeastern Univ, Chicago, IL USA. [Lee, Sang; Kim, Byoung Woo; Lee, Myung Joo; Kuster, Jake; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Phenotype Genotype Project Addict & Mood Disorder, Chicago, IL USA. [Lee, Nick; Chamberlain, Laura] Aston Univ, Aston Business Sch, Mkt Grp, Birmingham B4 7ET, W Midlands, England. [Raman, Kalyan; Calder, Bobby] Northwestern Univ, Dept Mkt, Kellogg Sch Management, Evanston, IL USA. RP Breiter, HC (reprint author), Northwestern Univ, Warren Wright Adolescent Ctr, Dept Psychiat & Behav Sci, Feinberg Sch Med, 710 N Lake Shore Dr,Abbott Hall 1301, Chicago, IL 60611 USA. EM h-breiter@northwestern.edu FU NIDA, Bethesda, MD [14 118, 026002, 026104, 027804]; Office of National Drug Control Policy-Counterdrug Technology Assessment Center, Washington, D.C.; Warren Wright Adolescent Center at Northwestern Memorial Hospital and Northwestern University, Chicago IL, USA; NINDS, Washington, D.C. [052368]; Dystonia Medical Research Foundation; [DARK39-03-0098]; [DABK39-03-C-0098] FX This work was supported by grants to HCB (#14 118, 026002, 026104, 027804) from the NIDA, Bethesda, MD, and grants (DARK39-03-0098 and 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 HCB by the Warren Wright Adolescent Center at Northwestern Memorial Hospital and Northwestern University, Chicago IL, USA. Support was also provided by a grant to AJB (#052368) from NINDS, Washington, D.C., and a grant from the Dystonia Medical Research Foundation to AJB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 2 Z9 2 U1 1 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD APR 30 PY 2015 VL 9 AR 176 DI 10.3389/jnhum.2015.00176 PG 12 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CK1ZF UT WOS:000356007900001 PM 25983682 ER PT J AU Brown, JR O'Brien, S Kingsley, CD Eradat, H Pagel, JM Lymp, J Hirata, J Kipps, TJ AF Brown, Jennifer R. O'Brien, Susan Kingsley, C. Daniel Eradat, Herbert Pagel, John M. Lymp, James Hirata, Jamie Kipps, Thomas J. TI Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PREVIOUSLY UNTREATED PATIENTS; II TRIAL; RITUXIMAB; CHLORAMBUCIL; FLUDARABINE; ANTIBODY; GA101; CHEMOIMMUNOTHERAPY; CYCLOPHOSPHAMIDE AB Obinutuzumab is a type 2, glycoengineered, anti-CD20 antibody recently approved with chlorambucil for the initial therapy of chronic lymphocytic leukemia (CLL). In this nonrandomized, parallel-cohort, phase 1b, multicenter study, we explored the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy of previously untreated fit patients with CLL. Patients received up to 6 cycles of G-B (n = 20) or G-FC (n = 21). The primary end point was safety, with infusion-related reactions (88%, grade 3-4 20%) being the most common adverse event and grade 3-4 neutropenia in 55% on G-B and 48% on G-FC. Mean cycles completed were 5.7 for G-B and 5.1 for G-FC, with 2 and 7 early discontinuations, respectively. The objective response rate (ORR) for G-B was 90% (18/20) with 20% complete response (CR) and 25% CR with incomplete marrow recovery (CRi). The ORR for G-FC was 62% (13/21), with 10% CR and 14% CRi, including 4 patients not evaluable. With a median follow-up of 23.5 months in the G-B cohort and 20.7 months in the G-FC cohort, no patient has relapsed or died. We conclude that obinutuzumab with either B or FC shows manageable toxicity and has promising activity. C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kingsley, C. Daniel] Clearview Canc Inst, Huntsville, AL USA. [Eradat, Herbert] Univ Calif Los Angeles, Los Angeles, CA USA. [Pagel, John M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Pagel, John M.] Univ Washington, Dept Med, Seattle, WA USA. [Lymp, James; Hirata, Jamie] Genentech Inc, San Francisco, CA 94080 USA. [Kipps, Thomas J.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM jennifer_brown@dfci.harvard.edu FU F. Hoffmann-La Roche FX The authors thank the patients and their families and the following investigators that participated in GALTON (GAO4779g): Paul Barr (James P. Wilmot Cancer Center, University of Rochester), Leonard T. Heffner (Winship Cancer Institute, Emory University), Robert Hermann (Northwest Georgia Oncology Centers, PC, William S. Gibbons Cancer Research Institute), Viran Holden (Mercy Medical Research Institute), Moacyr Ribeiro De Oliveira (Northwest Medical Specialties), and Javier Pinilla-Ibarz (H. Lee Moffitt Cancer Center). They also thank the GALTON study management team (Roche/Genentech), Mijanur Rahman and Ross Farrugia for statistical programming support, Nicola Tyson for biostatistical support, and David Carlile and Michael Brewster for pharmacokinetic analysis support. The GALTON study was sponsored by F. Hoffmann-La Roche. Editorial assistance was provided by Cheryl Wright at Gardiner-Caldwell Communications (Macclesfield, United Kingdom) and funded by F. Hoffmann-La Roche. NR 18 TC 23 Z9 24 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 APR 30 PY 2015 VL 125 IS 18 BP 2779 EP 2785 DI 10.1182/blood-2014-12-613570 PG 7 WC Hematology SC Hematology GA CJ7OR UT WOS:000355686600010 PM 25769620 ER PT J AU Kuo, B Bhasin, M Jacquart, J Scult, MA Slipp, L Riklin, EIK Lepoutre, V Comosa, N Norton, BA Dassatti, A Rosenblum, J Thurler, AH Surjanhata, BC Hasheminejad, NN Kagan, L Slawsby, E Rao, SR Macklin, EA Fricchione, GL Benson, H Libermann, TA Korzenik, J Denninger, JW AF Kuo, Braden Bhasin, Manoj Jacquart, Jolene Scult, Matthew A. Slipp, Lauren Riklin, Eric Isaac Kagan Lepoutre, Veronique Comosa, Nicole Norton, Beth-Ann Dassatti, Allison Rosenblum, Jessica Thurler, Andrea H. Surjanhata, Brian C. Hasheminejad, Nicole N. Kagan, Leslee Slawsby, Ellen Rao, Sowmya R. Macklin, Eric A. Fricchione, Gregory L. Benson, Herbert Libermann, Towia A. Korzenik, Joshua Denninger, John W. TI Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease SO PLOS ONE LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; BEHAVIORAL TREATMENT; ULCERATIVE-COLITIS; STRESS-MANAGEMENT; OXIDATIVE STRESS; CROHNS-DISEASE; T-CELLS; EXPRESSION AB Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-kappa B as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-kappa B) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-kappa B is a target focus molecule in both IBS and IBD- and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. C1 [Kuo, Braden; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Korzenik, Joshua] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Bhasin, Manoj; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Bhasin, Manoj; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, Dept Med, Genom Prote Bioinformat & Syst Biol Ctr, Boston, MA 02215 USA. [Bhasin, Manoj; Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Denninger, John W.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Lepoutre, Veronique; Benson, Herbert; Korzenik, Joshua] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fricchione, Gregory L.; Denninger, John W.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. RP Denninger, JW (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. EM jdenninger@mgh.harvard.edu OI Scult, Matthew/0000-0001-5554-8186; Libermann, Towia/0000-0002-4006-8179; Macklin, Eric/0000-0003-1618-3502 FU Center for Disease Control and Prevention [R01DP000339]; International Foundation for Functional Gastrointestinal Diseases (Neuroenteric Research Program Grant) FX This study was supported by the Center for Disease Control and Prevention (Grant R01DP000339) and the International Foundation for Functional Gastrointestinal Diseases (Neuroenteric Research Program Grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 7 Z9 8 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 APR 30 PY 2015 VL 10 IS 4 AR UNSP e0123861 DI 10.1371/journal.pone.0123861 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0MA UT WOS:000353713100024 PM 25927528 ER PT J AU Kahn, K Saxena, S Eskandar, E Thakor, N Schieber, M Gale, JT Averbeck, B Eden, U Sarma, SV AF Kahn, Kevin Saxena, Shreya Eskandar, Emad Thakor, Nitish Schieber, Marc Gale, John T. Averbeck, Bruno Eden, Uri Sarma, Sridevi V. TI A systematic approach to selecting task relevant neurons SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Task-related neurons; Neuron selection; Model based; Point processes ID NEURAL SPIKING ACTIVITY; PRIMARY MOTOR CORTEX; FINGER MOVEMENTS; CELLS AB Background: Since task related neurons cannot be specifically targeted during surgery, a critical decision to make is to select which neurons are task-related when performing data analysis. Including neurons unrelated to the task degrade decoding accuracy and confound neurophysiological results. Traditionally, task-related neurons are selected as those with significant changes in firing rate when a stimulus is applied. However, this assumes that neurons' encoding of stimuli are dominated by their firing rate with little regard to temporal dynamics. New method: This paper proposes a systematic approach for neuron selection, which uses a likelihood ratio test to capture the contribution of stimulus to spiking activity while taking into account task-irrelevant intrinsic dynamics that affect firing rates. This approach is denoted as the model deterioration excluding stimulus (MDES) test. Results: MDES is compared to firing rate selection in four case studies: a simulation, a decoding example, and two neurophysiology examples. Comparison with existing methods: The MDES rankings in the simulation match closely with ideal rankings, while firing rate rankings are skewed by task-irrelevant parameters. For decoding, 95% accuracy is achieved using the top 8 MDES-ranked neurons, while the top 12 firing-rate ranked neurons are needed. In the neurophysiological examples, MDES matches published results when firing rates do encode salient stimulus information, and uncovers oscillatory modulations in task-related neurons that are not captured when neurons are selected using firing rates. Conclusions: These case studies illustrate the importance of accounting for intrinsic dynamics when selecting task-related neurons and following the MDES approach accomplishes that. MDES selects neurons that encode task-related information irrespective of these intrinsic dynamics which can bias firing rate based selection. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kahn, Kevin; Thakor, Nitish; Sarma, Sridevi V.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. [Saxena, Shreya] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Schieber, Marc] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44195 USA. [Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH 44195 USA. [Averbeck, Bruno] NIH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Eden, Uri] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Kahn, K (reprint author), Johns Hopkins Univ, Inst Computat Med, 3400 N Charles St,Hackerman Hall,Room 318, Baltimore, MD 21218 USA. EM kkahn6@jhmi.edu RI Thakor, Nitish/G-9110-2015 OI Thakor, Nitish/0000-0002-9981-9395 FU Burroughs Wellcome Fund [100727401]; National Science Foundation [1137237] FX K Kahn and SV Sarma were supported by the Burroughs Wellcome Fund (100727401) and the National Science Foundation (1137237). NR 31 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2015 VL 245 BP 156 EP 168 DI 10.1016/j.jneumeth.2015.02.020 PG 13 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CG8XN UT WOS:000353599100015 PM 25746150 ER PT J AU Bradner, JE AF Bradner, James E. TI CANCER An essential passenger with p53 SO NATURE LA English DT Editorial Material ID VULNERABILITIES AB Deletion of the TP53 gene, an event seen in colorectal cancers, often occurs with co-deletion of a gene that encodes an enzyme subunit governing gene transcription. This creates a vulnerability ripe for therapeutic development. See Letter p.697 C1 [Bradner, James E.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu NR 7 TC 2 Z9 2 U1 4 U2 16 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 APR 30 PY 2015 VL 520 IS 7549 BP 626 EP 627 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0DQ UT WOS:000353689700036 PM 25901678 ER PT J AU Kagawa, S Natsuizaka, M Whelan, KA Facompre, N Naganuma, S Ohashi, S Kinugasa, H Egloff, AM Basu, D Gimotty, PA Klein-Szanto, AJ Bass, AJ Wong, KK Diehl, JA Rustgi, AK Nakagawa, H AF Kagawa, S. Natsuizaka, M. Whelan, K. A. Facompre, N. Naganuma, S. Ohashi, S. Kinugasa, H. Egloff, A. M. Basu, D. Gimotty, P. A. Klein-Szanto, A. J. Bass, A. J. Wong, K-K Diehl, J. A. Rustgi, A. K. Nakagawa, H. TI Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities SO ONCOGENE LA English DT Article ID HUMAN ESOPHAGEAL KERATINOCYTES; TO-MESENCHYMAL TRANSITION; ZEB TRANSCRIPTION FACTORS; EPITHELIAL-CELLS; TGF-BETA; PREMATURE SENESCENCE; SQUAMOUS CANCER; NOTCH; CARCINOMA; P53 AB Notch activity regulates tumor biology in a context-dependent and complex manner. Notch may act as an oncogene or a tumor-suppressor gene even within the same tumor type. Recently, Notch signaling has been implicated in cellular senescence. Yet, it remains unclear as to how cellular senescence checkpoint functions may interact with Notch-mediated oncogenic and tumor-suppressor activities. Herein, we used genetically engineered human esophageal keratinocytes and esophageal squamous cell carcinoma cells to delineate the functional consequences of Notch activation and inhibition along with pharmacological intervention and RNA interference experiments. When expressed in a tetracycline-inducible manner, the ectopically expressed activated form of Notch1 (ICN1) displayed oncogene-like characteristics inducing cellular senescence corroborated by the induction of G0/G1 cell-cycle arrest, Rb dephosphorylation, flat and enlarged cell morphology and senescence-associated beta-galactosidase activity. Notch-induced senescence involves canonical CSL/RBPJ-dependent transcriptional activity and the p16(INK4A)-Rb pathway. Loss of p16(INK4A) or the presence of human papilloma virus (HPV) E6/E7 oncogene products not only prevented ICN1 from inducing senescence but permitted ICN1 to facilitate anchorage-independent colony formation and xenograft tumor growth with increased cell proliferation and reduced squamous-cell differentiation. Moreover, Notch1 appears to mediate replicative senescence as well as transforming growth factor-beta-induced cellular senescence in non-transformed cells and that HPV E6/E7 targets Notch1 for inactivation to prevent senescence, revealing a tumor-suppressor attribute of endogenous Notch1. In aggregate, cellular senescence checkpoint functions may influence dichotomous Notch activities in the neoplastic context. C1 [Kagawa, S.; Natsuizaka, M.; Whelan, K. A.; Naganuma, S.; Ohashi, S.; Kinugasa, H.; Rustgi, A. K.; Nakagawa, H.] Univ Penn, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA. [Kagawa, S.; Natsuizaka, M.; Whelan, K. A.; Naganuma, S.; Ohashi, S.; Kinugasa, H.; Gimotty, P. A.; Diehl, J. A.; Rustgi, A. K.; Nakagawa, H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Natsuizaka, M.] Hokkaido Univ, Dept Gastroenterol & Hepatol, Sapporo, Hokkaido, Japan. [Facompre, N.; Basu, D.] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Facompre, N.; Basu, D.] Univ Penn, Dept Head & Neck Surg, Philadelphia, PA 19104 USA. [Facompre, N.; Basu, D.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Naganuma, S.] Kochi Univ, Sch Med, Dept Pathol, Kochi 780, Japan. [Ohashi, S.] Kyoto Univ, Grad Sch Med, Dept Therapeut Oncol, Kyoto, Japan. [Kinugasa, H.] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol, Okayama 7008530, Japan. [Egloff, A. M.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Gimotty, P. A.] Univ Penn, Div Biostat, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Klein-Szanto, A. J.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Bass, A. J.; Wong, K-K] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bass, A. J.; Wong, K-K] Dana Farber Canc Inst, Div Cellular & Mol Oncol, Boston, MA 02115 USA. [Diehl, J. A.] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA. [Rustgi, A. K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Nakagawa, H (reprint author), Univ Penn, Div Gastroenterol, Dept Med, 956 BRB,421 Curie Blvd, Philadelphia, PA 19104 USA. EM nakagawh@mail.med.upenn.edu FU NIH [P01CA098101, U01CA143056, R01DK077005, K26 RR032714]; Pennsylvania CURE Program Grant [F32-CA174176, F32-DE024685, K08DE022842]; Trio/ACS Career Award; VA CPPF Grant [K07CA137140]; University of Pennsylvania University Research Foundation Award; University of Pennsylvania; Abramson Cancer Center Pilot Project Grant; American Cancer Society [RP-10-033-01-CCE] FX We thank Dr Hiroshi Shirasawa (Chiba University, Chiba, Japan) for the gift of EN60 cells. We are grateful to the Molecular Pathology & Imaging, Molecular Biology/Gene Expression and Cell Culture Core Facilities of the NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30-DK050306) and of the NIH P01CA098101. This study was supported in part by NIH Grants P01CA098101 (to SK, MN, KAW, DB, HK, SN, SO, PAG, AJK-S, AB, K-KW, JAD, HN and AKR), U01CA143056 (to AKR), R01DK077005 (to HN), K26 RR032714 (to HN), Pennsylvania CURE Program Grant (to HN), F32-CA174176 (to KAW), F32-DE024685 to (NF), K08DE022842, Trio/ACS Career Award and VA CPPF Grant (to DB), K07CA137140 (to AME), University of Pennsylvania University Research Foundation Award (to HN), University of Pennsylvania, Abramson Cancer Center Pilot Project Grant (to HN), and the American Cancer Society RP-10-033-01-CCE (to AKR). NR 67 TC 13 Z9 14 U1 0 U2 6 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 APR 30 PY 2015 VL 34 IS 18 BP 2347 EP 2359 DI 10.1038/onc.2014.169 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CH2AH UT WOS:000353824800008 PM 24931169 ER PT J AU Serrao, E Ballandras-Colas, A Cherepanov, P Maertens, GN Engelman, AN AF Serrao, Erik Ballandras-Colas, Allison Cherepanov, Peter Maertens, Goedele N. Engelman, Alan N. TI Key determinants of target DNA recognition by retroviral intasomes SO RETROVIROLOGY LA English DT Article DE Retrovirus; Integrase; DNA flexibility; Dinucleotide steps; Integration sites; Nucleosomes; BET proteins ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTEGRATION SITE SELECTION; T-CELL LEUKEMIA; TYPE-1 PREINTEGRATION COMPLEXES; HUMAN ENDOGENOUS RETROVIRUS; TRANSCRIPTION START SITES; MAMMARY-TUMOR VIRUS; NUCLEOTIDE-SEQUENCE; FOAMY VIRUS; IN-VITRO AB Background: Retroviral integration favors weakly conserved palindrome sequences at the sites of viral DNA joining and generates a short (4-6 bp) duplication of host DNA flanking the provirus. We previously determined two key parameters that underlie the target DNA preference for prototype foamy virus (PFV) and human immunodeficiency virus type 1 (HIV-1) integration: flexible pyrimidine (Y)/purine (R) dinucleotide steps at the centers of the integration sites, and base contacts with specific integrase residues, such as Ala188 in PFV integrase and Ser119 in HIV-1 integrase. Here we examined the dinucleotide preference profiles of a range of retroviruses and correlated these findings with respect to length of target site duplication (TSD). Results: Integration datasets covering six viral genera and the three lengths of TSD were accessed from the literature or generated in this work. All viruses exhibited significant enrichments of flexible YR and/or selection against rigid RY dinucleotide steps at the centers of integration sites, and the magnitude of this enrichment inversely correlated with TSD length. The DNA sequence environments of in vivo-generated HIV-1 and PFV sites were consistent with integration into nucleosomes, however, the local sequence preferences were largely independent of target DNA chromatinization. Integration sites derived from cells infected with the gammaretrovirus reticuloendotheliosis virus strain A (Rev-A), which yields a 5 bp TSD, revealed the targeting of global chromatin features most similar to those of Moloney murine leukemia virus, which yields a 4 bp duplication. In vitro assays revealed that Rev-A integrase interacts with and is catalytically stimulated by cellular bromodomain containing 4 protein. Conclusions: Retroviral integrases have likely evolved to bend target DNA to fit scissile phosphodiester bonds into two active sites for integration, and viruses that cut target DNA with a 6 bp stagger may not need to bend DNA as sharply as viruses that cleave with 4 bp or 5 bp staggers. For PFV and HIV-1, the selection of signature bases and central flexibility at sites of integration is largely independent of chromatin structure. Furthermore, global Rev-A integration is likely directed to chromatin features by bromodomain and extraterminal domain proteins. C1 [Serrao, Erik; Ballandras-Colas, Allison; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Cherepanov, Peter; Maertens, Goedele N.] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London, England. [Cherepanov, Peter] Francis Crick Inst, Clare Hall Labs, London, England. RP Engelman, AN (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI Cherepanov, Peter/F-6859-2010; OI Cherepanov, Peter/0000-0002-0634-538X; Maertens, Goedele/0000-0002-1963-8026 FU US National Institutes of Health [AI070042, AI060354] FX We thank Joseph Dougherty for the generous gift of pJD215 plasmid DNA. We additionally thank the following individuals for graciously sharing with us the coordinates of the following retroviral integration site datasets: Frederic Bushman, MoMLV and EIAV; Charles Bangham, HTLV-1, Jeroen de Ridder, MMTV. This work was supported by US National Institutes of Health grants AI070042 (to A.E. and P.C.) and AI060354 (Harvard University Center for AIDS Research). NR 103 TC 16 Z9 16 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD APR 30 PY 2015 VL 12 AR 39 DI 10.1186/s12977-015-0167-3 PG 18 WC Virology SC Virology GA CH4HC UT WOS:000353993600001 PM 25924943 ER PT J AU Janne, PA Yang, JCH Kim, DW Planchard, D Ohe, Y Ramalingam, SS Ahn, MJ Kim, SW Su, WC Horn, L Haggstrom, D Felip, E Kim, JH Frewer, P Cantarini, M Brown, KH Dickinson, PA Ghiorghiu, S Ranson, M AF Jaenne, Pasi A. Yang, James Chih-Hsin Kim, Dong-Wan Planchard, David Ohe, Yuichiro Ramalingam, Suresh S. Ahn, Myung-Ju Kim, Sang-We Su, Wu-Chou Horn, Leora Haggstrom, Daniel Felip, Enriqueta Kim, Joo-Hang Frewer, Paul Cantarini, Mireille Brown, Kathryn H. Dickinson, Paul A. Ghiorghiu, Serban Ranson, Malcolm TI AZD9291 in EGFR Inhibitor-Resistant Non-Small-Cell Lung Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; IRREVERSIBLE EGFR; OPEN-LABEL; GEFITINIB; MUTATIONS; CHEMOTHERAPY; ERLOTINIB; AFATINIB; TRIAL AB BACKGROUND The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. METHODS We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy. RESULTS A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients. CONCLUSIONS AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Yang, James Chih-Hsin] Natl Taiwan Univ, Taipei 10764, Taiwan. [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Su, Wu-Chou] Cheng Kung Univ Hosp, Taipei, Taiwan. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Ahn, Myung-Ju] Yonsei Univ Hlth Syst, Samsung Med Ctr, Seoul, South Korea. [Kim, Sang-We] Yonsei Univ Hlth Syst, Asan Med Ctr, Seoul, South Korea. [Kim, Joo-Hang] Yonsei Univ Hlth Syst, Yonsei Canc Ctr, Seoul, South Korea. [Planchard, David] Inst Gustave Roussy, Villejuif, France. [Ohe, Yuichiro] Natl Canc Ctr, Tokyo, Japan. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Haggstrom, Daniel] Carolinas Healthcare Syst, Levine Canc Inst, Charlotte, NC USA. [Felip, Enriqueta] Vall dHebron Univ Hosp, Barcelona, Spain. [Felip, Enriqueta] Vall dHebron Inst Oncol, Barcelona, Spain. [Frewer, Paul; Cantarini, Mireille; Brown, Kathryn H.; Dickinson, Paul A.; Ghiorghiu, Serban] AstraZeneca, Macclesfield, Cheshire, England. [Ranson, Malcolm] Univ Manchester, Christie Hosp, Manchester, Lancs, England. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM 223, Boston, MA 02215 USA. EM pasi_janne@dfci.harvard.edu FU AstraZeneca; Boehringer Ingelheim; Chugai Pharmaceuticals; Pfizer; Merrimack Pharmaceuticals; Clovis Oncology; Roche; Novartis; Merck Sharp Dohme; Roche-Genentech; Eli Lilly; Merck Serono; Astellas Pharma; Celgene; InnoPharma; Genentech; Amgen; Biodesix; Ariad Pharmaceuticals; Bristol-Myers Squibb; Merck FX Supported by AstraZeneca.; Dr. Janne reports receiving consulting fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceuticals, Pfizer, Merrimack Pharmaceuticals, and Clovis Oncology and lecture fees from Roche and owning stock in Gatekeeper Pharmaceuticals. He also reports receiving royalties from patents related to a method of determining responsiveness of cancer to epidermal growth factor receptor (EGFR)-targeting treatments from LabCorp (U.S. patent numbers, 7,294,468; 8,465,916; 7,964,349; and 8,105,769; licensed to LabCorp) and a pending patent related to EGFR inhibitors and methods of treating disorders (U.S. patent application number, 13/319,079; licensed to Gatekeeper Pharmaceuticals). Dr. Yang reports receiving fees for serving on advisory boards from AstraZeneca, Clovis Oncology, Novartis, Boehringer Ingelheim, Merck Sharp & Dohme, Roche-Genentech, Eli Lilly, Pfizer, Merck Serono, Astellas Pharma, Celgene, and InnoPharma, lecture fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly, travel support from AstraZeneca, Boehringer Ingelheim, Roche-Genentech, and Eli Lilly, grant support from Boehringer Ingelheim, and supplies for preclinical laboratory work from AstraZeneca and Boehringer Ingelheim. Dr. D.-W. Kim reports receiving consulting fees from Novartis and honoraria from Pfizer. Dr. Planchard reports receiving fees for serving on advisory boards from AstraZeneca, Roche, and Boehringer Ingelheim. Dr. Ramalingam reports receiving fees for serving on advisory boards from Genentech, Boehringer Ingelheim, Amgen, Biodesix, Ariad Pharmaceuticals, Eli Lilly, Bristol-Myers Squibb, Celgene, and Novartis. Dr. Horn reports serving on a steering committee for Bayer, acting as an unpaid consultant for Xcovery, and receiving fees for serving on advisory boards from Clovis Oncology, Genentech, and Merck, lecture fees from Boehringer Ingelheim, and grant support from Astellas Pharma. Dr. Felip reports receiving consulting fees from Eli Lilly, Pfizer, Roche, and Boehringer Ingelheim and lecture fees from AstraZeneca and Novartis. Mr. Frewer and Drs. Cantarini, Brown, Dickinson, and Ghiorghiu report being employees of and holding stock in AstraZeneca. Dr. Ranson reports serving on an independent data and safety monitoring committee for AstraZeneca. No other potential conflict of interest relevant to this article was reported. NR 27 TC 362 Z9 385 U1 22 U2 86 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 APR 30 PY 2015 VL 372 IS 18 BP 1689 EP 1699 DI 10.1056/NEJMoa1411817 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000004 PM 25923549 ER PT J AU Sequist, LV Soria, JC Goldman, JW Wakelee, HA Gadgeel, SM Varga, A Papadimitrakopoulou, V Solomon, BJ Oxnard, GR Dziadziuszko, R Aisner, DL Doebele, RC Galasso, C Garon, EB Heist, RS Logan, J Neal, JW Mendenhall, MA Nichols, S Piotrowska, Z Wozniak, AJ Raponi, M Karlovich, CA Jaw-Tsai, S Isaacson, J Despain, D Matheny, SL Rolfe, L Allen, AR Camidge, DR AF Sequist, L. V. Soria, J-C Goldman, J. W. Wakelee, H. A. Gadgeel, S. M. Varga, A. Papadimitrakopoulou, V. Solomon, B. J. Oxnard, G. R. Dziadziuszko, R. Aisner, D. L. Doebele, R. C. Galasso, C. Garon, E. B. Heist, R. S. Logan, J. Neal, J. W. Mendenhall, M. A. Nichols, S. Piotrowska, Z. Wozniak, A. J. Raponi, M. Karlovich, C. A. Jaw-Tsai, S. Isaacson, J. Despain, D. Matheny, S. L. Rolfe, L. Allen, A. R. Camidge, D. R. TI Rociletinib in EGFR-Mutated Non-Small-Cell Lung Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYROSINE KINASE INHIBITORS; PHASE-II TRIAL; ACQUIRED-RESISTANCE; MUTATIONS; ERLOTINIB; GEFITINIB; AFATINIB; CHEMOTHERAPY; ADENOCARCINOMA AB BACKGROUND Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M. METHODS In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles. RESULTS A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51). CONCLUSIONS Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. C1 [Sequist, L. V.; Heist, R. S.; Logan, J.; Piotrowska, Z.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sequist, L. V.; Oxnard, G. R.; Heist, R. S.; Piotrowska, Z.] Harvard Univ, Sch Med, Boston, MA USA. [Oxnard, G. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Soria, J-C] Univ Paris 11, Drug Dev Dept, Villejuif, France. [Varga, A.] Inst Gustave Roussy, Villejuif, France. [Goldman, J. W.; Garon, E. B.; Mendenhall, M. A.; Nichols, S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wakelee, H. A.; Neal, J. W.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Gadgeel, S. M.; Galasso, C.; Wozniak, A. J.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Solomon, B. J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Dziadziuszko, R.] Med Univ Gdansk, Gdansk, Poland. [Aisner, D. L.; Camidge, D. R.] Univ Colorado, Aurora, CO USA. [Doebele, R. C.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Raponi, M.; Karlovich, C. A.; Jaw-Tsai, S.; Matheny, S. L.; Allen, A. R.] Clovis Oncol, San Francisco, CA USA. [Isaacson, J.; Despain, D.] Clovis Oncol, Boulder, CO USA. [Rolfe, L.] Clovis Oncol, Cambridge, England. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Dept Med, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM lvsequist@partners.org FU Clovis Oncology FX Supported by Clovis Oncology. NR 25 TC 243 Z9 251 U1 7 U2 39 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 APR 30 PY 2015 VL 372 IS 18 BP 1700 EP 1709 DI 10.1056/NEJMoa1413654 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000005 PM 25923550 ER PT J AU Aiello, LP Sun, WJ Das, A Gangaputra, S Kiss, S Klein, R Cleary, PA Lachin, JM Nathan, DM AF Aiello, Lloyd Paul Sun, Wanjie Das, Arup Gangaputra, Sapna Kiss, Szilard Klein, Ronald Cleary, Patricia A. Lachin, John M. Nathan, David M. CA DCCT EDIC Res Grp TI Intensive Diabetes Therapy and Ocular Surgery in Type 1 Diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CATARACT-SURGERY; COMPLICATIONS TRIAL; CARDIOVASCULAR-DISEASE; FOLLOW-UP; PROGRESSION; RETINOPATHY; INTERVENTIONS; EPIDEMIOLOGY; GLYCATION AB BACKGROUND The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes. METHODS Between 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies. RESULTS Over a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P = 0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P = 0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P = 0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up. CONCLUSIONS Intensive therapy in patients with type 1 diabetes was associated with a substantial reduction in the long-term risk of ocular surgery. C1 [Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Aiello, Lloyd Paul; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Sun, Wanjie; Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Biostat Ctr, Rockville, MD 20852 USA. [Das, Arup] Univ New Mexico, Albuquerque, NM 87131 USA. [Gangaputra, Sapna; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Kiss, Szilard] Weill Cornell Med Coll, New York, NY USA. [Kiss, Szilard] New York Presbyterian Hosp, New York, NY USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lachin, JM (reprint author), George Washington Univ, Biostat Ctr, 6110 Execut Blvd, Rockville, MD 20852 USA. EM jml@bsc.gwu.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841 FU Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK094176, U01 DK094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Center Program; Clinical and Translational Science Center FX 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 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 Awards Program (2006-present). Free or discounted supplies or equipment were contributed by Abbott Diabetes Care, Animas, Becton Dickinson, Diabetes Care by Bayer, Eli Lilly, Extend Nutrition, Insulet, LifeScan, Medtronic Diabetes, Nipro Home Diagnostics, Nova Diabetes Care, Omron, Perrigo Diabetes Care, Roche Diabetes Care, and Sanofi-Aventis. NR 34 TC 18 Z9 18 U1 0 U2 3 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 APR 30 PY 2015 VL 372 IS 18 BP 1722 EP 1733 DI 10.1056/NEJMoa1409463 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000007 ER PT J AU Shea, BS Sharma, A Mark, EJ AF Shea, Barry S. Sharma, Amita Mark, Eugene J. TI Case 14-2015: A 58-Year-Old Woman with Shortness of Breath SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTERSTITIAL LUNG-DISEASE; IDIOPATHIC PLEUROPARENCHYMAL FIBROELASTOSIS; CRYPTOGENIC ORGANIZING PNEUMONIA; CHRONIC EOSINOPHILIC PNEUMONIA; PULMONARY-FIBROSIS; STATINS; SARCOIDOSIS; ENTITY C1 [Shea, Barry S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shea, Barry S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shea, BS (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 32 TC 2 Z9 2 U1 0 U2 3 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 APR 30 PY 2015 VL 372 IS 18 BP 1749 EP 1758 DI 10.1056/NEJMcpc1415200 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000011 PM 25923555 ER PT J AU Ruberg, FL Berk, JL Semigan, MJ AF Ruberg, Frederick L. Berk, John L. Semigan, Marc J. TI V122I Transthyretin Variant in Elderly Black Americans SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARDIAC AMYLOIDOSIS C1 [Ruberg, Frederick L.; Berk, John L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Semigan, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ruberg, FL (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 30 PY 2015 VL 372 IS 18 BP 1768 EP 1768 DI 10.1056/NEJMc1503222 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000019 PM 25923563 ER PT J AU Smith, PK Hung, JW Michler, RE AF Smith, Peter K. Hung, Judy W. Michler, Robert E. TI Surgical Treatment of Moderate Ischemic Mitral Regurgitation REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Smith, Peter K.] Duke Univ, Durham, NC 27708 USA. [Hung, Judy W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. RP Smith, PK (reprint author), Duke Univ, Durham, NC 27708 USA. EM smith058@mc.duke.edu FU NHLBI NIH HHS [UM1 HL088939, U01 HL088942] NR 5 TC 1 Z9 1 U1 0 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 APR 30 PY 2015 VL 372 IS 18 BP 1773 EP 1774 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CG9RF UT WOS:000353655000027 PM 25923565 ER PT J AU Wolkowitz, OM Mellon, SH Lindqvist, D Epel, ES Blackburn, EH Lin, J Reus, VI Burke, H Rosser, R Mahan, L Mackin, S Yang, T Weiner, M Mueller, S AF Wolkowitz, Owen M. Mellon, Synthia H. Lindqvist, Daniel Epel, Elissa S. Blackburn, Elizabeth H. Lin, Jue Reus, Victor I. Burke, Heather Rosser, Rebecca Mahan, Laura Mackin, Scott Yang, Tony Weiner, Michael Mueller, Susanne TI PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Telomeres; Telomerase; Hippocampus; Leukocytes; Brain; Depression ID SHORTER TELOMERES; BRAIN-INJURY; REVERSE-TRANSCRIPTASE; COGNITIVE PERFORMANCE; NEUROTROPHIC FACTOR; CATALYTIC SUBUNIT; EMERGING ROLES; T-LYMPHOCYTES; DNA-DAMAGE; STRESS AB Accelerated cell aging, indexed in peripheral leukocytes by telomere shortness and in peripheral blood mononuclear cells (PBMCs) by telomerase activity, has been reported in several studies of major depressive disorder (MDD). However, the relevance of these peripheral measures for brain indices that are presumably more directly related to MDD pathophysiology is unknown. In this study, we explored the relationship between PBMC telomerase activity and leukocyte telomere length and magnetic resonance imaging-estimated hippocampal volume in un-medicated depressed individuals and healthy controls. We predicted that to the extent peripheral and central telomerase activity are directly related, PBMC telomerase activity would be positively correlated with hippocampal volume, perhaps due to hippocampal telomerase-associated neurogenesis, neuroprotection or neurotrophic facilitation, and that this effect would be clearer in individuals with increased PBMC telomerase activity, as previously reported in un-medicated MDD. We did not have specific hypotheses regarding the relationship between leukocyte telomere length and hippocampal volume, due to conflicting reports in the published literature. We found, in 25 un-medicated MDD subjects, that PBMC telomerase activity was significantly positively correlated with hippocampal volume; this relationship was not observed in 18 healthy controls. Leukocyte telomere length was not significantly related to hippocampal volume in either group (19 unmedicated MDD subjects and 17 healthy controls). Although the nature of the relationship between peripheral telomerase activity and telomere length and the hippocampus is unclear, these preliminary data are consistent with the possibility that PBMC telomerase activity indexes, and may provide a novel window into, hippocampal neuroprotection and/or neurogenesis in MDD. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Wolkowitz, Owen M.; Epel, Elissa S.; Reus, Victor I.; Burke, Heather; Rosser, Rebecca; Mahan, Laura; Mackin, Scott; Yang, Tony] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Mellon, Synthia H.] Univ Calif San Francisco, Sch Med, Dept OBGYN & Reprod Endocrinol, San Francisco, CA 94143 USA. [Lindqvist, Daniel] Lund Univ, Dept Clin Sci, Sect Psychiat, Lund, Sweden. [Blackburn, Elizabeth H.; Lin, Jue] Univ Calif San Francisco, Sch Med, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Weiner, Michael; Mueller, Susanne] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. [Weiner, Michael; Mueller, Susanne] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Wolkowitz, OM (reprint author), Univ Calif San Francisco, Sch Med, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM Owen.Wolkowitz@ucsf.edu RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU NIMH [1 R01 MH083784]; O'Shaughnessy Foundation; Tinberg Family; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health through UCSF-CTSI [UL1 RR024131] FX The research reported was supported by NIMH grant 1 R01 MH083784 (Co-PI's: O.M.W., E.S.E., S.H.M.), the UCSF Academic Senate and private donations from the O'Shaughnessy Foundation and the Tinberg Family. This project was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 68 TC 5 Z9 5 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2015 VL 232 IS 1 BP 58 EP 64 DI 10.1016/j.pscychresns.2015.01.007 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CG9HJ UT WOS:000353625300005 PM 25773002 ER PT J AU Ramchandani, R Finkelstein, DM Schoenfeld, DA AF Ramchandani, Ritesh Finkelstein, Dianne M. Schoenfeld, David A. TI A model-informed rank test for right-censored data with intermediate states SO STATISTICS IN MEDICINE LA English DT Article DE survival; auxiliary information; multi-state models; Gehan-Wilcoxon; rank test ID MULTISTATE MARKOV-MODELS; KAPLAN-MEIER STATISTICS; DISEASE PROGRESSION; SURVIVAL-DATA; PANEL-DATA; INFORMATION; INFECTION; MARKERS; SAMPLE; STAY AB The generalized Wilcoxon and log-rank tests are commonly used for testing differences between two survival distributions. We modify the Wilcoxon test to account for auxiliary information on intermediate disease states that subjects may pass through before failure. For a disease with multiple states where patients are monitored periodically but exact transition times are unknown (e.g. staging in cancer), we first fit a multi-state Markov model to the full data set; when censoring precludes the comparison of survival times between two subjects, we use the model to estimate the probability that one subject will have survived longer than the other given their censoring times and last observed status, and use these probabilities to compute an expected rank for each subject. These expected ranks form the basis of our test statistic. Simulations demonstrate that the proposed test can improve power over the log-rank and generalized Wilcoxon tests in some settings while maintaining the nominal type 1 error rate. The method is illustrated on an amyotrophic lateral sclerosis data set. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Ramchandani, Ritesh; Finkelstein, Dianne M.; Schoenfeld, David A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Finkelstein, Dianne M.; Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Ramchandani, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. EM ritesh@mail.harvard.edu FU National Institute of Health [T32NS048005, 5U01NS049640] FX This research was supported by National Institute of Health grants T32NS048005 and 5U01NS049640. We would also like to thank the referees for their helpful comments. NR 46 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD APR 30 PY 2015 VL 34 IS 9 BP 1454 EP 1466 DI 10.1002/sim.6417 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA CF4MV UT WOS:000352524100002 PM 25582933 ER PT J AU Kida, K Marutani, E Nguyen, RK Ichinose, F AF Kida, Kotaro Marutani, Eizo Nguyen, Rebecca K. Ichinose, Fumito TI Inhaled hydrogen sulfide prevents neuropathic pain after peripheral nerve injury in mice SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Neuropathic pain; Hydrogen sulfide; Microglia; Inflammatory cytokine ID ROOT GANGLION NEURONS; EXPRESSION; RATS; MONONEUROPATHY; HYPERALGESIA; ATF3; GLIA; INTERLEUKIN-6; INFLAMMATION; MODULATION AB Increasing evidence suggests that the pathogenesis of neuropathic pain is mediated through activation of microglia in the spinal cord. Hydrogen sulfide attenuates microglial activation and central nervous system inflammation; however, the role of hydrogen sulfide in neuropathic pain is unclear. In this study, we examined the effects of hydrogen sulfide breathing on neuropathic pain in mice. C57BL/6J mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. After CCI, mice breathed air alone or air mixed with hydrogen sulfide at 40 ppm for 8 h on 7 consecutive days. The expression levels of inflammatory cytokines including interleukin 6 (IL-6) were measured in the spinal cord. Effects of hydrogen sulfide on IL-6-induced activation of microglia were examined in primary rat microglia. Mice that breathed air alone exhibited the neuropathic pain behavior including mechanical allodynia and thermal hyperalgesia and increased mRNA levels of IL-6 and chemokine CC motif ligand 2 (CCL2) after CCI. Inhaled hydrogen sulfide prevented the neuropathic pain behavior and attenuated the upregulation of inflammatory cytokines. Sodium sulfide inhibited IL-6-induced activation of primary microglia. These results suggest that inhaled hydrogen sulfide prevents the development of neuropathic pain in mice possibly via inhibition of the activation of microglia in the spinal cord. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kida, Kotaro; Marutani, Eizo; Nguyen, Rebecca K.; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kida, Kotaro; Marutani, Eizo; Nguyen, Rebecca K.; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4315, Charlestown, MA 02129 USA. EM fichinose@mgh.harvard.edu FU American Heart Association's Founders Affiliate [13POST14530016]; Massachusetts General Hospital Tosteson Fund for Medical Discovery; R01 grant from the NHLBI [HL101930] FX This work was supported by postdoctoral fellowships from the American Heart Association's Founders Affiliate 13POST14530016 and from the Massachusetts General Hospital Tosteson Fund for Medical Discovery to KK and R01 grant from the NHLBI HL101930 to FI. NR 40 TC 3 Z9 3 U1 0 U2 10 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 APR 30 PY 2015 VL 46 SI SI BP 87 EP 92 DI 10.1016/j.niox.2014.11.014 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE0GY UT WOS:000351483700012 PM 25461302 ER PT J AU Adrich, LN Kuo, SY Castoreno, AB Goel, G Kuballa, P Rees, MG Seashore-Ludlow, BA Cheah, JH Latorre, IJ Schreiber, SL Shamji, AF Xavier, RJ AF Adrich, Leslie N. Kuo, Szu-Yu Castoreno, Adam B. Goel, Gautam Kuballa, Petric Rees, Matthew G. Seashore-Ludlow, Brinton A. Cheah, Jaime H. Latorre, Isabel J. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. TI Discovery of a Small-Molecule Probe for V-ATPase Function SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LYSOSOMAL MEMBRANE-PROTEINS; VACUOLAR H+-ATPASE; BUILD/COUPLE/PAIR STRATEGY; TUBULAR-ACIDOSIS; AMINO-ACIDS; AUTOPHAGY; INHIBITORS; IMMUNITY; INFLAMMATION; CHOLESTEROL AB Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been implicated in a number of diseases. Recent studies have elucidated roles for the lysosome in the regulation of protein synthesis, metabolism, membrane integrity, and other processes involved in homeostasis. Complex small-molecule natural products have greatly contributed to the investigation of lysosomal function in cellular physiology, Here we report the discovery of a novel, small-molecule modulator of lysosomal acidification derived from diversity-oriented synthesis through high-content screening. C1 [Adrich, Leslie N.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Adrich, Leslie N.; Kuo, Szu-Yu; Castoreno, Adam B.; Rees, Matthew G.; Seashore-Ludlow, Brinton A.; Cheah, Jaime H.; Latorre, Isabel J.; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Kuo, Szu-Yu] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Goel, Gautam; Kuballa, Petric; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Goel, Gautam; Kuballa, Petric; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Goel, Gautam; Kuballa, Petric; Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Schreiber, Stuart L.] Broad Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA. RP Schreiber, SL (reprint author), Broad Inst, Ctr Sci Therapeut, 415 Main St, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; ashamji@broadinstitute.org; xavier@molbio.mgh.harvard.edu OI Seashore-Ludlow, Brinton/0000-0001-8658-5967; Latorre, Isabel/0000-0003-0638-1783 FU Helmsley Charitable Trust [500203]; NIAID-sponsored Center for Excellence in Translational Research [U19AI109725]; National Institutes of Health [DK097485, U01CA176152] FX The authors would like to thank the Compound Management Team (Broad Institute) for providing compound plates and synthetic intermediates; Dr. Stephen Johnston (Broad Institute) for analytical support; and Dr. Michelle Stewart, Dr. Kara Lassen, Dr. Vlado Dancik, and Dr. Paul Clemons (Broad Institute) for valuable discussions. This research was supported by the Helmsley Charitable Trust (500203, S.L.S. and R.J.X.), the NIAID-sponsored Center for Excellence in Translational Research (U19AI109725, S.L.S., A.F.S., R.J.X.), and the National Institutes of Health (DK097485, R.J.X., and U01CA176152, S.L.S.). S.L.S. is an Investigator of the Howard Hughes Medical Institute. NR 38 TC 0 Z9 0 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 29 PY 2015 VL 137 IS 16 BP 5563 EP 5568 DI 10.1021/jacs.5b02150 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA CH3LF UT WOS:000353931500050 ER PT J AU Knabel, MK Ramachandran, K Karhadkar, S Hwang, HW Creamer, TJ Chivukula, RR Sheikh, F Clark, KR Torbenson, M Montgomery, RA Cameron, AM Mendell, JT Warren, DS AF Knabel, Matthew K. Ramachandran, Kalyani Karhadkar, Sunil Hwang, Hun-Way Creamer, Tyler J. Chivukula, Raghu R. Sheikh, Farooq Clark, K. Reed Torbenson, Michael Montgomery, Robert A. Cameron, Andrew M. Mendell, Joshua T. Warren, Daniel S. TI Systemic Delivery of scAAV8-Encoded MiR-29a Ameliorates Hepatic Fibrosis in Carbon Tetrachloride-Treated Mice SO PLOS ONE LA English DT Article ID ADENOASSOCIATED VIRUS; COLLAGEN EXPRESSION; PULMONARY-FIBROSIS; RENAL FIBROSIS; HUMAN-DISEASE; MICRORNAS; CELLS; CANCER; TRANSDUCTION; REGULATOR AB Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include miR-29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-beta. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of miR-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders. C1 [Knabel, Matthew K.; Ramachandran, Kalyani; Creamer, Tyler J.; Montgomery, Robert A.; Cameron, Andrew M.; Warren, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Knabel, Matthew K.; Ramachandran, Kalyani; Creamer, Tyler J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Karhadkar, Sunil] Temple Univ, Sch Med, Dept Surg, Philadelphia, PA 19122 USA. [Hwang, Hun-Way] Rockefeller Univ, Lab Mol Neurooncol, New York, NY 10021 USA. [Chivukula, Raghu R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sheikh, Farooq] Washington Hosp Ctr, Dept Cardiol, Washington, DC 20010 USA. [Clark, K. Reed] Nationwide Childrens Hosp, Ctr Gene Therapy, Res Inst, Columbus, OH USA. [Torbenson, Michael] Mayo Clin, Dept Pathol, Rochester, MN USA. [Mendell, Joshua T.] UT Southwestern Med Ctr, Dept Mol Biol, Dallas, TX USA. [Mendell, Joshua T.] UT Southwestern Med Ctr, Ctr Regenerat Sci & Med, Dallas, TX USA. [Mendell, Joshua T.] UT Southwestern Med Ctr, Simmons Canc Ctr, Dallas, TX USA. RP Warren, DS (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM warren@jhmi.edu OI Hwang, Hun-Way/0000-0003-0522-1577 FU NIH [R01CA120185, P01CA134292]; Cancer Prevention and Research Institute of Texas; Charles T. Bauer Foundation FX This work was supported by NIH grants R01CA120185 and P01CA134292 (J. Mendell), the Cancer Prevention and Research Institute of Texas (J. Mendell) and by a grant from the Charles T. Bauer Foundation (D. Warren). K. Reed Clark's participation occurred during his prior affiliation with the Center for Gene Therapy at The Research Institute at Nationwide Children's Hospital in Columbus, Ohio. Therefore, Dimension Therapeutics did not provide any financial support in the form of authors' salaries and/or research materials and played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 10 Z9 10 U1 0 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 APR 29 PY 2015 VL 10 IS 4 AR e0124411 DI 10.1371/journal.pone.0124411 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0LO UT WOS:000353711600083 PM 25923107 ER PT J AU Ma, J Guo, CY Guo, CW Sun, Y Liao, T Beattie, U Lopez, FJ Chen, DF Lashkari, K AF Ma, Jie Guo, Chenying Guo, Caiwei Sun, Yu Liao, Tiffany Beattie, Ursula Lopez, Francisco J. Chen, Dong Feng Lashkari, Kameran TI Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-I; PLURIPOTENT STEM-CELLS; NECROSIS-FACTOR-ALPHA; MOUSE MODEL; TRANSGENIC MICE; POSTNATAL-DEVELOPMENT; INTRAOCULAR-PRESSURE; VENTRICULAR MYOCYTES; BINDING PROTEIN-2; INSULIN-RECEPTOR AB We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNP(IGF-TD) cells displayed enhanced survival, and increased neurite extension and branching as compared to hNP(TD) or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNP(IGF-TD) cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNP(IGF-TD) cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma. C1 [Ma, Jie; Guo, Chenying; Guo, Caiwei; Sun, Yu; Liao, Tiffany; Beattie, Ursula; Chen, Dong Feng; Lashkari, Kameran] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. [Lopez, Francisco J.] GlaxoSmithKline, Ophthalmol DPU RD Alternat Discovery & Dev, King Of Prussia, PA 19406 USA. RP Lashkari, K (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM kameran_lashkari@meei.harvard.edu FU Canary Charitable Foundation, New York, NY FX This work was funded from an unrestricted grant from Canary Charitable Foundation, New York, NY to KL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 5 Z9 5 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 APR 29 PY 2015 VL 10 IS 4 AR e0125695 DI 10.1371/journal.pone.0125695 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0LO UT WOS:000353711600158 PM 25923430 ER PT J AU Sise, ME Backman, ES Wenger, JB Wood, BR Sax, PE Chung, RT Thadhani, R Kim, AY AF Sise, Meghan E. Backman, Elke S. Wenger, Julia B. Wood, Brian R. Sax, Paul E. Chung, Raymond T. Thadhani, Ravi Kim, Arthur Y. TI Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study SO PLOS ONE LA English DT Article ID ACUTE-RENAL-FAILURE; CHRONIC HCV INFECTION; GENOTYPE 1; DISEASE; RISK; THERAPY; INJURY; ASSOCIATION; OUTCOMES; PEGINTERFERON AB Background Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment. Methods Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine >= 0.3mg/dL from baseline during treatment with telaprevir. Results Between July 2011 to January 2013, seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m(2) compared to the group with baseline eGFR >= 90 mL/min/ 1.73m(2) (12 vs. 18 mL/min/1.73m(2), P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m(2) decrease in estimated glomerular filtration rate at twelve months in an adjusted model. Conclusions Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m(2) as previously reported. C1 [Sise, Meghan E.; Wenger, Julia B.; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. [Backman, Elke S.] Harvard Univ, Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02115 USA. [Wood, Brian R.] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sax, Paul E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Sise, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. EM msise@mgh.harvard.edu FU National Institute of Health [K24 DK078772]; American Society of Nephrology Foundation Fellowship Grant FX Funding provided by National Institute of Health - K24 DK078772 (RTC); American Society of Nephrology Foundation Fellowship Grant (MES), https://www.asn-online.org/grants/fellowships/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 1 Z9 1 U1 0 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 APR 29 PY 2015 VL 10 IS 4 AR e0124139 DI 10.1371/journal.pone.0124139 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0LO UT WOS:000353711600072 PM 25923243 ER PT J AU Hanley, PJ Melenhorst, JJ Nikiforow, S Scheinberg, P Blaney, JW Demmler-Harrison, G Cruz, CR Lam, S Krance, RA Leung, KS Martinez, CA Liu, H Douelc, DC Heslop, HE Rooney, CM Shpall, EJ Barrett, AJ Rodgers, JR Bollard, CM AF Hanley, Patrick J Melenhorst, Jan J Nikiforow, Sarah N Scheinberg, Phillip S Blaney, James W Demmler-Harrison, Gail D Cruz, C. Russell Lam, Sharon Krance, Robert A. Leung, Kathryn S. Martinez, Caridad A. Liu, Hao Douelc, Daniel C. Heslop, Helen E. Rooney, Cliona M. Shpall, Elizabeth J. Barrett, A. John Rodgers, John R. Bollard, Catherine M. TI CMV-specific T cells generated from naive T cells recognize atypical epitopes and may be protective in vivo SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; CELLULAR IMMUNE-RESPONSES; UMBILICAL-CORD BLOOD; VERSUS-HOST-DISEASE; PROPHYLACTIC INFUSION; ADOPTIVE TRANSFER; VIRAL-INFECTIONS; PROTEIN PP65; CYTOMEGALOVIRUS; TRANSPLANTATION AB Adoptive transfer of cytomegalovirus (CMV)-specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naive cells for T cell therapy. Naive T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities. CMV-seropositive individuals also had T cells recognizing these atypical epitopes, but these cells had a lower avidity than those derived from the seronegative subjects, which suggests that high-avidity T cells to these epitopes may be lost over time. Indeed, recipients of cord blood (CB) grafts who did not develop CMV were found by clonotypic analysis to have T cells recognizing atypical CMVpp65 epitopes. Therefore, we examined unmanipulated CB units and found that T cells with T cell receptors restricted by atypical epitopes were the most common, which may explain why these T cells expanded. When infused to recipients, naive donor-derived virus-specific T cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission. These data suggest that naive-derived T cells from seronegative patients may be an additional source of cells for CMV immunoprophylaxis. C1 [Hanley, Patrick J; Blaney, James W; Cruz, C. Russell; Lam, Sharon; Krance, Robert A.; Leung, Kathryn S.; Martinez, Caridad A.; Liu, Hao; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Hanley, Patrick J; Blaney, James W; Cruz, C. Russell; Lam, Sharon; Krance, Robert A.; Leung, Kathryn S.; Martinez, Caridad A.; Liu, Hao; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Houston Methodist Hosp, Houston, TX USA. [Hanley, Patrick J; Lam, Sharon; Rooney, Cliona M.; Rodgers, John R.; Bollard, Catherine M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Hanley, Patrick J; Cruz, C. Russell; Lam, Sharon; Bollard, Catherine M.] George Washington Univ, Program Cell Enhancement & Technol Immunotherapy, Sheikh Zayed Inst Pediat Surg Innovat, Ctr Canc & Immunol Res, Washington, DC 20052 USA. [Hanley, Patrick J; Lam, Sharon; Bollard, Catherine M.] George Washington Univ, Div Blood & Marrow Transplantat, Childrens Natl Hlth Syst, Washington, DC 20052 USA. [Melenhorst, Jan J; Scheinberg, Phillip S; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Nikiforow, Sarah N] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Demmler-Harrison, Gail D; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Krance, Robert A.; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Douelc, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Rooney, Cliona M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Shpall, Elizabeth J.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Bollard, CM (reprint author), Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. EM cbollard@cnmc.org FU American Cancer Society [PF-13e046e01-LIB]; Cancer Prevention Research Institute of Texas [RO1 RP100469]; National Cancer Institute [PO1 CA148600e02] FX Funding: This work was supported by a postdoctoral fellowship, PF-13e046e01-LIB, from the American Cancer Society awarded to P.J.H., Cancer Prevention Research Institute of Texas RO1 RP100469 (to C.M.B.), and National Cancer Institute PO1 CA148600e02 (to C.M.B. and E.J.S.) awards. NR 50 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 29 PY 2015 VL 7 IS 285 AR 285ra63 DI 10.1126/scitranslmed.aaa2546 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CH1MB UT WOS:000353784700006 PM 25925682 ER PT J AU Serano, P Angelone, LM Katnani, H Eskandar, E Bonmassar, G AF Serano, Peter Angelone, Leonardo M. Katnani, Husam Eskandar, Emad Bonmassar, Giorgio TI A Novel Brain Stimulation Technology Provides Compatibility with MRI SO Scientific Reports LA English DT Article ID ABSORPTION RATE; HUMAN HEAD; 1.5 T; METALLIC IMPLANTS; OBLIQUE-INCIDENCE; SIMULTANEOUS EEG; IN-VITRO; DEEP; ELECTRODES; SYSTEMS AB Clinical electrical stimulation systems - such as pacemakers and deep brain stimulators (DBS) - are an increasingly common therapeutic option to treat a large range of medical conditions. Despite their remarkable success, one of the significant limitations of these medical devices is the limited compatibility with magnetic resonance imaging (MRI), a standard diagnostic tool in medicine. During an MRI exam, the leads used with these devices, implanted in the body of the patient, act as an electric antenna potentially causing a large amount of energy to be absorbed in the tissue, which can lead to serious heat-related injury. This study presents a novel lead design that reduces the antenna effect and allows for decreased tissue heating during MRI. The optimal parameters of the wire design were determined by a combination of computational modeling and experimental measurements. The results of these simulations were used to build a prototype, which was tested in a gel phantom during an MRI scan. Measurement results showed a three-fold decrease in heating when compared to a commercially available DBS lead. Accordingly, the proposed design may allow a significantly increased number of patients with medical implants to have safe access to the diagnostic benefits of MRI. C1 [Serano, Peter; Angelone, Leonardo M.; Bonmassar, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Serano, Peter] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. [Serano, Peter; Angelone, Leonardo M.] US FDA, Ctr Devices & Radiol Hlth, Div Biomed Phys, Off Sci & Engn Labs, Silver Spring, MD USA. [Katnani, Husam; Eskandar, Emad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Bonmassar, G (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM giorgio.bonmassar@mgh.harvard.edu FU NIH/NINDS [U01-NS075026]; NIH/NIBIB [1R21EB016449-01A1]; National Center for Research Resources [P41-RR14075]; MIND institute FX The authors acknowledge Karen Lindell, Richard Gray, Sunder Rajan, Bruce Rosen, Brian Beard, and Devashish Shrivastava for scientific discussion, and John Kirsch for software support with the temperature measurements. This research was supported by the grants U01-NS075026 (NIH/NINDS), 1R21EB016449-01A1 (NIH/NIBIB), the National Center for Research Resources (P41-RR14075), and by the MIND institute. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 61 TC 3 Z9 3 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 29 PY 2015 VL 5 AR 9805 DI 10.1038/srep09805 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9GB UT WOS:000353621700001 PM 25924189 ER PT J AU Haghighi, F Galfalvy, H Chen, S Huang, YY Cooper, TB Burke, AK Oquendo, MA Mann, JJ Sublette, ME AF Haghighi, Fatemeh Galfalvy, Hanga Chen, Sean Huang, Yung-yu Cooper, Thomas B. Burke, Ainsley K. Oquendo, Maria A. Mann, J. John Sublette, M. Elizabeth TI DNA methylation perturbations in genes involved in polyunsaturated fatty acid biosynthesis associated with depression and suicide risk SO FRONTIERS IN NEUROLOGY LA English DT Article DE DNA methylation; epigenetics; suicide; major depressive disorder; polyunsaturated omega-3/omega-6; fatty acids; Fads1 fatty acid desaturase; elongation of very long-chain fatty acids protein 5 ID EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; PREFRONTAL CORTEX; DESATURASE; DISORDER; SUPPLEMENTATION; METAANALYSIS; METABOLISM; EFFICACY; TRIALS AB Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and a-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n =22) and without (n=39) history of suicide attempt, and age- and sex-matched healthy volunteers (n=59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads 1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (ElovI5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in ElovI5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of ElovI5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. C1 [Haghighi, Fatemeh] James J Peters Vet Affairs Med Ctr, Dept Psychiat, New York, NY USA. [Haghighi, Fatemeh; Chen, Sean] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Haghighi, Fatemeh; Chen, Sean] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Galfalvy, Hanga; Cooper, Thomas B.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John; Sublette, M. Elizabeth] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Galfalvy, Hanga] New York State Psychiat Inst & Hosp, Div Biostat, New York, NY 10032 USA. [Huang, Yung-yu; Cooper, Thomas B.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John; Sublette, M. Elizabeth] New York State Psychiat Inst & Hosp, Div Mol Imaging & Neuropathol, New York, NY 10032 USA. [Cooper, Thomas B.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Mann, J. John] Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. RP Haghighi, F (reprint author), Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, 1425 Madison Ave,Floor 10,Room 10-70D, New York, NY 10029 USA. EM fatemeh.haghighi@mssm.edu RI Sublette, M/A-8391-2009 OI Sublette, M/0000-0001-7378-4262 NR 47 TC 6 Z9 6 U1 1 U2 9 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 APR 28 PY 2015 VL 6 AR UNSP 92 DI 10.3389/fneur.2015.00092 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU8GR UT WOS:000363780200001 PM 25972837 ER PT J AU Song, WG Cajigas, I Brownz, EN Giszter, SF AF Song, Weiguo Cajigas, Iahn Brownz, Emery N. Giszter, Simon F. TI Adaptation to elastic loads and BMI robot controls during rat locomotion examined with point-process GLMs SO FRONTIERS IN SYSTEMS NEUROSCIENCE LA English DT Article DE augmenting BMI; elastic field; point-process general linear model; exoskeleton robot model system; motor adaptation ID NEURAL SPIKING ACTIVITY; FUNCTIONAL CONNECTIVITY; ACTION-POTENTIALS; MOTOR CORTEX; NEURONS; ENSEMBLE; INFORMATION; INTERFACES; STABILITY; TRAINS AB Currently little is known about how a mechanically coupled BMI system's actions are integrated into ongoing body dynamics. We tested a locomotor task augmented with a BMI system driving a robot mechanically interacting with a rat under three conditions: control locomotion (BL), "simple elastic load" (E) and "BMI with elastic load" (BMI/E). The effect of the BMI was to allow compensation of the elastic load as a function of the neural drive. Neurons recorded here were close to one another in cortex, all within a 200 micron diameter horizontal distance of one another. The interactions of these close assemblies of neurons may differ from those among neurons at longer distances in BMI tasks and thus are important to explore. A point process generalized linear model (GLM), was used to examine connectivity at two different binning timescales (1 ms vs. 10 ms). We used GLM models to fit non-Poisson neural dynamics solely using other neurons' prior neural activity as covariates. Models at different timescales were compared based on Kolmogorov-Smirnov (KS) goodness-of-fit and parsimony. About 15% of cells with non-Poisson firing were well fitted with the neuron-to-neuron models alone. More such cells were fitted at the 1 ms binning than 10 ms. Positive connection parameters ("excitation" 70%) exceeded negative parameters ("inhibition" 30%). Significant connectivity changes in the GLM determined networks of well-fitted neurons occurred between the conditions. However, a common core of connections comprising at least 15% of connections persisted between any two of the three conditions. Significantly almost twice as many connections were in common between the two load conditions (-27%), compared to between either load condition and the baseline. This local point process GLM identified neural correlation structure and the changes seen across task conditions in the rats in this neural subset may be intrinsic to cortex or due to feedback and input reorganization in adaptation. C1 [Song, Weiguo; Giszter, Simon F.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Cajigas, Iahn; Brownz, Emery N.] MIT, Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brownz, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Brownz, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Giszter, Simon F.] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA. RP Giszter, SF (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19104 USA. EM sgiszter@drexelmed.edu FU NIGMS NIH HHS [R01 GM104948]; NIH HHS [DP1 OD003646]; NINDS NIH HHS [F31 NS058275, R01 NS054894] NR 44 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5137 J9 FRONT SYST NEUROSCI JI Front. Syst. Neurosci. PD APR 28 PY 2015 VL 9 AR 62 DI 10.3389/fnsys.2015.00062 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CU6YX UT WOS:000363682400001 PM 25972789 ER PT J AU Povoa, P Salluh, JIF Martinez, ML Guillamat-Prats, R Gallup, D Al-Khalidi, HR Thompson, BT Ranieri, VM Artigas, A AF Povoa, Pedro Salluh, Jorge I. F. Martinez, Maria L. Guillamat-Prats, Raquel Gallup, Dianne Al-Khalidi, Hussein R. Thompson, B. Taylor Ranieri, V. Marco Artigas, Antonio TI Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial SO CRITICAL CARE LA English DT Article ID SURVIVING SEPSIS CAMPAIGN; RANDOMIZED CONTROLLED-TRIAL; ACTIVATED PROTEIN-C; INTERNATIONAL GUIDELINES; CRITICAL ILLNESS; UNITED-STATES; HYDROCORTISONE; CORTICOSTEROIDS; MANAGEMENT; THERAPY AB Introduction: The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. Methods: We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. Results: A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. Conclusions: In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo. C1 [Povoa, Pedro] Ctr Hosp Lisboa Ocidental, Sao Francisco Xavier Hosp, Polyvalent Intens Care Unit, Lisbon, Portugal. [Povoa, Pedro] Univ Nova Lisboa, CEDOC, NOVA Med Sch, Lisbon, Portugal. [Salluh, Jorge I. F.] Dor Inst Res & Educ, Rio De Janeiro, Brazil. [Salluh, Jorge I. F.] Inst Nacl Canc, Postgrad Program, Rio De Janeiro, Brazil. [Martinez, Maria L.; Guillamat-Prats, Raquel; Artigas, Antonio] Univ Autonoma Barcelona, Sabadell Hosp, Crit Care Ctr, Sabadell, Spain. [Martinez, Maria L.; Guillamat-Prats, Raquel; Artigas, Antonio] CIBER Enfermedades Resp CIBERES, Madrid, Spain. [Gallup, Dianne; Al-Khalidi, Hussein R.] Duke Clin Res Inst, Durham, NC USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Ranieri, V. Marco] Univ Turin, Azienda Osped Citta Salute & Sci Torino Molinette, Dipartimento Anestesiol & Rianimaz, Turin, Italy. RP Povoa, P (reprint author), Ctr Hosp Lisboa Ocidental, Sao Francisco Xavier Hosp, Polyvalent Intens Care Unit, Lisbon, Portugal. EM pedrorpovoa@gmail.com RI Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Guillamat-Prats, Raquel/0000-0001-6960-0985 FU Eli Lilly; XIX CBMI - Brazilian Congress of Intensive Care FX Eli Lilly funded the PROWESS-Shock trial [15]: the database of the trial was used for the present study. We thank the Steering Committee of the PROWESS-Shock trial (funded by Eli Lilly) for accepting the proposal of the present substudy, the Data Monitoring Committee and PROWESS-Shock investigators; all data are provided in: Supplement to Ranieri VM et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012;366:2055-64 [15]. We thank Karen Pieper for her insights in the analyses of study data and assistance in the preparation of the manuscript. This work was presented in part at the XIX CBMI - Brazilian Congress of Intensive Care, 6 to 8 November 2014, Goiania, Brazil. NR 39 TC 3 Z9 3 U1 0 U2 3 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 APR 28 PY 2015 VL 19 AR 193 DI 10.1186/s13054-015-0921-x PG 10 WC Critical Care Medicine SC General & Internal Medicine GA CK8HY UT WOS:000356480300001 PM 25928214 ER PT J AU Ahmed, MY Chioza, BA Rajab, A Schmitz-Abe, K Al-Khayat, A Al-Turki, S Baple, EL Patton, MA Al-Memar, AY Hurles, ME Partlow, JN Hill, RS Evrony, GD Servattalab, S Markianos, K Walsh, CA Crosby, AH Mochida, GH AF Ahmed, Mustafa Y. Chioza, Barry A. Rajab, Anna Schmitz-Abe, Klaus Al-Khayat, Aisha Al-Turki, Saeed Baple, Emma L. Patton, Michael A. Al-Memar, Ali Y. Hurles, Matthew E. Partlow, Jennifer N. Hill, R. Sean Evrony, Gilad D. Servattalab, Sarah Markianos, Kyriacos Walsh, Christopher A. Crosby, Andrew H. Mochida, Ganeshwaran H. TI Loss of PCLO function underlies pontocerebellar hypoplasia type III SO NEUROLOGY LA English DT Article ID PICCOLO; BASSOON; MAPS AB Objective:To identify the genetic cause of pontocerebellar hypoplasia type III (PCH3).Methods:We studied the original reported pedigree of PCH3 and performed genetic analysis including genome-wide single nucleotide polymorphism genotyping, linkage analysis, whole-exome sequencing, and Sanger sequencing. Human fetal brain RNA sequencing data were then analyzed for the identified candidate gene.Results:The affected individuals presented with severe global developmental delay and seizures starting in the first year of life. Brain MRI of an affected individual showed diffuse atrophy of the cerebrum, cerebellum, and brainstem. Genome-wide single nucleotide polymorphism analysis confirmed the linkage to chromosome 7q we previously reported, and showed no other genomic areas of linkage. Whole-exome sequencing of 2 affected individuals identified a shared homozygous, nonsense variant in the PCLO (piccolo) gene. This variant segregated with the disease phenotype in the pedigree was rare in the population and was predicted to eliminate the PDZ and C2 domains in the C-terminus of the protein. RNA sequencing data of human fetal brain showed that PCLO was moderately expressed in the developing cerebral cortex.Conclusions:Here, we show that a homozygous, nonsense PCLO mutation underlies the autosomal recessive neurodegenerative disorder, PCH3. PCLO is a component of the presynaptic cytoskeletal matrix, and is thought to be involved in regulation of presynaptic proteins and synaptic vesicles. Our findings suggest that PCLO is crucial for the development and survival of a wide range of neuronal types in the human brain. C1 [Ahmed, Mustafa Y.; Chioza, Barry A.; Baple, Emma L.; Crosby, Andrew H.] Univ Exeter, Sch Med, RILD Wellcome Wolfson Ctr, Monogen Mol Genet,Royal Devon & Exeter NHS Fdn Tr, Exeter, Devon, England. [Ahmed, Mustafa Y.; Chioza, Barry A.; Baple, Emma L.; Patton, Michael A.; Crosby, Andrew H.] Univ London, Ctr Human Genet, London WC1E 7HU, England. [Rajab, Anna] Minist Hlth, Natl Genet Ctr, Muscat, Oman. [Schmitz-Abe, Klaus; Partlow, Jennifer N.; Hill, R. Sean; Evrony, Gilad D.; Servattalab, Sarah; Markianos, Kyriacos; Walsh, Christopher A.; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA. [Schmitz-Abe, Klaus; Partlow, Jennifer N.; Hill, R. Sean; Evrony, Gilad D.; Servattalab, Sarah; Markianos, Kyriacos; Walsh, Christopher A.; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Partlow, Jennifer N.; Hill, R. Sean; Evrony, Gilad D.; Servattalab, Sarah; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. [Schmitz-Abe, Klaus; Markianos, Kyriacos; Walsh, Christopher A.; Mochida, Ganeshwaran H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Evrony, Gilad D.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Schmitz-Abe, Klaus; Markianos, Kyriacos; Walsh, Christopher A.] Broad Inst MIT & Harvard Univ, Program Med & Populat Genet, Cambridge, MA USA. [Al-Khayat, Aisha] Sultan Qaboos Univ, Dept Biol, Coll Sci, Muscat, Oman. [Al-Turki, Saeed; Hurles, Matthew E.] Wellcome Trust Genome Campus, Trust Sanger Inst, Cambridge, England. [Al-Memar, Ali Y.] Univ London St Georges Hosp, Dept Neurol, Atkinson Morley Wing, London, England. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mochida, GH (reprint author), Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA. EM ganesh.mochida@childrens.harvard.edu FU Manton Center for Orphan Disease Research, National Institute of Neurological Disorders and Stroke [R01NS035129]; NIH/Fogarty International Center [R21TW008223]; Dubai Harvard Foundation for Medical Research; Qatar National Research Fund; Boston Children's Hospital Faculty Career Development Award; Medical Research Council [G1002279]; Newlife Foundation for Disabled Children; F. Hoffmann-La Roche Ltd. FX The study was supported by grants from the Manton Center for Orphan Disease Research, National Institute of Neurological Disorders and Stroke (R01NS035129), NIH/Fogarty International Center (R21TW008223), Dubai Harvard Foundation for Medical Research, Qatar National Research Fund, Boston Children's Hospital Faculty Career Development Award, Medical Research Council (G1002279), and Newlife Foundation for Disabled Children. C.A.W. is an investigator of the Howard Hughes Medical Institute. G.H.M. was also supported by grants from F. Hoffmann-La Roche Ltd., Qatar National Research Fund, and Boston Children's Hospital Faculty Career Development Award. NR 19 TC 4 Z9 4 U1 1 U2 3 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 APR 28 PY 2015 VL 84 IS 17 BP 1745 EP 1750 DI 10.1212/WNL.0000000000001523 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CH5GB UT WOS:000354062200011 PM 25832664 ER PT J AU Su, M Yang, CC Trikamji, B Mishra, S AF Su, Michael Yang, Chih-Chao Trikamji, Bhavesh Mishra, Shri TI HISTORY OF NEUROLOGY IN TAIWAN SO NEUROLOGY LA English DT Article AB Neurology, as an independent medical specialty, is a relatively young field, originally stemming from internal medicine and psychiatry. The roots of neurology in Taiwan are no different. Modern neurology in Taiwan was established in the 1950s. Prior to that, neurologic diseases were uncommon and mainly consisted of infectious diseases of CNS. The 1950s brought on the establishment of dedicated neurology clinics and primary neurology training at various sites in Taiwan.(1) The expansion of these sites continued to flourish over the next several decades. Neurology was further developed with the creation and induction of academic societies and conferences, as well as adoption of modern diagnostic techniques and therapeutics. This has firmly set neurology as a stand-alone specialty in Taiwan. C1 [Su, Michael] UCLA Med Ctr, Dept Neurol, Los Angeles, CA USA. [Yang, Chih-Chao] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan. [Trikamji, Bhavesh] Olive View UCLA Med Ctr, Dept Neurol, Sylmar, CA 91342 USA. [Trikamji, Bhavesh] VA Greater Los Angeles HCS, Dept Neurol, Los Angeles, CA USA. [Mishra, Shri] VA Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. RP Mishra, S (reprint author), VA Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. EM smishra@usc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 28 PY 2015 VL 84 IS 17 BP 1803 EP 1804 DI 10.1212/WNL.0000000000001513 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CH5GB UT WOS:000354062200019 PM 25917485 ER PT J AU Lin, YW Chen, CC Lin, LC Lee, SP AF Lin, Yu-Wei Chen, Chia-Chun Lin, Li-Ching Lee, Steve P. TI The Impact of Reduced-Volume, Intensity-Modulated Radiation Therapy on Disease Control in Nasopharyngeal Carcinoma SO PLOS ONE LA English DT Article ID NECK-CANCER; CLINICAL-OUTCOMES; TARGET VOLUMES; RADIOTHERAPY; HEAD; EXPERIENCE; PATTERNS; FAILURE; IRRADIATION; DELINEATION AB Objective To investigate the feasibility of using intensity-modulated radiotherapy (IMRT) with reduced, high-dose target volumes for nasopharyngeal carcinoma (NPC). Methods The first 57 patients (admitted from October 2005 to May 2008) were treated with large-target-volume IMRT (LV-IMRT). For the LV-IMRT group, the CTV at 70 Gy (CTV70) was delineated as the gross target volume (GTV) plus 7mm, with or without the first-echelon lymphnode region. The next 56 patients (admitted from June 2008 to November 2011) were treated with reduced-target-volume IMRT (RV-IMRT). For the RV-IMRT group, the CTV70 was delineated as the GTV alone. Results The 4-year local recurrence-free, regional recurrence-free, distant metastasis-free, progression-free, and overall survival rates were 77.2%, 80.1%, 83.2%, 61.2%, and 74.4% for the LV-IMRT group and 83.5%, 92.6%, 89.1%, 78.5, and 91.0% for the RV-IMRT group, respectively. Late toxicity scoring of xerostomia was lesser in the RV-IMRT group than the LV-IMRT group (P < 0.001). Conclusions The use of RV-IMRT for the treatment of NPC did not negatively affect survival rates but did reduce the late xerostomia events compared to LV-IMRT. C1 [Lin, Yu-Wei; Lin, Li-Ching] Chi Mei Med Ctr, Dept Radiat Oncol, Tainan, Taiwan. [Lin, Yu-Wei] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan. [Lin, Yu-Wei] Kaohsiung Med Univ, Sch Med, Kaohsiung, Taiwan. [Chen, Chia-Chun] Chi Mei Med Ctr, Dept Radiat Oncol, Tainan, Taiwan. [Lin, Li-Ching] Taipei Med Univ, Sch Med, Taipei, Taiwan. [Lee, Steve P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Lee, Steve P.] VA Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. RP Lin, YW (reprint author), Chi Mei Med Ctr, Dept Radiat Oncol, Tainan, Taiwan. EM marklin1108@gmail.com; splee@mednet.ucla.edu NR 32 TC 2 Z9 2 U1 2 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 APR 28 PY 2015 VL 10 IS 4 AR e0125283 DI 10.1371/journal.pone.0125283 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9SE UT WOS:000353659400079 PM 25919285 ER PT J AU Neely, BA Ferrante, JA Chaves, JM Soper, JL Almeida, JS Arthur, JM Gulland, FMD Janech, MG AF Neely, Benjamin A. Ferrante, Jason A. Chaves, J. Mauro Soper, Jennifer L. Almeida, Jonas S. Arthur, John M. Gulland, Frances M. D. Janech, Michael G. TI Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus) Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis SO PLOS ONE LA English DT Article ID TOXICITY; NMDA; GLYCOSYLATION; NEUROTOXICITY; PATHOLOGY; EPILEPSY; NEURONS; DISEASE; MODEL; RATS AB Domoic acid toxicosis (DAT) in California sea lions (Zalophus californianus) is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05). Interestingly, 11 apolipoprotein E (ApoE) charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value) and high specificity (92.3% with 85.7% positive predictive value). These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers. C1 [Neely, Benjamin A.; Ferrante, Jason A.; Chaves, J. Mauro; Arthur, John M.; Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Ferrante, Jason A.; Janech, Michael G.] Coll Charleston, Grice Marine Lab, Charleston, SC 29401 USA. [Soper, Jennifer L.; Gulland, Frances M. D.] Marine Mammal Ctr, Sausalito, CA USA. [Almeida, Jonas S.] SUNY Stony Brook, Dept Biomed Informat, Long Isl City, NY USA. [Arthur, John M.; Janech, Michael G.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Janech, MG (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. EM janechmg@musc.edu OI Neely, Benjamin/0000-0001-6120-7695 FU Office of Naval Research [N00014-08-1-0341] FX Funding: Funding for this work, and for BAN JAF JMC JLS JSA JMA FMDG MGJ, was provided by the Office of Naval Research (N00014-08-1-0341). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 3 Z9 3 U1 2 U2 11 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 APR 28 PY 2015 VL 10 IS 4 AR e0123295 DI 10.1371/journal.pone.0123295 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9SE UT WOS:000353659400026 ER PT J AU Catalano, OA Nicolai, E Rosen, BR Luongo, A Catalano, M Iannace, C Guimaraes, A Vangel, MG Mahmood, U Soricelli, A Salvatore, M AF Catalano, O. A. Nicolai, E. Rosen, B. R. Luongo, A. Catalano, M. Iannace, C. Guimaraes, A. Vangel, M. G. Mahmood, U. Soricelli, A. Salvatore, M. TI Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients SO BRITISH JOURNAL OF CANCER LA English DT Article DE PET-CT; PET-MR; skeletal metastases; osseous metastases; breast cancer ID POSITRON-EMISSION-TOMOGRAPHY; WHOLE-BODY MRI; IMAGING BONE METASTASES; DUAL-TIME-POINT; LUNG-CANCER; PROSTATE-CANCER; LYMPH-NODES; SCINTIGRAPHY; CARCINOMA; DIAGNOSIS AB Background: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 (Tc-99) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. Methods: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET- MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a chi(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. Results: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%+/- 7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. Conclusions: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT. C1 [Catalano, O. A.; Soricelli, A.] Univ Naples Parthenope, SDN IRCCS, Dept Radiol, I-80143 Naples, Na, Italy. [Nicolai, E.] SDN IRCCS, Dept Nucl Med, I-80143 Naples, Na, Italy. [Rosen, B. R.; Mahmood, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Luongo, A.; Catalano, M.] Univ Naples Federico II, Dept Radiol, I-80131 Naples, NA, Italy. [Iannace, C.] G Moscati Hosp, Dept Surg, Breast Unit, I-83100 Avellino, AV, Italy. [Guimaraes, A.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Vangel, M. G.] Harvard Univ, Sch Med, MGH Biostat Ctr, Dept Radiol, Charlestown, MA 02129 USA. [Vangel, M. G.] Harvard Univ, Sch Med, MGH Martinos Ctr, Charlestown, MA 02129 USA. [Salvatore, M.] SDN IRCCS, Dept Radiol & Nucl Med, I-80143 Naples, Na, Italy. RP Catalano, OA (reprint author), Univ Naples Parthenope, SDN IRCCS, Dept Radiol, Via F Acton 38, I-80143 Naples, Na, Italy. EM onofriocatalano@yahoo.it RI Nicolai, Emanuele/K-6678-2016; soricelli, andrea/C-1133-2009; Salvatore, Marco/K-8083-2016 OI Nicolai, Emanuele/0000-0003-3171-368X; soricelli, andrea/0000-0001-7011-7667; Salvatore, Marco/0000-0001-9734-7702 NR 41 TC 13 Z9 15 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 28 PY 2015 VL 112 IS 9 BP 1452 EP 1460 DI 10.1038/bjc.2015.112 PG 9 WC Oncology SC Oncology GA CG9SG UT WOS:000353659800005 PM 25871331 ER PT J AU Corapi, KM Dooley, MA Pendergraft, WF AF Corapi, Kristin M. Dooley, Mary Anne Pendergraft, William F., III TI Comparison and evaluation of lupus nephritis response criteria in lupus activity indices and clinical trials SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID RHEUMATOLOGY DAMAGE INDEX; SURROGATE END-POINTS; STAGE RENAL-DISEASE; REVISED SLAM-R; MYCOPHENOLATE-MOFETIL; INTRAVENOUS CYCLOPHOSPHAMIDE; ACTIVITY QUESTIONNAIRE; ERYTHEMATOSUS; EFFICACY; THERAPY AB Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations. Although the approval of new therapies includes only one agent in 50 years, a number of promising new drugs are in development. Lupus nephritis is a dreaded complication of SLE as it is associated with significant morbidity and mortality. Advancing the treatment of lupus nephritis requires well-designed clinical trials and this can be challenging in SLE. The major obstacles involve identifying the correct population of patients to enroll and ensuring that a clinically appropriate and patient-centered endpoint is being measured. In this review, we will first discuss the clinical utility of endpoints chosen to represent lupus nephritis in global disease activity scales. Second, we will review completed and active trials focused on lupus nephritis and discuss the endpoints chosen. There are many important lessons to be learned from existing assessment tools and clinical trials. Reviewing these points will help ensure that future efforts will yield meaningful disease activity measures and well-designed clinical trials to advance our understanding of lupus management. C1 [Corapi, Kristin M.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Dooley, Mary Anne; Pendergraft, William F., III] Univ N Carolina, Kidney Ctr, Dept Med, Div Nephrol, Chapel Hill, NC 27599 USA. RP Corapi, KM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 55 Fruit St, Boston, MA 02114 USA. EM kcorapi@partners.org NR 48 TC 3 Z9 3 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD APR 28 PY 2015 VL 17 AR 110 DI 10.1186/s13075-015-0621-6 PG 13 WC Rheumatology SC Rheumatology GA CG6XX UT WOS:000353447100001 PM 25927414 ER PT J AU Wasfy, JH Borden, WB Secemsky, EA McCabe, JM Yeh, RW AF Wasfy, Jason H. Borden, William B. Secemsky, Eric A. McCabe, James M. Yeh, Robert W. TI Public Reporting in Cardiovascular Medicine Accountability, Unintended Consequences, and Promise for Improvement SO CIRCULATION LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; NEW-YORK-STATE; PROFILING HOSPITAL PERFORMANCE; ASSISTED REPRODUCTIVE TECHNOLOGY; ALTERNATIVE QUALITY CONTRACT; CAUSE READMISSION RATES; CARDIAC-SURGERY; CLINICAL-OUTCOMES; MEDICARE BENEFICIARIES C1 [Wasfy, Jason H.; Secemsky, Eric A.; Yeh, Robert W.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. [Borden, William B.] George Washington Univ, Sch Med, Div Cardiol, Washington, DC USA. [Secemsky, Eric A.; Yeh, Robert W.] Harvard Clin Res Inst, Boston, MA USA. [McCabe, James M.] Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org NR 84 TC 6 Z9 6 U1 1 U2 4 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 APR 28 PY 2015 VL 131 IS 17 BP 1518 EP + DI 10.1161/CIRCULATIONAHA.114.014118 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CG8LX UT WOS:000353560600011 PM 25918041 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI What to Expect When Measuring High-Sensitivity Troponin Practical Advice for Clinicians SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE acute coronary syndrome; assay; chest pain; myocardial infarction ID MYOCARDIAL-INFARCTION C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 7 TC 7 Z9 7 U1 1 U2 1 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 APR 28 PY 2015 VL 65 IS 16 BP 1665 EP 1667 DI 10.1016/j.jacc.2015.02.045 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5MZ UT WOS:000353337300010 PM 25908072 ER PT J AU Benedetti, M Pontiggia, D Raggi, S Cheng, ZY Scaloni, F Ferrari, S Ausubel, FM Cervone, F De Lorenzo, G AF Benedetti, Manuel Pontiggia, Daniela Raggi, Sara Cheng, Zhenyu Scaloni, Flavio Ferrari, Simone Ausubel, Frederick M. Cervone, Felice De Lorenzo, Giulia TI Plant immunity triggered by engineered in vivo release of oligogalacturonides, damage-associated molecular patterns SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE plant immunity; DAMPs; polygalacturonase; PGIP; oligogalacturonides ID HOST-PATHOGEN INTERACTIONS; POLYGALACTURONASE-INHIBITING PROTEIN; SALICYLIC-ACID; BOTRYTIS-CINEREA; TRANSLATIONAL INHIBITION; ARABIDOPSIS-THALIANA; DEFENSE RESPONSES; SIGNALING PATHWAY; RESISTANCE; ELICITORS AB Oligogalacturonides (OGs) are fragments of pectin that activate plant innate immunity by functioning as damage-associated molecular patterns (DAMPs). We set out to test the hypothesis that OGs are generated in planta by partial inhibition of pathogen-encoded polygalacturonases (PGs). A gene encoding a fungal PG was fused with a gene encoding a plant polygalacturonase-inhibiting protein (PGIP) and expressed in transgenic Arabidopsis plants. We show that expression of the PGIP-PG chimera results in the in vivo production of OGs that can be detected by mass spectrometric analysis. Transgenic plants expressing the chimera under control of a pathogen-inducible promoter are more resistant to the phytopathogens Botrytis cinerea, Pectobacterium carotovorum, and Pseudomonas syringae. These data provide strong evidence for the hypothesis that OGs released in vivo act as a DAMP signal to trigger plant immunity and suggest that controlled release of these molecules upon infection may be a valuable tool to protect plants against infectious diseases. On the other hand, elevated levels of expression of the chimera cause the accumulation of salicylic acid, reduced growth, and eventually lead to plant death, consistent with the current notion that trade-off occurs between growth and defense. C1 [Benedetti, Manuel; Pontiggia, Daniela; Raggi, Sara; Scaloni, Flavio; Ferrari, Simone; Cervone, Felice; De Lorenzo, Giulia] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, I-00185 Rome, Italy. [Cheng, Zhenyu; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Cheng, Zhenyu; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu; felice.cervone@uniroma1.it RI De Lorenzo, Giulia/F-5475-2013; OI De Lorenzo, Giulia/0000-0002-1707-5418; PONTIGGIA, DANIELA/0000-0002-0980-107X FU European Research Council [233083]; Ministero delle Politiche Agricole, Alimentari e Forestali Grant BIOMASSVAL; Grant FITOLISI; Ministero dell'Universita e della Ricerca Scientifica [PRIN2009]; Institute Pasteur-Fondazione Cenci Bolognetti; Banting Postdoctoral fellowship; National Science Foundation [IOS-0929226]; National Institutes of Health [R37-GM48707] FX This work was supported by the European Research Council Advanced Grant 233083 "FUEL-PATH" (to F.C.); the Ministero delle Politiche Agricole, Alimentari e Forestali Grant BIOMASSVAL (to F.C.); Grant FITOLISI (to G.D.L.); Ministero dell'Universita e della Ricerca Scientifica Grant PRIN2009 (to G.D.L.); the Institute Pasteur-Fondazione Cenci Bolognetti; a Banting Postdoctoral fellowship (to Z.C.); and National Science Foundation Grant IOS-0929226 and National Institutes of Health Grant R37-GM48707 (to F.M.A.). NR 56 TC 19 Z9 20 U1 9 U2 56 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 APR 28 PY 2015 VL 112 IS 17 BP 5533 EP 5538 DI 10.1073/pnas.1504154112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG8JR UT WOS:000353554000073 PM 25870275 ER PT J AU Zhou, C Chen, XY Zhang, Q Wang, J Wu, MX AF Zhou, Chang Chen, Xinyuan Zhang, Qi Wang, Ji Wu, Mei X. TI Laser mimicking mosquito bites for skin delivery of malaria sporozoite vaccines SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Laser; Malaria; Sporozoites; Vaccine; Delivery ID PLASMODIUM-BERGHEI SPOROZOITES; FALCIPARUM-MALARIA; INTRADERMAL IMMUNIZATION; PROTECTIVE IMMUNITY; MICE; RADIATION; PARASITES; ABSORPTION; EFFICACY; ROUTE AB Immunization with radiation-attenuated sporozoites (RAS) via mosquito bites has been shown to induce sterile immunity against malaria in humans, but this route of vaccination is neither practical nor ethical. The importance of delivering RAS to the liver through circulation in eliciting immunity against this parasite has been recently verified by human studies showing that high-level protection was achieved only by intravenous (IV) administration of RAS, not by intradermal (ID) or subcutaneous (SC) vaccination. Here, we report in a murine model that ID inoculation of RAS into laser-illuminated skin confers immune protection against malarial infection almost as effectively as IV immunization. Brief illumination of the inoculation site with a low power 532 nm Nd:YAG laser enhanced the permeability of the capillary beneath the skin, owing to hemoglobin-specific absorbance of the light. The increased blood vessel permeability appeared to facilitate an association of RAS with blood vessel walls by an as-yet-unknown mechanism, ultimately promoting a 7-fold increase in RAS entering circulation and reaching the liver over ID administration. Accordingly, ID immunization of RAS at a laser-treated site stimulated much stronger sporozoite-specific antibody and CD8(+) IFN-gamma(+) T cell responses than ID vaccination and provided nearly full protection against malarial infection, whereas ID immunization alone was ineffective. This novel, safe, and convenient strategy to augment efficacy of ID sporozoite-based vaccines warrants further investigation in large animals and in humans. (C) 2015 Elsevier B.V. All rights reserved. C1 [Zhou, Chang; Chen, Xinyuan; Zhang, Qi; Wang, Ji; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health [AI089779, AI097696] FX We thank Dr. Richard R. Anderson for stimulating discussions, William Farinelli for suggestions and technical assistance in operation and maintenance of various laser machines, Jeffrey H. Wu for editing, Jenny Zhao and Denny Cao in our Photopathology Core for helping with confocal microscopy and flow cytometry, and Sanaria company for purified sporozoites. This work was supported by the National Institutes of Health grants AI089779 and AI097696 to M.X.W. NR 35 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD APR 28 PY 2015 VL 204 BP 30 EP 37 DI 10.1016/j.jconrel.2015.02.031 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA CE9EL UT WOS:000352146500005 PM 25725360 ER PT J AU Weiser, TG Haynes, AB Molina, G Lipsitz, SR Esquivel, MM Uribe-Leitz, T Fu, R Azad, T Chao, TE Berry, WR Gawande, AA AF Weiser, Thomas G. Haynes, Alex B. Molina, George Lipsitz, Stuart R. Esquivel, Micaela M. Uribe-Leitz, Tarsicio Fu, Rui Azad, Tej Chao, Tiffany E. Berry, William R. Gawande, Atul A. TI Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Weiser, Thomas G.; Esquivel, Micaela M.; Uribe-Leitz, Tarsicio] Stanford Univ, Dept Surg, Sch Med, Stanford, CA 94305 USA. [Haynes, Alex B.; Molina, George; Lipsitz, Stuart R.; Berry, William R.; Gawande, Atul A.] Ariadne Labs, Boston, MA USA. [Haynes, Alex B.; Molina, George; Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Haynes, Alex B.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Dept Hlth Policy & Management, T H Chan Sch Publ Hlth, Boston, MA 02115 USA. [Lipsitz, Stuart R.; Berry, William R.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Fu, Rui] Stanford Univ, Management Sci & Engn, Stanford, CA 94305 USA. [Fu, Rui; Azad, Tej] Stanford Univ, Sch Med, Stanford, CA 94305 USA. EM tweiser@stanford.edu NR 0 TC 19 Z9 19 U1 2 U2 2 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 APR 27 PY 2015 VL 385 SU 2 BP 11 EP 11 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400012 ER PT J AU Shrime, MG Daniels, KM Meara, JG AF Shrime, Mark G. Daniels, Kimberly M. Meara, John G. TI How much surgery is enough? Aligning surgical delivery with best-performing health systems SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.; Meara, John G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA USA. [Daniels, Kimberly M.; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. EM shrime@mail.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 13 EP 13 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400014 ER PT J AU Uribe-Leitz, T Esquivel, MM Molina, G Lipsitz, SR Verguet, S Rose, J Bickler, SW Gawande, AA Haynes, AB Weiser, TG AF Uribe-Leitz, Tarsicio Esquivel, Micaela M. Molina, George Lipsitz, Stuart R. Verguet, Stephane Rose, John Bickler, Stephen W. Gawande, Atul A. Haynes, Alex B. Weiser, Thomas G. TI Projections to achieve minimum surgical rate threshold: an observational study SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Uribe-Leitz, Tarsicio; Esquivel, Micaela M.; Weiser, Thomas G.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Rose, John] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Molina, George; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lipsitz, Stuart R.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Verguet, Stephane] Harvard Univ, Dept Global Hlth & Populat, T H Chan Sch Publ Hlth, Boston, MA 02115 USA. [Rose, John; Bickler, Stephen W.] Univ Calif San Diego, Dept Surg, Rady Childrens Hosp, San Diego, CA 92103 USA. EM pturibe@stanford.edu 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 14 EP 14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400015 ER PT J AU Raykar, NP Bowder, AN Liu, C Vega, M Kim, JH Boye, G Greenberg, SLM Riesel, JN Gillies, RD Meara, JG Roy, N AF Raykar, Nakul P. Bowder, Alexis N. Liu, Charles Vega, Martha Kim, Jong H. Boye, Gloria Greenberg, Sarah L. M. Riesel, Johanna N. Gillies, Rowan D. Meara, John G. Roy, Nobhojit TI Geospatial mapping to estimate timely access to surgical care in nine low-income and middle-income countries SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Raykar, Nakul P.; Bowder, Alexis N.; Liu, Charles; Vega, Martha; Greenberg, Sarah L. M.; Riesel, Johanna N.; Gillies, Rowan D.; Meara, John G.] Harvard Univ, Program Global Surg & Social Change, Sch Med, Boston, MA 02115 USA. [Raykar, Nakul P.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Bowder, Alexis N.] Univ Nebraska, Sch Med, Omaha, NE 68198 USA. [Kim, Jong H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Boye, Gloria] Boston Childrens Hosp, Boston, MA USA. [Greenberg, Sarah L. M.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Roy, Nobhojit] BARC Hosp, Dept Surg, Mumbai, Maharashtra, India. [Roy, Nobhojit] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden. EM nraykar@bidmc.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR 27 PY 2015 VL 385 SU 2 BP 16 EP 16 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400017 ER PT J AU Molina, G Esquivel, MM Uribe-Leitz, T Lipsitz, SR Azad, T Shah, N Semrau, K Berry, WR Gwande, AA Weiser, TG Haynes, AB AF Molina, George Esquivel, Micaela M. Uribe-Leitz, Tarsicio Lipsitz, Stuart R. Azad, Tej Shah, Neel Semrau, Katherine Berry, William R. Gwande, Atul A. Weiser, Thomas G. Haynes, Alex B. TI Avoidable maternal and neonatal deaths associated with improving access to caesarean delivery in countries with low caesarean delivery rates: an ecological modelling analysis SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Molina, George; Lipsitz, Stuart R.; Shah, Neel; Semrau, Katherine; Berry, William R.; Gwande, Atul A.; Haynes, Alex B.] Harvard Univ, Brigham & Womens Hosp, T H Chan Sch Publ Hlth, Ariadne Labs, Boston, MA 02115 USA. [Molina, George; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Esquivel, Micaela M.; Uribe-Leitz, Tarsicio; Azad, Tej; Weiser, Thomas G.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Shah, Neel] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. EM abhaynes@mgh.harvard.edu 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 33 EP 33 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400034 ER PT J AU Weiser, TG Uribe-Leitz, T Fu, R Jaramillo, J Maurer, L Esquivel, MM Gawande, AA Haynes, AB AF Weiser, Thomas G. Uribe-Leitz, Tarsicio Fu, Rui Jaramillo, Joshua Maurer, Lydia Esquivel, Micaela M. Gawande, Atul A. Haynes, Alex B. TI Variability in mortality after caesarean delivery, appendectomy, and groin hernia repair in low-income and middle-income countries: implications for expanding surgical services SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Weiser, Thomas G.; Uribe-Leitz, Tarsicio; Esquivel, Micaela M.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Fu, Rui] Stanford Univ, Management Sci & Engn, Stanford, CA 94305 USA. [Jaramillo, Joshua; Maurer, Lydia] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Gawande, Atul A.; Haynes, Alex B.] Ariadne Labs, Boston, MA USA. [Gawande, Atul A.; Haynes, Alex B.] Harvard Univ, Dept Hlth Policy & Management, T H Chan Sch Publ Hlth, Boston, MA 02115 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Haynes, Alex B.] Massachussetts Gen Hosp, Dept Surg, Boston, MA USA. EM tweiser@stanford.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 34 EP 34 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400035 ER PT J AU Kagwa, S Hoeft, MA Firth, PG Ttendo, S Modest, VE AF Kagwa, Sadic Hoeft, Mark A. Firth, Paul G. Ttendo, Stephen Modest, Vicki E. TI Ultrasound guided transversus abdominis plane versus sham blocks after caesarean section in an Ugandan village hospital: a prospective, randomised, double-blinded, single-centre study SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Kagwa, Sadic; Ttendo, Stephen] Mbarara Reg Referral Hosp, Dept Anaesthesia & Crit Care, Mbarara, Uganda. [Hoeft, Mark A.; Firth, Paul G.; Modest, Vicki E.] Massachusetts Gen Hosp, DACCPM, Boston, MA 02114 USA. EM vmodest@mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 36 EP 36 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400037 ER PT J AU Holmer, H Shrime, MG Riesel, JN Meara, JG Hagander, L AF Holmer, Hampus Shrime, Mark G. Riesel, Johanna N. Meara, John G. Hagander, Lars TI Towards closing the gap of the global surgeon, anaesthesiologist, and obstetrician workforce: thresholds and projections towards 2030 SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Holmer, Hampus; Hagander, Lars] Lund Univ, Fac Med, Dept Clin Sci Lund, Paediat Surg & Global Paediat, Lund, Sweden. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Riesel, Johanna N.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02115 USA. [Riesel, Johanna N.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Meara, John G.] Boston Childrens Hosp, Boston, MA USA. EM hampus.holmer@med.lu.se NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 40 EP 40 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400041 ER PT J AU Daniels, KM Riesel, JN Meara, JG AF Daniels, Kimberly M. Riesel, Johanna N. Meara, John G. TI The scale-up of the surgical workforce SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Daniels, Kimberly M.; Riesel, Johanna N.; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Daniels, Kimberly M.; Riesel, Johanna N.; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM Jriesel@mgh.harvard.edu 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 41 EP 41 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400042 ER PT J AU Federspiel, F Mukhopadhyay, S Milsom, P Scott, JW Riesel, JN Meara, JG AF Federspiel, Frederik Mukhopadhyay, Swagoto Milsom, Penelope Scott, John W. Riesel, Johanna N. Meara, John G. TI Global surgical and anaesthetic task shifting: a systematic literature review and survey SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Federspiel, Frederik] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Federspiel, Frederik] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Mukhopadhyay, Swagoto] Univ Connecticut, Integrated Residency Programs, Dept Surg, Storrs, CT USA. [Mukhopadhyay, Swagoto; Riesel, Johanna N.; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Mukhopadhyay, Swagoto; Milsom, Penelope; Scott, John W.; Riesel, Johanna N.; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Scott, John W.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM frederikfederspiel@gmail.com 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 46 EP 46 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400047 ER PT J AU Gutnik, LA Dielman, J Dare, AJ Ramos, MS Riviello, R Meara, JG Yamey, G Shrime, MG AF Gutnik, Lily A. Dielman, Joseph Dare, Anna J. Ramos, Margarita S. Riviello, Robert Meara, John G. Yamey, Gavin Shrime, Mark G. TI Funding flows to global surgery: an analysis of contributions from the USA SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Gutnik, Lily A.] Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA. [Gutnik, Lily A.] UNC Project Malawi, Lilongwe, Malawi. [Dielman, Joseph] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Dare, Anna J.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Dare, Anna J.] Kings Coll London, London WC2R 2LS, England. [Ramos, Margarita S.; Riviello, Robert] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Gutnik, Lily A.; Riviello, Robert] Ctr Surg & Publ Hlth, Boston, MA USA. [Meara, John G.] Harvard Univ, Sch Med, Boston, MA USA. [Meara, John G.] Boston Childrens Hosp, Boston, MA USA. [Yamey, Gavin] Univ Calif San Francisco, Evidence Policy Initiat, Global Hlth Grp, San Francisco, CA 94143 USA. [Shrime, Mark G.] Harvard Univ, Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Childrens Hosp Boston, Program Global Surg & Social Change, Boston, MA USA. EM Lily.gutnik@mail.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 51 EP 51 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400052 ER PT J AU Gutnik, LA Yamey, G Dare, AJ Ramos, MS Riviello, R Meara, JG Shrime, MG AF Gutnik, Lily A. Yamey, Gavin Dare, Anna J. Ramos, Margarita S. Riviello, Robert Meara, John G. Shrime, Mark G. TI Financial contribution to global surgery: an analysis of 160 international charitable organisations SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Gutnik, Lily A.] Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA. [Gutnik, Lily A.] UNC Project Malawi, Lilongwe, Malawi. [Shrime, Mark G.] Harvard Univ, Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Childrens Hosp Boston, Program Global Surg & Social Change, Boston, MA USA. [Dare, Anna J.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Dare, Anna J.] Kings Coll London, London WC2R 2LS, England. [Ramos, Margarita S.; Riviello, Robert] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Gutnik, Lily A.; Riviello, Robert] Ctr Surg & Publ Hlth, Boston, MA USA. [Yamey, Gavin] Univ Calif San Francisco, Evidence Policy Initiat, Global Hlth Grp, San Francisco, CA 94143 USA. [Meara, John G.] Harvard Univ, Sch Med, Boston, MA USA. [Meara, John G.] Boston Childrens Hosp, Boston, MA USA. EM lily.gutnik@mail.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 52 EP 52 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400053 ER PT J AU Ng-Kamstra, JS Arya, S Chung, TE Weston, B Frankfurter, C Gutnik, LA Kreutzer, T Riesel, JN Meara, JG AF Ng-Kamstra, Joshua S. Arya, Sumedha Chung, Timothy E. Weston, Brad Frankfurter, Claudia Gutnik, Lily A. Kreutzer, Tino Riesel, Johanna N. Meara, John G. TI Mapping the playing field-a novel web-based strategy to identify non-governmental actors in global surgery SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Ng-Kamstra, Joshua S.; Riesel, Johanna N.; Meara, John G.] Harvard Univ, Program Global Surg & Social Change, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Ng-Kamstra, Joshua S.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Arya, Sumedha; Chung, Timothy E.; Weston, Brad; Frankfurter, Claudia] Univ Toronto, Fac Med, Toronto, ON, Canada. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kreutzer, Tino] Harvard Humanitarian Initiat, Boston, MA USA. [Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Gutnik, Lily A.] Ctr Surg & Publ Hlth, Boston, MA USA. [Gutnik, Lily A.] UNC Project Malawi, Lilongwe, Malawi. [Gutnik, Lily A.] Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA. EM John.meara@childrens.harvard.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 55 EP 55 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400056 ER PT J AU Alkire, BC Bergmark, RW Chambers, K Cheney, ML Meara, JG AF Alkire, Blake C. Bergmark, Regan W. Chambers, Kyle Cheney, Mack L. Meara, John G. TI Head and neck cancer in South Asia: macroeconomic consequences and the role of surgery SO LANCET LA English DT Meeting Abstract CT Lancet Commission on Global Surgery Meeting CY JAN 17-18, 2014 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch C1 [Alkire, Blake C.; Bergmark, Regan W.; Chambers, Kyle; Cheney, Mack L.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Alkire, Blake C.; Cheney, Mack L.; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Dept Global Hlth Equ, Boston, MA USA. [Alkire, Blake C.; Bergmark, Regan W.; Chambers, Kyle; Cheney, Mack L.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Meara, John G.] Boston Childrens Hosp, Dept Plast & Reconstruct Surg, Boston, MA USA. EM blakealkire@gmail.com 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 27 PY 2015 VL 385 SU 2 BP 56 EP 56 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ4KK UT WOS:000360573400057 ER PT J AU Zhang, XC Millet, YA Cheng, Z Bush, J Ausubel, FM AF Zhang, Xue-Cheng Millet, Yves A. Cheng, Zhenyu Bush, Jenifer Ausubel, Frederick M. TI Jasmonate signalling in Arabidopsis involves SGT1b-HSP70-HSP90 chaperone complexes SO NATURE PLANTS LA English DT Article ID PLANT HORMONE-RECEPTORS; RESISTANCE PROTEIN; IMMUNE-RESPONSES; UBIQUITIN LIGASE; AUXIN RESPONSE; HSP90; SGT1; ACCUMULATION; PERCEPTION; STABILIZATION AB Plant hormones play pivotal roles in growth, development and stress responses. Although it is essential to our understanding of hormone signalling, how plants maintain a steady state level of hormone receptors is poorly understood. We show that mutation of the Arabidopsis thaliana co-chaperone SGT1b impairs responses to the plant hormones jasmonate, auxin and gibberellic acid, but not brassinolide and abscisic acid, and that SGT1b and its homologue SGT1a are involved in maintaining the steady state levels of the F-box proteins COI1 and TIR1, receptors for jasmonate and auxin, respectively. The association of SGT1b with COI1 is direct and is independent of the Arabidopsis SKP1 protein, ASK1. We further show that COI1 is a client protein of SGT1b-HSP70-HSP90 chaperone complexes and that the complexes function in hormone signalling by stabilizing the COI1 protein. This study extends the SGT1b-HSP90 client protein list and broadens the functional scope of SGT1b-HSP70-HSP90 chaperone complexes. C1 [Zhang, Xue-Cheng; Millet, Yves A.; Cheng, Zhenyu; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Xue-Cheng; Millet, Yves A.; Cheng, Zhenyu; Bush, Jenifer; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM ausubel@molbio.mgh.harvard.edu FU NSF [MCB-0519898, IOS-0929226]; NIH [GM48707, P30 DK040561] FX We thank D. Bartenstein, C. Mankiw and M. Cerulli for help in EMS mutant screening, C. Queitsch for providing the HSP90 RNAi-A1 and RNAi-C1 constructs, M. Borowsky for computational analyses of the Illumina sequencing reads and mapping of the hsm1 mutant, C. Haney and D. McEwan for discussion and critical reading, and J. Li, O. Liu, Y. Niu, L. Li and J. Sheen for plasmids, constructs and technical advice. This work was supported by NSF grants MCB-0519898 and IOS-0929226 and NIH grants GM48707 and P30 DK040561 awarded to F.M.A. NR 40 TC 3 Z9 3 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2055-026X EI 2055-0278 J9 NAT PLANTS JI Nat. Plants PD APR 27 PY 2015 VL 1 IS 5 AR UNSP 15049 DI 10.1038/NPLANTS.2015.49 PG 8 WC Plant Sciences SC Plant Sciences GA CV6RU UT WOS:000364398800002 ER PT J AU Pai, M Habib, N Senturk, H Lakhtakia, S Reddy, N Cicinnati, VR Kaba, I Beckebaum, S Drymousis, P Kahaleh, M Brugge, W AF Pai, Madhava Habib, Nagy Senturk, Hakan Lakhtakia, Sundeep Reddy, Nageshwar Cicinnati, Vito R. Kaba, Iyad Beckebaum, Susanne Drymousis, Panagiotis Kahaleh, Michel Brugge, William TI Endoscopic ultrasound guided radiofrequency ablation, for pancreatic cystic neoplasms and neuroendocrine tumors SO WORLD JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Endoscopic ultrasound; Radiofrequency ablation; Pancreas; Cystic neoplasms; Neuroendocrine tumors ID HEPATOCELLULAR-CARCINOMA; PORCINE PANCREAS; LIVER; CANCER; FEASIBILITY; ACTIVATION; SURVIVAL; IMMUNITY; PROBE AB AIM: To outline the feasibility, safety, adverse events and early results of endoscopic ultrasound (EUS)-radiofrequency ablation (RFA) in pancreatic neoplasms using a novel probe. METHODS: This is a multi-center, pilot safety feasibility study. The intervention described was radiofrequency ablation (RF) which was applied with an innovative monopolar RF probe (1.2 mm Habib EUS-RFA catheter) placed through a 19 or 22 gauge fine needle aspiration (FNA) needle once FNA was performed in patients with a tumor in the head of the pancreas. The Habib (TM) EUS-RFA is a 1 Fr wire (0.33 mm, 0.013") with a working length of 190 cm, which can be inserted through the biopsy channel of an echoendoscope. RF power is applied to the electrode at the end of the wire to coagulate tissue in the liver and pancreas. RESULTS: Eight patients [median age of 65 (range 27-82) years; 7 female and 1 male] were recruited in a prospective multicenter trial. Six had a pancreatic cystic neoplasm (four a mucinous cyst, one had intraductal papillary mucinous neoplasm and one a microcystic adenoma) and two had a neuroendocrine tumors (NET) in the head of pancreas. The mean size of the cystic neoplasm and NET were 36.5 mm (SD +/- 17.9 mm) and 27.5 mm (SD +/- 17.7 mm) respectively. The EUS-RFA was successfully completed in all cases. Among the 6 patients with a cystic neoplasm, post procedure imaging in 3-6 mo showed complete resolution of the cysts in 2 cases, whilst in three more there was a 48.4% reduction [mean pre RF 38.8 mm (SD +/- 21.7 mm) vs mean post RF 20 mm (SD +/- 17.1 mm)] in size. In regards to the NET patients, there was a change in vascularity and central necrosis after EUS-RFA. No major complications were observed within 48 h of the procedure. Two patients had mild abdominal pain that resolved within 3 d. CONCLUSION: EUS-RFA of pancreatic neoplasms with a novel monopolar RF probe was well tolerated in all cases. Our preliminary data suggest that the procedure is straightforward and safe. The response ranged from complete resolution to a 50% reduction in size. C1 [Pai, Madhava; Habib, Nagy; Drymousis, Panagiotis] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, HPB Unit, London W12 0HR, England. [Habib, Nagy] Emcision Ltd, London W12 0HS, England. [Senturk, Hakan] Bezmi Alem Univ, Dept Gastroenterol, TR-34093 Istanbul, Turkey. [Lakhtakia, Sundeep; Reddy, Nageshwar] Asian Inst Gastroenterol, Hyderabad 500082, Andhra Pradesh, India. [Cicinnati, Vito R.; Kaba, Iyad; Beckebaum, Susanne] Univ Hosp Munster, Dept Transplant Med, D-48149 Munster, Germany. [Kahaleh, Michel] Weill Cornell Med Coll, Div Gastroenterol & Hepatol, Dept Med, New York, NY 10065 USA. [Brugge, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Habib, N (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, HPB Unit, Dept Surg, Ducane Rd, London W12 0HR, England. EM nagy.habib@imperial.ac.uk NR 33 TC 17 Z9 18 U1 1 U2 1 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1948-9366 J9 WORLD J GASTROINT SU JI World J. Gastrointest. Surg. PD APR 27 PY 2015 VL 7 IS 4 BP 52 EP 59 DI 10.4240/wjgs.v7.i4.52 PG 8 WC Surgery SC Surgery GA CR0FK UT WOS:000360993600001 PM 25914783 ER PT J AU Panenka, WJ Lange, RT Bouix, S Shewchuk, JR Heran, MKS Brubacher, JR Eckbo, R Shenton, ME Iverson, GL AF Panenka, William J. Lange, Rael T. Bouix, Sylvain Shewchuk, Jason R. Heran, Manraj K. S. Brubacher, Jeffrey R. Eckbo, Ryan Shenton, Martha E. Iverson, Grant L. TI Neuropsychological Outcome and Diffusion Tensor Imaging in Complicated versus Uncomplicated Mild Traumatic Brain Injury SO PLOS ONE LA English DT Article ID POST-CONCUSSION SYNDROME; HEAD-INJURY; WHITE-MATTER; COMPUTED-TOMOGRAPHY; MILITARY PERSONNEL; AXONAL INJURY; CT-SCAN; MODERATE; PREDICTION; SEQUELAE AB This study examined whether intracranial neuroimaging abnormalities in those with mild traumatic brain injury (MTBI) (i.e., "complicated" MTBIs) are associated with worse subacute outcomes as measured by cognitive testing, symptom ratings, and/or diffusion tensor imaging (DTI). We hypothesized that (i) as a group, participants with complicated MTBIs would report greater symptoms and have worse neurocognitive outcomes than those with uncomplicated MTBI, and (ii) as a group, participants with complicated MTBIs would show more Diffusion Tensor Imaging (DTI) abnormalities. Participants were 62 adults with MTBIs (31 complicated and 31 uncomplicated) who completed neurocognitive testing, symptom ratings, and DTI on a 3T MRI scanner approximately 6-8 weeks post injury. There were no statistically significant differences between groups on symptom ratings or on a broad range of neuropsychological tests. When comparing the groups using tract-based spatial statistics for DTI, no significant difference was found for axial diffusivity or mean diffusivity. However, several brain regions demonstrated increased radial diffusivity (purported to measure myelin integrity), and decreased fractional anisotropy in the complicated group compared with the uncomplicated group. Finally, when we extended the DTI analysis, using a multivariate atlas based approach, to 32 orthopedic trauma controls (TC), the findings did not reveal significantly more areas of abnormal DTI signal in the complicated vs. uncomplicated groups, although both MTBI groups had a greater number of areas with increased radial diffusivity compared with the trauma controls. This study illustrates that macrostructural neuroimaging changes following MTBI are associated with measurable changes in DTI signal. Of note, however, the division of MTBI into complicated and uncomplicated subtypes did not predict worse clinical outcome at 6-8 weeks post injury. C1 [Panenka, William J.; Lange, Rael T.; Iverson, Grant L.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Bouix, Sylvain; Eckbo, Ryan; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA USA. [Shewchuk, Jason R.; Heran, Manraj K. S.] Univ British Columbia, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Brubacher, Jeffrey R.] Univ British Columbia, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Panenka, WJ (reprint author), Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. EM wpanenka@mail.ubc.ca FU Canadian Institute of Health Research [200903MOP-200377-BSB-CAAA-161276]; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX Primary funding for this study was provided by the Canadian Institute of Health Research (200903MOP-200377-BSB-CAAA-161276); provided to RTL as PI). MES and GLI note that this work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 3 Z9 3 U1 2 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 APR 27 PY 2015 VL 10 IS 4 AR e0122746 DI 10.1371/journal.pone.0122746 PG 27 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9SB UT WOS:000353659100011 PM 25915776 ER PT J AU Yost, S Duran-Pinedo, AE Teles, R Krishnan, K Frias-Lopez, J AF Yost, Susan Duran-Pinedo, Ana E. Teles, Ricardo Krishnan, Keerthana Frias-Lopez, Jorge TI Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis SO Genome Medicine LA English DT Article ID LACTAMASE-PRODUCING-BACTERIA; GINGIVAL CREVICULAR FLUID; PORPHYROMONAS-GINGIVALIS; TREPONEMA-DENTICOLA; ATTACHMENT LOSS; RNA-SEQ; DIFFERENTIAL EXPRESSION; POTASSIUM-TRANSPORT; DISEASE PROGRESSION; SUBGINGIVAL PLAQUE AB Background: Periodontitis is a polymicrobial biofilm-induced inflammatory disease that affects 743 million people worldwide. The current model to explain periodontitis progression proposes that changes in the relative abundance of members of the oral microbiome lead to dysbiosis in the host-microbiome crosstalk and then to inflammation and bone loss. Using combined metagenome/metatranscriptome analysis of the subgingival microbiome in progressing and non-progressing sites, we have characterized the distinct molecular signatures of periodontitis progression. Methods: Metatranscriptome analysis was conducted on samples from subgingival biofilms from progressing and stable sites from periodontitis patients. Community-wide expression profiles were obtained using Next Generation Sequencing (Illumina). Sequences were aligned using 'bowtie2' against a constructed oral microbiome database. Differential expression analysis was performed using the non-parametric algorithm implemented on the R package 'NOISeqBio'. We summarized global functional activities of the oral microbial community by set enrichment analysis based on the Gene Ontology (GO) orthology. Results: Gene ontology enrichment analysis showed an over-representation in the baseline of active sites of terms related to cell motility, lipid A and peptidoglycan biosynthesis, and transport of iron, potassium, and amino acids. Periodontal pathogens (Tannerella forsythia and Porphyromonas gingivalis) upregulated different TonB-dependent receptors, peptidases, proteases, aerotolerance genes, iron transport genes, hemolysins, and CRISPR-associated genes. Surprisingly, organisms that have not been usually associated with the disease (Streptococcus oralis, Streptococcus mutans, Streptococcus intermedius, Streptococcus mitis, Veillonella parvula, and Pseudomonas fluorenscens) were highly active transcribing putative virulence factors. We detected patterns of activities associated with progression of clinical traits. Among those we found that the profiles of expression of cobalamin biosynthesis, proteolysis, and potassium transport were associated with the evolution towards disease. Conclusions: We identified metabolic changes in the microbial community associated with the initial stages of dysbiosis. Regardless of the overall composition of the community, certain metabolic signatures are consistent with disease progression. Our results suggest that the whole community, and not just a handful of oral pathogens, is responsible for an increase in virulence that leads to progression. C1 [Yost, Susan; Duran-Pinedo, Ana E.; Krishnan, Keerthana; Frias-Lopez, Jorge] Forsyth Inst, Cambridge, MA 02142 USA. [Frias-Lopez, Jorge] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Teles, Ricardo] Univ N Carolina, Sch Dent, Chapel Hill, NC 27599 USA. RP Frias-Lopez, J (reprint author), Forsyth Inst, 245 First St, Cambridge, MA 02142 USA. EM jfrias@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [DE021553, DE021127] FX Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers DE021553 and DE021127. NR 89 TC 21 Z9 21 U1 3 U2 33 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 APR 27 PY 2015 VL 7 AR 27 DI 10.1186/s13073-015-0153-3 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA CG8BP UT WOS:000353532500001 PM 25918553 ER PT J AU McFarland, LV Malfertheiner, P Huang, Y Wang, L AF McFarland, Lynne V. Malfertheiner, Peter Huang, Ying Wang, Lin TI Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events SO WORLD JOURNAL OF META-ANALYSIS LA English DT Review DE Probiotics; Safety; Saccharomyces boulardii; Helicobacter pylori; Meta-analysis; Adverse reactions; Diarrhea; Lactobacillus rhamnosus; Randomized clinical trials ID PLACEBO-CONTROLLED TRIAL; ANTIBIOTIC-ASSOCIATED DIARRHEA; LACTOBACILLUS GG SUPPLEMENTATION; RANDOMIZED CONTROLLED-TRIALS; SACCHAROMYCES-BOULARDII; DOUBLE-BLIND; INTESTINAL MICROBIOTA; FERMENTED MILK; TRIPLE THERAPY; PARALLEL-GROUP AB AIM: To assess the efficacy and safety of single strain probiotics for the: (1) eradication of Helicobacter pylori (H. pylori); (2) prevention of adverse events; and (3) prevention of antibiotic-associated diarrhea associated with eradication therapy. METHODS: We searched PubMed (1960-2014), EMBASE (1974-2014), Cochrane Database of Systematic Reviews (1990-2014), and ISI Web of Science (2000-2014). Additionally, we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. Randomized controlled trials of H. pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included. The primary outcomes were the rates of eradication of H. pylori and frequency of patients with adverse events or antibiotic-associated diarrhea. Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on daily probiotic dose, study population, and quality of the study. The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria. RESULTS: A total of 25 randomized controlled trials (28 treatment arms, with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy. Only one probiotic strain significantly improved H. pylori eradication rates: Saccharomyces boulardii (S. boulardii) CNCM I-745 [pooled relative risks (pRR) = 1.11, 95% CI: 1.07-1.16]. Only one probiotic strain (S. boulardii CNCM I-745) significantly prevented any adverse events (pRR = 0.42, 95% CI: 0.28-0.62). Both S. boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantly reduced antibiotic-associated diarrhea (pRR = 0.47, 95%CI: 0.37-0.60 and pRR = 0.29, 95%CI: 0.17-0.48, respectively) associated with H. pylori eradication therapy. Meta-regression of sub-groups did not detect significant differences by dose, adult vs pediatric, symptom status, or study quality, but did find significant differences by the strain of probiotic. Potential mild publication bias was found for antibiotic-associated diarrhea, but not for eradication or adverse event outcomes. Analysis of the study quality illuminated areas for improvement in future studies (use of placebos, study size calculations, attrition reasons and discussion of limitations and generalizability). CONCLUSION: The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies. The type of probiotic strain was the most important factor in predicting efficacy. C1 [McFarland, Lynne V.] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Malfertheiner, Peter] Univ Klinikum Magdeburg AOR, D-39120 Magdeburg, Germany. [Huang, Ying; Wang, Lin] Fudan Univ, Childrens Hosp, Shanghai 201102, Peoples R China. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Metropolitan Pk West,1100 Olive Way 1400, Seattle, WA 98101 USA. EM lvmcfarl@u.washington.edu NR 96 TC 3 Z9 4 U1 2 U2 6 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 2308-3840 J9 WORLD J META-ANAL JI World J. Meta-Anal. PD APR 26 PY 2015 VL 3 IS 2 BP 97 EP 117 PG 21 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CR0GB UT WOS:000360995400004 ER PT J AU Blein, S Bardel, C Danjean, V McGuffog, L Healey, S Barrowdale, D Lee, A Dennis, J Kuchenbaecker, KB Soucy, P Terry, MB Chung, WK Goldgar, DE Buys, SS Janavicius, R Tihomirova, L Tung, N Dorfling, CM van Rensburg, EJ Neuhausen, SL Ding, YC Gerdes, AM Ejlertsen, B Nielsen, FC Hansen, TVO Osorio, A Benitez, J Conejero, RA Segota, E Weitzel, JN Thelander, M Peterlongo, P Radice, P Pensotti, V Dolcetti, R Bonanni, B Peissel, B Zaffaroni, D Scuvera, G Manoukian, S Varesco, L Capone, GL Papi, L Ottini, L Yannoukakos, D Konstantopoulou, I Garber, J Hamann, U Donaldson, A Brady, A Brewer, C Foo, C Evans, DG Frost, D Eccles, D Douglas, F Cook, J Adlard, J Barwell, J Walker, L Izatt, L Side, LE Kennedy, MJ Tischkowitz, M Rogers, MT Porteous, ME Morrison, PJ Platte, R Eeles, R Davidson, R Hodgson, S Cole, T Godwin, AK Isaacs, C Claes, K De Leeneer, K Meindl, A Gehrig, A Wappenschmidt, B Sutter, C Engel, C Niederacher, D Steinemann, D Plendl, H Kast, K Rhiem, K Ditsch, N Arnold, N Varon-Mateeva, R Schmutzler, RK Preisler-Adams, S Markov, NB Wang-Gohrke, S de Pauw, A Lefol, C Lasset, C Leroux, D Rouleau, E Damiola, F Dreyfus, H Barjhoux, L Golmard, L Uhrhammer, N Bonadona, V Sornin, V Bignon, YJ Carter, J Van Le, L Piedmonte, M DiSilvestro, PA de la Hoya, M Caldes, T Nevanlinna, H Aittomaki, K Jager, A van den Ouweland, AMW Kets, CM Aalfs, CM van Leeuwen, FE Hogervorst, FBL Meijers-Heijboer, HEJ Oosterwijk, JC van Roozendaal, KEP Rookus, MA Devilee, P van der Luijt, RB Olah, E Diez, O Teule, A Lazaro, C Blanco, I Del Valle, J Jakubowska, A Sukiennicki, G Gronwald, J Lubinski, J Durda, K Jaworska-Bieniek, K Agnarsson, BA Maugard, C Amadori, A Montagna, M Teixeira, MR Spurdle, AB Foulkes, W Olswold, C Lindor, NM Pankratz, VS Szabo, CI Lincoln, A Jacobs, L Corines, M Robson, M Vijai, J Berger, A Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Greene, MH Mai, PL Rennert, G Imyanitov, EN Mulligan, AM Glendon, G Andrulis, IL Tchatchou, S Toland, AE Pedersen, IS Thomassen, M Kruse, TA Jensen, UB Caligo, MA Friedman, E Zidan, J Laitman, Y Lindblom, A Melin, B Arver, B Loman, N Rosenquist, R Olopade, OI Nussbaum, RL Ramus, SJ Nathanson, KL Domchek, SM Rebbeck, TR Arun, BK Mitchell, G Karlan, BY Lester, J Orsulic, S Stoppa-Lyonnet, D Thomas, G Simard, J Couch, FJ Offit, K Easton, DF Chenevix-Trench, G Antoniou, AC Mazoyer, S Phelan, CM Sinilnikova, OM Cox, DG AF Blein, Sophie Bardel, Claire Danjean, Vincent McGuffog, Lesley Healey, Sue Barrowdale, Daniel Lee, Andrew Dennis, Joe Kuchenbaecker, Karoline B. Soucy, Penny Terry, Mary Beth Chung, Wendy K. Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Tihomirova, Laima Tung, Nadine Dorfling, Cecilia M. van Rensburg, Elizabeth J. Neuhausen, Susan L. Ding, Yuan Chun Gerdes, Anne-Marie Ejlertsen, Bent Nielsen, Finn C. Hansen, Thomas V. O. Osorio, Ana Benitez, Javier Andres Conejero, Raquel Segota, Ena Weitzel, Jeffrey N. Thelander, Margo Peterlongo, Paolo Radice, Paolo Pensotti, Valeria Dolcetti, Riccardo Bonanni, Bernardo Peissel, Bernard Zaffaroni, Daniela Scuvera, Giulietta Manoukian, Siranoush Varesco, Liliana Capone, Gabriele L. Papi, Laura Ottini, Laura Yannoukakos, Drakoulis Konstantopoulou, Irene Garber, Judy Hamann, Ute Donaldson, Alan Brady, Angela Brewer, Carole Foo, Claire Evans, D. Gareth Frost, Debra Eccles, Diana Douglas, Fiona Cook, Jackie Adlard, Julian Barwell, Julian Walker, Lisa Izatt, Louise Side, Lucy E. Kennedy, M. John Tischkowitz, Marc Rogers, Mark T. Porteous, Mary E. Morrison, Patrick J. Platte, Radka Eeles, Ros Davidson, Rosemarie Hodgson, Shirley Cole, Trevor Godwin, Andrew K. Isaacs, Claudine Claes, Kathleen De Leeneer, Kim Meindl, Alfons Gehrig, Andrea Wappenschmidt, Barbara Sutter, Christian Engel, Christoph Niederacher, Dieter Steinemann, Doris Plendl, Hansjoerg Kast, Karin Rhiem, Kerstin Ditsch, Nina Arnold, Norbert Varon-Mateeva, Raymonda Schmutzler, Rita K. Preisler-Adams, Sabine Markov, Nadja Bogdanova Wang-Gohrke, Shan de Pauw, Antoine Lefol, Cedrick Lasset, Christine Leroux, Dominique Rouleau, Etienne Damiola, Francesca Dreyfus, Helene Barjhoux, Laure Golmard, Lisa Uhrhammer, Nancy Bonadona, Valerie Sornin, Valerie Bignon, Yves-Jean Carter, Jonathan Van Le, Linda Piedmonte, Marion DiSilvestro, Paul A. de la Hoya, Miguel Caldes, Trinidad Nevanlinna, Heli Aittomaki, Kristiina Jager, Agnes van den Ouweland, Ans M. W. Kets, Carolien M. Aalfs, Cora M. van Leeuwen, Flora E. Hogervorst, Frans B. L. Meijers-Heijboer, Hanne E. J. Oosterwijk, Jan C. van Roozendaal, Kees E. P. Rookus, Matti A. Devilee, Peter van der Luijt, Rob B. Olah, Edith Diez, Orland Teule, Alex Lazaro, Conxi Blanco, Ignacio Del Valle, Jesus Jakubowska, Anna Sukiennicki, Grzegorz Gronwald, Jacek Lubinski, Jan Durda, Katarzyna Jaworska-Bieniek, Katarzyna Agnarsson, Bjarni A. Maugard, Christine Amadori, Alberto Montagna, Marco Teixeira, Manuel R. Spurdle, Amanda B. Foulkes, William Olswold, Curtis Lindor, Noralane M. Pankratz, Vernon S. Szabo, Csilla I. Lincoln, Anne Jacobs, Lauren Corines, Marina Robson, Mark Vijai, Joseph Berger, Andreas Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Geschwantler Pfeiler, Georg Tea, Muy-Kheng Greene, Mark H. Mai, Phuong L. Rennert, Gad Imyanitov, Evgeny N. Mulligan, Anna Marie Glendon, Gord Andrulis, Irene L. Tchatchou, Sandrine Toland, Amanda Ewart Pedersen, Inge Sokilde Thomassen, Mads Kruse, Torben A. Jensen, Uffe Birk Caligo, Maria A. Friedman, Eitan Zidan, Jamal Laitman, Yael Lindblom, Annika Melin, Beatrice Arver, Brita Loman, Niklas Rosenquist, Richard Olopade, Olufunmilayo I. Nussbaum, Robert L. Ramus, Susan J. Nathanson, Katherine L. Domchek, Susan M. Rebbeck, Timothy R. Arun, Banu K. Mitchell, Gillian Karlan, Beth Y. Lester, Jenny Orsulic, Sandra Stoppa-Lyonnet, Dominique Thomas, Gilles Simard, Jacques Couch, Fergus J. Offit, Kenneth Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. Mazoyer, Sylvie Phelan, Catherine M. Sinilnikova, Olga M. Cox, David G. CA Breast Canc Family Registry EMBRACE GEMO Study Collaborators HEBON TI An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENETIC MODIFIERS; OXIDATIVE STRESS; DNA HAPLOGROUPS; SUSCEPTIBILITY; OVARIAN; CONSORTIUM; VARIANTS; MULTIPLE; DISEASES AB Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects. C1 [Blein, Sophie; Damiola, Francesca; Barjhoux, Laure; Sornin, Valerie; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM U1052,UMR5286, F-69365 Lyon, France. [Blein, Sophie; Bardel, Claire; Jager, Agnes; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon, F-69000 Lyon, France. [Blein, Sophie; Bardel, Claire; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon 1, F-69100 Villeurbanne, France. [Bardel, Claire; Lasset, Christine; Bonadona, Valerie] Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut LBBE Biometrie & Bio, UMR 5558, F-69622 Villeurbanne, France. [Danjean, Vincent] Univ Grenoble Alpes, Lab Informat Grenoble LIG, Equipe Projet Multiprogrammat & Ordonnancement Re, UMR 5217, F-38041 Grenoble, France. [Danjean, Vincent] INRIA Rhone Alpes, Equipe Projet MOAIS, F-38334 Saint Ismier, France. [McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B.; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] QIMR Berghofer, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Soucy, Penny; Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Ctr Rech, Charlesbourg, PQ, Canada. [Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10027 USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA. [Breast Canc Family Registry] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA. [Janavicius, Ramunas] Vilnius State Univ, Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania. State Res Inst, Ctr Innovat Med, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0028 Pretoria, South Africa. [Neuhausen, Susan L.; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Gerdes, Anne-Marie] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Nielsen, Finn C.; Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain. [Andres Conejero, Raquel] Hosp Clin Univ Lozano Blesa, Med Oncol Serv, Zaragoza 50009, Spain. [Segota, Ena] Holy Cross Hosp, Michael & Dianne Bienes Comprehens Canc Ctr, Ft Lauderdale, FL USA. [Weitzel, Jeffrey N.; Pensotti, Valeria] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Div Clin Canc Genet, Duarte, CA 91010 USA. [Thelander, Margo] John Muir Med Ctr, Walnut Creek, CA USA. [Thelander, Margo] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA 91010 USA. [Peterlongo, Paolo] Ist FIRC Oncol Mol IFOM, I-20139 Milan, Italy. [Radice, Paolo] Ist Nazl Tumori, IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Pensotti, Valeria] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Dolcetti, Riccardo] Ctr Riferimento Oncol CRO, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy. [Bonanni, Bernardo; Rennert, Gad] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush] Ist Nazl Tumori, IRCCS, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy. [Varesco, Liliana] Azienda Osped Univ San Martino Genova, IST Ist Nazl Ric Cancro, IRCCS, Dept Epidemiol Prevent & Special Funct,Unit Hered, I-16132 Genoa, Italy. [Capone, Gabriele L.] FiorGen Fdn Pharmacogen, I-50019 Sesto Fiorentino, Italy. [Capone, Gabriele L.; Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy. Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Yannoukakos, Drakoulis] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Sch Med, Dept Med Oncol, GR-54006 Thessaloniki, Greece. [Konstantopoulou, Irene] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece. Dana Farber Canc Inst, Boston, MA 02215 USA. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, Heidelberg, Germany. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol BS2 8EG, Avon, England. [Brady, Angela] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England. Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Foo, Claire] Liverpool Womens NHS Fdn Trust, Merseyside & Cheshire Clin Genet Serv, Liverpool L8 7SS, Merseyside, England. Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England. [Frost, Debra; Platte, Radka; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. [Eccles, Diana] Univ Southampton, Southampton Univ Hosp, NHS Trust, Fac Med, Southampton SO16 6YD, Hants, England. [Douglas, Fiona] Newcastle Upon Tyne Hosp, NHS Trust, Int Ctr Life, Inst Human Genet,Northern Genet Serv, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Adlard, Julian] Leeds Teaching Hosp, NHS Trust, Old Med Sch, Yorkshire Reg Genet Serv, Leeds LS1 3EX, W Yorkshire, England. Univ Hosp Leicester, NHS Trust, Leicester Royal Infirm, Dept Clin Genet,Leicestershire Clin Genet Serv, Leicester LE1 5WW, Leics, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LE, England. [Izatt, Louise] Guys Hosp, Guys & St Thomas NHS Fdn Trust, Clin Genet Serv, London SE1 9RT, England. [Side, Lucy E.; Kennedy, M. John] Great Ormond St Hosp Sick Children, NHS Trust, North East Thames Reg Genet Serv, London WC1N 3BH, England. Trinity Coll Dublin, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland. St James Hosp, Med Oncol Serv, Dublin 8, Ireland. [Tischkowitz, Marc] Cambridge Univ Hosp, Addenbrookes Hosp, NHS Fdn Trust, Addenbrookes Treatment Ctr,Dept Clin Genet,East A, Cambridge CB2 0QQ, England. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF14 4XW, S Glam, Wales. [Porteous, Mary E.] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Morrison, Patrick J.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland. [Morrison, Patrick J.] Belfast City Hosp, Belfast Hlth & Social Care Trust, Dept Med Genet, Belfast BT9 7AB, Antrim, North Ireland. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW7 3RP, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London SW7 3RP, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow G3 8SJ, Lanark, Scotland. [Hodgson, Shirley] Univ London St Georges Hosp, Dept Med Genet, South West Thames Reg Genet Serv, London SW17 0RE, England. [Cole, Trevor] Birmingham Womens Hosp, Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Isaacs, Claudine] MedStar Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. 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[Amadori, Alberto] Univ Padua, Dept Surg Sci Oncol & Gastroenterol, Clin Surg 2, I-35124 Padua, Italy. [Amadori, Alberto; Montagna, Marco] IRCCS, IOV, Immunol & Mol Oncol Unit, I-35128 Padua, Italy. [Teixeira, Manuel R.] Portuguese Oncol Inst IPO PORTO, Dept Genet, P-4200072 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, ICBAS, P-4050313 Oporto, Portugal. [Foulkes, William] McGill Univ, Dept Human Genet & Oncol, Program Canc Genet, Montreal, PQ J2W 1S6, Canada. [Olswold, Curtis; Pankratz, Vernon S.; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Lincoln, Anne; Jacobs, Lauren; Corines, Marina] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10065 USA. [Robson, Mark; Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10065 USA. [Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng] AKH Wien, Med Univ Vienna, Univ Klin Frauenheilkun, Comprehens Canc Ctr Vienna,Dept Obstet & Gynecol, A-1090 Vienna, Austria. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Rennert, Gad] Natl Israeli Canc Control Ctr, IL-34361 Haifa, Israel. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Clalit Hlth Serv, IL-34361 Haifa, Israel. [Rennert, Gad] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, IL-34362 Haifa, Israel. [Imyanitov, Evgeny N.] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia. [Mulligan, Anna Marie; Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5S 1A8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1T8, Canada. [Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Glendon, Gord; Andrulis, Irene L.; Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Toland, Amanda Ewart] Dept Human Canc Genet, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Wexner Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Arthur G James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Richard J Solove Res Inst OSUCCC James, Columbus, OH 43210 USA. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, DK-9000 Aalborg, Denmark. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. 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[Olopade, Olufunmilayo I.] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA. [Ramus, Susan J.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Div Canc Med, Houston, TX 77230 USA. [Mitchell, Gillian] Peter MacCallum Canc Ctr, Familial Canc Ctr, Sir Peter MacCallum Dept Oncol, East Melbourne, Vic 3002, Australia. [Mitchell, Gillian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Stoppa-Lyonnet, Dominique] INSERM, Inst Curie, Serv Genet Oncol, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Sorbonne Paris Cite, F-75006 Paris, France. [Thomas, Gilles] Univ Lyon 1, Fac Med Lyon Est, Genet Med, F-69373 Lyon 08, France. [Thomas, Gilles] Ctr Leon Berard, Fdn Synergie Lyon Canc, Inst Natl Canc INCa, F-69008 Lyon 08, France. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon 08, France. [Segota, Ena] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA 91010 USA. RP Cox, DG (reprint author), Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM U1052,UMR5286, F-69365 Lyon, France. EM david.cox@lyon.unicancer.fr RI del Valle, Jesus/I-2527-2015; montagna, marco/E-2225-2012; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Dolcetti, Riccardo/O-3832-2015; Teixeira, Manuel/E-4885-2011; Andrulis, Irene/E-7267-2013; Cox, David/A-2023-2009; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; OI Evans, Gareth/0000-0002-8482-5784; Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; Barrowdale, Daniel/0000-0003-1661-3939; del Valle, Jesus/0000-0003-3607-7045; Papi, Laura/0000-0003-4552-9517; Joseph, Vijai/0000-0002-7933-151X; Tommasi, Stefania/0000-0002-2157-2978; Yannoukakos, Drakoulis/0000-0001-7509-3510; VENAT-BOUVET, Laurence/0000-0002-0716-2550; montagna, marco/0000-0002-4929-2150; Dolcetti, Riccardo/0000-0003-1625-9853; Teixeira, Manuel/0000-0002-4896-5982; Cox, David/0000-0002-2152-9259; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Robson, Mark/0000-0002-3109-1692; benitez, javier/0000-0002-0923-7202; Eeles, Rosalind/0000-0002-3698-6241 FU European Commission Seventh Framework Program [223175: HEALTH-F2-2009-223175]; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; National Health and Medical Research Council (NHMRC) program; National Health and Medical Research Council (NHMRC); American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Intramural Research Program of the National Cancer Institute, National Institutes of Health; National Cancer Institute, National Institutes of Health [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; LSC [10.0010.08]; European Social Fund [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja City Council, Liepaja, Latvia; Breast Cancer Research Foundation; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research; NEYE Foundation; Spanish Association against Cancer (Asociacion Espanola Contra el Cancer) [AECC08]; Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) [RTICC 06/0020/1060]; Spanish Ministry of Science and Innovation [FIS PI08 1120]; Fondo de Investigacion Sanitaria (FIS) [SAF2010-20493]; Fundacion Mutua Madrilena (FMMA); City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN); National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Italian citizens; Fondazione IRCCS Istituto Nazionale Tumori; Italian Association for Cancer Research (AIRC); European Union (European Social Fund (ESF); Greek national funds through the "Education and Lifelong Learning" operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; "Heracleitus II: Investing in knowledge society through the European Social Fund"; Deutsches Krebsforschungszentrum (DKFZ); National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK; NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program; GOA [BOF10/GOA/019]; Ghent University Hospital; National Cancer Institute grants to the GOG Administrative Office and Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOG's Cancer Prevention and Control Committee [CA 101165]; Instituto de Salud Carlos III (ISCIII), Madrid, Spain [RD12/00369/0006, 12/00539]; European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds; Helsinki University Central Hospital Research Fund; Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; Biobanking and Molecular Resource Infrastructure (BBMRI) [NWO 184.021.007/CP46]; Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) [KTIA-OTKA CK-80745, KTIA-OTKA K-112228]; Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer; Spanish Health Research Foundation; Ramon Areces Foundation; Instituto de Salud Carlos III (ISCIII); Catalan Health Institute; Autonomous Government of Catalonia; International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) [PBZ_KBN_122/P05/2004]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research (CIHR) for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance [019511]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Ministero della Salute and a "5 x 1,000" Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; National Institutes of Health (NIH) through the National Cancer Institute (NCI) [CA 116167, CA 128978, CA 176785]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; US Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]; Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute [MMCI 00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ. 1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Intramural Research Program of the National Cancer Institute; Westat, Inc, Rockville, MD, USA [N02-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York, NY, USA; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Ohio State University Comprehensive Cancer Center; Istituto Toscano Tumori (ITT); Israeli Inherited Breast Cancer Consortium; Swedish Breast Cancer; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation; University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center; Cancer Research UK; University of Pennsylvania: National Institutes of Health (NIH) [R01 CA102776, R01 CA083855]; Susan G Komen for the Cure, Basser Center for BRCA; Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation; [5U01 CA113916]; [R01 CA140323]; [ISCIIIRETIC RD06/0020/1051]; [PI09/02483]; [PI10/01422]; [PI10/00748]; [PI13/00285]; [PI13/00189 2009SGR290]; [PI13/00189 2009SGR283]; [CA125183]; [R01 CA142996]; [1U01CA161032] FX Higher-level funding: The COGS project is funded through a European Commission Seventh Framework Program grant (agreement number 223175: HEALTH-F2-2009-223175). The CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. SH is supported by a National Health and Medical Research Council (NHMRC) program grant (to GCT).; Individual researcher support: ACA is a Cancer Research UK Senior Cancer Research Fellow (C12292/A11174). DFE is a Principal Research Fellow of Cancer Research UK. GC, MCS and IC are supported by the National Health and Medical Research Council (NHMRC). BK holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). MHG and PLM were supported by funding from the Intramural Research Program of the National Cancer Institute, National Institutes of Health. OIO is an American Cancer Society Clinical Research Professor. JS is Chairholder of the Canada Research Chair in Oncogenetics.; Funding of constituent studies: The Breast Cancer Family Registry (BCFR) was supported by grant UM1 CA164920 from the National Cancer Institute, National Institutes of Health. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC) is partly supported by Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; BFBOCC-LV (Latvia) is partly supported by LSC grant 10.0010.08 and in part by a grant from the European Social Fund number 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and the Liepaja City Council, Liepaja, Latvia; Beth Israel Deaconess Medical Center Cancer Center is supported by the Breast Cancer Research Foundation; BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J van Rensburg; SLN (Beckman Research Institute, City of Hope, Duarte, CA, USA) was partially supported by the Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research; the Copenhagen Breast Cancer Study (CBCS) was supported by the NEYE Foundation; the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas (CNIO)) was partially supported by the Spanish Association against Cancer (Asociacion Espanola Contra el Cancer AECC08), Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) RTICC 06/0020/1060, Spanish Ministry of Science and Innovation grants FIS PI08 1120 (Fondo de Investigacion Sanitaria (FIS)) and SAF2010-20493, and the Fundacion Mutua Madrilena (FMMA); the City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN), supported in part by award number RC4CA153828 (Principal Investigator: JNW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella, Italy (CONSIT Team): Funds from Italian citizens who allocated the "5 x 1,000" share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (Istituto Nazionale dei Tumori (INT) institutional strategic project "5 x 1,000") (to SM); the Italian Association for Cancer Research (AIRC) (to LO); National Centre for Scientific Research "Demokritos" has been cofinanced by the European Union (European Social Fund (ESF)) and Greek national funds through the "Education and Lifelong Learning" operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; "Heracleitus II: Investing in knowledge society through the European Social Fund"; the DKFZ study was supported by the Deutsches Krebsforschungszentrum (DKFZ); Epidemiological Study of BRCA1 and BRCA2 Mutation Carriers (EMBRACE) is supported by Cancer Research UK grants C1287/A10118 and C1287/A11990; DGE and FL are supported by a National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK; the investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London; RE and EB are supported by Cancer Research UK grant C5047/A8385; Kansas University Medical Center: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program; AKG was funded by grants 5U01 CA113916 and R01 CA140323 and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship; The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by German Cancer Aid (grant 109076 (to RKS) and by the Center for Molecular Medicine Cologne (CMMC); GC-HBOC is deeply grateful to Dr Sabine Preisler-Adam for providing information and samples; the GEMO Study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program; G-FAST: KDL is supported by GOA grant BOF10/GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital; the Gynecologic Oncology Group (GOG) was supported by National Cancer Institute grants to the GOG Administrative Office and Tissue Bank (grant CA 27469), the GOG Statistical and Data Center (grant CA 37517) and GOG's Cancer Prevention and Control Committee (grant CA 101165); HCSC was supported by grants RD12/00369/0006 and 12/00539 from Instituto de Salud Carlos III (ISCIII), Madrid, Spain, partially supported by European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds; the Helsinki Breast Cancer Study (HEBCS) was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation; HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088 and NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and Biobanking and Molecular Resource Infrastructure (BBMRI) grant NWO 184.021.; 007/CP46; HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection; the High Risk Breast Cancer Program (HRBCP) is supported by the Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong; the Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) research grants KTIA-OTKA CK-80745 and KTIA-OTKA K-112228; Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer; Spanish Health Research Foundation; Ramon Areces Foundation; Instituto de Salud Carlos III (ISCIII); Catalan Health Institute; and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, PI13/00285, PI13/00189 2009SGR290 and PI13/00189 2009SGR283; the International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) was supported by grant PBZ_KBN_122/P05/2004; Landspitali - The National University Hospital of Iceland was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund; the Interdisciplinary Health Research Internal Team Breast Cancer Susceptibility Study (INHERIT) was supported by the Canadian Institutes of Health Research (CIHR) for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance grant 019511 and Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701; the Istituto Oncologico Veneto Hereditary Breast and Ovarian Cancer Study (IOVHBOCS) is supported by the Ministero della Salute and a "5 x 1,000" Istituto Oncologico Veneto grant; the Portuguese Oncology Institute-Porto Breast Cancer Study (IPOBCS) was supported in part by Liga Portuguesa Contra o Cancro; kConFab is supported by a grant from the National Breast Cancer Foundation and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; the Mayo Clinic is supported by National Institutes of Health (NIH) grants CA 116167, CA 128978 and CA 176785 through the National Cancer Institute (NCI), an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a US Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research Foundation, a generous gift from the David F and Margaret T Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation; McGill University Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade; Modifier Study of Quantitative Effects on Disease (ModSQuaD) was supported by the Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute (MH CZ - DRO) (MMCI 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ. 1.05/2.1.00/03.; 0101) (to LF), and by Charles University in Prague project UNCE204024 (MZ); Memorial Sloan Kettering Cancer Center (MSKCC) is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative; National Cancer Institute, National Institutes of Health: The research of MHG and PLM was supported by the Intramural Research Program of the National Cancer Institute and by support services contracts N02-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD, USA; the National Israeli Cancer Control Center (NICCC) is supported by Clalit Health Services in Israel; some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York, NY, USA; NN Petrov Institute of Oncology has been supported by the Russian Federation for Basic Research (grants 11-04-00227, 12-04-00928 and 12-04-01490) and the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780); The Ohio State University Clinical Cancer Genetics (OSUCCG) is supported by The Ohio State University Comprehensive Cancer Center; the Pisa Breast Cancer Study (PBCS) was supported by Istituto Toscano Tumori (ITT) grants 2011-2013; Sheba Medical Center was partially funded through a grant from the Israel Cancer Association and funding for the Israeli Inherited Breast Cancer Consortium; the Swedish Breast Cancer Study collaborators are supported by the Swedish Cancer Society; The University of Chicago is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996 and 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer Research Foundation; University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation; University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center; UK Familial Ovarian Cancer Registry (UKFOCR) was supported by a project grant from Cancer Research UK (to Paul DP Pharoah); the University of Pennsylvania: National Institutes of Health (NIH) grants R01 CA102776 and R01 CA083855; the Breast Cancer Research Foundation; the Susan G Komen for the Cure, Basser Center for BRCA; Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation; The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). NR 54 TC 3 Z9 3 U1 7 U2 32 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 APR 25 PY 2015 VL 17 AR 61 DI 10.1186/s13058-015-0567-2 PG 15 WC Oncology SC Oncology GA CL2KV UT WOS:000356773600001 PM 25925750 ER PT J AU Okuma, CH Andrade, TAM Caetano, GF Finci, LI Maciel, NR Topan, JF Cefali, LC Polizello, ACM Carlo, T Rogerio, AP Spadaro, ACC Isaac, VLB Frade, MAC Rocha, PA AF Okuma, C. H. Andrade, T. A. M. Caetano, G. F. Finci, L. I. Maciel, N. R. Topan, J. F. Cefali, L. C. Polizello, A. C. M. Carlo, T. Rogerio, A. P. Spadaro, A. C. C. Isaac, V. L. B. Frade, M. A. C. Rocha-Filho, P. A. TI Development of lamellar gel phase emulsion containing marigold oil (Calendula officinalis) as a potential modern wound dressing SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Calendula officinalis oil; Lamellar gel phase emulsion; Liquid crystal; Stability tests; Wound healing ID DRUG-DELIVERY SYSTEMS; NONIONIC SURFACTANT; FLOWER EXTRACT; MICE AB Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of tissue repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold (Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats. LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion (15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic activity (50-1000 mu g/mL) was observed in marigold oil. In the wound healing rat model, the LGP (15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7, but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of re-epithelialization of the wound itself. The methodology utilized in the present study has produced a potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve the wound healing process. (C) 2015 Elsevier B.V. All rights reserved. C1 [Okuma, C. H.; Maciel, N. R.; Topan, J. F.; Rocha-Filho, P. A.] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-1404090 Ribeirao Preto, SP, Brazil. [Andrade, T. A. M.; Caetano, G. F.; Frade, M. A. C.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Internal Med, Div Dermatol, BR-05508 Sao Paulo, Brazil. [Finci, L. I.] Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Finci, L. I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cefali, L. C.; Isaac, V. L. B.] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci Araraquara, Sao Paulo, Brazil. [Polizello, A. C. M.; Spadaro, A. C. C.] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-05508 Sao Paulo, Brazil. [Okuma, C. H.; Carlo, T.; Rogerio, A. P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Pulm & Crit Care Med Div,Dept Internal Med, Boston, MA 02115 USA. [Rogerio, A. P.] Univ Fed Triangulo Mineiro, Uberaba, Brazil. RP Okuma, CH (reprint author), Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, Ave Cafe S-N, BR-1404090 Ribeirao Preto, SP, Brazil. EM cindhana@hotmail.com RI Andrade, Thiago/G-9359-2012; de Paula Rogerio, Alexandre/K-8866-2013; OI Andrade, Thiago/0000-0003-3788-2847; de Paula Rogerio, Alexandre/0000-0001-5913-3703; FRADE, MARCO ANDREY/0000-0003-2700-5971 FU CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brazil); CNPq; FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - Brazil) FX This work was supported by CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brazil), CNPq and FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - Brazil). NR 41 TC 4 Z9 4 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 EI 1879-0720 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD APR 25 PY 2015 VL 71 BP 62 EP 72 DI 10.1016/j.ejps.2015.01.016 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE4NN UT WOS:000351807400007 PM 25684193 ER PT J AU Minikel, EV Vallabh, SM Lek, M Estrada, KO Samocha, KE Sathirapongsasuti, JF McLean, CY Tung, JY Yu, LPC Gambetti, P Blevins, J Zhang, SL Cohen, Y Chen, W Yamada, M Hamaguchi, T Sanjo, N Mizusawa, H Nakamura, Y Kitamoto, T Collins, SJ Boyd, A Will, RG Knight, R Ponto, C Zerr, I Kraus, TFJ Eigenbrod, S Giese, A Calero, M de Pedro-Cuesta, J Haik, S Laplanche, JL Bouaziz-Amar, E Brandel, JP Capellari, S Parchi, P O'Donnell-Luria, AH Karczewski, KJ Marshall, JL Boehnke, M Laakso, M Mohlke, KL Kahler, A Chambert, K McCarroll, S Sullivan, PF Hultman, CM Purcell, SM Sklar, P van der Lee, SJ Rozemuller, A Jansen, C Hofman, A Kraaij, R van Rooij, JGJ Ikram, MA Uitterlinden, AG van Duijn, CM Daly, MJ MacArthur, DG AF Minikel, Eric Vallabh Vallabh, Sonia M. Lek, Monkol Estrada, Karol O. Samocha, Kaitlin E. Sathirapongsasuti, J. Fah McLean, Cory Y. Tung, Joyce Y. Yu, Linda P. C. Gambetti, Pierluigi Blevins, Janis Zhang, Shulin Cohen, Yvonne Chen, Wei Yamada, Masahito Hamaguchi, Tsuyoshi Sanjo, Nobuo Mizusawa, Hidehiro Nakamura, Yosikazu Kitamoto, Tetsuyuki Collins, Steven J. Boyd, Alison Will, Robert G. Knight, Richard Ponto, Claudia Zerr, Inga Kraus, Theo F. J. Eigenbrod, Sabina Giese, Armin Calero, Miguel de Pedro-Cuesta, Jesus Haik, Stephane Laplanche, Jean-Louis Bouaziz-Amar, Elodie Brandel, Jean-Philippe Capellari, Sabina Parchi, Piero O'Donnell-Luria, Anne H. Karczewski, Konrad J. Marshall, Jamie L. Boehnke, Michael Laakso, Markku Mohlke, Karen L. Kahler, Anna Chambert, Kimberly McCarroll, Steven Sullivan, Patrick F. Hultman, Christina M. Purcell, Shaun M. Sklar, Pamela van der Lee, Sven J. Rozemuller, Annemieke Jansen, Casper Hofman, Albert Kraaij, Robert van Rooij, Jeroen G. J. Ikram, M. Arfan Uitterlinden, Andre G. van Duijn, Cornelia M. Daly, Mark J. MacArthur, Daniel G. CA Exome Aggregation Consortium ExAC TI Assessing the pathogenicity of rare PRNP variants by comparing case and control allele frequency SO PRION LA English DT Meeting Abstract C1 [Minikel, Eric Vallabh; Vallabh, Sonia M.] Prion Alliance, Cambridge, MA 02114 USA. [Minikel, Eric Vallabh; Vallabh, Sonia M.; Lek, Monkol; Estrada, Karol O.; Samocha, Kaitlin E.; O'Donnell-Luria, Anne H.; Karczewski, Konrad J.; Marshall, Jamie L.; Daly, Mark J.; MacArthur, Daniel G.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Minikel, Eric Vallabh; Lek, Monkol; Estrada, Karol O.; Samocha, Kaitlin E.; O'Donnell-Luria, Anne H.; Karczewski, Konrad J.; Marshall, Jamie L.; Daly, Mark J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA USA. [Minikel, Eric Vallabh; Vallabh, Sonia M.; Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Sathirapongsasuti, J. Fah; McLean, Cory Y.; Tung, Joyce Y.; Yu, Linda P. C.] 23andMe Inc, Res, Mountain View, CA USA. [Gambetti, Pierluigi; Blevins, Janis; Cohen, Yvonne; Chen, Wei] Natl Prion Dis Pathol Surveillance Ctr, Cleveland, OH USA. [Zhang, Shulin] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Yamada, Masahito; Hamaguchi, Tsuyoshi] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol Aging, Kanazawa, Ishikawa, Japan. [Sanjo, Nobuo] Tokyo Med & Dent Univ, Grad Sch, Dept Neurol & Neurol Sci, Tokyo, Japan. [Mizusawa, Hidehiro] Natl Ctr Neurol & Psychiat, Natl Ctr Hosp, Tokyo, 980, Japan. [Nakamura, Yosikazu] Jichi Med Univ, Dept Publ Hlth, Shimotsuke, 3052, Japan. [Kitamoto, Tetsuyuki] Tohoku Univ, Dept Neurol Sci, Grad Sch Med, Sendai EH4 2XU, Miyagi, Japan. [Collins, Steven J.; Boyd, Alison] Univ Melbourne, Australian Natl Creutzfeldt Jakob Dis Registry, D-37073 Parkville, Vic, Australia. [Will, Robert G.; Knight, Richard] Western Gen Hosp, Natl Creutzfeldt Jakob Dis Res & Surveillance Uni, Edinburgh, Midlothian, Scotland. [Ponto, Claudia; Zerr, Inga] Univ Gottingen, Natl Reference Ctr TSE, Gottingen, Germany. [Kraus, Theo F. J.; Eigenbrod, Sabina; Giese, Armin] Univ Munich, Ctr Neuropathol & Prion Res ZNP, Munich, Germany. [Calero, Miguel; de Pedro-Cuesta, Jesus] Inst Salud Carlos III, Madrid, Spain. [Calero, Miguel; de Pedro-Cuesta, Jesus] CIBERNED, F-75634 Madrid, Spain. [Haik, Stephane; Brandel, Jean-Philippe] Univ Paris 06, Inst Cerveau & Moelle Epiniere, Sorbonne Univ, CNRS,Inserm,U1127,UMR 7225,UMR S 1127,ICM, F-75475 Paris, France. [Haik, Stephane; Brandel, Jean-Philippe] Grp Hosp Pitie Salpetriere, AP HP, Cellule Natl Reference Malad Creutzfeldt Jakob, Paris, France. [Laplanche, Jean-Louis; Bouaziz-Amar, Elodie] Hop Lariboisiere, Serv Biochim & Biol Mol, Paris, France. [Capellari, Sabina; Parchi, Piero] IRCCS Inst Neurol Sci, Bologna, Italy. [Capellari, Sabina; Parchi, Piero] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, 48109, Italy. [O'Donnell-Luria, Anne H.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, SF-70210 Ann Arbor, MI USA. [Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Laakso, Markku] Kuopio Univ Hosp, Kuopio, Finland. [Mohlke, Karen L.; Sullivan, Patrick F.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Kahler, Anna; Sullivan, Patrick F.; Hultman, Christina M.] Karolinska Inst, Stockholm, 10029, Sweden. [Chambert, Kimberly; McCarroll, Steven] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, New York, NY USA. [van der Lee, Sven J.; Hofman, Albert; Ikram, M. Arfan; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rozemuller, Annemieke; Jansen, Casper] Univ Med Ctr, Prion Surveillance Ctr, Dept Pathol, Utrecht, Netherlands. [Kraaij, Robert; van Rooij, Jeroen G. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. RI Giese, Armin/F-3271-2010; Calero, Miguel/H-5691-2015; Parchi, Piero/L-9833-2015; LAPLANCHE, Jean-Louis/S-8707-2016 OI Giese, Armin/0000-0002-8238-4102; Calero, Miguel/0000-0001-5366-3324; Parchi, Piero/0000-0002-9444-9524; NR 0 TC 0 Z9 0 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.150 BP S90 EP S91 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900168 ER PT J AU Clifton, MC Dranow, DM Leed, A Fulroth, B Fairman, JW Abendroth, J Atkins, KA Wallace, E Fan, DZ Xu, GP Ni, ZJ Daniels, D Van Drie, J Wei, G Burgin, AB Golub, TR Hubbard, BK Serrano-Wu, MH AF Clifton, Matthew C. Dranow, David M. Leed, Alison Fulroth, Ben Fairman, James W. Abendroth, Jan Atkins, Kateri A. Wallace, Ellen Fan, Dazhong Xu, Guoping Ni, Z. J. Daniels, Doug Van Drie, John Wei, Guo Burgin, Alex B. Golub, Todd R. Hubbard, Brian K. Serrano-Wu, Michael H. TI A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1 SO PLOS ONE LA English DT Article ID CELL-DEATH; CANCER; INHIBITORS; DISCOVERY; POTENT; REFINEMENT; ACTIVATION; APOPTOSIS; SURVIVAL AB Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligandbound structures. The ability to obtain fragment-bound structures advances structurebased drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors. C1 [Leed, Alison; Fulroth, Ben; Daniels, Doug; Wei, Guo; Burgin, Alex B.; Golub, Todd R.; Hubbard, Brian K.; Serrano-Wu, Michael H.] Broad Inst, Cambridge, MA USA. [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Clifton, Matthew C.; Dranow, David M.; Fairman, James W.; Abendroth, Jan; Atkins, Kateri A.; Wallace, Ellen] Beryllium, Bedford, MA 01730 USA. [Fan, Dazhong; Xu, Guoping; Ni, Z. J.] Acme Biosci, Palo Alto, CA USA. [Van Drie, John] Van Drie Res, N Andover, MA USA. RP Clifton, MC (reprint author), Beryllium, Bedford, MA 01730 USA. EM mclifton@be4.com; swu@broadinstitute.org OI Daniels, Douglas/0000-0003-0238-9403 FU Carlos Slim Health Institute; Robertson Foundation; Van Drie Research FX This study was funded by the Broad Institute with generous support from the Carlos Slim Health Institute and the Robertson Foundation. AL, BF, D. Daniels, GW, AB, TRG, BKH, and MSW are employees of the Broad Institute and received funding for this study in the form of a salary. MCC, D. Dranow, JWF, JA, KAA, and EW are employees of Beryllium and received funding for this study in the form of a salary. DF, ZN, and GX are employees of Acme Bioscience and received funding for this study in the form of a salary. JVD is the sole proprietor of Van Drie Research and received funding for this study in the form of a salary. The Broad Institute, Beryllium, Acme, and Van Drie Research played a role in study design, data collection and analysis, decision to publish and preparation of the manuscript. NR 32 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 APR 24 PY 2015 VL 10 IS 4 AR UNSP e0125010 DI 10.1371/journal.pone.0125010 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG6AH UT WOS:000353376800121 PM 25909780 ER PT J AU Oldenburg, CE Perez-Brumer, AG Hatzenbuehler, ML Krakower, D Novak, DS Mimiaga, MJ Mayer, KH AF Oldenburg, Catherine E. Perez-Brumer, Amaya G. Hatzenbuehler, Mark L. Krakower, Douglas Novak, David S. Mimiaga, Matthew J. Mayer, Kenneth H. TI State-level structural sexual stigma and HIV prevention in a national online sample of HIV-uninfected MSM in the United States SO AIDS LA English DT Article DE HIV; MSM; postexposure prophylaxis; pre-exposure prophylaxis; structural stigma ID POSTEXPOSURE PROPHYLAXIS; TRANSGENDER WOMEN; RISK BEHAVIOR; MEN; HEALTH; GAY; METAANALYSIS; INFECTION; WORKERS; ADHERENCE AB Background:Stigmatizing social environments (of which structural stigma' is one component) negatively affect health-related outcomes. However, few studies have examined structural stigma related to sexual minority status as a risk factor for HIV outcomes among MSM.Methods:In August 2013, members of a large MSM social and sexual networking site in the United States completed a survey about HIV-prevention practices. A previously validated composite index provided values for state-level structural stigma, including density of same-sex couples, proportion of public high schools with Gay-Straight Alliances, state laws protecting sexual minorities, and public opinion toward homosexuality. Multivariable logistic generalized estimating equations assessed the relationship between structural stigma and condomless anal intercourse, use and awareness of antiretroviral-based HIV-prevention strategies (i.e. pre and postexposure prophylaxis, or PEP and PrEP), and comfort discussing male-male sex with primary care providers.Results:Among the 4098 HIV-uninfected MSM, lower state-level structural stigma was associated with decreased odds of condomless anal intercourse [adjusted odds ratio (aOR) 0.97 per one unit increase in structural stigma score, 95% confidence interval (CI) 0.94-0.99], increased odds of awareness of PEP (aOR 1.06, 95% CI 1.02-1.09), and PrEP (aOR 1.06, 95% CI 1.02-1.10), having taken PEP (aOR 1.15, 95% CI 1.05-1.26) and PrEP (aOR 1.21, 95% CI 1.01-1.44), and comfort discussing male-male sex with providers (aOR 1.08, 95% CI 1.05-1.11), after adjusting for social and state-level confounders.Conclusion:MSM living in more stigmatizing environments had decreased use of antiretroviral-based HIV-prevention strategies compared to those in less stigmatizing environments. Legal reforms protecting sexual minorities should be evaluated as structural interventions that could reduce HIV risk among MSM. C1 [Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Perez-Brumer, Amaya G.; Hatzenbuehler, Mark L.] Columbia Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Krakower, Douglas; Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Dept Internal Med, Cambridge, MA USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Oldenburg, CE (reprint author), 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu FU Gilead Sciences; National Institute of Allergy and Infectious Disease NRSA [T32AI007535]; National Institute of Drug Abuse NRSA [T32DA013911]; Eunice Kennedy Shriver National Institute of Child Health & Human Development [T32 HD049339]; National Institutes of Mental Health [R25 MH083620, MH098795]; National Institute of Drug Abuse Mentored Research Scientist Development Award [K01 DA032558] FX Funding: This work was funded by an unrestricted research grant from Gilead Sciences.; C.E.O. was supported by a National Institute of Allergy and Infectious Disease T32 NRSA grant (T32AI007535; PI: Seage). C.E.O. is currently supported by a National Institute of Drug Abuse T32 NRSA (T32DA013911 PI: Flanigan). A.P.B. is supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development T32 HD049339 (PI: Nathanson) and the National Institutes of Mental Health R25 MH083620 (PI: Flanigan). M.L.H. is supported by a National Institute of Drug Abuse Mentored Research Scientist Development Award (K01 DA032558). D.S.K. is supported by a National Institutes of Mental Health Career Development Award (MH098795). NR 37 TC 13 Z9 13 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD APR 24 PY 2015 VL 29 IS 7 BP 837 EP 845 DI 10.1097/QAD.0000000000000622 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA CG7FV UT WOS:000353469000011 PM 25730508 ER PT J AU Liao, KP Cai, TX Savova, GK Murphy, SN Karlson, EW Ananthakrishnan, AN Gainer, VS Shaw, SY Xia, ZQ Szolovits, P Churchill, S Kohane, I AF Liao, Katherine P. Cai, Tianxi Savova, Guergana K. Murphy, Shawn N. Karlson, Elizabeth W. Ananthakrishnan, Ashwin N. Gainer, Vivian S. Shaw, Stanley Y. Xia, Zongqi Szolovits, Peter Churchill, Susanne Kohane, Isaac TI Development of phenotype algorithms using electronic medical records and incorporating natural language processing SO BMJ-British Medical Journal LA English DT Article ID RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; ULCERATIVE-COLITIS; DISCOVERY RESEARCH; HEALTH RECORDS; IDENTIFICATION; NORMALIZATION; RISK; CLASSIFICATION; PREVALENCE C1 [Liao, Katherine P.; Karlson, Elizabeth W.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Liao, Katherine P.; Karlson, Elizabeth W.; Shaw, Stanley Y.; Xia, Zongqi; Churchill, Susanne; Kohane, Isaac] Harvard Univ, Sch Med, Boston, MA USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Savova, Guergana K.] Childrens Hosp Boston, Dept Pediat, Boston, MA USA. [Murphy, Shawn N.; Kohane, Isaac] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Gastroenterol, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Gainer, Vivian S.] Partners HealthCare Syst, Partners Res Comp, Boston, MA USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Xia, Zongqi] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Szolovits, Peter] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM kliao@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU US National Institutes of Health [U54LM008748, AR 060257, K08 K23 DK097142]; Harold and Duval Bowen Fund FX This study was funded by grants from the US National Institutes of Health (U54LM008748, AR 060257, K08 K23 DK097142), and the Harold and Duval Bowen Fund. NR 35 TC 7 Z9 8 U1 1 U2 9 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 APR 24 PY 2015 VL 350 AR h1885 DI 10.1136/bmj.h1885 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CG8RC UT WOS:000353577000004 PM 25911572 ER PT J AU Bonaca, MP Creager, MA AF Bonaca, Marc P. Creager, Mark A. TI Pharmacological Treatment and Current Management of Peripheral Artery Disease SO CIRCULATION RESEARCH LA English DT Article DE medical therapy; peripheral artery disease ID RANDOMIZED CONTROLLED-TRIAL; PROTEASE-ACTIVATED RECEPTORS; PLACEBO-CONTROLLED TRIAL; SWEDISH-TICLOPIDINE-MULTICENTER; CARDIOVASCULAR EVENT RATES; AMERICAN-HEART-ASSOCIATION; ACUTE CORONARY SYNDROMES; CRITICAL LIMB ISCHEMIA; HIGH-DOSE ATORVASTATIN; HIGH-RISK PATIENTS AB Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise, as well as optimal medical therapy. Pharmacological therapies for patients with PAD are targeted both at modifying broad risk factors for major adverse cardiovascular events, as well as reducing limb-related morbidity. Observational data suggest that indicated pharmacological treatments are greatly underutilized in PAD, underscoring the need for improvements in patient identification and care delivery. Ongoing trials of novel therapies in patients with PAD will further inform pharmacological strategies to reduce both systemic cardiovascular risk and limb-related morbidity. C1 Brigham & Womens Hosp, Vasc Med Sect, Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU National Heart, Lung, and Blood Institute [K12 HL083786] FX Dr Bonaca was supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. Dr Creager is the Simon C. Fireman Scholar in Cardiovascular Medicine at Brigham and Women's Hospital. NR 130 TC 23 Z9 24 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD APR 24 PY 2015 VL 116 IS 9 BP 1579 EP 1598 DI 10.1161/CIRCRESAHA.114.303505 PG 20 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CG6CR UT WOS:000353383600007 PM 25908730 ER PT J AU Thukkani, AK Kinlay, S AF Thukkani, Arun K. Kinlay, Scott TI Endovascular Intervention for Peripheral Artery Disease SO CIRCULATION RESEARCH LA English DT Article DE endovascular procedures; intermittent claudication; peripheral artery disease ID SUPERFICIAL FEMORAL-ARTERY; CRITICAL LIMB ISCHEMIA; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; NITINOL STENT IMPLANTATION; RANDOMIZED CONTROLLED-TRIAL; CHRONIC TOTAL OCCLUSIONS; CRITICAL LEG ISCHEMIA; DRUG-ELUTING BALLOON; BARE-METAL STENTS; EXPERT CONSENSUS STATEMENT AB Advances in endovascular therapies during the past decade have broadened the options for treating peripheral vascular disease percutaneously. Endovascular treatment offers a lower risk alternative to open surgery in many patients with multiple comorbidities. Noninvasive physiological tests and arterial imaging precede an endovascular intervention and help localize the disease and plan the procedure. The timing and need for revascularization are broadly related to the 3 main clinical presentations of claudication, critical limb ischemia, and acute limb ischemia. Many patients with claudication can be treated by exercise and medical therapy. Endovascular procedures are considered when these fail to improve quality of life and function. In contrast, critical limb ischemia and acute limb ischemia threaten the limb and require more urgent revascularization. In general, endovascular treatments have greater long-term durability for aortoiliac disease than femoral popliteal disease. Infrapopliteal revascularization is generally reserved for critical and acute limb ischemia. Balloon angioplasty and stenting are the mainstays of endovascular therapy. New well-tested innovations include drug-eluting stents and drug-coated balloons. Adjunctive devices for crossing chronic total occlusions or debulking plaque with atherectomy are less rigorously studied and have niche roles. Patients receiving endovascular procedures need a structured surveillance plan for follow-up care. This includes intensive treatment of cardiovascular risk factors to prevent myocardial infarction and stroke, which are the main causes of death. Limb surveillance aims to identify restenosis and new disease beyond the intervened segments, both of which may jeopardize patency and lead to recurrent symptoms, functional impairment, or a threatened limb. C1 [Thukkani, Arun K.] Missouri Baptist Hosp, BJCMG Cardiol, St Louis, MO USA. [Kinlay, Scott] VA Boston Healthcare Syst, Cardiovasc Div, West Roxbury, MA 02132 USA. Brigham & Womens Hosp, 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 FU VA Clinical Science Research and Development Awards [1/01CX000440, 1/21CX000793] FX This study was supported by VA Clinical Science Research and Development Awards 1/01CX000440 and 1/21CX000793. NR 133 TC 15 Z9 19 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD APR 24 PY 2015 VL 116 IS 9 BP 1599 EP 1613 DI 10.1161/CIRCRESAHA.116.303503 PG 15 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CG6CR UT WOS:000353383600008 PM 25908731 ER PT J AU Duda, T Wen, XH Isayama, T Sharma, RK Makino, CL AF Duda, Teresa Wen, Xiao-Hong Isayama, Tomoki Sharma, Rameshwar K. Makino, Clint L. TI Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARBONIC-ANHYDRASE ACTIVITY; HYDROGEN-ION BUFFERS; OUTER SEGMENT; VERTEBRATE PHOTORECEPTOR; FUNCTIONAL CONSEQUENCES; CONGENITAL AMAUROSIS; BIOLOGICAL-RESEARCH; TISSUE METABOLISM; RETINAL DISEASE; FLASH RESPONSES AB By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca2+](i) to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS-GC2. The effect required neither Ca2+ nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca2+]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. C1 [Duda, Teresa; Sharma, Rameshwar K.] Salus Univ, Div Biochem Res, Unit Regulatory & Mol Biol, Elkins Pk, PA 19027 USA. [Duda, Teresa; Sharma, Rameshwar K.] Salus Univ, Res Div Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA 19027 USA. [Wen, Xiao-Hong; Isayama, Tomoki; Makino, Clint L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Wen, Xiao-Hong; Isayama, Tomoki; Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makino, CL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU National Institutes of Health [EY011358, EY014104, EY023980]; Research to Prevent Blindness; Howe Laboratory Endowment of the Massachusetts Eye and Ear Infirmary FX This work was supported, in whole or in part, by National Institutes of Health Grants EY011358, EY014104, and EY023980. This work was also supported by Research to Prevent Blindness and the Howe Laboratory Endowment of the Massachusetts Eye and Ear Infirmary. NR 70 TC 4 Z9 4 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 2015 VL 290 IS 17 BP 11052 EP 11060 DI 10.1074/jbc.M115.650408 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG6IX UT WOS:000353404500041 PM 25767116 ER PT J AU Hyle, EP Alame, D AF Hyle, Emily P. Alame, Diana TI Case 13-2015: A 27-Year-Old Woman with Arthralgias and a Rash SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DENGUE CASE CLASSIFICATION; CLINICAL PRESENTATION; CHIKUNGUNYA FEVER; LABORATORY FEATURES; UNITED-STATES; OUTBREAK; INFECTION; ARTHRITIS; DISEASE; VIRUS C1 [Hyle, Emily P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alame, Diana] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hyle, Emily P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Alame, Diana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hyle, EP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 35 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 APR 23 PY 2015 VL 372 IS 17 BP 1657 EP 1664 DI 10.1056/NEJMcpc1415172 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CG4XX UT WOS:000353294000013 PM 25901430 ER PT J AU Sahni, N Yi, S Taipale, M Bass, JIF Coulombe-Huntington, J Yang, F Peng, J Weile, J Karras, GI Wang, Y Kovacs, IA Kamburov, A Krykbaeva, I Lam, MH Tucker, G Khurana, V Sharma, A Liu, YY Yachie, N Zhong, Q Shen, Y Palagi, A San-Miguel, A Fan, CY Balcha, D Dricot, A Jordan, DM Walsh, JM Shah, AA Yang, XP Stoyanova, AK Leighton, A Calderwood, MA Jacob, Y Cusick, ME Salehi-Ashtiani, K Whitesell, LJ Sunyaev, S Berger, B Barabasi, AL Charloteaux, B Hill, DE Hao, T Roth, FP Xia, Y Walhout, AJM Lindquist, S Vidal, M AF Sahni, Nidhi Yi, Song Taipale, Mikko Bass, Juan I. Fuxman Coulombe-Huntington, Jasmin Yang, Fan Peng, Jian Weile, Jochen Karras, Georgios I. Wang, Yang Kovacs, Istvan A. Kamburov, Atanas Krykbaeva, Irina Lam, Mandy H. Tucker, George Khurana, Vikram Sharma, Amitabh Liu, Yang-Yu Yachie, Nozomu Zhong, Quan Shen, Yun Palagi, Alexandre San-Miguel, Adriana Fan, Changyu Balcha, Dawit Dricot, Amelie Jordan, Daniel M. Walsh, Jennifer M. Shah, Akash A. Yang, Xinping Stoyanova, Ani K. Leighton, Alex Calderwood, Michael A. Jacob, Yves Cusick, Michael E. Salehi-Ashtiani, Kourosh Whitesell, Luke J. Sunyaev, Shamil Berger, Bonnie Barabasi, Albert-Laszlo Charloteaux, Benoit Hill, David E. Hao, Tong Roth, Frederick P. Xia, Yu Walhout, Albertha J. M. Lindquist, Susan Vidal, Marc TI Widespread Macromolecular Interaction Perturbations in Human Genetic Disorders SO CELL LA English DT Article ID ONE-HYBRID ASSAYS; SEQUENCE VARIATION; PROTEIN COMPLEXES; HUMAN-DISEASE; MUTATIONS; NETWORK; CANCER; EXPRESSION; CHAPERONE; GENOME AB How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays. The majority of disease-associated alleles exhibit wild-type chaperone binding profiles, suggesting they preserve protein folding or stability. While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving most other interactions unperturbed. With transcription factors, many alleles that leave protein-protein interactions intact affect DNA binding. Different mutations in the same gene leading to different interaction profiles often result in distinct disease phenotypes. Thus disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread. C1 [Sahni, Nidhi; Yi, Song; Yang, Fan; Weile, Jochen; Wang, Yang; Kovacs, Istvan A.; Sharma, Amitabh; Yachie, Nozomu; Shen, Yun; Fan, Changyu; Balcha, Dawit; Dricot, Amelie; Calderwood, Michael A.; Cusick, Michael E.; Barabasi, Albert-Laszlo; Charloteaux, Benoit; Hill, David E.; Hao, Tong; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Genom Anal Network, Perturbat Ctr Excellence Genom Sci CEGS, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Yang, Fan; Weile, Jochen; Wang, Yang; Kovacs, Istvan A.; Kamburov, Atanas; Sharma, Amitabh; Liu, Yang-Yu; Yachie, Nozomu; Zhong, Quan; Shen, Yun; Palagi, Alexandre; San-Miguel, Adriana; Fan, Changyu; Balcha, Dawit; Dricot, Amelie; Walsh, Jennifer M.; Shah, Akash A.; Yang, Xinping; Stoyanova, Ani K.; Calderwood, Michael A.; Jacob, Yves; Cusick, Michael E.; Salehi-Ashtiani, Kourosh; Barabasi, Albert-Laszlo; Charloteaux, Benoit; Hill, David E.; Hao, Tong; Roth, Frederick P.; Xia, Yu; Walhout, Albertha J. M.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Yang, Fan; Weile, Jochen; Wang, Yang; Kovacs, Istvan A.; Kamburov, Atanas; Sharma, Amitabh; Liu, Yang-Yu; Yachie, Nozomu; Zhong, Quan; Shen, Yun; Palagi, Alexandre; San-Miguel, Adriana; Fan, Changyu; Balcha, Dawit; Dricot, Amelie; Walsh, Jennifer M.; Shah, Akash A.; Yang, Xinping; Stoyanova, Ani K.; Calderwood, Michael A.; Jacob, Yves; Cusick, Michael E.; Salehi-Ashtiani, Kourosh; Barabasi, Albert-Laszlo; Charloteaux, Benoit; Hill, David E.; Hao, Tong; Roth, Frederick P.; Xia, Yu; Walhout, Albertha J. M.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Wang, Yang; Kamburov, Atanas; Zhong, Quan; Shen, Yun; Palagi, Alexandre; San-Miguel, Adriana; Fan, Changyu; Balcha, Dawit; Dricot, Amelie; Walsh, Jennifer M.; Shah, Akash A.; Yang, Xinping; Stoyanova, Ani K.; Calderwood, Michael A.; Jacob, Yves; Cusick, Michael E.; Salehi-Ashtiani, Kourosh; Charloteaux, Benoit; Hill, David E.; Hao, Tong; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Taipale, Mikko; Karras, Georgios I.; Krykbaeva, Irina; Khurana, Vikram; Whitesell, Luke J.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Bass, Juan I. Fuxman; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Mol Med, Program Syst Biol, Worcester, MA 01605 USA. [Coulombe-Huntington, Jasmin; Xia, Yu] McGill Univ, Fac Engn, Dept Bioengn, Montreal, PQ H3A 0C3, Canada. [Yang, Fan; Weile, Jochen; Yachie, Nozomu; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Yang, Fan; Weile, Jochen; Yachie, Nozomu; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. [Yang, Fan; Weile, Jochen; Lam, Mandy H.; Walhout, Albertha J. M.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Yang, Fan; Weile, Jochen; Yachie, Nozomu; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Peng, Jian; Tucker, George; Leighton, Alex; Berger, Bonnie] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Kovacs, Istvan A.; Sharma, Amitabh; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res CCNR, Boston, MA 02115 USA. [Kovacs, Istvan A.; Sharma, Amitabh; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Kovacs, Istvan A.; Sharma, Amitabh; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Kovacs, Istvan A.; Sharma, Amitabh; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Jordan, Daniel M.; Sunyaev, Shamil] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Jordan, Daniel M.] Harvard Univ, Program Biophys, Cambridge, MA 02139 USA. [Jacob, Yves] CNRS, Dept Virol, Unite Genet Mol Virus ARN GMVR, Inst Pasteur,UMR3569, Paris, France. [Jacob, Yves] Univ Paris Diderot, Paris, France. [Whitesell, Luke J.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Whitesell, Luke J.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Sunyaev, Shamil] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Berger, Bonnie] MIT, Dept Math & Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada. [Lindquist, Susan] Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM lindquist@wi.mit.edu; marc_vidal@dfci.harvard.edu RI Calderwood, Mike/B-2475-2014; Roth, Frederick/H-6308-2011; San Miguel, Adriana/C-3937-2017; OI Liu, Yang-Yu/0000-0003-2728-4907; Karras, Georgios/0000-0003-2933-1535; Calderwood, Mike/0000-0001-6475-1418; Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Jordan, Daniel/0000-0002-5318-8225; Walhout, Marian/0000-0001-5587-3608; San Miguel, Adriana/0000-0003-0172-2163; Taipale, Mikko/0000-0003-3811-1761; Xia, Yu/0000-0002-5596-5518; Roth, Frederick/0000-0002-6628-649X FU NHGRI [P50HG004233, RC4HG006066, R01HG001715]; NIGMS [GM082971]; NSF [CCF-1219007]; NSERC [RGPIN-2014-03892]; Krembil Foundation; Canada Excellence Research Chair; Ontario Research Fund-Research Excellence Award; Pew Latin American Fellowship; EMBO Long-Term Fellowship FX We thank the members of the DFCI Center for Cancer Systems Biology (CCSB) for valuable discussions and acknowledge A.A. Chen, M. Koeva, and E. Guney for helpful suggestions. This work was supported by NHGRI (P50HG004233 to M.V., F.P.R. and A.-L.B.; RC4HG006066 to M.V., T.H., D.E.H., K.S.-A., L.J.W., and S.L.; and R01HG001715 to M.V., D.E.H., and F.P.R.), NIGMS (GM082971 to A.J.M.W.), NSF (CCF-1219007 to Y.X.), NSERC (RGPIN-2014-03892 to Y.X.), and the Krembil Foundation, a Canada Excellence Research Chair, an Ontario Research Fund-Research Excellence Award awarded to F.P.R. J.I.F.B. is supported by a Pew Latin American Fellowship. A.K. is supported by an EMBO Long-Term Fellowship. S.L. is an investigator of the Howard Hughes Medical Institute. M.V. is a Chercheur Qualifie Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation). NR 47 TC 68 Z9 68 U1 7 U2 24 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 APR 23 PY 2015 VL 161 IS 3 BP 647 EP 660 DI 10.1016/j.cell.2015.04.013 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG8JN UT WOS:000353553600022 PM 25910212 ER PT J AU Bass, JIF Sahni, N Shrestha, S Garcia-Gonzalez, A Mori, A Bhat, N Yi, S Hill, DE Vidal, M Walhout, AJM AF Bass, Juan I. Fuxman Sahni, Nidhi Shrestha, Shaleen Garcia-Gonzalez, Aurian Mori, Akihiro Bhat, Numana Yi, Song Hill, David E. Vidal, Marc Walhout, Albertha J. M. TI Human Gene-Centered Transcription Factor Networks for Enhancers and Disease Variants SO CELL LA English DT Article ID ONE-HYBRID ASSAYS; REGULATORY NETWORK; PROTEIN-DNA; LHX4 GENE; MUTATIONS; PROMOTER; BINDING; MOUSE AB Gene regulatory networks (GRNs) comprising interactions between transcription factors (TFs) and regulatory loci control development and physiology. Numerous disease-associated mutations have been identified, the vast majority residing in non-coding regions of the genome. As current GRN mapping methods test one TF at a time and require the use of cells harboring the mutation(s) of interest, they are not suitable to identify TFs that bind to wildtype and mutant loci. Here, we use gene-centered yeast one-hybrid (eY1H) assays to interrogate binding of 1,086 human TFs to 246 enhancers, as well as to 109 non-coding disease mutations. We detect both loss and gain of TF interactions with mutant loci that are concordant with target gene expression changes. This work establishes eY1H assays as a powerful addition to the toolkit of mapping human GRNs and for the high-throughput characterization of genomic variants that are rapidly being identified by genome-wide association studies. C1 [Bass, Juan I. Fuxman; Shrestha, Shaleen; Garcia-Gonzalez, Aurian; Mori, Akihiro; Bhat, Numana; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. [Bass, Juan I. Fuxman; Shrestha, Shaleen; Garcia-Gonzalez, Aurian; Mori, Akihiro; Bhat, Numana; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Sahni, Nidhi; Yi, Song; Hill, David E.; Vidal, Marc; Walhout, Albertha J. M.] Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA. [Sahni, Nidhi; Yi, Song; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Walhout, AJM (reprint author), Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. EM walhout@umassmed.edu OI Walhout, Marian/0000-0001-5587-3608 FU US NIH [GM082971, HG004233, HG006066]; Pew Latin American Fellows Program FX We thank members of the A.J.M.W. laboratory, R. McCord, N. Kaplan, and J. Dekker for discussions and critical reading of the manuscript. We thank J. Gibcus for the pGL4 plasmid and expression vectors and advice on the luciferase assays. We thank N. Beittel and B. Parmentier for technical assistance. This work was supported by US NIH grants GM082971 to A.J.M.W., HG004233 to M.V., and HG006066 to M.V. and D.E.H. J.I.F.B. was partially supported by a postdoctoral fellowship from the Pew Latin American Fellows Program. NR 39 TC 8 Z9 8 U1 6 U2 10 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 APR 23 PY 2015 VL 161 IS 3 BP 661 EP 673 DI 10.1016/j.cell.2015.03.003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG8JN UT WOS:000353553600023 ER PT J AU Komrokji, RS Seymour, JF Roberts, AW Wadleigh, M To, LB Scherber, R Turba, E Dorr, A Zhu, J Wang, LX Granston, T Campbell, MS Mesa, RA AF Komrokji, Rami S. Seymour, John F. Roberts, Andrew W. Wadleigh, Martha To, L. Bik Scherber, Robyn Turba, Elyce Dorr, Andrew Zhu, Joy Wang, Lixia Granston, Tanya Campbell, Mary S. Mesa, Ruben A. TI Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis SO BLOOD LA English DT Article ID INTERNATIONAL-WORKING-GROUP; TYROSINE KINASE JAK2; MYELOID METAPLASIA; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; SCORING SYSTEM; MUTATION; RUXOLITINIB; NEOPLASMS AB Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate-or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000x 10(9)/L. Upto week 24, 8 of 26 evaluable patients (31%) achieved a >= 35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a >= 50% reduction in spleen size by physical examination. Median MF symptom improvement was >= 50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.govas#NCT00745550. C1 [Komrokji, Rami S.; Turba, Elyce] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Seymour, John F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Seymour, John F.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia. [Roberts, Andrew W.] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic, Australia. [Roberts, Andrew W.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [To, L. Bik] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. [Scherber, Robyn; Mesa, Ruben A.] Mayo Clin, Scottsdale, AZ USA. [Dorr, Andrew] Independent Consultant S BIO Pte Ltd, Singapore, Singapore. [Zhu, Joy] S BIO Pte Ltd, Singapore, Singapore. [Wang, Lixia; Granston, Tanya; Campbell, Mary S.] CTI BioPharma, Seattle, WA USA. RP Komrokji, RS (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM rami.komrokji@moffitt.org RI Roberts, Andrew/C-6736-2012 OI Roberts, Andrew/0000-0002-7341-5720 FU S*Bio Pte Ltd, Singapore FX This study was sponsored by S*Bio Pte Ltd, Singapore. No grant support was received. All views expressed in this article are those of the authors and not an official position of the funding institution. NR 21 TC 38 Z9 38 U1 1 U2 7 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 APR 23 PY 2015 VL 125 IS 17 BP 2649 EP 2655 DI 10.1182/blood-2013-02-484832 PG 7 WC Hematology SC Hematology GA CJ7DF UT WOS:000355653600012 PM 25762180 ER PT J AU Jiang, WX Lee, BJ Li, C Dubois, RL Gostissa, M Alt, FW Zha, S AF Jiang, Wenxia Lee, Brian J. Li, Chen Dubois, Richard L. Gostissa, Monica Alt, Frederick W. Zha, Shan TI Aberrant TCR delta rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; TUMOR-SUPPRESSOR; ACCESSIBILITY; PARADIGM; ENHANCER; LOCUS; MICE AB Ataxia telangiectasia mutated (ATM) is a protein kinase and a master regulator of DNA-damage responses. Germline ATM inactivation causes ataxia-telangiectasia (A-T) syndrome with severe lymphocytopenia and greatly increased risk for T-cell lymphomas/leukemia. Both A-T and T-cell prolymphoblastic leukemia patients with somatic mutations of ATM frequently carry inv(14;14) between the T-cell receptor alpha/delta (TCR alpha/delta) and immunoglobulin H loci, but the molecular origin of this translocation remains elusive. ATM(-/-) mice recapitulate lymphocytopenia of A-T patients and routinely succumb to thymic lymphomas with t(12;14) translocation, syntenic to inv(14;14) in humans. Here we report that deletion of the TCR delta enhancer (E delta), which initiates TCR delta rearrangement, significantly improves alpha beta T cell output and effectively prevents t(12;14) translocations in ATM(-/-) mice. These findings identify the genomic instability associated with V(D)J recombination at the TCRd locus as the molecular origin of both lymphocytopenia and the signature t(12;14) translocations associated with ATM deficiency. C1 [Jiang, Wenxia; Lee, Brian J.; Li, Chen; Dubois, Richard L.; Zha, Shan] Columbia Univ, Med Ctr, Inst Canc Genet, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Jiang, Wenxia; Lee, Brian J.; Li, Chen; Dubois, Richard L.; Zha, Shan] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Res Ctr, New York, NY 10032 USA. [Gostissa, Monica; Alt, Frederick W.] Boston Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA USA. [Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Zha, Shan] Columbia Univ, Dept Pediat, Div Hematol Oncol & Stem Cell Transplantat, Coll Phys & Surg,Med Ctr, New York, NY 10027 USA. RP Zha, S (reprint author), Columbia Univ, Med Ctr, Inst Canc Genet, 1130 St Nicholas Ave,Room 503B, New York, NY 10032 USA. EM sz2296@columbia.edu FU National Institutes of Health (NIH) National Cancer Institute [5R01CA158073, 1R01CA184187, 1P01CA174653-01]; American Cancer Society [RSG-13-038-01 DMC]; NIH National Cancer Institute [P01CA109901, T32-CA09503] FX This work was supported in part by National Institutes of Health (NIH) National Cancer Institute grants 5R01CA158073, 1R01CA184187, and 1P01CA174653-01 and American Cancer Society Research Scholar Grant RSG-13-038-01 DMC (S.Z.) and by NIH National Cancer Institute grant P01CA109901 (F.W.A.). S.Z. was a St Baldrick's Scholar for Pediatric Cancer and is a Leukemia Lymphoma Society Scholar. W.J. was supported in part by NIH National Cancer Institute grant T32-CA09503. F.W.A. is a Howard Hughes Medical Institute investigator. NR 16 TC 5 Z9 5 U1 0 U2 0 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 APR 23 PY 2015 VL 125 IS 17 BP 2665 EP 2668 DI 10.1182/blood-2015-01-622621 PG 4 WC Hematology SC Hematology GA CJ7DF UT WOS:000355653600014 PM 25721125 ER PT J AU Wang, J Mikse, O Liao, RG Li, Y Tan, L Janne, PA Gray, NS Wong, KK Hammerman, PS AF Wang, J. Mikse, O. Liao, R. G. Li, Y. Tan, L. Janne, P. A. Gray, N. S. Wong, K-k Hammerman, P. S. TI Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells SO ONCOGENE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR RECEPTOR-3; BREAST-CANCER; LUNG-CANCER; KINASE INHIBITORS; MULTIPLE-MYELOMA; TYROSINE KINASE; SENSITIVE FGFR2; BLADDER-CANCER; EGF RECEPTOR AB Somatic alterations of fibroblast growth factor receptors (FGFRs) have been described in a wide range of malignancies. A number of anti-FGFR therapies are currently under investigation in clinical trials for subjects with FGFR gene amplifications, mutations and translocations. Here, we develop cell line models of acquired resistance to FGFR inhibition by exposure of cell lines harboring FGFR3 gene amplification and translocation to the selective FGFR inhibitor BGJ398 and multitargeted FGFR inhibitor ponatinib. We show that the acquisition of resistance is rapid, reversible and characterized by an epithelial to mesenchymal transition and a switch from dependency on FGFR3 to ERBB family members. Acquired resistance was associated with demonstrable changes in gene expression including increased production of ERBB2/3 ligands, which were sufficient to drive resistance in the setting of FGFR3 dependency but not dependency on other FGFR family members. These data support the concept that activation of ERBB family members is sufficient to bypass dependency on FGFR3 and suggest that concurrent inhibition of these two pathways may be desirable when targeting FGFR3-dependent cancers. C1 [Wang, J.; Mikse, O.; Liao, R. G.; Li, Y.; Janne, P. A.; Wong, K-k; Hammerman, P. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wang, J.] Fudan Univ, Shanghai Med Coll, Dept Integrat Med & Neurobiol, Shanghai 200433, Peoples R China. [Liao, R. G.; Li, Y.; Hammerman, P. S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Tan, L.; Gray, N. S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Janne, P. A.; Wong, K-k] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. RP Hammerman, PS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 810A, Boston, MA 02215 USA. EM phammerman@partners.org OI Liao, Rachel/0000-0002-7830-1976 FU NCI [K08 CA163677]; V Foundation the Stephen D; Alice Cutler Fund; NSFC [81202746]; CSC FX PSH is supported by NCI K08 CA163677, the V Foundation the Stephen D and Alice Cutler Fund. We thank M Meyerson for assisting with the planning of this study. JW is supported by NSFC 81202746 and CSC. NR 46 TC 9 Z9 9 U1 0 U2 10 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 APR 23 PY 2015 VL 34 IS 17 BP 2167 EP 2177 DI 10.1038/onc.2014.161 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CG7HG UT WOS:000353473000003 PM 24909170 ER PT J AU Chou, SD Murshid, A Eguchi, T Gong, J Calderwood, SK AF Chou, S-D Murshid, A. Eguchi, T. Gong, J. Calderwood, S. K. TI HSF1 regulation of beta-catenin in mammary cancer cells through control of HuR/elavL1 expression SO ONCOGENE LA English DT Article ID HEAT-SHOCK FACTOR-1; BINDING PROTEIN HUR; TRANSCRIPTION FACTOR HSF1; RNA STABILITY FACTOR; BREAST-CANCER; STEM-CELLS; RICH ELEMENTS; PHOSPHORYLATION; CARCINOGENESIS; ACTIVATION AB There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumour progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor beta-catenin in immortalized human mammary epithelial and carcinoma cells. We found HSF1 to be involved in regulating the translation of beta-catenin, by investigating effects of gain and loss of HSF1 on this protein. Interestingly, although HSF1 is a potent transcription factor, it was not directly involved in regulating levels of beta-catenin mRNA. Instead, our data suggest a complex role in translational regulation. HSF1 was shown to regulate levels of the RNA-binding protein HuR that controlled beta-catenin translation. An extra complexity was added to this scenario when it was shown that the long non-coding RNA molecule lincRNA-p21, known to be involved in beta-catenin mRNA (CTNNB1) translational regulation, was controlled by HSF1 repression. We have shown previously that HSF1 was positively regulated through phosphorylation by mammalian target of rapamycin (mTOR) kinase on a key residue, serine 326, essential for transcriptional activity. In this study, we found that mTOR knockdown not only decreased HSF1-S326 phosphorylation in mammary cells, but also decreased beta-catenin expression through a mechanism requiring HuR. Our data point to a complex role for HSF1 in the regulation of HuR and beta-catenin expression that may be significant in mammary carcinogenesis. C1 [Chou, S-D; Murshid, A.; Eguchi, T.; Calderwood, S. K.] Harvard Univ, Sch Med, Dept Radiat Oncol, BIDMC, Boston, MA 02215 USA. [Gong, J.] Boston Univ, Med Ctr, Boston, MA USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, BIDMC, 21-27 Burlington Ave,99 Brookline Ave, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu FU NIH [RO-1CA047407, R01CA119045, RO-1CA094397] FX We thank the Department of Radiation Oncology, Beth Israel Deaconess Medical Center for support and encouragement. We are very grateful for help with construct preparation from Dr Tom Prince. This work was supported by NIH research grants RO-1CA047407, R01CA119045 and RO-1CA094397. NR 47 TC 11 Z9 11 U1 0 U2 3 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 APR 23 PY 2015 VL 34 IS 17 BP 2178 EP 2188 DI 10.1038/onc.2014.177 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CG7HG UT WOS:000353473000004 PM 24954509 ER PT J AU Sausgruber, N Coissieux, MM Britschgi, A Wyckoff, J Aceto, N Leroy, C Stadler, MB Voshol, H Bonenfant, D Bentires-Alj, M AF Sausgruber, N. Coissieux, M-M Britschgi, A. Wyckoff, J. Aceto, N. Leroy, C. Stadler, M. B. Voshol, H. Bonenfant, D. Bentires-Alj, M. TI Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast cancer through the activation of SRC-family kinases SO ONCOGENE LA English DT Article ID FOCAL ADHESION KINASE; GROWTH-FACTOR; IN-VIVO; C-SRC; MIGRATION; PAXILLIN; PHOSPHORYLATION; METASTASIS; TUMORS; DEPHOSPHORYLATION AB Tumor cell migration has a fundamental role in early steps of metastasis, the fatal hallmark of cancer. In the present study, we investigated the effects of the tyrosine phosphatase, SRC-homology 2 domain-containing phosphatase 2 (SHP2), on cell migration in metastatic triple-negative breast cancer (TNBC), an aggressive disease associated with a poor prognosis for which a targeted therapy is not yet available. Using mouse models and multiphoton intravital imaging, we have identified a crucial effect of SHP2 on TNBC cell motility in vivo. Further, analysis of TNBC cells revealed that SHP2 also influences cell migration, chemotaxis and invasion in vitro. Unbiased phosphoproteomics and biochemical analysis showed that SHP2 activates several SRC-family kinases and downstream targets, most of which are inducers of migration and invasion. In particular, direct interaction between SHP2 and c-SRC was revealed by a fluorescence resonance energy transfer assay. These results suggest that SHP2 is a crucial factor during early steps of TNBC migration to distant organs. C1 [Sausgruber, N.; Coissieux, M-M; Britschgi, A.; Wyckoff, J.; Aceto, N.; Leroy, C.; Stadler, M. B.; Bentires-Alj, M.] Friedrich Miescher Inst FMI Biomed Res, Mechanisms Canc, CH-4058 Basel, Switzerland. [Wyckoff, J.] MIT, Koch Inst Integrated Canc Res, Cambridge, MA 02139 USA. [Aceto, N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Leroy, C.; Voshol, H.; Bonenfant, D.] Novartis Inst Biomed Res, Analyt Sci & Imaging, Basel, Switzerland. [Stadler, M. B.] Swiss Inst Bioinformat, Basel, Switzerland. RP Bentires-Alj, M (reprint author), Friedrich Miescher Inst FMI Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland. EM bentires@fmi.ch RI Mohamed, Bentires-Alj/F-4484-2015; Aceto, Nicola/O-2484-2014 OI Mohamed, Bentires-Alj/0000-0001-6344-1127; Aceto, Nicola/0000-0001-9579-6918 FU FP7 Marie-Curie Fellowship; Novartis Research Foundation; European Research Council (ERC starting grant) [243211-PTPsBDC]; Swiss Cancer League; Krebsliga Beider Basel FX We thank C Kuperwasser for the SUM159 cells and S Gambhir for the pFU-Luc2-eGFP construct, L Bonapace for technical assistance with the intravital microscope, L Gelman for help with the FRET experiments, S Bourke and M Kirschmann for help with image acquisition and analysis, and I Klebba and H Brinkhaus for technical assistance. M-MC is supported by a FP7 Marie-Curie Fellowship and NA is a fellow of the Swiss National Science Foundation and the Human Frontiers Science Program. Research in the laboratory of MB-A is supported by the Novartis Research Foundation, the European Research Council (ERC starting grant 243211-PTPsBDC), the Swiss Cancer League and the Krebsliga Beider Basel. NR 29 TC 10 Z9 10 U1 3 U2 10 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 APR 23 PY 2015 VL 34 IS 17 BP 2272 EP 2278 DI 10.1038/onc.2014.170 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CG7HG UT WOS:000353473000012 PM 24931162 ER PT J AU Walter, D Lier, A Geiselhart, A Thalheimer, FB Huntscha, S Sobotta, MC Moehrle, B Brocks, D Bayindir, I Kaschutnig, P Muedder, K Klein, C Jauch, A Schroeder, T Geiger, H Dick, TP Holland-Letz, T Schmezer, P Lane, SW Rieger, MA Essers, MAG Williams, DA Trumpp, A Milsom, MD AF Walter, Dagmar Lier, Amelie Geiselhart, Anja Thalheimer, Frederic B. Huntscha, Sina Sobotta, Mirko C. Moehrle, Bettina Brocks, David Bayindir, Irem Kaschutnig, Paul Muedder, Katja Klein, Corinna Jauch, Anna Schroeder, Timm Geiger, Hartmut Dick, Tobias P. Holland-Letz, Tim Schmezer, Peter Lane, Steven W. Rieger, Michael A. Essers, Marieke A. G. Williams, David A. Trumpp, Andreas Milsom, Michael D. TI Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells SO NATURE LA English DT Article ID FANCONI-ANEMIA; TARGETED DISRUPTION; SELF-RENEWAL; NICHE; CYCLE; MICE; LYMPHOCYTES; QUIESCENCE; CYTOKINES; DEFECTS AB Haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation'. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia'''. However, the physiological source of DNA damage in HSCs from both normal and diseased individuals remains unclear. Here we show in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss. Repeated activation of HSCs out of their dormant state provoked the attrition of normal HSCs and, in the case of mice with a nonfunctional Fanconi anaemia DNA repair pathway, led to a complete collapse of the haematopoietic system, which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia patients. Our findings establish a novel link between physiological stress and DNA damage in normal HSCs and provide a mechanistic explanation for the universal accumulation of DNA damage in HSCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients. C1 [Walter, Dagmar; Lier, Amelie; Huntscha, Sina; Klein, Corinna; Essers, Marieke A. G.; Trumpp, Andreas; Milsom, Michael D.] Heidelberg Inst Stem Cell Technol & Expt Med gGmb, D-69120 Heidelberg, Germany. [Geiselhart, Anja; Brocks, David; Bayindir, Irem; Kaschutnig, Paul; Milsom, Michael D.] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, Expt Hematol Grp, D-69120 Heidelberg, Germany. [Thalheimer, Frederic B.; Rieger, Michael A.] Goethe Univ Frankfurt, LOEWE Ctr Cell & Gene Therapy, D-60595 Frankfurt, Germany. [Thalheimer, Frederic B.; Rieger, Michael A.] Goethe Univ Frankfurt, Dept Hematol Oncol, D-60595 Frankfurt, Germany. [Sobotta, Mirko C.; Dick, Tobias P.] DKFZ ZMBH Alliance, Deutsch Krebsforschungszentrum DKFZ, Div Redox Regulat, D-69120 Heidelberg, Germany. [Moehrle, Bettina; Geiger, Hartmut] Univ Ulm, Inst Mol Med Stem Cells & Aging, D-89081 Ulm, Germany. [Muedder, Katja; Trumpp, Andreas] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, D-69120 Heidelberg, Germany. [Jauch, Anna] Heidelberg Univ, Inst Human Genet, D-69120 Heidelberg, Germany. [Schroeder, Timm] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. [Geiger, Hartmut] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Holland-Letz, Tim] Deutsch Krebsforschungszentrum DKFZ, Div Biostat, D-69120 Heidelberg, Germany. [Schmezer, Peter] Deutsch Krebsforschungszentrum DKFZ, Div Epigen & Canc Risk Factors, D-69120 Heidelberg, Germany. [Lane, Steven W.] Univ Queensland, QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Essers, Marieke A. G.] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, Hematopoiet Stem Cells & Stress Grp, D-69120 Heidelberg, Germany. [Williams, David A.] Boston Childrens Hosp, Boston, MA 02115 USA. [Williams, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, David A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Williams, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Milsom, MD (reprint author), Heidelberg Inst Stem Cell Technol & Expt Med gGmb, D-69120 Heidelberg, Germany. EM m.milsom@hi-stem.de RI Essers, Marieke/B-7758-2017 OI Essers, Marieke/0000-0003-3117-1809 FU Animal Laboratory Services Deutsches Krebsforschungszentrum (DKFZ) core facility; BioRN Leading-Edge Cluster "Cell-Based and Molecular Medicine" - German Federal Ministry of Education and Research; Dietmar Hopp Foundation; LOEWE Center for Cell and Gene Therapy Frankfurt, Hessisches Ministerium fur Wissenschaft und Kunst [III L 4-518/17.004]; Deutsche Forschungsgemeinschaft [SFB873]; Helmholtz International Graduate School; Leukemia Foundation of Australia; Cure Cancer Australia Foundation; National Health and Medical Research Foundation of Australia FX We thank R. Gliniorz, S. Blaszkiewicz, V. Vogel and B. Schoell for technical assistance, B. Walter for help with figures and S. Frohling, M. Sprick and T. Oskarsson for critical proofreading of this manuscript. We also acknowledge support from the Animal Laboratory Services Deutsches Krebsforschungszentrum (DKFZ) core facility and S. Schmitt, A. Atzberger, J. Hartwig and K. Hexel from the Imaging and Cytometry DKFZ core facility. We are grateful to K. J. Patel for anti-mouse FANCD2 antibody and T. Southgate for the SF-CS-I-G retroviral vector. D.W., A.L., M.A.G.E., A.T. and M.D.M. were supported by the BioRN Leading-Edge Cluster "Cell-Based and Molecular Medicine" funded by the German Federal Ministry of Education and Research, and the Dietmar Hopp Foundation. M.A.R. was supported by the LOEWE Center for Cell and Gene Therapy Frankfurt, Hessisches Ministerium fur Wissenschaft und Kunst (III L 4-518/17.004 (2014)). A.T. and M.A.G.E. were also supported by the SFB873 funded by the Deutsche Forschungsgemeinschaft. A.G. and P.K. are funded by a fellowship from the Helmholtz International Graduate School and S.W.L. received support from the Leukemia Foundation of Australia, Cure Cancer Australia Foundation and the National Health and Medical Research Foundation of Australia. NR 32 TC 82 Z9 83 U1 5 U2 36 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 APR 23 PY 2015 VL 520 IS 7548 BP 549 EP + DI 10.1038/nature14131 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5LX UT WOS:000353334500045 PM 25707806 ER PT J AU Nelson, CP Hamby, SE Saleheen, D Hopewell, JC Zeng, L Assimes, TL Kanoni, S Willenborg, C Burgess, S Amouyel, P Anand, S Blankenberg, S Boehm, BO Clarke, RJ Collins, R Dedoussis, G Farrall, M Franks, PW Groop, L Hall, AS Hamsten, A Hengstenberg, C Hovingh, GK Ingelsson, E Kathiresan, S Kee, F Konig, IR Kooner, J Lehtimaki, T Marz, W McPherson, R Metspalu, A Nieminen, MS O'Donnell, CJ Palmer, CNA Peters, A Perola, M Reilly, MP Ripatti, S Roberts, R Salomaa, V Shah, SH Schreiber, S Siegbahn, A Thorsteinsdottir, U Veronesi, G Wareham, N Willer, CJ Zalloua, PA Erdmann, J Deloukas, P Watkins, H Schunkert, H Danesh, J Thompson, JR Samani, NJ AF Nelson, C. P. Hamby, S. E. Saleheen, D. Hopewell, J. C. Zeng, L. Assimes, T. L. Kanoni, S. Willenborg, C. Burgess, S. Amouyel, P. Anand, S. Blankenberg, S. Boehm, B. O. Clarke, R. J. Collins, R. Dedoussis, G. Farrall, M. Franks, P. W. Groop, L. Hall, A. S. Hamsten, A. Hengstenberg, C. Hovingh, G. Kees Ingelsson, E. Kathiresan, S. Kee, F. Koenig, I. R. Kooner, J. Lehtimaeki, T. Maerz, W. McPherson, R. Metspalu, A. Nieminen, M. S. O'Donnell, C. J. Palmer, C. N. A. Peters, A. Perola, M. Reilly, M. P. Ripatti, S. Roberts, R. Salomaa, V. Shah, S. H. Schreiber, S. Siegbahn, A. Thorsteinsdottir, U. Veronesi, G. Wareham, N. Willer, C. J. Zalloua, P. A. Erdmann, J. Deloukas, P. Watkins, H. Schunkert, H. Danesh, J. Thompson, J. R. Samani, N. J. CA CARDIoGRAM C4D Consortium TI Genetically Determined Height and Coronary Artery Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BODY-MASS INDEX; BLOOD-PRESSURE; ASSOCIATION; RISK; LOCI; ATHEROSCLEROSIS; METAANALYSIS; VARIANTS; PLAQUES; LIPIDS AB BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quar-tile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. C1 [Nelson, C. P.; Hamby, S. E.; Samani, N. J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [Thompson, J. R.] Univ Leicester, Dept Hlth Sci, Leicester LE3 9QP, Leics, England. [Nelson, C. P.; Hamby, S. E.; Samani, N. J.] Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Saleheen, D.; Burgess, S.; Danesh, J.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Ripatti, S.; Deloukas, P.] Wellcome Trust Sanger Inst, Cambridge, England. [Wareham, N.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. [Hopewell, J. C.; Clarke, R. J.; Collins, R.] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, J. C.; Clarke, R. J.; Collins, R.] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Farrall, M.; Watkins, H.] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England. [Farrall, M.; Watkins, H.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Kanoni, S.; Deloukas, P.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Boehm, B. O.] Univ London Imperial Coll Sci Technol & Med, London, England. [Kooner, J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Hall, A. S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Kee, F.] Queens Univ Belfast, Clin Res Collaborat Ctr Excellence Publ Hlth Nort, Belfast, Antrim, North Ireland. [Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Saleheen, D.] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, D.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Reilly, M. P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Zeng, L.; Clarke, R. J.; Collins, R.; Hengstenberg, C.; Schunkert, H.] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Zeng, L.; Clarke, R. J.; Collins, R.; Hengstenberg, C.; Schunkert, H.] Partner Site Munich Heart Alliance, Deutsch Zentrum Herz Kreislauf Forsch, Munich, Germany. [Peters, A.] German Ctr Cardiovasc Res Partner Site Munich, Munich, Germany. [Willenborg, C.; Erdmann, J.] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Willenborg, C.; Erdmann, J.] Partner Site Hamburg Lubeck Kiel, German Ctr Cardiovasc Res, Lubeck, Germany. [Koenig, I. R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Blankenberg, S.] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Boehm, B. O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany. [Maerz, W.] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Maerz, W.] Heidelberg Univ, Mannheim Med Fac, Med Clin 5, Synlab Acad,Synlab Serv, Mannheim, Germany. [Peters, A.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Schreiber, S.] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Assimes, T. L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Amouyel, P.] Univ Lille Nord France, INSERM, U744, Inst Pasteur Lille, Lille, France. [Anand, S.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [McPherson, R.; Roberts, R.] Univ Ottawa Heart Inst, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [McPherson, R.; Roberts, R.] Univ Ottawa Heart Inst, Atherogen Lab, Ottawa, ON, Canada. [Boehm, B. O.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Dedoussis, G.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Franks, P. W.] Lund Univ, Ctr Diabet, Skane Univ Hosp, Genet & Mol Epidemiol Unit,Dept Clin Sci, Malmo, Sweden. [Groop, L.] Lund Univ, Univ Hosp Malmo, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Franks, P. W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hamsten, A.] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [Ingelsson, E.] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Siegbahn, A.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kathiresan, S.] Massachusetts Gen Hosp, Div Cardiol, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, S.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, S.] Harvard Univ, Sch Med, Boston, MA USA. [Kathiresan, S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [O'Donnell, C. J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Lehtimaeki, T.] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaeki, T.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nieminen, M. S.] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Perola, M.; Salomaa, V.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Ripatti, S.] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Ripatti, S.] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Metspalu, A.; Perola, M.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Shah, S. H.] Duke Univ, Dept Med, Div Cardiol, Duke Mol Physiol Inst, Durham, NC USA. [Thorsteinsdottir, U.] deCODE Genet, Reykjavik, Iceland. [Veronesi, G.] Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, Varese, Italy. [Willer, C. J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Willer, C. J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Willer, C. J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Zalloua, P. A.] Lebanese Amer Univ, Beirut, Lebanon. [Deloukas, P.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. RP Samani, NJ (reprint author), Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, BHF Cardiovasc Res Ctr, Groby Rd, Leicester LE3 9QP, Leics, England. EM njs@le.ac.uk RI Erdmann, Jeanette/P-7513-2014; Palmer, Colin/C-7053-2008; Boehm, Bernhard/F-8750-2015; Veronesi, Giovanni/E-3859-2010; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Tregouet, David-Alexandre/E-3961-2016; Deloukas, Panos/B-2922-2013; Study, GoDARTS/K-9448-2016; Konig, Inke/A-4544-2009 OI Assimes, Themistocles/0000-0003-2349-0009; Burgess, Stephen/0000-0001-5365-8760; Kleber, Marcus/0000-0003-0663-7275; Peters, Annette/0000-0001-6645-0985; Esko, Tonu/0000-0003-1982-6569; Shungin, Dmitry/0000-0001-7900-5856; Ouwehand, Willem/0000-0002-7744-1790; Kristiansson, Kati/0000-0003-4688-107X; Erdmann, Jeanette/0000-0002-4486-6231; Gigante, Bruna/0000-0003-4508-7990; zalloua, pierre/0000-0002-8494-5081; Kuulasmaa, Kari/0000-0003-2165-1411; Watkins, Hugh/0000-0002-5287-9016; Palmer, Colin/0000-0002-6415-6560; Veronesi, Giovanni/0000-0002-4119-6615; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Deloukas, Panos/0000-0001-9251-070X; FU British Heart Foundation FX Funded by the British Heart Foundation and others. NR 27 TC 48 Z9 48 U1 5 U2 21 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 APR 23 PY 2015 VL 372 IS 17 BP 1608 EP 1618 DI 10.1056/NEJMoa1404881 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CG4XX UT WOS:000353294000006 PM 25853659 ER PT J AU David, WS AF David, William S. TI Case 3-2015: A Woman with Abdominal Pain, Dyspnea, and Diplopia REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP David, WS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 23 PY 2015 VL 372 IS 17 BP 1675 EP 1675 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CG4XX UT WOS:000353294000026 PM 25901441 ER PT J AU Guo, SS Guo, YM Ergun, A Lu, L Walker, WA Ganguli, K AF Guo, Shuangshuang Guo, Yuming Ergun, Ayla Lu, Lei Walker, W. Allan Ganguli, Kriston TI Secreted Metabolites of Bifidobacterium infantis and Lactobacillus acidophilus Protect Immature Human Enterocytes from IL-1 beta-Induced Inflammation: A Transcription Profiling Analysis SO PLoS One LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; BIRTH-WEIGHT INFANTS; NECROTIZING ENTEROCOLITIS; EXTRACELLULAR-MATRIX; PROBIOTICS REDUCE; TIGHT JUNCTIONS; MODULATION; APOPTOSIS; PATHWAYS AB Combination regimens of Bifidobacterium infantis and Lactobacillus acidophilus have been demonstrated to prevent necrotizing enterocolitis (NEC) in clinical trials. However, the molecular mechanisms responsible for this protective effect are not well understood. Additionally, conditioned media from individual cultures of these two probiotics show strain specific modulation of inflammation using in vitro human intestinal NEC models. Here we report a transcription profiling analysis of gene expression in immature human fetal intestinal epithelial cells (H4 cells) pretreated with conditioned media from B. infantis (BCM) or L. acidophilus (LCM) prior to IL-1 beta stimulation. Compared with control media, the two probiotic-conditioned media (PCM) treatments altered the expression of hundreds of genes involved in the immune response, apoptosis and cell survival, cell adhesion, the cell cycle, development and angiogenesis. In IL-1 beta-stimulated cells, PCM treatment decreased the upregulation of genes in the NF-kappa B activation pathway and downregulated genes associated with extracellular matrix (ECM) remodeling. Compared with LCM, BCM showed more significant modulatory effects on ECM remodeling, reflected by a lower p value. IL-6 and IL-8 production was significantly reduced in IL-1 beta-stimulated cells pretreated with PCM (p<0.05), which was consistent with their altered gene expression. Western blot analysis showed that compared with IL-1 beta stimulation alone, PCM treatment attenuated the decrease of cytoplasmic I kappa B alpha and NF-kappa B p65 levels as well as the increase of nuclear NF-kappa B p65 levels in the stimulated cells (p<0.05). In conclusion, PCM treatment exerted anti-inflammatory effects in immature human fetal enterocytes primarily by modulating genes in the NF-kappa B signaling and ECM remodeling pathways. Additionally, some components of these signaling pathways, particularly the ECM remodeling pathway, were more profoundly affected by BCM than LCM. C1 [Guo, Shuangshuang; Guo, Yuming] China Agr Univ, Coll Anim Sci & Technol, State Key Lab Anim Nutr, Beijing 100094, Peoples R China. [Guo, Shuangshuang; Walker, W. Allan; Ganguli, Kriston] Massachusetts Gen Hosp Children, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. [Guo, Shuangshuang; Walker, W. Allan; Ganguli, Kriston] Harvard Univ, Sch Med, Charlestown, MA USA. [Ergun, Ayla] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lu, Lei] Univ Chicago, Dept Pediat, Sect Neonatol, Chicago, IL 60637 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp Children, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. EM wwalker@partners.org; kganguli@partners.org FU National Institutes of Health [R01-HD012437, R01-HD059126, P01-DK033506, P30-DK040561] FX This work was supported by grants from National Institutes of Health R01-HD012437; R01-HD059126; P01-DK033506 and P30-DK040561. WAW received the funding. The URL of National Institutes of Health is http://www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 9 Z9 10 U1 2 U2 12 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 APR 23 PY 2015 VL 10 IS 4 AR e0124549 DI 10.1371/journal.pone.0124549 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5KZ UT WOS:000353332000074 PM 25906317 ER PT J AU Winkler, T Melo, MFV Degani-Costa, LH Harris, RS Correia, JA Musch, G Venegas, JG AF Winkler, Tilo Melo, Marcos F. Vidal Degani-Costa, Luiza H. Harris, R. Scott Correia, John A. Musch, Guido Venegas, Jose G. TI Estimation of Noise-Free Variance to Measure Heterogeneity SO PLoS One LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PULMONARY PERFUSION; FRACTAL ANALYSIS; PET IMAGES; QUANTITATIVE-ANALYSIS; LUNG PERFUSION; BLOOD-FLOW; 3D PET; VENTILATION; STATISTICS AB Variance is a statistical parameter used to characterize heterogeneity or variability in data sets. However, measurements commonly include noise, as random errors superimposed to the actual value, which may substantially increase the variance compared to a noise-free data set. Our aim was to develop and validate a method to estimate noise-free spatial heterogeneity of pulmonary perfusion using dynamic positron emission tomography (PET) scans. On theoretical grounds, we demonstrate a linear relationship between the total variance of a data set derived from averages of n multiple measurements, and the reciprocal of n. Using multiple measurements with varying n yields estimates of the linear relationship including the noise-free variance as the constant parameter. In PET images, n is proportional to the number of registered decay events, and the variance of the image is typically normalized by the square of its mean value yielding a coefficient of variation squared (CV2). The method was evaluated with a Jaszczak phantom as reference spatial heterogeneity (CVr2) for comparison with our estimate of noise-free or ' true' heterogeneity (CVt2). We found that CVt2 was only 5.4% higher than CVr2. Additional evaluations were conducted on 38 PET scans of pulmonary perfusion using (NN)-N-13-saline injection. The mean CVt2 was 0.10 (range: 0.03-0.30), while the mean CV2 including noise was 0.24 (range: 0.10-0.59). CVt2 was in average 41.5% of the CV2 measured including noise (range: 17.8-71.2%). The reproducibility of CVt(2) was evaluated using three repeated PET scans from five subjects. Individual CVt2 were within 16% of each subject's mean and paired t-tests revealed no difference among the results from the three consecutive PET scans. In conclusion, our method provides reliable noise-free estimates of CVt2 in PET scans, and may be useful for similar statistical problems in experimental data. C1 [Winkler, Tilo; Melo, Marcos F. Vidal; Musch, Guido; Venegas, Jose G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Winkler, Tilo; Melo, Marcos F. Vidal; Degani-Costa, Luiza H.; Harris, R. Scott; Correia, John A.; Musch, Guido; Venegas, Jose G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Degani-Costa, Luiza H.; Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Correia, John A.] Massachusetts Gen Hosp, Dept Radiol, Radiol Cyclotron Lab, Boston, MA 02114 USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM twinkler@mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL087281, R01HL068011, R01HL121228] FX Research reported in this publication was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers R01HL087281, R01HL068011, and R01HL121228. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 0 Z9 0 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 APR 23 PY 2015 VL 10 IS 4 AR e0123417 DI 10.1371/journal.pone.0123417 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5KZ UT WOS:000353332000030 PM 25906374 ER PT J AU Bates, GP Dorsey, R Gusella, JF Hayden, MR Kay, C Leavitt, BR Nance, M Ross, CA Scahill, RI Wetzel, R Wild, EJ Tabrizi, SJ AF Bates, Gillian P. Dorsey, Ray Gusella, James F. Hayden, Michael R. Kay, Chris Leavitt, Blair R. Nance, Martha Ross, Christopher A. Scahill, Rachael I. Wetzel, Ronald Wild, Edward J. Tabrizi, Sarah J. TI Huntington disease SO NATURE REVIEWS DISEASE PRIMERS LA English DT Article ID QUALITY-OF-LIFE; CAG-REPEAT LENGTH; NEURONAL INTRANUCLEAR INCLUSIONS; R6/2 MOUSE MODEL; MUTANT HUNTINGTIN; CLINICAL-TRIALS; POLYGLUTAMINE-EXPANSION; MAMMALIAN-CELLS; NATURAL-HISTORY; NEURODEGENERATIVE DISEASES AB Huntington disease is devastating to patients and their families - with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course, and a combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene that encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confer toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype, as well as the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials. For an illustrated summary of this Primer, visit: http://go.nature.com/hPMENh C1 [Scahill, Rachael I.; Wild, Edward J.; Tabrizi, Sarah J.] UCL, Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England. [Bates, Gillian P.] Kings Coll London, Dept Med & Mol Genet, London, England. [Dorsey, Ray] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Gusella, James F.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA USA. [Gusella, James F.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Hayden, Michael R.; Kay, Chris; Leavitt, Blair R.] Univ British Columbia, Child & Family Res Inst, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. [Nance, Martha] Struthers Parkinsons Ctr, Minneapolis, MN USA. [Nance, Martha] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Wetzel, Ronald] Univ Pittsburgh, Sch Med, Dept Struct Biol, Pittsburgh, PA USA. [Wetzel, Ronald] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA USA. RP Tabrizi, SJ (reprint author), UCL, Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England. EM s.tabrizi@ucl.ac.uk RI Wetzel, Ronald/G-7453-2011; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU Auspex Pharmaceuticals; Biogen; Davis Phinney Foundation; Great Lakes Neurotechnologies; Huntington Study Group; Lundbeck; Michael J. Fox Foundation; US National Science Foundation; Patient-Centered Outcomes Research Institute; Prana Biotechnology; Sage Bionetworks; CHDI; Teva; Canadian Institutes of Health Research; Michael Smith Foundation; Lundbeck Inc.; Teva Pharmaceuticals; NeuroSearch; Johnson & Johnson/Janssen Pharma; University College London, UK FX S.J.T. has served on advisory boards or had consultancies with GlaxoSmithKline, Ixico Technologies, Isis Pharmaceuticals, Novartis, Roche, Sanofi-Aventis, Siena Biotech Takeda Pharmaceuticals International and TEVA Pharmaceuticals. All honoraria paid for these consultancies and advisory boards go to University College London, UK, S.J.T.'s employer. R.D. has received compensation for consulting activities from Clintrex, Lundbeck, mc10, Shire and the US National Institute of Neurological Disorders and Stroke; research support from Auspex Pharmaceuticals, Biogen, Davis Phinney Foundation, Great Lakes Neurotechnologies, Huntington Study Group, Lundbeck, The Michael J. Fox Foundation, US National Science Foundation, Patient-Centered Outcomes Research Institute, Prana Biotechnology and Sage Bionetworks; and has stock options in Grand Rounds. R.D. is an uncompensated advisor to SBR Health and Vidyo. M.R.H. is president of Global R&D and Chief Scientific Officer at Teva. B.R.L. is the Co-Chair of the Huntington Study Group; has acted as a consultant for Novartis, Pfizer, Siena Biotech, Teva and Isis; and has received relevant research grant support from CHDI, Teva, the Canadian Institutes of Health Research and the Michael Smith Foundation. M.N. has served on paid advisory boards for Lundbeck Inc. and Auspex Pharmaceuticals, and receives research grant funding from Teva Pharmaceuticals and NeuroSearch. C.A.R. currently acts as a consultant for Raptor Pharma; has consulted for Isis, Pfizer, Delbiopharm and Lundbeck; and receives research funding from Johnson & Johnson/Janssen Pharma. The other authors declare no competing interests. NR 253 TC 36 Z9 37 U1 22 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2056-676X J9 NAT REV DIS PRIMERS JI Nat. Rev. Dis. Primers PD APR 23 PY 2015 VL 1 AR 15005 DI 10.1038/nrdp.2015.5 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA DT2JB UT WOS:000381305500005 PM 27188817 ER PT J AU Schadendorf, D Fisher, DE Garbe, C Gershenwald, JE Grob, JJ Halpern, A Herlyn, M Marchetti, MA McArthur, G Ribas, A Roesch, A Hauschild, A AF Schadendorf, Dirk Fisher, David E. Garbe, Claus Gershenwald, Jeffrey E. Grob, Jean-Jacques Halpern, Allan Herlyn, Meenhard Marchetti, Michael A. McArthur, Grant Ribas, Antoni Roesch, Alexander Hauschild, Axel TI Melanoma SO NATURE REVIEWS DISEASE PRIMERS LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; IN-SITU HYBRIDIZATION; LYMPH-NODE BIOPSY; HIGH-RISK MELANOMA; EXCISED MELANOCYTIC LESIONS; CELL TRANSFER IMMUNOTHERAPY; RAF INHIBITOR RESISTANCE; TERT PROMOTER MUTATIONS; BRAF-MUTATED MELANOMA AB Melanoma is a common cancer in the Western world with an increasing incidence. Sun exposure is still considered to be the major risk factor for melanoma. The prognosis of patients with malignant (advanced-stage) melanoma differs widely between countries, but public campaigns advocating early detection have led to significant reductions in mortality rates. As well as sun exposure, distinct genetic alterations have been identified as associated with melanoma. For example, families with melanoma who have germline mutations in CDKN2A are well known, whereas the vast majority of sporadic melanomas have mutations in the mitogen-activated protein kinase cascade, which is the pathway with the highest oncogenic and therapeutic relevance for this disease. BRAF and NRAS mutations are typically found in cutaneous melanomas, whereas KIT mutations are predominantly observed in mucosal and acral melanomas. GNAQ and GNA11 mutations prevail in uveal melanomas. Additionally, the PI3K-AKT-PTEN pathway and the immune checkpoint pathways are important. The finding that programmed cell death protein 1 ligand 1 (PDL1) and PDL2 are expressed by melanoma cells, T cells, B cells and natural killer cells led to the recent development of programmed cell death protein 1 (PD1)-specific antibodies (for example, nivolumab and pembrolizumab). Alongside other new drugs-namely, BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib and cobimetinib)-these agents are very promising and have been shown to significantly improve prognosis for patients with advanced-stage metastatic disease. Early signs are apparent that these new treatment modalities are also improving long-term clinical benefit and the quality of life of patients. This Primer summarizes the current understanding of melanoma, from mechanistic insights to clinical progress. For an illustrated summary of this Primer, visit: http://go.nature.com/vX2N9s C1 [Schadendorf, Dirk; Roesch, Alexander] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Hufelandstr 55, D-45147 Essen, Germany. [Schadendorf, Dirk; Garbe, Claus] German Canc Consortium DKTK, Heidelberg, Germany. [Fisher, David E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Garbe, Claus] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Grob, Jean-Jacques] Aix Marseille Univ, APHM Timone Hosp, Dept Dermatol & Skin Canc, Marseille, France. [Halpern, Allan; Marchetti, Michael A.] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10021 USA. [Herlyn, Meenhard] Wistar Inst Anat & Biol, Melanoma Res Ctr, Philadelphia, PA 19104 USA. [McArthur, Grant] Peter MacCallum Canc Ctr, Div Canc Med & Res, Melbourne, Vic, Australia. [Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Ribas, Antoni] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ribas, Antoni] Univ Calif Los Angeles, Dept Med & Mol Pharmacol, Los Angeles, CA USA. [Hauschild, Axel] Univ Hosp Schleswig Holstein UKSH, Dept Dermatol, Kiel, Germany. RP Schadendorf, D (reprint author), Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Hufelandstr 55, D-45147 Essen, Germany. EM dirk.schadendorf@uk-essen.de FU Roche; TEVA; Novartis; Amgen; GlaxoSmithKline; MSD; Bristol-Myers Squibb; Celgene; Pfizer FX D.S. and A. Hauschild declare an association with the following companies: Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck/MSD, Novartis, Pfizer, Boehringer Ingelheim and Roche. C.G. declares personal fees from Amgen, Merck/MSD and Novartis, and declares grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline and Roche outside of the submitted work. A. Roesch has received travel grants and honoraria from Roche and TEVA, and research grants from Novartis. M.A.M. has received honoraria from Next Meeting Generation for speaking on the topic of dermoscopy at the American Dermoscopy Meeting. A. Halpern serves as a consultant to Caliber Imaging and Diagnostics, Canfield Scientific, DermTech and SciBase AB, and serves on the data safety and monitoring board of Quintiles and Janssen Research and Development LLC. J.-J.G. has received fees for advisory boards and lectures from Amgen, GlaxoSmithKline, MSD, Novartis and Roche, and has received research grants from Bristol-Myers Squibb and Roche. J.E.G. serves on the global advisory board for Merck. A. Ribas has served as consultant for Amgen, Astellas, Genentech-Roche, GlaxoSmithKline, Merck, Novartis and Pierre Fabre, and serves on the scientific advisory board and has stock options for Compugen, Flexus Biosciences and Kite Pharma. G.M. has received consulting income from Provectus, and has received research support from Celgene and Pfizer. M.H. and D.E.F. declare no competing interests. NR 252 TC 17 Z9 18 U1 6 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2056-676X J9 NAT REV DIS PRIMERS JI Nat. Rev. Dis. Primers PD APR 23 PY 2015 VL 1 AR 15003 DI 10.1038/nrdp.2015.3 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA DT2JB UT WOS:000381305500003 PM 27188223 ER PT J AU Farandos, NM Yetisen, AK Monteiro, MJ Lowe, CR Yun, SH AF Farandos, Nicholas M. Yetisen, Ali K. Monteiro, Michael J. Lowe, Christopher R. Yun, Seok Hyun TI Contact Lens Sensors in Ocular Diagnostics SO ADVANCED HEALTHCARE MATERIALS LA English DT Review ID HOLOGRAPHIC GLUCOSE SENSORS; TEAR PROTEIN-PATTERNS; INTRAOCULAR-PRESSURE; QUANTITATIVE-ANALYSIS; PROTEOMIC ANALYSIS; DIABETES-MELLITUS; CORNEAL THICKNESS; HEALTHY-SUBJECTS; OVERNIGHT WEAR; EYE DISEASE AB Contact lenses as a minimally invasive platform for diagnostics and drug delivery have emerged in recent years. Contact lens sensors have been developed for analyzing the glucose composition of tears as a surrogate for blood glucose monitoring and for the diagnosis of glaucoma by measuring intraocular pressure. However, the eye offers a wider diagnostic potential as a sensing site and therefore contact lens sensors have the potential to improve the diagnosis and treatment of many diseases and conditions. With advances in polymer synthesis, electronics and micro/nanofabrication, contact lens sensors can be produced to quantify the concentrations of many biomolecules in ocular fluids. Non-or minimally invasive contact lens sensors can be used directly in a clinical or point-of-care setting to monitor a disease state continuously. This article reviews the state-of-the-art in contact lens sensor fabrication, their detection, wireless powering, and readout mechanisms, and integration with mobile devices and smartphones. High-volume manufacturing considerations of contact lenses are also covered and a case study of an intraocular pressure contact lens sensor is provided as an example of a successful product. This Review further analyzes the contact lens market and the FDA regulatory requirements for commercialization of contact lens sensors. C1 [Farandos, Nicholas M.] Univ London Imperial Coll Sci Technol & Med, Dept Chem Engn, London SW7 2AZ, England. [Yetisen, Ali K.] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 1QT, England. [Monteiro, Michael J.] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia. [Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yetisen, AK (reprint author), Univ Cambridge, Dept Chem Engn & Biotechnol, Tennis Court Rd, Cambridge CB2 1QT, England. EM ay283@cam.ac.uk RI Monteiro, Michael/C-5658-2009 OI Monteiro, Michael/0000-0001-5624-7115 NR 172 TC 32 Z9 32 U1 14 U2 102 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 APR 22 PY 2015 VL 4 IS 6 BP 792 EP 810 DI 10.1002/adhm.201400504 PG 19 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA CG5SD UT WOS:000353353500001 PM 25400274 ER PT J AU Beissner, F Brunner, F Fink, M Meissner, K Kaptchuk, TJ Napadow, V AF Beissner, Florian Bruenner, Franziska Fink, Maria Meissner, Karin Kaptchuk, Ted J. Napadow, Vitaly TI Placebo-Induced Somatic Sensations: A Multi-Modal Study of Three Different Placebo Interventions SO PLOS ONE LA English DT Article ID MCGILL PAIN QUESTIONNAIRE; PERSONALITY-TRAIT; NOVELTY SEEKING; MUSCLE PAIN; ACUPUNCTURE; BRAIN; PERCEPTION; MICROSTIMULATION; SYNAESTHESIA; MIGRAINE AB Somatic sensations induced by placebos are a frequent phenomenon whose etiology and clinical relevance remains unknown. In this study, we have evaluated the quantitative, qualitative, spatial, and temporal characteristics of placebo-induced somatic sensations in response to three different placebo interventions: (1) placebo irritant solution, (2) placebo laser stimulation, and (3) imagined laser stimulation. The quality and intensity of evoked sensations were assessed using the McGill pain questionnaire and visual analogue scales (VAS), while subjects' sensation drawings processed by a geographic information system (GIS) were used to measure their spatial characteristics. We found that all three interventions are capable of producing robust sensations most frequently described as "tingling" and "warm" that can reach consider-able spatial extent (<= 205mm(2)) and intensity (<= 80/100 VAS). Sensations from placebo stimulation were often referred to areas remote from the stimulation site and exhibit considerable similarity with referred pain. Interestingly, there was considerable similarity of qualitative features as well as spatial patterns across subjects and placebos. However, placebo laser stimulation elicited significantly stronger and more widespread sensations than placebo irritant solution. Finally, novelty seeking, a character trait assessed by the Temperament and Character Inventory and associated with basal dopaminergic activity, was less pronounced in subjects susceptible to report placebo-induced sensations. Our study has shown that placebo-induced sensations are frequent and can reach considerable intensity and extent. As multiple somatosensory subsystems are involved despite the lack of peripheral stimulus, we propose a central etiology for this phenomenon. C1 [Beissner, Florian] Hannover Med Sch, Somatosensory & Auton Therapy Res, Inst Neuroradiol, D-30625 Hannover, Germany. [Beissner, Florian; Napadow, Vitaly] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02129 USA. [Bruenner, Franziska; Fink, Maria] Jena Univ Hosp, Pain & Auton Integrat Res PAIR, Dept Psychiat & Psychotherapy, D-07743 Jena, Germany. [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80336 Munich, Germany. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Beissner, F (reprint author), Hannover Med Sch, Somatosensory & Auton Therapy Res, Inst Neuroradiol, D-30625 Hannover, Germany. EM beissner.florian@mh-hannover.de FU Horst Gortz Foundation; German Research Foundation [BE4677/1-1]; Schweizer-Arau Foundation; Theophrastus Foundation; NIH [K24-AT004095, P01-AT006663, R01-AT007550, R01-AR064367] FX This study was supported by Horst Gortz Foundation (FBe, FBr), German Research Foundation BE4677/1-1 (FB), Schweizer-Arau Foundation (KM), Theophrastus Foundation (KM) and NIH grants K24-AT004095 (TJK), P01-AT006663 (VN, TJK), R01-AT007550 (VN), and R01-AR064367 (VN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 2 Z9 2 U1 10 U2 18 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 APR 22 PY 2015 VL 10 IS 4 AR e0124808 DI 10.1371/journal.pone.0124808 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5KV UT WOS:000353331500100 PM 25901350 ER PT J AU Iacono, MI Neufeld, E Akinnagbe, E Bower, K Wolf, J Oikonomidis, IV Sharma, D Lloyd, B Wilm, BJ Wyss, M Pruessmann, KP Jakab, A Makris, N Cohen, ED Kuster, N Kainz, W Angelone, LM AF Iacono, Maria Ida Neufeld, Esra Akinnagbe, Esther Bower, Kelsey Wolf, Johanna Oikonomidis, Ioannis Vogiatzis Sharma, Deepika Lloyd, Bryn Wilm, Bertram J. Wyss, Michael Pruessmann, Klaas P. Jakab, Andras Makris, Nikos Cohen, Ethan D. Kuster, Niels Kainz, Wolfgang Angelone, Leonardo M. TI MIDA: A Multimodal Imaging-Based Detailed Anatomical Model of the Human Head and Neck SO PLOS ONE LA English DT Article ID INDUCED CURRENT DENSITIES; MONTE-CARLO CALCULATIONS; REALISTIC ANTHROPOMORPHIC PHANTOM; RADIATION PROTECTION DOSIMETRY; EXTERNAL PHOTON IRRADIATION; VISIBLE HUMAN PROJECT; FEMALE VOXEL PHANTOM; CONVERSION COEFFICIENTS; INTERNAL DOSIMETRY; ABSORBED FRACTIONS AB Computational modeling and simulations are increasingly being used to complement experimental testing for analysis of safety and efficacy of medical devices. Multiple voxel- and surface-based whole-and partial-body models have been proposed in the literature, typically with spatial resolution in the range of 1-2 mm and with 10-50 different tissue types resolved. We have developed a multimodal imaging-based detailed anatomical model of the human head and neck, named "MIDA". The model was obtained by integrating three different magnetic resonance imaging (MRI) modalities, the parameters of which were tailored to enhance the signals of specific tissues: i) structural T1- and T2-weighted MRIs; a specific heavily T2-weighted MRI slab with high nerve contrast optimized to enhance the structures of the ear and eye; ii) magnetic resonance angiography (MRA) data to image the vasculature, and iii) diffusion tensor imaging (DTI) to obtain information on anisotropy and fiber orientation. The unique multimodal high-resolution approach allowed resolving 153 structures, including several distinct muscles, bones and skull layers, arteries and veins, nerves, as well as salivary glands. The model offers also a detailed characterization of eyes, ears, and deep brain structures. A special automatic atlas-based segmentation procedure was adopted to include a detailed map of the nuclei of the thalamus and midbrain into the head model. The suitability of the model to simulations involving different numerical methods, discretization approaches, as well as DTI-based tensorial electrical conductivity, was examined in a case-study, in which the electric field was generated by transcranial alternating current stimulation. The voxel- and the surface-based versions of the models are freely available to the scientific community. C1 [Iacono, Maria Ida; Akinnagbe, Esther; Bower, Kelsey; Cohen, Ethan D.; Kainz, Wolfgang; Angelone, Leonardo M.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biomed Phys, Silver Spring, MD 20993 USA. [Neufeld, Esra; Wolf, Johanna; Oikonomidis, Ioannis Vogiatzis; Sharma, Deepika; Lloyd, Bryn; Kuster, Niels] ITIS Fdn Res Informat Technol Soc, Zurich, Switzerland. [Wolf, Johanna; Oikonomidis, Ioannis Vogiatzis; Sharma, Deepika; Kuster, Niels] Swiss Fed Inst Technol, CH-8092 Zurich, Switzerland. [Wilm, Bertram J.; Wyss, Michael; Pruessmann, Klaas P.] Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. [Wilm, Bertram J.; Wyss, Michael; Pruessmann, Klaas P.] Swiss Fed Inst Technol, Zurich, Switzerland. [Jakab, Andras] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Computat Imaging Res Lab, Vienna, Austria. [Jakab, Andras] Swiss Fed Inst Technol, Comp Vision Lab, Zurich, Switzerland. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal,Dept Psychiat & Neurol, Charlestown, MA 02129 USA. RP Angelone, LM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biomed Phys, Silver Spring, MD 20993 USA. EM Leonardo.angelone@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health [1R21EB016449-01A1]; U.S. Food and Drug Administration; CTI [14930.1 PFLS-LS]; Center for Devices and Radiological Health FX This research was supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health (1R21EB016449-01A1), in part by the U.S. Food and Drug Administration's Critical Path Initiative, in part by CTI (14930.1 PFLS-LS), and in part by the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 9 Z9 9 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 22 PY 2015 VL 10 IS 4 AR e0124126 DI 10.1371/journal.pone.0124126 PG 35 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5KV UT WOS:000353331500078 PM 25901747 ER PT J AU Naseem, M Murray, J Hilton, JF Karamchandani, J Muradali, D Faragalla, H Polenz, C Han, D Bell, DC Brezden-Masley, C AF Naseem, Madiha Murray, Joshua Hilton, John F. Karamchandani, Jason Muradali, Derek Faragalla, Hala Polenz, Chanele Han, Dolly Bell, David C. Brezden-Masley, Christine TI Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis SO BMC CANCER LA English DT Article DE Microcalcifications; Breast imaging; Mammography; Tumorigenesis; Breast pathology; HER-2 ID MALIGNANT-APPEARING MICROCALCIFICATIONS; CASTING-TYPE CALCIFICATIONS; IN-SITU; CARCINOMAS; OVEREXPRESSION; APPEARANCE; FEATURES; DISEASE; BIOLOGY; TUMORS AB Background: Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs. Methods: A retrospective chart review was performed for 937 women treated for breast cancer during 2000-2012 at St. Michael's Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 over-expression and presence of MCs were collected. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All p-values less than 0.05 were considered statistically significant. Results: A total of 937 patient charts were included. About 38.3% of the patients presented with mammographic MCs on routine mammographic screening. Patients were more likely to have MCs if they were HER-2 positive (52.9%; p < 0.001). There was a significant association between MCs and peri-menopausal status with a mean age of 50 (64%; p = 0.012). Patients with invasive ductal carcinomas (40.9%; p = 0.001) were more likely to present with MCs than were patients with other tumor histologies. Patients with a heterogeneous breast density (p = 0.031) and multifocal breast disease (p = 0.044) were more likely to have MCs on mammograms. There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%). A total of 52.2% of MCs were missed on mammograms which were visible on pathology (p < 0.001). Conclusion: This is the largest study suggesting the appearance of MCs on mammograms is strongly associated with HER-2 over-expression, invasive ductal carcinomas, peri-menopausal status, heterogeneous breast density and multifocal disease. C1 [Naseem, Madiha; Polenz, Chanele; Han, Dolly; Brezden-Masley, Christine] St Michaels Hosp, Dept Hematol Oncol, Toronto, ON M5B 1W8, Canada. [Naseem, Madiha; Karamchandani, Jason; Faragalla, Hala; Brezden-Masley, Christine] Univ Toronto, Fac Med, Toronto, ON M5S 1A8, Canada. [Murray, Joshua] Moncton Hosp, Horizon Hlth Network, Moncton, NB E1C 6Z8, Canada. [Hilton, John F.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. [Hilton, John F.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Karamchandani, Jason; Faragalla, Hala; Bell, David C.] St Michaels Hosp, Dept Lab Med & Pathol, Toronto, ON M5B 1W8, Canada. [Muradali, Derek] St Michaels Hosp, Dept Med Imaging, Toronto, ON M5B 1W8, Canada. RP Naseem, M (reprint author), St Michaels Hosp, Dept Hematol Oncol, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM madiha.naseem@utoronto.ca NR 22 TC 2 Z9 4 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 22 PY 2015 VL 15 AR 307 DI 10.1186/s12885-015-1312-z PG 9 WC Oncology SC Oncology GA CG5HC UT WOS:000353320700001 PM 25896922 ER PT J AU Bharat, A Cunningham, SA Budinger, GRS Kreisel, D Dewet, CJ Gelman, AE Waites, K Crabb, D Xiao, L Bhorade, S Ambalavanan, N Dilling, DF Lowery, EM Astor, T Hachem, R Krupnick, AS DeCamp, MM Ison, MG Patel, R AF Bharat, Ankit Cunningham, Scott A. Budinger, G. R. Scott Kreisel, Daniel Dewet, Charl J. Gelman, Andrew E. Waites, Ken Crabb, Donna Xiao, Li Bhorade, Sangeeta Ambalavanan, Namasivayam Dilling, Daniel F. Lowery, Erin M. Astor, Todd Hachem, Ramsey Krupnick, Alexander S. DeCamp, Malcolm M. Ison, Michael G. Patel, Robin TI Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans SO Science Translational Medicine LA English DT Article ID ORTHOTOPIC LUNG TRANSPLANTATION; MYCOPLASMA-HOMINIS; UREALYTICUM; HYDROLYSIS; PATIENT; UREA AB Hyperammonemia syndrome is a fatal complication affecting immunosuppressed patients. Frequently refractory to treatment, it is characterized by progressive elevations in serum ammonia of unknown etiology, ultimately leading to cerebral edema and death. In mammals, ammonia produced during amino acid metabolism is primarily cleared through the hepatic production of urea, which is eliminated in the kidney. Ureaplasma species, commensals of the urogenital tract, are Mollicutes dependent on urea hydrolysis to ammonia and carbon dioxide for energy production. We hypothesized that systemic infection with Ureaplasma species might pose a unique challenge to human ammonia metabolism by liberating free ammonia resulting in the hyperammonemia syndrome. We used polymerase chain reaction, specialized culture, and molecular resistance profiling to identify systemic Ureaplasma infection in lung transplant recipients with hyperammonemia syndrome, but did not detect it in any lung transplant recipients with normal ammonia concentrations. Administration of Ureaplasmadirected antimicrobials to patients with hyperammonemia syndrome resulted in biochemical and clinical resolution of the disorder. Relapse in one patient was accompanied by recurrent Ureaplasma bacteremia with antimicrobial resistance. Our results provide evidence supporting a causal relationship between Ureaplasma infection and hyperammonemia, suggesting a need to test for this organism and provide empiric antimicrobial treatment while awaiting microbiological confirmation. C1 [Bharat, Ankit; Bhorade, Sangeeta; DeCamp, Malcolm M.; Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Cunningham, Scott A.; Budinger, G. R. Scott; Patel, Robin] Mayo Clin, Rochester, MN 55905 USA. [Kreisel, Daniel; Dewet, Charl J.; Gelman, Andrew E.; Hachem, Ramsey; Krupnick, Alexander S.] Washington Univ, St Louis, MO 63110 USA. [Waites, Ken; Crabb, Donna; Xiao, Li; Ambalavanan, Namasivayam] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Dilling, Daniel F.; Lowery, Erin M.] Loyola Univ, Chicago Stritch Sch Med, Chicago, IL 60153 USA. [Dilling, Daniel F.] Hines VA Hosp, Hines, IL USA. [Dilling, Daniel F.] RML Specialty Hosp, Hinsdale, IL 60521 USA. [Astor, Todd] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Bharat, A (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM abharat@nm.org OI Ambalavanan, Namasivayam/0000-0003-0731-9092 FU Veterans Administration; Anolinx; Chimerix; GlaxoSmithKline; ViroPharma; Gibbon Research grant by American Association of Thoracic Surgeons; NIH/National Institute on Alcohol Abuse and Alcoholism [K23AA022126]; Barnes Jewish Research Foundation; [HL092963]; [ES015024]; [ES013995]; [HL071643]; [R01HL113931]; [1R01HL113436] FX G.R.S.B. is supported by HL092963, ES015024, ES013995, HL071643, and the Veterans Administration. M.G.I. receives grant support from Anolinx, Chimerix, GlaxoSmithKline, and ViroPharma. A.B. is supported by Gibbon Research grant by American Association of Thoracic Surgeons. E.M.L. is supported by NIH/National Institute on Alcohol Abuse and Alcoholism K23AA022126. A.E.G. received funds from The Barnes Jewish Research Foundation and 1R01HL113436, both of which contributed to collection of BAL samples used in this manuscript. A.S.K. was supported by R01HL113931 on Mechanisms of Lung Allograft Acceptance. NR 24 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 22 PY 2015 VL 7 IS 284 AR 284re3 DI 10.1126/scitranslmed.aaa8419 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CG6AN UT WOS:000353377400012 PM 25904745 ER PT J AU Crane, NA Schuster, RM Mermelstein, RJ Gonzalez, R AF Crane, Natania A. Schuster, Randi Melissa Mermelstein, Robin J. Gonzalez, Raul TI Neuropsychological sex differences associated with age of initiated use among young adult cannabis users SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE THC; Sex differences; Cognition; Marijuana; Cannabis ID NEUROCOGNITIVE PERFORMANCE; PREFRONTAL CORTEX; MARIJUANA USE; TASK; ADOLESCENTS; CHILDHOOD; BRAIN; ONSET; DYSFUNCTION; DISORDER AB Introduction. Earlier initiation of cannabis use is associated with poorer neuropsychological functioning across several domains. Given well-documented sex differences in neuromaturation during adolescence, initiation of cannabis use during this time may affect neuropsychological functioning differently for males and females. Method: In the current study, we examined sex differences in the relationship between age of initiated cannabis use and neuropsychological performance after controlling for amount of lifetime cannabis use in 44 male and 25 female young adult cannabis users. Results: We found that an earlier age of initiated use was related to poorer episodic memory, especially immediate recall, in females, but not in males. On the other hand, we found that, surprisingly, an earlier age of initiated use was associated with better decision making overall. However, exploratory analyses found sex-specific factors associated with decision making and age of initiated use, specifically that attention-deficit/hyperactivity disorder (ADHD) symptoms in females may drive the relationship between an earlier age of initiated use and better decision making. Further, an earlier age of initiated use was associated with less education, a lower IQ, and fewer years of mother's education for females, but more lifetime cannabis use for males. Conclusions: Taken together, our findings suggest there are sex differences in the associations between age of initiated cannabis use and neuropsychological functioning. The current study provides preliminary evidence that males and females may have different neuropsychological vulnerabilities that place them at risk for initiating cannabis use and continued cannabis use, highlighting the importance of examining the impact of cannabis on neuropsychological functioning separately for males and females. C1 [Crane, Natania A.; Mermelstein, Robin J.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Crane, Natania A.; Mermelstein, Robin J.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. [Schuster, Randi Melissa] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Gonzalez, Raul] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. RP Gonzalez, R (reprint author), 11200 SW 8th St, Miami, FL 33199 USA. EM raul.gonzalezjr@fiu.edu FU National Institute on Drug Abuse (NIDA) [K23DA023560, R01DA031176, R01DA0331560, F31DA038388-01]; National Institute of Mental Health (NIMH) [T32MH067631]; National Cancer Institute (NCI) [P01CA098262] FX This publication was funded by the National Institute on Drug Abuse (NIDA) [grant number K23DA023560], [grant number R01DA031176], [grant number R01DA0331560], PI: R.G., and [grant number F31DA038388-01], PI: N.A.C.; the National Institute of Mental Health (NIMH) [grant number T32MH067631, to N.A.C.]; and the National Cancer Institute (NCI) [grant number P01CA098262], PI: R.M. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDA, NCI, or the National Institutes of Health. NR 53 TC 8 Z9 8 U1 6 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR 21 PY 2015 VL 37 IS 4 BP 389 EP 401 DI 10.1080/13803395.2015.1020770 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI7GP UT WOS:000354931400005 PM 25832823 ER PT J AU Rajamuthiah, R Fuchs, BB Conery, AL Kim, W Jayamani, E Kwon, B Ausubel, FM Mylonakis, E AF Rajamuthiah, Rajmohan Fuchs, Beth Burgwyn Conery, Annie L. Kim, Wooseong Jayamani, Elamparithi Kwon, Bumsup Ausubel, Frederick M. Mylonakis, Eleftherios TI Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus SO PLOS ONE LA English DT Article ID CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA; VIRULENCE FACTORS; MODEL HOST; ACINETOBACTER-BAUMANNII; INTRINSIC RESISTANCE; INFECTION MODEL; EFFLUX PUMP(S); PATHOGENESIS; INHIBITORS AB Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 mu g/ml respectively; minimum effective concentration: <= 0.78 mu g/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 mu g/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 mu g/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. C1 [Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Kim, Wooseong; Jayamani, Elamparithi; Mylonakis, Eleftherios] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Infect Dis, Providence, RI 02912 USA. [Kwon, Bumsup] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Neurol, Providence, RI 02912 USA. [Rajamuthiah, Rajmohan; Conery, Annie L.; Jayamani, Elamparithi; Ausubel, Frederick M.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mylonakis, E (reprint author), Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Infect Dis, Providence, RI 02912 USA. EM emylonakis@lifespan.org RI Kim, Wooseong/A-9256-2017 OI Kim, Wooseong/0000-0002-4597-8374 FU National Institutes of Health [P01 AI083214, R01 AI085581] FX This study was supported by National Institutes of Health grant P01 AI083214 to EM and FMA and National Institutes of Health grant R01 AI085581 to FMA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 11 Z9 11 U1 1 U2 11 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 APR 21 PY 2015 VL 10 IS 4 AR UNSP e0124595 DI 10.1371/journal.pone.0124595 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG3XJ UT WOS:000353212600076 PM 25897961 ER PT J AU Kurz, FT Derungs, T Aon, MA O'Rourke, B Armoundas, AA AF Kurz, Felix T. Derungs, Thomas Aon, Miguel A. O'Rourke, Brian Armoundas, Antonis A. TI Mitochondrial Networks in Cardiac Myocytes Reveal Dynamic Coupling Behavior SO BIOPHYSICAL JOURNAL LA English DT Article ID WHOLE-CELL OSCILLATIONS; INDIVIDUAL MITOCHONDRIA; HEART-FAILURE; METABOLIC OSCILLATIONS; REDOX; SYNCHRONIZATION; REGULARIZATION; ORGANIZATION; CRITICALITY; MECHANISMS AB Oscillatory behavior of mitochondrial inner membrane potential (Delta psi(m)) is commonly observed in cells subjected to oxidative or metabolic stress. In cardiac myocytes, the activation of inner membrane pores by reactive oxygen species (ROS) is a major factor mediating intermitochondrial coupling, and ROS-induced ROS release has been shown to underlie propagated waves of Delta psi(m) depolarization as well as synchronized limit cycle oscillations of Delta psi(m) in the network. The functional impact of Delta psi(m) instability on cardiac electrophysiology, Ca2+ handling, and even cell survival, is strongly affected by the extent of such intermitochondrial coupling. Here, we employ a recently developed wavelet-based analytical approach to examine how different substrates affect mitochondrial coupling in cardiac cells, and we also determine the oscillatory coupling properties of mitochondria in ventricular cells in intact perfused hearts. The results show that the frequency of Delta psi(m) oscillations varies inversely with the size of the oscillating mitochondrial cluster, and depends on the strength of local intermitochondrial coupling. Time-varying coupling constants could be quantitatively determined by applying a stochastic phase model based on extension of the well-known Kuramoto model for networks of coupled oscillators. Cluster size-frequency relationships varied with different substrates, as did mitochondrial coupling constants, which were significantly larger for glucose (7.78 x 10(-2) +/- 0.98 x 10(-2) s(-1)) and pyruvate (7.49 x 10(-2) +/- 1.65 x 10(-2) s(-1)) than lactate (4.83 x 10(-2) +/- 1.25 x 10(-2) s(-1)) or beta-hydroxybutyrate (4.11 x 10(-2) +/- 0.62 x 10(-2) s(-1)). The findings indicate that mitochondrial spatiotemporal coupling and oscillatory behavior is influenced by substrate selection, perhaps through differing effects on ROS/redox balance. In particular, glucose-perfusion generates strong intermitochondrial coupling and temporal oscillatory stability. Pathological changes in specific catabolic pathways, which are known to occur during the progression of cardiovascular disease, could therefore contribute to altered sensitivity of the mitochondrial network to oxidative stress and emergent Delta psi(m) instability, ultimately scaling to produce organ level dysfunction. C1 [Kurz, Felix T.; Derungs, Thomas; Armoundas, Antonis A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Kurz, Felix T.] Univ Heidelberg Hosp, Dept Neuroradiol, Heidelberg, Germany. [Kurz, Felix T.] Charite, Dept Cardiol, D-13353 Berlin, Germany. [Derungs, Thomas] Max Delbruck Ctr Mol Med, Expt & Clin Res Ctr, Berlin, Germany. [Derungs, Thomas] Charite, D-13353 Berlin, Germany. [Aon, Miguel A.; O'Rourke, Brian] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. RP Armoundas, AA (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM aarmoundas@partners.org RI Aon, Miguel/A-6564-2008 OI Aon, Miguel/0000-0002-4355-5431 FU Boehringer Ingelheim Fonds fellowship FX The work was supported by a Boehringer Ingelheim Fonds fellowship given to F.T.K. NR 53 TC 8 Z9 9 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD APR 21 PY 2015 VL 108 IS 8 BP 1922 EP 1933 DI 10.1016/j.bpj.2015.01.040 PG 12 WC Biophysics SC Biophysics GA CG5PG UT WOS:000353344400011 PM 25902432 ER PT J AU Nahrendorf, M Frantz, S Swirski, FK Mulder, WJM Randolph, G Ertl, G Ntziachristos, V Piek, JJ Stroes, ES Schwaiger, M Mann, DL Fayad, ZA AF Nahrendorf, Matthias Frantz, Stefan Swirski, Filip K. Mulder, Willem J. M. Randolph, Gwendalyn Ertl, Georg Ntziachristos, Vasilis Piek, Jan J. Stroes, Erik S. Schwaiger, Markus Mann, Douglas L. Fayad, Zahi A. TI Imaging Systemic Inflammatory Networks in Ischemic Heart Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE atherosclerosis; heart failure; hematopoiesis; leukocytes; myocardial infarction; spleen ID ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE NANOPARTICLES; IN-VIVO; MONOCYTE SUBSETS; ATHEROSCLEROTIC LESIONS; LY-6C(HIGH) MONOCYTES; ARTERIAL INFLAMMATION; CARDIOVASCULAR EVENTS; PROGENITOR CELLS; DENDRITIC CELLS AB While acute myocardial infarction mortality declines, patients continue to face reinfarction and/or heart failure. The immune system, which intimately interacts with healthy and diseased tissues through resident and recruited leukocytes, is a central interface for a global host response to ischemia. Pathways that enhance the systemic leukocyte supply may be potential therapeutic targets. Pre-clinically, imaging helps to identify immunity's decision nodes, which may serve as such targets. In translating the rapidly-expanding pre-clinical data on immune activity, the difficulty of obtaining multiple clinical tissue samples from involved organs is an obstacle that whole-body imaging can help overcome. In patients, molecular and cellular imaging can be integrated with blood-based diagnostics to assess the translatability of discoveries, including the activation of hematopoietic tissues after myocardial infarction, and serve as an endpoint in clinical trials. In this review, we discuss these concepts while focusing on imaging immune activity in organs involved in ischemic heart disease. (C) 2015 by the American College of Cardiology Foundation. C1 [Nahrendorf, Matthias; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Frantz, Stefan; Ertl, Georg] Univ Klinikum Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany. [Frantz, Stefan] Univ Klinikum Halle, Univ Klin & Poliklin Innere Med 3, Halle, Saale, Germany. [Mulder, Willem J. M.; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Dept Radiol, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Mulder, Willem J. M.; Stroes, Erik S.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Randolph, Gwendalyn] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ertl, Georg] Univ Klinikum Wurzburg, Med Klin & Poliklin 1, Wurzburg, Germany. [Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, Neuherberg, Germany. [Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Neuherberg, Germany. [Piek, Jan J.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Schwaiger, Markus] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-80290 Munich, Germany. [Mann, Douglas L.] Washington Univ, Sch Med, Dept Med, Ctr Cardiovasc Res,Div Cardiol, St Louis, MO 63110 USA. RP Nahrendorf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@partners.org RI 刘, 李陆/H-8469-2015; Frantz, Stefan/G-1723-2012; OI schwaiger, markus /0000-0002-2305-7144 FU Federal Ministry of Education and Research (BMBF); German Research Foundation FX Dr. Frantz has received a grant from the Federal Ministry of Education and Research (BMBF). Dr. Ertl has served on steering committees for Novartis, Bayer, and Pfizer. Dr. Ntziachristos is a shareholder in iThera Medical GmbH. Dr. Piek has served on the medical advisory board of Abbott Vascular; and has served as a consultant to Miracor. Dr. Schwaiger has received a research grant from the German Research Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Nahrendorf and Frantz contributed equally to this work. James De Lemos, MD, served as Guest Editor for this paper. NR 73 TC 13 Z9 14 U1 0 U2 10 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 APR 21 PY 2015 VL 65 IS 15 BP 1583 EP 1591 DI 10.1016/j.jacc.2015.02.034 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG0KW UT WOS:000352956500012 PM 25881940 ER PT J AU Haggarty, SJ AF Haggarty, Stephen J. TI Epigenetic diagnostics for neuropsychiatric disorders Above the genome SO NEUROLOGY LA English DT Editorial Material AB Martin and Bell's(1) 1943 report of a pedigree with a sex-linked form of intellectual disability described what is now referred to as fragile X syndrome (FXS), caused by an expanded (>200) CGG trinucleotide repeat within the 5 untranslated region of the fragile X mental retardation 1 (FMR1) gene. This results in epigenetic silencing of the encoded fragile X mental retardation protein (FMRP).(1,2) The term epigenetic refers to chemical modifications of DNA and associated chromatin proteins that alter activity states of the genome without requiring heritable changes to DNA itself.(3) Studies of inherited neuropsychiatric disorders have contributed greatly to our understanding of the molecular basis of human cognition, mood, and behavior; the field of neuroepigenetics continues to expand and gain importance.(43 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years. C1 [Krumholz, Allan] Univ Maryland, Sch Med, Dept Neurol, Maryland Epilepsy Ctr, Baltimore, MD 21201 USA. [Sanchez, Ana M.; Kabir, Arif A.; Martello, Justin P.; Hopp, Jennifer L.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Krumholz, Allan] US Dept Vet Affairs, Maryland Healthcare Syst, Epilepsy Ctr Excellence, Baltimore, MD USA. [Wiebe, Samuel] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Gronseth, Gary S.] Univ Kansas, Dept Neurol, Sch Med, Kansas City, KS USA. [Gloss, David S.] Geisinger Hlth Syst, Dept Neurol, Danville, PA USA. [Liferidge, Aisha T.] George Washington Univ, Sch Med, Dept Emergency Med, Washington, DC USA. [Kanner, Andres M.] Univ Miami, Miller Sch Med, Int Ctr Epilepsy, Dept Neurol, Coral Gables, FL 33124 USA. [Shinnar, Shlomo] Yeshiva Univ, Dept Neurol, Albert Einstein Coll Med, Bronx, NY USA. [Shinnar, Shlomo] Yeshiva Univ, Dept Pediat, Albert Einstein Coll Med, Bronx, NY USA. [Shinnar, Shlomo] Yeshiva Univ, Dept Epidemiol, Albert Einstein Coll Med, Bronx, NY USA. [Shinnar, Shlomo] Yeshiva Univ, Dept Populat Hlth, Albert Einstein Coll Med, Bronx, NY USA. [French, Jacqueline A.] NYU, Comprehens Epilepsy Ctr, New York, NY USA. RI French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU American Academy of Neurology FX This guideline was developed with financial support from the American Academy of Neurology. NR 38 TC 29 Z9 29 U1 0 U2 12 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 APR 21 PY 2015 VL 84 IS 16 BP 1705 EP 1713 DI 10.1212/WNL.0000000000001487 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CG4GJ UT WOS:000353243200018 PM 25901057 ER PT J AU Wang, J Li, B Wu, MX AF Wang, Ji Li, Bo Wu, Mei X. TI Effective and lesion-free cutaneous influenza vaccination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biodegradable microneedle; nonablative fractional laser; dsDNA ID CYCLIC GMP-AMP; INTRADERMAL DELIVERY; SKIN VACCINATION; DENDRITIC CELLS; CYTOSOLIC DNA; ANTIMICROBIAL PEPTIDE; MICRONEEDLE ARRAYS; LASER TECHNOLOGY; DRUG-DELIVERY; IMMUNOGENICITY AB The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other "danger" signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies. C1 [Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM mwu5@mgh.harvard.edu FU National Institutes of Health [AI089779, AI070785, AI097696, DA028378] FX We thank Photopathology Core for their help in the histology and flow cytometry analysis during this project and Jeffrey H. Wu for editing. This work is supported in part by the National Institutes of Health Grants AI089779, AI070785, AI097696, and DA028378 (to M.X.W.). NR 43 TC 13 Z9 13 U1 3 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 21 PY 2015 VL 112 IS 16 BP 5005 EP 5010 DI 10.1073/pnas.1500408112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100054 PM 25848020 ER PT J AU Bai, XY Shang, SB Henao-Tamayo, M Basaraba, RJ Ovrutsky, AR Matsuda, JL Takeda, K Chan, MM Dakhama, A Kinney, WH Trostel, J Bai, A Honda, JR Achcar, R Hartney, J Joosten, LAB Kim, SH Orme, I Dinarello, CA Ordway, DJ Chan, ED AF Bai, Xiyuan Shang, Shaobin Henao-Tamayo, Marcela Basaraba, Randall J. Ovrutsky, Alida R. Matsuda, Jennifer L. Takeda, Katsuyuki Chan, Mallory M. Dakhama, Azzeddine Kinney, William H. Trostel, Jessica Bai, An Honda, Jennifer R. Achcar, Rosane Hartney, John Joosten, Leo A. B. Kim, Soo-Hyun Orme, Ian Dinarello, Charles A. Ordway, Diane J. Chan, Edward D. TI Human IL-32 expression protects mice against a hypervirulent strain of Mycobacterium tuberculosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokine; transgenic mouse; tuberculosis; host immunity; interleukin-32 ID PROINFLAMMATORY CYTOKINE; RHEUMATOID-ARTHRITIS; INTERLEUKIN-32; INFECTION; CELLS; INFLAMMATION; IL-32-GAMMA; ISOFORM AB Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of Mycobacterium tuberculosis (MTB) but the role of IL-32 in vivo against MTB remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human IL-32 gamma gene is expressed using the surfactant protein C promoter (SPC-IL-32 gamma Tg). Wild-type and SPC-IL-32 gamma Tg mice were infected with a low-dose aerosol of a hypervirulent strain of MTB (W-Beijing HN878). At 30 and 60 d after infection, the transgenic mice had 66% and 85% fewer MTB in the lungs and 49% and 68% fewer MTB in the spleens, respectively; the transgenic mice also exhibited greater survival. Increased numbers of host-protective innate and adaptive immune cells were present in SPC-IL-32 gamma Tg mice, including tumor necrosis factor-alpha (TNF alpha) positive lung macrophages and dendritic cells, and IFN-gamma (IFN gamma) and TNF alpha positive CD4(+) and CD8(+) T cells in the lungs and mediastinal lymph nodes. Alveolar macrophages from transgenic mice infected with MTB ex vivo had reduced bacterial burden and increased colocalization of green fluorescent protein-labeled MTB with lysosomes. Furthermore, mouse macrophages made to express IL-32. but not the splice variant IL-32 beta were better able to limit MTB growth than macrophages capable of producing both. The lungs of patients with tuberculosis showed increased IL-32 expression, particularly in macrophages of granulomas and airway epithelial cells but also B cells and T cells. We conclude that IL-32 gamma enhances host immunity to MTB. C1 [Bai, Xiyuan; Ovrutsky, Alida R.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80206 USA. [Shang, Shaobin; Henao-Tamayo, Marcela; Basaraba, Randall J.; Orme, Ian; Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Bai, Xiyuan; Ovrutsky, Alida R.; Matsuda, Jennifer L.; Chan, Mallory M.; Kinney, William H.; Trostel, Jessica; Bai, An; Honda, Jennifer R.; Hartney, John; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Takeda, Katsuyuki; Dakhama, Azzeddine] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA. [Achcar, Rosane] Natl Jewish Hlth, Dept Pathol, Denver, CO 80206 USA. [Joosten, Leo A. B.; Dinarello, Charles A.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands. [Kim, Soo-Hyun] Konkuk Univ, Dept Biomed Sci & Technol, Seoul, South Korea. [Ovrutsky, Alida R.; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Dinarello, Charles A.] Univ Colorado, Div Infect Dis, Aurora, CO 80045 USA. RP Bai, XY (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80206 USA. EM BaiX@NJHealth.org; cdinare333@aol.com; ChanE@NJHealth.org RI Joosten, Leo/H-3138-2015; Shang, Shaobin/K-5669-2015; Henao-Tamayo, Marcela/D-8189-2017 OI Shang, Shaobin/0000-0003-4407-1911; Henao-Tamayo, Marcela/0000-0002-4249-9650 FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development [1 I01 BX001028-01A2]; National Institutes of Health (NIH) [AI15614]; National Research Foundation of Korea; NIH [R21 AI081959, 1DP2OD006450]; American Recovery and Reinvestment Act funds FX We thank Dr. Stephan W. Glasser (University of Cincinnati) for providing the SPC expression vector pUC18SPC3.7, Drs. Carlyne Cool and Steve Groshong of National Jewish Health for advice on the use of the Aperio technology, and Drs. Su Young and Jida Choi for measuring the IL-32 levels in the lungs of the SPC-IL-32 gamma Tg mice. This study was funded by grants from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development 1 I01 BX001028-01A2 (to E.D.C.); National Institutes of Health (NIH) AI15614 (to C.A.D.); National Research Foundation of Korea (S.-H.K.); and NIH R21 AI081959, NIH Innovation Award 1DP2OD006450, and American Recovery and Reinvestment Act funds (to D.J.O.). NR 29 TC 5 Z9 6 U1 2 U2 10 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 APR 21 PY 2015 VL 112 IS 16 BP 5111 EP 5116 DI 10.1073/pnas.1424302112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100072 PM 25820174 ER PT J AU Becker, A Kannan, TR Taylor, AB Pakhomova, ON Zhang, Y Somarajan, SR Galaleldeen, A Holloway, SP Baseman, JB Hart, PJ AF Becker, Argentina Kannan, T. R. Taylor, Alexander B. Pakhomova, Olga N. Zhang, Yanfeng Somarajan, Sudha R. Galaleldeen, Ahmad Holloway, Stephen P. Baseman, Joel B. Hart, P. John TI Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from Mycoplasma pneumoniae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mycoplasma cytotoxin; single-crystal X-ray diffraction; ADP-ribosyltransferase; vacuolation; reactive airway disease ID DISTRESS-SYNDROME TOXIN; SURFACTANT PROTEIN-A; CHOLERA-TOXIN; PULMONARY SURFACTANT; CRYSTAL-STRUCTURE; BINDING SITE; INFLAMMATION; PATHOGEN; ASTHMA; LIPIDS AB Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and "walking" pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. Here we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem beta-trefoil domains associate to form an overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal beta-trefoil domain. The results enhance our understanding of Mp pathogenicity and suggest a novel avenue for the development of therapies to treat Mp-associated asthma and other acute and chronic airway diseases. C1 [Becker, Argentina; Taylor, Alexander B.; Pakhomova, Olga N.; Zhang, Yanfeng; Galaleldeen, Ahmad; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Kannan, T. R.; Somarajan, Sudha R.; Baseman, Joel B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, Ctr Airway Inflammat Res, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, XRay Crystallog Core Lab, San Antonio, TX 78229 USA. [Pakhomova, Olga N.] Old Dominion Univ, Frank Reidy Ctr Bioelect, Norfolk, VA 23508 USA. [Galaleldeen, Ahmad] St Marys Univ, Dept Biol Sci, San Antonio, TX 78228 USA. [Hart, P. John] US Dept Vet Affairs, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Baseman, JB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, Ctr Airway Inflammat Res, San Antonio, TX 78229 USA. EM baseman@uthscsa.edu; pjh@biochem.uthscsa.edu OI Pakhomova, Olga/0000-0003-4950-4130 FU National Institutes of Health [U19 AI070412, P41 GM103403]; Kleberg Foundation; R.A. Welch Foundation [AQ-1399]; US Department of Energy [DE-AC02-06CH11357]; Office of the Vice President for Research; San Antonio Cancer Institute Grant [P30 CA054174] FX We thank Jonathan Schuermann for technical support. J.B.B., P.J.H., and coauthors are supported by National Institutes of Health Grant U19 AI070412. J.B.B. is also supported by the Kleberg Foundation. P.J.H. is also supported by R.A. Welch Foundation Grant AQ-1399. Support for Northeastern Collaborative Access Team beamline 24-ID-E is provided by National Institutes of Health Grant P41 GM103403 and US Department of Energy Grant DE-AC02-06CH11357. The University of Texas Health Science Center at San Antonio's X-Ray Crystallography Core Laboratory is supported in part by the Office of the Vice President for Research and by San Antonio Cancer Institute Grant P30 CA054174. NR 49 TC 8 Z9 11 U1 3 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 APR 21 PY 2015 VL 112 IS 16 BP 5165 EP 5170 DI 10.1073/pnas.1420308112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100081 PM 25848012 ER PT J AU Sholukh, AM Watkins, JD Vyas, HK Gupta, S Lakhashe, SK Thorat, S Zhou, M Hemashettar, G Bachler, BC Forthal, DN Villinger, F Sattentau, QJ Weiss, RA Agatic, G Corti, D Lanzavecchia, A Heeney, JL Ruprecht, RM AF Sholukh, Anton M. Watkins, Jennifer D. Vyas, Hemant K. Gupta, Sandeep Lakhashe, Samir K. Thorat, Swati Zhou, Mingkui Hemashettar, Girish Bachler, Barbara C. Forthal, Donald N. Villinger, Francois Sattentau, Quentin J. Weiss, Robin A. Agatic, Gloria Corti, Davide Lanzavecchia, Antonio Heeney, Jonathan L. Ruprecht, Ruth M. TI Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: Complete protection of rhesus monkeys from mucosal SHIV challenge SO VACCINE LA English DT Article DE IgA; IgG; Complete protection; Passive immunization; Rhesus monkey; SHIV-C mucosal challenge (6 max) ID VACCINE EFFICACY TRIAL; HIV-1-INFECTED INDIVIDUALS; 1-INFECTED INDIVIDUALS; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; AIDS VACCINE; VIRAL LOAD; MACAQUES; INFECTION; PREVENTION AB Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgAl) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1 + dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Sholukh, Anton M.; Vyas, Hemant K.; Lakhashe, Samir K.; Zhou, Mingkui; Ruprecht, Ruth M.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78245 USA. [Ruprecht, Ruth M.] Southwest Natl Primate Res Ctr, San Antonio, TX USA. [Sholukh, Anton M.; Watkins, Jennifer D.; Vyas, Hemant K.; Lakhashe, Samir K.; Thorat, Swati; Hemashettar, Girish; Bachler, Barbara C.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sholukh, Anton M.; Watkins, Jennifer D.; Vyas, Hemant K.; Lakhashe, Samir K.; Thorat, Swati; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Sandeep; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Villinger, Francois] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Sattentau, Quentin J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Weiss, Robin A.] UCL, Div Infect & Immun, London WC1E 6BT, England. [Agatic, Gloria; Corti, Davide] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland. [Corti, Davide; Lanzavecchia, Antonio] Inst Res Biomed, CH-6500 Bellinzona, Switzerland. [Lanzavecchia, Antonio] ETH, CH-8093 Zurich, Switzerland. [Heeney, Jonathan L.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England. RP Ruprecht, RM (reprint author), Texas Biomed Res Inst, POB 760549, San Antonio, TX 78245 USA. EM rruprecht@txbiomed.org OI Heeney, Jonathan/0000-0003-2702-1621 FU Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) UCL-VDC Grant [38637]; NIH [P01 AI048240, R01 AI100703, R37 AI034266]; Office of Research Infrastructure Programs [P51 RR013986, OD P51 OD011133]; [P51 OD011132] FX We thank Dr. J. Mascola for providing mAb VRC01, Dr. S.-L. Hu for providing SHIV-1157ip Env proteins, and Dr. W. Marasco for providing mAb Fm-6. We thank Dr. K. Rogers and K. Kinsley for TRIM5 alpha genotype analysis, Dr. S. Lee for assistance in statistical analysis, V. Shanmuganathan for technical assistance, and Juan Esquivel for assistance with the preparation of the manuscript. This was work supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) UCL-VDC Grant 38637 (R.A.W.). This project was also funded in part by NIH grants P01 AI048240, R01 AI100703 and R37 AI034266 to RMR. Base grant P51 OD011132 provided support to the Yerkes National Primate Research Center. The Southwest National Primate Research Center is supported by an NIH primate center base grant (previously NCRR grant P51 RR013986; currently Office of Research Infrastructure Programs/OD P51 OD011133). NR 48 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 21 PY 2015 VL 33 IS 17 BP 2086 EP 2095 DI 10.1016/j.vaccine.2015.02.020 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CG2BE UT WOS:000353079100014 PM 25769884 ER PT J AU Closson, EF Colby, DJ Nguyen, T Cohen, SS Biello, K Mimiaga, MJ AF Closson, Elizabeth F. Colby, Donn J. Thi Nguyen Cohen, Samuel S. Biello, Katie Mimiaga, Matthew J. TI The balancing act: Exploring stigma, economic need and disclosure among male sex workers in Ho Chi Minh City, Vietnam SO GLOBAL PUBLIC HEALTH LA English DT Article DE sex work; Vietnam; stigma; MSM; HIV ID HIV RISK; SEROSTATUS DISCLOSURE; TRANSACTIONAL SEX; MEN; GAY; HEALTH; DISCRIMINATION; VICTIMIZATION; ORIENTATION; PREVENTION AB In Vietnam, there is an emerging HIV epidemic among men who have sex with men (MSM). Male sex workers engage in high-risk sexual behaviours that make them particularly vulnerable to HIV infection. In 2010, 23 MSM in Ho Chi Minh City (HCMC) who recently received payment for sex with another man completed in-depth qualitative interviews exploring motivations for sex work, patterns of sex work disclosure and experiences of social stigma. Interviews were recorded, transcribed and translated into English and analysed using a qualitative descriptive approach. Low wages, unstable employment and family remittances were motivating factors for MSM in HCMC to sell sex. Participants described experiences of enacted and felt social stigma related to their involvement in sex work. In response, they utilised stigma management techniques aimed at concealment of involvement in sex work. Such strategies restricted sexual communication with non-paying sex partners and potentially limited their ability to seek social support from family and friends. Departing from decontextualized depictions of sex work disclosure, our findings describe how decisions to reveal involvement in sex work are shaped by social and structural factors such as social stigma, techniques to minimise exposure to stigma, economic imperatives and familial responsibilities. C1 [Closson, Elizabeth F.; Cohen, Samuel S.; Biello, Katie; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Colby, Donn J.] Ctr Appl Res Men & Hlth, Ho Chi Minh City, Vietnam. [Colby, Donn J.; Thi Nguyen] Harvard Med Sch AIDS Initiat Vietnam HAIVN, Ho Chi Minh City, Vietnam. [Biello, Katie; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Closson, EF (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. EM rclosson@fenwayhealth.org OI colby, donn/0000-0003-3931-5926 FU Harvard University Catalyst/The Harvard University Clinical and Translational Science Center; NIH [1 UL1 RR 025758-02] FX This work was supported by a pilot grant from Harvard University Catalyst/The Harvard University Clinical and Translational Science Center (PIs: Colby and Mimiaga); NIH [grant number #1 UL1 RR 025758-02]; and financial contributions from participating institutions. NR 41 TC 3 Z9 3 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 EI 1744-1706 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PD APR 21 PY 2015 VL 10 IS 4 BP 520 EP 531 DI 10.1080/17441692.2014.992452 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CC4XF UT WOS:000350358000008 PM 25555192 ER PT J AU Osaka, E Kelly, AD Spentzos, D Choy, E Yang, XQ Shen, JK Yang, P Mankin, HJ Hornicek, FJ Duan, ZF AF Osaka, Eiji Kelly, Andrew D. Spentzos, Dimitrios Choy, Edwin Yang, Xiaoqian Shen, Jacson K. Yang, Pei Mankin, Henry J. Hornicek, Francis J. Duan, Zhenfeng TI MicroRNA-155 expression is independently predictive of outcome in chordoma SO ONCOTARGET LA English DT Article DE miRNA-155 (miR-155); chordoma; prognosis; miRNA microarray assay; RT-PCR ID NEGATIVE BREAST-CANCER; PROMOTES TUMOR-GROWTH; B-CELL LYMPHOMA; PANCREATIC-CANCER; UP-REGULATION; LUNG-CANCER; STEM-CELLS; MIR-155; PROLIFERATION; PATHWAY AB Background: Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma. Methods: The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively. Results: The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells. Conclusions: We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma. C1 [Osaka, Eiji; Choy, Edwin; Yang, Xiaoqian; Shen, Jacson K.; Yang, Pei; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. [Osaka, Eiji] Nihon Univ, Sch Med, Dept Orthopaed Surg, Tokyo 1738610, Japan. [Kelly, Andrew D.] Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. [Spentzos, Dimitrios] Beth Israel Deaconess Med Ctr, Dept Med, Sarcoma Program, Div Hematol Oncol, Boston, MA 02215 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Stephan L. Harris Fund; Chordoma Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopedic Surgery; Gattegno fund; Wechsler fund FX The authors thank Dr. Silke Bruderlein (University Hospitals of Ulm, Germany) for kindly providing the cell line, U-CH1. This project was partially supported by grants from the Stephan L. Harris Fund, and the Gattegno and Wechsler funds. Support was also provided by the Chordoma Foundation. Dr. Duan is supported, in part, through a grant from the Sarcoma Foundation of America (SFA), a grant from the National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA151452-01, a pilot grant from Sarcoma SPORE/NIH, and a grant from an Academic Enrichment Fund of MGH Orthopedic Surgery. NR 64 TC 4 Z9 4 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 20 PY 2015 VL 6 IS 11 BP 9125 EP 9139 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CN9NB UT WOS:000358774600050 PM 25823817 ER PT J AU Bill, A Gutierrez, A Kulkarni, S Kemp, C Bonenfant, D Voshol, H Duvvuri, U Gaither, LA AF Bill, Anke Gutierrez, Abraham Kulkarni, Sucheta Kemp, Carolyn Bonenfant, Debora Voshol, Hans Duvvuri, Umamaheswar Gaither, L. Alex TI ANO1/TMEM16A interacts with EGFR and correlates with sensitivity to EGFR-targeting therapy in head and neck cancer SO ONCOTARGET LA English DT Article DE epidermal growth factor receptor (EGFR); EGFR-targeted therapy; biomarker; calcium-activated chloride channel; protein-protein interaction ID GROWTH-FACTOR RECEPTOR; SQUAMOUS-CELL CARCINOMA; ACTIVATED CHLORIDE CHANNEL; INTERSTITIAL-CELLS; TYROSINE KINASES; PHASE-II; TMEM16A; EXPRESSION; PROTEIN; ANO1 AB The epidermal growth factor receptor (EGFR) contributes to the pathogenesis of head&neck squamous cell carcinoma (HNSCC). However, only a subset of HNSCC patients benefit from anti-EGFR targeted therapy. By performing an unbiased proteomics screen, we found that the calcium-activated chloride channel ANO1 interacts with EGFR and facilitates EGFR-signaling in HNSCC. Using structural mutants of EGFR and ANO1 we identified the trans/juxtamembrane domain of EGFR to be critical for the interaction with ANO1. Our results show that ANO1 and EGFR form a functional complex that jointly regulates HNSCC cell proliferation. Expression of ANO1 affected EGFR stability, while EGFR-signaling elevated ANO1 protein levels, establishing a functional and regulatory link between ANO1 and EGFR. Co-inhibition of EGFR and ANO1 had an additive effect on HNSCC cell proliferation, suggesting that co-targeting of ANO1 and EGFR could enhance the clinical potential of EGFR-targeted therapy in HNSCC and might circumvent the development of resistance to single agent therapy. HNSCC cell lines with amplification and high expression of ANO1 showed enhanced sensitivity to Gefitinib, suggesting ANO1 overexpression as a predictive marker for the response to EGFR-targeting agents in HNSCC therapy. Taken together, our results introduce ANO1 as a promising target and/or biomarker for EGFR-directed therapy in HNSCC. C1 [Bill, Anke; Gutierrez, Abraham; Gaither, L. Alex] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Kulkarni, Sucheta; Kemp, Carolyn; Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Med Ctr, Pittsburgh, PA 15213 USA. [Bonenfant, Debora; Voshol, Hans] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. [Duvvuri, Umamaheswar] VA Pittsburgh HealthCare Syst, Pittsburgh, PA 15213 USA. RP Gaither, LA (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM duvvuriu@upmc.edu; alex.gaither@novartis.com FU Department of Veterans Affairs BLSR&D PNC Foundation FX This work was supported in part by funds from the Department of Veterans Affairs BLSR&D PNC Foundation (U.D.). NR 62 TC 10 Z9 10 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 20 PY 2015 VL 6 IS 11 BP 9173 EP 9188 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CN9NB UT WOS:000358774600053 PM 25823819 ER PT J AU Gao, Y Foster, R Yang, XQ Feng, Y Shen, JK Mankin, HJ Hornicek, FJ Amiji, MM Duan, ZF AF Gao, Yan Foster, Rosemary Yang, Xiaoqian Feng, Yong Shen, Jacson K. Mankin, Henry J. Hornicek, Francis J. Amiji, Mansoor M. Duan, Zhenfeng TI Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer SO ONCOTARGET LA English DT Article DE ovarian cancer; CD44; tissue microarray; Pgp; paclitaxel ID SMALL INTERFERING RNA; PACLITAXEL RESISTANCE; MULTIDRUG-RESISTANCE; SELECTIN LIGAND; CARCINOMA CELLS; RISK-FACTORS; EXPRESSION; ADHESION; TUMORIGENICITY; IDENTIFICATION AB The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer. C1 [Gao, Yan; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K.; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K.; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gao, Yan; Yang, Xiaoqian] Zhengzhou Univ, Dept Gynecol & Obstet, Affiliated Hosp 3, Zhengzhou 450052, Henan Province, Peoples R China. [Foster, Rosemary] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Amiji, Mansoor M.] Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Gattegno fund; Wechsler fund; Sarcoma Foundation of America (SFA) a pilot grant from Sarcoma SPORE/NIH; National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA 151452]; China Scholarship Council; Excellent Doctorial Dissertations Grant of Zhengzhou University FX This work was supported in part by grants from the Gattegno and Wechsler funds. Dr. Duan is supported, in part, through a grant from the Sarcoma Foundation of America (SFA) a pilot grant from Sarcoma SPORE/NIH, and a grant from the National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452. Dr. Gao is supported by scholarship from the China Scholarship Council and Excellent Doctorial Dissertations Grant of Zhengzhou University. NR 49 TC 18 Z9 19 U1 2 U2 11 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 20 PY 2015 VL 6 IS 11 BP 9313 EP 9326 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CN9NB UT WOS:000358774600062 PM 25823654 ER PT J AU Mitsui, Y Hirata, H Arichi, N Hiraki, M Yasumoto, H Chang, I Fukuhara, S Yamamura, S Shahryari, V Deng, GR Saini, S Majid, S Dahiya, R Tanaka, Y Shiina, H AF Mitsui, Yozo Hirata, Hiroshi Arichi, Naoko Hiraki, Miho Yasumoto, Hiroaki Chang, Inik Fukuhara, Shinichiro Yamamura, Soichiro Shahryari, Varahram Deng, Guoren Saini, Sharanjot Majid, Shahana Dahiya, Rajvir Tanaka, Yuichiro Shiina, Hiroaki TI Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways SO ONCOTARGET LA English DT Article DE bone morphogenetic protein 2; renal cell carcinoma; DNA methylation; molecular marker ID CANCER CELLS; EXTERNAL VALIDATION; EXPRESSION; DIFFERENTIATION; INHIBITOR; GROWTH; METHYLATION; POPULATION; RECEPTORS; P27(KIP1) AB We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21(WAF1/CIP1) and p27(KIP1) expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2'-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC. C1 [Mitsui, Yozo; Arichi, Naoko; Hiraki, Miho; Yasumoto, Hiroaki; Shiina, Hiroaki] Shimane Univ, Fac Med, Dept Urol, Enya, Izumo, Japan. [Mitsui, Yozo; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Mitsui, Yozo; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Inik] Yonsei Univ, Coll Densitry, Dept Oral Biol, Seoul 120749, South Korea. [Fukuhara, Shinichiro] Osaka Univ, Grad Sch Med, Dept Urol, Suita, Osaka, Japan. RP Mitsui, Y (reprint author), Shimane Univ, Fac Med, Dept Urol, Enya, Izumo, Japan. EM mitsui@med.shimane-u.ac.jp FU National Center for Research Resources of the NIH [RO1CA130860]; VA Merit Review and VA Program Project FX Address all correspondence and requests for Yozo Mitsui, MD, PhD, Departments of Urology, Shimane University Faculty of Medicine, 89-1 Enya-cho, 693-8501 Izumo, Japan. E-mail: mitsui@med.shimane-u.ac.jp. We thank Dr. Roger Erickson for his support and assistance with the preparation of the manuscript. This research study was supported by the National Center for Research Resources of the NIH through Grant Number RO1CA130860 and VA Merit Review and VA Program Project. NR 42 TC 3 Z9 3 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 20 PY 2015 VL 6 IS 11 BP 9577 EP 9591 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CN9NB UT WOS:000358774600083 PM 25797254 ER PT J AU Morris, MJ Molina, A Small, EJ de Bono, JS Logothetis, CJ Fizazi, K de Souza, P Kantoff, PW Higano, CS Li, JH Kheoh, T Larson, SM Matheny, SL Naini, V Burzykowski, T Griffin, TW Scher, HI Ryan, CJ AF Morris, Michael J. Molina, Arturo Small, Eric J. de Bono, Johann S. Logothetis, Christopher J. Fizazi, Karim de Souza, Paul Kantoff, Philip W. Higano, Celestia S. Li, Jinhui Thian Kheoh Larson, Steven M. Matheny, Shannon L. Naini, Vahid Burzykowski, Tomasz Griffin, Thomas W. Scher, Howard I. Ryan, Charles J. TI Radiographic Progression-Free Survival As a Response Biomarker in Metastatic Castration-Resistant Prostate Cancer: COU-AA-302 Results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ABIRATERONE ACETATE; CLINICAL-TRIALS; END-POINTS; CHEMOTHERAPY; PREDNISONE; PHASE-3; MEN AB Purpose Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods rPFS was defined as two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, two new confirmed lesions on any scan 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials. (C) 2015 by American Society of Clinical Oncology C1 [Morris, Michael J.; Larson, Steven M.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Morris, Michael J.; Larson, Steven M.; Scher, Howard I.] Weill Cornell Med Coll, New York, NY USA. [Molina, Arturo; Thian Kheoh; Matheny, Shannon L.; Naini, Vahid; Griffin, Thomas W.] Janssen Res & Dev, Los Angeles, CA USA. [Small, Eric J.; Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 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. [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Villejuif, France. [de Souza, Paul] Univ Western Sydney, Sch Med, Ingham Inst, Liverpool, Merseyside, England. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Li, Jinhui] Janssen Res & Dev, Raritan, NJ USA. [Burzykowski, Tomasz] Int Inst Drug Dev, Louvain La Neuve, Belgium. RP Morris, MJ (reprint author), Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10065 USA. EM morrism@mskcc.org OI Morris, Michael J./0000-0002-9454-0096 FU Ortho Biotech Oncology Research and Development (unit of Cougar Biotechnology, now Janssen Research Development); Prostate Cancer Clinical Trials Consortium - Department of Defense FX Supported by Ortho Biotech Oncology Research and Development (unit of Cougar Biotechnology, now Janssen Research & Development), by the Prostate Cancer Clinical Trials Consortium, sponsored by the Department of Defense, and by Janssen Global Services, which provided writing assistance. NR 26 TC 27 Z9 27 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 APR 20 PY 2015 VL 33 IS 12 BP 1356 EP + DI 10.1200/JCO.2014.55.3875 PG 9 WC Oncology SC Oncology GA CK2RH UT WOS:000356058800009 PM 25624432 ER PT J AU Goel, S Krop, IE AF Goel, Shom Krop, Ian E. TI Deciphering the Role of Phosphatidylinositol 3-Kinase Mutations in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TRASTUZUMAB RESISTANCE; ADJUVANT TRASTUZUMAB; ANTI-HER2 THERAPIES; PIK3CA MUTATIONS; HER2 RECEPTOR; BENEFIT; TRIAL; INHIBITION; CELLS; PTEN C1 [Goel, Shom; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goel, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ikrop@partners.org NR 40 TC 3 Z9 3 U1 0 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 APR 20 PY 2015 VL 33 IS 12 BP 1407 EP + DI 10.1200/JCO.2014.60.0742 PG 5 WC Oncology SC Oncology GA CK2RH UT WOS:000356058800015 PM 25800754 ER PT J AU Huang, XY Liu, W Hooker, JM Groves, JT AF Huang, Xiongyi Liu, Wei Hooker, Jacob M. Groves, John T. TI Targeted Fluorination with the Fluoride Ion by Manganese-Catalyzed Decarboxylation SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE decarboxylation; fluoride; fluorination; labeling with F-18; manganese porphyrins ID C-H FLUORINATION; POSITRON-EMISSION-TOMOGRAPHY; CARBOXYLIC-ACIDS; LATE-STAGE; OXIDATIVE DECARBOXYLATION; ALLYLIC FLUORINATION; POTASSIUM FLUORIDE; DRUG-METABOLISM; MODEL SYSTEMS; PET AB We describe the first catalytic decarboxylative fluorination reaction based on the nucleophilic fluoride ion. The reported method allows the facile replacement of various aliphatic carboxylic acid groups with fluorine. Moreover, the potential of this method for PET imaging has been demonstrated by the successful F-18 labeling of a variety of carboxylic acids with radiochemical conversions up to 50%, representing a targeted decarboxylative F-18 labeling method with no-carrier-added [F-18] fluoride. Mechanistic probes suggest that the reaction proceeds through the interaction of the manganese catalyst with iodine(III) carboxylates formed in situ from iodosylbenzene and the carboxylic acid substrates. C1 [Huang, Xiongyi; Liu, Wei; Groves, John T.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. [Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Cambridge, MA 02138 USA. RP Groves, JT (reprint author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. EM jtgroves@princeton.edu RI Huang, Xiongyi/H-3079-2013 FU US National Science Foundation [CHE-1148597]; Center for Catalytic Hydrocarbon Functionalization, an Energy Frontier Research Center, U.S. Department of Energy, Office of Science, Basic Energy Sciences [DE SC0001298]; Center for Functional Neuroimaging Technologies [P41EB015896, S10RR017208, S10RR023452]; Howard Hughes Medical Institute; Merck, Inc. FX This research was supported by the US National Science Foundation award CHE-1148597 (J.T.G.) and in part by the Center for Catalytic Hydrocarbon Functionalization, an Energy Frontier Research Center, U.S. Department of Energy, Office of Science, Basic Energy Sciences, under Award No. DE SC0001298 (J.T.G.). A portion of this research was carried out at the Martinos Center for Biomedical Imaging using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, and shared instrumentation grants S10RR017208 and S10RR023452. X.H. thanks the Howard Hughes Medical Institute for fellowship support. W.L. thanks Merck, Inc. for fellowship support. NR 61 TC 33 Z9 34 U1 15 U2 89 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD APR 20 PY 2015 VL 54 IS 17 BP 5241 EP 5245 DI 10.1002/anie.201500399 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CH7BO UT WOS:000354190800050 PM 25736895 ER PT J AU Giri, J Parikh, SA Kennedy, KF Weinberg, I Donaldson, C Hawkins, BM McCormick, DJ Jackson, B Armstrong, EJ Ramchand, P White, CJ Jaff, MR Rosenfield, K Yeh, RW AF Giri, Jay Parikh, Sahil A. Kennedy, Kevin F. Weinberg, Ido Donaldson, Cameron Hawkins, Beau M. McCormick, Daniel J. Jackson, Benjamin Armstrong, Ehrin J. Ramchand, Preethi White, Christopher J. Jaff, Michael R. Rosenfield, Kenneth Yeh, Robert W. TI Proximal Versus Distal Embolic Protection for Carotid Artery Stenting A National Cardiovascular Data Registry Analysis SO JACC-Cardiovascular Interventions LA English DT Article DE carotid artery stenosis; carotid artery stenting; embolic protection devices; stroke ID CEREBRAL PROTECTION; RANDOMIZED-TRIAL; DEVICES AB OBJECTIVES The aim of this study was to compare the stroke/death rates between proximal embolic protection devices (P-EPDs) and distal filter embolic protection devices (F-EPDs) in elective carotid artery stenting (CAS). BACKGROUND P-EPDs have theoretical advantages that may make them superior to F-EPDs for stroke prevention during CAS. METHODS We examined 10,246 consecutive elective CAS procedures performed with embolic protection in the NCDR CARE registry between January 2009 and March 2013. We analyzed crude and propensity-matched rates of in-hospital combined death/stroke in patients treated with P-EPDs versus F-EPDs. Secondary analyses included 30-day adverse event rates and stroke rates by the involved cerebrovascular territory. RESULTS P-EPDs were used in 590 of 10,246 cases (5.8%). Patients treated with P-EPDs had higher rates of symptomatic lesion status (46.8% vs. 39.7%, p < 0.001), atrial fibrillation/flutter (16.1% vs. 13.0%, p = 0.03), and history of a neurological event (51.2% vs. 46.6%, p = 0.03). In unadjusted and propensity-matched analyses, differences in in-hospital stroke/death between P-EPD and F-EPD cohorts were nonsignificant (1.5% vs. 2.4%, p = 0.16 and 1.6% vs. 2.0%, p = 0.56, respectively). For patients with available data (n = 7,693, 75.1%), 30-day adverse events rates were similar for P-EPDs and F-EPDs before (2.5% vs. 4.2%, p = 0.07) and after (2.7% vs. 4.0%, p = 0.22) propensity matching. CONCLUSIONS Use of a P-EPD during CAS was associated with low rates of in-hospital stroke/death similar to those with an F-EPD in the first comparative effectiveness study of the devices. An adequately powered randomized trial comparing clinical outcomes between these devices is unlikely to be feasible. (C) 2015 by the American College of Cardiology Foundation. C1 [Giri, Jay; McCormick, Daniel J.] Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Parikh, Sahil A.] Univ Hosp Cleveland, Harrington Heart & Vasc Inst, Cleveland, OH 44106 USA. [Parikh, Sahil A.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Kennedy, Kevin F.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, KS USA. [Weinberg, Ido; Donaldson, Cameron; Jaff, Michael R.; Rosenfield, Kenneth; Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Heart Vasc & Stroke Care, Boston, MA USA. [Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Cardiovasc Sect, Oklahoma City, OK USA. [Jackson, Benjamin] Univ Penn, Perelman Sch Med, Div Vasc Surg, Philadelphia, PA 19104 USA. [Armstrong, Ehrin J.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. [Ramchand, Preethi] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [White, Christopher J.] John Ochsner Heart & Vasc Inst, Ochsner Med Ctr, New Orleans, LA USA. RP Giri, J (reprint author), Hosp Univ Penn, Div Cardiovasc Med, 9th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Giri.jay@gmail.com RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 12 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD APR 20 PY 2015 VL 8 IS 4 BP 609 EP 615 DI 10.1016/j.jcin.2015.02.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5PO UT WOS:000353345300021 PM 25907088 ER PT J AU Sunaguchi, N Yuasa, T Sun, FR Gupta, R Ando, M AF Sunaguchi, Naoki Yuasa, Tetsuya Sun, Fengrong Gupta, Rajiv Ando, Masami TI Limited view reconstruction for differential phase-contrast computed tomography SO OPTICS EXPRESS LA English DT Article ID GRADIENT VECTOR-FIELD; DARK-FIELD; REFRACTION-CONTRAST; INDEX; PRINCIPLES; ALGORITHM; ANALYZER; BREAST; CT AB This paper describes an algebraic reconstruction algorithm that uses total variation (TV) regularization for differential phase contrast computed tomography (DPC-CT) using a limited number of views. In order to overcome over-flattening inherent in TV regularization, a two-step reconstruction process is used: we first reconstruct tomographic images of gradient refractive index from differential projections with TV regularization; these images are then used to compute tomographic images of refractive index by solving the Poisson equation. We incorporate TV regularization in the reconstruction process because the distribution of gradient refractive index is much more flattened than the refractive index. Simulations of the proposed method demonstrate that it can achieve satisfactory image quality from a much smaller number of projections than is required by the Nyquist sampling theorem. We experimentally prove the feasibility of the proposed method using dark field imaging optics at PF-14C beamline at the Photon Factory, KEK. The differential phase contrast projection data was experimentally acquired from a biological sample and DPC-CT images were reconstructed. We show that far fewer projections are needed when the proposed algorithm is used. (C) 2015 Optical Society of America C1 [Sunaguchi, Naoki] Gunma Univ, Grad Sch Engn, Kiryu, Gumma 3768515, Japan. [Yuasa, Tetsuya] Yamagata Univ, Grad Sch Engn & Sci, Yonezawa, Yamagata 9928510, Japan. [Sun, Fengrong] Shandong Univ, Sch Informat Sci & Engn, Jinan, Shandong, Peoples R China. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gupta, Rajiv] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ando, Masami] Tokyo Univ Sci, Res Inst Sci & Technol, Noda, Chiba 2788510, Japan. RP Sunaguchi, N (reprint author), Gunma Univ, Grad Sch Engn, Kiryu, Gumma 3768515, Japan. EM sunaguchi@gunma-u.ac.jp FU Japanese Ministry of Education Science and Culture [23602002, 26350494, 26750142]; JGC-S scholarship foundation; Sumitomo Foundation; Yazaki Memorial Foundation FX This research was partially supported by a Grant-In-Aid for Scientific Research (#23602002, #26350494, #26750142) from the Japanese Ministry of Education Science and Culture, JGC-S scholarship foundation, Sumitomo Foundation, and Yazaki Memorial Foundation for Science and Technology. The experiment was performed under the auspices of KEK (2014G002). NR 26 TC 2 Z9 2 U1 2 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD APR 20 PY 2015 VL 23 IS 8 BP 9717 EP 9729 DI 10.1364/OE.23.009717 PG 13 WC Optics SC Optics GA CG4ZY UT WOS:000353299300018 PM 25969010 ER PT J AU Ogdie, A Pang, WG Forde, KA Samir, BD Mulugeta, L Chang, KM Kaplan, DE Amorosa, VK Kostman, JR Reddy, RK Schumacher, RH Lo Re, V AF Ogdie, Alexis Pang, Wyki Gina Forde, Kimberly A. Samir, Bhangle D. Mulugeta, Lakeisha Chang, Kyong-Mi Kaplan, David E. Amorosa, Valerianna K. Kostman, Jay R. Reddy, Rajender K. Schumacher, Ralph H. Lo Re, Vincent, III TI Prevalence and risk factors for patient-reported joint pain among patients with HIV/Hepatitis C coinfection, Hepatitis C monoinfection, and HIV monoinfection SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Hepatitis c; HIV; Arthralgia; Epidemiology ID HEALTH-ASSESSMENT QUESTIONNAIRE; RHEUMATIC-DISEASES; VIRUS-INFECTION; ROUTINE ASSESSMENT; INDEX; MDHAQ; CARE; MANIFESTATIONS; FIBROMYALGIA; SYMPTOMS AB Background: To determine the prevalence of patient-reported joint pain among patients with human immunodeficiency virus (HIV)/chronic hepatitis C virus (HCV) coinfection, chronic HCV monoinfection, and HIV monoinfection followed in hepatology and infectious disease outpatient practices. Methods: Standardized interviews were performed among 79 HIV/HCV-coinfected, 93 HCV-monoinfected, and 30 HIV-monoinfected patients in a cross-sectional study within hepatology and infectious disease clinics at three centers. The Multi-Dimensional Health Assessment Questionnaire was used to ascertain joint pain and associated symptoms. Information on potential risk factors for joint pain was obtained during the interview and by chart review. Logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of joint pain associated with risk factors of interest among chronic HCV-infected and HIV-infected patients. Results: Joint pain was more commonly reported in HCV-monoinfected than HIV/HCV-coinfected (71% versus 56%; p = 0.038) and HIV-monoinfected (71% versus 50%; p = 0.035) patients. A previous diagnosis of arthritis and current smoking were risk factors for joint pain among HCV-infected patients (arthritis: aOR, 4.25; 95% CI, 1.84-9.81; smoking: aOR, 5.02; 95% CI, 2.15-11.74) and HIV-infected (arthritis: aOR, 5.36; 95% CI, 2.01-14.25; smoking: aOR, 6.07; 95% CI, 2.30-16.00) patients. Conclusion: Patient-reported joint pain was prevalent among all three groups, but more common among chronic HCV-monoinfected than either HIV/HCV-coinfected or HIV-monoinfected patients. A prior diagnosis of arthritis and current smoking were risk factors for patient-reported joint pain among both HCV-infected and HIV-infected patients. C1 [Ogdie, Alexis] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Div Rheumatol, Philadelphia, PA 19104 USA. [Pang, Wyki Gina] Tufts Univ, Sch Med, Maine Med Ctr, Portland, ME USA. [Forde, Kimberly A.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Med,Div Gastroenterol, Philadelphia, PA 19104 USA. [Samir, Bhangle D.] Seacoast Arthrit & Osteoporosis Ctr, Dover, NH 03820 USA. [Mulugeta, Lakeisha] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Kyong-Mi; Kaplan, David E.] Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Div Gastroenterol, Philadelphia, PA 19104 USA. [Amorosa, Valerianna K.; Kostman, Jay R.] Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Div Infect Dis, Philadelphia, PA 19104 USA. [Reddy, Rajender K.] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Schumacher, Ralph H.] Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Med,Div Infect Dis, Philadelphia, PA 19104 USA. RP Ogdie, A (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Div Rheumatol, Penn Tower Room 1407,1 Convent Ave, Philadelphia, PA 19104 USA. EM Alexis.ogdie@uphs.upenn.edu RI Lo Re, Vincent/N-7817-2015; OI Ogdie, Alexis/0000-0002-4639-0775 FU American College of Rheumatology Research Foundation Ephram Engleman Preceptorship Award; American College of Rheumatology Research Foundation Investigator Award; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23 AR063764]; National Institute of Allergy and Infectious Diseases [K01 AI 070001] FX We would like to thank Janet Dinella and Yihui Connie Jiang for administrative support and Melissa Nezamzadeh for assistance with database management. This study was funded by the American College of Rheumatology Research Foundation Ephram Engleman Preceptorship Award. During this study, Dr. Ogdie was supported by an American College of Rheumatology Research Foundation Investigator Award and research grant K23 AR063764 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Dr. Lo Re was supported by research grant K01 AI 070001 from the National Institute of Allergy and Infectious Diseases. NR 31 TC 1 Z9 1 U1 3 U2 3 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 APR 19 PY 2015 VL 16 AR 93 DI 10.1186/s12891-015-0552-z PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CG3QB UT WOS:000353193600001 PM 25896674 ER PT J AU Gale, RC Asch, SM Taylor, T Nelson, KM Luck, J Meredith, LS Helfrich, CD AF Gale, Randall C. Asch, Steven M. Taylor, Thomas Nelson, Karin M. Luck, Jeff Meredith, Lisa S. Helfrich, Christian D. TI The most used and most helpful facilitators for patient-centered medical home implementation SO Implementation Science LA English DT Article DE Patient-centered medical home; Implementation resources; Provider self-efficacy ID PRIMARY-CARE; HEALTH; LESSONS; SUPPORT; HISTORY AB Background: Like other transformative healthcare initiatives, patient-centered medical home (PCMH) implementation requires substantial investments of time and resources. Even though PCMH and PCMH-like models are being implemented by multiple provider practices and health systems, little is known about what facilitates their implementation. The purpose of this study was to assess which PCMH-implementation resources are most widely used, by whom, and which resources primary care personnel find most helpful. Methods: This study is an analysis of data from a cross-sectional survey of primary care personnel in the Veterans Health Administration in 2012, in which respondents were asked to rate whether they were aware of and accessed PCMH-implementation resources, and to rate their helpfulness. Logistic regression was used to produce odds ratios for the outcomes (1) resource use and (2) resource helpfulness. Respondents were nested within clinics, nested, in turn, within 135 parent hospitals. Results: Teamlet huddles were the most widely accessed (80.4% accessed) and most helpful (90.4% rated helpful) resource; quality-improvement methods to conduct small tests of change were the least frequently accessed (42.4% accessed) resource though two-thirds (66.7%) of users reported as helpful. Supervisors were significantly more likely (ORs, 1.46 to 1.86) to use resources than non-supervisors but were less likely to rate the majority (8 out of 10) of resources as "somewhat/very helpful" than non-supervisors (ORs, 0.72 to 0.84). Longer-tenured employees tended to rate resources as more helpful. Conclusions: These findings are the first in the PCMH literature that we are aware of that systematically assesses primary care staff's access to and the helpfulness of PCMH implementation resources. Supervisors generally reported greater access to resources, relative to non-supervisors, but rated resources as less helpful, suggesting that information about them may not have been optimally disseminated. Knowing what resources primary care staff use and find helpful can inform administrators' and policymakers' investments in PCMH-implementation resources. The implications of our model extend beyond just PCMH implementation but also to considerations when providing implementation resources for other complex quality-improvement initiatives. C1 [Gale, Randall C.; Asch, Steven M.; Taylor, Thomas] Ctr Innovat Implementat Ci2i, VA Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA. [Asch, Steven M.] Stanford Univ, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. [Nelson, Karin M.; Helfrich, Christian D.] US Dept Vet Affairs, Seattle Denver Ctr Innovat Vet Ctr & Value Driven, Seattle, WA USA. [Nelson, Karin M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Nelson, Karin M.; Helfrich, Christian D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Luck, Jeff] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. [Meredith, Lisa S.] VA HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. [Meredith, Lisa S.] RAND Corp, Santa Monica, CA USA. RP Gale, RC (reprint author), Ctr Innovat Implementat Ci2i, VA Palo Alto Hlth Care Syst, 790 Willow Rd, Menlo Pk, CA 94025 USA. EM Randall.Gale@va.gov NR 31 TC 2 Z9 2 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD APR 19 PY 2015 VL 10 AR 52 DI 10.1186/s13012-015-0246-9 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CG9RW UT WOS:000353657900001 PM 25924611 ER PT J AU Powell, RA Emanuel, L Handzo, G Lantos, J Dunn, LB Idler, EL Wilkie, DJ Massey, K Summerfelt, WT Barnes, MJD Quest, TE Kestenbaum, A Steinhauser, K Fitchett, G Zollfrank, A Olsen, AK Balboni, TA Sommer, D AF Powell, Richard A. Emanuel, Linda Handzo, George Lantos, John Dunn, Laura B. Idler, Ellen L. Wilkie, Diane J. Massey, Kevin Summerfelt, William T. Barnes, Marilyn J. D. Quest, Tammie E. Kestenbaum, Allison Steinhauser, Karen Fitchett, George Zollfrank, Angelika Olsen, Annette K. Balboni, Tracy A. Sommer, Dane TI Transcending differences to study the transcendent: an exploratory study of researchers' and chaplains' reflections on interdisciplinary spiritual care research collaboration SO BMC PALLIATIVE CARE LA English DT Article DE Spiritual; Care; Biomedical; Interdisciplinary; Collaboration ID PALLIATIVE CARE; QUALITY AB Background: Despite recognition of the centrality of professional board-certified chaplains (BCC) in palliative care, the discipline has little research to guide its practices. To help address this limitation, HealthCare Chaplaincy Network funded six proposals in which BCCs worked collaboratively with established researchers. Recognizing the importance of interdisciplinary collaboration in the development of a new field, this paper reports on an exploratory study of project members' reflections over time on the benefits and challenges of conducting inter-disciplinary spiritual care research. Methods: Data collection occurred in two stages. Stage 1 entailed two independent, self-reflective focus groups, organized by professional discipline, mid-way through the site projects. Stage 2 entailed end-of-project site reports and a conference questionnaire. Results: Eighteen professionals participated in the group discussions. Stage 1: researchers perceived chaplains as eager workers passionately committed to their patients and to research, and identified challenges faced by chaplains in learning to conduct research. Chaplains perceived researchers as passionate about their work, were concerned research might uncover negative findings for their profession, and sensed they used a dissimilar paradigm from their research colleagues regarding the 'ways of relating' to knowledge and understanding. Stage 2: researchers and chaplains noted important changes they ascribed to the interdisciplinary collaboration that were classified into six domains of cultural and philosophical understanding: respect; learning; discovery; creativity; fruitful partnerships; and learning needs. Conclusions: Chaplains and researchers initially expressed divergent perspectives on the research collaborations. During the projects' lifespans, these differences were acknowledged and addressed. Mutual appreciation for each discipline's strengths and contributions to inter-professional dialogue emerged. C1 [Powell, Richard A.] HealthCare Chaplaincy Network, Res, New York, NY 10006 USA. [Emanuel, Linda] HealthCare Chaplaincy Network, Res & Educ, New York, NY 10006 USA. [Emanuel, Linda] Northwestern Univ, Feinberg Sch Med, Geriatr Med, Chicago, IL 60611 USA. [Emanuel, Linda] Northwestern Univ, Feinberg Sch Med, Buehler Ctr Aging Hlth & Soc, Chicago, IL 60611 USA. [Handzo, George] HealthCare Chaplaincy Network, Hlth Serv Res & Qual, New York, NY 10006 USA. [Lantos, John] Childrens Mercy Hosp, Pediat, Kansas City, MO 64108 USA. [Lantos, John] Univ Missouri, Kansas City, MO 64110 USA. [Dunn, Laura B.] Univ Calif San Francisco, Dept Psychiat, UCSF Helen Diller Family Comprehens Canc Ctr, Psychiat, San Francisco, CA USA. [Idler, Ellen L.] Emory Univ, Atlanta, GA 30322 USA. [Wilkie, Diane J.] Univ Illinois, Coll Nursing, Dept Biobehav Hlth Sci, Ctr Excellence End Of Life Transit Res, Chicago, IL USA. [Massey, Kevin] Advocate Lutheran Gen Hosp, Miss & Spiritual Care, Chicago, IL USA. [Summerfelt, William T.] Downers Grove, Advocate Hlth Care, Chicago, IL USA. [Barnes, Marilyn J. D.] Advocate Lutheran Gen Hosp, Dept Miss & Spiritual Care, Chicago, IL USA. [Quest, Tammie E.] Emory Univ, Emory Palliat Care Ctr, Atlanta, GA 30322 USA. [Kestenbaum, Allison] Jewish Theol Seminary, Ctr Pastoral Educ, Assoc Clin Pastoral Educ, New York, NY USA. [Steinhauser, Karen] Duke Univ, Dept Med, Durham, NC 27706 USA. [Fitchett, George] Rush Univ, Med Ctr, Coll Hlth Sci, Dept Relig Hlth & Human Values, Chicago, IL 60612 USA. [Zollfrank, Angelika] Yale New Haven Med Ctr, Clin Pastoral Educ, New Haven, CT 06504 USA. [Olsen, Annette K.] Duke Univ, Med Ctr, Clin Adm Chaplain, Durham, NC USA. [Balboni, Tracy A.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Sommer, Dane] Childrens Mercy Hosp, Chaplaincy Serv, Kansas City, MO 64108 USA. RP Emanuel, L (reprint author), HealthCare Chaplaincy Network, Res & Educ, 65 Broadway,12th Floor, New York, NY 10006 USA. EM l-emanuel@northwestern.edu FU John Templeton Foundation [22399] FX The authors acknowledge the contribution of the following to the development of this paper: George H. Grant, Shoshanna Sofaer, Kenneth I. Pargament and Dylan M. Smith. The authors also thank Mary Ellen Hudson, at Children's Mercy Hospital, Kansas City, Missouri, and Carolyn Sebron at HealthCare Chaplaincy Network, New York, for their invaluable support with this study. Financial support for this initiative was provided by the John Templeton Foundation (grant reference number 22399). The funder played no role in the design, collection, analysis, and interpretation of data, or in the writing of the manuscript and the decision to submit the manuscript for publication. NR 10 TC 0 Z9 0 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-684X J9 BMC PALLIAT CARE JI BMC Palliat. Care PD APR 18 PY 2015 VL 14 AR 12 DI 10.1186/s12904-015-0004-4 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CG2KZ UT WOS:000353104800001 PM 25927207 ER PT J AU Graber, DJ Costine, BA Hickey, WF AF Graber, David J. Costine, Beth A. Hickey, William F. TI Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets SO Journal of Neuroinflammation LA English DT Article DE Cytokines; Cerebral cortex; Chemokines; Injury; Mouse; Pig; Prostaglandin-endoperoxide synthase-2; Slice ID CLOSED-HEAD INJURY; SYSTEM AB Background: The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression. Methods: To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury. Results: Interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical slices. Chemokine and PTGS2 mRNAs remained elevated in slices at 24 h, whereas IL-1 beta and TNF-alpha expressions decreased from earlier peak levels. At 24 h after cortical injury in 1-month-old piglets, the expression of CCL2 mRNA was significantly increased in the lesion core and in the penumbra region. The expression of PTGS2, IL-1 beta, and TNF-alpha was variable among the piglets. Conclusions: These in vitro and large animal models of cortical injury expand our understanding of the early timing and spread of the immunological response and can serve as preclinical systems to facilitate the discovery of therapeutic agents for TBI aimed at regulating inflammatory mediator expression. C1 [Graber, David J.; Hickey, William F.] Geisel Sch Med Dartmouth, Dept Pathol, Lebanon, NH 03756 USA. [Costine, Beth A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Costine, Beth A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Graber, DJ (reprint author), Geisel Sch Med Dartmouth, Dept Pathol, One Med Ctr Dr, Lebanon, NH 03756 USA. EM David.J.Graber@Dartmouth.Edu FU Hitchcock Foundation (Geisel School of Medicine at Dartmouth); Nicholas T. Zervas Chair Fund (Harvard Medical School); Hitchcock Foundation (Dartmouth-Hitchcock Medical Center) FX This research was supported in part by a grant from the Hitchcock Foundation (Geisel School of Medicine at Dartmouth and the Dartmouth-Hitchcock Medical Center) and Nicholas T. Zervas Chair Fund (Harvard Medical School). NR 30 TC 4 Z9 4 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD APR 18 PY 2015 VL 12 AR 76 DI 10.1186/s12974-015-0298-4 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CG4PQ UT WOS:000353269000002 PM 25895671 ER PT J AU Pery, E Sheehy, A Nebane, NM Brazier, AJ Misra, V Rajendran, KS Buhrlage, SJ Mankowski, MK Rasmussen, L White, EL Ptak, RG Gabuzda, D AF Pery, Erez Sheehy, Ann Nebane, N. Miranda Brazier, Andrew Jay Misra, Vikas Rajendran, Kottampatty S. Buhrlage, Sara J. Mankowski, Marie K. Rasmussen, Lynn White, E. Lucile Ptak, Roger G. Gabuzda, Dana TI Identification of a Novel HIV-1 Inhibitor Targeting Vif-dependent Degradation of Human APOBEC3G Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Antiviral Agent; Cytidine Deaminase; High Throughput Screening (HTS); Human Immunodeficiency Virus (HIV); Viral Protein; Virology ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRION INFECTIVITY FACTOR; E3 UBIQUITIN LIGASE; SMALL-MOLECULE INHIBITION; AMINO-ACID-RESIDUES; CD4(+) T-CELLS; CYTIDINE DEAMINATION; ANTIVIRAL ACTIVITY; SOCS-BOX; CBF-BETA AB Background: The interaction between HIV Vif protein and innate antiviral factor APOBEC3G represents a potential therapeutic target. Results: Screening for inhibitors of Vif-APOBEC3G interaction identified a small molecule, N.41, that protects APOBEC3G from Vif-mediated degradation and exhibits antiviral activity. Conclusion: N.41 is a lead for further development as an antiviral. Significance: These findings suggest new strategies for developing anti-HIV therapeutics. APOBEC3G (A3G) is a cellular cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA and by deamination-independent mechanisms. HIV-1 Vif binds to A3G, resulting in its degradation via the 26 S proteasome. Therefore, this interaction represents a potential therapeutic target. To identify compounds that inhibit interaction between A3G and HIV-1 Vif in a high throughput format, we developed a homogeneous time-resolved fluorescence resonance energy transfer assay. A 307,520 compound library from the NIH Molecular Libraries Small Molecule Repository was screened. Secondary screens to evaluate dose-response performance and off-target effects, cell-based assays to identify compounds that attenuate Vif-dependent degradation of A3G, and assays testing antiviral activity in peripheral blood mononuclear cells and T cells were employed. One compound, N.41, showed potent antiviral activity in A3G(+) but not in A3G(-) T cells and had an IC50 as low as 8.4 m and a TC50 of >100 m when tested against HIV-1(Ba-L) replication in peripheral blood mononuclear cells. N.41 inhibited the Vif-A3G interaction and increased cellular A3G levels and incorporation of A3G into virions, thereby attenuating virus infectivity in a Vif-dependent manner. N.41 activity was also species- and Vif-dependent. Preliminary structure-activity relationship studies suggest that a hydroxyl moiety located at a phenylamino group is critical for N.41 anti-HIV activity and identified N.41 analogs with better potency (IC50 as low as 4.2 m). These findings identify a new lead compound that attenuates HIV replication by liberating A3G from Vif regulation and increasing its innate antiviral activity. C1 [Pery, Erez; Brazier, Andrew Jay; Misra, Vikas; Rajendran, Kottampatty S.; Gabuzda, Dana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Buhrlage, Sara J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pery, Erez; Rajendran, Kottampatty S.] 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), CLS 1010,450 Brookline Ave, Boston, MA 02215 USA. EM dana_gabuzda@dfci.harvard.edu FU 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 high throughput screening and Dr. Marintha Heil, Southern Research Institute Department of Infectious Disease Research, for helpful discussions and advice. 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 70 TC 10 Z9 11 U1 0 U2 10 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 APR 17 PY 2015 VL 290 IS 16 BP 10504 EP 10517 DI 10.1074/jbc.M114.626903 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG4FU UT WOS:000353241100049 PM 25724652 ER PT J AU Lin, TY Ebb, DH Boepple, PA Thiele, EA Rincon, SP Mordes, DA AF Lin, Ting-Yi Ebb, David H. Boepple, Paul A. Thiele, Elizabeth A. Rincon, Sandra P. Mordes, Daniel A. TI Case 12-2015: A Newborn Boy with Respiratory Distress, Lethargy, and Hypernatremia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MECONIUM ASPIRATION SYNDROME; BECKWITH-WIEDEMANN-SYNDROME; CONGENITAL BRAIN-TUMORS; CLINICAL-COURSE; RHABDOID TUMOR; RISK-FACTORS; INFANTS; INTRAPARTUM; MANAGEMENT; CHILDREN C1 [Lin, Ting-Yi; Ebb, David H.; Boepple, Paul A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rincon, Sandra P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mordes, Daniel A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lin, Ting-Yi; Ebb, David H.; Boepple, Paul A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Thiele, Elizabeth A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Rincon, Sandra P.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mordes, Daniel A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lin, TY (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 34 TC 1 Z9 2 U1 0 U2 3 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 APR 16 PY 2015 VL 372 IS 16 BP 1550 EP 1562 DI 10.1056/NEJMcpc1400837 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA CF9BL UT WOS:000352856500012 PM 25875261 ER PT J AU Ferreira, AR Saini, KS Metzger, O AF Ferreira, Arlindo R. Saini, Kamal S. Metzger-Filho, Otto TI Treatment of early-stage HER2+ breast cancer-an evolving field SO ECANCERMEDICALSCIENCE LA English DT Article DE breast neoplasm; trastuzumab; neoadjuvant therapy; adjuvant therapy; antibodies; monoclonal; humanised ID RANDOMIZED PHASE-3 TRIAL; PARALLEL HER2-NEGATIVE COHORT; CONTROLLED SUPERIORITY TRIAL; PERTUZUMAB PLUS TRASTUZUMAB; ADJUVANT TRASTUZUMAB; OPEN-LABEL; NEOADJUVANT THERAPY; CONCURRENT TRASTUZUMAB; CARDIAC SAFETY; NSABP B-31 AB The evolving field of HER2-targeted therapy has significantly improved the outcome of women diagnosed with HER2-positive invasive breast cancer. In this review, we sought to summarise the efficacy of trastuzumab-based regimens in the adjuvant and neoadjuvant setting with a special emphasis on relevant clinical questions: treatment duration, sequence of trastuzumab administration, toxicity, the role of anthracycline-based regimens, and optimal management of small HER2+ tumours. Controversial topics are discussed taking into consideration the development of modern anti-HER2 agents. C1 [Ferreira, Arlindo R.; Metzger-Filho, Otto] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ferreira, Arlindo R.] Univ Lisbon, Hosp Santa Maria, P-1649035 Lisbon, Portugal. [Ferreira, Arlindo R.] Univ Lisbon, Inst Med Mol, P-1649035 Lisbon, Portugal. [Saini, Kamal S.] Univ Libre Bruxelles, Inst Jules Bordet, B-1000 Brussels, Belgium. RP Metzger, O (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM otto_metzger@dfci.harvard.edu OI Ferreira, Arlindo/0000-0002-1567-9322 NR 56 TC 5 Z9 5 U1 1 U2 2 PU CANCER INTELLIGENCE LTD PI BRISTOL PA 11 ALMA VALE RD,, BRISTOL, BS8 2HL, ENGLAND SN 1754-6605 J9 ECANCERMEDICALSCIENC JI eCancerMedicalScience PD APR 16 PY 2015 VL 9 AR 523 DI 10.3332/ecancer.2015.523 PG 15 WC Oncology SC Oncology GA CQ4YR UT WOS:000360611000001 PM 25932047 ER PT J AU Wolach, O Stone, RM AF Wolach, Ofir Stone, Richard M. TI How I treat mixed-phenotype acute leukemia SO BLOOD LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BIPHENOTYPIC ACUTE-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; AMBIGUOUS LINEAGE; CLINICAL CHARACTERISTICS; LYMPHOID LEUKEMIA; ADULT PATIENTS; CASE SERIES; STEM-CELLS; EXPRESSION AB Mixed-phenotype acute leukemia (MPAL) encom passes a heterogeneous group of rare leukemias in which assigning a single lineage of origin is not possible. A variety of different terms and classification systems have been used historically to describe this entity. MPAL is currently defined by a limited set of lineage-specific markers proposed in the 2008 World Health Organization monograph on classification of tumors of hematopoietic and lymphoid tissues. In adult patients, MPAL is characterized by relative therapeutic resistance that may be attributed in part to the high proportion of patients with adverse cytogenetic abnormalities. No prospective, controlled trials exist to guide therapy. The limited available data suggest that an "acute lymphoblastic leukemia-like" regimen followed by allogeneic stem-cell transplant may be advisable; addition of a tyrosine kinase inhibitor in patients with t(9; 22) translocation is recommended. The role of immunophenotypic and genetic markers in guiding chemotherapy choice and postremission strategy, as well as the utility of targeted therapies innon-Ph-positiveMPALs is unknown. C1 [Wolach, Ofir; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Room D2053, Boston, MA 02115 USA. EM rstone@partners.org NR 70 TC 10 Z9 10 U1 0 U2 7 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 APR 16 PY 2015 VL 125 IS 16 BP 2477 EP 2485 DI 10.1182/blood-2014-10-551465 PG 9 WC Hematology SC Hematology GA CI4VK UT WOS:000354751700009 PM 25605373 ER PT J AU Alinari, L Mahasenan, KV Yan, FT Karkhanis, V Chung, JH Smith, EM Quinion, C Smith, PL Kim, L Patton, JT Lapalombella, R Yu, B Wu, Y Roy, S De Leo, A Pileri, S Agostinelli, C Ayers, L Bradner, JE Chen-Kiang, S Elemento, O Motiwala, T Majumder, S Byrd, JC Jacob, S Sif, S Li, CL Baiocchi, RA AF Alinari, Lapo Mahasenan, Kiran V. Yan, Fengting Karkhanis, Vrajesh Chung, Ji-Hyun Smith, Emily M. Quinion, Carl Smith, Porsha L. Kim, Lisa Patton, John T. Lapalombella, Rosa Yu, Bo Wu, Yun Roy, Satavisha De Leo, Alessandra Pileri, Stefano Agostinelli, Claudio Ayers, Leona Bradner, James E. Chen-Kiang, Selina Elemento, Olivier Motiwala, Tasneem Majumder, Sarmila Byrd, John C. Jacob, Samson Sif, Said Li, Chenglong Baiocchi, Robert A. TI Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; NF-KAPPA-B; LATENT MEMBRANE-PROTEIN-1; LINE ESTABLISHMENT; GENE-EXPRESSION; PRMT5; METHYLATION; RECEPTOR; ACTIVATION; TRANSCRIPTION AB Epigenetic events that are essential drivers of lymphocyte transformation remain incompletely characterized. We used models of Epstein-Barr virus (EBV)-induced B-cell transformation to document the relevance of protein arginine methyltransferase 5 (PRMT5) to regulation of epigenetic-repressive marks during lymphomagenesis. EBV+ lymphomas and transformed cell lines exhibited abundant expression of PRMT5, a type II PRMT enzyme that promotes transcriptional silencing of target genes by methylating arginine residues on histone tails. PRMT5 expression was limited to EBV-transformed cells, not resting or activated B lymphocytes, validating it as an ideal therapeutic target. We developed a first-in-class, small-molecule PRMT5 inhibitor that blocked EBV-driven B-lymphocyte transformation and survival while leaving normal B cells unaffected. Inhibition of PRMT5 led to lost recruitment of a PRMT5/p65/HDAC3-repressive complex on the miR96 promoter, restored miR96 expression, and PRMT5 down regulation. RNA-sequencing and chromatin immunoprecipitation experiments identified several tumor suppressor genes, including the protein tyrosine phosphatase gene PTPROt, which became silenced during EBV-driven B-cell transformation. Enhanced PTPROt expression following PRMT5 inhibition led to dephosphorylation of kinases that regulate B-cell receptor signaling. We conclude that PRMT5 is critical to EBV-driven B-cell transformation and maintenance of the malignant phenotype, and that PRMT5 inhibition shows promise as a novel therapeutic approach for B-cell lymphomas. C1 [Alinari, Lapo; Yan, Fengting; Smith, Emily M.; Quinion, Carl; Smith, Porsha L.; Kim, Lisa; Patton, John T.; Lapalombella, Rosa; Yu, Bo; Wu, Yun; Byrd, John C.; Baiocchi, Robert A.] Ohio State Univ, Div Hematol, Dept Internal Med, Columbus, OH 43210 USA. [Mahasenan, Kiran V.; Byrd, John C.; Li, Chenglong] Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. [Karkhanis, Vrajesh; Chung, Ji-Hyun; Roy, Satavisha; Motiwala, Tasneem; Majumder, Sarmila; Jacob, Samson] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [De Leo, Alessandra] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Rome, Italy. [Pileri, Stefano; Agostinelli, Claudio] Univ Bologna, Dept Expt Diagnost & Specialty Med, Hematopathol Unit, Bologna, Italy. [Ayers, Leona] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Chen-Kiang, Selina] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. [Sif, Said] Qatar Univ, Coll Arts & Sci, Dept Biol & Environm Sci, Doha, Qatar. RP Baiocchi, RA (reprint author), Ohio State Univ, Div Hematol, Dept Internal Med, B420 Starling Loving Hall,320 West 10th Ave, Columbus, OH 43210 USA. EM ssif@qu.edu.qa; robert.baiocchi@osumc.edu RI Li, Chenglong/E-7182-2010; Lapalombella, Rosa/C-2837-2014 OI Li, Chenglong/0000-0003-3174-8719; FU American Society of Hematology/European Hematology Association; Leukemia & Lymphoma Society Translational Research Project (LLS TRP); Friends of Jason Gould Foundation; Ohio State University Drug Development Institute; National Institutes of Health; National Institute of Neurological Disorders and Stroke [R21NS071346]; National Cancer Institute [R01CA116093] FX This work was supported by grants from the American Society of Hematology/European Hematology Association (L. Alinari), the Leukemia & Lymphoma Society Translational Research Project (LLS TRP) (R.A.B.), Friends of Jason Gould Foundation (R.A.B., P.L.S., J.T.P.), The Ohio State University Drug Development Institute (R.A.B., C.L.), National Institutes of Health, National Institute of Neurological Disorders and Stroke grant R21NS071346 (R.A.B., C.L.) and National Cancer Institute grant R01CA116093 (S.S., R.A.B.). NR 49 TC 18 Z9 18 U1 5 U2 16 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 APR 16 PY 2015 VL 125 IS 16 BP 2530 EP 2543 DI 10.1182/blood-2014-12619783 PG 14 WC Hematology SC Hematology GA CI4VK UT WOS:000354751700014 PM 25742700 ER PT J AU Vandiver, AR Irizarry, RA Hansen, KD Garza, LA Runarsson, A Li, X Chien, AL Wang, TS Leung, SG Kang, S Feinberg, AP AF Vandiver, Amy R. Irizarry, Rafael A. Hansen, Kasper D. Garza, Luis A. Runarsson, Arni Li, Xin Chien, Anna L. Wang, Timothy S. Leung, Sherry G. Kang, Sewon Feinberg, Andrew P. TI Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin SO GENOME BIOLOGY LA English DT Article ID EPIGENOME-WIDE ASSOCIATION; DIFFERENTIALLY METHYLATED REGIONS; EMBRYONIC STEM-CELLS; CPG ISLAND SHORES; DNA METHYLATION; IMMUNOHISTOCHEMICAL ANALYSIS; PHOTONUMERIC SCALE; GENE-EXPRESSION; HUMAN EPIDERMIS; CANCER AB Background: Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans. Results: We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples. Conclusions: These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging. C1 [Vandiver, Amy R.; Irizarry, Rafael A.; Hansen, Kasper D.; Runarsson, Arni; Li, Xin; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Hansen, Kasper D.] Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21205 USA. [Hansen, Kasper D.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. [Garza, Luis A.; Chien, Anna L.; Wang, Timothy S.; Leung, Sherry G.; Kang, Sewon] Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21287 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Rangos 570,855N Wolfe St, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu OI Hansen, Kasper/0000-0003-0086-0687 FU NIH [AG042187, AR064297] FX We thank Rebecca Curley for making sequencing libraries, Helen Xu for hematoxylin and eosin staining, Winston Timp for guidance in experimental design and technique. This work was supported by NIH grant AG042187 to APF. LG was supported by NIH grant AR064297. NR 61 TC 14 Z9 14 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD APR 16 PY 2015 VL 16 AR 80 DI 10.1186/s13059-015-0644-y PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CH4SN UT WOS:000354023300001 PM 25886480 ER PT J AU Strasser-Weippl, K Horick, N Smith, IE O'Shaughnessy, J Ejlertsen, B Boyle, F Buzdar, AU Fumoleau, P Gradishar, W Martin, M Moy, B Piccart-Gebhart, M Pritchard, KI Lindquist, D Rappold, E Finkelstein, DM Goss, PE AF Strasser-Weippl, Kathrin Horick, Nora Smith, Ian E. O'Shaughnessy, Joyce Ejlertsen, Bent Boyle, Frances Buzdar, Aman U. Fumoleau, Pierre Gradishar, William Martin, Miguel Moy, Beverly Piccart-Gebhart, Martine Pritchard, Kathleen I. Lindquist, Deborah Rappold, Erica Finkelstein, Dianne M. Goss, Paul E. TI Long-term hazard of recurrence in HER2+breast cancer patients untreated with anti-HER2 therapy SO BREAST CANCER RESEARCH LA English DT Article ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; TRASTUZUMAB; RATES; TIME; HER2 AB Introduction: Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2-positive) early breast cancer (BC) do not receive adjuvant trastuzumab. Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described. Methods: Using data from 1,260 patients randomized to placebo in the adjuvant TEACH trial, we report 10-year annual hazards of recurrence in HER2+ patients not treated with anti-HER2 therapy. Results: Disease-free survival (DFS) was 75% after 5 and 61% after 10 years, respectively. Patients with HER2+ hormone receptor-positive (HR+ (hormone receptor-positive); ER+ (estrogen receptor-positive) or PR+ (progesterone receptor-positive)) disease had a significantly better DFS than patients with HER2+ HR-(ER-/PR-) disease (hazard ratio 0.72, P = 0.02). This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2+ HR-compared to HER2+ HR+ patients, with a mean risk of recurrence of 9%/year for HR-versus 5%/year in HR+ patients (hazard ratio 0.59, P = 0.002 for years 1 to 5). The high early risk of recurrence of HER2+ HR-patients declined sharply over time, so that it was similar to that seen in HER2+ HR+ patients in years 6 to 10 (hazard ratio 0.97, P = 0.92 for years 6 to 10). Conclusions: Our results show that outcomes in HER2+ patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression. The very high early risk of relapse seen in HER2+ HR-patients is particularly relevant in health care settings with limited access to adjuvant anti-HER2 treatment. The event rates shown for subpopulations of HER2+ BC patients suggest that in resource-constrained environments patients with HER2+ HR-early BC should be prioritized for consideration of adjuvant anti-HER2 therapy. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol & Hematol, A-1160 Vienna, Austria. [Horick, Nora; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02478 USA. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. [O'Shaughnessy, Joyce] US Oncol, Baylor Sammons Canc Ctr, Texas Oncol, Dallas, TX 75246 USA. [Ejlertsen, Bent] Rigshosp, DBCG Secretariat, DK-2100 Copenhagen, Denmark. [Boyle, Frances] Mater Hosp, Sydney, NSW 2060, Australia. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fumoleau, Pierre] Ctr GF Leclerc, F-21000 Dijon, France. [Gradishar, William] Northwestern Univ, Evanston, IL 60208 USA. [Martin, Miguel] Univ Complutense Madrid, Hosp Univ Gregorio Maranon, E-28040 Madrid, Spain. [Moy, Beverly; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Piccart-Gebhart, Martine] Univ Libre Bruxelles, Inst Jules Bordet, B-1000 Brussels, Belgium. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Lindquist, Deborah] US Oncol, Arizona Oncol, Sedona, AZ 86336 USA. [Rappold, Erica] GlaxoSmithKline, Collegeville, PA 19426 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM pgoss@partners.org FU GlaxoSmithKline; Avon Foundation, NY FX This work was supported by GlaxoSmithKline; and the Avon Foundation, NY. NR 19 TC 3 Z9 3 U1 1 U2 3 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 APR 16 PY 2015 VL 17 AR 56 DI 10.1186/s13058-015-0568-1 PG 7 WC Oncology SC Oncology GA CH3SD UT WOS:000353949700001 PM 25888246 ER PT J AU Cohen, SP Hanling, S Bicket, MC White, R Veiz, E Kurihara, C Zhao, Z Hayek, S Guthmiller, KB Griffith, SR Gordin, V White, MA Vorobeychik, Y Pasquina, PF AF Cohen, Steven P. Hanling, Steven Bicket, Mark C. White, Ronald Veiz, Elias Kurihara, Connie Zhao, Zirong Hayek, Salim Guthmiller, Kevin B. Griffith, Scott R. Gordin, Vitaly White, Mirinda Anderson Vorobeychik, Yakov Pasquina, Paul F. TI Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study SO BMJ-British Medical Journal LA English DT Article ID LOW-BACK-PAIN; NEUROPATHIC PAIN; CONTROLLED-TRIAL; CORTICOSTEROID INJECTIONS; POSTHERPETIC NEURALGIA; LEEDS ASSESSMENT; CLINICAL-TRIALS; LUMBAR RADICULOPATHY; SCIATICA; PLACEBO AB OBJECTIVE To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy. DESIGN A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes. SETTINGS Eight military, Veterans Administration, and civilian hospitals. PARTICIPANTS 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain. INTERVENTIONS Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin. MAIN OUTCOME MEASURES Average leg pain one and three months after the injection on a 0-10 numerical rating scale. A positive outcome was defined as a >= 2 point decrease in leg pain coupled with a positive global perceived effect. All patients had one month follow-up visits; patients whose condition improved remained blinded for their three month visit. RESULTS There were no significant differences for the primary outcome measure at one month (mean pain score 3.3 (SD 2.6) and mean change from baseline -2.2 (SD 2.4) in epidural steroid injection group versus 3.7 (SD 2.6) and -1.7 (SD 2.6) in gabapentin group; adjusted difference 0.4, 95% confidence interval -0.3 to 1.2; P=0.25) and three months (mean pain score 3.4 (SD 2.7) and mean change from baseline -2.0 (SD 2.6) versus 3.7 (SD 2.8) and -1.6 (SD 2.7), respectively; adjusted difference 0.3, -0.5 to 1.2; P=0.43). Among secondary outcomes, one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain (-3.0, SD 2.8) than those treated with gabapentin (-2.0, SD 2.9; P=0.04) and were more likely to experience a positive successful outcome (66% v 46%; number needed to treat=5.0, 95% confidence interval 2.8 to 27.0; P=0.02). At three months, there were no significant differences between treatments. CONCLUSIONS Although epidural steroid injection might provide greater benefit than gabapentin for some outcome measures, the differences are modest and are transient for most people. C1 [Cohen, Steven P.] Johns Hopkins Sch Med, Dept Anesthesiol, Blaustein Pain Treatment Ctr, Baltimore, MD 21287 USA. [Cohen, Steven P.; Griffith, Scott R.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Hanling, Steven] Naval Med Ctr, Dept Anesthesiol, Pain Med Div, San Diego, CA USA. [Bicket, Mark C.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [White, Ronald] Landstuhl Reg Med Ctr, Dept Surg, Interdisciplinary Pain Med, Landstuhl, Germany. [Veiz, Elias] Case Western Univ, Louis Stokes Cleveland VA Med Ctr, Dept Anesthesiol, Pain Med Serv, Cleveland, OH USA. [Kurihara, Connie] Walter Reed Natl Mil Med Ctr, Dept Surg, Anesthesia Serv, Bethesda, MD USA. [Zhao, Zirong] Dist Columbia VA Hosp, Dept Neurol, Washington, DC USA. [Zhao, Zirong] Dist Columbia VA Hosp, Dept Neurol, Washington, MD USA. [Zhao, Zirong] George Washington Univ, Dept Med, Washington, DC USA. [Zhao, Zirong] George Washington Univ, Dept Med, Washington, MD USA. [Hayek, Salim] Case Western Reserve Sch Med, Dept Anesthesiol, Pain Med Div, Cleveland, OH USA. [Guthmiller, Kevin B.] San Antonio Mil Med Ctr, Dept Anesthesiol, Interdisciplinary Pain Management Clin, San Antonio, TX USA. [Guthmiller, Kevin B.] San Antonio Mil Med Ctr, Dept Anesthesiol, Pain Med Fellowship Program, San Antonio, TX USA. [Gordin, Vitaly] Penn State Hershey Med Ctr, Dept Anesthesiol, Pain Med Div, Hershey, PA USA. [White, Mirinda Anderson] Johns Hopkins Sch Med, Dept Anesthesiol, Baltimore, MD USA. [Vorobeychik, Yakov] Penn State Hershey Med Ctr, Dept Anesthesiol, Hershey, PA USA. [Vorobeychik, Yakov] Penn State Hershey Med Ctr, Dept Neurol, Hershey, PA USA. [Pasquina, Paul F.] Univ Hlth Sci, Walter Reed Natl Mil Med Ctr & Uniformed Serv, Dept Phys Med & Rehabil, Bethesda, MD USA. RP Cohen, SP (reprint author), Johns Hopkins Sch Med, Dept Anesthesiol, Blaustein Pain Treatment Ctr, Baltimore, MD 21287 USA. EM scohen40@jhmi.edu FU Center for Rehabilitation Sciences Research, Bethesda, MD FX This study was funded by a congressional grant from the Center for Rehabilitation Sciences Research, Bethesda, MD. The funders paid for personnel, medications, and procedures. NR 61 TC 15 Z9 15 U1 6 U2 11 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 APR 16 PY 2015 VL 350 AR h1748 DI 10.1136/bmj.h1748 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CG5JV UT WOS:000353328700005 PM 25883095 ER PT J AU Tang, V Boscardin, WJ Stijacic-Cenzer, I Lee, SJ AF Tang, Victoria Boscardin, W. John Stijacic-Cenzer, Irena Lee, Sei J. TI Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials SO BMJ-British Medical Journal LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; FOLLOW-UP; COLONOSCOPY; PREVENTION; MORTALITY AB OBJECTIVE To determine the time to benefit of using flexible sigmoidoscopy for colorectal cancer screening. DESIGN Survival meta-analysis. DATA SOURCES A Cochrane Collaboration systematic review published in 2013, Medline, and Cochrane Library databases. ELIGIBILITY CRITERIA Randomized controlled trials comparing screening flexible sigmoidoscopy with no screening. Trials with fewer than 100 flexible sigmoidoscopy screenings were excluded. RESULTS Four studies were eligible (total n=459 814). They were similar for patients' age (50-74 years), length of follow-up (11.2-11.9 years), and relative risk for colorectal cancer related mortality (0.69-0.78 with flexible sigmoidoscopy screening). For every 1000 people screened at five and 10 years, 0.3 and 1.2 colorectal cancer related deaths, respectively, were prevented. It took 4.3 years (95% confidence interval 2.8 to 5.8) to observe an absolute risk reduction of 0.0002 (one colorectal cancer related death prevented for every 5000 flexible sigmoidoscopy screenings). It took 9.4 years (7.6 to 11.3) to observe an absolute risk reduction of 0.001 (one colorectal cancer related death prevented for every 1000 flexible sigmoidoscopy screenings). CONCLUSION Our findings suggest that screening flexible sigmoidoscopy is most appropriate for older adults with a life expectancy greater than approximately 10 years. C1 [Tang, Victoria; Boscardin, W. John; Stijacic-Cenzer, Irena; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Boscardin, W. John; Stijacic-Cenzer, Irena; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Tang, V (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM Victoria.Tang@ucsf.edu FU Beeson career development award through the American Federation of Aging Research; National Institute on Aging [K23AG040779] FX SJL was supported by the Beeson career development award through the American Federation of Aging Research and National Institute on Aging (K23AG040779). The funding source had no involvement in the design or conduct of the study and had no influence on the collection, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the paper for publication. NR 30 TC 5 Z9 5 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 APR 16 PY 2015 VL 350 AR h1662 DI 10.1136/bmj.h1662 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CG5JV UT WOS:000353328700003 PM 25881903 ER PT J AU Jeong, JY Levine, MS Abayasekara, N Berliner, N Laubach, J Vanasse, GJ AF Jeong, Jee-Yeong Levine, Michelle S. Abayasekara, Nirmalee Berliner, Nancy Laubach, Jacob Vanasse, Gary J. TI The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article C1 [Jeong, Jee-Yeong; Levine, Michelle S.; Abayasekara, Nirmalee; Berliner, Nancy; Vanasse, Gary J.] Brigham & Womens Hosp, Harvard Med Sch, Divis Hematol, Boston, MA 02115 USA. [Jeong, Jee-Yeong] Kosin Univ Coll Med, Department Biochem, Busan, South Korea. [Jeong, Jee-Yeong] Kosin Univ Coll Med, Cancer Res Inst, Busan, South Korea. [Laubach, Jacob] Dana Farber Canc Inst, Department Med Oncol, Boston, MA USA. [Vanasse, Gary J.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Jeong, JY (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Divis Hematol, Boston, MA 02115 USA. FU GlaxoSmithKline; Korea National Research Foundation (KNRF) [2014M3C1A3051981, 2012R1A1A2042188] FX The authors would like to thank Dr. Constantine Mitsiades for generously providing human multiple myeloma cell lines. These studies were supported by research funds provided by GlaxoSmithKline to Dana-Farber/Partners Cancer Care GJV) and in part by Korea National Research Foundation (KNRF) grant 2014M3C1A3051981 and 2012R1A1A2042188 (JYJ). The funding organizations had no role in study design, data collection and analysis, or preparation of the manuscript. NR 0 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD APR 16 PY 2015 VL 8 AR 37 DI 10.1186/s13045-015-0136-2 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CG3OC UT WOS:000353188500002 PM 25886818 ER PT J AU Hnisz, D Schuijers, J Lin, CY Weintraub, AS Abraham, BJ Lee, TI Bradner, JE Young, RA AF Hnisz, Denes Schuijers, Jurian Lin, Charles Y. Weintraub, Abraham S. Abraham, Brian J. Lee, Tong Ihn Bradner, James E. Young, Richard A. TI Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers SO MOLECULAR CELL LA English DT Article ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; IDENTITY GENES; DISEASE; INFLAMMATION; LEUKEMIA; ELEMENTS; VARIANTS; TARGET; MICE AB Super-enhancers and stretch enhancers (SEs) drive expression of genes that play prominent roles in normal and disease cells, but the functional importance of these clustered enhancer elements is poorly understood, so it is not clear why genes key to cell identity have evolved regulation by such elements. Here, we show that SEs consist of functional constituent units that concentrate multiple developmental signaling pathways at key pluripotency genes in embryonic stem cells and confer enhanced responsiveness to signaling of their associated genes. Cancer cells frequently acquire SEs at genes that promote tumorigenesis, and we show that these genes are especially sensitive to perturbation of oncogenic signaling pathways. Super-enhancers thus provide a platform for signaling pathways to regulate genes that control cell identity during development and tumorigenesis. C1 [Hnisz, Denes; Schuijers, Jurian; Weintraub, Abraham S.; Abraham, Brian J.; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lin, Charles Y.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Weintraub, Abraham S.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU NHGRI NIH HHS [HG002668, R01 HG002668]; NIGMS NIH HHS [T32 GM007287] NR 38 TC 59 Z9 60 U1 1 U2 17 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 APR 16 PY 2015 VL 58 IS 2 BP 362 EP 370 DI 10.1016/j.molcel.2015.02.014 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG4AR UT WOS:000353222900016 PM 25801169 ER PT J AU Moody, SE Schinzel, AC Singh, S Izzo, F Strickland, MR Luo, L Thomas, SR Boehm, JS Kim, SY Wang, ZC Hahn, WC AF Moody, S. E. Schinzel, A. C. Singh, S. Izzo, F. Strickland, M. R. Luo, L. Thomas, S. R. Boehm, J. S. Kim, S. Y. Wang, Z. C. Hahn, W. C. TI PRKACA mediates resistance to HER2-targeted therapy in breast cancer cells and restores anti-apoptotic signaling SO ONCOGENE LA English DT Article ID DEPENDENT PROTEIN-KINASE; ADRENAL CUSHINGS-SYNDROME; TRASTUZUMAB RESISTANCE; MONOCLONAL-ANTIBODY; SINGLE-AGENT; BETA-CATENIN; PHOSPHORYLATION; LAPATINIB; ACTIVATION; CHEMOTHERAPY AB Targeting HER2 with antibodies or small molecule inhibitors in HER2-positive breast cancer leads to improved survival, but resistance is a common clinical problem. To uncover novel mechanisms of resistance to anti-HER2 therapy in breast cancer, we performed a kinase open reading frame screen to identify genes that rescue HER2-amplified breast cancer cells from HER2 inhibition or suppression. In addition to multiple members of the MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase) signaling pathways, we discovered that expression of the survival kinases PRKACA and PIM1 rescued cells from anti-HER2 therapy. Furthermore, we observed elevated PRKACA expression in trastuzumab-resistant breast cancer samples, indicating that this pathway is activated in breast cancers that are clinically resistant to trastuzumab-containing therapy. We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro-apoptotic protein BAD, the BCl-2-associated death promoter, thereby permitting survival signaling through BCL-XL. Pharmacological blockade of BCL-XL/BCL-2 partially abrogated the rescue effects conferred by PRKACA and PIM1, and sensitized cells to lapatinib treatment. These observations suggest that combined targeting of HER2 and the BCL-XL/BCL-2 anti-apoptotic pathway may increase responses to anti-HER2 therapy in breast cancer and decrease the emergence of resistant disease. C1 [Moody, S. E.; Schinzel, A. C.; Singh, S.; Izzo, F.; Strickland, M. R.; Luo, L.; Hahn, W. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Moody, S. E.; Luo, L.; Hahn, W. C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Moody, S. E.; Luo, L.; Wang, Z. C.; Hahn, W. C.] Harvard Univ, Sch Med, Boston, MA USA. [Thomas, S. R.; Boehm, J. S.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kim, S. Y.] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC USA. [Wang, Z. C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Wang, Z. C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu FU Department of Defense [W81XWH-10-1-0575]; Komen Grant [CCR13262292]; Breast Cancer Research Foundation; NIH [R01 CA130988, U01 CA176058, U54 CA112962] FX We wish to thank Drs Ines Luis, Nancy Lin and Eric Winer for assistance in obtaining patient tissue samples. This work was supported by the Department of Defense Grant W81XWH-10-1-0575 and the Komen Grant CCR13262292 (to SEM), by the Breast Cancer Research Foundation (to ZCW), and by the NIH grants R01 CA130988, U01 CA176058 and U54 CA112962 (to WCH). NR 42 TC 13 Z9 13 U1 1 U2 10 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 APR 16 PY 2015 VL 34 IS 16 BP 2061 EP 2071 DI 10.1038/onc.2014.153 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CG3IL UT WOS:000353173400006 PM 24909179 ER PT J AU Dellinger, AL Cunin, P Lee, D Kung, AL Brooks, DB Zhou, ZG Nigrovic, PA Kepley, CL AF Dellinger, Anthony L. Cunin, Pierre Lee, David Kung, Andrew L. Brooks, D. Bradford Zhou, Zhiguo Nigrovic, Peter A. Kepley, Christopher L. TI Inhibition of Inflammatory Arthritis Using Fullerene Nanomaterials SO PLOS ONE LA English DT Article ID NF-KAPPA-B; COLLAGEN-INDUCED ARTHRITIS; HUMAN MAST-CELLS; RHEUMATOID-ARTHRITIS; REACTIVE OXYGEN; IN-VITRO; MICE; ANTIOXIDANTS; PATHOGENESIS; THERAPY AB Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked Fc gamma R-and TNF-alpha-induced mediator release from MC; TNF-alpha-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and Fc gamma R-mediated increases in cellular reactive oxygen species and NF-kappa B activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-alpha. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis. C1 [Dellinger, Anthony L.; Kepley, Christopher L.] Univ N Carolina, Joint Sch Nanosci & Nanoengn, Greensboro, NC 27412 USA. [Cunin, Pierre; Nigrovic, Peter A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Cunin, Pierre; Nigrovic, Peter A.] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Lee, David] Novartis Inst Biomed Res, Basel, Switzerland. [Kung, Andrew L.] Dana Farber Inst, Boston, MA USA. [Brooks, D. Bradford; Zhou, Zhiguo] Luna Innovat Inc, Danville, VA USA. RP Kepley, CL (reprint author), Univ N Carolina, Joint Sch Nanosci & Nanoengn, Greensboro, NC 27412 USA. EM clkepley@uncg.edu OI Kung, Andrew/0000-0002-9091-488X FU Novartis Institutes for Biomedical Research; Luna Innovations Incorporated FX Novartis Institutes for Biomedical Research and Luna Innovations Incorporated provided support in the form of salaries for authors DL, DBB and ZZ, 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 roles of these authors are articulated in the 'author contributions' section. NR 72 TC 3 Z9 3 U1 0 U2 10 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 APR 16 PY 2015 VL 10 IS 4 AR UNSP e0126290 DI 10.1371/journal.pone.0126290 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1ES UT WOS:000353016500120 PM 25879437 ER PT J AU Gotink, RA Chu, P Busschbach, JJV Benson, H Fricchione, GL Hunink, MGM AF Gotink, Rinske A. Chu, Paula Busschbach, Jan J. V. Benson, Herbert Fricchione, Gregory L. Hunink, M. G. Myriam TI Standardised Mindfulness-Based Interventions in Healthcare: An Overview of Systematic Reviews and Meta-Analyses of RCTs SO PLOS ONE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; STRESS REDUCTION; COGNITIVE THERAPY; RELAXATION RESPONSE; CANCER CARE; MEDITATION; DEPRESSION; EFFICACY; DISEASE; PREVENTION AB Background Mindfulness-based therapies are being used in a wide range of common chronic conditions in both treatment and prevention despite lack of consensus about their effectiveness in different patient categories. Objective To systematically review the evidence of effectiveness MBSR and MBCT in different patient categories. Methods A systematic review and meta-analysis of systematic reviews of RCTs, using the standardized MBSR or MBCT programs. We used PRISMA guidelines to assess the quality of the included reviews and performed a random effects meta-analysis with main outcome measure Cohen's d. All types of participants were considered. Results The search produced 187 reviews: 23 were included, covering 115 unique RCTs and 8,683 unique individuals with various conditions. Compared to wait list control and compared to treatment as usual, MBSR and MBCT significantly improved depressive symptoms (d= 0.37; 95% CI 0.28 to 0.45, based on 5 reviews, N = 2814), anxiety (d = 0.49; 95% CI 0.37 to 0.61, based on 4 reviews, N = 2525), stress (d = 0.51; 95% CI 0.36 to 0.67, based on 2 reviews, N = 1570), quality of life (d = 0.39; 95% CI 0.08 to 0.70, based on 2 reviews, N = 511) and physical functioning (d = 0.27; 95% CI 0.12 to 0.42, based on 3 reviews, N = 1015). Limitations include heterogeneity within patient categories, risk of publication bias and limited long-term follow-up in several studies. Conclusion The evidence supports the use of MBSR and MBCT to alleviate symptoms, both mental and physical, in the adjunct treatment of cancer, cardiovascular disease, chronic pain, depression, anxiety disorders and in prevention in healthy adults and children. C1 [Gotink, Rinske A.; Hunink, M. G. Myriam] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Gotink, Rinske A.; Busschbach, Jan J. V.] Erasmus MC, Dept Psychiat, Sect Med Psychol & Psychotherapy, Rotterdam, Netherlands. [Gotink, Rinske A.; Hunink, M. G. Myriam] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Chu, Paula] Harvard Univ, Dept Hlth Policy, Cambridge, MA 02138 USA. [Benson, Herbert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Benson Henry Inst Mind Body Med, Boston, MA USA. [Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Benson, Herbert; Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Hunink, M. G. Myriam] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hunink, MGM (reprint author), Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. EM m.hunink@erasmusmc.nl OI Busschbach, Jan/0000-0002-8602-0381; Gotink, Rinske/0000-0002-4760-3226 FU Erasmus MC grant FX There was no sponsor involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Funding for this study was provided by an internal Erasmus MC grant. NR 61 TC 19 Z9 19 U1 12 U2 104 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 APR 16 PY 2015 VL 10 IS 4 AR UNSP e0124344 DI 10.1371/journal.pone.0124344 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1ES UT WOS:000353016500094 PM 25881019 ER PT J AU Han, M Kim, K Jang, SJ Cho, HS Bouma, BE Oh, WY Ryu, S AF Han, Myounghee Kim, Kyunghun Jang, Sun-Joo Cho, Han Saem Bouma, Brett E. Oh, Wang-Yuhl Ryu, Sukyoung TI GPU-Accelerated Framework for Intracoronary Optical Coherence Tomography Imaging at the Push of a Button SO PLOS ONE LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; INCOMPLETE STENT APPOSITION; GRAPHICS PROCESSING UNIT; DRUG-ELUTING STENTS; MYOCARDIAL-INFARCTION; IN-VIVO; ARTERY; INSIGHTS; OCT; CPU AB Frequency domain optical coherence tomography (FD-OCT) has become one of the important clinical tools for intracoronary imaging to diagnose and monitor coronary artery disease, which has been one of the leading causes of death. To help more accurate diagnosis and monitoring of the disease, many researchers have recently worked on visualization of various coronary microscopic features including stent struts by constructing three-dimensional (3D) volumetric rendering from series of cross-sectional intracoronary FD-OCT images. In this paper, we present the first, to our knowledge, "push-of-a-button" graphics processing unit (GPU)-accelerated framework for intracoronary OCT imaging. Our framework visualizes 3D microstructures of the vessel wall with stent struts from raw binary OCT data acquired by the system digitizer as one seamless process. The framework reports the state-of-the-art performance; from raw OCT data, it takes 4.7 seconds to provide 3D visualization of a 5-cm-long coronary artery (of size 1600 samples x 1024 A-lines x 260 frames) with stent struts and detection of malapposition automatically at the single push of a button. C1 [Han, Myounghee; Kim, Kyunghun; Ryu, Sukyoung] Korea Adv Inst Sci & Technol, Dept Comp Sci, Taejon 305701, South Korea. [Jang, Sun-Joo; Cho, Han Saem; Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. [Jang, Sun-Joo] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA USA. [Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Ryu, S (reprint author), Korea Adv Inst Sci & Technol, Dept Comp Sci, Taejon 305701, South Korea. EM sryu.cs@kaist.ac.kr RI Ryu, Sukyoung/C-2080-2011 FU National Research Foundation of Korea [NRF-2010-0017465, NRF-2014R1A2A2A01003235, NRF-2008-0062609]; Ministry of Science, ICT and Future Planning of Korea [GFP/CISS-2012M3A6A6054200, NIPA-2013-H0401-13-1007]; National Institute of Health [P41 EB015903] FX This research was funded in part by the National Research Foundation of Korea to WO (NRF-2010-0017465) and SR (NRF-2014R1A2A2A01003235, NRF-2008-0062609), by the Ministry of Science, ICT and Future Planning of Korea (GFP/CISS-2012M3A6A6054200, NIPA-2013-H0401-13-1007) to WO, and by the National Institute of Health (P41 EB015903) to BEB. 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 5 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 16 PY 2015 VL 10 IS 4 AR UNSP e0124192 DI 10.1371/journal.pone.0124192 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1ES UT WOS:000353016500088 PM 25880375 ER PT J AU Rana, Y Haberer, J Huang, HJ Kambugu, A Mukasa, B Thirumurthy, H Wabukala, P Wagner, GJ Linnemayr, S AF Rana, Yashodhara Haberer, Jessica Huang, Haijing Kambugu, Andrew Mukasa, Barbara Thirumurthy, Harsha Wabukala, Peter Wagner, Glenn J. Linnemayr, Sebastian TI Short Message Service (SMS)-Based Intervention to Improve Treatment Adherence among HIV-Positive Youth in Uganda: Focus Group Findings SO PLOS ONE LA English DT Article ID BEHAVIORAL SKILLS MODEL; ANTIRETROVIRAL THERAPY; INFORMATION; ADOLESCENTS; MOTIVATION; MANAGEMENT AB This paper presents one of the first qualitative studies to discuss programmatic barriers to SMS-based interventions for HIV-positive youth and discusses pathways through which youth perceive them to work. We conducted six focus groups with 20 male and 19 female HIV-positive youths in two clinics in Kampala, Uganda. We find that youth commonly use SMS as over 90% of this study's youths knew how to read, write and send messages and almost three-fourths of them had phones. Youth strongly felt that the success of this intervention hinged on ensuring confidentiality about their HIV-positive status. Key programmatic challenges discussed where restrictions on phone use and phone sharing that could exclude some youth. Participants felt that the intervention would improve their adherence by providing them with needed reminders and social support. Youths' suggestions about intervention logistics related to content, frequency, timing and two-way messages will be helpful to practitioners in the field. C1 [Rana, Yashodhara; Huang, Haijing; Wagner, Glenn J.; Linnemayr, Sebastian] RAND Corp, RAND Hlth, Santa Monica, CA 90401 USA. [Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kambugu, Andrew] Infect Dis Inst, Kampala, Uganda. [Mukasa, Barbara; Wabukala, Peter] Mildmay Uganda, Kampala, Uganda. [Thirumurthy, Harsha] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. RP Rana, Y (reprint author), RAND Corp, RAND Hlth, Santa Monica, CA 90401 USA. EM yrana@rand.org FU National Institute of Child Health and Human Development [R01HD074925] FX This research was sponsored by Grant R01HD074925 from The National Institute of Child Health and Human Development (PI Sebastian Linnemayr). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 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 APR 16 PY 2015 VL 10 IS 4 AR e0125187 DI 10.1371/journal.pone.0125187 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1ES UT WOS:000353016500115 PM 25881059 ER PT J AU Wang, SX Zhai, X Li, SY McCabe, MF Wang, X Rong, PJ AF Wang, Shuxing Zhai, Xu Li, Shaoyuan McCabe, Michael F. Wang, Xing Rong, Peijing TI Transcutaneous Vagus Nerve Stimulation Induces Tidal Melatonin Secretion and Has an Antidiabetic Effect in Zucker Fatty Rats SO PLOS ONE LA English DT Article ID FAR-FIELD POTENTIALS; BRAIN-STEM; HALF-LIFE; CELLS; RECEPTORS; INSULIN; MOUSE; OBESITY; PLASMA AB Melatonin plays a protective role in type 2 diabetes (T2D) through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS) is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa) and Zucker lean (ZL, +/fa) littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naive ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbA(lc)) levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbA(lc) levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world. C1 [Wang, Shuxing; Wang, Xing] Xinxiang Med Univ, Dept Anat, Xinxiang, Henan Province, Peoples R China. [Wang, Shuxing; Zhai, Xu; Li, Shaoyuan; Rong, Peijing] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Dept Physiol, Beijing, Peoples R China. [Wang, Shuxing; McCabe, Michael F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA USA. [Wang, Shuxing] Guangdong Landau Biotechnol Inc Ltd, Guangzhou, Guangdong, Peoples R China. RP Wang, SX (reprint author), Guangdong Entomol Inst, Guangzhou, Guangdong, Peoples R China. EM shuxingw@yahoo.com; rongpj@hotmail.com FU National Natural Science Foundation of China [81271243, 81473780]; Natural Science Foundation of Beijing [7111007]; National Basic Research Program of China (973 Program) [2012CB518503]; [2012BAF14B10] FX This work was supported by National Natural Science Foundation of China-81271243, 81473780; Natural Science Foundation of Beijing, 7111007; National Basic Research Program of China (973 Program) -2012CB518503; and Project Supported National Science and Technology Ministry-2012BAF14B10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 3 Z9 3 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 16 PY 2015 VL 10 IS 4 AR e0124195 DI 10.1371/journal.pone.0124195 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1ES UT WOS:000353016500089 PM 25880500 ER PT J AU Giancardo, L Sanchez-Ferro, A Butterworth, I Mendoza, CS Hooker, JM AF Giancardo, L. Sanchez-Ferro, A. Butterworth, I. Mendoza, C. S. Hooker, J. M. TI Psychomotor Impairment Detection via Finger Interactions with a Computer Keyboard During Natural Typing SO SCIENTIFIC REPORTS LA English DT Article ID KEYSTROKE DYNAMICS; SLEEP INERTIA; AUTHENTICATION; VERIFICATION; PERFORMANCE; NIGHT AB Modern digital devices and appliances are capable of monitoring the timing of button presses, or finger interactions in general, with a sub-millisecond accuracy. However, the massive amount of high resolution temporal information that these devices could collect is currently being discarded. Multiple studies have shown that the act of pressing a button triggers well defined brain areas which are known to be affected by motor-compromised conditions. In this study, we demonstrate that the daily interaction with a computer keyboard can be employed as means to observe and potentially quantify psychomotor impairment. We induced a psychomotor impairment via a sleep inertia paradigm in 14 healthy subjects, which is detected by our classifier with an Area Under the ROC Curve (AUC) of 0.93/0.91. The detection relies on novel features derived from key-hold times acquired on standard computer keyboards during an uncontrolled typing task. These features correlate with the progression to psychomotor impairment (p < 0.001) regardless of the content and language of the text typed, and perform consistently with different keyboards. The ability to acquire longitudinal measurements of subtle motor changes from a digital device without altering its functionality may allow for early screening and follow-up of motor-compromised neurodegenerative conditions, psychological disorders or intoxication at a negligible cost in the general population. C1 [Giancardo, L.; Sanchez-Ferro, A.; Butterworth, I.; Mendoza, C. S.; Hooker, J. M.] MIT, Elect Res Lab, Madrid MIT M Vis Consortium, Cambridge, MA 02139 USA. [Hooker, J. M.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Giancardo, L (reprint author), MIT, Elect Res Lab, Madrid MIT M Vis Consortium, Cambridge, MA 02139 USA. EM gianca@mit.edu FU Comunidad de Madrid FX This research is being financially supported by the Comunidad de Madrid. We thank the M + Vision IDEA3 faculty panel for their assistance in developing this project. We also thank our many clinical collaborators at MGH in Boston, at "12 de Octubre'' and Hospital Clinico in Madrid for their insightful contributions. NR 36 TC 3 Z9 3 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 16 PY 2015 VL 5 AR 9678 DI 10.1038/srep09678 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4RT UT WOS:000353275100001 PM 25882641 ER PT J AU Kim, D Fiske, BP Birsoy, K Freinkman, E Kami, K Possemato, RL Chudnovsky, Y Pacold, ME Chen, WW Cantor, JR Shelton, LM Gui, DY Kwon, M Ramkissoon, SH Ligon, KL Kang, SW Snuderl, M Vander Heiden, MG Sabatini, DM AF Kim, Dohoon Fiske, Brian P. Birsoy, Kivanc Freinkman, Elizaveta Kami, Kenjiro Possemato, Richard L. Chudnovsky, Yakov Pacold, Michael E. Chen, Walter W. Cantor, Jason R. Shelton, Laura M. Gui, Dan Y. Kwon, Manjae Ramkissoon, Shakti H. Ligon, Keith L. Kang, Seong Woo Snuderl, Matija Vander Heiden, Matthew G. Sabatini, David M. TI SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance SO NATURE LA English DT Article ID PYRUVATE-KINASE M2; ONE-CARBON METABOLISM; STEM-CELLS; TUMOR HYPOXIA; CANCER-CELLS; SERINE; PROLIFERATION; TUMORIGENESIS; METHYLGLYOXAL; AMINOACETONE AB Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment(1-3). Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. Inhuman glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumour environment, but also renders these cells sensitive to glycine cleavage system inhibition. C1 [Kim, Dohoon; Birsoy, Kivanc; Freinkman, Elizaveta; Possemato, Richard L.; Chudnovsky, Yakov; Pacold, Michael E.; Chen, Walter W.; Cantor, Jason R.; Kwon, Manjae; Kang, Seong Woo; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Kim, Dohoon; Birsoy, Kivanc; Freinkman, Elizaveta; Possemato, Richard L.; Chudnovsky, Yakov; Pacold, Michael E.; Chen, Walter W.; Cantor, Jason R.; Kang, Seong Woo; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Kim, Dohoon; Birsoy, Kivanc; Freinkman, Elizaveta; Possemato, Richard L.; Chudnovsky, Yakov; Pacold, Michael E.; Chen, Walter W.; Cantor, Jason R.; Kwon, Manjae; Kang, Seong Woo; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Kim, Dohoon; Fiske, Brian P.; Birsoy, Kivanc; Freinkman, Elizaveta; Possemato, Richard L.; Chudnovsky, Yakov; Pacold, Michael E.; Chen, Walter W.; Cantor, Jason R.; Gui, Dan Y.; Kang, Seong Woo; Vander Heiden, Matthew G.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kim, Dohoon; Fiske, Brian P.; Birsoy, Kivanc; Freinkman, Elizaveta; Possemato, Richard L.; Chudnovsky, Yakov; Pacold, Michael E.; Chen, Walter W.; Cantor, Jason R.; Gui, Dan Y.; Kang, Seong Woo; Vander Heiden, Matthew G.; Sabatini, David M.] Broad Inst Harvard & MIT, Seven Cambridge Ctr, Cambridge, MA 02142 USA. [Kami, Kenjiro] Human Metabolome Technol Inc, Tsuruoka, Yamagata 9970052, Japan. [Pacold, Michael E.; Ramkissoon, Shakti H.; Ligon, Keith L.; Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Shelton, Laura M.] Human Metabolome Technol Ameri Inc, Boston, MA 02134 USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Snuderl, Matija] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA. [Snuderl, Matija] NYU, Sch Med, New York, NY 10016 USA. RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu OI Possemato, Richard/0000-0002-2401-0030; Snuderl, Matija/0000-0003-0752-0917 FU Basic Research Fellowship from the American Brain Tumor Association; MIT School of Science Fellowship in Cancer Research; National Institutes of Health (NIH) [T32GM007287, K99 CA168940, K08-NS087118, R01CA168653, 5P30CA14051]; Jane Coffin Childs Memorial Fund; Leukemia and Lymphoma Society; American Cancer Society; American Brain Tumor Association Discovery Grant; US National Institute of Aging; Smith Family Foundation; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Stern family; DOD CDMRP Discovery Award; David H. Koch Institute for Integrative Cancer Research at MIT; Alexander and Margaret Stewart Trust Fund; NIH [CA103866, CA129105, AI07389] FX We thank members of the Sabatini laboratory for assistance and feedback, in particular Y. Shaul, T. Wang, S. Wang and O. Yilmaz. Authors would like to thank J. Taylor for GBM sample collection, and T. DiCesare for illustrations. This work was supported by a Basic Research Fellowship from the American Brain Tumor Association to D.K.; MIT School of Science Fellowship in Cancer Research and National Institutes of Health (NIH) T32GM007287 to B.P.F., fellowships from the Jane Coffin Childs Memorial Fund and Leukemia and Lymphoma Society to K.B.; a grant from the NIH (K99 CA168940) to R.P.; an American Cancer Society fellowship and an American Brain Tumor Association Discovery Grant to Y.C.; a fellowship from the US National Institute of Aging to W.W.C.; NIH (K08-NS087118) to S.H.R.; support from NIH (R01CA168653, 5P30CA14051), the Smith Family Foundation, the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, and the Stern family to M.G.V.H.; DOD CDMRP Discovery Award, grants from the David H. Koch Institute for Integrative Cancer Research at MIT, The Alexander and Margaret Stewart Trust Fund, and NIH (CA103866, CA129105, and AI07389) to D.M.S.; D.M.S. is an investigator of the Howard Hughes Medical Institute. NR 39 TC 53 Z9 54 U1 13 U2 44 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 APR 16 PY 2015 VL 520 IS 7547 BP 363 EP + DI 10.1038/nature14363 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG0RI UT WOS:000352974200042 PM 25855294 ER PT J AU Pugh, TJ Banerji, S Meyerson, M AF Pugh, Trevor J. Banerji, Shantanu Meyerson, Matthew TI MAGI3-AKT3 fusion in breast cancer amended Reply SO NATURE LA English DT Letter ID MUTATIONS C1 [Pugh, Trevor J.] Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [Banerji, Shantanu] Univ Manitoba, Dept Internal Med, Fac Hlth Sci, Winnipeg, MB R3E 0V9, Canada. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Meyerson, Matthew] Broad Inst, Canc Program, Cambridge, MA 02142 USA. RP Pugh, TJ (reprint author), Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. EM matthew_meyerson@dfci.harvard.edu NR 6 TC 2 Z9 2 U1 1 U2 7 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 APR 16 PY 2015 VL 520 IS 7547 BP E12 EP E14 DI 10.1038/nature14266 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG0RI UT WOS:000352974200002 PM 25877207 ER PT J AU Sabatine, MS Giugliano, RP Wiviott, SD Raal, FJ Blom, DJ Robinson, J Ballantyne, CM Somaratne, R Legg, J Wasserman, SM Scott, R Koren, MJ Stein, EA AF Sabatine, Marc S. Giugliano, Robert P. Wiviott, Stephen D. Raal, Frederick J. Blom, Dirk J. Robinson, Jennifer Ballantyne, Christie M. Somaratne, Ransi Legg, Jason Wasserman, Scott M. Scott, Robert Koren, Michael J. Stein, Evan A. CA Open-Label Study Long-Term TI Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; SUBTILISIN/KEXIN TYPE 9; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; PLACEBO-CONTROLLED TRIAL; MONOCLONAL-ANTIBODY; AMG 145; RANDOMIZED-TRIAL; DOUBLE-BLIND; LDL-C; PCSK9 INHIBITION AB BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data. METHODS In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2: 1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined. RESULTS As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003). CONCLUSIONS During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. C1 [Sabatine, Marc S.; Giugliano, Robert P.; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. [Sabatine, Marc S.; Giugliano, Robert P.; Wiviott, Stephen D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Raal, Frederick J.] Univ Witwatersrand, Fac Hlth Sci, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa. [Blom, Dirk J.] Univ Cape Town, Dept Med, Div Lipidol, ZA-7925 Cape Town, South Africa. [Robinson, Jennifer] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Robinson, Jennifer] Univ Iowa, Dept Med, Coll Publ Hlth, Iowa City, IA 52242 USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Ballantyne, Christie M.] Houston Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Somaratne, Ransi; Legg, Jason; Wasserman, Scott M.; Scott, Robert] Amgen Inc, Thousand Oaks, CA USA. [Koren, Michael J.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. [Stein, Evan A.] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org; esteinmrl@aol.com OI Scott, Robert/0000-0001-8266-1061; Blom, Dirk/0000-0003-3965-5912 FU Amgen FX Funded by Amgen; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers, NCT01439880 and NCT01854918. NR 31 TC 375 Z9 387 U1 12 U2 31 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 APR 16 PY 2015 VL 372 IS 16 BP 1500 EP 1509 DI 10.1056/NEJMoa1500858 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CF9BL UT WOS:000352856500005 PM 25773607 ER PT J AU Lee, A Vazquez, R AF Lee, Alexander Vazquez, Rafael TI Venous Gas Embolism Caused by Fibrin Sealant Application to the Prostate During Greenlight Laser Photoselective Vaporization SO A & A CASE REPORTS LA English DT Article ID AIR-EMBOLISM; NITROUS-OXIDE; SURGERY; POSITION AB Venous gas embolism is a complication of fibrin sealant application and is a well-described event during various modes of prostate resection. We describe the case of a nitrogen venous gas embolism during Greenlight laser photovaporization of the prostate during the application of fibrin sealant to the operative site for hemostasis. Fibrin sealant application by a compressed gas applicator is a cause of venous air embolism, and this case highlights the need to keep venous gas embolism in mind when compressed gas applicators are used. C1 [Lee, Alexander; Vazquez, Rafael] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lee, A (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM alee39@partners.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD APR 15 PY 2015 VL 4 IS 8 BP 100 EP 102 DI 10.1213/XAA.0000000000000138 PG 3 WC Anesthesiology SC Anesthesiology GA CM3GV UT WOS:000357571000002 PM 25867193 ER PT J AU McKibben, RA Margolick, JB Grinspoon, S Li, XH Palella, FJ Kingsley, LA Witt, MD George, RT Jacobson, LP Budoff, M Tracy, RP Brown, TT Post, WS AF McKibben, Rebeccah A. Margolick, Joseph B. Grinspoon, Steven Li, Xiuhong Palella, Frank J., Jr. Kingsley, Lawrence A. Witt, Mallory D. George, Richard T. Jacobson, Lisa P. Budoff, Matthew Tracy, Russell P. Brown, Todd T. Post, Wendy S. TI Elevated Levels of Monocyte Activation Markers Are Associated With Subclinical Atherosclerosis in Men With and Those Without HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE human immunodeficiency virus; inflammation; monocyte activation; atherosclerosis; plaque ID HUMAN-IMMUNODEFICIENCY-VIRUS; CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; MULTICENTER AIDS COHORT; CHEMOATTRACTANT PROTEIN-1; SOLUBLE CD163; RHEUMATOID-ARTHRITIS; PROGNOSTIC VALUE AB Background. Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study. Methods. We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of >= 50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors. Results. Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of >= 50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque. Conclusions. sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection. C1 [McKibben, Rebeccah A.; George, Richard T.; Brown, Todd T.; Post, Wendy S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Margolick, Joseph B.; Li, Xiuhong; Jacobson, Lisa P.; Post, Wendy S.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Grinspoon, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palella, Frank J., Jr.] Northwestern Univ, Chicago, IL 60611 USA. [Kingsley, Lawrence A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Witt, Mallory D.; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Burlington, VT 05405 USA. RP Post, WS (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. EM wpost@jhmi.edu FU National Heart Lung and Blood Institute [RO1 HL095129]; National Center for Advancing Translational Sciences, a component of the National Institutes of Health; National Institutes of Health Roadmap for Medical Research [UL1-RR025005]; University of Washington CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center [5R01 HL095126]; American Heart Association [13PRE16970094]; Johns Hopkins University; National Institute of Allergy and Infectious Diseases; National Cancer Institute [UL1-RR025005, UO1-AI-35042, UL1-TR000124, UM1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041] FX This work was supported by the National Heart Lung and Blood Institute (RO1 HL095129 to W. S. P.); the National Center for Advancing Translational Sciences, a component of the National Institutes of Health and the National Institutes of Health Roadmap for Medical Research (grant UL1-RR025005); the University of Washington CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center (grant 5R01 HL095126); the American Heart Association (predoctoral fellowship award 13PRE16970094 to R. A. M.); Johns Hopkins University (predoctoral research program award to R. A. M.); and the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute (grants UO1-AI-35042, UL1-RR025005, UL1-TR000124, UM1-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041 to the MACS). NR 45 TC 34 Z9 35 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2015 VL 211 IS 8 BP 1219 EP 1228 DI 10.1093/infdis/jiu594 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4LP UT WOS:000354720900006 PM 25362192 ER PT J AU Navarro-Gomez, D Leipzig, J Shen, LS Lott, M Stassen, APM Wallace, DC Wiggs, JL Falk, MJ van Oven, M Gai, XW AF Navarro-Gomez, Daniel Leipzig, Jeremy Shen, Lishuang Lott, Marie Stassen, Alphons P. M. Wallace, Douglas C. Wiggs, Janey L. Falk, Marni J. van Oven, Mannis Gai, Xiaowu TI Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier SO BIOINFORMATICS LA English DT Article ID CONSISTENT TREATMENT; CONTROL REGION; DNA; VARIANTS; SEQUENCE; GENOME; TREE AB Motivation: All current mitochondrial haplogroup classification tools require variants to be detected from an alignment with the reference sequence and to be properly named according to the canonical nomenclature standards for describing mitochondrial variants, before they can be compared with the haplogroup determining polymorphisms. With the emergence of high-throughput sequencing technologies and hence greater availability of mitochondrial genome sequences, there is a strong need for an automated haplogroup classification tool that is alignment-free and agnostic to reference sequence. Results: We have developed a novel mitochondrial genome haplogroup-defining algorithm using a k-mer approach namely Phy-Mer. Phy-Mer performs equally well as the leading haplogroup classifier, HaploGrep, while avoiding the errors that may occur when preparing variants to required formats and notations. We have further expanded Phy-Mer functionality such that next-generation sequencing data can be used directly as input. C1 [Navarro-Gomez, Daniel; Shen, Lishuang; Wiggs, Janey L.; Gai, Xiaowu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02163 USA. [Leipzig, Jeremy] Childrens Hosp Philadelphia, Ctr Biomed Informaticsand, Philadelphia, PA 19104 USA. [Lott, Marie; Wallace, Douglas C.] Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA. [Stassen, Alphons P. M.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands. [Wallace, Douglas C.; Falk, Marni J.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Falk, Marni J.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [van Oven, Mannis] Univ Med Ctr Rotterdam, Erasmus MC, Dept Forens Mol Biol, Rotterdam, Netherlands. RP Gai, XW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02163 USA. EM Xiaowu_Gai@meei.harvard.edu RI Shen, Lishuang/B-3040-2013; OI Leipzig, Jeremy/0000-0001-7224-9620; van Oven, Mannis/0000-0003-0026-7998 FU Massachusetts Eye and Ear Infirmary (MEEI) for MEEI Bioinformatics Center; National Institutes of Health (North American Mitochondrial Disease Consortium pilot award) [U54-NS078059, U41-HG006834, NAMDC7407, NS021328]; United Mitochondrial Disease Foundation (UMDF); Netherlands Genomic Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) within Forensic Genomics Consortium Netherlands (FGCN) FX This work was largely supported by institutional fund provided by Massachusetts Eye and Ear Infirmary (MEEI) for MEEI Bioinformatics Center (X.G.). It was also supported in part by the National Institutes of Health (U54-NS078059-North American Mitochondrial Disease Consortium pilot award #NAMDC7407 to M.J.F. and X.G.; and U41-HG006834) and the United Mitochondrial Disease Foundation (UMDF) support for MSeqDR (https://mseqdr.org). J.L., M.L., and D.C.W. were supported in part by the National Institutes of Health grant NS021328 (D.C.W.). MvO was supported in part by a grant from the Netherlands Genomic Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands (FGCN). NR 15 TC 6 Z9 6 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2015 VL 31 IS 8 BP 1310 EP 1312 DI 10.1093/bioinformatics/btu825 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA CI0UK UT WOS:000354453700026 PM 25505086 ER PT J AU Brune, K Frank, J Schwingshackl, A Finigan, J Sidhaye, VK AF Brune, Kieran Frank, James Schwingshackl, Andreas Finigan, James Sidhaye, Venkataramana K. TI Pulmonary epithelial barrier function: some new players and mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Review DE lung; epithelial barrier; permeability; transport; ions ID ACUTE LUNG INJURY; GROWTH-FACTOR RECEPTOR; RESPIRATORY-DISTRESS-SYNDROME; POTASSIUM CHANNEL TREK-1; NA-K-ATPASE; TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMAN AIRWAY EPITHELIA; TIGHT JUNCTION PERMEABILITY; ALVEOLAR FLUID CLEARANCE; BETA-CATENIN AB The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells. In this review, we will discuss a few emerging paradigms of permeability changes through altered ion transport and paracellular regulation by which the epithelium gates its response to potentially detrimental luminal stimuli. This review is a summary of talks presented during a symposium in Experimental Biology geared toward novel and less recognized methods of epithelial barrier regulation. First, we will discuss mechanisms of dynamic regulation of cell-cell contacts in the context of repetitive exposure to inhaled infectious and noninfectious insults. In the second section, we will briefly discuss mechanisms of transcellular ion homeostasis specifically focused on the role of claudins and paracellular ion-channel regulation in chronic barrier dysfunction. In the next section, we will address transcellular ion transport and highlight the role of Trek-1 in epithelial responses to lung injury. In the final section, we will outline the role of epithelial growth receptor in barrier regulation in baseline, acute lung injury, and airway disease. We will then end with a summary of mechanisms of epithelial control as well as discuss emerging paradigms of the epithelium role in shifting between a structural element that maintains tight cell-cell adhesion to a cell that initiates and participates in immune responses. C1 [Brune, Kieran; Sidhaye, Venkataramana K.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Frank, James] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Frank, James] Vet Hlth Res Inst, NCIRE, San Francisco, CA 94143 USA. [Schwingshackl, Andreas] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Finigan, James] Natl Jewish Hlth, Ctr Canc, Div Oncol, Denver, CO USA. RP Sidhaye, VK (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, Dept Med, 4B-59,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM vsidhay1@jhmi.edu FU NHLBI NIH HHS [K08 HL118118, R01 HL111674, R21 HL111707, R56 HL088440] NR 212 TC 8 Z9 8 U1 3 U2 17 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 APR 15 PY 2015 VL 308 IS 8 BP L731 EP L745 DI 10.1152/ajplung.00309.2014 PG 15 WC Physiology; Respiratory System SC Physiology; Respiratory System GA CH3JP UT WOS:000353927300001 PM 25637609 ER PT J AU Grazioli, S Gil, S An, D Kajikawa, O Farnand, AW Hanson, JF Birkland, T Chen, P Duffield, J Schnapp, LM Altemeier, WA Matute-Bello, G AF Grazioli, Serge Gil, Sucheol An, Dowon Kajikawa, Osamu Farnand, Alex W. Hanson, Josiah F. Birkland, Timothy Chen, Peter Duffield, Jeremy Schnapp, Lynn M. Altemeier, William A. Matute-Bello, Gustavo TI CYR61 (CCN1) overexpression induces lung injury in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE Cysteine-rich protein-61; CCN1; acute lung injury ID CELL-MIGRATION MODULATOR; IMMEDIATE-EARLY GENE; MATRICELLULAR PROTEINS; GROWTH-FACTOR; EPITHELIAL-CELLS; EXPRESSION; FIBROSIS; PROLIFERATION; ADHESION; INFLAMMATION AB Cysteine- rich protein-61 (CYR61), also known as connective tissue growth factor, CYR61, and nephroblastoma overexpressed gene 1 (CCN1), is a heparin-binding protein member of the CCN family of matricellular proteins. Gene expression profiles showed that Cyr61 is upregulated in human acute lung injury (ALI), but its functional role is unclear. We hypothesized that CYR61 contributes to ALI in mice. First, we demonstrated that CYR61 expression increases after bleomycin-induced lung injury. We then used adenovirus-mediated gene transfer to determine whether CYR61 overexpression in the lungs was sufficient to cause ALI. Mice instilled with CYR61 adenovirus showed greater weight loss, increased bronchoalveolar lavage total neutrophil counts, increased protein concentrations, and increased mortality compared with mice instilled with empty-vector adenovirus. Immunohistochemical studies in lungs from humans with idiopathic pulmonary fibrosis revealed CYR61 expression on the luminal membrane of alveolar epithelial cells in areas of injury. We conclude that CYR61 is upregulated in ALI and that CYR61 overexpression exacerbates ALI in mice. C1 [Grazioli, Serge] Univ Hosp Geneva, Pediat Crit Care Unit, Geneva, Switzerland. [Grazioli, Serge; Gil, Sucheol; An, Dowon; Kajikawa, Osamu; Farnand, Alex W.; Hanson, Josiah F.; Birkland, Timothy; Chen, Peter; Schnapp, Lynn M.; Altemeier, William A.; Matute-Bello, Gustavo] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Med, Seattle, WA USA. [Duffield, Jeremy] Univ Washington, Dept Med, Div Nephrol, Seattle, WA USA. [Matute-Bello, Gustavo] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Matute-Bello, G (reprint author), 850 Republican St,Box 358052, Seattle, WA 98109 USA. RI Grazioli, Serge/A-1457-2016; OI Chen, Peter/0000-0002-5330-1718 FU Swiss National Science Foundation [PBGEP3-142293]; NIH:NHLBI [HL081764]; NHLBI grant [HL086883, HL103868, HL120947] FX This work was supported by Swiss National Science Foundation Grant PBGEP3-142293 (S. Grazioli), NIH:NHLBI grant HL081764 (G. MatuteBello), NHLBI grant HL086883 (W. Altemeier), HL103868 (P. Chen), and HL120947 (P. Chen). NR 34 TC 4 Z9 4 U1 1 U2 5 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 APR 15 PY 2015 VL 308 IS 8 BP L759 EP L765 DI 10.1152/ajplung.00190.2014 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA CH3JP UT WOS:000353927300003 PM 25713320 ER PT J AU Lin, T Maita, D Thundivalappil, SR Riley, FE Hambsch, J Van Marter, LJ Christou, HA Berra, L Fagan, S Christiani, DC Warren, HS AF Lin, Tian Maita, Dayana Thundivalappil, Sujatha R. Riley, Frank E. Hambsch, Jasmin Van Marter, Linda J. Christou, Helen A. Berra, Lorenzo Fagan, Shawn Christiani, David C. Warren, H. Shaw TI Hemopexin in severe inflammation and infection: mouse models and human diseases SO CRITICAL CARE LA English DT Article ID RED-BLOOD-CELLS; NECROTIZING ENTEROCOLITIS; HEMOLYTIC DISEASES; FREE HEMOGLOBIN; HEME; SEPSIS; MICE; INTERLEUKIN-6; ASSOCIATION; MORTALITY AB Introduction: Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients. Methods: We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants. Results: Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations. Conclusions: Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration. C1 [Lin, Tian; Maita, Dayana; Thundivalappil, Sujatha R.; Riley, Frank E.; Hambsch, Jasmin] Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Charlestown, MA 02129 USA. [Van Marter, Linda J.; Christou, Helen A.; Berra, Lorenzo; Fagan, Shawn; Christiani, David C.; Warren, H. Shaw] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Van Marter, Linda J.; Christou, Helen A.] Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Fagan, Shawn] Massachusetts Gen Hosp, Dept Surg, MGH Burn Serv, Boston, MA 02114 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med Pulm & Crit Care Med, Charlestown, MA 02129 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Pediat & Med, Infect Dis Unit, Charlestown, MA 02129 USA. RP Lin, T (reprint author), Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. EM tlin7@mgh.harvard.edu FU National Institute of Health [AI059010]; Shriners Hospital for Crippled Children [87200]; DARPA [W911NF-13-1-0070, W911NF-10-1-0271]; Gerber Foundation; Clinical Translational Science Award [UL1RR025758]; BWH from the National Center for Research Resources FX This work was supported by the National Institute of Health (grant number AI059010); the Shriners Hospital for Crippled Children (grant number 87200); DARPA (grant numbers W911NF-13-1-0070, W911NF-10-1-0271); Gerber Foundation and Clinical Translational Science Award (UL1RR025758) to Harvard University and BWH from the National Center for Research Resources. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. We acknowledge the assistance of Maryelizabet Bilodeau in Division of Burns in MGH, and Marcia Filip and Yvonne Sheldon in BWH. NR 31 TC 4 Z9 4 U1 0 U2 3 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 APR 15 PY 2015 VL 19 AR 166 DI 10.1186/s13054-015-0885-x PG 8 WC Critical Care Medicine SC General & Internal Medicine GA CH7UV UT WOS:000354243000001 PM 25888135 ER PT J AU Masse, NY Jarosiewicz, B Simeral, JD Bacher, D Stavisky, SD Cash, SS Oakley, EM Berhanu, E Eskandar, E Friehs, G Hochberg, LR Donoghue, JP AF Masse, Nicolas Y. Jarosiewicz, Beata Simeral, John D. Bacher, Daniel Stavisky, Sergey D. Cash, Sydney S. Oakley, Erin M. Berhanu, Etsub Eskandar, Emad Friehs, Gerhard Hochberg, Leigh R. Donoghue, John P. TI Reprint of "Non-causal spike filtering improves decoding of movement intention for intracortical BCIs" SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Spike sorting; Neural decoding; Threshold crossing; Non-causal filter; Brain-computer interface; Microelectrode array ID LOCAL-FIELD POTENTIALS; MULTIUNIT ACTIVITY; PREMOTOR CORTICES; GRASP; MOTOR; REACH; TETRAPLEGIA; SIGNAL AB Background: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. New method: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4 ms lag between recording and filtering neural signals. Results: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7 degrees for participant S3, who was implanted 5.4 years prior to this study, and by 3.5 degrees for participant T2, who was implanted 3 months prior to this study. Conclusions: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs. (C) 2015 Published by Elsevier B.V. C1 [Masse, Nicolas Y.; Jarosiewicz, Beata; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Masse, Nicolas Y.; Jarosiewicz, Beata; Simeral, John D.; Bacher, Daniel; Hochberg, Leigh R.; Donoghue, John P.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Jarosiewicz, Beata; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.] Dept Vet Affairs Med Ctr, Rehabil R&D Serv, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Simeral, John D.; Bacher, Daniel; Stavisky, Sergey D.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Cash, Sydney S.; Oakley, Erin M.; Berhanu, Etsub; Hochberg, Leigh R.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Eskandar, Emad; Friehs, Gerhard] Massachusetts Gen Hosp, Neurosurg, Boston, MA 02114 USA. [Cash, Sydney S.; Eskandar, Emad; Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA USA. RP Masse, NY (reprint author), Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. EM masse@uchicago.edu OI Masse, Nicolas/0000-0002-9094-1298 FU NIH: NIDCD [R01DC009899]; NICHD-NCMRR [N01HD53403, N01HD10018]; Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6453R, A6779I]; Doris Duke Charitable Foundation; Craig H. Neilsen Foundation; MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation; Cyberkinetics Neurotechnology Systems (CKI) FX We thank participants S3 and T2 for their dedication to this research. We thank David Rosler, Laurie Barefoot, Katherine Centrella, and the caregiver staff at the Boston Home for their contributions to this research. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. This work was supported by NIH: NIDCD (R01DC009899) and NICHD-NCMRR (N01HD53403, N01HD10018); Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs (Merit Review Awards B6453R and A6779I); Doris Duke Charitable Foundation, Craig H. Neilsen Foundation, MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke, and the Katie Samson Foundation. The pilot clinical trial into which participant S3 was recruited was sponsored in part by Cyberkinetics Neurotechnology Systems (CKI). The BrainGate clinical trial is directed by Massachusetts General Hospital. NR 28 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 15 PY 2015 VL 244 SI SI BP 94 EP 103 DI 10.1016/j.jneumeth.2015.02.001 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CH1BA UT WOS:000353754900012 PM 25681017 ER PT J AU Steward, R Tambe, D Hardin, CC Krishnan, R Fredberg, JJ AF Steward, Robert, Jr. Tambe, Dhananjay Hardin, C. Corey Krishnan, Ramaswamy Fredberg, Jeffrey J. TI Fluid shear, intercellular stress, and endothelial cell alignment SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE endothelial cell; cell alignment; laminar fluid shear; intercellular stress; tractions ID CYTOSKELETAL REARRANGEMENT; ADHERENS JUNCTIONS; MECHANICAL TENSION; FORCE-GENERATION; TRACTION FORCES; MIGRATION; DYNAMICS; FLOW; PROLIFERATION; PERMEABILITY AB Endothelial cell alignment along the direction of laminar fluid flow is widely understood to be a defining morphological feature of vascular homeostasis. While the role of associated signaling and structural events have been well studied, associated intercellular stresses under laminar fluid shear have remained ill-defined and the role of these stresses in the alignment process has remained obscure. To fill this gap, we report here the tractions as well as the complete in-plane intercellular stress fields measured within the human umbilical vein endothelial cell (HUVEC) monolayer subjected to a steady laminar fluid shear of 1 Pa. Tractions, intercellular stresses, as well as their time course, heterogeneity, and anisotropy, were measured using monolayer traction microscopy and monolayer stress microscopy. Prior to application of laminar fluid flow, intercellular stresses were largely tensile but fluctuated dramatically in space and in time (317 +/- 122 Pa). Within 12 h of the onset of laminar fluid flow, the intercellular stresses decreased substantially but continued to fluctuate dramatically (142 +/- 84 Pa). Moreover, tractions and intercellular stresses aligned strongly and promptly (within 1 h) along the direction of fluid flow, whereas the endothelial cell body aligned less strongly and substantially more slowly (12 h). Taken together, these results reveal that steady laminar fluid flow induces prompt reduction in magnitude and alignment of tractions and intercellular stress tensor components followed by the retarded elongation and alignment of the endothelial cell body. Appreciably smaller intercellular stresses supported by cell-cell junctions logically favor smaller incidence of gap formation and thus improved barrier integrity. C1 [Steward, Robert, Jr.; Fredberg, Jeffrey J.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Tambe, Dhananjay] Univ S Alabama, Mobile, AL 36688 USA. [Hardin, C. Corey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hardin, C. Corey; Krishnan, Ramaswamy] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Krishnan, Ramaswamy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Fredberg, JJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Program Mol & Integrat Physiol Sci MIPS, Rm 1-313,665 Huntington Ave, Boston, MA 02115 USA. EM jfredber@hsph.harvard.edu FU National Heart, Lung, and Blood Institute [T32HL007118, R01HL107561, P01HL120839] FX This research was supported by the National Heart, Lung, and Blood Institute Grants T32HL007118, R01HL107561, and P01HL120839. NR 51 TC 7 Z9 7 U1 2 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR 15 PY 2015 VL 308 IS 8 BP C657 EP C664 DI 10.1152/ajpcell.00363.2014 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CH3WA UT WOS:000353960200009 PM 25652451 ER PT J AU Bamman, MM Ferrando, AA Evans, RP Stec, MJ Kelly, NA Gruenwald, JM Corrick, KL Trump, JR Singh, JA AF Bamman, Marcas M. Ferrando, Arny A. Evans, Richard P. Stec, Michael J. Kelly, Neil A. Gruenwald, Johannes M. Corrick, Katie L. Trump, Jesse R. Singh, Jasvinder A. TI Muscle inflammation susceptibility: a prognostic index of recovery potential after hip arthroplasty? SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE total hip arthroplasty; muscle atrophy; inflammation; muscle protein metabolism; muscle regeneration ID TOTAL KNEE ARTHROPLASTY; HUMAN SKELETAL-MUSCLE; PAIN MEDICATIONS; POOR PAIN; ATROPHY; REGENERATION; OSTEOARTHRITIS; PREDICTORS; EXPRESSION; CELLS AB While elective total hip arthroplasty (THA) for end-stage osteoarthritis (OA) improves pain, mobility function, and quality of life in most cases, a large proportion of patients suffer persistent muscle atrophy, pain, and mobility impairment. Extensive skeletal muscle damage is unavoidable in these surgical procedures, and it stands to reason that poor recovery and long-term mobility impairment among some individuals after THA is linked to failed muscle regeneration and regrowth following surgery and that local muscle inflammation susceptibility (MuIS) is a major contributing factor. Here we present results of two integrated studies. In study 1, we compared muscle inflammation and protein metabolism signaling in elective THA (n = 15) vs. hip fracture/trauma (HFX; n = 11) vs. nonsurgical controls (CON; n = 19). In study 2, we compared two subgroups of THA patients dichotomized into MuIS((+)) (n = 7) or MuIS((-)) (n = 7) based on muscle expression of TNF-like weak inducer of apoptosis (TWEAK) receptor (Fn14). As expected, HFX demonstrated overt systemic and local muscle inflammation and hypermetabolism. By contrast, no systemic inflammation was detected in elective THA patients; however, local muscle inflammation in the perioperative limb was profound in MuIS((+)) and was accompanied by suppressed muscle protein synthesis compared with MuIS((-)). Muscle from the contralateral limb of MuIS((+)) was unaffected, providing evidence of a true inflammation susceptibility localized to the muscle surrounding the hip with end-stage OA. We suggest MuIS status assessed at the time of surgery may be a useful prognostic index for muscle recovery potential and could therefore provide the basis for a personalized approach to postsurgery rehabilitation. C1 [Bamman, Marcas M.; Stec, Michael J.; Kelly, Neil A.; Corrick, Katie L.; Trump, Jesse R.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. [Ferrando, Arny A.] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. [Ferrando, Arny A.] Univ Arkansas Med Sci, Ctr Translat Res Aging & Longev, Little Rock, AR 72205 USA. [Evans, Richard P.] Univ Arkansas Med Sci, Dept Orthoped Surg, Little Rock, AR 72205 USA. [Gruenwald, Johannes M.] Univ Arkansas Med Sci, Dept Trauma Surg, Little Rock, AR 72205 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Bamman, Marcas M.; Stec, Michael J.; Kelly, Neil A.; Singh, Jasvinder A.] Univ Alabama Birmingham, UAB Ctr Exercise Med, Birmingham, AL 35294 USA. [Bamman, Marcas M.; Singh, Jasvinder A.] Univ Alabama Birmingham, Comprehens Arthrit Musculoskeletal & Autoimmun Ct, Birmingham, AL 35294 USA. [Bamman, Marcas M.] Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. RP Bamman, MM (reprint author), Univ Alabama Birmingham, UAB Ctr Exercise Med, MCLM 966,1918 Univ Blvd, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU National Institutes of Health [R01-AR-052293, P30-AG-028718]; Veterans Affairs Merit Review Award; UAB Center for Exercise Medicine Core Muscle Research Laboratory FX The research was supported in part by National Institutes of Health Grants R01-AR-052293 (to A. A. Ferrando) and P30-AG-028718 (to A. A. Ferrando), a Veterans Affairs Merit Review Award (to M. M. Bamman), and the UAB Center for Exercise Medicine Core Muscle Research Laboratory (to M. M. Bamman). NR 35 TC 2 Z9 2 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR 15 PY 2015 VL 308 IS 8 BP E670 EP E679 DI 10.1152/ajpendo.00576.2014 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA CH3SS UT WOS:000353951200007 PM 25670829 ER PT J AU Herak-Kramberger, CM Breljak, D Ljubojevic, M Matokanovic, M Lovric, M Rogic, D Brzica, H Vrhovac, I Karaica, D Micek, V Dupor, JI Brown, D Sabolic, I AF Herak-Kramberger, Carol M. Breljak, Davorka Ljubojevic, Marija Matokanovic, Mirela Lovric, Mila Rogic, Dunja Brzica, Hrvoje Vrhovac, Ivana Karaica, Dean Micek, Vedran Dupor, Jana Ivkovic Brown, Dennis Sabolic, Ivan TI Sex-dependent expression of water channel AQP1 along the rat nephron SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin 1; castration; sex differences; immunocytochemistry; ovariectomy; sex steroids; Western blotting ID SPONTANEOUSLY HYPERTENSIVE-RATS; RENIN-ANGIOTENSIN SYSTEM; INDUCED DOWN-REGULATION; GENDER-DIFFERENCES; PROXIMAL TUBULE; URETERAL OBSTRUCTION; BLOOD-PRESSURE; DECREASED EXPRESSION; RENAL EXPRESSION; AQUAPORIN 1 AB In the mammalian kidney, nonglycosylated and glycosylated forms of aquaporin protein 1 (AQP1) coexist in the luminal and basolateral plasma membranes of proximal tubule and descending thin limb. Factors that influence AQP1 expression in (patho) physiological conditions are poorly known. Thus far, only angiotensin II and hypertonicity were found to upregulate AQP1 expression in rat proximal tubule in vivo and in vitro (Bouley R, Palomino Z, Tang SS, Nunes P, Kobori H, Lu HA, Shum WW, Sabolic I, Brown D, Ingelfinger JR, Jung FF. Am J Physiol Renal Physiol 297: F1575-F1586, 2009), a phenomenon that may be relevant for higher blood pressure observed in men and male experimental animals. Here we investigated the sex-dependent AQP1 protein and mRNA expression in the rat kidney by immunochemical methods and qRT-PCR in tissue samples from prepubertal and intact gonadectomized animals and sex hormone-treated gonadectomized adult male and female animals. In adult rats, the overall renal AQP1 protein and mRNA expression was similar to 80% and similar to 40% higher, respectively, in males than in females, downregulated by gonadectomy in both sexes and upregulated strongly by testosterone and moderately by progesterone treatment; estradiol treatment had no effect. In prepubertal rats, the AQP1 protein expression was low compared with adults and slightly higher in females, whereas the AQP1 mRNA expression was low and similar in both sexes. The observed differences in AQP1 protein expression in various experiments mainly reflect changes in the glycosylated form. The male-dominant expression of renal AQP1 in rats, which develops after puberty largely in the glycosylated form of the protein, may contribute to enhanced fluid reabsorption following the androgen-or progesterone-stimulated activities of sodium-reabsorptive mechanisms in proximal tubules. C1 [Herak-Kramberger, Carol M.; Breljak, Davorka; Ljubojevic, Marija; Matokanovic, Mirela; Brzica, Hrvoje; Vrhovac, Ivana; Karaica, Dean; Micek, Vedran; Sabolic, Ivan] Inst Med Res & Occupat Hlth, Mol Toxicol, Zagreb 10000, Croatia. [Lovric, Mila; Rogic, Dunja] Univ Hosp Ctr, Clin Inst Lab Diag, Zagreb, Croatia. [Dupor, Jana Ivkovic] Univ Rijeka, Dept Biotechnol, Rijeka, Croatia. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Mol Toxicol, Ksaverska Cesta 2, Zagreb 10000, Croatia. EM sabolic@imi.hr FU Ministry for Science, Education, and Sports, Republic of Croatia [022-0222148-2146]; Croatian Science Foundation [1481]; NIH [DK096586] FX This work was supported partially by grant no. 022-0222148-2146 (I. Sabolic) from the Ministry for Science, Education, and Sports, Republic of Croatia, and partially by grant no. 1481 (I. Sabolic) from the Croatian Science Foundation. D. Brown was supported by NIH grant DK096586. NR 71 TC 5 Z9 5 U1 0 U2 2 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 APR 15 PY 2015 VL 308 IS 8 BP F809 EP F821 DI 10.1152/ajprenal.00368.2014 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CH3UZ UT WOS:000353957300003 PM 25656365 ER PT J AU Sakely, H Corbo, J Coley, K McGivney, M Thorpe, C Klatt, P Schleiden, L Zaharoff, J Cox-Vance, L Balestrino, V AF Sakely, Heather Corbo, Jason Coley, Kim McGivney, Melissa Thorpe, Carolyn Klatt, Patricia Schleiden, Loren Zaharoff, John Cox-Vance, Lora Balestrino, Vincent TI Pharmacist-led collaborative practice for older adults SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID MEDICATION USE; CARE; RECONCILIATION C1 [Sakely, Heather] UPMC St Margaret, Geriatr Pharmacotherapy, Pittsburgh, PA 15215 USA. [Corbo, Jason] UPMC St Margaret, Geriatr, Pittsburgh, PA 15215 USA. [Coley, Kim] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [McGivney, Melissa] Univ Pittsburgh, Sch Pharm, Community Partnerships, Pittsburgh, PA 15260 USA. [McGivney, Melissa] Univ Pittsburgh, Sch Pharm, Pharm & Therapeut, Pittsburgh, PA 15260 USA. [Thorpe, Carolyn] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Thorpe, Carolyn] Univ Pittsburgh, Sch Pharm, Pharm & Therapeut, Pittsburgh, PA 15260 USA. [Klatt, Patricia] UPMC St Margaret, Adv Pharmacist Practice, Pittsburgh, PA USA. [Schleiden, Loren] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. [Zaharoff, John] Willows, Presbyterian SeniorCare, Oakmont, PA USA. [Cox-Vance, Lora] UPMC St Margaret, Geriatr Fellowship, Pittsburgh, PA USA. [Balestrino, Vincent] UPMC St Margaret, Family Med Residency, Pittsburgh, PA USA. RP Sakely, H (reprint author), UPMC St Margaret, Geriatr Pharmacotherapy, Pittsburgh, PA 15215 USA. EM sakelyh@upmc.edu OI Coley, Kim/0000-0002-5454-5300 NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 15 PY 2015 VL 72 IS 8 BP 606 EP + DI 10.2146/ajhp140228 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG2BH UT WOS:000353079400008 PM 25825181 ER PT J AU Beca, F Pereira, M Cameselle-Teijeiro, JF Martins, D Schmitt, F AF Beca, Francisco Pereira, Miguel Cameselle-Teijeiro, Jorge F. Martins, Diana Schmitt, Fernando TI Altered PPP2R2A and Cyclin D1 expression defines a subgroup of aggressive luminal-like breast cancer SO BMC CANCER LA English DT Article DE Breast cancer; Immunohistochemistry; TCGA PPP2R2A (B55 alpha); Cyclin D1; Prognosis ID PROTEIN PHOSPHATASE 2A; CCND1 AMPLIFICATION; PROGNOSIS; PHOSPHORYLATION; RECOMMENDATIONS; PROGRESSION; INHIBITION; TAMOXIFEN; B55-ALPHA; CELLS AB Background: PPP2R2A deletions were recently linked to a subgroup of luminal breast carcinoma (BC) that exhibits poor survival. This subgroup also exhibited amplification of a chromosome region containing the Cyclin D1 coding gene, CCND1. Therefore, we aimed to investigate whether a combination of PPP2R2A (B55 alpha) and Cyclin D1 expression statuses evaluated by immunohistochemistry (IHC) could define a subgroup of luminal BC that exhibits poor survival. Methods: First we conducted a retrospective cohort study using sequencing data from The Cancer Genome Atlas initiative to correlate PPP2R2A copy number alteration (CNA) status with its expression level and the corresponding overall survival (OS). Next, also using a retrospective cohort study design, we evaluated the PPP2R2A (B55 alpha) expression levels by IHC in a total of 807 BC patients from two independent cohorts (discovery cohort n = 349 and validation cohort n = 458). Cyclin D1 expression was also evaluated, and the PPP2R2A (B55 alpha)(-/low)/Cyclin D1(high) phenotype was evaluated as a predictor of disease-free survival (DFS) and OS in luminal-like BC patients. Results: Deletions in the PPP2R2A gene strongly correlate with lower mRNA expression and poorer OS. PPP2R2A (B55 alpha)(-/low) carcinomas have significantly shorter DFS and OS. Furthermore, in univariate analysis, the PPP2R2A (B55 alpha)(-/low)/Cyclin D1(high) phenotype is significantly associated with poorer DFS and OS. In a multivariate analysis, the PPP2R2A (B55 alpha)(-/low)/Cyclin D1(high) phenotype is significantly associated with poor DFS, thus defining a group of luminal-like BC with higher risk of relapse. Conclusion: We demonstrate that BCs harboring PPP2R2A deletions are associated with worse OS. Moreover, this is the first study to demonstrate that the combination of altered PPP2R2A (B55 alpha) and high Cyclin D1 expression by IHC defines a subgroup of luminal-like BC patients with a high risk of relapse and death. C1 [Beca, Francisco] Univ Porto, Inst Mol Pathol & Immunol, IPATIMUP, P-4200465 Oporto, Porto, Portugal. [Beca, Francisco] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Pereira, Miguel] Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Ctr Canc, Boston, MA 02114 USA. [Cameselle-Teijeiro, Jorge F.] Univ Vigo, Complexo Hosp, CHUVI, Vigo 362004, Spain. [Martins, Diana] Univ Porto, IBMC, P-4150180 Oporto, Portugal. [Schmitt, Fernando] Lab Natl Sante 1, Dept Pathol & Med, L-3555 Dudelange, Luxembourg. RP Schmitt, F (reprint author), Lab Natl Sante 1, Dept Pathol & Med, Rue Louis Reche, L-3555 Dudelange, Luxembourg. EM fschmitt@ipatimup.pt OI Beca, Francisco/0000-0002-4409-012X FU Portuguese National Funds through Fundacao para a Ciencia e Tecnologia (FCT) of the Harvard Medical School-Portugal Program [FCT:HMSP-ICJ/0006/2012]; FCT FX This work was partially supported by Portuguese National Funds through Fundacao para a Ciencia e Tecnologia (FCT) (project reference FCT:HMSP-ICJ/0006/2012) in the framework of the Harvard Medical School-Portugal Program. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT. NR 33 TC 3 Z9 5 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 15 PY 2015 VL 15 AR 285 DI 10.1186/s12885-015-1266-1 PG 10 WC Oncology SC Oncology GA CG7AN UT WOS:000353454400002 PM 25879784 ER PT J AU Kimmelman, AC AF Kimmelman, Alec C. TI Metabolic Dependencies in RAS-Driven Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED SOLID TUMORS; PANCREATIC-CANCER; SELECTIVE AUTOPHAGY; GLUTAMINE-METABOLISM; TRANSFORMED CELLS; MEK INHIBITORS; ONCOGENIC KRAS; HYDROXYCHLOROQUINE; GROWTH; MACROPINOCYTOSIS AB The ability to inhibit the RAS oncogene has been the holy grail of oncology because of the critical role of this gene in a multitude of tumor types. In addition, RAS-mutant tumors are among the most aggressive and refractory to treatment. Although directly targeting the RAS oncogene has proven challenging, an alternative approach for treating RAS-driven cancers is to inhibit critical downstream events that are required for tumor maintenance. Indeed, much focus has been put on inhibiting signaling cascades downstream of RAS. Recent studies have shown that oncogenic RAS promotes a metabolic reprogramming of tumor cells, shifting them toward an anabolic metabolism necessary to produce biomass to support unconstrained proliferation. These cancers also use a diverse set of fuel sources to meet their metabolic needs and have even developed a variety of mechanisms to act as metabolic scavengers to obtain necessary metabolic substrates from both extracellular and intracellular sources. Collectively, these adaptations can create "metabolic bottle-necks" whereby tumor cells rely on particular pathways or rate-limiting metabolites. In this regard, inhibiting individual or combinations of these metabolic pathways can attenuate growth in preclinical models. Because these dependencies are tumor selective and downstream of oncogenic RAS, there is the opportunity for therapeutic intervention. Although targeting tumor metabolism is still in the early days of translation to patients, our continued advances in understanding critical metabolic adaptations in RAS-driven cancers, as well as the ability to study this altered metabolism in relevant tumor models, will accelerate the development of new therapeutic approaches. (C)2015 AACR. C1 [Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Kimmelman, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM 221, Boston, MA 02215 USA. EM alec_kimmelman@dfci.harvard.edu FU NCI of the NIH [R01CA157490]; American Cancer Society Research Scholar [RSG-13-298-01-TBG]; Lustgarten Foundation FX A.C. Kimmelman was supported by the NCI of the NIH under award number R01CA157490, an American Cancer Society Research Scholar Grant (RSG-13-298-01-TBG), and the Lustgarten Foundation. NR 70 TC 34 Z9 34 U1 2 U2 18 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 APR 15 PY 2015 VL 21 IS 8 BP 1828 EP 1834 DI 10.1158/1078-0432.CCR-14-2425 PG 7 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200010 PM 25878364 ER PT J AU Shapiro, GI Bell-McGuinn, KM Molina, JR Bendell, J Spicer, J Kwak, EL Pandya, SS Millham, R Borzillo, G Pierce, KJ Han, LX Houk, BE Gallo, JD Alsina, M Brana, I Tabernero, J AF Shapiro, Geoffrey I. Bell-McGuinn, Katherine M. Molina, Julian R. Bendell, Johanna Spicer, James Kwak, Eunice L. Pandya, Susan S. Millham, Robert Borzillo, Gary Pierce, Kristen J. Han, Lixin Houk, Brett E. Gallo, Jorge D. Alsina, Maria Brana, Irene Tabernero, Josep TI First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED SOLID TUMORS; CELL LUNG-CANCER; PHASE-I; MUTATIONS; PATHWAY; TARGET; GROWTH; SAFETY; PX-866 AB Purpose: To evaluate safety (primary endpoint), tolerability, pharmacokinetics, pharmacodynamic profile, and preliminary activity of the intravenous, pan-class I isoform PI3K/mTOR inhibitor PF-05212384 in patients with advanced solid tumors. Experimental Design: Part 1 of this open-label phase I study was designed to estimate the maximum-tolerated dose (MTD) in patients with nonselected solid tumors, using a modified continual reassessment method to guide dose escalation. Objectives of part 2 were MTD confirmation and assessment of preliminary activity in patients with selected tumor types and PI3K pathway dysregulation. Results: Seventy-seven of the 78 enrolled patients received treatment. The MTD for PF-05212384, administered intravenously once weekly, was estimated to be 154 mg. The most common treatment-related adverse events (AE) were mucosal inflammation/ stomatitis (58.4%), nausea (42.9%), hyperglycemia (26%), decreased appetite (24.7%), fatigue (24.7%), and vomiting (24.7%). The majority of patients treated at the MTD experienced only grade 1 treatment-related AEs. Grade 3 treatment-related AEs occurred in 23.8% of patients at the MTD. No treatment-related grade 4-5 AEs were reported at any dose level. Antitumor activity was noted in this heavily pretreated patient population, with two partial responses (PR) and an unconfirmed PR. Eight patients had long-lasting stable disease (>6 months). Pharmacokinetic analyses showed a biphasic concentration-time profile for PF-05212384 (half-life, 30-37 hours after multiple dosing). PF-05212384 inhibited downstream effectors of the PI3K pathway in paired tumor biopsies. Conclusions: These findings demonstrate the manageable safety profile and antitumor activity of the PI3K/mTOR inhibitor PF-05212384, supporting further clinical development for patients with advanced solid malignancies. (C)2015 AACR. C1 [Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA USA. [Bell-McGuinn, Katherine M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Molina, Julian R.] Mayo Clin, Rochester, MN USA. [Bendell, Johanna] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Spicer, James] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [Kwak, Eunice L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pandya, Susan S.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Millham, Robert; Borzillo, Gary; Pierce, Kristen J.] Pfizer Oncol, Groton, CT USA. [Han, Lixin] Pfizer Oncol, Cambridge, MA USA. [Houk, Brett E.] Pfizer Oncol, La Jolla, CA USA. [Gallo, Jorge D.] Pfizer Oncol, Milan, Italy. [Alsina, Maria; Brana, Irene; Tabernero, Josep] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona 08035, Spain. [Alsina, Maria; Brana, Irene; Tabernero, Josep] Univ Autonoma Barcelona, Inst Oncol, Barcelona 08035, Spain. RP Tabernero, J (reprint author), Univ Autonoma Barcelona, Dept Med Oncol, Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, P Vall dHebron 119-129, Barcelona 08035, Spain. EM jtabernero@vhio.net FU Pfizer Inc.; UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC); King's College Hospital NHS Foundation Trust (NIHR Clinical Research Facility) FX This study was sponsored by Pfizer Inc. Medical writing support was provided by S. Mariani, MD, PhD, of Engage Scientific, Envision Pharma, and was funded by Pfizer Inc. J. Spicer acknowledges financial support from the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust (and NIHR Clinical Research Facility). NR 26 TC 13 Z9 13 U1 0 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 APR 15 PY 2015 VL 21 IS 8 BP 1888 EP 1895 DI 10.1158/1078-0432.CCR-14-1306 PG 8 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200017 PM 25652454 ER PT J AU Pokorny, JL Calligaris, D Gupta, SK Iyekegbe, DO Mueller, D Bakken, KK Carlson, BL Schroeder, MA Evans, DL Lou, Z Decker, PA Eckel-Passow, JE Pucci, V Ma, B Shumway, SD Elmquist, WF Agar, NYR Sarkaria, JN AF Pokorny, Jenny L. Calligaris, David Gupta, Shiv K. Iyekegbe, Dennis O., Jr. Mueller, Dustin Bakken, Katrina K. Carlson, Brett L. Schroeder, Mark A. Evans, Debra L. Lou, Zhenkun Decker, Paul A. Eckel-Passow, Jeanette E. Pucci, Vincenzo Ma, Bennett Shumway, Stuart D. Elmquist, William F. Agar, Nathalie Y. R. Sarkaria, Jann N. TI The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; KINASE INHIBITOR; STEM GLIOMAS; TUMOR-CELLS; S-PHASE; REPLICATION; CANCER; RADIOSENSITIZATION; RADIOTHERAPY; XENOGRAFTS AB Purpose: Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme (GBM) xenograft models alone and in combination with radiation and/or temozolomide. Experimental Design: In vitro MK-1775 efficacy alone and in combination with temozolomide, and the impact on DNA damage, was analyzed by Western blotting and gamma H2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI)-MS imaging. Results: GBM22 (IC50 = 68 nmol/L) was significantly more sensitive to MK-1775 compared with five other GBM xenograft lines, including GBM6 (IC50 > 300 nmol/L), and this was associated with a significant difference in pan-nuclear gamma H2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with temozolomide in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with temozolomide, whereas in a flank model of GBM22, MK-1775 exhibited both single-agent and combinatorial activity with temozolomide. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared with heterotopic GBM22 tumors. Conclusions: Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. (C)2015 AACR. C1 [Pokorny, Jenny L.; Gupta, Shiv K.; Iyekegbe, Dennis O., Jr.; Mueller, Dustin; Bakken, Katrina K.; Carlson, Brett L.; Schroeder, Mark A.; Sarkaria, Jann N.] Mayo Clin, Dept Radiat Oncol, Rochester, MN 55905 USA. [Calligaris, David; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurosurg, Boston, MA 02115 USA. [Evans, Debra L.; Lou, Zhenkun] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Decker, Paul A.; Eckel-Passow, Jeanette E.] Mayo Clin, Hlth Sci Res, Rochester, MN USA. [Pucci, Vincenzo] Merck & Co Inc, Dept Pharmacokinet Pharmacodynam & Drug Metab, Boston, MA USA. [Ma, Bennett] Merck & Co Inc, Dept Pharmacokinet Pharmacodynam & Drug Metab, West Point, PA USA. [Shumway, Stuart D.] Merck & Co Inc, Dept Oncol, Boston, MA USA. [Elmquist, William F.] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. [Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sarkaria, JN (reprint author), Mayo Clin, Dept Radiat Oncol, 200 First St SW, Rochester, MN 55905 USA. EM sarkaria.jann@mayo.edu FU Merck Research Laboratories, Mayo Clinic; NIH [RO1 CA176830, RO1 NS77921]; Mayo Brain Tumor SPORE [P50 CA108961]; U.S. NIH Director's New Innovator Award [1DP2OD007383-01]; Dana-Farber PLGA Foundation; Daniel E. Ponton funds for the Neurosciences FX This work was supported by Merck Research Laboratories, Mayo Clinic and funding from the NIH RO1 CA176830, RO1 NS77921, and the Mayo Brain Tumor SPORE P50 CA108961 (to J.N. Sarkaria); U.S. NIH Director's New Innovator Award (1DP2OD007383-01), Dana-Farber PLGA Foundation, and Daniel E. Ponton funds for the Neurosciences (to N.Y.R. Agar). NR 37 TC 17 Z9 17 U1 2 U2 12 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 APR 15 PY 2015 VL 21 IS 8 BP 1916 EP 1924 DI 10.1158/1078-0432.CCR-14-2588 PG 9 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200020 PM 25609063 ER PT J AU Lombardi, AJ Hoskins, EE Foglesong, GD Wikenheiser-Brokamp, KA Wiesmuller, L Hanenberg, H Andreassen, PR Jacobs, AJ Olson, SB Keeble, WW Hays, LE Wells, SI AF Lombardi, Anne J. Hoskins, Elizabeth E. Foglesong, Grant D. Wikenheiser-Brokamp, Kathryn A. Wiesmueller, Lisa Hanenberg, Helmut Andreassen, Paul R. Jacobs, Allison J. Olson, Susan B. Keeble, Winifred W. Hays, Laura E. Wells, Susanne I. TI Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE-1; CLINICAL RADIOSENSITIVITY; SYNTHETIC LETHALITY; REPAIR; PATHWAY; TRANSCRIPTION; DEFICIENCY AB Purpose: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Experimental Design: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/)-mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). Results: Surprisingly, interstrand crosslinker (ICL) sensitivity was notnecessarily Fanconi anemia-dependent inhuman or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. Conclusions: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. C1 [Lombardi, Anne J.; Hoskins, Elizabeth E.; Foglesong, Grant D.; Andreassen, Paul R.; Wells, Susanne I.] Cincinnati Childrens Hosp Res Fdn, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Wikenheiser-Brokamp, Kathryn A.] Cincinnati Childrens Hosp Med Ctr, Pathol & Lab Med, Cincinnati, OH 45229 USA. [Wikenheiser-Brokamp, Kathryn A.] Cincinnati Childrens Hosp Med Ctr, Pulm Biol, Cincinnati, OH 45229 USA. [Wikenheiser-Brokamp, Kathryn A.] Univ Cincinnati, Cincinnati, OH USA. [Wiesmueller, Lisa] Univ Ulm, Dept Obstet & Gynaecol, D-89069 Ulm, Germany. [Hanenberg, Helmut] Indiana Univ Sch Med, Dept Pediat & Med & Mol Genet, Indianapolis, IN 46202 USA. [Hanenberg, Helmut] Univ Dusseldorf, Sch Med, Dept Otorhinolaryngol ENT HNO, Dusseldorf, Germany. [Jacobs, Allison J.; Keeble, Winifred W.; Hays, Laura E.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Hematol Oncol, Portland, OR 97201 USA. [Jacobs, Allison J.; Keeble, Winifred W.; Hays, Laura E.] Portland VA Med Ctr, Portland, OR USA. [Olson, Susan B.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. RP Wells, SI (reprint author), Cincinnati Childrens Hosp Res Fdn, Room S7-206 MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM laura@fanconi.org; susanne.wells@cchmc.org FU NIH [RO1 CA102357]; NHLBI [PO1HL048546]; Fanconi Anemia Research Fund FX This work was supported in part by NIH award RO1 CA102357 (to S.I. Wells), NHLBI grant PO1HL048546 (to S.B. Olson), and a grant from the Fanconi Anemia Research Fund (to L.E. Hays). NR 50 TC 2 Z9 2 U1 0 U2 1 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 APR 15 PY 2015 VL 21 IS 8 BP 1962 EP 1972 DI 10.1158/1078-0432.CCR-14-2616 PG 11 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200025 PM 25609062 ER PT J AU Soustek, MS Puigserver, P AF Soustek, Meghan S. Puigserver, Pere TI Interrupting synoviolin play at the ER: a plausible action to elevate mitochondrial energetics and silence obesity SO EMBO JOURNAL LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM STRESS; E3 UBIQUITIN LIGASE AB Obesity is a global concern, which has been linked to increased risk for cardiovascular disease, type 2 diabetes, atherosclerosis, non-alcoholic fatty liver, and cancer. In this issue of The EMBO Journal, Fujita et al (2015) describe the role of an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase, synoviolin, and its ability to control body weight and energy expenditure by targeting PGC-1 beta, a transcriptional modulator of mitochondrial oxidative metabolism. C1 [Soustek, Meghan S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Soustek, MS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 15 PY 2015 VL 34 IS 8 BP 981 EP 983 DI 10.15252/embj.201591240 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG0XK UT WOS:000352997000003 PM 25736377 ER PT J AU Gao, S Moreno, M Eliason, S Cao, HJ Li, X Yu, WJ Bidlack, FB Margolis, HC Baldini, A Amendt, BA AF Gao, Shan Moreno, Myriam Eliason, Steven Cao, Huojun Li, Xiao Yu, Wenjie Bidlack, Felicitas B. Margolis, Henry C. Baldini, Antonio Amendt, Brad A. TI TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMELOGENIN GENE-EXPRESSION; CARDIO-FACIAL SYNDROME; TOOTH MORPHOGENESIS; AMELOBLAST DIFFERENTIATION; CARDIOVASCULAR DEFECTS; EPITHELIAL-CELLS; STEM-CELLS; PITX2; MOUSE; PHARYNGEAL AB T-box transcription factor TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS, DiGeorge syndrome/Velo-cardio-facial syndrome), whose phenotypes include craniofacial malformations such as dental defects and cleft palate. In this study, Tbx1 was conditionally deleted or over-expressed in the oral and dental epithelium to establish its role in odontogenesis and craniofacial developmental. Tbx1 lineage tracing experiments demonstrated a specific region of Tbx1-positive cells in the labial cervical loop (LaCL, stem cell niche). We found that Tbx1 conditional knockout (Tbx1(cKO)) mice featured microdontia, which coincides with decreased stem cell proliferation in the LaCL of Tbx1(cKO) mice. In contrast, Tbx1 overexpression increased dental epithelial progenitor cells in the LaCL. Furthermore, microRNA-96 (miR-96) repressed Tbx1 expression and Tbx1 repressed miR-96 expression, suggesting that miR-96 and Tbx1 work in a regulatory loop to maintain the correct levels of Tbx1. Cleft palate was observed in both conditional knockout and over-expression mice, consistent with the craniofacial/tooth defects associated with TBX1 deletion and the gene duplication that leads to 22q11.2DS. The biochemical analyses of TBX1 human mutations demonstrate functional differences in their transcriptional regulation of miR-96 and co-regulation of PITX2 activity. TBX1 interacts with PITX2 to negatively regulate PITX2 transcriptional activity and the TBX1 N-terminus is required for its repressive activity. Overall, our results indicate that Tbx1 regulates the proliferation of dental progenitor cells and craniofacial development through miR-96-5p and PITX2. Together, these data suggest a new molecular mechanism controlling pathogenesis of dental anomalies in human 22q11.2DS. C1 [Gao, Shan; Cao, Huojun] Texas A&M Univ, Hlth Sci Ctr, Houston, TX USA. [Moreno, Myriam; Eliason, Steven; Li, Xiao; Yu, Wenjie; Amendt, Brad A.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Moreno, Myriam; Eliason, Steven; Li, Xiao; Yu, Wenjie; Amendt, Brad A.] Univ Iowa, Craniofacial Anomalies Res Ctr, Iowa City, IA USA. [Bidlack, Felicitas B.] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA USA. [Margolis, Henry C.] Forsyth Inst, Ctr Biomineralizat, Dept Appl Oral Sci, Cambridge, MA USA. [Baldini, Antonio] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Baldini, Antonio] CNR, Inst Genet & Biophys, I-80125 Naples, Italy. RP Amendt, BA (reprint author), Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. EM brad-amendt@uiowa.edu FU University of Iowa; National Institute of Dental and Craniofacial Research [DE 13941] FX Support for this research was provided by funds from the University of Iowa and grant DE 13941 from the National Institute of Dental and Craniofacial Research to B.A.A. NR 74 TC 6 Z9 7 U1 3 U2 9 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 APR 15 PY 2015 VL 24 IS 8 BP 2330 EP 2348 DI 10.1093/hmg/ddu750 PG 19 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1WM UT WOS:000353066200019 PM 25556186 ER PT J AU Quintero-Rivera, F Xi, QCJ Keppler-Noreuil, KM Lee, JH Higgins, AW Anchan, RM Roberts, AE Seong, IS Fan, XP Lage, K Lu, LY Tao, JN Hu, XC Berezney, R Gelb, BD Kamp, A Moskowitz, IP Lacro, RV Lu, WN Morton, CC Gusella, JF Maas, RL AF Quintero-Rivera, Fabiola Xi, Qiongchao J. Keppler-Noreuil, Kim M. Lee, Ji Hyun Higgins, Anne W. Anchan, Raymond M. Roberts, Amy E. Seong, Ihn Sik Fan, Xueping Lage, Kasper Lu, Lily Y. Tao, Joanna Hu, Xuchen Berezney, Ronald Gelb, Bruce D. Kamp, Anna Moskowitz, Ivan P. Lacro, Ronald V. Lu, Weining Morton, Cynthia C. Gusella, James F. Maas, Richard L. TI MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus SO HUMAN MOLECULAR GENETICS LA English DT Article ID OUTFLOW TRACT DEVELOPMENT; CONGENITAL HEART-DISEASE; DOMINANT DISTAL MYOPATHY; CAUSE CHAR-SYNDROME; CARDIOVASCULAR MALFORMATIONS; SCIENTIFIC STATEMENT; CARDIAC DEVELOPMENT; ENDOTHELIAL-CELLS; CURRENT KNOWLEDGE; GENETIC-BASIS AB Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive evelopmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts the 5'TR of AHDC1, which encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating mutations have recently been described in a syndrome that includes developmental delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y., Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam, R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum. Genet., 94, 784-789]. On the other hand, the 5q translocation breakpoint disrupts the 3'UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse Matr3 is strongly expressed in neural crest, developing heart and great vessels, whereas Ahdc1 is not. To further establish MATR3 3'UTR disruption as the cause of the proband's LVOT defects, we prepared a mouse Matr3(Gt-ex13) gene trap allele that disrupted the 3'portion of the gene. Matr3(Gt-ex13) homozygotes are early embryo lethal, but Matr3(Gt-ex13) heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV). Both the human MATR3 translocation breakpoint and the mouse Matr3(Gt-ex13) gene trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin 3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations in Matrin 3 expression appear to cause similar LVOT defects in human and mouse. C1 [Quintero-Rivera, Fabiola; Lee, Ji Hyun; Seong, Ihn Sik; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA 02115 USA. [Quintero-Rivera, Fabiola; Lee, Ji Hyun; Seong, Ihn Sik; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Quintero-Rivera, Fabiola] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Xi, Qiongchao J.; Anchan, Raymond M.; Lu, Lily Y.; Tao, Joanna; Hu, Xuchen; Maas, Richard L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Higgins, Anne W.; Anchan, Raymond M.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Keppler-Noreuil, Kim M.] Univ Iowa Hosp & Clin, Div Med Genet, Iowa City, IA 52242 USA. [Roberts, Amy E.; Lacro, Ronald V.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Roberts, Amy E.] Boston Childrens Hosp, Div Genet, Dept Med, Boston, MA USA. [Fan, Xueping; Lu, Weining] Boston Univ, Med Ctr, Dept Med, Renal Sect, Boston, MA USA. [Lage, Kasper] Massachusetts Gen Hosp Children, Dept Surg, Pediat Surg Res Labs, Boston, MA USA. [Berezney, Ronald] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA. [Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Dept Pediat, New York, NY 10029 USA. [Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Dept Genet & Genom Sci, New York, NY 10029 USA. [Kamp, Anna; Moskowitz, Ivan P.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Kamp, Anna; Moskowitz, Ivan P.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Gusella, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA 02115 USA. EM gusella@helix.mgh.harvard.edu; maas@genetics.med.harvard.edu FU NIH [P01GM061354, R01HD060050, R01HL071207]; March of Dimes [6-FY13-145] FX This study was supported by NIH grants P01GM061354, R01HD060050 and R01HL071207, and by #6-FY13-145 from the March of Dimes. Funding to pay the Open Access publication charges for this article was provided by March of Dimes grant #6-FY13-145. NR 48 TC 11 Z9 11 U1 1 U2 7 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 APR 15 PY 2015 VL 24 IS 8 BP 2375 EP 2389 DI 10.1093/hmg/ddv004 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1WM UT WOS:000353066200022 PM 25574029 ER PT J AU Robertson, CL Ishibashi, K Mandelkern, MA Brown, AK Ghahremani, DG Sabb, F Bilder, R Cannon, T Borg, J London, ED AF Robertson, Chelsea L. Ishibashi, Kenji Mandelkern, Mark A. Brown, Amira K. Ghahremani, Dara G. Sabb, Fred Bilder, Robert Cannon, Tyrone Borg, Jacqueline London, Edythe D. TI Striatal D-1- and D-2-type Dopamine Receptors Are Linked to Motor Response Inhibition in Human Subjects SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; impulsivity; PET imaging ID REACTION-TIME-TASK; STOP-SIGNAL TASK; TEST-RETEST RELIABILITY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS CORE; REFERENCE TISSUE MODEL; IMPULSIVE BEHAVIOR; BASAL GANGLIA; PREFRONTAL CORTEX AB Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D-1- and D-2-type receptors are unclear. Although evidence supports dissociable contributions of D-1- and D-2-type receptors to response inhibition in rats and associations of D-2-type receptors to response inhibition in humans, the relationship between D-1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D-1- and D-2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D-1- and D-2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [C-11]NNC-112 and [F-18] fallypride, respectively. Stop-signal reaction time was negatively correlated with D-1- and D-2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D-1- and D-2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D-1- and D-2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. C1 [Robertson, Chelsea L.; London, Edythe D.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [Cannon, Tyrone; Borg, Jacqueline] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychol, Los Angeles, CA 90024 USA. [Ishibashi, Kenji; Brown, Amira K.; Ghahremani, Dara G.; Sabb, Fred; Bilder, Robert; London, Edythe D.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Ishibashi, Kenji; London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; Mandelkern, Mark A.; London, Edythe D.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92697 USA. RP London, ED (reprint author), Univ Calif Los Angeles, Semel Inst, 760 Westwood Plaza,C8-831, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 FU Consortium for Neuropsychiatric Phenomics (National Institutes of Health Roadmap for Medical Research) [UL1-DE019580, RL1MH083269, RL1DA024853, PL1MH083271]; UCLA Training Program in Translational Neuroscience of Drug Abuse [T32DA024635]; Marjorie Greene Trust FX This work was supported by the Consortium for Neuropsychiatric Phenomics (National Institutes of Health Roadmap for Medical Research Grants UL1-DE019580, RL1MH083269, RL1DA024853, and PL1MH083271), The UCLA Training Program in Translational Neuroscience of Drug Abuse (Grant T32DA024635), and Endowments from the Thomas P. and Katherine P. Pike Chair in Addiction Studies and the Marjorie Greene Trust. NR 80 TC 6 Z9 6 U1 3 U2 16 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 5990 EP 5997 DI 10.1523/JNEUROSCI.4850-14.2015 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600011 PM 25878272 ER PT J AU Schumacher, MA Aihara, E Feng, R Engevik, A Shroyer, NF Ottemann, KM Worrell, RT Montrose, MH Shivdasani, RA Zavros, Y AF Schumacher, Michael A. Aihara, Eitaro Feng, Rui Engevik, Amy Shroyer, Noah F. Ottemann, Karen M. Worrell, Roger T. Montrose, Marshall H. Shivdasani, Ramesh A. Zavros, Yana TI The use of murine-derived fundic organoids in studies of gastric physiology SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SMALL-INTESTINAL SUBMUCOSA; STEM-CELLS; PROGENITOR-CELL; IN-VITRO; EPITHELIAL-CELLS; STOMACH; IDENTIFICATION; EXPRESSION; REPAIR; BOWEL AB An in vitro approach to study gastric development is primary mouse-derived epithelium cultured as three-dimensional spheroids known as organoids. We have devised two unique gastric fundic-derived organoid cultures: model 1 for the expansion of gastric fundic stem cells, and model 2 for the maintenance of mature cell lineages. Organoids maintained in co-culture with immortalized stomach mesenchymal cells express robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells. Histamine induced a significant decrease in intraluminal pH that was reversed by omeprazole in fundic organoids and indicated functional activity and regulation of parietal cells. Localized photodamage resulted in rapid cell exfoliation coincident with migration of neighbouring cells to the damaged area, sustaining epithelial continuity. We report the use of these models for studies of epithelial cell biology and cell damage and repair. AbstractStudies of gastric function and disease have been limited by the lack of extended primary cultures of the epithelium. An in vitro approach to study gastric development is primary mouse-derived antral epithelium cultured as three-dimensional spheroids known as organoids. There have been no reports on the use of organoids for gastric function. We have devised two unique gastric fundic-derived organoid cultures: model 1 for the expansion of gastric fundic stem cells, and model 2 for the maintenance of mature cell lineages. Both models were generated from single glands dissociated from whole fundic tissue and grown in basement membrane matrix (Matrigel) and organoid growth medium. Model 1 enriches for a stem cell-like niche via simple passage of the organoids. Maintained in Matrigel and growth medium, proliferating organoids expressed high levels of stem cell markers CD44 and Lgr5. Model 2 is a system of gastric organoids co-cultured with immortalized stomach mesenchymal cells (ISMCs). Organoids maintained in co-culture with ISMCs express robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells. Histamine induced a significant decrease in intraluminal pH that was reversed by omeprazole in fundic organoids and indicated functional activity and regulation of parietal cells. Localized photodamage resulted in rapid cell exfoliation coincident with migration of neighbouring cells to the damaged area, sustaining epithelial continuity. Thus, we report the use of these models for studies of epithelial cell biology and cell damage and repair. C1 [Schumacher, Michael A.; Aihara, Eitaro; Feng, Rui; Engevik, Amy; Worrell, Roger T.; Montrose, Marshall H.; Zavros, Yana] Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA. [Shroyer, Noah F.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Ottemann, Karen M.] Univ Calif Santa Cruz, Dept Microbiol & Environm Toxicol, Santa Cruz, CA 95064 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Zavros, Y (reprint author), Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, 231 Albert B Sabin Way,Room 4255 MSB, Cincinnati, OH 45267 USA. EM yana.zavros@uc.edu OI Shroyer, Noah/0000-0002-5934-2852 FU American Gastroenterological Association: Robert and Sally Funderburg Research Award in Gastric Cancer; Albert J. Ryan Fellowship; PHS [P30 DK078392]; NIH of the Digestive Diseases Research Core Centre in Cincinnati [AR-47363]; [R01 DK083402]; [R01 DK54940] FX This work was supported by the American Gastroenterological Association: Robert and Sally Funderburg Research Award in Gastric Cancer and R01 DK083402 grant (Y.Z.), the Albert J. Ryan Fellowship (M.A.S.) and R01 DK54940 (M.H.M.). This project was supported in part by PHS Grant P30 DK078392 (Integrative Morphology Core) and NIH AR-47363 (Research Flow Cytometry Core in the Division of Rheumatology) of the Digestive Diseases Research Core Centre in Cincinnati. NR 43 TC 18 Z9 18 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 2015 VL 593 IS 8 BP 1809 EP 1827 DI 10.1113/jphysiol.2014.283028 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CG1PC UT WOS:000353044300017 PM 25605613 ER PT J AU Biundo, R Weis, L Facchini, S Formento-Dojot, P Vallelunga, A Pilleri, M Weintraub, D Antonini, A AF Biundo, Roberta Weis, Luca Facchini, Silvia Formento-Dojot, Patrizia Vallelunga, Annamaria Pilleri, Manuela Weintraub, Daniel Antonini, Angelo TI Patterns of Cortical Thickness Associated With Impulse Control Disorders in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; impulse control disorders; fronto-striatal-limbic networks; QUIP-RS; cortical thickness ID VENTROMEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; SOCIETY TASK-FORCE; RATING-SCALE; DOPAMINE-AGONISTS; DECISION-MAKING; CONNECTIVITY; BEHAVIOR AB Previous functional neuroimaging studies in Parkinson's disease (PD) patients with impulse control disorders (ICDs) demonstrated dysfunction of the reward network, although the extent of anatomical changes is unclear. The aim of this study was to measure brain cortical thickness and subcortical volumes, and to assess their relationship with presence and severity of symptoms, in PD patients with and without ICDs. We studied 110 PD patients (N=58 with ICDs) and 33 healthy controls (all negative for ICDs) who underwent an extensive neurological, neuropsychological, and behavioral assessment as well as structural 1.5 Tesla magnetic resonance imaging (MRI). Between-group differences in brain cortical thickness and subcortical volumes, assessed with the FreeSurfer 5.1 tool, were analyzed. In patients with ICDs, we found significant cortical thinning in fronto-striatal circuitry, specifically in the right superior orbitofrontal, left rostral middle frontal, bilateral caudal middle frontal region, and corpus callosum, as well as volume reduction in the right accumbens and increase in the left amygdala. Finally, we observed a positive association relationship between severity of impulsive symptoms and left rostral middle frontal, inferior parietal, and supramarginal areas. These results support the involvement of both reward and response inhibition networks in PD patients with ICDs. Moreover, their severity is associated with alterations in brain regions linked with reward and top-down control networks. Increased understanding of the mechanisms underlying impulsive and compulsive behaviors might help improve therapeutic strategies for these important disorders. (c) 2015 International Parkinson and Movement Disorder Society C1 [Biundo, Roberta; Weis, Luca; Facchini, Silvia; Formento-Dojot, Patrizia; Vallelunga, Annamaria; Pilleri, Manuela; Antonini, Angelo] Fdn Osped San Camillo IRCCS, Parkinson & Movement Disorders Unit, Venice, Italy. [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, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. RP Biundo, R (reprint author), Fdn Osped San Camillo IRCCS, Parkinson & Movement Disorders Unit, Via Alberoni 70, I-30126 Venice Lido, Italy. EM roberta.biundo@ospedalesancamillo.net FU Italian Research Grant [N RF-2009-1530177] FX This study was supported by Italian Research Grant N RF-2009-1530177. NR 45 TC 11 Z9 11 U1 3 U2 12 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 APR 15 PY 2015 VL 30 IS 5 BP 688 EP 695 DI 10.1002/mds.26154 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CF8FE UT WOS:000352790700013 PM 25649923 ER PT J AU Srivatsal, S Cholerton, B Leverenz, JB Wszolek, ZK Uitti, RJ Dickson, DW Weintraub, D Trojanowski, JQ Van Deerlin, VM Quinn, JF Chung, KA Peterson, AL Factor, SA Wood-Siverio, C Goldman, JG Stebbins, GT Bernard, B Ritz, B Rausch, R Espay, AJ Revilla, FJ Devoto, J Rosenthal, LS Dawson, TM Albert, MS Mata, IF Hu, SC Montine, KS Johnson, C Montine, TJ Edwards, KL Zhang, J Zabetian, CP AF Srivatsal, Sindhu Cholerton, Brenna Leverenz, James B. Wszolek, Zbigniew K. Uitti, Ryan J. Dickson, Dennis W. Weintraub, Daniel Trojanowski, John Q. Van Deerlin, Vivianna M. Quinn, Joseph F. Chung, Kathryn A. Peterson, Amie L. Factor, Stewart A. Wood-Siverio, Cathy Goldman, Jennifer G. Stebbins, Glenn T. Bernard, Bryan Ritz, Beate Rausch, Rebecca Espay, Alberto J. Revilla, Fredy J. Devoto, Johnna Rosenthal, Liana S. Dawson, Ted M. Albert, Marilyn S. Mata, Ignacio F. Hu, Shu-Ching Montine, Kathleen S. Johnson, Catherine Montine, Thomas J. Edwards, Karen L. Zhang, Jing Zabetian, Cyrus P. TI Cognitive Profile of LRRK2-Related Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE cognition; LRRK2; neuropsychological tests; Parkinson's disease; working memory ID MINI-MENTAL-STATE; LRRK2 MUTATIONS; NORMATIVE DATA; DEMENTIA; PERFORMANCE; IMPAIRMENT; ONSET; RISK; DYSFUNCTION; CARRIERS AB BackgroundIncreasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. MethodsA cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. ResultsLRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). ConclusionsOur cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline. (c) 2015 International Parkinson and Movement Disorder Society C1 [Srivatsal, Sindhu] Virginia Mason Neurosci Inst, Seattle, WA USA. [Cholerton, Brenna; Mata, Ignacio F.; Hu, Shu-Ching; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Cholerton, Brenna] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.] Cleveland Clin, Neurol Inst, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44106 USA. [Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie L.] Portland VA Med Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Factor, Stewart A.; Wood-Siverio, Cathy] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Goldman, Jennifer G.; Stebbins, Glenn T.; Bernard, Bryan] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA. [Ritz, Beate; Rausch, Rebecca] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Rosenthal, Liana S.; Dawson, Ted M.; Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Hu, Shu-Ching; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Montine, Kathleen S.; Montine, Thomas J.; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Johnson, Catherine; Edwards, Karen L.] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Ritz, Beate/E-3043-2015 FU National Institutes of Health [K23 NS060949, P50 NS062684, P50 NS053488, P50 NS038367, P50 NS038377, P50 NSO72187, R01 NS065070, R01 NS057567, U01 NS082133]; U.S. Department of Veterans Affairs Merit Award [1I01BX000531]; Parkinson's Disease Foundation; Nancy and Buster Alvord Endowment; Jane and Lee Seidman Fund; Consolidated Anti-Aging Foundation FX This research was supported by the National Institutes of Health (K23 NS060949, P50 NS062684, P50 NS053488, P50 NS038367, P50 NS038377, P50 NSO72187, R01 NS065070, R01 NS057567, and U01 NS082133), the U.S. Department of Veterans Affairs Merit Award (1I01BX000531), the Parkinson's Disease Foundation, the Nancy and Buster Alvord Endowment, the Jane and Lee Seidman Fund, the Consolidated Anti-Aging Foundation, and gifts from Carl Edward Bolch, Jr, and Susan Bass Bolch. The funding sources did not provide scientific input for the study. The contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 37 TC 13 Z9 13 U1 0 U2 9 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 APR 15 PY 2015 VL 30 IS 5 BP 728 EP 733 DI 10.1002/mds.26161 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CF8FE UT WOS:000352790700019 PM 25650144 ER PT J AU Bosch, A Li, ZQ Bergamaschi, A Ellis, H Toska, E Prat, A Tao, JJ Spratt, DE Viola-Villegas, NT Castel, P Minuesa, G Morse, N Rodon, J Ibrahim, Y Cortes, J Perez-Garcia, J Galvan, P Grueso, J Guzman, M Katzenellenbogen, JA Kharas, M Lewis, JS Dickler, M Serra, V Rosen, N Chandarlapaty, S Scaltriti, M Baselga, J AF Bosch, Ana Li, Zhiqiang Bergamaschi, Anna Ellis, Haley Toska, Eneda Prat, Aleix Tao, Jessica J. Spratt, Daniel E. Viola-Villegas, Nerissa T. Castel, Pau Minuesa, Gerard Morse, Natasha Rodon, Jordi Ibrahim, Yasir Cortes, Javier Perez-Garcia, Jose Galvan, Patricia Grueso, Judit Guzman, Marta Katzenellenbogen, John A. Kharas, Michael Lewis, Jason S. Dickler, Maura Serra, Violeta Rosen, Neal Chandarlapaty, Sarat Scaltriti, Maurizio Baselga, Jose TI PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GENE-EXPRESSION; RESISTANCE; MUTATIONS; KINASE; GROWTH; ALPHA; ANTIESTROGENS; TRANSCRIPTION; DEPRIVATION; FULVESTRANT AB Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors, and selective phosphatidylinositol 3-kinase alpha (PI3K alpha) inhibitors are in clinical development. The activity of these agents, however, is not homogeneous, and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single-agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling results in induction of ER-dependent transcriptional activity, as demonstrated by changes in expression of genes containing ER-binding sites and increased occupancy by the ER of promoter regions of up-regulated genes. Furthermore, expression of ESR1 mRNA and ER protein were also increased upon PI3K inhibition. These changes in gene expression were confirmed in vivo in xenografts and patient-derived models and in tumors from patients undergoing treatment with the PI3K alpha inhibitor BYL719. The observed effects on transcription were enhanced by the addition of estradiol and suppressed by the anti-ER therapies fulvestrant and tamoxifen. Fulvestrant markedly sensitized ER-positive tumors to PI3K alpha inhibition, resulting in major tumor regressions in vivo. We propose that increased ER transcriptional activity may be a reactive mechanism that limits the activity of PI3K inhibitors and that combined PI3K and ER inhibition is a rational approach to target these tumors. C1 [Bosch, Ana; Li, Zhiqiang; Ellis, Haley; Toska, Eneda; Castel, Pau; Morse, Natasha; Chandarlapaty, Sarat; Scaltriti, Maurizio; Baselga, Jose] Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Bergamaschi, Anna] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Prat, Aleix] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Prat, Aleix] VHIO, Translat Genom Grp, Barcelona 08035, Spain. [Tao, Jessica J.] Hosp Clin Barcelona, August Pi & Sunyer Biomed Res Inst, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona 08035, Spain. [Spratt, Daniel E.; Viola-Villegas, Nerissa T.; Lewis, Jason S.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Minuesa, Gerard] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Rodon, Jordi; Cortes, Javier; Perez-Garcia, Jose] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Rodon, Jordi] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Ibrahim, Yasir; Grueso, Judit; Guzman, Marta; Serra, Violeta] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA. [Katzenellenbogen, John A.] VHIO, Dept Med Oncol, Barcelona 08035, Spain. [Chandarlapaty, Sarat; Baselga, Jose] Univ Autonoma Barcelona, Bellaterra 08193, Spain. [Chandarlapaty, Sarat; Baselga, Jose] VHIO, Expt Therapeut Grp, Barcelona 08035, Spain. [Chandarlapaty, Sarat; Scaltriti, Maurizio] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Chandarlapaty, Sarat; Baselga, Jose] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Med Serv, New York, NY 10065 USA. [Chandarlapaty, Sarat; Baselga, Jose] Weill Cornell Med Coll, New York, NY 10065 USA. RP Chandarlapaty, S (reprint author), Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA. EM chandars@mskcc.org; scaltrim@mskcc.org; baselgaj@mskcc.org RI Prat, Aleix/P-8561-2014; OI Cortes, Javier/0000-0001-7623-1583; Prat, Aleix/0000-0003-2377-540X; Kharas, Michael/0000-0002-1165-6991; Li, Zhiqiang/0000-0002-2768-5332; Spratt, Daniel/0000-0002-5973-4741; Castel, Pau/0000-0002-4972-4347 FU Stand Up To Cancer Dream Team Translational Cancer Research Grant, a program of the Entertainment Industry Foundation [SU2C-AACR-DT0209]; Breast Cancer Research Foundation; European Research Council [AdG09250244]; Instituto de Salud Carlos III [PSO9/00623, FIS PI13/01714]; Banco Bilbao Vizcaya Argentaria Foundation (Tumor Biomarker Research Program); Spanish Society of Medical Oncology; GHD/FERO grant; Louis Gerstner YIA; Damon Runyon Foundation; Bayer; K99/R00 Pathway to Independence award [1K99CA181492-01A1]; PHS [5R01 CA 025836] FX This work was funded by a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a program of the Entertainment Industry Foundation (SU2C-AACR-DT0209 to J.B.), the Breast Cancer Research Foundation (to J.B.), the European Research Council (AdG09250244 to J.B.), the Instituto de Salud Carlos III (Intrasalud PSO9/00623 to J.B.), and Banco Bilbao Vizcaya Argentaria Foundation (Tumor Biomarker Research Program). A. Bosch holds a Translational Research Fellowship from the Spanish Society of Medical Oncology. V.S. is a recipient of an Instituto de Salut Carlos III grant (FIS PI13/01714) and a GHD/FERO grant. S.C. receives research funding from a Louis Gerstner YIA and the Damon Runyon Foundation. N.R. receives research funding from Bayer. N.T.V.-V. held a K99/R00 Pathway to Independence award (1K99CA181492-01A1). J.A.K. was funded by PHS 5R01 CA 025836. NR 45 TC 23 Z9 24 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 15 PY 2015 VL 7 IS 283 AR 283ra51 DI 10.1126/scitranslmed.aaa4442 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CG6AJ UT WOS:000353377000002 PM 25877889 ER PT J AU Choy, E Flamand, Y Balasubramanian, S Butrynski, JE Harmon, DC George, S Cote, GM Wagner, AJ Morgan, JA Sirisawad, M Mani, C Hornicek, FJ Duan, ZF Demetri, GD AF Choy, Edwin Flamand, Yael Balasubramanian, Sriram Butrynski, James E. Harmon, David C. George, Suzanne Cote, Gregory M. Wagner, Andrew J. Morgan, Jeffrey A. Sirisawad, Mint Mani, Chitra Hornicek, Francis J. Duan, Zhenfeng Demetri, George D. TI Phase 1 Study of Oral Abexinostat, a Histone Deacetylase Inhibitor, in Combination With Doxorubicin in Patients With Metastatic Sarcoma SO CANCER LA English DT Article DE sarcoma; histone deacetylase; doxorubicin; abexinostat; maximum tolerated dose ID CELL-LINES; IN-VITRO; CHEMOTHERAPY; PCI-24781; APOPTOSIS; DIFFERENTIATION; GROWTH; DEATH; ACID; VIVO AB BACKGROUNDIt has been demonstrated that several inhibitors of histone deacetylase (HDAC) can enhance chemotherapy-induced apoptosis and reduce sarcoma tumor volume in preclinical models. The authors sought to determine the maximum tolerated dose, pharmacokinetics/pharmacodynamics, safety, and toxicity of the HDAC inhibitor abexinostat (PCI-24781) when administered with doxorubicin to patients with metastatic sarcomas. METHODSParticipants were enrolled in a standard, phase 1, 3+3, dose-escalation study design. Abexinostat was administered on days 1 through 5 with 75 mg/m(2) of doxorubicin administered on day 4 of every 21-day cycle until patients developed disease progression or drug intolerance or reached a cumulative lifetime doxorubicin dose of 450 mg/m(2). Granulocyte-colony-stimulating factor (G-CSF) support was provided at physician discretion on arm A and was provided to all participants in arm B. From 3 to 6 participants initially received abexinostat 30 mg/m(2) twice daily, and subsequent cohorts were administered doses of 15 mg/m(2), 45 mg/m(2), or 60 mg/m(2) twice daily. All patients without progressive disease after receiving a cumulative lifetime doxorubicin dose of 450 mg/m(2) were given the option to continue with abexinostat as a single agent until they developed disease progression. RESULTSIn total, 22 participants (10 who had previously experienced tumor growth after doxorubicin therapy) were enrolled (6 in arm A, 14 in arm B), 20 were evaluable for dose-limiting toxicity (DLT), and 17 were evaluable for radiologic response. In arm A, participants received abexinostat 15 mg/m(2) or 30 mg/m(2) twice daily. DLTs of grade 3 and 4 neutropenia were observed in 2 of 3 participants who received abexinostat 30 mg/m(2) twice daily. Neither of those patients received G-CSF prophylaxis. In arm B, participants received abexinostat at doses of 30 mg/m(2), 45 mg/m(2), or 60 mg/m(2) twice daily, all with mandated G-CSF support. Two DLTs were observed at the 60 mg/m(2) twice-daily dose (grade 3 infection, grade 4 thrombocytopenia). The pharmacokinetics of abexinostat were not affected by doxorubicin. HDAC activity, as measured by histone acetylation in peripheral blood mononuclear cells, was maximally inhibited at the abexinostat 30 mg/m(2) twice-daily dose. Of the 17 participants who were evaluable for radiologic response, 1 patient had a partial response, 9 patients had stable disease, and 7 patients had progressive disease as their best response; and 8 patients completed 5 cycles. Three of those participants had stable disease as their most recent disease status when the current report was written. Four participants who continued on monotherapy remained in stable disease for a median of 9.8 weeks after completing doxorubicin. The most common toxicities were fatigue, thrombocytopenia, and anemia. No study-related deaths were observed. CONCLUSIONSThe maximum tolerated dose for abexinostat was 45 mg/m(2) twice daily administered on days 1 through 5 when patients received doxorubicin 75 mg/m(2) on day 4 of a 3-week cycle and G-CSF support was mandated. Toxicities were manageable, and tumor responses were observed. Additional studies are needed to further define the specific contributions of HDAC inhibition in patients who receive doxorubicin for the treatment of metastatic sarcoma. Cancer 2015;121:1223-1230. (c) 2014 American Cancer Society. In this phase 1 study, the histone deacetylase inhibitor abexinostat (PCI-24781) is administered in combination with doxorubicin to patients with metastatic sarcoma. The maximum tolerated dose for abexinostat is 45 mg/m(2) twice daily when administered on days 1 through 5 with doxorubicin at a dose of 75 mg/m(2) on day 4 of a 3-week cycle, and granulocyte-colony-stimulating factor support is mandated. C1 [Choy, Edwin; Harmon, David C.; Cote, Gregory M.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. [Flamand, Yael] Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. [Balasubramanian, Sriram] Janssen Res & Dev LLC, Raritan, NJ USA. [Butrynski, James E.; George, Suzanne; Wagner, Andrew J.; Morgan, Jeffrey A.; Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Sirisawad, Mint; Mani, Chitra] Pharmacyclics Inc, Sunnyvale, CA USA. [Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Demetri, George D.] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA USA. RP Choy, E (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM echoy@partners.org OI Cote, Gregory/0000-0003-0181-886X FU Pharmacyclics, Inc.; Ludwig Institute for Cancer Research; Jennifer Hunter Yates Foundation; Brian MacIsaac Sarcoma Foundation; KL2 Medical Research Investigator Training (MeRIT) grant through Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Institutes of Health) [1KL2RR025757]; National Cancer Institute of the National Institutes of Health [U54CA168512] FX This research was supported by funds from Pharmacyclics, Inc. The study also was supported by funding from the Ludwig Institute for Cancer Research, the Jennifer Hunter Yates Foundation, the Brian MacIsaac Sarcoma Foundation, the KL2 Medical Research Investigator Training (MeRIT) grant awarded to E.C. through Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Institutes of Health grant 1KL2RR025757), and the National Cancer Institute of the National Institutes of Health under Award U54CA168512. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 22 TC 10 Z9 11 U1 0 U2 4 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 APR 15 PY 2015 VL 121 IS 8 BP 1223 EP 1230 DI 10.1002/cncr.29175 PG 8 WC Oncology SC Oncology GA CF7CG UT WOS:000352713100015 PM 25536954 ER PT J AU Dawes, AJ Hemmelgarn, M Nguyen, DK Sacks, GD Clayton, SM Cope, JR Ganz, PA Maggard-Gibbons, M AF Dawes, Aaron J. Hemmelgarn, Marian Nguyen, David K. Sacks, Greg D. Clayton, Sheilah M. Cope, Jacqueline R. Ganz, Patricia A. Maggard-Gibbons, Melinda TI Are Primary Care Providers Prepared to Care for Survivors of Breast Cancer in the Safety Net? SO CANCER LA English DT Article DE breast cancer; survivorship; safety-net providers; primary care physicians ID QUALITY-OF-LIFE; TOP 5 LIST; FOLLOW-UP; CLINICAL ONCOLOGY; AMERICAN SOCIETY; RANDOMIZED-TRIAL; PHYSICIANS; SURVEILLANCE; MAMMOGRAPHY; PLANS AB BACKGROUNDWith the growing number of survivors of breast cancer outpacing the capacity of oncology providers, there is pressure to transition patients back to primary care. Primary care providers (PCPs) working in safety-net settings may have less experience treating survivors, and little is known about their knowledge and views on survivorship care. The current study was performed to determine the knowledge, attitudes, and confidence of PCPs in the safety net at delivering care to survivors of breast cancer. METHODSA modified version of the National Cancer Institute's Survey of Physician Attitudes Regarding Care of Cancer Survivors was given to providers at 2 county hospitals and 5 associated clinics (59 providers). Focus groups were held to understand barriers to survivorship care. RESULTSAlthough the majority of providers believed PCPs have the skills necessary to provide cancer-related follow-up, the vast majority were not comfortable providing these services themselves. Providers were adherent to American Society of Clinical Oncology recommendations for mammography (98%) and physical examination (87%); less than one-third were guideline-concordant for laboratory testing and only 6 providers (10%) met all recommendations. PCPs universally requested additional training on clinical guidelines and the provision of written survivorship care plans before transfer. Concerns voiced in qualitative sessions included unfamiliarity with the management of endocrine therapy and confusion regarding who would be responsible for certain aspects of care. CONCLUSIONSSafety-net providers currently lack knowledge of and confidence in providing survivorship care to patients with breast cancer. Opportunities exist for additional training in evidence-based guidelines and improved coordination of care between PCPs and oncology specialists. Cancer 2015;121:1249-1256. (c) 2014 American Cancer Society. Primary care providers working in safety-net settings report low knowledge and confidence in their ability to care for survivors of breast cancer. Additional training concerning aspects of survivorship care, including compliance with American Society of Clinical Oncology guidelines, is needed before survivors can be successfully transitioned to primary care. C1 [Dawes, Aaron J.; Nguyen, David K.; Sacks, Greg D.; Maggard-Gibbons, Melinda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Maggard-Gibbons, Melinda] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA USA. [Hemmelgarn, Marian; Maggard-Gibbons, Melinda] Olive View Univ Calif Los Angeles, Med Ctr, Dept Surg, Sylmar, CA USA. [Clayton, Sheilah M.] Martin Luther King Jr Charles R Drew Univ Med Ctr, Dept Med, Div Canc Res & Training, Los Angeles, CA USA. [Clayton, Sheilah M.] Martin Luther King Jr Multi Serv Ambulatory Care, Los Angeles, CA USA. [Cope, Jacqueline R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. [Cope, Jacqueline R.] Los Angeles Cty Dept Hlth Serv, Ambulatory Care Network, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ronald Reagan UCLA Med Ctr, 757 Westwood Plaza,B711, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu1 OI Dawes, Aaron/0000-0003-4574-6765 FU National Cancer Institute/National Institutes of Health [U54 CA143931] FX Supported in part by a grant from the National Cancer Institute/National Institutes of Health (U54 CA143931). NR 24 TC 9 Z9 9 U1 1 U2 3 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 APR 15 PY 2015 VL 121 IS 8 BP 1249 EP 1256 DI 10.1002/cncr.29201 PG 8 WC Oncology SC Oncology GA CF7CG UT WOS:000352713100018 PM 25536301 ER PT J AU Inverso, G Mahal, BA Aizer, AA Donoff, RB Chau, NG Haddad, RI AF Inverso, Gino Mahal, Brandon A. Aizer, Ayal A. Donoff, R. Bruce Chau, Nicole G. Haddad, Robert I. TI Marital Status and Head and Neck Cancer Outcomes SO CANCER LA English DT Article DE head and neck cancer; marriage; Surveillance; Epidemiology; and End Results; cancer outcomes; cancer social support ID PROSTATE-CANCER; SOCIAL SUPPORT; HEALTH; DIAGNOSIS; SURVIVAL; STAGE; RISK; MARRIAGE; ALCOHOL; SMOKING AB BACKGROUNDThe objective of this study was to examine the effects of marital status on stage at presentation, receipt of treatment, and survival in patients with head and neck cancer (HNC). METHODSThe Surveillance, Epidemiology, and End Results database was used to analyze 51,272 patients who were diagnosed with HNC from 2007 to 2010. The impact of marital status on cancer stage at presentation, receipt of definitive treatment, and HNC-specific mortality (HNCSM) was determined using multivariable logistic and Fine and Gray competing-risks regression models, as appropriate. RESULTSMarriage had a protective effect against metastatic presentation of oral and laryngeal cancers (oral cancer: adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.60-0.87; P<.001; laryngeal cancer: AOR, 0.53; 95% CI, 0.42-0.67; P<.001) but not against oropharyngeal, hypopharyngeal, or nasopharyngeal cancers. Among patients with nonmetastatic disease, married patients were more likely to receive definitive treatment (overall AOR, 1.77; 95% CI, 1.60-1.95; P<.001) and had a lower risk of HNCSM (overall adjusted hazard ratio, 0.72; 95% CI, 0.68-0.77; P<.001); these associations remained significant across all HNC sites. CONCLUSIONSAmong patients with oral and laryngeal cancers, those who are married are less likely to present with metastatic disease. In addition, married patients are more likely to receive definitive treatment and less likely to die from HNC across all HNC sites. This suggests that spousal support may have a role in the surveillance of visual and symptomatic HNC types and leads to higher rates of treatment and better survival across all HNC sites. Cancer 2015;121:1273-1278. (c) 2014 American Cancer Society. Married patients are less likely than unmarried patients to present with metastatic oral and laryngeal cancers, more likely to receive definitive treatment across the 5 head and neck cancer sites (oral, oropharyngeal, hypopharyngeal, nasopharyngeal, and laryngeal), and less likely to die from cancers of these 5 sites. These findings suggest that spousal support may play a role in the surveillance of patients who have visual and symptomatic head and neck cancers and can lead to higher rates of treatment and better survival across all head and neck cancer types. C1 [Inverso, Gino; Donoff, R. Bruce] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Mahal, Brandon A.] Harvard Univ, Sch Med, Boston, MA USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Donoff, R. Bruce] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chau, Nicole G.; Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Haddad, RI (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM robert_haddad@dfci.harvard.edu FU Boehringer Ingelheim; BMS; Merck; VentiRx FX Dr. Haddad reports grants from Boehringer Ingelheim, BMS, Merck, and VentiRx and personal fees from EISAI outside the submitted work. NR 33 TC 17 Z9 17 U1 4 U2 8 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 APR 15 PY 2015 VL 121 IS 8 BP 1273 EP 1278 DI 10.1002/cncr.29171 PG 6 WC Oncology SC Oncology GA CF7CG UT WOS:000352713100021 PM 25524565 ER PT J AU Zaynagetdinov, R Sherrill, TP Gleaves, LA McLoed, AG Saxon, JA Habermann, AC Connelly, L Dulek, D Peebles, RS Fingleton, B Yull, FE Stathopoulos, GT Blackwell, TS AF Zaynagetdinov, Rinat Sherrill, Taylor P. Gleaves, Linda A. McLoed, Allyson G. Saxon, Jamie A. Habermann, Arun C. Connelly, Linda Dulek, Daniel Peebles, R. Stokes, Jr. Fingleton, Barbara Yull, Fiona E. Stathopoulos, Georgios T. Blackwell, Timothy S. TI Interleukin-5 Facilitates Lung Metastasis by Modulating the Immune Microenvironment SO CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; INNATE LYMPHOID-CELLS; FACTOR-KAPPA-B; AIRWAY HYPERRESPONSIVENESS; EXCESSIVE EOSINOPHILIA; TISSUE EOSINOPHILIA; CANCER METASTASIS; FLOW-CYTOMETRY; ASTHMA MODEL; IN-VIVO AB Although the lung is the most common metastatic site for cancer cells, biologic mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma, and colon cancer. IL5 neutralization protected subjects from metastasis, whereas IL5 reconstitution or adoptive transfer of eosinophils into IL5-deficient mice exerted prometastatic effects. However, IL5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells to the lungs. During early stages of metastasis, Treg created a protumorigenic microenvironment, potentially by suppressing IFN?-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis. (C) 2015 AACR C1 [Zaynagetdinov, Rinat; Sherrill, Taylor P.; Gleaves, Linda A.; Habermann, Arun C.; Peebles, R. Stokes, Jr.; Blackwell, Timothy S.] Vanderbilt Univ, Dept Med, Dept Med Pulm & Crit Care Med, Div Allergy, Nashville, TN 37232 USA. [McLoed, Allyson G.; Saxon, Jamie A.; Fingleton, Barbara; Yull, Fiona E.; Blackwell, Timothy S.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. [Connelly, Linda] Univ Hawaii, Dept Pharmaceut Sci, Hilo, HI 96720 USA. [Dulek, Daniel] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. [Peebles, R. Stokes, Jr.; Blackwell, Timothy S.] US Dept Vet Affairs, Nashville, TN USA. [Yull, Fiona E.; Blackwell, Timothy S.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Stathopoulos, Georgios T.] Univ Patras, Dept Physiol, Lab Mol Resp Carcinogenesis, Rion, Greece. [Blackwell, Timothy S.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. RP Zaynagetdinov, R (reprint author), Vanderbilt Univ, Sch Med, 1161 21st Ave South,T-1218 MCN, Nashville, TN 37232 USA. EM rinat.z.zaynagetdinov@vanderbilt.edu FU Cancer Initiative of North Carolina; NIH [T32HL094296]; European Research Council Starting Independent Investigator Grant [FP7-IDEAS-ERC-StG-2010-260524-KRASHIMPE]; Department of Veterans Affairs; Vanderbilt-Ingram Cancer Center Spore Grant FX This work was supported by a grant from the Lung Cancer Initiative of North Carolina and Free to Breathe (R. Zaynagetdinov), NIH grant T32HL094296 (R. Zaynagetdinov), European Research Council Starting Independent Investigator Grant FP7-IDEAS-ERC-StG-2010-260524-KRASHIMPE (G.T. Stathopoulos), the Department of Veterans Affairs (T.S. Blackwell), and by a Vanderbilt-Ingram Cancer Center Spore Grant 2010 (T.S. Blackwell). NR 49 TC 8 Z9 8 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2015 VL 75 IS 8 BP 1624 EP 1634 DI 10.1158/0008-5472.CAN-14-2379 PG 11 WC Oncology SC Oncology GA CF9PH UT WOS:000352896900009 PM 25691457 ER PT J AU Perez, SE He, B Nadeem, M Wuu, J Scheff, SW Abrahamson, EE Ikonomovic, MD Mufson, EJ AF Perez, Sylvia E. He, Bin Nadeem, Muhammad Wuu, Joanne Scheff, Stephen W. Abrahamson, Eric E. Ikonomovic, Milos D. Mufson, Elliott J. TI Resilience of Precuneus Neurotrophic Signaling Pathways Despite Amyloid Pathology in Prodromal Alzheimer's Disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; Amyloid; Mild cognitive impairment; Neuropathology; Neurotrophic factors; Tau ID MILD COGNITIVE IMPAIRMENT; NERVE GROWTH-FACTOR; CHOLINERGIC BASAL FOREBRAIN; TRANSGENIC MOUSE; DEFAULT NETWORK; TAU PATHOLOGY; OLDER PERSONS; EARLY-ONSET; IN-VITRO; PRO-NGF AB BACKGROUND: Reduction of precuneus choline acetyltransferase activity co-occurs with greater beta-amyloid (A beta) in Alzheimer's disease (AD). Whether this cholinergic deficit is associated with alteration in nerve growth factor (NGF) signaling and its relation to A beta plaque and neurofibrillary tangle (NFT) pathology during disease onset is unknown. METHODS: Precuneus NGF upstream and downstream signaling levels relative to A beta and NFT pathology were evaluated using biochemistry and histochemistry in 62 subjects with a premortem diagnosis of non-cognitively impaired (NCI; n = 23), mild cognitive impairment (MCI; n = 21), and mild to moderate AD (n = 18). RESULTS: Immunoblots revealed increased levels of proNGF in AD subjects but not MCI subjects, whereas cognate receptors were unchanged. There were no significant differences in protein level for the downstream survival kinasesignaling proteins Erk and phospho-Erk among groups. Apoptotic phospho-JNK, phospho-JNK/JNK ratio, and Bcl-2 were significantly elevated in AD subjects. Soluble A beta(1-42) and fibrillar A beta measured by [H-3] Pittsburgh compound-B ([H-3] PiB) binding were significantly higher in AD subjects compared with MCI and NCI subjects. The density of plaques showed a trend to increase, but only 6-CN-PiB-positive plaques reached significance in AD subjects. AT8-positive, TOC-1-positive, and Tau C3-positive NFT densities were unchanged, whereas only AT8-positive neuropil thread density was statistically higher in AD subjects. A negative correlation was found between proNGF, phospho-JNK, and Bcl-2 levels and phospho-JNK/JNK ratio and cognition, whereas proNGF correlated positively with 6-CNPiB-positive plaques during disease progression. CONCLUSIONS: Data indicate that precuneus neurotrophin pathways are resilient to amyloid toxicity during the onset of AD. C1 [Perez, Sylvia E.; He, Bin; Nadeem, Muhammad; Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Wuu, Joanne] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Scheff, Stephen W.] Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Ctr, Pittsburgh, PA USA. RP Mufson, EJ (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1735 W Harrison St,Suite 310, Chicago, IL 60612 USA. EM emufson@rush.edu FU National Institute on Aging [PO1AG14449, PO1AG9466, P30AG10161, RO1AG025204, RO1AG043375] FX We thank the nuns, priests, and brothers from across the country that participated in the Rush Religious Order Study and the staff of the Rush Alzheimer's Disease Center. We also thank patients and research participants at the University of Kentucky Alzheimer's Disease Center. This study was supported by National Institute on Aging Grant Nos. PO1AG14449, PO1AG9466, P30AG10161, RO1AG025204, and RO1AG043375. NR 72 TC 12 Z9 12 U1 0 U2 7 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 APR 15 PY 2015 VL 77 IS 8 BP 693 EP 703 DI 10.1016/j.biopsych.2013.12.016 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LB UT WOS:000352092700007 PM 24529280 ER PT J AU Silverberg, ND Gardner, AJ Brubacher, JR Panenka, WJ Li, JJ Iverson, GL AF Silverberg, Noah D. Gardner, Andrew J. Brubacher, Jeffrey R. Panenka, William J. Li, Jun Jian Iverson, Grant L. TI Systematic Review of Multivariable Prognostic Models for Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Review DE concussion; systematic review; traumatic brain injury; prognosis ID POST-CONCUSSION SYMPTOMS; PREDICTING POSTCONCUSSION SYNDROME; MINOR HEAD-INJURY; EMERGENCY-DEPARTMENT; OUTCOME PREDICTION; PEDIATRIC CONCUSSION; FOLLOW-UP; CHILDREN; RECOVERY; EPIDEMIOLOGY AB Prognostic models can guide clinical management and increase statistical power in clinical trials. The availability and adequacy of prognostic models for mild traumatic brain injury (MTBI) is uncertain. The present study aimed to (1) identify and evaluate multivariable prognostic models for MTBI, and (2) determine which pre-, peri-, and early post-injury variables have independent prognostic value in the context of multivariable models. An electronic search of MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL databases for English-language MTBI cohort studies from 1970-2013 was supplemented by Web of Science citation and hand searching. This search strategy identified 7789 articles after removing duplicates. Of 182 full-text articles reviewed, 26 met eligibility criteria including (1) prospective inception cohort design, (2) prognostic information collected within 1 month post-injury, and (3) 2+variables combined to predict clinical outcome (e.g., post-concussion syndrome) at least 1 month later. Independent reviewers extracted sample characteristics, study design features, clinical outcome variables, predictor selection methods, and prognostic model discrimination, calibration, and cross-validation. These data elements were synthesized qualitatively. The present review found no multivariable prognostic model that adequately predicts individual patient outcomes from MTBI. Suboptimal methodology limits their reproducibility and clinical usefulness. The most robust prognostic factors in the context of multivariable models were pre-injury mental health and early post-injury neuropsychological functioning. Women and adults with early post-injury anxiety also have worse prognoses. Relative to these factors, the severity of MTBI had little long-term prognostic value. Future prognostic studies should consider a broad range of biopsychosocial predictors in large inception cohorts. C1 [Silverberg, Noah D.] Univ British Columbia, Vancouver, BC V5Z 2G9, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Vancouver, BC V5Z 2G9, Canada. [Gardner, Andrew J.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Waratah, NSW, Australia. [Brubacher, Jeffrey R.] Univ British Columbia, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada. [Panenka, William J.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Li, Jun Jian] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Iverson, Grant L.] Harvard Univ, Dept Phys Med & Rehabil, Med Sch, Charlestown, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Charlestown, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Sport Concuss Clin, Charlestown, MA USA. [Iverson, Grant L.] Red Sox Fdn, Charlestown, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Charlestown, MA USA. RP Silverberg, ND (reprint author), Univ British Columbia, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada. EM noah.silverberg@vch.ca RI Gardner, Andrew/J-5162-2013 FU Vancouver Coastal Health Research Institute; Michael Smith Foundation for Health Research; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX NDS is supported by the Vancouver Coastal Health Research Institute and JRB by a scholar award from the Michael Smith Foundation for Health Research. GLI notes that this work was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). NR 71 TC 14 Z9 14 U1 1 U2 22 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 APR 15 PY 2015 VL 32 IS 8 BP 517 EP 526 DI 10.1089/neu.2014.3600 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CF2BS UT WOS:000352352900001 PM 25222514 ER PT J AU Waljas, M Iverson, GL Lange, RT Hakulinen, U Dastidar, P Huhtala, H Liimatainen, S Hartikainen, K Ohman, J AF Waljas, Minna Iverson, Grant L. Lange, Rael T. Hakulinen, Ullamari Dastidar, Prasun Huhtala, Heini Liimatainen, Suvi Hartikainen, Kaisa Ohman, Juha TI A Prospective Biopsychosocial Study of the Persistent Post-Concussion Symptoms following Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE traumatic brain injury; cognitive function; diffusion tensor imaging; prospective study; outcome measures ID SPORTS-RELATED CONCUSSION; TENSOR IMAGING FINDINGS; MINOR HEAD-INJURY; POSTTRAUMATIC-STRESS-DISORDER; DIFFUSE AXONAL INJURY; DSM-IV CRITERIA; POSTCONCUSSION SYNDROME; WHITE-MATTER; DIAGNOSTIC-CRITERIA; RISK-FACTORS AB This study examined multiple biopsychosocial factors relating to post-concussion symptom (PCS) reporting in patients with mild traumatic brain injuries (mTBI), including structural (computed tomography and magnetic resonance imaging [MRI]) and microstructural neuroimaging (diffusion tensor imaging [DTI]). Patients with mTBIs completed several questionnaires and cognitive testing at approximately one month (n=126) and one year (n=103) post-injury. At approximately three weeks post-injury, DTI was undertaken using a Siemens 3T scanner in a subgroup (n=71). Measures of fractional anisotropy were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient were calculated for 10 ROIs. Patients were compared with healthy control subjects. Using International Classification of Diseases, Tenth Revision (ICD-10) PCS criteria and mild or greater symptom reporting, 59% of the mTBI sample met criteria at one month and 38% met criteria at one year. However, 31% of the healthy control sample also met criteria for the syndrome-illustrating a high false-positive rate. Significant predictors of ICD-10 PCS at one month were pre-injury mental health problems and the presence of extra-cranial bodily injuries. Being symptomatic at one month was a significant predictor of being symptomatic at one year, and depression was significantly related to PCS at both one month and one year. Intracranial abnormalities visible on MRI were present in 12.1% of this sample, and multifocal areas of unusual white matter as measured by DTI were present in 50.7% (compared with 12.4% of controls). Structural MRI abnormalities and microstructural white matter findings were not significantly associated with greater post-concussion symptom reporting. The personal experience and reporting of post-concussion symptoms is likely individualized, representing the cumulative effect of multiple variables, such as genetics, mental health history, current life stress, medical problems, chronic pain, depression, personality factors, and other psychosocial and environmental factors. The extent to which damage to the structure of the brain contributes to the persistence of post-concussion symptoms remains unclear. C1 [Waljas, Minna; Liimatainen, Suvi; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, Tampere, Finland. [Hakulinen, Ullamari; Dastidar, Prasun] Tampere Univ Hosp, Dept Radiol, Tampere, Finland. [Waljas, Minna; Dastidar, Prasun; Ohman, Juha] Univ Tampere Med Sch, Tampere, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Lange, Rael T.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Lange, Rael T.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Hakulinen, Ullamari] Tampere Univ Technol, Dept Elect & Commun Engn, FIN-33101 Tampere, Finland. [Huhtala, Heini] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Hartikainen, Kaisa] Pirkanmaa Hosp Dist, Behav Neurol Res Unit, Tampere, Finland. RP Waljas, M (reprint author), Tampere Univ Hosp, Dept Neurosurg, POB 2000, FIN-3521 Tampere, Finland. EM minna.waljas@pshp.fi OI Ohman, Juha/0000-0002-6592-1367 FU Pirkanmaa Hospital District, Tampere University Hospital; University of Tampere; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX This research was funded by Competitive Research Funding of the Pirkanmaa Hospital District, Tampere University Hospital and Research Funding of University of Tampere. This study was done as part of the first author's PhD thesis research program. Dr. Iverson notes that he was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). The authors thank Pasi Jolma (MD, PhD) for recruiting the patients and conducting neurological examinations and Annika Vuorinen (MSc) for assistance in recruitment and assessment of the control sample. Preliminary results of this study were presented at the International Neuropsychological Society, Boston, MA, in February 2011. NR 107 TC 16 Z9 17 U1 4 U2 32 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 APR 15 PY 2015 VL 32 IS 8 BP 534 EP 547 DI 10.1089/neu.2014.3339 PG 14 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CF2BS UT WOS:000352352900003 PM 25363626 ER PT J AU Long, JA Watts, LT Chemello, J Huang, SL Shen, Q Duong, TQ AF Long, Justin Alexander Watts, Lora Talley Chemello, Jonathan Huang, Shiliang Shen, Qiang Duong, Timothy Q. TI Multiparametric and Longitudinal MRI Characterization of Mild Traumatic Brain Injury in Rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavioral assessments; diffusion tensor imaging; immunohistochemistry; TBI; controlled cortical impact; quantitative magnetic resonance imaging ID DIFFUSE AXONAL INJURY; CEREBRAL-BLOOD-FLOW; IMAGING FINDINGS; NEURONAL DEGENERATION; FLUORO-JADE; PERFUSION; EDEMA; DYNAMICS; HYPOXIA; MODELS AB This study reports T-2 and diffusion-tensor magnetic resonance imaging (MRI) studies of a mild open-skull, controlled cortical impact injury in rats (n=6) from 3 h to up to 14 d after traumatic brain injury (TBI). Comparison was made with longitudinal behavioral measurements and end-point histology. The impact was applied over the left primary forelimb somatosensory cortex (S1FL). The major findings were: 1) In the S1FL, T-2 increased and fractional anisotropy (FA) decreased at 3 h after TBI and gradually returned toward normal by Day 14; 2) in the S1FL, the apparent diffusion coefficient (ADC) increased at 3 h, peaked on Day 2, and gradually returned toward normal at Day 14; 3) in the corpus callosum underneath the S1FL, FA decreased at 3 h to Day 2 but returned to normal at Day 7 and 14, whereas T-2 and ADC were normal throughout; 4) heterogeneous hyperintense and hypointense T-2 map intensities likely indicated the presence of hemorrhage but were not independently verified; 5) lesion volumes defined by abnormal T-2, ADC, and FA showed similar temporal patterns, peaking around Day 2 and returning toward normal on Day 14; 6) the temporal profiles of lesion volumes were consistent with behavioral scores assessed by forelimb placement and forelimb foot fault tests; and 7) at 14 d post-TBI, there was substantial tissue recovery by MRI, which could either reflect true tissue recovery or reabsorption of edema. Histology performed 14 d post-TBI, however, showed a small cavitation and significant neuronal degeneration surrounding the cavitation in S1FL. Thus, the observed improvement of behavioral scores likely involves both functional recovery and functional compensation. C1 [Long, Justin Alexander; Watts, Lora Talley; Chemello, Jonathan; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Watts, Lora Talley] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora Talley; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthamol, Radiol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH/NINDS [R01 NS45879]; TL1 grant; Clinical Translational Science Awards (CTSA) [KL2 TR001118, UL1TR000149, TL1TR001119] FX The authors wish to thank Timothy Schallert and Theresa Jones of UT Austin for their assistance in the setup of the behavioral assays utilized in this study. This work was supported in part by NIH/NINDS R01 NS45879 (TQD), a TL1 grant (JAL) and KL2 TR001118 (LTW) via the Clinical Translational Science Awards (CTSA, parent grant UL1TR000149 and TL1TR001119). Images were generated in the Core Optical Imaging Facility which is supported by UTHSCSA, NIH/NCI P30CA54174 and NIH/NIA P01AG19316. NR 40 TC 12 Z9 12 U1 0 U2 4 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 APR 15 PY 2015 VL 32 IS 8 BP 598 EP 607 DI 10.1089/neu.2014.3563 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CF2BS UT WOS:000352352900010 PM 25203249 ER PT J AU Goldkorn, A Ely, B Tangen, CM Tai, YC Xu, T Li, HL Twardowski, P Van Veldhuizen, PJ Agarwal, N Carducci, MA Monk, JP Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Vogelzang, NJ Thompson, IM Cote, RJ Quinn, DI AF Goldkorn, Amir Ely, Benjamin Tangen, Catherine M. Tai, Yu-Chong Xu, Tong Li, Hongli Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Carducci, Michael A. Monk, J. Paul, III Garzotto, Mark Mack, Philip C. Lara, Primo, Jr. Higano, Celestia S. Hussain, Maha Vogelzang, Nicholas J. Thompson, Ian M., Jr. Cote, Richard J. Quinn, David I. TI Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE circulating tumor cells; telomerase activity; prostate cancer; prognosis; biomarker ID PREDICTIVE BIOMARKER; DOCETAXEL; PLACEBO; MICROFILTER; ATRASENTAN; S0421; MEN AB Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count 5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p=0.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p=0.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step towards molecular CTC-based precision cancer management. C1 [Goldkorn, Amir; Xu, Tong; Quinn, David I.] Univ So Calif, Keck Sch Med, Div Med Oncol, Dept Med, Los Angeles, CA 90033 USA. [Goldkorn, Amir; Xu, Tong; Quinn, David I.] Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Ely, Benjamin; Tangen, Catherine M.; Li, Hongli] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, SWOG Stat Ctr, Seattle, WA 98104 USA. [Tai, Yu-Chong] CALTECH, Pasadena, CA 91125 USA. [Twardowski, Przemyslaw] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Van Veldhuizen, Peter J.] Univ Kansas, Ctr Canc, Hem Onc Div, Westwood, KS USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Div Oncol, Salt Lake City, UT USA. [Carducci, Michael A.] Johns Hopkins Univ, Dept Urol, Baltimore ECOG, Baltimore, MD USA. [Carducci, Michael A.] Johns Hopkins Univ, Dept Oncol, Baltimore ECOG, Baltimore, MD USA. [Monk, J. Paul, III] Ohio State Univ, CALGB, Div Med Oncol, Columbus, OH 43210 USA. [Garzotto, Mark] Portland VA Med Ctr, Dept Urol, Portland, OR USA. [Mack, Philip C.; Lara, Primo, Jr.] Univ Calif Davis, Div Hematol & Oncol, Sacramento, CA 95817 USA. [Higano, Celestia S.] Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Div Oncol,Dept Med,Dept Urol, Seattle, WA 98195 USA. [Hussain, Maha] Univ Michigan, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Div Med Oncol, Las Vegas, NV USA. [Vogelzang, Nicholas J.] US Oncol Res, Las Vegas, NV USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Cote, Richard J.] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. RP Goldkorn, A (reprint author), Univ So Calif, Keck Sch Med, Div Med Oncol, Dept Internal Med, Los Angeles, CA 90033 USA. EM agoldkor@med.usc.edu RI Quinn, David/F-4343-2015 OI Quinn, David/0000-0002-1411-0417 FU National Cancer Institute at the National Institutes of Health; DHHS [CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433]; DHHS. [CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844]; DHHS; [CA68183, CA11083, CA63845, CA76447, CA35128, CA13612, CA35431, CA76448, CA35178, CA35176, CA35119, CA35421, CA128567, CA04919, CA45560, CA37981, CA58723, CA21115, CA31946, CA16116, CA31949, CA014089-38, CCSRI 015469, CA141077] FX Grant sponsors: PHS Cooperative Agreement grants by the National Cancer Institute at the National Institutes of Health and DHHS; Grant numbers: CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433, CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844, CA11083, CA63845, CA76447, CA35128, CA13612, CA35431, CA76448, CA35178, CA35176, CA35119, CA35421, CA128567, CA04919, CA68183, CA45560, CA37981, CA58723, CA21115, CA31946, CA16116, CA31949, CA014089-38, CCSRI 015469 and CA141077; Grant sponsors: Hope Foundation and Abbott Laboratories and Sanofi-Aventis NR 27 TC 10 Z9 11 U1 0 U2 12 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 APR 15 PY 2015 VL 136 IS 8 BP 1856 EP 1862 DI 10.1002/ijc.29212 PG 7 WC Oncology SC Oncology GA CB4SS UT WOS:000349619000011 PM 25219358 ER PT J AU Alonso-Alconada, L Santacana, M Garcia-Sanz, P Muinelo-Romay, L Colas, E Mirantes, C Monge, M Cueva, J Oliva, E Soslow, RA Lopez, MA Palacios, J Prat, J Valls, J Krakstad, C Salvesen, H Gil-Moreno, A Lopez-Lopez, R Dolcet, X Moreno-Bueno, G Reventos, J Matias-Guiu, X Abal, M AF Alonso-Alconada, Lorena Santacana, Maria Garcia-Sanz, Pablo Muinelo-Romay, Laura Colas, Eva Mirantes, Cristina Monge, Marta Cueva, Juan Oliva, Esther Soslow, Robert A. Angeles Lopez, Maria Palacios, Jose Prat, Jaime Valls, Joan Krakstad, Camilla Salvesen, Helga Gil-Moreno, Antonio Lopez-Lopez, Rafael Dolcet, Xavier Moreno-Bueno, Gema Reventos, Jaume Matias-Guiu, Xavier Abal, Miguel TI Annexin-A2 as predictor biomarker of recurrent disease in endometrial cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE endometrial cancer; recurrent disease; metastasis; ANXA2; biomarker ID CIRCULATING TUMOR-CELLS; BREAST-CANCER; PROTEOMIC ANALYSIS; FREE SURVIVAL; A2; PROGRESSION; CARCINOMA; METASTASIS; MARKER; TRIAL AB Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine-confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy. C1 [Alonso-Alconada, Lorena; Muinelo-Romay, Laura; Cueva, Juan; Lopez-Lopez, Rafael; Abal, Miguel] SERGAS, Fdn Ramon Dominguez, Hlth Res Inst Santiago IDIS, Santiago De Compostela 15706, Spain. [Santacana, Maria; Mirantes, Cristina; Valls, Joan; Dolcet, Xavier; Matias-Guiu, Xavier] Univ Lleida, Hosp Univ Arnau de Vilanova, Dept Pathol & Mol Genet, Irblleida, Lleida, Spain. [Santacana, Maria; Mirantes, Cristina; Valls, Joan; Dolcet, Xavier; Matias-Guiu, Xavier] Univ Lleida, Hosp Univ Arnau de Vilanova, Res Lab, Irblleida, Lleida, Spain. [Garcia-Sanz, Pablo; Moreno-Bueno, Gema] Fdn MD Anderson Canc Ctr Madrid, Madrid, Spain. [Colas, Eva; Monge, Marta; Gil-Moreno, Antonio; Reventos, Jaume] Vall dHebron Res Inst & Hosp, Res Unit Biomed, Barcelona, Spain. [Colas, Eva; Monge, Marta; Gil-Moreno, Antonio; Reventos, Jaume] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Angeles Lopez, Maria; Palacios, Jose] Hosp Univ Ramon y Cajal, Dept Pathol, Madrid, Spain. [Prat, Jaime] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona, Spain. [Krakstad, Camilla; Salvesen, Helga] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Krakstad, Camilla; Salvesen, Helga] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway. [Moreno-Bueno, Gema] Univ Autonoma Madrid, Dept Biochem, Inst Invest Biomed Alberto Sols CSIC UAM, IdiPAZ, Madrid, Spain. [Reventos, Jaume] Univ Int Catalunya, Dept Ciencies Basiques, Barcelona, Spain. [Reventos, Jaume] IDIBELL, Inst Invest Biomed Bellvitge, Lhospitalet De Llobregat, Spain. RP Matias-Guiu, X (reprint author), SERGAS, Fdn Ramon Dominguez, Hlth Res Inst Santiago IDIS, Trav Choupana S-N, Santiago De Compostela 15706, Spain. EM miguel.abal.posada@sergas.es; fjmatiasguiu.lleida.ics@gencat.cat RI Monge , Marta/I-3667-2015; matias-guiu, xavier/C-3039-2009; Gil-Moreno, Antonio/C-1122-2016; Moreno-Bueno, Gema/K-9354-2016; salvesen, Helga/C-1187-2017; OI Monge , Marta/0000-0002-9839-4903; matias-guiu, xavier/0000-0002-7201-6605; Gil-Moreno, Antonio/0000-0003-1106-5590; Moreno-Bueno, Gema/0000-0002-5030-6687; salvesen, Helga/0000-0002-4438-8831; Colas, Eva/0000-0002-4439-4254; Soslow, Robert/0000-0002-7269-5898 FU Innovation in Nanomedicine (InveNNta) [ISCIII PI11/00873]; Operational Program for Cross-border Cooperation: Spain-Portugal (POCTEP); European Regional Development Fund (ERDF); Fundacion Asociacion Espanola Contra el Cancer (AECC); Grupos Estables; Basque Government (Spain) FX Grant sponsor: Innovation in Nanomedicine (InveNNta); Grant number: ISCIII PI11/00873; Grant sponsors: Operational Program for Cross-border Cooperation: Spain-Portugal (POCTEP), European Regional Development Fund (ERDF), Fundacion Asociacion Espanola Contra el Cancer (AECC), Grupos Estables 2011 and Basque Government (Spain) NR 35 TC 5 Z9 6 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 APR 15 PY 2015 VL 136 IS 8 BP 1863 EP 1873 DI 10.1002/ijc.29213 PG 11 WC Oncology SC Oncology GA CB4SS UT WOS:000349619000012 PM 25219463 ER PT J AU Farvid, MS Cho, E Chen, WY Eliassen, A Willett, WC AF Farvid, Maryam S. Cho, Eunyoung Chen, Wendy Y. Eliassen, A. Heather Willett, Walter C. TI Adolescent meat intake and breast cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PHASEOLUS-VULGARIS L.; EPIDEMIOLOGIC ANALYSES; PROSPECTIVE COHORT; DIETARY-INTAKE; YOUNG-WOMEN; CONSUMPTION; FOOD; DAIRY; FAT; RED AB The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of total red meat in adolescence was significantly associated with higher premenopausal breast cancer risk (highest vs. lowest quintiles, RR, 1.43; 95%CI, 1.05-1.94; P-trend=0.007), but not postmenopausal breast cancer. Adolescent intake of poultry was associated with lower risk of breast cancer overall (RR, 0.76; 95%CI, 0.60-0.97; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 15% lower risk of breast cancer overall (RR, 0.85; 95%CI, 0.74-0.96) and a 23% lower risk of premenopausal breast cancer (RR, 0.77; 95%CI, 0.64-0.92). In conclusion, higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. C1 [Farvid, Maryam S.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Farvid, Maryam S.] Shahid Beheshti Univ Med Sci, Fac Nutr Sci & Food Technol, Dept Community Nutr, Tehran, Iran. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Cho, Eunyoung; Chen, Wendy Y.; Eliassen, A. Heather; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Cho, Eunyoung; Chen, Wendy Y.; Eliassen, A. Heather; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Eliassen, A. Heather; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Farvid, MS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM mfarvid@hsph.harvard.edu FU National Institutes of Health [R01CA050385] FX Grant sponsor: National Institutes of Health; Grant number: R01CA050385 NR 45 TC 12 Z9 12 U1 7 U2 62 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 APR 15 PY 2015 VL 136 IS 8 BP 1909 EP 1920 DI 10.1002/ijc.29218 PG 12 WC Oncology SC Oncology GA CB4SS UT WOS:000349619000017 PM 25220168 ER PT J AU Song, EK Tai, WM Messersmith, WA Bagby, S Purkey, A Quackenbush, KS Pitts, TM Wang, GL Blatchford, P Yahn, R Kaplan, J Tan, AC Atreya, CE Eckhardt, G Kelley, RK Venook, A Kwak, EL Ryan, D Arcaroli, JJ AF Song, Eun-Kee Tai, W. M. Messersmith, Wells A. Bagby, Stacey Purkey, Alicia Quackenbush, Kevin S. Pitts, Todd M. Wang, Guoliang Blatchford, Patrick Yahn, Rachel Kaplan, Jeffrey Tan, Aik Choon Atreya, Chloe E. Eckhardt, Gail Kelley, Robin K. Venook, Alan Kwak, Eunice L. Ryan, David Arcaroli, John J. TI Potent antitumor activity of cabozantinib, a c- MET and VEGFR2 inhibitor, in a colorectal cancer patient- derived tumor explant model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colorectal cancer; angiogenesis; c-MET; RET; VEGFR2; PIK3CA ID MEDULLARY-THYROID CANCER; COLON-CANCER; PANCREATIC-CANCER; PHASE-3 TRIAL; METASTASIS; INVASION; ANGIOGENESIS; ACTIVATION; MUTATIONS; RECEPTOR AB Antiangiogenic therapy is commonly used for the treatment of colorectal cancer (CRC). Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to antiangiogenic therapy. MET is upregulated in response to vascular endothelial growth factor pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study, we set out to determine the efficacy of cabozantinib in a preclinical CRC patient-derived tumor xenograft model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. C1 [Song, Eun-Kee; Tai, W. M.; Messersmith, Wells A.; Bagby, Stacey; Purkey, Alicia; Quackenbush, Kevin S.; Pitts, Todd M.; Wang, Guoliang; Blatchford, Patrick; Yahn, Rachel; Kaplan, Jeffrey; Tan, Aik Choon; Eckhardt, Gail; Arcaroli, John J.] Univ Colorado Denver, Div Med Oncol, Aurora, CO USA. [Song, Eun-Kee; Tai, W. M.; Messersmith, Wells A.; Bagby, Stacey; Purkey, Alicia; Quackenbush, Kevin S.; Pitts, Todd M.; Wang, Guoliang; Blatchford, Patrick; Yahn, Rachel; Kaplan, Jeffrey; Tan, Aik Choon; Eckhardt, Gail; Arcaroli, John J.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Song, Eun-Kee] Chonbuk Natl Univ, Sch Med, Dept Internal Med, Jeonju 561756, South Korea. [Atreya, Chloe E.; Kelley, Robin K.; Venook, Alan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kwak, Eunice L.; Ryan, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwak, Eunice L.; Ryan, David] Harvard Univ, Sch Med, Boston, MA USA. RP Arcaroli, JJ (reprint author), 12801 E 17th Ave,MS 8117, Aurora, CO 80045 USA. EM john.arcaroli@ucdenver.edu RI Tan, Aik Choon/A-3135-2011; OI Tan, Aik Choon/0000-0003-2955-8369 FU Exelixis; Chonbuk National University; American Cancer Society [11-183-01-TBG]; Alliance for Clinical Trials in Oncology Foundation; Mt. Zion Health Fund; Gump Cancer Fund from the Resource Evaluation and Allocation Committee; Helen Diller Family Comprehensive Cancer Center under the National Institutes of Health [K08CA17515301]; National Cancer Institute under the National Institutes of Health [K08CA17515301] FX This preclinical work was supported with research funds from Exelixis (to J.J.A.). This article was supported by research funds of Chonbuk National University in 2012. C.E.A. gratefully acknowledges support from American Cancer Society Postdoctoral Fellowship 11-183-01-TBG; the Alliance for Clinical Trials in Oncology Foundation; the Mt. Zion Health Fund, Gump Cancer Fund from the Resource Evaluation and Allocation Committee, and Helen Diller Family Comprehensive Cancer Center and National Cancer Institute under the National Institutes of Health Award K08CA17515301. NR 42 TC 9 Z9 9 U1 1 U2 15 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 APR 15 PY 2015 VL 136 IS 8 BP 1967 EP 1975 DI 10.1002/ijc.29225 PG 9 WC Oncology SC Oncology GA CB4SS UT WOS:000349619000023 PM 25242168 ER PT J AU Cohen, N Sabhachandani, P Golberg, A Konry, T AF Cohen, Noa Sabhachandani, Pooja Golberg, Alexander Konry, Tania TI Approaching near real-time biosensing: Microfluidic microsphere based biosensor for real-time analyte detection SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Microsphere; Real time detection; Lab on a chip; TNF-alpha; Cytokine; Antibody ID NECROSIS-FACTOR-ALPHA; LINKED-IMMUNOSORBENT-ASSAY; TNF-ALPHA; BINDING-KINETICS; NEXT-GENERATION; IMMUNOASSAYS; ANTIBODY; SYSTEMS; MICROARRAY; SEPARATION AB In this study we describe a simple lab-on-a-chip (LOC) biosensor approach utilizing well mixed microfluidic device and a microsphere-based assay capable of performing near real-time diagnostics of clinically relevant analytes such cytokines and antibodies. We were able to overcome the adsorption kinetics reaction rate-limiting mechanism, which is diffusion-controlled in standard immunoassays, by introducing the microsphere-based assay into well-mixed yet simple microfluidic device with turbulent flow profiles in the reaction regions. The integrated microsphere-based LOC device performs dynamic detection of the analyte in minimal amount of biological specimen by continuously sampling micro-liter volumes of sample per minute to detect dynamic changes in target analyte concentration. Furthermore we developed a mathematical model for the well-mixed reaction to describe the near real time detection mechanism observed in the developed LOC method. To demonstrate the specificity and sensitivity of the developed real time monitoring LOC approach, we applied the device for clinically relevant analytes: Tumor Necrosis Factor (TNF)-alpha cytokine and its clinically used inhibitor, anti-TNF-alpha antibody. Based on the reported results herein, the developed LOC device provides continuous sensitive and specific near real-time monitoring method for analytes such as cytokines and antibodies, reduces reagent volumes by nearly three orders of magnitude as well as eliminates the washing steps required by standard immunoassays. (C) 2014 Elsevier B.V. All rights reserved. C1 [Cohen, Noa; Sabhachandani, Pooja; Konry, Tania] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Golberg, Alexander] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. RP Konry, T (reprint author), Northeastern Univ, Dept Pharmaceut Sci, 140 Fenway,Room 441-446,360 Huntington Ave, Boston, MA 02115 USA. EM konry.tania@gmail.com NR 44 TC 13 Z9 13 U1 5 U2 74 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 EI 1873-4235 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2015 VL 66 BP 454 EP 460 DI 10.1016/j.bios.2014.11.018 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA CA0PR UT WOS:000348619800067 PM 25497985 ER PT J AU Kim, J Hudson, NE Springer, TA AF Kim, Jongseong Hudson, Nathan E. Springer, Timothy A. TI Force-induced on-rate switching and modulation by mutations in gain-of-function von Willebrand diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCOPROTEIN IB-ALPHA; PROTEIN-PROTEIN ASSOCIATION; PHYSIOLOGICAL FLOW-RATES; FACTOR A1 DOMAIN; PLATELET-ADHESION; SINGLE-MOLECULE; ENCOUNTER COMPLEXES; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING AB Mutations in the ultralong vascular protein von Willebrand factor (VWF) cause the common human bleeding disorder, von Willebrand disease (VWD). The A1 domain in VWF binds to glycoprotein Ib alpha (GPIb alpha) on platelets, in a reaction triggered, in part, by alterations in flow during bleeding. Gain-of-function mutations in A1 and GPIb alpha in VWD suggest conformational regulation. We report that force application switches A1 and/or GPIb alpha to a second state with faster on-rate, providing a mechanism for activating VWF binding to platelets. Switching occurs near 10 pN, a force that also induces a state of the receptor-ligand complex with slower off-rate. Force greatly increases the effects of VWD mutations, explaining pathophysiology. Conversion of single molecule k(on) (s(-1)) to bulk phase k(on) (s(-1)M(-1)) and the k(on) and k(off) values extrapolated to zero force for the low-force pathways show remarkably good agreement with bulk-phase measurements. C1 [Springer, Timothy A.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. EM Timothy.Springer@childrens.harvard.edu RI Kim, Jongseong/M-9940-2014; OI Kim, Jongseong/0000-0001-9595-2765; Hudson, Nathan/0000-0003-0573-7661 FU National Institutes of Health [HL-108248] FX We are extremely grateful to Olga Dudko, Christopher Pierse, Cheng-Zhong Zhang, Darren Yang, and Wesley Wong for insightful discussions on physical models and calculations. The research was supported by National Institutes of Health Grant HL-108248. NR 37 TC 3 Z9 3 U1 1 U2 10 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 APR 14 PY 2015 VL 112 IS 15 BP 4648 EP 4653 DI 10.1073/pnas.1501689112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800048 PM 25810255 ER PT J AU Nieman, K Hoffmann, U AF Nieman, Koen Hoffmann, Udo TI Cardiac computed tomography in patients with acute chest pain SO EUROPEAN HEART JOURNAL LA English DT Review DE Computed tomography; Acute chest pain; Acute coronary syndrome; Myocardial infarction; Diagnostic triage; Review ID CORONARY CT ANGIOGRAPHY; EMERGENCY-DEPARTMENT; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; DIAGNOSTIC-ACCURACY; BLOOD-FLOW; TRIAL; PERFUSION; STENOSIS; METAANALYSIS AB The efficient and reliable evaluation of patients with acute chest pain is one of the most challenging tasks in the emergency department. Coronary computed tomography (CT) angiographymay play a major role, since it permits ruling out coronary artery disease with high accuracy if performed with expertise in properly selected and prepared patients. Several randomized trials have established early cardiac CT as a viable safe and potentially more efficient alternative to functional testing in the evaluation of acute chest pain. Ongoing investigations explore whether advanced anatomic and functional assessments such as high-risk coronary plaque, resting myocardial perfusion, and left ventricular function, or the simulation of the fractional coronary flow reserve will add information to the anatomic assessment for stenosis, which would allow expanding the benefits of cardiac CT from triage to treatment decisions. Especially, the combination of high-sensitive troponins and coronary computed tomography angiography may play a valuable role in future strategies for the management of patients presenting with acute chest pain. C1 [Nieman, Koen] Erasmus MC, Dept Cardiol, NL-3000 CA Rotterdam, Netherlands. [Nieman, Koen] Erasmus MC, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nieman, K (reprint author), Erasmus MC, Dept Cardiol, Room Hs207,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM koennieman@hotmail.com FU Siemens Medical Solutions; Bayer Healthcare; GE Healthcare FX K.N. has received institutional research support from Siemens Medical Solutions, Bayer Healthcare and GE Healthcare. NR 35 TC 5 Z9 5 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR 14 PY 2015 VL 36 IS 15 BP 906 EP 914 DI 10.1093/eurheartj/ehv034 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG8FE UT WOS:000353541800010 PM 25687351 ER PT J AU Shore, S Ho, PM Lambert-Kerzner, A Glorioso, TJ Carey, EP Cunningham, F Longo, L JackeviciusPharmD, C Rose, A Turakhia, MP AF Shore, Supriya Ho, P. Michael Lambert-Kerzner, Anne Glorioso, Thomas J. Carey, Evan P. Cunningham, Fran Longo, Lisa Jackevicius, Cynthia Rose, Adam Turakhia, Mintu P. TI Site-Level Variation in and Practices Associated With Dabigatran Adherence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ATRIAL-FIBRILLATION; MEDICATION ADHERENCE; MYOCARDIAL-INFARCTION; STROKE PREVENTION; PHARMACY RECORDS; PATIENT-OUTCOMES; TREAT-AF; HEALTH; ANTICOAGULATION; WARFARIN AB IMPORTANCE Unlike warfarin, which requires routine laboratory testing and dose adjustment, target-specific oral anticoagulants like dabigatran do not. However, optimal follow-up infrastructure and modifiable site-level factors associated with improved adherence to dabigatran are unknown. OBJECTIVES To assess site-level variation in dabigatran adherence and to identify site-level practices associated with higher dabigatran adherence. DESIGN, SETTING, AND PARTICIPANTS Mixed-methods study involving retrospective quantitative and cross-sectional qualitative data. A total of 67 Veterans Health Administration sites with 20 or more patients filling dabigatran prescriptions between 2010 and 2012 for nonvalvular atrial fibrillation were sampled (4863 total patients; median, 51 patients per site). Forty-seven pharmacists from 41 eligible sites participated in the qualitative inquiry. EXPOSURE Site-level practices identified included appropriate patient selection, pharmacist-driven patient education, and pharmacist-led adverse event and adherence monitoring. MAIN OUTCOMES AND MEASURES Dabigatran adherence (intensity of drug use during therapy) defined by proportion of days covered (ratio of days supplied by prescription to follow-up duration) of 80% or more. RESULTS The median proportion of patients adherent to dabigatran was 74% (interquartile range [IQR], 66%-80%). After multivariable adjustment, dabigatran adherence across sites varied by a median odds ratio of 1.57. Review of practices across participating sites showed that appropriate patient selection was performed at 31 sites, pharmacist-led education was provided at 30 sites, and pharmacist-led monitoring at 28 sites. The proportion of adherent patients was higher at sites performing appropriate selection (75% vs 69%), education (76% vs 66%), and monitoring (77% vs 65%). Following multivariable adjustment, association between pharmacist-led education and dabigatran adherence was not statistically significant (relative risk [RR], 0.94; 95% Cl, 0.83-1.06). Appropriate patient selection (RR, 1.14; 95% Cl, 1.05-1.25), and provision of pharmacist-led monitoring (RR, 1.25; 95% Cl, 1.11-1.40 were associated with better patient adherence. Additionally, longer duration of monitoring and providing more intensive care to nonadherent patients in collaboration with the clinician improved adherence. CONCLUSIONS AND RELEVANCE Among nonvalvular atrial fibrillation patients treated with dabigatran, there was variability in patient medication adherence across Veterans Health Administration sites. Specific pharmacist-based activities were associated with greater patient adherence to dabigatran. C1 [Shore, Supriya] Emory Univ, Sch Med, Atlanta, GA USA. [Ho, P. Michael; Lambert-Kerzner, Anne; Glorioso, Thomas J.; Carey, Evan P.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Ho, P. Michael; Glorioso, Thomas J.; Carey, Evan P.] Univ Colorado, Aurora, CO USA. [Ho, P. Michael; Lambert-Kerzner, Anne; Glorioso, Thomas J.; Carey, Evan P.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Cunningham, Fran; Longo, Lisa] Pharm Benefits Management Serv, Vet Affairs, Hines, IL USA. [Cunningham, Fran; Longo, Lisa] Ctr Medicat Safety, Hines, IL USA. [Jackevicius, Cynthia] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Jackevicius, Cynthia] Western Univ Hlth Sci, Pomona, CA USA. [Rose, Adam] Bedford Veterabs Affairs Med Ctr, Bedford, MA USA. [Rose, Adam] Boston Univ, Boston, MA 02215 USA. [Turakhia, Mintu P.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Turakhia, Mintu P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Turakhia, MP (reprint author), VA Palo Alto Hlth Care Syst, Dept Cardiol, 3801 Miranda Ave,Ste 111C, Palo Alto, CA 94304 USA. EM mintu@stanford.edu FU Career Development Award from VA Health Services Research Development; American Heart Association National Scientist Development Grant; Gilead Sciences Cardiovascular Research Scholars Program award FX Dr Turakhia is supported by a Career Development Award from VA Health Services Research & Development, an American Heart Association National Scientist Development Grant, and a Gilead Sciences Cardiovascular Research Scholars Program award. NR 24 TC 26 Z9 26 U1 0 U2 5 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 APR 14 PY 2015 VL 313 IS 14 BP 1443 EP 1450 DI 10.1001/jama.2015.2761 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CF8OK UT WOS:000352821200020 PM 25871670 ER PT J AU Chung, J Bauer, DE Ghamari, A Nizzi, CP Deck, KM Kingsley, PD Yien, YY Huston, NC Chen, CY Schultz, IJ Dalton, AJ Wittig, JG Palis, J Orkin, SH Lodish, HF Eisenstein, RS Cantor, AB Paw, BH AF Chung, Jacky Bauer, Daniel E. Ghamari, Alireza Nizzi, Christopher P. Deck, Kathryn M. Kingsley, Paul D. Yien, Yvette Y. Huston, Nicholas C. Chen, Caiyong Schultz, Iman J. Dalton, Arthur J. Wittig, Johannes G. Palis, James Orkin, Stuart H. Lodish, Harvey F. Eisenstein, Richard S. Cantor, Alan B. Paw, Barry H. TI The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability SO SCIENCE SIGNALING LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; MESSENGER-RNA TRANSLATION; AMINO-ACID TRANSPORTER; REGULATED EIF2-ALPHA KINASE; PROTEIN-SYNTHESIS; BETA-THALASSEMIA; MAMMALIAN-CELLS; ERYTHROID-CELLS; IRON ASSIMILATION; IN-VIVO AB In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E-binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine. C1 [Chung, Jacky; Yien, Yvette Y.; Huston, Nicholas C.; Chen, Caiyong; Schultz, Iman J.; Dalton, Arthur J.; Wittig, Johannes G.; Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. [Bauer, Daniel E.; Ghamari, Alireza; Orkin, Stuart H.; Cantor, Alan B.; Paw, Barry H.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. [Bauer, Daniel E.; Ghamari, Alireza; Orkin, Stuart H.; Cantor, Alan B.; Paw, Barry H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Nizzi, Christopher P.; Deck, Kathryn M.; Eisenstein, Richard S.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Kingsley, Paul D.; Palis, James] Univ Rochester, Med Ctr, Ctr Pediat Biomed Res, Dept Pediat, Rochester, NY 14642 USA. [Lodish, Harvey F.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Paw, BH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. EM bpaw@rics.bwh.harvard.edu OI Wittig, Johannes/0000-0002-0598-2897 FU Canadian Institutes of Health Research (CIHR); Cooley's Anemia Foundation; Dutch National Science Fund-NWO; American Heart Association; March of Dimes Foundation [6-FY09-289]; NIH [K08 DK093705, T32 HL007574, F32 DK098866, R01 DK09361, R01 DK066600, R01 DK070838, P01 HL032262] FX This work was supported by grants from the Canadian Institutes of Health Research (CIHR Postdoctoral Fellowship, J.C.), the Cooley's Anemia Foundation (C.C.), the Dutch National Science Fund-NWO (I.J.S.), the American Heart Association (A.J.D.), the March of Dimes Foundation (6-FY09-289, B.H.P.), and the NIH (K08 DK093705, D.E.B.; T32 HL007574 and F32 DK098866, Y.Y.Y.; R01 DK09361, J.P.; R01 DK066600, R.S.E.; R01 DK070838, B.H.P.; P01 HL032262, B.H.P., A.B.C., H.F.L., and S.H.O.). NR 105 TC 9 Z9 9 U1 2 U2 9 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 APR 14 PY 2015 VL 8 IS 372 AR ra34 DI 10.1126/scisignal.aaa5903 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG0JI UT WOS:000352952400002 PM 25872869 ER PT J AU Nathan, DG AF Nathan, David G. TI Amino acid uptake in erythropoiesis SO SCIENCE SIGNALING LA English DT Article ID KINETICS AB Erythroblasts produce huge amounts of hemoglobin, for which they must incorporate vast stores of iron and amino acids. In the 14 April issue of Science Signaling, Chung et al. describe the complex mechanism linking neutral amino acid uptake to hemoglobin production in these hungry cells. C1 Harvard Univ, Boston Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 2 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 APR 14 PY 2015 VL 8 IS 372 AR fs9 DI 10.1126/scisignal.aab1203 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG0JI UT WOS:000352952400001 PM 25872868 ER PT J AU Dec, GW AF Dec, G. William TI RESPONSE: Advanced Heart Failure Care Aequanimitas and Compassion Are Both Essential SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM gdec@partners.org NR 3 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 14 PY 2015 VL 65 IS 14 BP 1483 EP 1483 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF3AG UT WOS:000352419100014 ER PT J AU Contreras-Valdes, FM Buxton, AE Josephson, ME Anter, E AF Contreras-Valdes, Fernando M. Buxton, Alfred E. Josephson, Mark E. Anter, Elad TI Atrial Fibrillation Ablation in Patients With Hypertrophic Cardiomyopathy Long-Term Outcomes and Clinical Predictors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID RECURRENCE C1 [Contreras-Valdes, Fernando M.; Buxton, Alfred E.; Josephson, Mark E.; Anter, Elad] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. RP Anter, E (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM eanter@bidmc.harvard.edu NR 3 TC 6 Z9 7 U1 2 U2 2 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 APR 14 PY 2015 VL 65 IS 14 BP 1485 EP 1487 DI 10.1016/j.jacc.2014.12.063 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF3AG UT WOS:000352419100016 PM 25857916 ER PT J AU Zhu, EF Gai, SA Opel, CF Kwan, BH Surana, R Mihm, MC Kauke, MJ Moynihan, KD Angelini, A Williams, RT Stephan, MT Kim, JS Yaffe, MB Irvine, DJ Weiner, LM Dranoff, G Wittrup, KD AF Zhu, Eric F. Gai, Shuning A. Opel, Cary F. Kwan, Byron H. Surana, Rishi Mihm, Martin C. Kauke, Monique J. Moynihan, Kelly D. Angelini, Alessandro Williams, Robert T. Stephan, Matthias T. Kim, Jacob S. Yaffe, Michael B. Irvine, Darrell J. Weiner, Louis M. Dranoff, Glenn Wittrup, K. Dane TI Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2 SO CANCER CELL LA English DT Article ID NON-HODGKINS-LYMPHOMA; TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; RENAL-CELL CARCINOMA; PHASE-I; CANCER-IMMUNOTHERAPY; POLYMORPHONUCLEAR NEUTROPHILS; RECOMBINANT INTERLEUKIN-2; CYTOKINE-RELEASE; BREAST-CANCER AB Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm'' and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory. C1 [Zhu, Eric F.; Gai, Shuning A.; Kauke, Monique J.; Wittrup, K. Dane] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Kwan, Byron H.; Moynihan, Kelly D.; Yaffe, Michael B.; Irvine, Darrell J.; Wittrup, K. Dane] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Williams, Robert T.; Yaffe, Michael B.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Stephan, Matthias T.; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Zhu, Eric F.; Gai, Shuning A.; Opel, Cary F.; Kwan, Byron H.; Kauke, Monique J.; Moynihan, Kelly D.; Angelini, Alessandro; Stephan, Matthias T.; Kim, Jacob S.; Yaffe, Michael B.; Irvine, Darrell J.; Wittrup, K. Dane] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Surana, Rishi; Weiner, Louis M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Mihm, Martin C.] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. [Irvine, Darrell J.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA. [Irvine, Darrell J.] Harvard Univ, Boston, MA 02129 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Wittrup, KD (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM wittrup@mit.edu OI /0000-0003-2398-5896; Moynihan, Kelly/0000-0001-6200-7863 FU National Cancer Institute [NCI CA174795]; NIH/NIGMS Biotechnology Training Program; NSF graduate research fellowship FX We thank Dr. Bronson for pathological analysis and the staff of the Swanson Biotechnology Center at the Koch Institute for technical assistance. This study was supported by National Cancer Institute Grant NCI CA174795. E.F.Z. was supported by the NIH/NIGMS Biotechnology Training Program. S.A.G. and C.F.O were supported by a NSF graduate research fellowship. NR 69 TC 20 Z9 20 U1 5 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD APR 13 PY 2015 VL 27 IS 4 BP 489 EP 501 DI 10.1016/j.ccell.2015.03.004 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CG0NF UT WOS:000352962600011 PM 25873172 ER PT J AU Elkabets, M Pazarentzos, E Juric, D Sheng, Q Pelossof, RA Brook, S Benzaken, AO Rodon, J Morse, N Yan, JJ Liu, M Das, R Chen, Y Tam, A Wang, HQ Liang, JS Gurski, JM Kerr, DA Rosell, R Teixido, C Huang, A Ghossein, RA Rosen, N Bivona, TG Scaltriti, M Baselga, J AF Elkabets, Moshe Pazarentzos, Evangelos Juric, Dejan Sheng, Qing Pelossof, Raphael A. Brook, Samuel Benzaken, Ana Oaknin Rodon, Jordi Morse, Natasha Yan, Jenny Jiacheng Liu, Manway Das, Rita Chen, Yan Tam, Angela Wang, Huiqin Liang, Jinsheng Gurski, Joseph M. Kerr, Darcy A. Rosell, Rafael Teixido, Cristina Huang, Alan Ghossein, Ronald A. Rosen, Neal Bivona, Trever G. Scaltriti, Maurizio Baselga, Jose TI AXL Mediates Resistance to PI3K alpha Inhibition by Activating the EGFR/PKC/mTOR Axis in Head and Neck and Esophageal Squamous Cell Carcinomas SO CANCER CELL LA English DT Article ID PROTEIN-KINASE-C; PLATINUM-BASED CHEMOTHERAPY; RECEPTOR TYROSINE KINASES; PHOSPHOLIPASE C-GAMMA-1; THERAPEUTIC TARGET; PLUS CETUXIMAB; BREAST-CANCER; TUMOR-CELLS; GROWTH; EGFR AB Phosphoinositide-3-kinase (PI3K)-alpha inhibitors have shown clinical activity in squamous cell carcinomas (SCCs) of head and neck (H&N) bearing PIK3CA mutations or amplification. Studying models of therapeutic resistance, we have observed that SCC cells that become refractory to PI3K alpha inhibition maintain PI3K-independent activation of the mammalian target of rapamycin (mTOR). This persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. AXL is overexpressed in resistant tumors from both laboratory models and patients treated with the PI3K alpha inhibitor BYL719. AXL dimerizes with and phosphorylates epidermal growth factor receptor (EGFR), resulting in activation of phospholipase C gamma (PLC gamma)-protein kinase C (PKC), which, in turn, activates mTOR. Combined treatment with PI3K alpha and either EGFR, AXL, or PKC inhibitors reverts this resistance. C1 [Elkabets, Moshe; Brook, Samuel; Morse, Natasha; Rosen, Neal; Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, HOPP, New York, NY 10065 USA. [Pazarentzos, Evangelos; Yan, Jenny Jiacheng; Bivona, Trever G.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, San Francisco, CA 94158 USA. [Juric, Dejan; Gurski, Joseph M.; Kerr, Darcy A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sheng, Qing; Liu, Manway; Das, Rita; Chen, Yan; Tam, Angela; Wang, Huiqin; Liang, Jinsheng; Huang, Alan] Novartis Inst BioMed Res, Oncol Translat Med, Cambridge, MA 02139 USA. [Pelossof, Raphael A.] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10065 USA. [Benzaken, Ana Oaknin; Rodon, Jordi] Vall dHebron Inst Oncol, Med Oncol, Barcelona 08035, Spain. [Rosell, Rafael] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Badalona 08916, Spain. [Rosell, Rafael; Teixido, Cristina] Hosp Univ Quiron Dexeus, Lab Oncol, Pangaea Biotech SL, Barcelona 08028, Spain. [Ghossein, Ronald A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Rosen, Neal] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. RP Scaltriti, M (reprint author), Mem Sloan Kettering Canc Ctr, HOPP, 1275 York Ave,Box 20, New York, NY 10065 USA. EM scaltrim@mskcc.org; baselgaj@mskcc.org OI Pazarentzos, Evangelos/0000-0002-5453-1646 FU Cycle for Survival; Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (Tumor Biomarker Research Program); Molecular Cytology Core Facility-Core grant [P30 CA0087748]; NIH Training Grant [T32 CA-71345-15]; NIH Director's Award [DP2 CA174497] FX This work was funded by the Cycle for Survival (to J.B. and M.S.), Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (Tumor Biomarker Research Program) and a Molecular Cytology Core Facility-Core grant (P30 CA0087748). M.E. is an International Sephardic Education Foundation postdoctoral fellow. D.J. is funded by a NIH Training Grant (T32 CA-71345-15). T.G.B. is funded by the NIH Director's Award DP2 CA174497. NR 40 TC 47 Z9 49 U1 9 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD APR 13 PY 2015 VL 27 IS 4 BP 533 EP 546 DI 10.1016/j.ccell.2015.03.010 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CG0NF UT WOS:000352962600014 PM 25873175 ER PT J AU Goonesekera, SD Fang, SC Piccolo, RS Florez, JC McKinlay, JB AF Goonesekera, Sunali D. Fang, Shona C. Piccolo, Rebecca S. Florez, Jose C. McKinlay, John B. TI Biogeographic Ancestry Is Associated with Higher Total Body Adiposity among African-American Females: The Boston Area Community Health Survey SO PLOS ONE LA English DT Article ID GENETIC ADMIXTURE; BACH SURVEY; SOCIOECONOMIC-STATUS; DIABETES-MELLITUS; OBESITY; WOMEN; RISK; DISPARITIES; BMI AB Objectives The prevalence of obesity is disproportionately higher among African-Americans and Hispanics as compared to whites. We investigated the role of biogeographic ancestry (BGA) on adiposity and changes in adiposity in the Boston Area Community Health Survey. Methods We evaluated associations between BGA, assessed via Ancestry Informative Markers, and adiposity (body mass index (BMI), percent body fat (PBF), and waist-to-hip ratio (WHR)) and changes in adiposity over 7 years for BMI and WHR and 2.5 years for PBF, per 10% greater proportion of BGA using multivariable linear regression. We also examined effect-modification by demographic and socio-behavioral variables. Results We observed positive associations between West-African ancestry and cross-sectional BMI (percent difference=0.62%; 95% CI: 0.04%, 1.20%), and PBF (beta=0.35; 95% CI: 0.11, 0.58). We also observed significant effect-modification of the association between West-African ancestry and BMI by gender (p-interaction: <0.002) with a substantially greater association in women. We observed no main associations between Native-American ancestry and adiposity but observed significant effect-modification of the association with BMI by diet (p-interaction: <0.003) with inverse associations among participants with higher Healthy Eating Scores. No associations were observed between BGA and changes in adiposity over time. Conclusion Findings support that West-African ancestry may contribute to high prevalence of total body adiposity among African-Americans, particularly African-American women. C1 [Goonesekera, Sunali D.; Fang, Shona C.; Piccolo, Rebecca S.; McKinlay, John B.] New England Res Inst, Dept Epidemiol & Biostat, Watertown, MA 02472 USA. [Fang, Shona C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA. RP Goonesekera, SD (reprint author), New England Res Inst, Dept Epidemiol & Biostat, 480 Pleasant St, Watertown, MA 02472 USA. EM sgoonesekera@neriscience.com FU National Institute of Diabetes and Digestive and Kidney Diseases [DK056842, DK080786] FX This study was funded by awards DK056842 and DK080786 from the National Institute of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 1 Z9 1 U1 1 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 APR 13 PY 2015 VL 10 IS 4 AR e0122808 DI 10.1371/journal.pone.0122808 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF8XK UT WOS:000352845100104 PM 25875902 ER PT J AU Sharei, A Trifonova, R Jhunjhunwala, S Hartoularos, GC Eyerman, AT Lytton-Jean, A Angin, M Sharma, S Poceviciute, R Mao, S Heimann, M Liu, S Talkar, T Khan, OF Addo, M von Andrian, UH Anderson, DG Langer, R Lieberman, J Jensen, KF AF Sharei, Armon Trifonova, Radiana Jhunjhunwala, Siddharth Hartoularos, George C. Eyerman, Alexandra T. Lytton-Jean, Abigail Angin, Mathieu Sharma, Siddhartha Poceviciute, Roberta Mao, Shirley Heimann, Megan Liu, Sophia Talkar, Tanya Khan, Omar F. Addo, Marylyn von Andrian, Ulrich H. Anderson, Daniel G. Langer, Robert Lieberman, Judy Jensen, Klavs F. TI Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells SO PLOS ONE LA English DT Article ID APTAMER-SIRNA CHIMERAS; SMALL INTERFERING RNAS; INTRACELLULAR DELIVERY; DENDRITIC CELLS; T-CELLS; ELECTROPORATION; INFECTION; NANOPARTICLES; PEPTIDES; PROTEINS AB Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies. C1 [Sharei, Armon; Hartoularos, George C.; Eyerman, Alexandra T.; Poceviciute, Roberta; Mao, Shirley; Heimann, Megan; Liu, Sophia; Talkar, Tanya; Anderson, Daniel G.; Langer, Robert; Jensen, Klavs F.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Angin, Mathieu; Sharma, Siddhartha; Addo, Marylyn; von Andrian, Ulrich H.] MIT, MGH, Ragon Inst, Cambridge, MA 02139 USA. [Angin, Mathieu; Sharma, Siddhartha; Addo, Marylyn; von Andrian, Ulrich H.] Harvard Univ, Cambridge, MA 02138 USA. [Sharei, Armon; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Sharei, Armon; Jhunjhunwala, Siddharth; Lytton-Jean, Abigail; Khan, Omar F.; Anderson, Daniel G.; Langer, Robert] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Trifonova, Radiana; Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02163 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02163 USA. EM judy.lieberman@childrens.harvard.edu; kfjensen@mit.edu RI Jensen, Klavs/F-2462-2012; OI Jensen, Klavs/0000-0001-7192-580X; Jhunjhunwala, Siddharth/0000-0001-8046-2288; Angin, Mathieu/0000-0002-6867-4680 FU National Institutes of Health Grant [R01GM101420-01A1]; Kathy and Curt Marble Cancer Research Fund; Ragon Institute of Harvard/MIT/MGH; National Cancer Institute Cancer Center Support (Core) Grant [P30-CA14051]; Mazumdar-Shaw International Oncology Fellowship FX This work was supported by National Institutes of Health Grants R01GM101420-01A1, the Kathy and Curt Marble Cancer Research Fund, the Ragon Institute of Harvard/MIT/MGH and partially by the National Cancer Institute Cancer Center Support (Core) Grants P30-CA14051. SJ is in receipt of the Mazumdar-Shaw International Oncology Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 2 Z9 2 U1 4 U2 23 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 APR 13 PY 2015 VL 10 IS 4 AR e0118803 DI 10.1371/journal.pone.0118803 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF8XK UT WOS:000352845100011 PM 25875117 ER PT J AU Shin, M Lee, KE Yang, EG Jeon, H Song, HK AF Shin, Miyoung Lee, Kyung-Eun Yang, Eun Gyeong Jeon, Hyesung Song, Hyun Kyu TI PEA-15 facilitates EGFR dephosphorylation via ERK sequestration at increased ER-PM contacts in TNBC cells SO FEBS LETTERS LA English DT Article DE EGFR dephosphorylation; ER-PM contact; PEA-15; pERK1/2; PTP1B; Triple-negative breast cancer cells ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; BREAST-CANCER; ENDOPLASMIC-RETICULUM; MEMBRANE CONTACTS; MAP KINASE; SITES; PHOSPHOPROTEIN; ASTROCYTES; ACTIVATION AB Phosphoprotein enriched in astrocytes of 15kDa (PEA-15) is known to sequester extracellular signal-regulated kinase (ERK) in the cytoplasm, inhibiting tumorigenesis of human breast cancer cells. Here, we describe how PEA-15 expression affects the dephosphorylation of epidermal growth factor receptor (EGFR) through endoplasmic reticulum (ER)-plasma membrane (PM) contacts in MDA-MB-468, triple-negative breast cancer (TNBC) cells. The increased intracellular calcium concentration resulting from increased cytoplasmic phosphorylated ERK facilitates movement of ER-anchored calcium sensors to the PM. The driving force of trans-localization of calcium-dependent proteins enhances the contact between the activated EGFR and ER-localized phosphatase, PTP1B. Consequently, our findings suggest a mechanism underneath the facilitation of EGFR dephosphorylation by cytoplasmic PEA-15 expression inside TNBC cells, which may be one of the dynamic mechanisms for down-regulation of activated EGFR in cancer cells. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Shin, Miyoung; Song, Hyun Kyu] Korea Univ, Div Life Sci, Seoul, South Korea. [Lee, Kyung-Eun; Yang, Eun Gyeong; Jeon, Hyesung] Korea Inst Sci & Technol, Biomed Res Inst, Ctr Theragnosis, Seoul, South Korea. [Lee, Kyung-Eun] Korea Inst Sci & Technol, Adv Anal Ctr, Seoul, South Korea. [Jeon, Hyesung] Dana Farber Canc Inst, Dept Canc Biol, Boston 02115, MA USA. RP Jeon, H (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM hjeon@red.dfci.harvard.edu; hksong@korea.ac.kr RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU National Research Foundation of Korea (NRF) - Korean government (MSIP) [NRF-2011-0028168, NRF-2013R1A1A2020177]; Intramural Research Program of the KIST; Korea University Grant FX This work was supported by Grants from the National Research Foundation of Korea (NRF), funded by the Korean government (MSIP) (NRF-2011-0028168 and NRF-2013R1A1A2020177). This study was also supported by the Intramural Research Program of the KIST, and a Korea University Grant. NR 32 TC 1 Z9 1 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD APR 13 PY 2015 VL 589 IS 9 BP 1033 EP 1039 DI 10.1016/j.febslet.2015.03.009 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CE6HC UT WOS:000351936500010 PM 25796184 ER PT J AU Wacharapluesadee, S Duengkae, P Rodpan, A Kaewpom, T Maneeorn, P Kanchanasaka, B Yingsakmongkon, S Sittidetboripat, N Chareesaen, C Khlangsap, N Pidthong, A Leadprathom, K Ghai, S Epstein, JH Daszak, P Olival, KJ Blair, PJ Callahan, MV Hemachudha, T AF Wacharapluesadee, Supaporn Duengkae, Prateep Rodpan, Apaporn Kaewpom, Thongchai Maneeorn, Patarapol Kanchanasaka, Budsabong Yingsakmongkon, Sangchai Sittidetboripat, Nuntaporn Chareesaen, Chaiyaporn Khlangsap, Nathawat Pidthong, Apisit Leadprathom, Kumron Ghai, Siriporn Epstein, Jonathan H. Daszak, Peter Olival, Kevin J. Blair, Patrick J. Callahan, Michael V. Hemachudha, Thiravat TI Diversity of coronavirus in bats from Eastern Thailand SO VIROLOGY JOURNAL LA English DT Article DE Coronavirus; Bats; Diversity; Eastern; Thailand ID RESPIRATORY SYNDROME CORONAVIRUS; SARS-LIKE CORONAVIRUSES; CHINESE HORSESHOE BATS; GENOMIC CHARACTERIZATION; BETACORONAVIRUS; GENE; ALPHACORONAVIRUS; LINEAGE; ALPHA AB Background: Bats are reservoirs for a diverse range of coronaviruses (CoVs), including those closely related to human pathogens such as Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome CoV. There are approximately 139 bat species reported to date in Thailand, of which two are endemic species. Due to the zoonotic potential of CoVs, standardized surveillance efforts to characterize viral diversity in wildlife are imperative. Findings: A total of 626 bats from 19 different bat species were individually sampled from 5 provinces in Eastern Thailand between 2008 and 2013 (84 fecal and 542 rectal swabs). Samples collected (either fresh feces or rectal swabs) were placed directly into RNA stabilization reagent, transported on ice within 24 hours and preserved at -80 degrees C until further analysis. CoV RNA was detected in 47 specimens (7.6%), from 13 different bat species, using broadly reactive consensus PCR primers targeting the RNA-Dependent RNA Polymerase gene designed to detect all CoVs. Thirty seven alphacoronaviruses, nine lineage D betacoronaviruses, and one lineage B betacoronavirus (SARS-CoV related) were identified. Six new bat CoV reservoirs were identified in our study, namely Cynopterus sphinx, Taphozous melanopogon, Hipposideros lekaguli, Rhinolophus shameli, Scotophilus heathii and Megaderma lyra. Conclusions: CoVs from the same genetic lineage were found in different bat species roosting in similar or different locations. These data suggest that bat CoV lineages are not strictly concordant with their hosts. Our phylogenetic data indicates high diversity and a complex ecology of CoVs in bats sampled from specific areas in eastern regions of Thailand. Further characterization of additional CoV genes may be useful to better describe the CoV divergence. C1 [Wacharapluesadee, Supaporn; Rodpan, Apaporn; Kaewpom, Thongchai; Yingsakmongkon, Sangchai; Sittidetboripat, Nuntaporn; Ghai, Siriporn; Callahan, Michael V.; Hemachudha, Thiravat] Chulalongkorn Univ, Fac Med, King Chulalongkorn Mem Hosp, World Hlth Org Collaborating Ctr Res & Training V, Bangkok 10330, Thailand. [Duengkae, Prateep; Khlangsap, Nathawat] Kasetsart Univ, Fac Forestry, Bangkok, Thailand. [Maneeorn, Patarapol; Kanchanasaka, Budsabong; Chareesaen, Chaiyaporn; Pidthong, Apisit] Dept Natl Pk Wildlife & Plant Conservat, Bangkok, Thailand. [Yingsakmongkon, Sangchai] Chulalongkorn Univ, Fac Grad Sch, Interdept Program Biomed Sci, Bangkok, Thailand. [Leadprathom, Kumron] Royal Forest Dept, Bangkok, Thailand. [Epstein, Jonathan H.; Daszak, Peter; Olival, Kevin J.] EcoHlth Alliance, New York, NY USA. [Blair, Patrick J.] Naval Med Res Ctr Asia, Singapore, Singapore. [Callahan, Michael V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wacharapluesadee, S (reprint author), Chulalongkorn Univ, Fac Med, King Chulalongkorn Mem Hosp, World Hlth Org Collaborating Ctr Res & Training V, Bangkok 10330, Thailand. EM spwa@hotmail.com FU Thailand Research Fund [RDG5420089]; Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University [RES560530148-HR]; Health and Biomedical Science Research Program by National Research Council of Thailand (NRCT); Health System Research Institute (HSRI); Research Chair Grant; National Science and Technology Development Agency (NSTDA), Thailand; Naval Health Research Center [BAA-10-93, W911NF-11-2-0041]; USAID Emerging Pandemic Threats PREDICT project; Thai Red Cross Society; Chulalongkorn University; Kasetsart University; Department of National Parks Wildlife and Plant Conservation FX This study was supported by a research grant from the Thailand Research Fund (RDG5420089), the Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University (RES560530148-HR), Health and Biomedical Science Research Program by National Research Council of Thailand (NRCT) and Health System Research Institute (HSRI), the Research Chair Grant, the National Science and Technology Development Agency (NSTDA), Thailand, the Naval Health Research Center (BAA-10-93) under the Cooperative Agreement no. W911NF-11-2-0041, and the USAID Emerging Pandemic Threats PREDICT project. We gratefully acknowledge the local support from the Thai Red Cross Society, Chulalongkorn University, Kasetsart University and the Department of National Parks Wildlife and Plant Conservation. The views expressed in this manuscript are those of the authors and do not reflect the official policy or opinions of the US Department of Defense or Department of the Navy. NR 29 TC 8 Z9 8 U1 3 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD APR 11 PY 2015 VL 12 AR 57 DI 10.1186/s12985-015-0289-1 PG 7 WC Virology SC Virology GA CG9ZV UT WOS:000353679500001 PM 25884446 ER PT J AU Glass, K Quackenbush, J Spentzos, D Haibe-Kains, B Yuan, GC AF Glass, Kimberly Quackenbush, John Spentzos, Dimitrios Haibe-Kains, Benjamin Yuan, Guo-Cheng TI A network model for angiogenesis in ovarian cancer SO BMC BIOINFORMATICS LA English DT Article DE Network modeling; Gene regulation; Regulatory networks; Ovarian cancer; Cancer subtypes; Angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT EPITHELIAL OVARIAN; BREAST-CANCER; COOPERATIVE INTERACTION; TRANSCRIPTION FACTOR; EPIGENETIC THERAPY; PRIMARY PERITONEAL; RECEPTOR AGONISTS; SMALL MOLECULES; TUMOR-GROWTH AB Background: We recently identified two robust ovarian cancer subtypes, defined by the expression of genes involved in angiogenesis, with significant differences in clinical outcome. To identify potential regulatory mechanisms that distinguish the subtypes we applied PANDA, a method that uses an integrative approach to model information flow in gene regulatory networks. Results: We find distinct differences between networks that are active in the angiogenic and non-angiogenic subtypes, largely defined by a set of key transcription factors that, although previously reported to play a role in angiogenesis, are not strongly differentially-expressed between the subtypes. Our network analysis indicates that these factors are involved in the activation (or repression) of different genes in the two subtypes, resulting in differential expression of their network targets. Mechanisms mediating differences between subtypes include a previously unrecognized pro-angiogenic role for increased genome-wide DNA methylation and complex patterns of combinatorial regulation. Conclusions: The models we develop require a shift in our interpretation of the driving factors in biological networks away from the genes themselves and toward their interactions. The observed regulatory changes between subtypes suggest therapeutic interventions that may help in the treatment of ovarian cancer. C1 [Glass, Kimberly; Quackenbush, John; Yuan, Guo-Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glass, Kimberly; Quackenbush, John; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Glass, Kimberly] Brigham & Womens Hosp, Boston, MA 02115 USA. [Spentzos, Dimitrios] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Haibe-Kains, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. RP Yuan, GC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM gcyuan@jimmy.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 FU [R01 HL089438]; [R01 HL111759]; [P01 HL105339] FX This project has been supported by R01 HL089438, R01 HL111759 and P01 HL105339. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 109 TC 9 Z9 9 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 11 PY 2015 VL 16 AR 115 DI 10.1186/s12859-015-0551-y PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CG5HT UT WOS:000353322500001 PM 25888305 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Surgery for Crohn's disease: look harder, act faster SO LANCET LA English DT Editorial Material ID MANAGEMENT; RECURRENCE; TRIAL; RATES C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu NR 12 TC 0 Z9 1 U1 0 U2 3 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 APR 11 PY 2015 VL 385 IS 9976 BP 1370 EP 1371 DI 10.1016/S0140-6736(14)62117-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CF7EU UT WOS:000352719800006 PM 25542619 ER PT J AU Kamisawa, T Zen, Y Pillai, S Stone, JH AF Kamisawa, Terumi Zen, Yoh Pillai, Shiv Stone, John H. TI IgG4-related disease SO LANCET LA English DT Review ID PRIMARY SCLEROSING CHOLANGITIS; IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; SERUM IGG4 CONCENTRATIONS; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; RETROPERITONEAL FIBROSIS; DIAGNOSTIC-CRITERIA; MIKULICZS-DISEASE; MULTIFOCAL FIBROSCLEROSIS; RIEDELS THYROIDITIS AB IgG4-related disease is a protean condition that mimics many malignant, infectious, and inflammatory disorders. This multi-organ immune-mediated condition links many disorders previously regarded as isolated, single-organ diseases without any known underlying systemic condition. It was recognised as a unified entity only 10 years ago. Histopathology is the key to diagnosis. The three central pathology features of IgG4-related disease are lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. The extent of fibrosis is an important determinant of responsiveness to immunosuppressive therapies. IgG4-related disease generally responds to glucocorticoids in its inflammatory stage, but recurrent or refractory cases are common. Important mechanistic insights have been derived from studies of patients treated by B-cell depletion. Greater awareness of this disease is needed to ensure earlier diagnoses, which can prevent severe organ damage, disabling tissue fibrosis, and even death. Identification of specific antigens and T-cell clones that drive the disease will be the first steps to elucidate the pathogenesis of IgG4-related disease. C1 [Kamisawa, Terumi] Tokyo Metropolitan Komagome Hosp, Dept Internal Med, Tokyo, Japan. [Zen, Yoh] Kobe Univ, Dept Pathol, Kobe, Hyogo 657, Japan. [Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA USA. [Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU Genentech FX JHS is the principal investigator in a Genentech-funded trial of rituximab in IgG4-related disease and has consulted for Genentech on this disease. The other authors declare no competing interests. NR 107 TC 106 Z9 118 U1 4 U2 21 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 APR 11 PY 2015 VL 385 IS 9976 BP 1460 EP 1471 DI 10.1016/S0140-6736(14)60720-0 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CF7EU UT WOS:000352719800034 PM 25481618 ER PT J AU Stone, RM Mazzola, E Neuberg, D Allen, SL Pigneux, A Stuart, RK Wetzler, M Rizzieri, D Erba, HP Damon, L Jang, JH Tallman, MS Warzocha, K Masszi, T Sekeres, MA Egyed, M Horst, HA Selleslag, D Solomon, SR Venugopal, P Lundberg, AS Powell, B AF Stone, Richard M. Mazzola, Emanuele Neuberg, Donna Allen, Steven L. Pigneux, Arnaud Stuart, Robert K. Wetzler, Meir Rizzieri, David Erba, Harry P. Damon, Lloyd Jang, Jun-Ho Tallman, Martin S. Warzocha, Krzysztof Masszi, Tamas Sekeres, Mikkael A. Egyed, Miklos Horst, Heinz-August Selleslag, Dominik Solomon, Scott R. Venugopal, Parameswaran Lundberg, Ante S. Powell, Bayard TI Phase III Open-Label Randomized Study of Cytarabine in Combination With Amonafide L-Malate or Daunorubicin As Induction Therapy for Patients With Secondary Acute Myeloid Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-GROUP; INHIBITOR AB Purpose Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m(2) continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m(2) IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m(2) IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A + C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML. (C) 2015 by American Society of Clinical Oncology C1 [Stone, Richard M.; Mazzola, Emanuele; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02215 USA. [Lundberg, Ante S.] Antisoma, Cambridge, MA USA. [Allen, Steven L.] Hofstra North Shore Long Isl Jewish Sch Med, Lake Success, NY USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pigneux, Arnaud] Hop Haut Leveque, Pessac, France. [Stuart, Robert K.] Med Univ S Carolina, Charleston, SC 29425 USA. [Rizzieri, David] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Powell, Bayard] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Erba, Harry P.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Damon, Lloyd] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jang, Jun-Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Warzocha, Krzysztof] Inst Hematol & Transfusiol, Warsaw, Poland. [Masszi, Tamas] Szent Istvan & Szent Laszlo Corp Hosp, Budapest, Hungary. [Egyed, Miklos] Kaposi Mor Cty Teaching Hosp, Kaposvar, Hungary. [Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Horst, Heinz-August] Univ Klinikum Schleswig Holstein, Kiel, Germany. [Selleslag, Dominik] Algemeen Ziekenhuis St Jan, Brugge, Belgium. [Solomon, Scott R.] Blood & Marrow Transplant Program, Atlanta, GA USA. [Solomon, Scott R.] Northside Hosp, Atlanta, GA USA. [Venugopal, Parameswaran] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Adult Leukemia Program, 450 Brookline Ave,D-2053, Boston, MA 02215 USA. EM rstone@partners.org OI Venugopal, Parameswaran/0000-0002-7518-9579; Allen, Steven/0000-0002-3482-3182 FU Antisoma FX Supported by Antisoma. NR 17 TC 11 Z9 11 U1 0 U2 7 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 APR 10 PY 2015 VL 33 IS 11 BP 1252 EP + DI 10.1200/JCO.2014.57.0952 PG 9 WC Oncology SC Oncology GA CK2RB UT WOS:000356058100006 PM 25732165 ER PT J AU Partridge, AH Rumble, RB Smith, IE AF Partridge, Ann H. Rumble, R. Bryan Smith, Ian E. TI Recognizing the Place of Trials With Treatment of Physician's Choice As the Control Arm Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rumble, R. Bryan] Amer Soc Clin Oncol, Alexandria, VA USA. [Smith, Ian E.] Royal Marsden Hosp, London SW3 6JJ, England. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 APR 10 PY 2015 VL 33 IS 11 BP 1301 EP + DI 10.1200/JCO.2014.60.2508 PG 2 WC Oncology SC Oncology GA CK2RB UT WOS:000356058100016 PM 25732166 ER PT J AU Sheridan, CM Grogan, TR Nguyen, HG Galet, C Rettig, MB Hsieh, AC Ruggero, D AF Sheridan, Christine Moore Grogan, Tristan R. Nguyen, Hao G. Galet, Colette Rettig, Matthew B. Hsieh, Andrew C. Ruggero, Davide TI YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence SO ONCOTARGET LA English DT Article DE translation control; prostate cancer; PSA recurrence; biomarker; YB-1 ID RADICAL PROSTATECTOMY AB Attempts to identify biomarkers to detect prostate tumorigenesis, and thus minimize prostate cancer progression and inform treatment decisions have primarily focused on alterations at the DNA and mRNA levels, ignoring alterations at the level of protein synthesis control. We have previously shown that the PI3K-AKT-mTOR pathway, frequently deregulated in prostate cancer, specifically induces the synthesis of proteins that contribute to metastasis, most notably YB-1 and MTA1, without altering mRNA levels thereby demonstrating the importance of translation control in driving the expression of these genes in cancer. Here, we analyze genomic sequencing and mRNA expression databases, as well as protein expression employing an annotated tissue microarray generated from 332 prostate cancer patients with 15 years of clinical follow-up to determine the combined prognostic capability of YB-1 and MTA1 alterations in forecasting prostate cancer outcomes. Remarkably, protein abundance, but not genomic or transcriptional alterations of YB-1 and MTA1, is predictive of disease recurrence, exhibiting a dose-dependent effect on time to PSA recurrence, an indicator of tumor relapse. Moreover, high protein levels of YB-1 and MTA1 are associated with a 3-fold increased risk for requiring future hormone therapy or radiation therapy. Importantly, YB-1 and MTA1 protein levels significantly increase the predictive capacity of a clinical model for prostate cancer recurrence. These findings demonstrate that protein abundance of YB-1 and MTA1, irrespective of DNA or mRNA status, can predict for prostate cancer relapse and uncover a vast underappreciated repository of biomarkers regulated at the level of protein expression. C1 [Sheridan, Christine Moore; Nguyen, Hao G.; Hsieh, Andrew C.; Ruggero, Davide] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Grogan, Tristan R.] Univ Calif Los Angeles, David Geffen Sch Med, Stat Core, Los Angeles, CA 90095 USA. [Galet, Colette; Rettig, Matthew B.] VA Greater Los Angeles Healthcare Syst West Los A, Dept Med, Los Angeles, CA 90073 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Hsieh, Andrew C.] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. RP Rettig, MB (reprint author), VA Greater Los Angeles Healthcare Syst West Los A, Dept Med, Los Angeles, CA 90073 USA. EM mrettig@mednet.ucla.edu; ahsieh@fredhutch.org; davide.ruggero@ucsf.edu FU Goldberg-Benioff Program in Cancer Translational Biology FX We thank the members of the Ruggero laboratory for critical discussion and support. We thank the Goldberg-Benioff Program in Cancer Translational Biology for their support and commitment to prostate cancer research. We thank Justin Pak (Keyence Corporation of America), DeLaine Larsen (UCSF, Nikon Imaging Center), and Kurt Thorn (UCSF, Nikon Imaging Center) for providing technical support for imaging. We thank Jennifer M. Shen and Christine Milentis for assistance with editing the manuscript. NR 18 TC 4 Z9 4 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 10 PY 2015 VL 6 IS 10 BP 7470 EP 7480 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI6QJ UT WOS:000354885300009 PM 25797255 ER PT J AU Zhang, L McCarthy, DM Sharma, N Bhide, PG AF Zhang, Lin McCarthy, Deirdre M. Sharma, Nutan Bhide, Pradeep G. TI Dopamine Receptor and Ga(olf) Expression in DYT1 Dystonia Mouse Models during Postnatal Development SO PLOS ONE LA English DT Article ID EARLY-ONSET DYSTONIA; TORSION DYSTONIA; D2 RECEPTOR; CEREBRAL-CORTEX; HUMAN BRAIN; GENE DYT1; MICE; PROTEIN; HYPERACTIVITY; LOCALIZATION AB Background DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (Delta GAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated. Methodology/Principal Findings We used Dyt1 knock out (Dyt1 KO), Dyt1 Delta GAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1hWT) or human Delta GAG mutant allele (DYT1hMT). D1R, D2R, and Ga(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Ga(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1hMT or DYT1hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1KO mice. Conclusion/Significance We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology. C1 [Zhang, Lin; McCarthy, Deirdre M.; Bhide, Pradeep G.] Florida State Univ, Dept Biomed Sci, Ctr Brain Repair, Coll Med, Tallahassee, FL 32306 USA. [Sharma, Nutan] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Sharma, Nutan] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, L (reprint author), Florida State Univ, Dept Biomed Sci, Ctr Brain Repair, Coll Med, Tallahassee, FL 32306 USA. EM lin.zhang@med.fsu.edu; pradeep.bhide@med.fsu.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU Brian Jackson Dystonia Research and Discovery Fund; NINDS [P01NS037409] FX Support was provided by the Brian Jackson Dystonia Research and Discovery Fund and NINDS P01NS037409. NR 46 TC 2 Z9 2 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 APR 10 PY 2015 VL 10 IS 4 AR e0123104 DI 10.1371/journal.pone.0123104 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5II UT WOS:000352590300078 PM 25860259 ER PT J AU Aaltonen, T Amerio, S Amidei, D Anastassov, A Annovi, A Antos, J Apollinari, G Appel, JA Arisawa, T Artikov, A Asaadi, J Ashmanskas, W Auerbach, B Aurisano, A Azfar, F Badgett, W Bae, T Barbaro-Galtieri, A Barnes, VE Barnett, BA Barria, P Bartos, P Bauce, M Bedeschi, F Behari, S Bellettini, G Bellinger, J Benjamin, D Beretvas, A Bhatti, A Bland, KR Blumenfeld, B Bocci, A Bodek, A Bortoletto, D Boudreau, J Boveia, A Brigliadori, L Bromberg, C Brucken, E Budagov, J Budd, HS Burkett, K Busetto, G Bussey, P Butti, P Buzatu, A Calamba, A Camarda, S Campanelli, M Canelli, F Carls, B Carlsmith, D Carosi, R Carrillo, S Casal, B Casarsa, M Castro, A Catastini, P Cauz, D Cavaliere, V Cerri, A Cerrito, L Chen, YC Chertok, M Chiarelli, G Chlachidze, G Cho, K Chokheli, D Clark, A Clarke, C Convery, ME Conway, J Corbo, M Cordelli, M Cox, CA Cox, DJ Cremonesi, M Cruz, D Cuevas, J Culbertson, R d'Ascenzo, N Datta, M de Barbaro, P Demortier, L Deninno, M D'Errico, M Devoto, F Di Canto, A Di Ruzza, B Dittmann, JR Donati, S D'Onofrio, M Dorigo, M Driutti, A Ebina, K Edgar, R Elagin, A Erbacher, R Errede, S Esham, B Farrington, S Ramos, JPF Field, R Flanagan, G Forrest, R Franklin, M Freeman, JC Frisch, H Funakoshi, Y Galloni, C Garfinkel, AF Garosi, P Gerberich, H Gerchtein, E Giagu, S Giakoumopoulou, V Gibson, K Ginsburg, CM Giokaris, N Giromini, P Glagolev, V Glenzinski, D Gold, M Goldin, D Golossanov, A Gomez, G Gomez-Ceballos, G Goncharov, M Lopez, OG Gorelov, I Goshaw, AT Goulianos, K Gramellini, E Grosso-Pilcher, C Group, RC da Costa, JG Hahn, SR Han, JY Happacher, F Hara, K Hare, M Harr, RF Harrington-Taber, T Hatakeyama, K Hays, C Heinrich, J Herndon, M Hocker, A Hong, Z Hopkins, W Hou, S Hughes, RE Husemann, U Hussein, M Huston, J Introzzi, G Iori, M Ivanov, A James, E Jang, D Jayatilaka, B Jeon, EJ Jindariani, S Jones, M Joo, KK Jun, SY Junk, TR Kambeitz, M Kamon, T Karchin, PE Kasmi, A Kato, Y Ketchum, W Keung, J Kilminster, B Kim, DH Kim, HS Kim, JE Kim, MJ Kim, SH Kim, SB Kim, YJ Kim, YK Kimura, N Kirby, M Knoepfel, K Kondo, K Kong, DJ Konigsberg, J Kotwal, AV Kreps, M Kroll, J Kruse, M Kuhr, T Kurata, M Laasanen, AT Lammel, S Lancaster, M Lannon, K Latino, G Lee, HS Lee, JS Leo, S Leone, S Lewis, JD Limosani, A Lipeles, E Lister, A Liu, H Liu, Q Liu, T Lockwitz, S Loginov, A Lucchesi, D Luca, A Lueck, J Lujan, P Lukens, P Lungu, G Lys, J Lysak, R Madrak, R Maestro, P Malik, S Manca, G Manousakis-Katsikakis, A Marchese, L Margaroli, F Marino, P Matera, K Mattson, ME Mazzacane, A Mazzanti, P McNulty, R Mehta, A Mehtala, P Mesropian, C Miao, T Mietlicki, D Mitra, A Miyake, H Moed, S Moggi, N Moon, CS Moore, R Morello, MJ Mukherjee, A Muller, T Murat, P Mussini, M Nachtman, J Nagai, Y Naganoma, J Nakano, I Napier, A Nett, J Neu, C Nigmanov, T Nodulman, L Noh, SY Norniella, O Oakes, L Oh, SH Oh, YD Oksuzian, I Okusawa, T Orava, R Ortolan, L Pagliarone, C Palencia, E Palni, P Papadimitriou, V Parker, W Pauletta, G Paulini, M Paus, C Phillips, TJ Piacentino, G Pianori, E Pilot, J Pitts, K Plager, C Pondrom, L Poprocki, S Potamianos, K Pranko, A Prokoshin, F Ptohos, F Punzi, G Fernandez, IR Renton, P Rescigno, M Rimondi, F Ristori, L Robson, A Rodriguez, T Rolli, S Ronzani, M Roser, R Rosner, JL Ruffini, F Ruiz, A Russ, J Rusu, V Sakumoto, WK Sakurai, Y Santi, L Sato, K Saveliev, V Savoy-Navarro, A Schlabach, P Schmidt, EE Schwarz, T Scodellaro, L Scuri, F Seidel, AS Seiya, Y Semenov, A Sforza, F Shalhout, SZ Shears, T Shepard, PF Shimojima, M Shochet, M Shreyber-Tecker, I Simonenko, A Sliwa, K Smith, JR Snider, FD Song, H Sorin, V St Denis, R Stancari, M Stentz, D Strologas, J Sudo, Y Sukhanov, A Suslov, I Takemasa, K Takeuchi, Y Tang, J Tecchio, M Teng, PK Thom, J Thomson, E Thukral, V Toback, D Tokar, S Tollefson, K Tomura, T Tonelli, D Torre, S Torretta, D Totaro, P Trovato, M Ukegawa, F Uozumi, S Vazquez, F Velev, G Vellidis, C Vernieri, C Vidal, M Vilar, R Vizan, J Vogel, M Volpi, G Wagner, P Wallny, R Wang, SM Waters, D Wester, WC Whiteson, D Wicklund, AB Wilbur, S Williams, HH Wilson, JS Wilson, P Winer, BL Wittich, P Wolbers, S Wolfe, H Wright, T Wu, X Wu, Z Yamamoto, K Yamato, D Yang, T Yang, UK Yang, YC Yao, WM Yeh, GP Yi, K Yoh, J Yorita, K Yoshida, T Yu, GB Yu, I Zanetti, AM Zeng, Y Zhou, C Zucchelli, S AF Aaltonen, T. Amerio, S. Amidei, D. Anastassov, A. Annovi, A. Antos, J. Apollinari, G. Appel, J. A. Arisawa, T. Artikov, A. Asaadi, J. Ashmanskas, W. Auerbach, B. Aurisano, A. Azfar, F. Badgett, W. Bae, T. Barbaro-Galtieri, A. Barnes, V. E. Barnett, B. A. Barria, P. Bartos, P. Bauce, M. Bedeschi, F. Behari, S. Bellettini, G. Bellinger, J. Benjamin, D. Beretvas, A. Bhatti, A. Bland, K. R. Blumenfeld, B. Bocci, A. Bodek, A. Bortoletto, D. Boudreau, J. Boveia, A. Brigliadori, L. Bromberg, C. Brucken, E. Budagov, J. Budd, H. S. Burkett, K. Busetto, G. Bussey, P. Butti, P. Buzatu, A. Calamba, A. Camarda, S. Campanelli, M. Canelli, F. Carls, B. Carlsmith, D. Carosi, R. Carrillo, S. Casal, B. Casarsa, M. Castro, A. Catastini, P. Cauz, D. Cavaliere, V. Cerri, A. Cerrito, L. Chen, Y. C. Chertok, M. Chiarelli, G. Chlachidze, G. Cho, K. Chokheli, D. Clark, A. Clarke, C. Convery, M. E. Conway, J. Corbo, M. Cordelli, M. Cox, C. A. Cox, D. J. Cremonesi, M. Cruz, D. Cuevas, J. Culbertson, R. d'Ascenzo, N. 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Simonenko, A. Sliwa, K. Smith, J. R. Snider, F. D. Song, H. Sorin, V. St Denis, R. Stancari, M. Stentz, D. Strologas, J. Sudo, Y. Sukhanov, A. Suslov, I. Takemasa, K. Takeuchi, Y. Tang, J. Tecchio, M. Teng, P. K. Thom, J. Thomson, E. Thukral, V. Toback, D. Tokar, S. Tollefson, K. Tomura, T. Tonelli, D. Torre, S. Torretta, D. Totaro, P. Trovato, M. Ukegawa, F. Uozumi, S. Vazquez, F. Velev, G. Vellidis, C. Vernieri, C. Vidal, M. Vilar, R. Vizan, J. Vogel, M. Volpi, G. Wagner, P. Wallny, R. Wang, S. M. Waters, D. Wester, W. C., III Whiteson, D. Wicklund, A. B. Wilbur, S. Williams, H. H. Wilson, J. S. Wilson, P. Winer, B. L. Wittich, P. Wolbers, S. Wolfe, H. Wright, T. Wu, X. Wu, Z. Yamamoto, K. Yamato, D. Yang, T. Yang, U. K. Yang, Y. C. Yao, W. -M. Yeh, G. P. Yi, K. Yoh, J. Yorita, K. Yoshida, T. Yu, G. B. Yu, I. Zanetti, A. M. Zeng, Y. Zhou, C. Zucchelli, S. CA CDF Collaboration TI Constraints on Models of the Higgs Boson with Exotic Spin and Parity using Decays to Bottom-Antibottom Quarks in the Full CDF Data Set SO PHYSICAL REVIEW LETTERS LA English DT Article ID PARTON DISTRIBUTIONS; STANDARD MODEL; CROSS-SECTIONS; DETECTOR; QCD; LHC; PERFORMANCE; STRAHLUNG AB A search for particles with the same mass and couplings as those of the standard model Higgs boson but different spin and parity quantum numbers is presented. We test two specific alternative Higgs boson hypotheses: a pseudoscalar Higgs boson with spin-parity J(P) = 0(-) and a gravitonlike Higgs boson with J(P) = 2(+), assuming for both a mass of 125 GeV/c(2). We search for these exotic states produced in association with a vector boson and decaying into a bottom-antibottom quark pair. The vector boson is reconstructed through its decay into an electron or muon pair, or an electron or muon and a neutrino, or it is inferred from an imbalance in total transverse momentum. We use expected kinematic differences between events containing exotic Higgs bosons and those containing standard model Higgs bosons. The data were collected by the CDF experiment at the Tevatron proton-antiproton collider, operating at a center-of-mass energy of root s = 1.96 TeV, and correspond to an integrated luminosity of 9.45 fb(-1). We exclude deviations from the predictions of the standard model with a Higgs boson of mass 125 GeV/c(2) at the level of 5 standard deviations, assuming signal strengths for exotic boson production equal to the prediction for the standard model Higgs boson, and set upper limits of approximately 30% relative to the standard model rate on the possible rate of production of each exotic state. C1 [Chen, Y. C.; Hou, S.; Mitra, A.; Teng, P. K.; Wang, S. M.] Acad Sinica, Inst Phys, Taipei 11529, Taiwan. [Auerbach, B.; Nodulman, L.; Wicklund, A. B.] Argonne Natl Lab, Argonne, IL 60439 USA. 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[Barria, P.; Bedeschi, F.; Bellettini, G.; Butti, P.; Carosi, R.; Chiarelli, G.; Cremonesi, M.; Di Canto, A.; Donati, S.; Galloni, C.; Garosi, P.; Introzzi, G.; Latino, G.; Leone, S.; Maestro, P.; Marino, P.; Morello, M. J.; Punzi, G.; Ristori, L.; Ronzani, M.; Scuri, F.; Sforza, F.; Trovato, M.; Vernieri, C.] Ist Nazl Fis Nucl, I-56127 Pisa, Italy. [Bellettini, G.; Butti, P.; Di Canto, A.; Donati, S.; Galloni, C.; Punzi, G.; Ronzani, M.; Sforza, F.] Univ Pisa, I-56127 Pisa, Italy. [Barria, P.; Garosi, P.; Latino, G.; Maestro, P.; Ruffini, F.] Univ Siena, I-56127 Pisa, Italy. [Marino, P.; Morello, M. J.; Trovato, M.; Vernieri, C.] Scuola Normale Super Pisa, I-56127 Pisa, Italy. [Introzzi, G.] Ist Nazl Fis Nucl, I-27100 Pavia, Italy. [Introzzi, G.] Univ Pavia, I-27100 Pavia, Italy. [Boudreau, J.; Gibson, K.; Nigmanov, T.; Shepard, P. F.; Song, H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Barnes, V. E.; Bortoletto, D.; Garfinkel, A. F.; Jones, M.; Laasanen, A. T.; Liu, Q.; Vidal, M.] Purdue Univ, W Lafayette, IN 47907 USA. [Bodek, A.; Budd, H. S.; de Barbaro, P.; Han, J. Y.; Sakumoto, W. K.] Univ Rochester, Rochester, NY 14627 USA. [Bhatti, A.; Demortier, L.; Goulianos, K.; Malik, S.; Mesropian, C.] Rockefeller Univ, New York, NY 10065 USA. [Giagu, S.; Iori, M.; Margaroli, F.; Rescigno, M.] Ist Nazl Fis Nucl, Sez Roma 1, I-00185 Rome, Italy. [Iori, M.] Univ Roma La Sapienza, I-00185 Rome, Italy. [Asaadi, J.; Aurisano, A.; Cruz, D.; Elagin, A.; Goldin, D.; Hong, Z.; Kamon, T.; Nett, J.; Thukral, V.; Toback, D.] Texas A&M Univ, Mitchell Inst Fundamental Phys & Astron, College Stn, TX 77843 USA. [Casarsa, M.; Cauz, D.; Dorigo, M.; Driutti, A.; Pagliarone, C.; Pauletta, G.; Santi, L.; Zanetti, A. M.] Ist Nazl Fis Nucl Trieste, I-33100 Udine, Italy. [Cauz, D.; Driutti, A.; Pauletta, G.; Santi, L.] Grp Collegato Udine, I-33100 Udine, Italy. [Cauz, D.; Driutti, A.; Pauletta, G.; Santi, L.] Univ Udine, I-33100 Udine, Italy. [Dorigo, M.] Univ Trieste, I-34127 Trieste, Italy. [Hara, K.; Kim, S. H.; Kurata, M.; Miyake, H.; Nagai, Y.; Sato, K.; Shimojima, M.; Takemasa, K.; Takeuchi, Y.; Tomura, T.; Ukegawa, F.] Univ Tsukuba, Tsukuba, Ibaraki 305, Japan. [Hare, M.; Napier, A.; Rolli, S.; Sliwa, K.] Tufts Univ, Medford, MA 02155 USA. [Group, R. C.; Liu, H.; Neu, C.; Oksuzian, I.] Univ Virginia, Charlottesville, VA 22906 USA. [Arisawa, T.; Ebina, K.; Funakoshi, Y.; Kimura, N.; Kondo, K.; Naganoma, J.; Sakurai, Y.; Yorita, K.] Waseda Univ, Tokyo 169, Japan. [Clarke, C.; Harr, R. F.; Karchin, P. E.; Mattson, M. E.] Wayne State Univ, Detroit, MI 48201 USA. [Bellinger, J.; Carlsmith, D.; Herndon, M.; Parker, W.; Pondrom, L.] Univ Wisconsin, Madison, WI 53706 USA. [Husemann, U.; Lockwitz, S.; Loginov, A.] Yale Univ, New Haven, CT 06520 USA. [Lister, A.] Univ British Columbia, Vancouver, BC V6T 1Z1, Canada. [Manca, G.] Ist Nazl Fis Nucl, Sez Cagliari, I-09042 Cagliari, Italy. [Lysak, R.] Univ Calif Irvine, Irvine, CA 92697 USA. [Lysak, R.] Acad Sci Czech Republic, Inst Phys, Prague 18221, Czech Republic. [Cerri, A.; Palencia, E.; Tonelli, D.] CERN, CH-1211 Geneva, Switzerland. [Hopkins, W.; Poprocki, S.; Thom, J.; Wittich, P.] Cornell Univ, Ithaca, NY 14853 USA. [Ptohos, F.] Univ Cyprus, CY-1678 Nicosia, Cyprus. [Rolli, S.] US DOE, Washington, DC 20585 USA. [McNulty, R.] Univ Coll Dublin, Dublin 4, Ireland. [Casal, B.; Wallny, R.] ETH, CH-8092 Zurich, Switzerland. [Yoshida, T.] Univ Fukui, Fukui 9100017, Japan. [Carrillo, S.; Vazquez, F.] Univ Iberoamer, Mexico City 01219, DF, Mexico. [Harrington-Taber, T.; Nachtman, J.; Yi, K.] Univ Iowa, Iowa City, IA 52242 USA. [Kato, Y.] Kinki Univ, Higashiosaka, Osaka 5778502, Japan. [Ivanov, A.] Kansas State Univ, Manhattan, KS 66506 USA. [Di Ruzza, B.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Piacentino, G.] Ist Nazl Fis Nucl, Sez Lecce, I-73100 Lecce, Italy. [Cerrito, L.] Univ London, London E1 4NS, England. [Limosani, A.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Flanagan, G.] Muons Inc, Batavia, IL 60510 USA. [Shimojima, M.] Nagasaki Inst Appl Sci, Nagasaki 8510193, Japan. [d'Ascenzo, N.; Saveliev, V.] Natl Res Nucl Univ, Moscow 115409, Russia. [Anastassov, A.; Stentz, D.] Northwestern Univ, Evanston, IL 60208 USA. [Lannon, K.] Univ Notre Dame, Notre Dame, IN 46556 USA. [Cuevas, J.] Univ Oviedo, E-33007 Oviedo, Spain. [Corbo, M.; Moon, C. S.; Savoy-Navarro, A.] CNRS, IN2P3, F-75205 Paris, France. [Prokoshin, F.] Univ Tecn Federico Santa Maria, Valparaiso 110V, Chile. [Hussein, M.] Univ Jordan, Amman 11942, Jordan. [Vizan, J.] Catholic Univ Louvain, B-1348 Louvain La Neuve, Belgium. [Canelli, F.; Kilminster, B.] Univ Zurich, CH-8006 Zurich, Switzerland. [Moore, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Datta, M.] Hampton Univ, Hampton, VA 23668 USA. [Ketchum, W.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. [Marchese, L.] Univ Naples Federico II, I-80138 Naples, Italy. RP Aaltonen, T (reprint author), Univ Helsinki, Dept Phys, Div High Energy Phys, FIN-00014 Helsinki, Finland. RI vilar, rocio/P-8480-2014; Paulini, Manfred/N-7794-2014; Chiarelli, Giorgio/E-8953-2012; Introzzi, Gianluca/K-2497-2015; Piacentino, Giovanni/K-3269-2015; Marino, Pietro/N-7030-2015; song, hao/I-2782-2012; Gorelov, Igor/J-9010-2015; maestro, paolo/E-3280-2010; Prokoshin, Fedor/E-2795-2012; Canelli, Florencia/O-9693-2016; Ruiz, Alberto/E-4473-2011 OI Toback, David/0000-0003-3457-4144; Jun, Soon Yung/0000-0003-3370-6109; Margaroli, Fabrizio/0000-0002-3869-0153; Group, Robert/0000-0002-4097-5254; Simonenko, Alexander/0000-0001-6580-3638; Casarsa, Massimo/0000-0002-1353-8964; Latino, Giuseppe/0000-0002-4098-3502; iori, maurizio/0000-0002-6349-0380; Hays, Chris/0000-0003-2371-9723; Farrington, Sinead/0000-0001-5350-9271; Robson, Aidan/0000-0002-1659-8284; Dorigo, Mirco/0000-0002-0681-6946; Brucken, Jens Erik/0000-0001-6066-8756; Paulini, Manfred/0000-0002-6714-5787; Chiarelli, Giorgio/0000-0001-9851-4816; Introzzi, Gianluca/0000-0002-1314-2580; Piacentino, Giovanni/0000-0001-9884-2924; Marino, Pietro/0000-0003-0554-3066; song, hao/0000-0002-3134-782X; Gorelov, Igor/0000-0001-5570-0133; maestro, paolo/0000-0002-4193-1288; Prokoshin, Fedor/0000-0001-6389-5399; Canelli, Florencia/0000-0001-6361-2117; Ruiz, Alberto/0000-0002-3639-0368 FU U.S. Department of Energy; National Science Foundation; Italian Istituto Nazionale di Fisica Nucleare; Ministry of Education, Culture, Sports, Science and Technology of Japan; Natural Sciences and Engineering Research Council of Canada; National Science Council of the Republic of China; Swiss National Science Foundation; A. P. Sloan Foundation; Bundesministerium fur Bildung und Forschung, Germany; Korean World Class University Program; National Research Foundation of Korea; Science and Technology Facilities Council; Royal Society, United Kingdom; Russian Foundation for Basic Research; Ministerio de Ciencia e Innovacion and Programa Consolider-Ingenio, Spain; Slovak RD Agency; Academy of Finland; Australian Research Council (ARC); EU community Marie Curie Fellowship [302103] FX We thank the Fermilab staff and the technical staffs of the participating institutions for their vital contributions. This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium fur Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, United Kingdom; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovacion, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; the Australian Research Council (ARC); and the EU community Marie Curie Fellowship Contract No. 302103. NR 47 TC 1 Z9 1 U1 2 U2 24 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 EI 1079-7114 J9 PHYS REV LETT JI Phys. Rev. Lett. PD APR 10 PY 2015 VL 114 IS 14 AR 141802 DI 10.1103/PhysRevLett.114.141802 PG 9 WC Physics, Multidisciplinary SC Physics GA CF6TB UT WOS:000352688000001 ER PT J AU Wang, JY Xia, JC Zhang, F Shi, YJ Wu, Y Pu, HJ Liou, AKF Leak, RK Yu, XG Chen, L Chen, J AF Wang, Jiayin Xia, Jinchao Zhang, Feng Shi, Yejie Wu, Yun Pu, Hongjian Liou, Anthony K. F. Leak, Rehana K. Yu, Xinguang Chen, Ling Chen, Jun TI Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury SO SCIENTIFIC REPORTS LA English DT Article ID PROMOTES AXONAL REGENERATION; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; FOCAL CEREBRAL-ISCHEMIA; WHITE-MATTER INJURY; SPINAL-CORD-INJURY; OXIDIZED GALECTIN-1; FUNCTIONAL RECOVERY; PERIPHERAL-NERVES; REGULATES NEUROGENESIS; STEM/PROGENITOR CELLS AB Galectin-1 (gal-1), a special lectin with high affinity to beta-galactosides, is implicated in protection against ischemic brain injury. The present study investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into ischemic brains and identified the mechanisms underlying protection. To accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural stem cells. Transient cerebral ischemia was induced in mice by middle cerebral artery occlusion for 60 minutes and s-NSCs were injected into the striatum and cortex within 2 hours post-ischemia. Brain infarct volume and neurological performance were assessed up to 28 days post-ischemia. s-NSC transplantation reduced infarct volume, improved sensorimotor and cognitive functions, and provided more robust neuroprotection than non-engineered NSCs or gal-1-overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by attenuating secretion of pro-inflammatory cytokines (TNF-alpha and nitric oxide) in response to LPS stimulation and enhancing production of anti-inflammatory cytokines (IL-10 and TGF-beta). Gal-1 also shifted microglia/macrophage polarization toward the beneficial M2 phenotype in vivo by reducing CD16 expression and increasing CD206 expression. In sum, s-NSC transplantation confers robust neuroprotection against cerebral ischemia, probably by alleviating white matter injury and modulating microglial/macrophage function. C1 [Wang, Jiayin; Wu, Yun] Capital Med Univ, Xuanwu Hosp, Cell Therapy Ctr, Beijing 100053, Peoples R China. [Xia, Jinchao] Zhengzhou Univ, Henan Prov Peoples Hosp, Cerebrovasc Ctr, Zhengzhou 450003, Peoples R China. [Wang, Jiayin; Xia, Jinchao; Zhang, Feng; Shi, Yejie; Wu, Yun; Pu, Hongjian; Liou, Anthony K. F.; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Yu, Xinguang; Chen, Ling] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg & PLA Inst Neurosurg, Beijing 100853, Peoples R China. [Zhang, Feng; Shi, Yejie; Pu, Hongjian; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. EM chlyz34@163.com; chenj2@upmc.edu OI Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU U.S. National Institutes of Health [NS036736, NS045048, NS089534]; U.S. Department of Veterans Affairs; High Level Talent Fund of the Beijing Healthcare System [2011-3-093]; Program for New Century Excellent Talents in University [NCET-12-0612]; National Natural Science Foundation of China [81301066]; Beijing Nova Program [2013019]; RRD Merit Review FX J.W. and J.X. contributed equally to the work. This project was supported by U.S. National Institutes of Health grants NS036736, NS045048, and NS089534 (to J.C.), U.S. Department of Veterans Affairs Research Career Scientist Award and RR&D Merit Review (to J.C.). L.C. was supported by the High Level Talent Fund of the Beijing Healthcare System (Grant No. 2011-3-093) and the Program for New Century Excellent Talents in University (Grant No. NCET-12-0612). J.W. was supported by the National Natural Science Foundation of China (Grant No. 81301066) and Beijing Nova Program (Grant No. 2013019). The authors are indebted to Carol Culver for excellent editorial assistance and Pat Strickler for excellent administrative support. NR 62 TC 8 Z9 10 U1 4 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 10 PY 2015 VL 5 AR 9621 DI 10.1038/srep09621 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF6AM UT WOS:000352638800001 PM 25858671 ER PT J AU Wang, XW Wei, L Cramer, JM Leibowitz, BJ Judge, C Epperly, M Greenberger, J Wang, FC Li, LH Stelzner, MG Dunn, JCY Martin, MG Lagasse, E Zhang, L Yu, J AF Wang, Xinwei Wei, Liang Cramer, Julie M. Leibowitz, Brian J. Judge, Colleen Epperly, Michael Greenberger, Joel Wang, Fengchao Li, Linheng Stelzner, Matthias G. Dunn, James C. Y. Martin, Martin G. Lagasse, Eric Zhang, Lin Yu, Jian TI Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation SO SCIENTIFIC REPORTS LA English DT Article ID COLORECTAL-CANCER CELLS; GASTROINTESTINAL-SYNDROME; CRANIAL IRRADIATION; HEMATOPOIETIC STEM; IN-VITRO; P53; PUMA; INDUCTION; DAMAGE; LGR5 AB Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr51 cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMAinduction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically. C1 [Wang, Xinwei; Wei, Liang; Cramer, Julie M.; Leibowitz, Brian J.; Judge, Colleen; Lagasse, Eric; Yu, Jian] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Wang, Xinwei; Wei, Liang; Leibowitz, Brian J.; Judge, Colleen; Epperly, Michael; Greenberger, Joel; Zhang, Lin; Yu, Jian] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Epperly, Michael; Greenberger, Joel; Yu, Jian] Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. [Wang, Fengchao; Li, Linheng] Univ Kansas, Med Ctr, Stowers Inst Med Res, Dept Pathol, Kansas City, MS 64110 USA. [Stelzner, Matthias G.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA. [Dunn, James C. Y.; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dunn, James C. Y.; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Zhang, Lin] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. RP Yu, J (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM yuj2@upmc.edu OI Judge, Colleen/0000-0001-9167-9650 FU NIH [U01-DK085570, CA129829, CA106348]; American Cancer Society [RGS-10-124-01-CCE, U01-DK085535, U01DK085507]; NIDDK; NIAID [U01]; [5T32GM008208]; [P30CA047904] FX We thank members in the Yu and Zhang labs for helpful discussions. This work is supported in part by NIH grants U01-DK085570, NIH grant CA129829, American Cancer Society grant RGS-10-124-01-CCE (J Yu), U01-DK085535 (M Martin), U01DK085507 (L Li), and NIH grant CA106348 (L Zhang). Yu, Li and Martin laboratories are members of the Intestinal Stem Cell Consortium, supported in part by NIDDK and NIAID (U01). C.J. was supported by 5T32GM008208. This project used the UPCI shared glassware, animal, and cell and tissue imaging facilities that were supported in part by award P30CA047904. NR 48 TC 11 Z9 11 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 10 PY 2015 VL 5 AR UNSP 8566 DI 10.1038/srep08566 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5ZX UT WOS:000352637300001 PM 25858503 ER PT J AU Geng, J Li, X Zhou, ZM Wu, CL Dai, M Bai, XY AF Geng, Jian Li, Xiao Zhou, Zhanmei Wu, Chin-Lee Dai, Meng Bai, Xiaoyan TI EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer SO CANCER LETTERS LA English DT Article DE Enhancer of Zeste Homologue 2; VEGF-A; PI3K/AKT signaling; Small interfering RNA; Non-small cell lung carcinoma ID GROWTH-FACTOR; FACTOR-I; EXPRESSION; ADENOCARCINOMA; ANGIOGENESIS; PATHWAY; METASTASIS; STATISTICS; MUTATIONS AB Enhancer of Zeste Homologue 2 (EZH2) accounts for aggressiveness and unfavorable prognosis of tumor. We investigated the mechanisms and signaling pathways of EZH2 in non-small cell lung carcinoma (NSCLC) progression. Increased expression of EZH2, vascular endothelial growth factor-A (VEGF-A) and AKT phosphorylation correlated with differentiation, lymph node metastasis, size and TNM stage in NSCLC. There was a positive correlation between EZH2 and VEGF-A expression and high EZH2 expression, as an independent prognostic factor, predicted a shorter overall survival time for NSCLC patients. The expression of VEGF-A and phosphorylated Ser473-AKT, cell proliferation, migration and metastasis were enhanced in EZH2-overexpressing A549 cells, but inhibited in parental H2087 cells with EZH2 silencing or GSK126 treatment. Ala activity was enhanced by recombinant human VEGF-165 but suppressed by bevacizumab. An Ala inhibitor MK-2206 blocked VEGF-A expression and AKT phosphorylation in parental H2087 and EZH2-overexpressing A549 cells. EZH2 activity was not affected by either VEGF-A stimulation/depletion or MK-2206 inhibition. These results demonstrate that EZH2 promotes lung cancer progression via the VEGF-A/AKT signaling pathway. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Geng, Jian; Zhou, Zhanmei; Bai, Xiaoyan] Southern Med Univ, Nanfang Hosp, Div Nephrol, Natl Key Lab Organ Failure Res, Guangzhou, Guangdong, Peoples R China. [Geng, Jian] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China. [Geng, Jian] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China. [Li, Xiao; Bai, Xiaoyan] Southern Med Univ, Nanfang Hosp, Dept Emergency, Guangzhou, Guangdong, Peoples R China. [Wu, Chin-Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dai, Meng] Southern Med Univ, Nanfang Hosp, Hlth Management Ctr, Guangzhou, Guangdong, Peoples R China. RP Bai, XY (reprint author), Southern Med Univ, Nanfang Hosp, Div Nephrol, Natl Key Lab Organ Failure Res, Guangzhou, Guangdong, Peoples R China. EM dm42298@21cn.com; xiaoyanb@126.com FU National Nature and Science Young Investigator Grant from the National Natural Science Foundation of China [81100496]; National Natural Science Foundation of China from Nanfang Hospital, Southern Medical University [G201203]; International Cooperation Special Fund from Guangzhou Science and Technology Planning Project [2013J4500040]; Key Clinical Specialty Discipline Construction Program FX This study was supported by National Nature and Science Young Investigator Grant (no. 81100496) from the National Natural Science Foundation of China, Matching Grant (no. G201203) of the National Natural Science Foundation of China from Nanfang Hospital, Southern Medical University to XB, International Cooperation Special Fund from Guangzhou Science and Technology Planning Project (no. 2013J4500040) to MD, and Key Clinical Specialty Discipline Construction Program. NR 32 TC 22 Z9 23 U1 4 U2 37 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD APR 10 PY 2015 VL 359 IS 2 BP 275 EP 287 DI 10.1016/j.canlet.2015.01.031 PG 13 WC Oncology SC Oncology GA CC7AC UT WOS:000350519100017 PM 25633838 ER PT J AU Castillo, JJ Bibas, M Miranda, RN AF Castillo, Jorge J. Bibas, Michele Miranda, Roberto N. TI The biology and treatment of plasmablastic lymphoma SO BLOOD LA English DT Review ID EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; MYC-INDUCED LYMPHOMAGENESIS; ORAL-CAVITY; C-MYC; TRANSCRIPTION FACTORS; NEGATIVE PATIENTS; INFECTED PATIENTS; GERMINAL CENTER AB Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with HIV infection. However, PBL can also be seen in patients with other immunodeficiencies as well as in immunocompetent individuals. Because of its distinct clinical and pathological features, such as lack of expression of CD20, plasmablastic morphology, and clinical course characterized by early relapses and subsequent chemotherapy resistance, PBL can represent a diagnostic and therapeutic challenge for pathologists and clinicians alike. Despite the recent advances in the therapy of HIV-associated and aggressive lymphomas, patients with PBL for the most part have poor outcomes. The objectives of this review are to summarize the current knowledge on the epidemiology, biology, clinical and pathological characteristics, differential diagnosis, therapy, prognostic factors, outcomes, and potential novel therapeutic approaches in patients with PBL and also to increase the awareness toward PBL in the medical community. C1 [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Bibas, Michele] Lazzaro Spallanzani Natl Inst Infect Dis, Dept Clin Res, Hematol, Rome, Italy. [Miranda, Roberto N.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. RP Castillo, JJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 71 TC 33 Z9 36 U1 2 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 APR 9 PY 2015 VL 125 IS 15 BP 2323 EP 2330 DI 10.1182/blood-2014-10-567479 PG 8 WC Hematology SC Hematology GA CI3DP UT WOS:000354628100006 PM 25636338 ER PT J AU Allen, JD Torres, MI Tom, LS Rustan, S Leyva, B Negron, R Linnan, LA Jandorf, L Ospino, H AF Allen, Jennifer D. Torres, Maria Idali Tom, Laura S. Rustan, Sarah Leyva, Bryan Negron, Rosalyn Linnan, Laura A. Jandorf, Lina Ospino, Hosffman TI Enhancing organizational capacity to provide cancer control programs among Latino churches: design and baseline findings of the CRUZA Study SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Latinos; Hispanics; Faith-based organizations; Catholic; Cancer screening; Evidence-based interventions; Implementation science; Organizational capacity enhancement; Capacity building; Community-based participatory research ID AFRICAN-AMERICAN WOMEN; RE-AIM FRAMEWORK; HEALTH-PROMOTION INTERVENTIONS; PHYSICAL-ACTIVITY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; SERVICES RESEARCH; VEGETABLE INTAKE; BLACK CHURCHES; IMPLEMENTATION; PREVENTION AB Background: Faith-based organizations (FBOs) have been successful in delivering health promotion programs for African Americans, though few studies have been conducted among Latinos. Even fewer have focused on organizational change, which is required to sustain community-based initiatives. We hypothesized that FBOs serving Latinos would be more likely to offer evidence-based strategies (EBS) for cancer control after receiving a capacity enhancement intervention to implement health programs, and designed the CRUZA trial to test this hypothesis. This paper describes the CRUZA design and baseline findings. Methods: We identified Catholic parishes in Massachusetts that provided Spanish-language mass (n = 65). A baseline survey assessed organizational characteristics relevant to adoption of health programs, including readiness for adoption, "fit" between innovation and organizational mission, implementation climate, and organizational culture. In the next study phase, parishes that completed the baseline assessment will be recruited to a randomized cluster trial, with the parish as the unit of analysis. Both groups will receive a Program Manual and Toolkit. Capacity Enhancement parishes will also be offered technical support, assistance forming health committees and building inter-institutional partnerships, and skills-based training. Results: Of the 49 parishes surveyed at baseline (75%), one-third (33%) reported having provided at least one health program in the prior year. However, only two program offerings were cancer-specific. Nearly one-fifth (18%) had an active health ministry. There was a high level of organizational readiness to adopt cancer control programs, high congruence between parish missions and CRUZA objectives, moderately conducive implementation climates, and organizational cultures supportive of CRUZA programming. Having an existing health ministry was significantly associated with having offered health programs within the past year. Relationships between health program offerings and other organizational characteristics were not statistically significant. Conclusions: Findings suggest that many parishes do not offer cancer control programs, yet many may be ready to do so. However, the perceptions about existing organizational practices and policies may not be conducive to program initiation. A capacity enhancement intervention may hold promise as a means of increasing health programming. The efficacy of such an intervention will be tested in phase two of this study. C1 [Allen, Jennifer D.; Tom, Laura S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Tufts Univ, Dept Publ Hlth & Community Med, Medford, MA 02155 USA. [Torres, Maria Idali; Rustan, Sarah; Negron, Rosalyn] Univ Massachusetts, Mauricio Gaston Inst Latino Community Dev & PublP, Boston, MA 02125 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Linnan, Laura A.] Univ N Carolina, Chapel Hill, NC USA. [Jandorf, Lina] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jennifer.allen@tufts.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [U54CA156732]; National Institute on Minority Health and Health Disparities [R21MD005976]; Centers for Disease Control and Prevention with the National Cancer Institute [U48DP001946] FX This work was supported in part by the National Cancer Institute (U54CA156732, UMASS Boston/Dana-Farber Harvard Cancer Center Comprehensive Cancer Partnership Program), the National Institute on Minority Health and Health Disparities (R21MD005976), and through a cooperative agreement by the Centers for Disease Control and Prevention with the National Cancer Institute (U48DP001946, Massachusetts Cancer Prevention and Control Research Network). The authors gratefully acknowledge the time and insights provided by study participants. We also acknowledge the many contributions made by Milagros Abreu, Francisco Anzoategui, Amanda Bartholomew, Lois Biener, Deb Bowen, Melissa Colon, Daisy Diaz, Karen Emmons, Ana Galeas, Ericka Gonzalez, Elizabeth Gonzalez Suarez, Elizabeth Harden, Christina Hernandez, Alan Juarez, Robert Kickham, Ruth Lederman, Carol Lowenstein, Yolanda Martins, Angel Matos, Scott McInerney, Jane Mendez, Moraima Mendoza, Hannah Mills, Sean O'Malley, Aida Palencia, Beninson Pena, John Perez, Triniese Polk, Luciano Ramos, Lori-Anne Ramsey, Bianka Recinos, Rosa Robledo, Jeffrey Sanchez, Maria Sesma, Sarfaraz Shaikh, Ling Shi, Emeli Valverde, Bryan Weiner, David Wright, and the UMASS Boston Center for Survey Research. NR 63 TC 3 Z9 3 U1 5 U2 17 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 APR 9 PY 2015 VL 15 AR 147 DI 10.1186/s12913-015-0735-1 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH6UC UT WOS:000354170800001 PM 25889628 ER PT J AU Heinze, KE Rodday, AM Nolan, MT Bingen, K Kupst, MJ Patel, SK Syrjala, K Harris, L Recklitis, C Schwartz, L Davies, S Guinan, EC Noll, R Chang, G Parsons, SK AF Heinze, Katherine E. Rodday, Angie Mae Nolan, Marie T. Bingen, Kristin Kupst, Mary Jo Patel, Sunita K. Syrjala, Karen Harris, Lynnette Recklitis, Christopher Schwartz, Lisa Davies, Stella Guinan, Eva C. Noll, Robert Chang, Grace Parsons, Susan K. TI The impact of pediatric blood and marrow transplant on parents: introduction of the parent impact scale SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article DE Blood and marrow transplantation; Caregiving; Stress; Parent impact ID STEM-CELL TRANSPLANT; QUALITY-OF-LIFE; CHILDREN; DISTRESS; HSCT; SCT; DISEASE; MOTHERS; STRESS; GRAFT AB Background: Parents often experience stress-related complications when their child requires blood and marrow transplant (BMT). Previous studies have described the emotional toll BMT places on parents during the acute phase of care and within the context of clinical complications. In this paper we introduce the Parent Impact Scale (PARimpact), designed to capture physical and emotional challenges of the child's health on the parent. The primary aim of this paper is to examine psychometric properties of PARimpact, and the secondary aim is to explore factors associated with PARimpact scores for further hypothesis generation. Methods: This analysis used a merged dataset of two longitudinal studies. Accompanying parents (n = 363) of children undergoing BMT were surveyed up to six times from pre-BMT baseline to one year after their child's BMT. For this analysis, pre-BMT baseline responses to PARimpact were used to examine the factor structure with Principal Component Analysis (PCA) and Exploratory Factor Analysis (EFA). Construct validity was assessed, and multivariable regression was used to examine relationships between PARimpact and BMT clinical variables. Results: PCA and EFA revealed a one-factor solution with acceptable item loading; Cronbach's a was 0.83 at baseline. Hypothesized differences in known groups were detected for BMT complications with significantly higher PARimpact scores for those with vs. without each complication. In the adjusted multivariable regression models, acute graft versus host disease (b = 5.3; p = 0.03), end organ toxicity (b = 5.9; p < 0.01), and systemic infection (b = 9.1; p < 0.01) were associated with significantly higher mean PARimpact scores in the first 3 months following transplant. After the first 3 months to 1 year post BMT, systemic infection was associated with increased mean PARimpact scores (b = 19.2; p < 0.01). Conclusions: Initial results suggest that the PARimpact is valid and reliable. Our finding that clinical complications increase the impact of BMT on the caretaking parent indicates the need for BMT healthcare professionals to identify these events and help parents navigate the BMT course. Clinical application of the PARimpact scale should be considered to identify high-risk families and provide targeted interventions to augment care. C1 [Heinze, Katherine E.; Nolan, Marie T.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. [Rodday, Angie Mae; Parsons, Susan K.] Tufts Med Ctr, Boston, MA 02111 USA. [Bingen, Kristin; Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Syrjala, Karen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Harris, Lynnette] Baylor Coll Med, Baylor, TX 77030 USA. [Recklitis, Christopher; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Schwartz, Lisa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Davies, Stella] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Noll, Robert] Childrens Hosp Pittsburgh PUMC, Pittsburgh, PA 15224 USA. [Chang, Grace] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Heinze, KE (reprint author), Johns Hopkins Univ, Sch Nursing, 525 N Wolfe St, Baltimore, MD 21205 USA. EM kgriff12@jhu.edu FU American Cancer Society Doctoral Degree Scholarship in Cancer Nursing [DSCN-13-268-01-SCN]; National Institute for Nursing Research [F31 NR014751-01A1]; American Cancer Society [RSG PB02-186-01-PBP]; National Cancer Institute [R01 CA119196] FX KH acknowledges the American Cancer Society Doctoral Degree Scholarship in Cancer Nursing (DSCN-13-268-01-SCN), and the National Institute for Nursing Research (F31 NR014751-01A1) for funding this analysis. SKP acknowledges the American Cancer Society (RSG PB02-186-01-PBP) and the National Cancer Institute (R01 CA119196) for funding the Journeys to Recovery and HSCT-CHESS (TM) studies, respectively. NR 34 TC 2 Z9 2 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD APR 9 PY 2015 VL 13 AR 46 DI 10.1186/s12955-015-0240-6 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CG6AV UT WOS:000353378300001 PM 25890070 ER PT J AU Bambury, RM Bhatt, AS Riester, M Pedamallu, CS Duke, F Bellmunt, J Stack, EC Werner, L Park, R Iyer, G Loda, M Kantoff, PW Michor, F Meyerson, M Rosenberg, JE AF Bambury, Richard M. Bhatt, Ami S. Riester, Markus Pedamallu, Chandra Sekhar Duke, Fujiko Bellmunt, Joaquim Stack, Edward C. Werner, Lillian Park, Rachel Iyer, Gopa Loda, Massimo Kantoff, Philip W. Michor, Franziska Meyerson, Matthew Rosenberg, Jonathan E. TI DNA copy number analysis of metastatic urothelial carcinoma with comparison to primary tumors SO BMC CANCER LA English DT Article ID INTEGRATIVE ANALYSIS; GENOMIC ANALYSIS; HUMAN CANCERS; BLADDER; TESTS; TRANSCRIPTOME; CLONALITY; REGIONS; TARGETS; GAIN AB Background: To date, there have been no reports characterizing the genome-wide somatic DNA chromosomal copy-number alteration landscape in metastatic urothelial carcinoma. We sought to characterize the DNA copy-number profile in a cohort of metastatic samples and compare them to a cohort of primary urothelial carcinoma samples in order to identify changes that are associated with progression from primary to metastatic disease. Methods: Using molecular inversion probe array analysis we compared genome-wide chromosomal copy-number alterations between 30 metastatic and 29 primary UC samples. Whole transcriptome RNA-Seq analysis was also performed in primary and matched metastatic samples which was available for 9 patients. Results: Based on a focused analysis of 32 genes in which alterations may be clinically actionable, there were significantly more amplifications/deletions in metastases (8.6% vs 4.5%, p < 0.001). In particular, there was a higher frequency of E2F3 amplification in metastases (30% vs 7%, p = 0.046). Paired primary and metastatic tissue was available for 11 patients and 3 of these had amplifications of potential clinical relevance in metastases that were not in the primary tumor including ERBB2, CDK4, CCND1, E2F3, and AKT1. The transcriptional activity of these amplifications was supported by RNA expression data. Conclusions: The discordance in alterations between primary and metastatic tissue may be of clinical relevance in the era of genomically directed precision cancer medicine. C1 [Bambury, Richard M.; Iyer, Gopa; Rosenberg, Jonathan E.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Bhatt, Ami S.; Riester, Markus; Pedamallu, Chandra Sekhar; Duke, Fujiko; Bellmunt, Joaquim; Stack, Edward C.; Werner, Lillian; Park, Rachel; Loda, Massimo; Kantoff, Philip W.; Michor, Franziska; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bhatt, Ami S.; Pedamallu, Chandra Sekhar; Duke, Fujiko; Loda, Massimo; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Bambury, RM (reprint author), Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. EM bamburyr@mskcc.org OI Rosenberg, Jonathan/0000-0003-2637-4249 NR 34 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 9 PY 2015 VL 15 AR 242 DI 10.1186/s12885-015-1192-2 PG 11 WC Oncology SC Oncology GA CF5NJ UT WOS:000352603600001 PM 25886454 ER PT J AU Goldberg, MS AF Goldberg, Michael S. TI Immunoengineering: How Nanotechnology Can Enhance Cancer Immunotherapy SO CELL LA English DT Review ID T-CELLS; TARGETING NANOPARTICLES; EXTRACELLULAR-MATRIX; DENDRITIC CELLS; TUMOR-CELLS; IN-VIVO; IMMUNITY AB Although cancer immunotherapy can lead to durable outcomes, the percentage of patients who respond to this disruptive approach remains modest to date. Encouragingly, nanotechnology can enhance the efficacy of immunostimulatory small molecules and biologics by altering their co-localization, biodistribution, and release kinetics. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_goldberg1@dfci.harvard.edu FU Cancer Research Institute; Melanoma Research Alliance; Ovarian Cancer Research Fund FX The author thanks the Cancer Research Institute, Melanoma Research Alliance, and Ovarian Cancer Research Fund for their support and apologizes to those investigators whose work could not be referenced because of space limitations. NR 23 TC 26 Z9 26 U1 18 U2 92 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 APR 9 PY 2015 VL 161 IS 2 BP 201 EP 204 DI 10.1016/j.cell.2015.03.037 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF7AL UT WOS:000352708300014 PM 25860604 ER PT J AU Karreth, FA Reschke, M Ruocco, A Ng, C Chapuy, B Leopold, V Sjoberg, M Keane, TM Verma, A Ala, U Tay, Y Wu, D Seitzer, N Velasco-Herrera, MD Bothmer, A Fung, J Langellotto, F Rodig, SJ Elemento, O Shipp, MA Adams, DJ Chiarle, R Pandolfi, PP AF Karreth, Florian A. Reschke, Markus Ruocco, Anna Ng, Christopher Chapuy, Bjoern Leopold, Valentine Sjoberg, Marcela Keane, Thomas M. Verma, Akanksha Ala, Ugo Tay, Yvonne Wu, David Seitzer, Nina Velasco-Herrera, Martin Del Castillo Bothmer, Anne Fung, Jacqueline Langellotto, Fernanda Rodig, Scott J. Elemento, Olivier Shipp, Margaret A. Adams, David J. Chiarle, Roberto Pandolfi, Pier Paolo TI The BRAF Pseudogene Functions as a Competitive Endogenous RNA and Induces Lymphoma In Vivo SO CELL LA English DT Article ID B-CELL LYMPHOMA; NONCODING-RNA; X-CHROMOSOME; CERNA HYPOTHESIS; GENE-EXPRESSION; MESSENGER-RNAS; TUMOR BIOLOGY; MOUSE OOCYTES; TARGET; MICRORNA AB Research over the past decade has suggested important roles for pseudogenes in physiology and disease. In vitro experiments demonstrated that pseudogenes contribute to cell transformation through several mechanisms. However, in vivo evidence for a causal role of pseudogenes in cancer development is lacking. Here, we report that mice engineered to overexpress either the full-length murine B-Raf pseudogene Braf-rs1 or its pseudo "CDS'' or "3' UTR'' develop an aggressive malignancy resembling human diffuse large B cell lymphoma. We show that Braf-rs1 and its human ortholog, BRAFP1, elicit their oncogenic activity, at least in part, as competitive endogenous RNAs (ceRNAs) that elevate BRAF expression and MAPK activation in vitro and in vivo. Notably, we find that transcriptional or genomic aberrations of BRAFP1 occur frequently in multiple human cancers, including B cell lymphomas. Our engineered mouse models demonstrate the oncogenic potential of pseudogenes and indicate that ceRNA-mediated microRNA sequestration may contribute to the development of cancer. C1 [Karreth, Florian A.; Reschke, Markus; Ruocco, Anna; Ng, Christopher; Leopold, Valentine; Ala, Ugo; Tay, Yvonne; Seitzer, Nina; Bothmer, Anne; Fung, Jacqueline; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Res Inst,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA. [Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sjoberg, Marcela; Keane, Thomas M.; Velasco-Herrera, Martin Del Castillo; Adams, David J.] Wellcome Trust Sanger Inst, Expt Canc Genet, Hinxton CB10 1HH, England. [Verma, Akanksha; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, Dept Physiol & Biophys, New York, NY 10021 USA. [Wu, David] Weill Cornell Med Coll, Meyer Canc Ctr, New York, NY 10021 USA. [Langellotto, Fernanda; Chiarle, Roberto] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Langellotto, Fernanda; Chiarle, Roberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chiarle, Roberto] Univ Torino, Dept Mol Biotechnol & Hlth Sci, I-10124 Turin, Italy. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Res Inst,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI Ala, Ugo/K-2029-2016; OI Ala, Ugo/0000-0001-5408-6397; Keane, Thomas/0000-0001-7532-6898 FU Department of Defense Prostate Cancer Research Program; American Cancer Society; German Academy of Sciences Leopoldina; CHB-MIT fellowship; Italian Association for Cancer Research (AIRC) [IG-9408]; Cancer Research UK; Wellcome Trust; FP7 ERC-StG grant [242965]; AIRC [IG-12023]; International Association for Cancer Research (AICR) [12-0216]; NIH [CA170158-01] FX We are grateful to L. Cantley for hosting F.A.K. in his lab for part of this study. We thank S. Lowe for CAG-rtTA3 mice; L. Cantley, B. Vogelstein, and P. Sharp for cell lines; G. DeNicola for helpful discussions; and the Nikon Imaging Center at Harvard Medical School for help with light microscopy, the Dana Farber/Harvard Cancer Center Specialized Histopathology Core for help with immunohistochemistry, J. Clohessy and B. Padmani for help with ultrasound imaging, and S. Annunziato, A. Nyein, A. Bester, and K Berry for technical assistance. F.A.K. was supported by fellowships from the Department of Defense Prostate Cancer Research Program and the American Cancer Society. M.R. was supported by the German Academy of Sciences Leopoldina, F.L. received a CHB-MIT fellowship, and U.A. acknowledges support from the Italian Association for Cancer Research (AIRC) under grant IG-9408. M.S., T.M.K., M.D.C.V.-H., and D.J.A. are funded by Cancer Research UK and the Wellcome Trust. R.C. was supported by a FP7 ERC-2009-StG grant (Proposal No. 242965, "Lunely''), AIRC grant IG-12023, and an International Association for Cancer Research (AICR) grant 12-0216. P.P.P. was supported by NIH grant CA170158-01. NR 44 TC 43 Z9 44 U1 2 U2 29 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 APR 9 PY 2015 VL 161 IS 2 BP 319 EP 332 DI 10.1016/j.cell.2015.02.043 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF7AL UT WOS:000352708300024 PM 25843629 ER PT J AU Steiner, ME Ness, PM Assmann, SF Triulzi, DJ Sloan, SR Delaney, M Granger, S Bennett-Guerrero, E Blajchman, MA Scavo, V Carson, JL Levy, JH Whitman, G D'Andrea, P Pulkrabek, S Ortel, TL Bornikova, L Raife, T Puca, KE Kaufman, RM Nuttall, GA Young, PP Youssef, S Engelman, R Greilich, PE Miles, R Josephson, CD Bracey, A Cooke, R McCullough, J Hunsaker, R Uhl, L McFarland, JG Park, Y Cushing, MM Klodell, CT Karanam, R Roberts, PR Dyke, C Hod, EA Stowell, CP AF Steiner, M. E. Ness, P. M. Assmann, S. F. Triulzi, D. J. Sloan, S. R. Delaney, M. Granger, S. Bennett-Guerrero, E. Blajchman, M. A. Scavo, V. Carson, J. L. Levy, J. H. Whitman, G. D'Andrea, P. Pulkrabek, S. Ortel, T. L. Bornikova, L. Raife, T. Puca, K. E. Kaufman, R. M. Nuttall, G. A. Young, P. P. Youssef, S. Engelman, R. Greilich, P. E. Miles, R. Josephson, C. D. Bracey, A. Cooke, R. McCullough, J. Hunsaker, R. Uhl, L. McFarland, J. G. Park, Y. Cushing, M. M. Klodell, C. T. Karanam, R. Roberts, P. R. Dyke, C. Hod, E. A. Stowell, C. P. TI Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-CELLS; TRANSFUSION; TRIAL; AGE; MORBIDITY; MORTALITY; OUTCOMES AB BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoingcardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P = 0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P = 0.43); 28-day mortality was 4.4% and 5.3%, respectively (P = 0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. C1 [Steiner, M. E.; Pulkrabek, S.; McCullough, J.] Fairview Univ Med Ctr, Minneapolis, MN USA. [Nuttall, G. A.] Mayo Clin, Rochester, MN USA. [Ness, P. M.; Whitman, G.] Johns Hopkins Univ, Baltimore, MD USA. [Cooke, R.] Univ Maryland, Baltimore, MD 21201 USA. [Assmann, S. F.; Granger, S.] New England Res Inst, Data Coordinating Ctr, Watertown, MA 02172 USA. [Sloan, S. R.] Boston Childrens Hosp, Boston, MA USA. [Bornikova, L.; Stowell, C. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaufman, R. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Engelman, R.] Tufts Univ, Boston, MA 02111 USA. [Hunsaker, R.] St Elizabeths Med Ctr, Boston, MA USA. [Uhl, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Engelman, R.] Baystate Med Ctr, Springfield, MA USA. [Triulzi, D. J.; D'Andrea, P.] Univ Pittsburgh, Pittsburgh, PA USA. [Triulzi, D. J.; D'Andrea, P.] Univ Pittsburgh, Mercy Hosp, Pittsburgh, PA USA. [Delaney, M.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Delaney, M.] Univ Washington, Seattle, WA 98195 USA. [Youssef, S.] Swedish Med Ctr, Seattle, WA USA. [Bennett-Guerrero, E.; Levy, J. H.; Ortel, T. L.] Duke Univ, Durham, NC USA. [Park, Y.] Univ N Carolina, Chapel Hill, NC USA. [Blajchman, M. A.] McMaster Univ, Hamilton, ON, Canada. [Scavo, V.] Indiana Ohio Heart, Ft Wayne, IN USA. [Scavo, V.] St Joseph Hosp, Ft Wayne, IN USA. [Carson, J. L.] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Karanam, R.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Raife, T.] Univ Iowa, Iowa City, IA USA. [Puca, K. E.] Aurora St Lukes Med Ctr, Milwaukee, WI USA. [McFarland, J. G.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA. [Miles, R.] Aspirus Heart & Vasc Inst, Wausau, WI USA. [Young, P. P.] Vanderbilt Univ, Nashville, TN 37235 USA. [Greilich, P. E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Josephson, C. D.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Josephson, C. D.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Bracey, A.] St Lukes Texas Heart Inst, Houston, TX USA. [Cushing, M. M.] Weill Cornell Med Coll, New York, NY USA. [Hod, E. A.] Columbia Univ, Med Ctr, New York, NY USA. [Klodell, C. T.] Univ Florida, Gainesville, FL USA. [Roberts, P. R.] Univ Oklahoma, Oklahoma City, OK USA. [Dyke, C.] Univ N Dakota, Sch Med & Hlth Sci, Fargo, ND USA. RP Steiner, ME (reprint author), Univ Minnesota, Dept Pediat, MB 532,2450 Riverside Ave, Minneapolis, MN 55454 USA. EM stein083@umn.edu OI Cushing, Melissa/0000-0001-8042-1494 FU National Heart, Lung, and Blood Institute FX Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341. NR 28 TC 116 Z9 119 U1 4 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 APR 9 PY 2015 VL 372 IS 15 BP 1419 EP 1429 DI 10.1056/NEJMoa1414219 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CF2ZV UT WOS:000352417900006 PM 25853746 ER PT J AU Treon, SP Tripsas, CK Meid, K Warren, D Varma, G Green, R Argyropoulos, KV Yang, G Cao, Y Xu, L Patterson, CJ Rodig, S Zehnder, JL Aster, JC Harris, NL Kanan, S Ghobrial, I Castillo, JJ Laubach, JP Hunter, ZR Salman, Z Li, JL Cheng, M Clow, F Graef, T Palomba, ML Advani, RH AF Treon, Steven P. Tripsas, Christina K. Meid, Kirsten Warren, Diane Varma, Gaurav Green, Rebecca Argyropoulos, Kimon V. Yang, Guang Cao, Yang Xu, Lian Patterson, Christopher J. Rodig, Scott Zehnder, James L. Aster, Jon C. Harris, Nancy Lee Kanan, Sandra Ghobrial, Irene Castillo, Jorge J. Laubach, Jacob P. Hunter, Zachary R. Salman, Zeena Li, Jianling Cheng, Mei Clow, Fong Graef, Thorsten Palomba, M. Lia Advani, Ranjana H. TI Ibrutinib in Previously Treated Waldenstrom's Macroglobulinemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; BRUTON TYROSINE KINASE; MYD88 L265P; MONOCLONAL GAMMOPATHY; SOMATIC MUTATION; TARGETING BTK; WHIM SYNDROME; PHASE-II AB BACKGROUND MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenstrom's macro-globulinemia. MYD88(L265P) triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib. METHODS We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenstrom's macroglobulinemia who had received at least one previous treatment, and we investigated the effect of MYD88 and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was administered orally until disease progression or the development of unacceptable toxic effects. RESULTS After the patients received ibrutinib, median serum IgM levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter, and bone marrow involvement decreased from 60% to 25% (P< 0.01 for all comparisons). The median time to at least a minor response was 4 weeks. The overall response rate was 90.5%, and the major response rate was 73.0%; these rates were highest among patients with MYD88(L265P)CXCR4(WT) (with WT indicating wild-type) (100% overall response rate and 91.2% major response rate), followed by patients with MYD88(L265P)CXCR4(WHIM) (85.7% and 61.9%, respectively) and patients with MYD88(WT)CXCR4(WT) (71.4% and 28.6%). The estimated 2-year progression-free and overall survival rates among all patients were 69.1% and 95.2%, respectively. Treatment-related toxic effects of grade 2 or higher included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%), which were more common in heavily pretreated patients; postprocedural bleeding (in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and atrial fibrillation associated with a history of arrhythmia (5%). CONCLUSIONS Ibrutinib was highly active, associated with durable responses, and safe in pretreated patients with Waldenstrm's macroglobulinemia. MYD88 and CXCR4 mutation status affected responses to this drug. C1 [Treon, Steven P.; Tripsas, Christina K.; Meid, Kirsten; Warren, Diane; Yang, Guang; Cao, Yang; Xu, Lian; Patterson, Christopher J.; Kanan, Sandra; Ghobrial, Irene; Castillo, Jorge J.; Laubach, Jacob P.; Hunter, Zachary R.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Treon, Steven P.; Yang, Guang; Cao, Yang; Rodig, Scott; Aster, Jon C.; Harris, Nancy Lee; Ghobrial, Irene; Castillo, Jorge J.; Laubach, Jacob P.] Harvard Univ, Sch Med, Boston, MA USA. [Rodig, Scott; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunter, Zachary R.] Boston Univ, Med Ctr, Dept Pathol, Boston, MA USA. [Green, Rebecca; Argyropoulos, Kimon V.; Palomba, M. Lia] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Varma, Gaurav; Zehnder, James L.; Advani, Ranjana H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Salman, Zeena; Li, Jianling; Cheng, Mei; Clow, Fong; Graef, Thorsten] Pharmacyclics, Sunnyvale, CA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M548,450 Brookline Ave, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu OI Varma, Gaurav/0000-0002-1903-9170; Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 FU Pharmacyclics FX Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01614821. NR 34 TC 131 Z9 133 U1 4 U2 22 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 APR 9 PY 2015 VL 372 IS 15 BP 1430 EP 1440 DI 10.1056/NEJMoa1501548 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CF2ZV UT WOS:000352417900007 PM 25853747 ER PT J AU Manian, FA Alame, D AF Manian, Farrin A. Alame, Diana TI Case 11-2015: A 28-Year-Old Woman with Headache, Fever, and a Rash SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BACTERIAL-MENINGITIS; MENINGOCOCCAL DISEASE; CLINICAL-FEATURES; PURPURA FULMINANS; ADULTS; DIAGNOSIS; SEPSIS; PATHOGENESIS; INFECTIONS; EPISODES C1 [Manian, Farrin A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alame, Diana] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Manian, Farrin A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Alame, Diana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 44 TC 0 Z9 0 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 9 PY 2015 VL 372 IS 15 BP 1454 EP 1462 DI 10.1056/NEJMcpc1415165 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CF2ZV UT WOS:000352417900012 PM 25853750 ER PT J AU Hibar, DP Stein, JL Renteria, ME Arias-Vasquez, A Desrivieres, S Jahanshad, N Toro, R Wittfeld, K Abramovic, L Andersson, M Aribisala, BS Armstrong, NJ Bernard, M Bohlken, MM Boks, MP Bralten, J Brown, AA Chakravarty, MM Chen, Q Ching, CRK Cuellar-Partida, G den Braber, A Giddaluru, S Goldman, AL Grimm, O Guadalupe, T Hass, J Woldehawariat, G Holmes, AJ Hoogman, M Janowitz, D Jia, TY Kim, S Klein, M Kraemer, B Lee, PH Loohuis, LMO Luciano, M Macare, C Mather, KA Mattheisen, M Milaneschi, Y Nho, K Papmeyer, M Ramasamy, A Risacher, SL Roiz-Santianez, R Rose, EJ Salami, A Samann, PG Schmaal, L Schork, AJ Shin, J Strike, LT Teumer, A van Donkelaar, MMJ van Eijk, KR Walters, RK Westlye, LT Whelan, CD Winkler, AM Zwiers, MP Alhusaini, S Athanasiu, L Ehrlich, S Hakobjan, MMH Hartberg, CB Haukvik, UK Heister, AJGAM Hoehn, D Kasperaviciute, D Liewald, DCM Lopez, LM Makkinje, RRR Matarin, M Naber, MAM Mckay, DR Needham, M Nugent, AC Putz, B Royle, NA Shen, L Sprooten, E Trabzuni, D van der Marel, SSL van Hulzen, KJE Walton, E Wolf, C Almasy, L Ames, D Arepalli, S Assareh, AA Bastin, ME Brodaty, H Bulayeva, KB Carless, MA Cichon, S Corvin, A Curran, JE Czisch, M de Zubicaray, GI Dillman, A Duggirala, R Dyer, TD Erk, S Fedko, IO Ferrucci, L Foroud, TM Fox, PT Fukunaga, M Gibbs, JR Goring, HHH Green, RC Guelfi, S Hansell, NK Hartman, CA Hegenscheid, K Heinz, A Hernandez, DG Heslenfeld, DJ Hoekstra, PJ Holsboer, F Homuth, G Hottenga, JJ Ikeda, M Jack, CR Jenkinson, M Johnson, R Kanai, R Keil, M Kent, JW Kochunov, P Kwok, JB Lawrie, SM Liu, XM Longo, DL McMahon, KL Meisenzah, E Melle, I Mahnke, S Montgomery, GW Mostert, JC Muhleisen, TW Nalls, MA Nichols, TE Nilsson, LG Nothen, MM Ohi, K Olvera, RL Perez-Iglesias, R Pike, GB Potkin, SG Reinvang, I Reppermund, S Rietschel, M Romanczuk-Seiferth, N Rosen, GD Rujescu, D Schnell, K Schofield, PR Smith, C Steen, VM Sussmann, JE Thalamuthu, A Toga, AW Traynor, BJ Troncoso, J Turner, JA Hernandez, MCV van't Ent, D van der Brug, M van der Wee, NJA van Tol, MJ Veltman, DJ Wassink, TH Westman, E Zielke, RH Zonderman, AB Ashbrook, DG Hager, R Lu, L McMahon, FJ Morris, DW Williams, RW Brunner, HG Buckner, RL Buitelaar, JK Cahn, W Calhoun, VD Cavalleri, GL Crespo-Facorro, B Dale, AM Davies, GE Delanty, N Depondt, C Djurovic, S Drevets, WC Espeseth, T Gollub, RL Ho, BC Hoffman, W Hosten, N Kahn, RS Le Hellard, S Meyer-Lindenberg, A Muller-Myhsok, B Nauck, M Nyberg, L Pandolfo, M Penninx, BWJH Roffman, JL Sisodiya, SM Smoller, JW van Bokhoven, H van Haren, NEM Volzke, H Walter, H Weiner, MW Wen, W White, T Agartz, I Andreassen, OA Blangero, J Boomsma, DI Brouwer, RM Cannon, DM Cookson, MR de Geus, EJC Deary, IJ Donohoe, G Fernandez, G Fisher, SE Francks, C Glahn, DC Grabe, HJ Gruber, O Hardy, J Hashimoto, R Pol, HEH Jonsson, EG Kloszewska, I Lovestone, S Mattay, VS Mecocci, P McDonald, C McIntosh, AM Ophoff, RA Paus, T Pausova, Z Ryten, M Sachdev, PS Saykin, AJ Simmons, A Singleton, A Soininen, H Wardlaw, JM Weale, ME Weinberger, DR Adams, HHH Launer, LJ Seiler, S Schmidt, R Chauhan, G Satizabal, CL Becker, JT Yanek, L van der Lee, SJ Ebling, M Fischl, B Longstreth, WT Greve, D Schmidt, H Nyquist, P Vinke, LN van Duijn, CM Xue, LT Mazoyer, B Bis, JC Gudnason, V Seshadri, S Ikram, MA Martin, NG Wright, MJ Schumann, G Franke, B Thompson, PM Medland, SE AF Hibar, Derrek P. Stein, Jason L. Renteria, Miguel E. Arias-Vasquez, Alejandro Desrivieres, Sylvane Jahanshad, Neda Toro, Roberto Wittfeld, Katharina Abramovic, Lucija Andersson, Micael Aribisala, Benjamin S. Armstrong, Nicola J. Bernard, Manon Bohlken, Marc M. Boks, Marco P. Bralten, Janita Brown, Andrew A. Chakravarty, M. Mallar Chen, Qiang Ching, Christopher R. K. Cuellar-Partida, Gabriel den Braber, Anouk Giddaluru, Sudheer Goldman, Aaron L. Grimm, Oliver Guadalupe, Tulio Hass, Johanna Woldehawariat, Girma Holmes, Avram J. Hoogman, Martine Janowitz, Deborah Jia, Tianye Kim, Sungeun Klein, Marieke Kraemer, Bernd Lee, Phil H. Loohuis, Loes M. Olde Luciano, Michelle Macare, Christine Mather, Karen A. Mattheisen, Manuel Milaneschi, Yuri Nho, Kwangsik Papmeyer, Martina Ramasamy, Adaikalavan Risacher, Shannon L. Roiz-Santianez, Roberto Rose, Emma J. Salami, Alireza Saemann, Philipp G. Schmaal, Lianne Schork, Andrew J. Shin, Jean Strike, Lachlan T. Teumer, Alexander van Donkelaar, Marjolein M. J. van Eijk, Kristel R. Walters, Raymond K. Westlye, Lars T. Whelan, Christopher D. Winkler, Anderson M. Zwiers, Marcel P. Alhusaini, Saud Athanasiu, Lavinia Ehrlich, Stefan Hakobjan, Marina M. H. Hartberg, Cecilie B. Haukvik, Unn K. Heister, Angelien J. G. A. M. Hoehn, David Kasperaviciute, Dalia Liewald, David C. M. Lopez, Lorna M. Makkinje, Remco R. R. Matarin, Mar Naber, Marlies A. M. McKay, D. Reese Needham, Margaret Nugent, Allison C. Puetz, Benno Royle, Natalie A. Shen, Li Sprooten, Emma Trabzuni, Daniah van der Marel, Saskia S. L. van Hulzen, Kimm J. E. Walton, Esther Wolf, Christiane Almasy, Laura Ames, David Arepalli, Sampath Assareh, Amelia A. Bastin, Mark E. Brodaty, Henry Bulayeva, Kazima B. Carless, Melanie A. Cichon, Sven Corvin, Aiden Curran, Joanne E. Czisch, Michael de Zubicaray, Greig I. Dillman, Allissa Duggirala, Ravi Dyer, Thomas D. Erk, Susanne Fedko, Iryna O. Ferrucci, Luigi Foroud, Tatiana M. Fox, Peter T. Fukunaga, Masaki Gibbs, J. Raphael Goering, Harald H. H. Green, Robert C. Guelfi, Sebastian Hansell, Narelle K. Hartman, Catharina A. Hegenscheid, Katrin Heinz, Andreas Hernandez, Dena G. Heslenfeld, Dirk J. Hoekstra, Pieter J. Holsboer, Florian Homuth, Georg Hottenga, Jouke-Jan Ikeda, Masashi Jack, Clifford R., Jr. Jenkinson, Mark Johnson, Robert Kanai, Ryota Keil, Maria Kent, Jack W., Jr. Kochunov, Peter Kwok, John B. Lawrie, Stephen M. Liu, Xinmin Longo, Dan L. McMahon, Katie L. Meisenzah, Eva Melle, Ingrid Mahnke, Sebastian Montgomery, Grant W. Mostert, Jeanette C. Muehleisen, Thomas W. Nalls, Michael A. Nichols, Thomas E. Nilsson, Lars G. Noethen, Markus M. Ohi, Kazutaka Olvera, Rene L. Perez-Iglesias, Rocio Pike, G. Bruce Potkin, Steven G. Reinvang, Ivar Reppermund, Simone Rietschel, Marcella Romanczuk-Seiferth, Nina Rosen, Glenn D. Rujescu, Dan Schnell, Knut Schofield, Peter R. Smith, Colin Steen, Vidar M. Sussmann, Jessika E. Thalamuthu, Anbupalam Toga, Arthur W. Traynor, Bryan J. Troncoso, Juan Turner, Jessica A. Valdes Hernandez, Maria C. van't Ent, Dennis van der Brug, Marcel van der Wee, Nic J. A. van Tol, Marie-Jose Veltman, Dick J. Wassink, Thomas H. Westman, Eric Zielke, Ronald H. Zonderman, Alan B. Ashbrook, David G. Hager, Reinmar Lu, Lu McMahon, Francis J. Morris, Derek W. Williams, Robert W. Brunner, Han G. Buckner, Randy L. Buitelaar, Jan K. Cahn, Wiepke Calhoun, Vince D. Cavalleri, Gianpiero L. Crespo-Facorro, Benedicto Dale, Anders M. Davies, Gareth E. Delanty, Norman Depondt, Chantal Djurovic, Srdjan Drevets, Wayne C. Espeseth, Thomas Gollub, Randy L. Ho, Beng-Choon Hoffman, Wolfgang Hosten, Norbert Kahn, Rene S. Le Hellard, Stephanie Meyer-Lindenberg, Andreas Mueller-Myhsok, Bertram Nauck, Matthias Nyberg, Lars Pandolfo, Massimo Penninx, Brenda W. J. H. Roffman, Joshua L. Sisodiya, Sanjay M. Smoller, Jordan W. van Bokhoven, Hans van Haren, Neeltje E. M. Voelzke, Henry Walter, Henrik Weiner, Michael W. Wen, Wei White, Tonya Agartz, Ingrid Andreassen, Ole A. Blangero, John Boomsma, Dorret I. Brouwer, Rachel M. Cannon, Dara M. Cookson, Mark R. de Geus, Eco J. C. Deary, Ian J. Donohoe, Gary Fernandez, Guillen Fisher, Simon E. Francks, Clyde Glahn, David C. Grabe, Hans J. Gruber, Oliver Hardy, John Hashimoto, Ryota Pol, Hilleke E. Hulshoff Joensson, Erik G. Kloszewska, Iwona Lovestone, Simon Mattay, Venkata S. Mecocci, Patrizia McDonald, Colm McIntosh, Andrew M. Ophoff, Roel A. Paus, Tomas Pausova, Zdenka Ryten, Mina Sachdev, Perminder S. Saykin, Andrew J. Simmons, Andy Singleton, Andrew Soininen, Hilkka Wardlaw, Joanna M. Weale, Michael E. Weinberger, Daniel R. Adams, Hieab H. H. Launer, Lenore J. Seiler, Stephan Schmidt, Reinhold Chauhan, Ganesh Satizabal, Claudia L. Becker, James T. Yanek, Lisa van der Lee, Sven J. Ebling, Maritza Fischl, Bruce Longstreth, W. T., Jr. Greve, Douglas Schmidt, Helena Nyquist, Paul Vinke, Louis N. van Duijn, Cornelia M. Xue, Luting Mazoyer, Bernard Bis, Joshua C. Gudnason, Vilmundur Seshadri, Sudha Ikram, M. Arfan Martin, Nicholas G. Wright, Margaret J. Schumann, Gunter Franke, Barbara Thompson, Paul M., Jr. Medland, Sarah E. CA Alzheimers Dis Neuroimaging CHARGE Consortium EPIGEN IMAGEN SYS TI Common genetic variants influence human subcortical brain structures SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; BASAL GANGLIA; NERVOUS-SYSTEM; EXPRESSION; CHROMATIN; KINECTIN; IDENTIFICATION; ORGANIZATION; SEGMENTATION; HIPPOCAMPAL AB The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. C1 [Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Ching, Christopher R. K.; Whelan, Christopher D.; Thompson, Paul M., Jr.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90292 USA. [Stein, Jason L.; Ching, Christopher R. K.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA. [Renteria, Miguel E.; Cuellar-Partida, Gabriel; Strike, Lachlan T.; Hansell, Narelle K.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Arias-Vasquez, Alejandro; Bralten, Janita; Hoogman, Martine; Klein, Marieke; van Donkelaar, Marjolein M. J.; Hakobjan, Marina M. H.; Heister, Angelien J. G. A. M.; Makkinje, Remco R. R.; Naber, Marlies A. M.; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Mostert, Jeanette C.; Brunner, Han G.; van Bokhoven, Hans; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Bralten, Janita; Buitelaar, Jan K.; Fernandez, Guillen] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Bralten, Janita; Ching, Christopher R. K.; Hoogman, Martine; Klein, Marieke; van Donkelaar, Marjolein M. J.; Zwiers, Marcel P.; Hakobjan, Marina M. H.; Heister, Angelien J. G. A. M.; Makkinje, Remco R. R.; Naber, Marlies A. M.; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Mostert, Jeanette C.; Brunner, Han G.; Buitelaar, Jan K.; van Bokhoven, Hans; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6500 GL Nijmegen, Netherlands. [Desrivieres, Sylvane; Jia, Tianye; Macare, Christine; Schumann, Gunter] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London SE5 8AF, England. [Toro, Roberto] Inst Pasteur, Lab Human Genet & Cognit Funct, F-75015 Paris, France. [Toro, Roberto] Inst Pasteur, CNRS, URA Genes Synapses & Cognit 2182, F-75015 Paris, France. [Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, F-75015 Paris, France. [Wittfeld, Katharina; Hoffman, Wolfgang] German Ctr Neurodegenerat Dis DZNE, D-17487 Greifswald, Germany. [Wittfeld, Katharina; Janowitz, Deborah; Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat, D-17489 Greifswald, Germany. [Abramovic, Lucija; Bohlken, Marc M.; Boks, Marco P.; van Eijk, Kristel R.; Cahn, Wiepke; Kahn, Rene S.; van Haren, Neeltje E. M.; Brouwer, Rachel M.; Pol, Hilleke E. Hulshoff; Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, NL-3584 CX Utrecht, Netherlands. [Andersson, Micael; Salami, Alireza; Nilsson, Lars G.; Nyberg, Lars] Umea Univ, Ctr Funct Brain Imaging UFBI, S-90187 Umea, Sweden. [Aribisala, Benjamin S.; Royle, Natalie A.; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. [Aribisala, Benjamin S.; Royle, Natalie A.; Wardlaw, Joanna M.] Lagos State Univ, Dept Comp Sci, Lagos, Nigeria. [Aribisala, Benjamin S.; Royle, Natalie A.; Bastin, Mark E.; Wardlaw, Joanna M.] Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh EH4 2XU, Midlothian, Scotland. [Armstrong, Nicola J.; Mather, Karen A.; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Reppermund, Simone; Thalamuthu, Anbupalam; Wen, Wei; Sachdev, Perminder S.] Univ New S Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW 2052, Australia. [Armstrong, Nicola J.] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia. [Bernard, Manon; Shin, Jean; Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Brown, Andrew A.; Athanasiu, Lavinia; Hartberg, Cecilie B.; Haukvik, Unn K.; Melle, Ingrid; Djurovic, Srdjan; Agartz, Ingrid; Andreassen, Ole A.; Joensson, Erik G.] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, N-0316 Oslo, Norway. [Brown, Andrew A.; Westlye, Lars T.; Athanasiu, Lavinia; Melle, Ingrid; Espeseth, Thomas; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, N-0424 Oslo, Norway. [Chakravarty, M. Mallar] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ H4H 1R3, Canada. [Chakravarty, M. Mallar] McGill Univ, Dept Psychiat & Biomed Engn, Montreal, PQ H3A 2B4, Canada. [Chen, Qiang; Goldman, Aaron L.; Mattay, Venkata S.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Ching, Christopher R. K.] Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA 90095 USA. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam, Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam Med Ctr, NL-1081 BT Amsterdam, Netherlands. [Giddaluru, Sudheer; Steen, Vidar M.; Le Hellard, Stephanie] Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5021 Bergen, Norway. [Giddaluru, Sudheer; Steen, Vidar M.; Le Hellard, Stephanie] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Grimm, Oliver; Rietschel, Marcella; Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. [Guadalupe, Tulio; Fisher, Simon E.; Francks, Clyde] Max Planck Inst Psycholinguist, Language & Genet Dept, NL-6525 XD Nijmegen, Netherlands. [Guadalupe, Tulio] Int Max Planck Res Sch Language, NL-6525 XD Nijmegen, Netherlands. [Hass, Johanna; Ehrlich, Stefan; Walton, Esther] Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [Woldehawariat, Girma; Nugent, Allison C.; Liu, Xinmin; McMahon, Francis J.; Drevets, Wayne C.; Cannon, Dara M.] NIMH, Human Genet Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Woldehawariat, Girma; Nugent, Allison C.; Liu, Xinmin; McMahon, Francis J.; Drevets, Wayne C.; Cannon, Dara M.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT 06511 USA. [Holmes, Avram J.; Lee, Phil H.; Ehrlich, Stefan; Buckner, Randy L.; Gollub, Randy L.; Roffman, Joshua L.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Shen, Li] Indiana Univ Sch Med, Ctr Computat Biol & Bloinformat, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Kraemer, Bernd; Keil, Maria; Gruber, Oliver] Univ Med Ctr, Dept Psychiat & Psychotherapy, Ctr Translat Res Syst Neurosci & Psychiat, D-37075 Gottingen, Germany. [Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02115 USA. [Lee, Phil H.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA 02141 USA. [Lee, Phil H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Loohuis, Loes M. Olde; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Luciano, Michelle; Liewald, David C. M.; Lopez, Lorna M.; Royle, Natalie A.; Bastin, Mark E.; Deary, Ian J.; McIntosh, Andrew M.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Mattheisen, Manuel] Aarhus Univ Hosp, Dept Biomed, DK-8000 Aarhus, Denmark. [Mattheisen, Manuel] iPSYCH, Ludbeck Fdn Initiat Integrat Psychiat Res, DK-8000 Aarhus, Denmark. [Mattheisen, Manuel] iPSYCH, Ludbeck Fdn Initiat Integrat Psychiat Res, DK-8000 Copenhagen, Denmark. [Mattheisen, Manuel] Aarhus Univ, iSEQ, Ctr Integrated Sequencing, DK-8000 Aarhus, Denmark. [Milaneschi, Yuri; Schmaal, Lianne; Veltman, Dick J.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr GGZ InGeest, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Papmeyer, Martina; Sprooten, Emma; Lawrie, Stephen M.; Sussmann, Jessika E.; McIntosh, Andrew M.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. [Ramasamy, Adaikalavan; Ryten, Mina; Weale, Michael E.] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England. [Ramasamy, Adaikalavan; Trabzuni, Daniah; Gibbs, J. Raphael; Guelfi, Sebastian; Hernandez, Dena G.; Hardy, John; Ryten, Mina] UCL, Inst Neurol, Reta Lila Weston Inst, London WC1N 3BG, England. [Ramasamy, Adaikalavan; Trabzuni, Daniah; Gibbs, J. Raphael; Guelfi, Sebastian; Hernandez, Dena G.; Hardy, John; Ryten, Mina] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Roiz-Santianez, Roberto; Crespo-Facorro, Benedicto] Univ Cantabria, IDIVAL, Sch Med, Dept Psychiat,Univ Hosp Marques de Valdecilla, Santander 39008, Spain. [Roiz-Santianez, Roberto; Perez-Iglesias, Rocio; Crespo-Facorro, Benedicto] Cibersam Ctr Invest Biomed Red Salud Mental, Madrid 28029, Spain. [Rose, Emma J.; Needham, Margaret; Corvin, Aiden; Morris, Derek W.; Donohoe, Gary] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Rose, Emma J.; Needham, Margaret; Corvin, Aiden; Morris, Derek W.; Donohoe, Gary] Univ Dublin Trinity Coll, Dept Psychiat, Trinity Coll Inst Psychiat, Dublin 2, Ireland. [Rose, Emma J.] Univ Maryland, Sch Med, Dept Psychiat, Translat Res Advers Neurodev & Subst Abuse C TRAN, Columbia, MD 21045 USA. [Salami, Alireza] Karolinska Inst, Aging Res Ctr, S-11330 Stockholm, Sweden. [Salami, Alireza] Stockholm Univ, S-11330 Stockholm, Sweden. [Saemann, Philipp G.; Hoehn, David; Puetz, Benno; Wolf, Christiane; Czisch, Michael; Holsboer, Florian; Mueller-Myhsok, Bertram; Gruber, Oliver] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Schork, Andrew J.] Univ Calif San Diego, Dept Neurosci, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Schork, Andrew J.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92161 USA. [Strike, Lachlan T.; de Zubicaray, Greig I.; Wright, Margaret J.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Strike, Lachlan T.; McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia. [Teumer, Alexander; Hoffman, Wolfgang; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany. [Walters, Raymond K.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Walters, Raymond K.] Broad Inst Harvard & MIT, Med & Populat Genet Program, Boston, MA 02142 USA. [Westlye, Lars T.; Reinvang, Ivar; Espeseth, Thomas] Univ Oslo, Dept Psychol, N-0373 Oslo, Norway. [Winkler, Anderson M.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England. [Winkler, Anderson M.; McKay, D. Reese; Sprooten, Emma; Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Alhusaini, Saud] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. [Alhusaini, Saud; Cavalleri, Gianpiero L.; Delanty, Norman] Royal Coll Surg, Mol & Cellular Therapeut, Dublin 2, Ireland. [Ehrlich, Stefan; Gollub, Randy L.; Ebling, Maritza; Fischl, Bruce; Greve, Douglas; Vinke, Louis N.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hartberg, Cecilie B.; Agartz, Ingrid] Diakonhjemmet Hosp, Dept Psychiat Res & Dev, N-0319 Oslo, Norway. [Kasperaviciute, Dalia; Sisodiya, Sanjay M.] UCL, Inst Neurol, London, England. [Kasperaviciute, Dalia; Sisodiya, Sanjay M.] Epilepsy Soc, London WC1N 3BG, England. [Kasperaviciute, Dalia] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W12 0NN, England. [Matarin, Mar] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. [McKay, D. Reese; Sprooten, Emma; Glahn, David C.] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06106 USA. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Almasy, Laura; Carless, Melanie A.; Curran, Joanne E.; Duggirala, Ravi; Dyer, Thomas D.; Goering, Harald H. H.; Kent, Jack W., Jr.; Blangero, John] Texas Biomed Res Inst, San Antonio, TX 78245 USA. [Almasy, Laura; Dyer, Thomas D.; Fox, Peter T.; Blangero, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ames, David] Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic 3052, Australia. [Ames, David; Gibbs, J. Raphael; Hernandez, Dena G.] Univ Melbourne, Acad Unit Psychiat Old Age, Melbourne, Vic 3101, Australia. [Arepalli, Sampath; Dillman, Allissa; Nalls, Michael A.; Traynor, Bryan J.; Cookson, Mark R.; Singleton, Andrew] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Bastin, Mark E.; Valdes Hernandez, Maria C.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland. [Bulayeva, Kazima B.] Russian Acad Sci, IN Vavilov Inst Gen Genet, Moscow 119333, Russia. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, CH-4055 Basel, Switzerland. [Cichon, Sven; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Cichon, Sven; Heinz, Andreas; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, D-53127 Bonn, Germany. [Cichon, Sven; Heinz, Andreas; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, D-53127 Bonn, Germany. [Erk, Susanne; Mahnke, Sebastian; Romanczuk-Seiferth, Nina; Walter, Henrik; Saykin, Andrew J.] Charite, CCM, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 20892 USA. [Foroud, Tatiana M.; Olvera, Rene L.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Fukunaga, Masaki] Osaka Univ, Immunol Frontier Res Ctr, Biofunct Imaging, Osaka 5650871, Japan. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Green, Robert C.; Gollub, Randy L.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hartman, Catharina A.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [Hegenscheid, Katrin; Hosten, Norbert] Univ Med Greifswald, Inst Diagnost Radiolou & Neuroradiol, D-17475 Greifswald, Germany. [Heslenfeld, Dirk J.] Vrije Univ Amsterdam, Dept Cognit, NL-1081 BT Amsterdam, Netherlands. [Heslenfeld, Dirk J.] Vrije Univ Amsterdam, Dept Clin Neuropsychol, NL-1081 BT Amsterdam, Netherlands. [Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17489 Greifswald, Germany. [Ikeda, Masashi] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan. [Jack, Clifford R., Jr.] Mayo Clin, Radiol, Rochester, MN 55905 USA. [Jenkinson, Mark; Nichols, Thomas E.] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England. [Johnson, Robert; Zielke, Ronald H.] Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA. [Kanai, Ryota] Univ Sussex, Sch Psychol, Brighton BN1 9QH, E Sussex, England. [Kanai, Ryota] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Kochunov, Peter] Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Kwok, John B.; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Kwok, John B.; Schofield, Peter R.] UNSW, Sch Med Sci, Sydney, NSW 2052, Australia. [Liu, Xinmin] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. [Meisenzah, Eva; Rujescu, Dan] Univ Munich, Dept Psychiat, D-80336 Munich, Germany. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, WMG, Coventry CV4 7AL, W Midlands, England. [Ohi, Kazutaka] Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka 5650871, Japan. [Perez-Iglesias, Rocio] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Pike, G. Bruce] Univ Calgary, Dept Neurol, Calgary, AB T2N 2T9, Canada. [Pike, G. Bruce] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 2T9, Canada. [Potkin, Steven G.] Univ Calif Irvine, Psychiat & Human Behav, Irvine, CA 92617 USA. [Rosen, Glenn D.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Rosen, Glenn D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schnell, Knut] Heidelberg Univ Hosp, Dept Gen Psychiat, D-69115 Heidelberg, Germany. [Smith, Colin] Univ Edinburgh, MRC, Sudden Death Brain Bank Project, Dept Neuropathol, Edinburgh EH8 9AG, Midlothian, Scotland. [Toga, Arthur W.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA 90033 USA. [Troncoso, Juan] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Turner, Jessica A.] Georgia State Univ, Neurosci Inst, Atlanta, GA 30302 USA. [van der Brug, Marcel] Genentech Inc, San Francisco, CA 94080 USA. [van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Psychiat, NL-2333 ZA Leiden, Netherlands. [van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Leiden Inst Brain & Cogniton, NL-2333 ZA Leiden, Netherlands. [van Tol, Marie-Jose] Univ Groningen, Univ Med Ctr Groningen, Neuroimaging Ctr, NL-9713 AW Groningen, Netherlands. [Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Westman, Eric] Karolinska Inst, Dept Neurobiol Care Sci & Soc, SE-14183 Stockholm, Sweden. [Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Intramural Res Program, Bethesda, MD 20892 USA. [Ashbrook, David G.; Hager, Reinmar] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Lu, Lu; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Ctr Integrat & Translat Genom, Memphis, TN 38163 USA. [Lu, Lu; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Dept Genet Genom & Informat, Memphis, TN 38163 USA. [Lu, Lu] Nantong Univ, Coll Med, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Peoples R China. [Morris, Derek W.; Donohoe, Gary] Natl Univ Ireland Galway, Sch Psychol, Cognit Genet & Therapy Grp, Galway, Ireland. [Morris, Derek W.; Donohoe, Gary] Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland. [Brunner, Han G.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands. 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[Depondt, Chantal; Pandolfo, Massimo] Univ Libre Bruxelles, Hop Erasme, Dept Neurol, B-1070 Brussels, Belgium. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, N-0450 Oslo, Norway. [Drevets, Wayne C.] Johnson & Johnson, Janssen Res & Dev, Titusville, NJ 08560 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany. [Mueller-Myhsok, Bertram] Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Weiner, Michael W.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [White, Tonya] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [White, Tonya; Adams, Hieab H. H.; Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, NL-3015 CN Rotterdam, Netherlands. [Agartz, Ingrid; Joensson, Erik G.] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. [Cannon, Dara M.; McDonald, Colm] Natl Univ Ireland Galway, Coll Med Nursing & Hlth Sci, Clin Neuroimaging Lab, Galway, Ireland. [Grabe, Hans J.] HELIOS Hosp, Dept Psychiat & Psychotherapy, D-18435 Stralsund, Germany. [Hashimoto, Ryota] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka 5650871, Japan. [Kloszewska, Iwona] Med Univ Lodz, PL-90419 Lodz, Poland. [Lovestone, Simon] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England. [Lovestone, Simon] Kings Coll London, NIHR Dementia Biomed Res Unit, London SE5 8AF, England. [Mattay, Venkata S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mecocci, Patrizia] Univ Perugia, Dept Med, Sect Gerontol & Geriat, I-06156 Perugia, Italy. [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Paus, Tomas] Univ Toronto, Dept Psychol, Toronto, ON M5T 1R8, Canada. 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[Becker, James T.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychol, Dietrich Sch Arts & Sci, Pittsburgh, PA 15260 USA. [Yanek, Lisa] Johns Hopkins Sch Med, Gen Internal Med, Baltimore, MD 21205 USA. [Ebling, Maritza; Fischl, Bruce; Greve, Douglas; Vinke, Louis N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Al Lab, Boston, MA 02141 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schmidt, Helena] Med Univ, Inst Mol Biol & Biochem, A-8010 Graz, Austria. [Nyquist, Paul] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA. [Xue, Luting] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Mazoyer, Bernard] CEA, Grp Imagerie Neurofonct, UMR5296, CNRS, F-33076 Bordeaux, France. [Mazoyer, Bernard] Univ Bordeaux, F-33076 Bordeaux, France. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Iceland Heart Assoc, IS-101 Reykjavik, Iceland. RP Thompson, PM (reprint author), Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90292 USA. EM pthomp@usc.edu; Sarah.Medland@qimrberghofer.edu.au RI Karen, Mather/O-9795-2016; Winkler, Anderson/P-7773-2016; Luciano, Michelle/F-7277-2010; Tzourio, christophe/B-4015-2009; Meyer-Lindenberg, Andreas/H-1076-2011; Cuellar Partida, Gabriel/C-6686-2017; Poustka, Luise/D-9299-2017; Montgomery, Grant/B-7148-2008; Makkinje, Remco/Q-2406-2015; Mattheisen, Manuel/B-4949-2012; Hager, Reinmar/F-8659-2012; Hansell, Narelle/A-4553-2016; Wright, Margaret/A-4560-2016; Hakobjan, Marina/A-5594-2016; Arias Vasquez, Alejandro/E-4762-2012; Kowall, Neil/G-6364-2012; Weale, Michael/F-2587-2010; McMahon, Katie/C-6440-2009; Matarin, Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Walter, Henrik/O-2612-2013; Pike, Bruce/K-5562-2014; Fernandez, Guillen/B-3771-2009; Franke, Barbara/D-4836-2009; Zwiers, Marcel/D-2968-2009; Gudnason, Vilmundur/K-6885-2015; Singleton, Andrew/C-3010-2009; Brunner, Han/C-9928-2013; Arias Vasquez, A./L-4175-2015; Williams, Steve/D-6979-2011; Bokhoven, J.H.L.M./H-8015-2014; Cavalleri, Gianpiero/A-6632-2010; McDonald, Colm/C-1430-2009; Jack, Clifford/F-2508-2010; Westman, Eric/H-5771-2011; Bralten, Janita/D-4647-2011; Hoogman, Martine/G-8958-2015; Roiz-Santianez, Roberto/H-6462-2015; Fisher, Simon/E-9130-2012; Hardy, John/C-2451-2009; Mostert, Jeanette/E-4745-2015; Lubbe, Steven/L-8261-2013; Simmons, Andrew/B-8848-2008; de Zubicaray, Greig/B-1763-2008; OI Karen, Mather/0000-0003-4143-8941; Winkler, Anderson/0000-0002-4169-9781; Luciano, Michelle/0000-0003-0935-7682; Tzourio, christophe/0000-0002-6517-2984; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Cuellar Partida, Gabriel/0000-0001-7648-4097; Ehrlich, Stefan/0000-0003-2132-4445; Nees, Frauke/0000-0002-7796-8234; Ashbrook, David/0000-0002-7397-8910; Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Hansell, Narelle/0000-0002-8229-9741; Wright, Margaret/0000-0001-7133-4970; Arias Vasquez, Alejandro/0000-0002-4786-0169; Kowall, Neil/0000-0002-6624-0213; Weale, Michael/0000-0003-4593-1186; McMahon, Katie/0000-0002-6357-615X; Matarin, Mar/0000-0002-4717-5735; Melle, Ingrid /0000-0002-9783-548X; McMahon, Francis/0000-0002-9469-305X; Jenkinson, Mark/0000-0001-6043-0166; Seshadri, Sudha/0000-0001-6135-2622; Corvin, Aiden/0000-0001-6717-4089; Walton, Esther/0000-0002-0935-2200; Nyberg, Lars/0000-0002-3367-1746; Delaney, Norman/0000-0002-3953-9842; Whelan, Christopher/0000-0003-0308-5583; Nugent, Allison/0000-0003-2569-2480; de Geus, Eco/0000-0001-6022-2666; Kanai, Ryota/0000-0002-0186-2687; McIntosh, Andrew/0000-0002-0198-4588; Pike, Bruce/0000-0001-8924-683X; Fernandez, Guillen/0000-0002-5522-0604; Franke, Barbara/0000-0003-4375-6572; Zwiers, Marcel/0000-0001-5483-2935; Gudnason, Vilmundur/0000-0001-5696-0084; Williams, Steve/0000-0003-4299-1941; Jack, Clifford/0000-0001-7916-622X; Hoogman, Martine/0000-0002-1261-7628; Roiz-Santianez, Roberto/0000-0002-5176-2983; Fisher, Simon/0000-0002-3132-1996; Mostert, Jeanette/0000-0002-0033-1622; Simmons, Andrew/0000-0003-2306-5811; de Zubicaray, Greig/0000-0003-4506-0579; Flor, Herta/0000-0003-4809-5398; Shen, Li/0000-0002-5443-0503; Zonderman, Alan B/0000-0002-6523-4778; Vaidya, Dhananjay/0000-0002-7164-1601; Beiser, Alexa/0000-0001-8551-7778; Medland, Sarah/0000-0003-1382-380X; Westlye, Lars T./0000-0001-8644-956X; Williams, Robert/0000-0001-8924-4447; Desrivieres, Sylvane/0000-0002-9120-7060; Preda, Adrian /0000-0003-3373-2438; Boks, Marco/0000-0001-6163-7484; Satizabal, Claudia/0000-0002-1115-4430; Westman, Eric/0000-0002-3115-2977; Cavalleri, Gianpiero/0000-0002-9802-0506; Jonsson, Erik/0000-0001-8368-6332; Brown, Andrew/0000-0002-8087-3033; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Sachdev, Perminder/0000-0002-9595-3220 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Chief Scientist Office [ETM/84]; Medical Research Council [G0700704, G0701120, G0802462, G0900908, G1001245, MR/K026992/1, MR/L016400/1]; NCATS NIH HHS [TL1 TR000096, UL1 TR001108, UL1 TR001120]; NIA NIH HHS [P50 AG005134, P50 AG005133, P50 AG005146, R01 AG033193, R01 AG040060, RF1 AG041915, U01 AG049505, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846, R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367]; NINDS NIH HHS [R01 NS017950, T32 NS048004]; NLM NIH HHS [K99 LM011384, R00 LM011384]; Wellcome Trust [100309, 104036] NR 57 TC 108 Z9 109 U1 23 U2 121 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 APR 9 PY 2015 VL 520 IS 7546 BP 224 EP U216 DI 10.1038/nature14101 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3NA UT WOS:000352454600040 PM 25607358 ER PT J AU Fillmore, CM Xu, CX Desai, PT Berry, JM Rowbotham, SP Lin, YJ Zhang, HK Marquez, VE Hammerman, PS Wong, KK Kim, CF AF Fillmore, Christine M. Xu, Chunxiao Desai, Pooja T. Berry, Joanne M. Rowbotham, Samuel P. Lin, Yi-Jang Zhang, Haikuo Marquez, Victor E. Hammerman, Peter S. Wong, Kwok-Kin Kim, Carla F. TI EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors SO NATURE LA English DT Article ID GENE-EXPRESSION PROFILES; CANCER CELL-LINES; DRUG-COMBINATION; MICROARRAY DATA; ADENOCARCINOMA; MUTATIONS; COMPLEXES; POLYCOMB; SURVIVAL; SWI/SNF AB Non-small-cell lung cancer is the leading cause of cancer-related death worldwide(1). Chemotherapies such as the topoisomerase II (TopoII) inhibitor etoposide effectively reduce disease in a minority of patients with this cancer(2,3); therefore, alternative drug targets, including epigenetic enzymes, are under consideration for therapeutic intervention(4). A promising potential epigenetic target is the methyltransferase EZH2, which in the context of the polycomb repressive complex 2 (PRC2) is well known to tri-methylate histone H3 at lysine 27 (H3K27me3) and elicit gene silencing(5). Here we demonstrate that EZH2 inhibition has differential effects on the TopoII inhibitor response of non-small-cell lung cancers in vitro and in vivo. EGFR and BRG1 mutations are genetic biomarkers that predict enhanced sensitivity to TopoII inhibitor in response to EZH2 inhibition. BRG1 loss-of-function mutant tumours respond to EZH2 inhibition with increased S phase, anaphase bridging, apoptosis and TopoII inhibitor sensitivity. Conversely, EGFR and BRG1 wild-type tumours upregulate BRG1 in response to EZH2 inhibition and ultimately become more resistant to TopoII inhibitor. EGFR gain-of-function mutant tumours are also sensitive to dual EZH2 inhibition and TopoII inhibitor, because of genetic antagonism between EGFR and BRG1. These findings suggest an opportunity for precision medicine in the genetically complex disease of non-small-cell lung cancer. C1 [Fillmore, Christine M.; Desai, Pooja T.; Berry, Joanne M.; Rowbotham, Samuel P.; Kim, Carla F.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Fillmore, Christine M.; Rowbotham, Samuel P.; Lin, Yi-Jang; Kim, Carla F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Fillmore, Christine M.; Rowbotham, Samuel P.; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Xu, Chunxiao; Zhang, Haikuo; Hammerman, Peter S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xu, Chunxiao; Zhang, Haikuo; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. RP Kim, CF (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM carla.kim@childrens.harvard.edu FU Ladies Auxiliary to the Veterans of Foreign Wars; American Cancer Society [PF-12-151-01-DMC]; Uniting Against Lung Cancer Young Investigator Award; Boston University Undergraduate Research Opportunities Program; American Cancer Society Research Scholar Grant [RSG-08-082-01-MGO]; V Foundation for Cancer Research; Basil O'Conner March of Dimes Starter Award; Harvard Stem Cell Institute; Lung Cancer Research Foundation; National Institutes of Health (NIH) [CA122794, CA140594, CA163896, CA166480, CA154303, CA120964]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NIH [K08 CA163677]; [RO1 HL090136]; [U01 HL100402 RFA-HL-09-004] FX We thank the Kim laboratory, F. Luo, P. Louis, K. Harrington, X. Wang and J. Brainson for technical assistance and discussions, and J. Crabtree, D. Hargreaves, C. Kadoch, L. Zon, K. Cichowski, M. Enos, S. Orkin, A. Gutierrez and C. Roberts for discussions. This work was supported in part by the Ladies Auxiliary to the Veterans of Foreign Wars, PF-12-151-01-DMC from the American Cancer Society, and the Uniting Against Lung Cancer Young Investigator Award supported by Meryl Bralower (C. M. F.), Boston University Undergraduate Research Opportunities Program (P.T.D.), RO1 HL090136, U01 HL100402 RFA-HL-09-004, American Cancer Society Research Scholar Grant RSG-08-082-01-MGO, the V Foundation for Cancer Research, a Basil O'Conner March of Dimes Starter Award, the Harvard Stem Cell Institute, and the Lung Cancer Research Foundation (C. F. K.), the National Institutes of Health (NIH) grants CA122794, CA140594, CA163896, CA166480, CA154303 and CA120964 (K.K.W.), the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (V.E.M.), and the NIH grant K08 CA163677 (P.S.H.). NR 51 TC 55 Z9 57 U1 13 U2 57 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 APR 9 PY 2015 VL 520 IS 7546 BP 239 EP U261 DI 10.1038/nature14122 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3NA UT WOS:000352454600043 PM 25629630 ER PT J AU Grover, S Balogun, OD Yamoah, K Groen, R Shah, M Rodin, D Martei, Y Olson, AC Slone, JS Shulman, LN Coleman, CN Hahn, SM AF Grover, Surbhi Balogun, Onyinye D. Yamoah, Kosj Groen, Reinou Shah, Mira Rodin, Danielle Martei, Yehoda Olson, Adam C. Slone, Jeremy S. Shulman, Lawrence N. Coleman, C. Norman Hahn, Stephen M. TI Training global oncologists: addressing the global cancer control problem SO FRONTIERS IN ONCOLOGY LA English DT Editorial Material DE global health; oncology training; radiation oncology; surgical oncology; medical oncology ID MIDDLE-INCOME-COUNTRIES; RADIATION ONCOLOGY; BREAST-CANCER; HEALTH; RESIDENTS; RADIOTHERAPY; EXPERIENCES; THERAPY; PROGRAM; WOMEN C1 [Grover, Surbhi; Hahn, Stephen M.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Balogun, Onyinye D.] NYU, Perlmutter Canc Ctr, Dept Radiat Oncol, New York, NY USA. [Yamoah, Kosj] Thomas Jefferson Univ, Dept Radiat Oncol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Groen, Reinou] Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Baltimore, MD 21287 USA. [Shah, Mira] Henry Ford Hlth Syst, Dept Radiat Oncol, Detroit, MI USA. [Rodin, Danielle] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Martei, Yehoda] Hosp Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Olson, Adam C.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Slone, Jeremy S.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Shulman, Lawrence N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coleman, C. Norman] NIH, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Coleman, C. Norman] Int Canc Expert Corps, Chevy Chase, MD USA. RP Grover, S (reprint author), Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. EM surbhi.grover@uphs.upenn.edu NR 33 TC 11 Z9 11 U1 0 U2 0 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 APR 8 PY 2015 VL 5 AR 80 DI 10.3389/fonc.2015.00080 PG 4 WC Oncology SC Oncology GA CO3UU UT WOS:000359086800001 PM 25905040 ER PT J AU Cash, SS Hochberg, LR AF Cash, Sydney S. Hochberg, Leigh R. TI The Emergence of Single Neurons in Clinical Neurology SO NEURON LA English DT Review ID PRIMARY MOTOR CORTEX; HIGH-FREQUENCY OSCILLATIONS; BRAIN-COMPUTER INTERFACE; HUMAN HIPPOCAMPAL-FORMATION; HUMAN EPILEPTIC BRAIN; HUMAN LIMBIC NEURONS; INTRACORTICAL-ELECTRODE-ARRAY; PYRAMIDAL TRACT ACTIVITY; TEMPORAL-LOBE EPILEPSY; FREE ARM MOVEMENTS AB Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. C1 [Cash, Sydney S.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Neurotechnol Trials Unit, Boston, MA 02114 USA. [Cash, Sydney S.; Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Providence VA Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI 02908 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurotechnol Trials Unit, Boston, MA 02114 USA. EM scash@mgh.harvard.edu; leigh@brown.edu FU National Institutes of Health: NIDCD [R01DC009899]; National Institutes of Health: NINDS [R01NS062092]; Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6453R, N9228-C] FX Support provided in part by the National Institutes of Health: NIDCD (R01DC009899), NINDS (R01NS062092), and the Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs (Merit Review Award B6453R and Center of Excellence Award N9228-C). The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. We wish to thank Wilson Truccolo, Eric Halgren, Beata Jarosiewicz, and David Brandman for assistance with the text and discussion of the content and to Mia Borzello for help with figure preparation. NR 209 TC 8 Z9 8 U1 3 U2 23 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 APR 8 PY 2015 VL 86 IS 1 BP 79 EP 91 DI 10.1016/j.neuron.2015.03.058 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CF4WE UT WOS:000352552900015 PM 25856488 ER PT J AU Andzelm, MM Cherry, TJ Harmin, DA Boeke, AC Lee, C Hemberg, M Pawlyk, B Malik, AN Flavell, SW Sandberg, MA Raviola, E Greenberg, ME AF Andzelm, Milena M. Cherry, Timothy J. Harmin, David A. Boeke, Annabel C. Lee, Charlotte Hemberg, Martin Pawlyk, Basil Malik, Athar N. Flavell, Steven W. Sandberg, Michael A. Raviola, Elio Greenberg, Michael E. TI MEF2D Drives Photoreceptor Development through a Genome-wide Competition for Tissue-Specific Enhancers SO NEURON LA English DT Article ID TRANSCRIPTION FACTOR ACTIVITY; CONE-ROD DYSTROPHY; HOMEOBOX GENE; CELL-DIFFERENTIATION; TARGET GENES; IN-VIVO; MUTATIONS; MICE; CRX; EXPRESSION AB Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors (TFs) play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites and redirects it to retina-specific enhancers that lack the consensus MEF2-binding sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs and through selective activation of these enhancers to regulate tissue-specific genes. C1 [Andzelm, Milena M.; Cherry, Timothy J.; Harmin, David A.; Boeke, Annabel C.; Lee, Charlotte; Malik, Athar N.; Flavell, Steven W.; Raviola, Elio; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Pawlyk, Basil; Sandberg, Michael A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Berman Gund Lab Study Retinal Deg, Boston, MA 02114 USA. [Hemberg, Martin] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. RP Greenberg, ME (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM michael_greenberg@hms.harvard.edu OI Flavell, Steven/0000-0001-9464-1877 FU Neural Imaging Center as part of an NINDS P30 Core Center [NS072030]; Stuart H.Q. & Victoria Quan Fellowship; Ruth L. Kirschstein NIH [T32GM007753]; Ruth L. Kirschstein Individual Postdoctoral Award [F32NS070544]; NIH [NS028829] FX We thank members of the Greenberg laboratory for helpful discussions, J. Zieg for help with figures, the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye), the EM Core (E. Benecchi), and the Rodent Pathophysiology Core (R. Bronson) for experimental assistance and advice and P. Zhang for help with mice. We thank the Neurobiology Department at Harvard Medical School and the Neurobiology Imaging Facility for consultation and instrument availability that supported this work. This facility is supported in part by the Neural Imaging Center as part of an NINDS P30 Core Center grant NS072030. The work presented in this paper was supported by a Stuart H.Q. & Victoria Quan Fellowship (M.M.A.), the Ruth L. Kirschstein NIH Training Grant T32GM007753 (M.M.A.), the Ruth L. Kirschstein Individual Postdoctoral Award F32NS070544 (T.J.C.), and NIH grant NS028829 (M.E.G.). NR 49 TC 8 Z9 9 U1 0 U2 2 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 APR 8 PY 2015 VL 86 IS 1 BP 247 EP 263 DI 10.1016/j.neuron.2015.02.038 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CF4WE UT WOS:000352552900025 PM 25801704 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 SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Postoperative mortality; Perioperative mortality; Simultaneous bilateral total hip arthroplasty; Register; Registry; Total hip replacement; One-stage bilateral THR/THA; Two-stage bilateral THR/THA ID TOTAL JOINT ARTHROPLASTY; ELECTIVE TOTAL HIP; 90-DAY MORTALITY; RHEUMATOID-ARTHRITIS; STATISTICAL-ANALYSIS; KNEE ARTHROPLASTY; OSTEOARTHRITIS; REPLACEMENT; OUTCOMES; COMPLICATIONS AB Background: Approximately a fifth of all total hip arthroplasty (THA) patients suffers from bilateral osteoarthritis of the hip. It is unclear whether mortality risks differ between simultaneous bilateral THA and staged bilateral THA. We investigated mortality after simultaneous THA compared with staged bilateral THA in the largest cohort hitherto reported. Methods: The 42,238 patients reported to have received bilateral primary THA from 1992 to 2012 in the Swedish Hip Arthroplasty Register were included. Tumours and fractures as underlying diagnoses were excluded. The time interval between the first and second THA was divided into four categories or treated as a continuous variable. Unadjusted survival was calculated according to Kaplan-Meier and adjusted Cox regression models were fitted in order to calculate crude and adjusted hazard ratios (HR) for the risk of death within different time frames. Results: Patients selected for simultaneous bilateral surgery were younger, more often male, and had lower ASA (American Society of Anesthesiologists) class than patients receiving staged procedures. The adjusted 90-day mortality after the second procedure did not differ between the four investigated groups (simultaneous bilateral [HR 1.3, CI 0.5-3.3], surgeries within 6 months [HR 1.1, CI 0.6-2.0], surgeries between 7 and 12 months [HR 0.7, CI 0.4-1.2], with second surgery after > 12 months as the reference group). For patients older than 75 years, men, patients with ASA class 3 or above, and for patients with rheumatoid arthritis (RA) the 90-day mortality was increased. The unadjusted risk of implant revision of any hip was slightly higher for patients with simultaneous bilateral THA compared to those with staged procedure within one year, but after adjustment for age, gender, diagnosis and implant fixation these differences were no longer statistically significant. Conclusion: There were no clinically relevant differences in early postoperative mortality between simultaneous and staged bilateral surgery in healthy patients. Advanced age, RA, a high ASA class and male sex increased the risk of death within 90 days. There may be an issue with enhanced risk of implant revision in patients with simultaneous bilateral THA that needs to be explored further. 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 02115 USA. RP Garland, A (reprint author), Visby Hosp, Dept Orthopaed, Visby, Sweden. EM anne.garland@gotland.se OI Rolfson, Ola/0000-0001-6534-1242 NR 36 TC 6 Z9 6 U1 0 U2 1 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 APR 8 PY 2015 VL 16 AR 77 DI 10.1186/s12891-015-0535-0 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CF5PN UT WOS:000352609400001 PM 25887667 ER PT J AU Braunstein, LZ Taghian, AG AF Braunstein, Lior Z. Taghian, Alphonse G. TI Hypofractionated Whole Breast Irradiation for Early-Stage Breast Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@mgh.harvard.edu 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 APR 7 PY 2015 VL 313 IS 13 BP 1370 EP 1371 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CF1OL UT WOS:000352315900026 PM 25849184 ER PT J AU Zygmanski, P Shrestha, S Elshahat, B Karellas, A Sajo, E AF Zygmanski, Piotr Shrestha, Suman Elshahat, Bassem Karellas, Andrew Sajo, Erno TI Dosimetric properties of high energy current (HEC) detector in keV x-ray beams SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE Auger electrons; x-rays; radiation detectors; quality assurance; x-ray imaging ID QUALITY-ASSURANCE AB We introduce a new x-ray radiation detector. The detector employs high-energy current (HEC) formed by secondary electrons consisting predominantly of photoelectrons and Auger electrons, to directly convert x-ray energy to detector signal without externally applied power and without amplification. The HEC detector is a multilayer structure composed of thin conducting layers separated by dielectric layers with an overall thickness of less than a millimeter. It can be cut to any size and shape, formed into curvilinear surfaces, and thus can be designed for a variety of QA applications. We present basic dosimetric properties of the detector as function of x-ray energy, depth in the medium, area and aspect ratio of the detector, as well as other parameters. The prototype detectors show similar dosimetric properties to those of a thimble ionization chamber, which operates at high voltage. The initial results obtained for kilovoltage x-rays merit further research and development towards specific medical applications. C1 [Zygmanski, Piotr] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Zygmanski, Piotr] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shrestha, Suman; Karellas, Andrew] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Elshahat, Bassem; Sajo, Erno] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. RP Zygmanski, P (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pzygmanski@lroc.harvard.edu RI Shrestha, Suman/E-6979-2013 OI Shrestha, Suman/0000-0003-1378-9605 NR 8 TC 5 Z9 5 U1 0 U2 1 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 APR 7 PY 2015 VL 60 IS 7 BP N121 EP N129 DI 10.1088/0031-9155/60/7/N121 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CF4JU UT WOS:000352516000003 PM 25789488 ER PT J AU Alsahafi, N Debbeche, O Sodroski, J Finzi, A AF Alsahafi, Nirmin Debbeche, Olfa Sodroski, Joseph Finzi, Andres TI Effects of the I559P gp41 Change on the Conformation and Function of the Human Immunodeficiency Virus (HIV-1) Membrane Envelope Glycoprotein Trimer SO PLOS ONE LA English DT Article ID GP120 INNER DOMAIN; INTERMOLECULAR DISULFIDE BOND; ALANINE-SCANNING MUTAGENESIS; 6-HELIX BUNDLE; TYPE-1 GP41; CRYOELECTRON MICROSCOPY; CD4-BOUND CONFORMATION; DEPENDENT EPITOPE; CYTOPLASMIC TAIL; ATOMIC-STRUCTURE AB The mature human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer is produced by proteolytic cleavage of a precursor and consists of three gp120 exterior and three gp41 transmembrane subunits. The metastable Env complex is induced to undergo conformational changes required for virus entry by the binding of gp120 to the receptors, CD4 and CCR5/CXCR4. An isoleucine-to-proline change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of HIV-1 Env trimers for structural characterization and for use as immunogens. In the native membrane-anchored HIV-1(BG505) Env, the I559P change modestly decreased proteolytic maturation, increased the non-covalent association of gp120 with the Env trimer, and resulted in an Env conformation distinctly different from that of the wild-type HIV-1(BG505) Env. Compared with the wild-type Env, the I559P Env was recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by several gp41-directed antibodies, by some antibodies against the CD4-binding site of gp120, and by antibodies that preferentially recognize the CD4-bound Env. Some of the gp120-associated antigenic differences between the wild-type HIV-1(BG505) Env and the I559P mutant were compensated by the SOS disulfide bond between gp120 and gp41, which has been used to stabilize cleaved soluble Env trimers. Nonetheless, regardless of the presence of the SOS changes, Envs with proline 559 were recognized less efficiently than Envs with isoleucine 559 by the VRC01 neutralizing antibody, which binds the CD4-binding site of gp120, and the PGT151 neutralizing antibody, which binds a hybrid gp120-gp41 epitope. The I559P change completely eliminated the ability of the HIV-1(BG505) Env to mediate cell-cell fusion and virus entry, and abolished the capacity of the SOS Env to support virus infection in the presence of a reducing agent. These results suggest that differences exist between the quaternary structures of functional Env spikes and I559P Envs. C1 [Alsahafi, Nirmin; Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. [Alsahafi, Nirmin; Debbeche, Olfa; Finzi, Andres] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ H2X 0A9, Canada. [Debbeche, Olfa; Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu; andres.finzi@umontreal.ca FU National Institutes of Health [AI24755, AI100645]; Canada Foundation [29866]; CIHR operating grants [119334, 134117]; FRQS Establishment of Young Scientist grant [26702]; Canada Research Chair on Retroviral Entry [950-229930]; King Abdullah scholarship for higher education from the Saudi Government FX This work was supported by grants from the National Institutes of Health (AI24755 and AI100645) and by the late William F. McCarty-Cooper to JS and by a Canada Foundation for Innovation Program Leader grant #29866, by CIHR operating grants #119334 and #134117, by a FRQS Establishment of Young Scientist grant #26702 to AF. AF is the recipient of a Canada Research Chair on Retroviral Entry #950-229930. NA is the recipient of a King Abdullah scholarship for higher education from the Saudi Government. NR 93 TC 9 Z9 9 U1 0 U2 11 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 APR 7 PY 2015 VL 10 IS 4 AR e0122111 DI 10.1371/journal.pone.0122111 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800099 PM 25849367 ER PT J AU Matthews, AGW Briggs, CE Yamanaka, K Small, TN Mooster, JL Bonilla, FA Oettinger, MA Butte, MJ AF Matthews, Adam G. W. Briggs, Christine E. Yamanaka, Keiichi Small, Trudy N. Mooster, Jana L. Bonilla, Francisco A. Oettinger, Marjorie A. Butte, Manish J. TI Compound Heterozygous Mutation of Rag1 Leading to Omenn Syndrome SO PLOS ONE LA English DT Article ID ACTIVATING GENE-1 DEFICIENCY; V(D)J RECOMBINATION ACTIVITY; COMBINED IMMUNE-DEFICIENCY; PRIMARY IMMUNODEFICIENCIES; PLANT HOMEODOMAIN; IN-VIVO; LYSINE-4; PROTEINS; CLEAVAGE; DISEASE AB Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility to infections and autoreactive T cells and resulting from defective genomic rearrangement of genes for the T cell and B cell receptors. The most frequent etiologies are hypomorphic mutations in "non-core" regions of the Rag1 or Rag2 genes, the protein products of which are critical members of the cellular apparatus for V(D)J recombination. In this report, we describe an infant with Omenn syndrome with a previously unreported termination mutation (p.R142*) in Rag1 on one allele and a partially characterized substitution mutation (p.V779M) in a "core" region of the other Rag1 allele. Using a cellular recombination assay, we found that while the p.R142* mutation completely abolished V(D) J recombination activity, the p.V779M mutation conferred a severe, but not total, loss of V(D) J recombination activity. The recombination defect of the V779 mutant was not due to overall misfolding of Rag1, however, as this mutant supported wild-type levels of V(D) J cleavage. These findings provide insight into the role of this poorly understood region of Rag1 and support the role of Rag1 in a post-cleavage stage of recombination. C1 [Matthews, Adam G. W.; Oettinger, Marjorie A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Matthews, Adam G. W.; Oettinger, Marjorie A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Matthews, Adam G. W.] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02481 USA. [Briggs, Christine E.] Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA. [Yamanaka, Keiichi] Mie Univ, Grad Sch Med, Dept Dermatol, Tsu, Mie 5148507, Japan. [Small, Trudy N.] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10065 USA. [Mooster, Jana L.; Bonilla, Francisco A.] Boston Childrens Hosp, Div Immunol Allergy & Rheumatol, Dept Pediat, Boston, MA 02115 USA. [Butte, Manish J.] Stanford Univ, Dept Pediat, Div Immunol Allergy & Rheumatol, Stanford, CA 94305 USA. RP Butte, MJ (reprint author), Stanford Univ, Dept Pediat, Div Immunol Allergy & Rheumatol, 300 Pasteur Dr, Stanford, CA 94305 USA. EM manish.butte@stanford.edu FU National Institutes of Health [K08 AI079268] FX This work was supported by National Institutes of Health K08 AI079268 (MJB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 1 Z9 1 U1 2 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 APR 7 PY 2015 VL 10 IS 4 AR e0121489 DI 10.1371/journal.pone.0121489 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800062 PM 25849362 ER PT J AU Shen, EY Jiang, Y Mao, WJ Futai, K Hock, H Akbarian, S AF Shen, Erica Y. Jiang, Yan Mao, Wenjie Futai, Kensuke Hock, Hanno Akbarian, Schahram TI Cognition and Mood-Related Behaviors in L3mbtl1 Null Mutant Mice SO PLOS ONE LA English DT Article ID ANXIETY-LIKE BEHAVIOR; HISTONE METHYLATION; OPEN-FIELD; EPIGENETIC MECHANISMS; RETT-SYNDROME; MOUSE MODEL; DEPRESSION; STRESS; CHROMATIN; PROTEIN AB Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression- related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors. C1 [Shen, Erica Y.; Jiang, Yan; Akbarian, Schahram] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA. [Mao, Wenjie; Futai, Kensuke] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. [Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hock, Hanno] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Akbarian, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA. EM schahram.akbarian@mssm.edu FU National Institutes of Health [R01MH086509, P50MH096890] FX This work was supported by National Institutes of Health grants R01MH086509 and P50MH096890. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 0 Z9 0 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 APR 7 PY 2015 VL 10 IS 4 AR UNSP e0121252 DI 10.1371/journal.pone.0121252 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800049 PM 25849281 ER PT J AU Tsai, AC AF Tsai, Alexander C. TI Home Foreclosure, Health, and Mental Health: A Systematic Review of Individual, Aggregate, and Contextual Associations SO PLOS ONE LA English DT Article ID STRESSFUL LIFE EVENTS; WEST NILE VIRUS; GREAT RECESSION; MORTGAGE DELINQUENCY; SEARCH STRATEGIES; SUICIDAL-BEHAVIOR; PERSONAL DEBT; PUBLIC-HEALTH; CRISIS; RISK AB Background The U.S. foreclosure crisis intensified markedly during the Great Recession of 2007-09, and currently an estimated five percent of U.S. residential properties are more than 90 days past due or in the process of foreclosure. Yet there has been no systematic assessment of the effects of foreclosure on health and mental health. Methods and Findings I applied systematic search terms to PubMed and PsycINFO to identify quantitative or qualitative studies about the relationship between home foreclosure and health or mental health. After screening the titles and abstracts of 930 publications and reviewing the full text of 76 articles, dissertations, and other reports, I identified 42 publications representing 35 unique studies about foreclosure, health, and mental health. The majority of studies (32 [91%]) concluded that foreclosure had adverse effects on health or mental health, while three studies yielded null or mixed findings. Only two studies examined the extent to which foreclosure may have disproportionate impacts on ethnic or racial minority populations. Conclusions Home foreclosure adversely affects health and mental health through channels operating at multiple levels: at the individual level, the stress of personally experiencing foreclosure was associated with worsened mental health and adverse health behaviors, which were in turn linked to poorer health status; at the community level, increasing degradation of the neighborhood environment had indirect, cross-level adverse effects on health and mental health. Early intervention may be able to prevent acute economic shocks from eventually developing into the chronic stress of foreclosure, with all of the attendant benefits this implies for health and mental health status. Programs designed to encourage early return of foreclosed properties back into productive use may have similar health and mental health benefits. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIH [K23MH096620]; Robert Wood Johnson Health and Society Scholars Program FX The author received no specific funding for this work. The author acknowledges salary support from NIH K23MH096620 and the Robert Wood Johnson Health and Society Scholars Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 112 TC 5 Z9 5 U1 1 U2 14 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 APR 7 PY 2015 VL 10 IS 4 AR e0123182 DI 10.1371/journal.pone.0123182 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800213 PM 25849962 ER PT J AU Kolodin, D van Panhuys, N Li, CR Magnuson, AM Cipolletta, D Miller, CM Wagers, A Germain, RN Benoist, C Mathis, D AF Kolodin, Dmitriy van Panhuys, Nicolas Li, Chaoran Magnuson, Angela M. Cipolletta, Daniela Miller, Christine M. Wagers, Amy Germain, Ronald N. Benoist, Christophe Mathis, Diane TI Antigen- and Cytokine-Driven Accumulation of Regulatory T Cells in Visceral Adipose Tissue of Lean Mice SO CELL METABOLISM LA English DT Article ID LYMPH-NODES; REG CELLS; INFLAMMATION; OBESITY; IL-33; DIFFERENTIATION; MACROPHAGES; POPULATION; MOLECULES; GENE AB A unique population of Foxp3(+)CD4(+) regulatory T (Treg) cells, with a distinct transcriptome and antigen-receptor repertoire, resides in visceral adipose tissue (VAT) of lean individuals. These cells regulate local inflammation and both local and systemic metabolic indices. Here we focus on expansion of the VAT Treg compartment in aging lean mice-assessing these cells' phenotypic conversion from conventional CD4(+) T cells, influx from lymphoid organs, and local population dynamics. Our findings establish that the VAT Treg compartment is seeded from thymocytes generated during the first weeks of life and expands beyond 10 weeks of age due to indolent proliferation, of certain clones in particular, coupled with enhanced survival. Accumulation of VAT Tregs depends on the antigen(s) presented by MHC class-II molecules and soluble mediators, notably interleukin(IL)-33. Addressing such factors therapeutically promises novel approaches for harnessing Tregs to stem the growing epidemic of obesity and consequent metabolic abnormalities. C1 [Kolodin, Dmitriy; Li, Chaoran; Magnuson, Angela M.; Cipolletta, Daniela; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [van Panhuys, Nicolas; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Miller, Christine M.; Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wagers, Amy] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu RI van Panhuys, Nicholas/E-1812-2011; OI van Panhuys, Nicholas/0000-0003-2199-852X FU NIH [R01DK092541, RO1HL088582]; JPB Foundation; NIAID, NIH; National Science Foundation; Juvenile Diabetes Research Foundation FX We thank K. Hattori, N. Asinovski, A. Ortiz-Lopez, K. Leatherbee, D. Jepson, K. Rothamel, S. Davis, H. Paik, R. Cruse, J. LaVecchio, and G. Buruzula for experimental support; C. Shu and D. Burzyn for valuable discussions; and A Rudensky, V. Kuchroo, O. Kanagawa, R. Lee, and A. MacKenzie for mouse lines. This work was supported by NIH R01DK092541 and the JPB Foundation to D.M., NIH RO1HL088582 to A.J.W., and in part by the Intramural Research Program of NIAID, NIH. Cell sorting was performed at the HSCI/DRC Flow Core (NIH P30DK036836). D.K. and A.M. were supported by fellowships from the National Science and Juvenile Diabetes Research Foundations, respectively. Content is solely the responsibility of the authors and does not represent the official view of the NIH or other funding agencies. NR 29 TC 48 Z9 48 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 543 EP 557 DI 10.1016/j.cmet.2015.03.005 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800010 PM 25863247 ER PT J AU Liu, XJ Xiao, JJ Zhu, H Wei, X Platt, C Damilano, F Xiao, CY Bezzerides, V Bostrom, P Che, L Zhang, CX Spiegelman, BM Rosenzweig, A AF Liu, Xiaojun Xiao, Junjie Zhu, Han Wei, Xin Platt, Colin Damilano, Federico Xiao, Chunyang Bezzerides, Vassilios Bostrom, Pontus Che, Lin Zhang, Chunxiang Spiegelman, Bruce M. Rosenzweig, Anthony TI miR-222 Is Necessary for Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling SO CELL METABOLISM LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEART-FAILURE; CELL-PROLIFERATION; MICE LACKING; HYPERTROPHY; P27(KIP1); MICRORNAS; HYPERPLASIA; INJURY; RATS AB Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart's capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1. Inhibition of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in response to exercise while reducing markers of cardiomyocyte proliferation. Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant to adverse cardiac remodeling and dysfunction after ischemic injury. These studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth and proliferation in the adult mammalian heart and show that it is sufficient to protect the heart against adverse remodeling. C1 [Liu, Xiaojun; Zhu, Han; Wei, Xin; Platt, Colin; Damilano, Federico; Xiao, Chunyang; Bezzerides, Vassilios; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Cardiovasc Div, Boston, MA 02215 USA. [Liu, Xiaojun; Zhu, Han; Wei, Xin; Platt, Colin; Damilano, Federico; Xiao, Chunyang; Bezzerides, Vassilios; Spiegelman, Bruce M.; Rosenzweig, Anthony] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Xiao, Junjie] Shanghai Univ, Sch Life Sci, Regenerat Lab, Shanghai 200444, Peoples R China. [Xiao, Junjie] Shanghai Univ, Sch Life Sci, Expt Ctr Life Sci, Shanghai 200444, Peoples R China. [Bezzerides, Vassilios] Boston Childrens Hosp, Cardiovasc Dept, Boston, MA 02215 USA. [Bostrom, Pontus] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden. [Che, Lin] Tongji Univ, Tongji Hosp, Sch Med, Shanghai 200065, Peoples R China. [Zhang, Chunxiang] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. [Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosenzweig, Anthony] Massachusetts Gen Hosp, Cardiovasc Div, Boston, MA 02115 USA. RP Rosenzweig, A (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, Boston, MA 02215 USA. EM arosenzweig@partners.org FU NIH [R21HL114352, 1UH2TR000901, R01HL110733, T32HL073734, T32GM007226, T32HL007572-27A1]; LaDue Fellowship Award from Harvard Medical School; National Natural Science Foundation of China [81200169]; Innovation Program of Shanghai Municipal Education Commission [13YZ014]; Foundation for University Young Teachers by Shanghai Municipal Education Commission; Shanghai University [sdcx2012038]; Program for the Integration of Production, Teaching and Research for University Teachers by Shanghai Municipal Education Commission FX We thank Dr. Ling Li for technical support and Dr. Serafima Zaltsman for managing the mouse colony. This research was supported by grants from the NIH (AR[R21HL114352, 1UH2TR000901, R01HL110733], XL[T32HL073734], FD [T32HL073734], and CP[T32GM007226]). V.B. was supported by grants from the NIH (T32HL007572-27A1) and a LaDue Fellowship Award from Harvard Medical School. J.X. was supported by the grants from the National Natural Science Foundation of China (81200169), Innovation Program of Shanghai Municipal Education Commission (13YZ014), Foundation for University Young Teachers by Shanghai Municipal Education Commission (2012), Innovation Fund from Shanghai University (sdcx2012038), and Program for the Integration of Production, Teaching and Research for University Teachers supported by the Shanghai Municipal Education Commission (2014). A.R. is a principal faculty member of the Harvard Stem Cell Institute. NR 49 TC 37 Z9 39 U1 7 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 584 EP 595 DI 10.1016/j.cmet.2015.02.014 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800013 PM 25863248 ER PT J AU Dai, N Zhao, LP Wrighting, D Kramer, D Majithia, A Wang, YQ Cracan, V Borges-Rivera, D Mootha, VK Nahrendorf, M Thorburn, DR Minichiello, L Altshuler, D Avruch, J AF Dai, Ning Zhao, Liping Wrighting, Diedra Kraemer, Dana Majithia, Amit Wang, Yanqun Cracan, Valentin Borges-Rivera, Diego Mootha, Vamsi K. Nahrendorf, Matthias Thorburn, David R. Minichiello, Liliana Altshuler, David Avruch, Joseph TI IGF2BP2/IMP2-Deficient Mice Resist Obesity through Enhanced Translation of Ucp1 mRNA and Other mRNAs Encoding Mitochondrial Proteins SO CELL METABOLISM LA English DT Article ID GENOME-WIDE ASSOCIATION; MAMMALIAN LIFE-SPAN; BINDING PROTEINS; SKELETAL-MUSCLE; THERMOGENESIS; REDUCTION; VARIANTS; DISEASE; COMPLEX; FAMILY AB Although variants in the IGF2BP2/IMP2 gene confer risk for type 2 diabetes, IMP2, an RNA binding protein, is not known to regulate metabolism. Imp2(-/-) mice gain less lean mass after weaning and have increased lifespan. Imp2(-/-) mice are highly resistant to diet-induced obesity and fatty liver and display superior glucose tolerance and insulin sensitivity, increased energy expenditure, and better defense of core temperature on cold exposure. Imp2(-/-) brown fat and Imp2(-/-) brown adipocytes differentiated in vitro contain more UCP1 polypeptide than Imp2(+/+) despite similar levels of Ucp1 mRNA; the Imp2(-/-) adipocytes also exhibit greater uncoupled oxygen consumption. IMP2 binds the mRNAs encoding Ucp1 and other mitochondrial components, and most exhibit increased translational efficiency in the absence of IMP2. In vitro IMP2 inhibits translation of mRNAs bearing the Ucp1 untranslated segments. Thus IMP2 limits longevity and regulates nutrient and energy metabolism in the mouse by controlling the translation of its client mRNAs. C1 [Dai, Ning; Zhao, Liping; Wrighting, Diedra; Majithia, Amit; Wang, Yanqun; Cracan, Valentin; Borges-Rivera, Diego; Mootha, Vamsi K.; Altshuler, David; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Dai, Ning; Zhao, Liping; Majithia, Amit; Mootha, Vamsi K.; Altshuler, David; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dai, Ning; Zhao, Liping; Majithia, Amit; Mootha, Vamsi K.; Altshuler, David; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wrighting, Diedra; Borges-Rivera, Diego; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Cracan, Valentin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wrighting, Diedra; Majithia, Amit; Borges-Rivera, Diego; Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kraemer, Dana; Minichiello, Liliana] European Mol Biol Lab, Mouse Biol Unit, I-00015 Monterotondo, Italy. [Minichiello, Liliana] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. [Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia. [Thorburn, David R.] Royal Childrens Hosp, Victorian Clin Genet Serv, Melbourne, Vic 3052, Australia. [Thorburn, David R.] Univ Melbourne, Dept Pediat, Melbourne, Vic 3010, Australia. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu; avruch@molbio.mgh.harvard.edu OI thorburn, david/0000-0002-7725-9470 FU NIH [R37DK17776, P30DK057521]; Instituto Carso de la Salud, A.C. via Slim Initiative in Genomic Medicine for the Americas; Lundbeck foundation [177/05]; EMBL; NHMRC FX This work was supported by NIH awards R37DK17776 (J.A.) and P30DK057521 (J.A.); the Instituto Carso de la Salud, A.C., via the Slim Initiative in Genomic Medicine for the Americas (D.A.); and institutional funds. D.K. and L.M. thank the EMBL-Monterotondo gene expression and transgenic services for the production of the Imp2-/- line. L.M. was supported in part by the Lundbeck foundation (grant 177/05). D.K. was supported by an EMBL-postdoctoral fellowship and D.R.T. by an NHMRC Principal Research Fellowship. We thank Evan Rosen, Paul Cohen, Bruce Spiegelman, Youn-Kyoung Lee, Chad Cowan, Gerald I. Shulman, Alex Soukas, and Finn C. Nielsen for discussions; Paul Cohen and Youn-Kyoung for preliminary experiments; O. Peroni for adipocyte size determination; and A. Laskowski and T. Stait for technical assistance. NR 33 TC 13 Z9 13 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 609 EP 621 DI 10.1016/j.cmet.2015.03.006 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800015 PM 25863250 ER PT J AU Luo, ML Gong, C Chen, CH Hu, H Huang, PY Zheng, M Yao, YD Wei, S Wulf, G Lieberman, J Zhou, XZ Song, EW Lu, KP AF Luo, Man-Li Gong, Chang Chen, Chun-Hau Hu, Hai Huang, Pengyu Zheng, Min Yao, Yandan Wei, Shuo Wulf, Gerburg Lieberman, Judy Zhou, Xiao Zhen Song, Erwei Lu, Kun Ping TI The Rab2A GTPase Promotes Breast Cancer Stem Cells and Tumorigenesis via Erk Signaling Activation SO CELL REPORTS LA English DT Article ID PROLYL-ISOMERASE PIN1; TUMOR-INITIATING CELLS; TRANSCRIPTIONAL ACTIVITY; KINASE; GENE; RAS; PATHWAY; IDENTIFICATION; TRANSFORMATION; LOCALIZATION AB Proline-directed phosphorylation is regulated by the prolyl isomerase Pin1, which plays a fundamental role in driving breast cancer stem-like cells (BCSCs). Rab2A is a small GTPase critical for vesicle trafficking. Here, we show that Pin1 increases Rab2A transcription to promote BCSC expansion and tumorigenesis in vitro and in vivo. Mechanistically, Rab2A directly interacts with and prevents dephosphorylation/inactivation of Erk1/2 by the MKP3 phosphatase, resulting in Zeb1 upregulation and b-catenin nuclear translocation. In cancer cells, Rab2A is activated via gene amplification, mutation or Pin1 overexpression. Rab2A overexpression or mutation endows BCSC traits to primary normal human breast epithelial cells, whereas silencing Rab2A potently inhibits the expansion and tumorigenesis of freshly isolated BCSCs. Finally, Rab2A overexpression correlates with poor clinical outcome in breast cancer patients. Thus, Pin1/Rab2A/Erk drives BCSC expansion and tumorigenicity, suggesting potential drug targets. C1 [Luo, Man-Li; Chen, Chun-Hau; Hu, Hai; Huang, Pengyu; Zheng, Min; Yao, Yandan; Wei, Shuo; Wulf, Gerburg; Zhou, Xiao Zhen; Lu, Kun Ping] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Luo, Man-Li; Chen, Chun-Hau; Hu, Hai; Huang, Pengyu; Zheng, Min; Yao, Yandan; Wei, Shuo; Wulf, Gerburg; Zhou, Xiao Zhen; Lu, Kun Ping] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA. [Luo, Man-Li; Gong, Chang; Yao, Yandan; Song, Erwei] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China. [Zheng, Min; Lu, Kun Ping] Fujian Med Univ, Inst Translat Med, Fuzhou 350108, Peoples R China. [Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02215 USA. RP Lu, KP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. EM klu@bidmc.harvard.edu FU DOD Breast Cancer Research Program; NIH [CA167677, AG039405, DA031663]; Komen for Cure grant; Ministry of Science and Technology of China 973 project; National Natural Science Foundation of China [U1205024] FX We are very grateful to Drs. Robert Weinberg and Wenjun Guo for providing expert advice and critical reagents, and we thank Drs. John Blenis and William C. Hahn for reagents and/or advice and members of K.P.L. and X.Z.Z. laboratories for constructive discussions. C.-H.C. is a DOD Breast Cancer Research Program Postdoctoral Fellow and a NIH T32 training grant awardee. This work was supported by a Komen for Cure grant (to X.Z.Z.), the Ministry of Science and Technology of China 973 project (to E.S.), and the National Natural Science Foundation of China (U1205024) and NIH (grants CA167677, AG039405, and DA031663 to K.P.L.). K.P.L. and X.Z.Z. are inventors of Pin1 technology, which was licensed by BIDMC to Pinteon Therapeutics. Both own equity in and consult for Pinteon. K.P.L. also serves on its board of directors. Their interests were reviewed and are managed by BIDMC in accordance with its conflict of interest policy. NR 56 TC 7 Z9 8 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD APR 7 PY 2015 VL 11 IS 1 BP 111 EP 124 DI 10.1016/j.celrep.2015.03.002 PG 14 WC Cell Biology SC Cell Biology GA CF1BY UT WOS:000352279800011 PM 25818297 ER PT J AU Jiang, W Liu, YT Liu, R Zhang, K Zhang, Y AF Jiang, Wei Liu, Yuting Liu, Rui Zhang, Kun Zhang, Yi TI The lncRNA DEANR1 Facilitates Human Endoderm Differentiation by Activating FOXA2 Expression SO CELL REPORTS LA English DT Article ID EMBRYONIC STEM-CELLS; LONG NONCODING RNAS; INSULIN-PRODUCING CELLS; IN-VITRO; GENOME ANNOTATION; BINDING PROTEIN; TRANSCRIPTION; GENE; MECHANISMS; LANDSCAPE AB Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including cell lineage specification. Here, we report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allows us to identify hundreds of lncRNAs that exhibit differentiation-stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an endoderm-specific lncRNA, definitive endoderm-associated lncRNA1 (DEANR1), and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating expression of the endoderm factor FOXA2. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for endoderm differentiation. C1 [Jiang, Wei; Liu, Yuting; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Jiang, Wei; Liu, Yuting; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Jiang, Wei; Liu, Yuting; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Liu, Rui; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Jiang, W (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM wei.jiang@childrens.harvard.edu; yzhang@genetics.med.harvard.edu RI Jiang, Wei/J-7993-2012 OI Jiang, Wei/0000-0002-6463-7356 FU NIH [U01-DK089565]; Juvenile Diabetes Research Foundation [3-2012-293] FX We thank Dr. Philip Streeter (Oregon Stem Cell Center) for providing the antibodies against HPi2 and HPa1. We also thank Drs. Donghui Zhang and Shinpei Yamaguchi for their help in making Figure 6F, Drs. Azusa Inoue and Shogo Matoba for advice on RNA-FISH, and Dr. Luis M. Tuesta for a critical reading of the manuscript. This work was supported by NIH grant U01-DK089565 (Y.Z.). W.J. is supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship (3-2012-293). Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 52 TC 14 Z9 19 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD APR 7 PY 2015 VL 11 IS 1 BP 137 EP 148 DI 10.1016/j.celrep.2015.03.008 PG 12 WC Cell Biology SC Cell Biology GA CF1BY UT WOS:000352279800013 PM 25843708 ER PT J AU Aranson, NJ Watkins, MT AF Aranson, Nathan J. Watkins, Michael T. TI Percutaneous Interventions in Aortic Disease SO CIRCULATION LA English DT Editorial Material DE aneurysm; angioplasty; therapeutics; vascular closure devices ID ENDOVASCULAR-ANEURYSM-REPAIR; VASCULAR-SURGERY DEVICE; STENT-GRAFT PLACEMENT; TERM-FOLLOW-UP; BALLOON ANGIOPLASTY; OCCLUSIVE DISEASE; PRECLOSE TECHNIQUE; INTRAVASCULAR ULTRASOUND; ISCHEMIC COMPLICATIONS; CLOSURE DEVICES C1 [Aranson, Nathan J.; Watkins, Michael T.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Dept Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Dept Surg, 15 Parkman St,Ste 440, Boston, MA 02114 USA. EM mtwatkins@mgh.harvard.edu NR 99 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 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 7 PY 2015 VL 131 IS 14 BP 1291 EP 1299 DI 10.1161/CIRCULATIONAHA.114.006512 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF1AG UT WOS:000352275300014 PM 25847980 ER PT J AU Kim, S Park, T Jang, SJ Nam, AS Vakoc, BJ Oh, WY AF Kim, SunHee Park, Taejin Jang, Sun-Joo Nam, Ahhyun S. Vakoc, Benjamin J. Oh, Wang-Yuhl TI Multi-functional angiographic OFDI using frequency-multiplexed dual-beam illumination SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; FLOW; VELOCITY; RETINA; SPEED; OCT; BIREFRINGENCE AB Detection of blood flow inside the tissue sample can be achieved by measuring the local change of complex signal over time in angiographic optical coherence tomography (OCT). In conventional angiographic OCT, the transverse displacement of the imaging beam during the time interval between a pair of OCT signal measurements must be significantly reduced to minimize the noise due to the beam scanning-induced phase decorrelation at the expense of the imaging speed. Recent introduction of dual-beam scan method either using polarization encoding or two identical imaging systems in spectral-domain (SD) OCT scheme shows potential for high-sensitivity vasculature imaging without suffering from spurious phase noise caused by the beam scanning-induced spatial decorrelation. In this paper, we present multi-functional angiographic optical frequency domain imaging (OFDI) using frequency-multiplexed dual-beam illumination. This frequency multiplexing scheme, utilizing unique features of OFDI, provides spatially separated dual imaging beams occupying distinct electrical frequency bands that can be demultiplexed in the frequency domain processing. We demonstrate the 3D multi-functional imaging of the normal mouse skin in the dorsal skin fold chamber visualizing distinct layer structures from the intensity imaging, information about mechanical integrity from the polarization-sensitive imaging, and depth-resolved microvasculature from the angiographic imaging that are simultaneously acquired and automatically co-registered. (C) 2015 Optical Society of America C1 [Kim, SunHee; Park, Taejin; Jang, Sun-Joo; Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon, South Korea. [Jang, Sun-Joo] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon, South Korea. [Nam, Ahhyun S.; Vakoc, Benjamin J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nam, Ahhyun S.; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, 291 Daehak Ro, Taejon, South Korea. EM woh1@kaist.ac.kr FU NRF of Korea [2010-0017465]; MSIP of Korea [GFP/(CISS-2012M3A6A6054200), NIPA-2013-H0401-13-1007]; HRHR project of KAIST; NIH [P41EB015903] FX This research was supported in part by the NRF of Korea, grant 2010-0017465, by the MSIP of Korea, grant GFP/(CISS-2012M3A6A6054200) and grant NIPA-2013-H0401-13-1007, by the HRHR project of KAIST, and by the NIH, grant P41EB015903. NR 26 TC 1 Z9 1 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD APR 6 PY 2015 VL 23 IS 7 BP 8939 EP 8947 DI 10.1364/OE.23.008939 PG 9 WC Optics SC Optics GA CF1FS UT WOS:000352290000096 PM 25968731 ER PT J AU Eisner, A Pazyra-Murphy, MF Durresi, E Zhou, PC Zhao, XS Chadwick, EC Xu, PX Hillman, RT Scott, MP Greenberg, ME Segal, RA AF Eisner, Adriana Pazyra-Murphy, Maria F. Durresi, Ershela Zhou, Pengcheng Zhao, Xuesong Chadwick, Emily C. Xu, Pin-Xian Hillman, R. Tyler Scott, Matthew P. Greenberg, Michael E. Segal, Rosalind A. TI The Eya1 Phosphatase Promotes Shh Signaling during Hindbrain Development and Oncogenesis SO DEVELOPMENTAL CELL LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SONIC HEDGEHOG; EYES ABSENT; BRANCHIOOTORENAL SYNDROME; TRANSCRIPTION FACTORS; CELL-PROLIFERATION; BOR SYNDROME; MOUSE MODEL; INNER-EAR; 6 FAMILY AB Sonic hedgehog (Shh) signaling is critical in development and oncogenesis, but the mechanisms regulating this pathway remain unclear. Although protein phosphorylation clearly affects Shh signaling, little is known about phosphatases governing the pathway. Here, we conducted a small hairpin RNA (shRNA) screen of the phosphatome and identified Eya1 as a positive regulator of Shh signaling. We find that the catalytically active phosphatase Eya1 cooperates with the DNA-binding protein Six1 to promote gene induction in response to Shh and that Eya1/Six1 together regulate Gli transcriptional activators. We show that Eya1, which is mutated in a human deafness disorder, branchio-oto-renal syndrome, is critical for Shh-dependent hindbrain growth and development. Moreover, Eya1 drives the growth of medulloblastoma, a Shh-dependent hindbrain tumor. Together, these results identify Eya1 and Six1 as key components of the Shh transcriptional network in normal development and in oncogenesis. C1 [Eisner, Adriana; Pazyra-Murphy, Maria F.; Zhou, Pengcheng; Zhao, Xuesong; Chadwick, Emily C.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Eisner, Adriana; Pazyra-Murphy, Maria F.; Zhou, Pengcheng; Zhao, Xuesong; Chadwick, Emily C.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Eisner, Adriana; Pazyra-Murphy, Maria F.; Durresi, Ershela; Zhou, Pengcheng; Zhao, Xuesong; Chadwick, Emily C.; Greenberg, Michael E.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Xu, Pin-Xian] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci Dev & Regenerat Biol, New York, NY 10029 USA. [Hillman, R. Tyler; Scott, Matthew P.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. [Hillman, R. Tyler; Scott, Matthew P.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Hillman, R. Tyler; Scott, Matthew P.] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. RP Segal, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU PLGA Foundation; NIH [R01 DK64640, NS045500, T32CA009361, DP1000839, CA142536] FX We thank William Hahn, So Young Kim, and the Broad Institute RNAi Consortium for help with the shRNA screen and Alexandra Smolyanskaya for help with analyzing the screen. We thank Lisa Goodrich, Clifford Tabin for providing probes for in situ hybridization studies, and Richard Pestell for the Eya1 WT and Eya1 D237A constructs in pCDF. We thank members of the Segal laboratory for help and advice. These studies were supported by grants from the NIH: T32CA009361 (A.E., R.A.S.), Director's Pioneer Award DP1000839 (R.A.S.), CA142536 (R.A.S.) and support from the PLGA Foundation; NIH R01 DK64640 (P.-X.X.); NIH NS045500 (M.E.G.). NR 66 TC 4 Z9 4 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD APR 6 PY 2015 VL 33 IS 1 BP 22 EP 35 DI 10.1016/j.devcel.2015.01.033 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CF3MX UT WOS:000352454200004 PM 25816987 ER PT J AU Shade, KTC Platzer, B Washburn, N Mani, V Bartsch, YC Conroy, M Pagan, JD Bosques, C Mempel, TR Fiebiger, E Anthony, RM AF Shade, Kai-Ting C. Platzer, Barbara Washburn, Nathaniel Mani, Vinidhra Bartsch, Yannic C. Conroy, Michelle Pagan, Jose D. Bosques, Carlos Mempel, Thorsten R. Fiebiger, Edda Anthony, Robert M. TI A single glycan on IgE is indispensable for initiation of anaphylaxis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNOGLOBULIN-E; FC-EPSILON-RI; HIGH-AFFINITY RECEPTOR; ALLERGIC DISEASE; GLYCOSYLATION; BINDING; CELLS; SITE; FRAGMENTS; ALPHA AB Immunoglobulin epsilon (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, Fc epsilon RI. Subsequent allergen exposure cross-links mast cell-bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (C epsilon 3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to Fc epsilon RI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology. C1 [Shade, Kai-Ting C.; Mani, Vinidhra; Bartsch, Yannic C.; Conroy, Michelle; Pagan, Jose D.; Mempel, Thorsten R.; Anthony, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Charlestown, MA 02129 USA. [Platzer, Barbara; Fiebiger, Edda] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Charlestown, MA 02115 USA. [Platzer, Barbara; Fiebiger, Edda] Harvard Univ, Sch Med, Dept Pediat, Charlestown, MA 02115 USA. [Washburn, Nathaniel; Bosques, Carlos] Momenta Pharmaceut, Cambridge, MA 02142 USA. RP Anthony, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Charlestown, MA 02129 USA. EM robert.anthony@mgh.harvard.edu FU National Institutes of Health [U19AI095261, 1K22AI091684, R01CA150975, K01DK093597, RO1AI075037]; Harvard Digestive Diseases Center [P30DK034854]; Mizutani Foundation for Glycoscience Research Grant FX This work was supported by National Institutes of Health grants U19AI095261 and 1K22AI091684 to R.M. Anthony, R01CA150975 to T.R. Mempel, K01DK093597 to B. Platzer, and RO1AI075037 to E. Fiebiger; Harvard Digestive Diseases Center grant P30DK034854 to E. Fiebiger; and a Mizutani Foundation for Glycoscience Research Grant to R.M. Anthony. NR 30 TC 21 Z9 22 U1 1 U2 17 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 APR 4 PY 2015 VL 212 IS 4 BP 457 EP 467 DI 10.1084/jem.20142182 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CF1CK UT WOS:000352281000003 PM 25824821 ER PT J AU Dutta, P Hoyer, FF Grigoryeva, LS Sager, HB Leuschner, F Courties, G Borodovsky, A Novobrantseva, T Ruda, VM Fitzgerald, K Iwamoto, Y Wojtkiewicz, G Sun, Y Da Silva, N Libby, P Anderson, DG Swirski, FK Weissleder, R Nahrendorf, M AF Dutta, Partha Hoyer, Friedrich Felix Grigoryeva, Lubov S. Sager, Hendrik B. Leuschner, Florian Courties, Gabriel Borodovsky, Anna Novobrantseva, Tatiana Ruda, Vera M. Fitzgerald, Kevin Iwamoto, Yoshiko Wojtkiewicz, Gregory Sun, Yuan Da Silva, Nicolas Libby, Peter Anderson, Daniel G. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; LIPID-LIKE MATERIALS; BONE-MARROW; ATHEROSCLEROTIC LESIONS; PROGENITOR CELLS; GENE-EXPRESSION; MARGINAL ZONE; TISSUE MACROPHAGE; MONOCYTE SUBSETS AB Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)(+) macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE(-/-) mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques. C1 [Dutta, Partha; Hoyer, Friedrich Felix; Grigoryeva, Lubov S.; Sager, Hendrik B.; Courties, Gabriel; Iwamoto, Yoshiko; Wojtkiewicz, Gregory; Sun, Yuan; Da Silva, Nicolas; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dutta, Partha; Hoyer, Friedrich Felix; Grigoryeva, Lubov S.; Sager, Hendrik B.; Courties, Gabriel; Iwamoto, Yoshiko; Wojtkiewicz, Gregory; Sun, Yuan; Da Silva, Nicolas; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Leuschner, Florian] Med Univ Hosp Heidelberg, Dept Cardiol, D-69120 Heidelberg, Germany. [Leuschner, Florian] DZHK German Ctr Cardiovascular Res, D-69120 Heidelberg, Germany. [Borodovsky, Anna; Novobrantseva, Tatiana; Ruda, Vera M.; Fitzgerald, Kevin] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02142 USA. [Anderson, Daniel G.] MIT, Inst Med Engn & Sci, Cambridge, MA 02142 USA. [Anderson, Daniel G.] Harvard Univ, Sch Med, Div Hlth Sci Technol, Cambridge, MA 02139 USA. [Anderson, Daniel G.] MIT, Cambridge, MA 02139 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM dutta.partha@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu FU National Institutes of Health [R01-HL114477, R01-HL117829, R01-NS084863, HHSN268201000044C, K99-HL121076, R01-HD069623]; Deutsche Forschungsgemeinschaft [SA1668/2-1] FX This work was funded in part by grants from the National Institutes of Health R01-HL114477, R01-HL117829, R01-NS084863 (M. Nahrendorf), HHSN268201000044C (R. Weissleder), K99-HL121076 (P. Dutta), and R01-HD069623 (N. Da Silva). H.B. Sager is funded by Deutsche Forschungsgemeinschaft (SA1668/2-1). NR 53 TC 24 Z9 24 U1 2 U2 11 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 APR 4 PY 2015 VL 212 IS 4 BP 497 EP 512 DI 10.1084/jem.20141642 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CF1CK UT WOS:000352281000006 PM 25800955 ER PT J AU Ecker, J Oehme, I Mazitschek, R Korshunov, A Kool, M Hielscher, T Kiss, J Selt, F Konrad, C Lodrini, M Deubzer, HE von Deimling, A Kulozik, AE Pfister, SM Witt, O Milde, T AF Ecker, Jonas Oehme, Ina Mazitschek, Ralph Korshunov, Andrey Kool, Marcel Hielscher, Thomas Kiss, Judit Selt, Florian Konrad, Carina Lodrini, Marco Deubzer, Hedwig E. von Deimling, Andreas Kulozik, Andreas E. Pfister, Stefan M. Witt, Olaf Milde, Till TI Targeting class I histone deacetylase 2 in MYC amplified group 3 medulloblastoma SO ACTA NEUROPATHOLOGICA COMMUNICATIONS LA English DT Article DE Medulloblastoma; HDAC; HDAC inhibitor; HDAC2; MYC ID REFRACTORY THYROID-CARCINOMA; SOLID TUMORS; PHASE-I; INHIBITOR VORINOSTAT; DISTINCT SUBGROUPS; CATALYTIC-ACTIVITY; CANCER; NEUROBLASTOMA; TRANSCRIPTION; EPENDYMOMA AB Introduction: Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Four subgroups with distinct genetic, epigenetic and clinical characteristics have been identified. Survival remains particularly poor in patients with Group 3 tumors harbouring a MYC amplification. We herein explore the molecular mechanisms and translational implications of class I histone deacetylase (HDAC) inhibition in MYC driven MBs. Material and Methods: Expression of HDACs in primary MB subgroups was compared to normal brain tissue. A panel of MB cell lines, including Group 3 MYC amplified cell lines, were used as model systems. Cells were treated with HDAC inhibitors (HDACi) selectively targeting class I or IIa HDACs. Depletion of HDAC2 was performed. Intracellular HDAC activity, cellular viability, metabolic activity, caspase activity, cell cycle progression, RNA and protein expression were analyzed. Results: HDAC2 was found to be overexpressed in MB subgroups with poor prognosis (SHH, Group 3 and Group 4) compared to normal brain and the WNT subgroup. Inhibition of the enzymatic activity of the class I HDACs reduced metabolic activity, cell number, and viability in contrast to inhibition of class IIa HDACs. Increased sensitivity to HDACi was specifically observed in MYC amplified cells. Depletion of HDAC2 increased H4 acetylation and induced cell death. Simulation of clinical pharmacokinetics showed time-dependent on target activity that correlated with binding kinetics of HDACi compounds. Conclusions: We conclude that HDAC2 is a valid drug target in patients with MYC amplified MB. HDACi should cover HDAC2 in their inhibitory profile and timing and dosing regimen in clinical trials should take binding kinetics of compounds into consideration. C1 [Ecker, Jonas; Oehme, Ina; Kiss, Judit; Selt, Florian; Konrad, Carina; Lodrini, Marco; Deubzer, Hedwig E.; Witt, Olaf; Milde, Till] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol G340, D-69120 Heidelberg, Germany. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mazitschek, Ralph] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Korshunov, Andrey; von Deimling, Andreas] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany. [Korshunov, Andrey; von Deimling, Andreas] German Canc Res Ctr, Clin Cooperat Unit Neuropathol G380, D-69120 Heidelberg, Germany. [Korshunov, Andrey; Kool, Marcel; von Deimling, Andreas; Pfister, Stefan M.] German Canc Consortium DKTK, Heidelberg, Germany. [Kool, Marcel; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol B062, D-69120 Heidelberg, Germany. [Hielscher, Thomas] German Canc Res Ctr, Div Biostat C060, D-69120 Heidelberg, Germany. [Kiss, Judit; Selt, Florian; Deubzer, Hedwig E.; Kulozik, Andreas E.; Pfister, Stefan M.; Witt, Olaf; Milde, Till] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, Sect Pediat Brain Tumors, D-69120 Heidelberg, Germany. [Lodrini, Marco; Deubzer, Hedwig E.] Charite, Dept Pediat Hematol Oncol & Bone Marrow Transplan, CVK, D-13353 Berlin, Germany. RP Milde, T (reprint author), German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol G340, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM t.milde@dkfz.de FU NCI NIH HHS [P50 CA086355, P50CA086355] NR 65 TC 11 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2051-5960 J9 ACTA NEUROPATHOL COM JI Acta Neuropathol. Commun. PD APR 3 PY 2015 VL 3 AR 22 DI 10.1186/s40478-015-0201-7 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CP9VT UT WOS:000360244000005 PM 25853389 ER PT J AU Gordon, AJ Jenkins, JA AF Gordon, Adam J. Jenkins, Jennifer A. TI The Time Is Now: The Role of Pharmacotherapies in Expanding Treatment for Opioid Use Disorder SO SUBSTANCE ABUSE LA English DT Editorial Material C1 [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Treatment Res & Educ Addict Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Jenkins, Jennifer A.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30,Mailcode 151-C, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu FU American Academy of Addiction Psychiatry (AAAP); Providers' Clinical Support System for Opioid Therapies from SAMHSA [5H79TI023439, 1H79TI025595] FX This special issue is supported by the American Academy of Addiction Psychiatry (AAAP). Funding for this initiative was made possible (in part) by Providers' Clinical Support System for Opioid Therapies (grant nos. 5H79TI023439 and 1H79TI025595) from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the US government. NR 12 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD APR 3 PY 2015 VL 36 IS 2 SI SI BP 127 EP 128 DI 10.1080/08897077.2015.1033884 PG 2 WC Substance Abuse SC Substance Abuse GA CK6UF UT WOS:000356363100001 PM 25826044 ER PT J AU Gordon, AJ Jenkins, JA Galanter, M AF Gordon, Adam J. Jenkins, Jennifer A. Galanter, Marc TI International Addiction Scholarship: Promise, Progress, and Results From the Annual Meeting of the International Society of Addiction Medicine SO SUBSTANCE ABUSE LA English DT Editorial Material ID BORDERS C1 [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Treatment Res & Educ Addict Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Jenkins, Jennifer A.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Galanter, Marc] NYU, Sch Med, Div Alcoholism & Drug Abuse, New York, NY USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30,Mailcode 151-C, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD APR 3 PY 2015 VL 36 IS 2 SI SI BP 129 EP 130 DI 10.1080/08897077.2015.1033887 PG 2 WC Substance Abuse SC Substance Abuse GA CK6UF UT WOS:000356363100002 PM 25826272 ER PT J AU Jenkins, JA Alford, DP Gordon, AJ AF Jenkins, Jennifer A. Alford, Daniel P. Gordon, Adam J. TI Building Connections and Bridging Interdisciplinary Leadership in Addictions: 2014 AMERSA Annual Conference and a Thank You to Reviewers SO SUBSTANCE ABUSE LA English DT Editorial Material C1 [Jenkins, Jennifer A.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Alford, Daniel P.] AMERSA, Cranston, RI USA. [Alford, Daniel P.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Treatment Res & Educ Addict Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30,Mailcode 151-C, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD APR 3 PY 2015 VL 36 IS 2 SI SI BP 131 EP 134 DI 10.1080/08897077.2015.1033910 PG 4 WC Substance Abuse SC Substance Abuse GA CK6UF UT WOS:000356363100003 PM 25826178 ER PT J AU Cochran, G Woo, B Lo-Ciganic, WH Gordon, AJ Donohue, JM Gellad, WF AF Cochran, Gerald Woo, Bongki Lo-Ciganic, Wei-Hsuan Gordon, Adam J. Donohue, Julie M. Gellad, Walid F. TI Defining Nonmedical Use of Prescription Opioids Within Health Care Claims: A Systematic Review SO SUBSTANCE ABUSE LA English DT Review DE systematic review; Non-medical use of prescription opioids; health insurance ID NATIONAL EPIDEMIOLOGIC SURVEY; MENTAL-HEALTH; UNITED-STATES; 10-YEAR PERSPECTIVE; IDENTIFY PATIENTS; USE DISORDERS; DRUG-USE; ABUSE; MISUSE; PAIN AB Background: Health insurance claims data may play an important role for health care systems and payers in monitoring the nonmedical use of prescription opioids (NMPO) among patients. However, these systems require valid methods for identifying NMPO if they are to target individuals for intervention. Limited efforts have been made to define NMPO using administrative data available to health systems and payers. We conducted a systematic review of publications that defined and measured NMPO within health insurance claims databases in order to describe definitions of NMPO and identify areas for improvement. Methods: We searched 8 electronic databases for articles that included terms related to NMPO and health insurance claims. A total of 2613 articles were identified in our search. Titles, abstracts, and article full texts were assessed according to predetermined inclusion/exclusion criteria. Following article selection, we extracted general information, conceptual and operational definitions of NMPO, methods used to validate operational definitions of NMPO, and rates of NMPO. Results: A total of 7 studies met all inclusion criteria. A range of conceptual NMPO definitions emerged, from concrete concepts of abuse to qualified definitions of probable misuse. Operational definitions also varied, ranging from variables that rely on diagnostic codes to those that rely on opioid dosage and/or filling patterns. Quantitative validation of NMPO definitions was reported in 3 studies (e.g., receiver operating curves or logistic regression), with each study indicating adequate validity. Three studies reported qualitative validation, using face and content validity. One study reported no validation efforts. Rates of NMPO among the studies' populations ranged from 0.75% to 10.32%. Conclusions: Disparate definitions of NMPO emerged from the literature, with little uniformity in conceptualization and operationalization. Validation approaches were also limited, and rates of NMPO varied across studies. Future research should prospectively test and validate a construct of NMPO to disseminate to payers and health officials. C1 [Cochran, Gerald] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15260 USA. [Cochran, Gerald; Lo-Ciganic, Wei-Hsuan; Gordon, Adam J.; Donohue, Julie M.; Gellad, Walid F.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA 15260 USA. [Woo, Bongki] Boston Coll, Sch Social Work, Boston, MA USA. [Gordon, Adam J.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, Adam J.; Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. RP Cochran, G (reprint author), Univ Pittsburgh, Sch Social Work, 4200 Forbes Ave,2117 CL, Pittsburgh, PA 15260 USA. EM gcochran@pitt.edu OI Donohue, Julie/0000-0003-2418-6017 FU CDC/NIDA [U01CE002496-01]; VA HSR&D Career Development Award [09-207] FX Drs. Cochran, Donohue, Gordon, and Gellad are supported by CDC/NIDA U01CE002496-01. Dr. Gellad is also supported by a VA HSR&D Career Development Award (09-207). Funders were not involved in study design, the collection, analysis, or interpretation of data, the writing of the report, or the decision to submit the manuscript for publication. The authors declare that they have no conflicts of interest. NR 39 TC 6 Z9 6 U1 5 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD APR 3 PY 2015 VL 36 IS 2 SI SI BP 192 EP 202 DI 10.1080/08897077.2014.993491 PG 11 WC Substance Abuse SC Substance Abuse GA CK6UF UT WOS:000356363100015 PM 25671499 ER PT J AU Farmer, CM Lindsay, D Williams, J Ayers, A Schuster, J Cilia, A Flaherty, MT Mandell, T Gordon, AJ Stein, BD AF Farmer, Carrie M. Lindsay, Dawn Williams, Jessica Ayers, Amanda Schuster, James Cilia, Alyssa Flaherty, Michael T. Mandell, Todd Gordon, Adam J. Stein, Bradley D. TI Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results ofanExpert Panel Process SO SUBSTANCE ABUSE LA English DT Article DE Buprenorphine; opioid use disorders; clinical practice guidelines ID 1ST 3 YEARS; SERVICE UTILIZATION; ALGORITHM PROJECT; MENTAL-DISORDERS; UNITED-STATES; ADDICTION; BARRIERS; DEPENDENCE; IMPLEMENTABILITY; COMORBIDITY AB ABSTRACT. Background: Although the number of physicians credentialed to prescribe buprenorphine has increased over time, many credentialed physicians may be reluctant to treat individuals with opioid use disorders due to discomfort with prescribing buprenorphine. Although prescribing physicians are required to complete a training course, many have questions about buprenorphine and treatment guidelines have not been updated to reflect clinical experience in recent years. We report on an expert panel process to update and expand buprenorphine guidelines. Methods: We identified candidate guidelines through expert opinion and a review of the literature and used a modified RAND/UCLA Appropriateness Method to assess the validity of the candidate guidelines. An expert panel completed 2 rounds of rating, with a meeting to discuss the guidelines between the first and second ratings. Results: Through the rating process, expert panel members rated 90 candidate guideline statements across 8 domains, including candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial counseling, and treatment of co-occurring depression and anxiety. A total of 65 guideline statements (72%) were rated as valid. Expert panel members had agreement in some areas, such as the treatment of co-occurring mental health problems, but disagreement in others, including the appropriate dosing of buprenorphine given patient complexities. Conclusions: Through an expert panel process, we developed an updated and expanded set of buprenorphine treatment guidelines; this additional guidance may increase credentialed physicians' comfort with prescribing buprenorphine to patients with opioid use disorders. Future efforts should focus on appropriate dosing guidance and ensuring that guidelines can be adapted to a variety of practice settings. C1 [Farmer, Carrie M.; Stein, Bradley D.] RAND Corp, Pittsburgh, PA 15213 USA. [Lindsay, Dawn; Williams, Jessica] Inst Res Educ & Training Addict, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Ayers, Amanda; Schuster, James; Cilia, Alyssa] Univ Pittsburgh, Med Ctr, Insurance Div, Community Care Behav Hlth Org, Pittsburgh, PA USA. [Flaherty, Michael T.] Clin Practice, Murrysville, PA USA. [Mandell, Todd] Community Subst Abuse Ctr, Westfield, MA USA. RP Farmer, CM (reprint author), RAND Corp, 4570 Fifth Ave,Suite 600, Pittsburgh, PA 15213 USA. EM cfarmer@rand.org FU NIDA NIH HHS [R01 DA032881] NR 52 TC 4 Z9 4 U1 4 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD APR 3 PY 2015 VL 36 IS 2 SI SI BP 209 EP 216 DI 10.1080/08897077.2015.1012613 PG 8 WC Substance Abuse SC Substance Abuse GA CK6UF UT WOS:000356363100017 PM 25844527 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Photography and Exploration SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PD APR 3 PY 2015 VL 13 IS 2 SI SI BP 174 EP 175 DI 10.1080/17460654.2015.1013254 PG 2 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA CI1ZL UT WOS:000354543800006 ER PT J AU Ornstein, RD AF Ornstein, Rafael D. TI Seeing Through the Fog: Learning to Work with Dissociation SO PSYCHOANALYTIC INQUIRY LA English DT Article AB Often the experience of learning from the patient is seamless, embedded in the unfolding clinical process. Patient and analyst bring their respective needs and capacities to this relationship and find new ways to collaborate toward the emotional growth of the patient, with the expectable amount of challenge and surprise along the way. Hopefully, analysts learn with every clinical encounter-but frequently it is when they are most challenged that they are aware of learning something particular from their patients about the therapeutic process. Patients with significant narcissistic vulnerabilities and corresponding narcissistic defenses can be quite challenging in treatment, especially in regards to the way that affects and whole sectors of the personality can be split-off and inaccessible in the treatment for a considerable time. It is the nature of this splitting-off, its subtle yet pervasive role in the treatment relationship, and the manner in which it led to both impasse and then insight, that became the focus of my learning from my patient. This article describes a treatment in which the dissociative process itself was dissociated, and how that came into awareness for both patient and analyst. C1 [Ornstein, Rafael D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ornstein, Rafael D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ornstein, Rafael D.] Boston Psychoanalyt Soc & Inst, Boston, MA USA. RP Ornstein, RD (reprint author), 1419 Beacon St,Suite 23, Brookline, MA 02446 USA. EM rornstein@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0735-1690 EI 1940-9133 J9 PSYCHOANAL INQ JI Psychoanal. Inq. PD APR 3 PY 2015 VL 35 IS 3 SI SI BP 257 EP 270 DI 10.1080/07351690.2015.1012460 PG 14 WC Psychology, Psychoanalysis SC Psychology GA CG7NH UT WOS:000353490000003 ER PT J AU Villar, J Cabrera-Benitez, NE Valladares, F Garcia-Hernandez, S Ramos-Nuez, A Martin-Barrasa, JL Muros, M Kacmarek, RM Slutsky, AS AF Villar, Jesus Cabrera-Benitez, Nuria E. Valladares, Francisco Garcia-Hernandez, Sonia Ramos-Nuez, Angela Luis Martin-Barrasa, Jose Muros, Mercedes Kacmarek, Robert M. Slutsky, Arthur S. TI Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury SO CRITICAL CARE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; MAST-CELL TRYPTASE; MECHANICAL VENTILATION; BETA-TRYPTASE; ACTIVATED RECEPTOR-2; EXPRESSION; COLLAGEN; FIBROPROLIFERATION; FIBROBLASTS; RESPONSES AB Introduction: Most patients with sepsis and acute lung injury require mechanical ventilation to improve oxygenation and facilitate organ repair. Mast cells are important in response to infection and resolution of tissue injury. Since tryptase secreted from mast cells has been associated with tissue fibrosis, we hypothesized that tryptase would be involved in the early development of ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis-induced lung injury. Methods: Prospective, randomized, controlled animal study using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. Animals were randomized to spontaneous breathing or two ventilatory strategies for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH(2)O positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20 ml/kg plus 2 cmH(2)O PEEP. Healthy, non-ventilated animals served as non-septic controls. We studied the following end points: histology, serum cytokine levels, hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2) protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical localization in the lungs. Results: All septic animals developed acute lung injury. Animals ventilated with high VT had a significant increase of pulmonary fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to septic controls (P < 0.0001). However, protective ventilation attenuated sepsis-induced lung injury and decreased lung tryptase and PAR-2 protein levels. Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the lungs. Conclusions: Mechanical ventilation modified tryptase and PAR-2 in injured lungs. Increased levels of these proteins were associated with development of sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis-induced lung injury. C1 [Villar, Jesus; Cabrera-Benitez, Nuria E.; Valladares, Francisco; Ramos-Nuez, Angela; Muros, Mercedes] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid 28029, Spain. [Villar, Jesus; Cabrera-Benitez, Nuria E.; Ramos-Nuez, Angela; Luis Martin-Barrasa, Jose] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria 35010, Spain. [Villar, Jesus; Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON M5B 1W8, Canada. [Valladares, Francisco; Garcia-Hernandez, Sonia] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife 38071, Spain. [Muros, Mercedes] Hosp Univ NS Candelaria, Dept Clin Biochem, Santa Cruz De Tenerife 38010, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. [Slutsky, Arthur S.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON M5G 2N2, Canada. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Monforte de Lemos 3-5, Madrid 28029, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III, Madrid, Spain [CB06/06/1088, PI10/0393]; Asociacion Cientifica Pulmon y Ventilacion Mecanica, Spain FX Supported in part by grants (CB06/06/1088, PI10/0393) from Instituto de Salud Carlos III, Madrid, Spain, and by Asociacion Cientifica Pulmon y Ventilacion Mecanica, Spain. NR 46 TC 0 Z9 0 U1 0 U2 5 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 APR 3 PY 2015 VL 19 AR 138 DI 10.1186/s13054-015-0878-9 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CF2CJ UT WOS:000352354600001 PM 25871971 ER PT J AU Sakurai, K Chen, J Khani, SC Kefalov, VJ AF Sakurai, Keisuke Chen, Jeannie Khani, Shahrokh C. Kefalov, Vladimir J. TI Regulation of Mammalian Cone Phototransduction by Recoverin and Rhodopsin Kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-PHOTON RESPONSES; VISUAL PIGMENT PHOSPHORYLATION; LIGHT ADAPTATION; ROD PHOTORECEPTORS; RETINAL RODS; GUANYLATE-CYCLASE; TRANSGENIC MICE; FROG RETINA; S-MODULIN; CALCIUM AB Cone photoreceptors function under daylight conditions and are essential for color perception and vision with high temporal and spatial resolution. A remarkable feature of cones is that, unlike rods, they remain responsive in bright light. In rods, light triggers a decline in intracellular calcium, which exerts a well studied negative feedback on phototransduction that includes calcium-dependent inhibition of rhodopsin kinase (GRK1) by recoverin. Rods and cones share the same isoforms of recoverin and GRK1, and photoactivation also triggers a calcium decline in cones. However, the molecular mechanisms by which calcium exerts negative feedback on cone phototransduction through recoverin and GRK1 are not well understood. Here, we examined this question using mice expressing various levels of GRK1 or lacking recoverin. We show that although GRK1 is required for the timely inactivation of mouse cone photoresponse, gradually increasing its expression progressively delays the cone response recovery. This surprising result is in contrast with the known effect of increasing GRK1 expression in rods. Notably, the kinetics of cone responses converge and become independent of GRK1 levels for flashes activating more than similar to 1% of cone pigment. Thus, mouse cone response recovery in bright light is independent of pigment phosphorylation and likely reflects the spontaneous decay of photoactivated visual pigment. We also find that recoverin potentiates the sensitivity of cones in dim light conditions but does not contribute to their capacity to function in bright light. C1 [Sakurai, Keisuke; Kefalov, Vladimir J.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Chen, Jeannie] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Chen, Jeannie] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. [Khani, Shahrokh C.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Khani, Shahrokh C.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kefalov, VJ (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA. EM kefalov@vision.wustl.edu FU National Institutes of Health [EY19543, EY19312, EY12703, EY12155, EY02687]; Research to Prevent Blindness; Uehara Memorial Foundation, Japan FX This work was supported, in whole or in part, by National Institutes of Health Grants EY19543 and EY19312 (to V. J. K.), EY12703 and EY12155 (to J. C.), and EY02687 (to Washington University Department Ophthalmology). This work was also supported by Research to Prevent Blindness and a grant from the Uehara Memorial Foundation, Japan (to K. S.). NR 52 TC 2 Z9 2 U1 2 U2 8 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 APR 3 PY 2015 VL 290 IS 14 BP 9239 EP 9250 DI 10.1074/jbc.M115.639591 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CF0BI UT WOS:000352207100045 PM 25673692 ER PT J AU Wesa, KM Segal, NH Cronin, AM Sjoberg, DD Jacobs, GN Coleton, MI Fleisher, M Dnistrian, AM Saltz, LB Cassileth, BR AF Wesa, Kathleen M. Segal, Neil H. Cronin, Angel M. Sjoberg, Daniel D. Jacobs, Gria N. Coleton, Marci I. Fleisher, Martin Dnistrian, Ann M. Saltz, Leonard B. Cassileth, Barrie R. TI Serum 25-Hydroxy Vitamin D and Survival in Advanced Colorectal Cancer: A Retrospective Analysis SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID D DEFICIENCY; D-RECEPTOR; BREAST-CANCER; COLON-CANCER; RECTAL-CANCER; HEALTH; RISK; POLYMORPHISMS; EXPRESSION; PREVENTION AB Higher serum 25-hydroxy vitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) incidence. In this retrospective study of Stage IV CRC patients, we evaluate whether 25(OH)D levels at diagnosis correlate with survival. Stored sera from carcinoembryonic antigen (CEA) measurements obtained between February 2005 and March 2006 were screened. The first 250 patients with CEA +/- 30days of Stage IV CRC diagnosis were included. Serum 25(OH)D levels were determined and categorized as adequate >= 30ng/mL, or deficient <30ng/mL. Multivariable Cox regression models controlling for albumin and Eastern Cooperative Oncology Group performance status were used to investigate whether higher 25(OH)D levels were associated with prolonged survival. A total of 207 patients (83%) were vitamin D-deficient (median = 21ng/mL), with deficiencies significantly more likely among non-Hispanic black patients (P = 0.009). Higher levels were associated with prolonged survival in categorical variable analysis: adequate vs. deficient, hazard ratio = 0.61, 95% confidence interval = 0.38-0.98, P = 0.041. A majority of newly diagnosed Stage IV CRC patients are vitamin D-deficient. Our data suggest that higher 25(OH)D levels are associated with better overall survival. Clinical trials to determine whether aggressive vitamin D repletion would improve outcomes for vitamin D-deficient CRC patients are warranted. C1 [Wesa, Kathleen M.; Jacobs, Gria N.; Coleton, Marci I.; Cassileth, Barrie R.] Mem Sloan Kettering Canc Ctr, Integrat Med Serv, New York, NY 10021 USA. [Segal, Neil H.; Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, New York, NY 10021 USA. [Cronin, Angel M.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Sjoberg, Daniel D.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Fleisher, Martin; Dnistrian, Ann M.] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10021 USA. RP Wesa, KM (reprint author), 139-15 89th Ave, Briarwood, NY 11435 USA. EM gopiwesa@gmail.com OI Saltz, Leonard/0000-0001-8353-4670 FU NIH/NCI Cancer Center Support Grant [P30 CA008748]; Gateway for Cancer Research Foundation FX This study was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748 and a grant from the Gateway for Cancer Research Foundation. NR 43 TC 5 Z9 7 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PD APR 3 PY 2015 VL 67 IS 3 BP 424 EP 430 DI 10.1080/01635581.2015.998838 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA CF1OO UT WOS:000352316200005 PM 25646565 ER PT J AU Mandinova, A Lee, SW AF Mandinova, Anna Lee, Sam W. TI p53 The Gene That Cracked the Cancer Code SO SCIENCE LA English DT Book Review C1 [Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Mandinova, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bldg 49,13th St, Charlestown, MA 02129 USA. EM amandinova@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 3 U2 13 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 APR 3 PY 2015 VL 348 IS 6230 BP 49 EP 49 DI 10.1126/science.aaa8194 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8GJ UT WOS:000352079500024 ER PT J AU Garrett, WS AF Garrett, Wendy S. TI Cancer and the microbiota SO SCIENCE LA English DT Review ID ENTEROTOXIGENIC BACTEROIDES-FRAGILIS; STEM-CELL TRANSPLANTATION; CHAIN FATTY-ACIDS; NF-KAPPA-B; INTESTINAL INFLAMMATION; FUSOBACTERIUM-NUCLEATUM; GUT MICROBIOTA; COLORECTAL-CANCER; COLON-CANCER; TUMOR PROGRESSION AB A host's microbiota may increase, diminish, or have no effect at all on cancer susceptibility. Assigning causal roles in cancer to specific microbes and microbiotas, unraveling host-microbiota interactions with environmental factors in carcinogenesis, and exploiting such knowledge for cancer diagnosis and treatment are areas of intensive interest. This Review considers how microbes and the microbiota may amplify or mitigate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complications. C1 [Garrett, Wendy S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Garrett, WS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM wendy_garrett@dfci.harvard.edu FU NIH [R01CA154426]; Burroughs Wellcome Career in Medical Sciences Award; Searle Scholars Award; Cancer Research Institute Investigator Award; Hoffman-LaRoche FX W.S.G. thanks C. Brennan, C. Gallini, G. Hold, C. Lesser, and M. Howitt for critical reading of the manuscript. Supported by NIH grant R01CA154426, a Burroughs Wellcome Career in Medical Sciences Award, a Searle Scholars Award, a Cancer Research Institute Investigator Award, and a research grant from Hoffman-LaRoche. W.S.G. is a Synlogic SAB member. NR 118 TC 74 Z9 76 U1 32 U2 152 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 APR 3 PY 2015 VL 348 IS 6230 BP 80 EP 86 DI 10.1126/science.aaa4972 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8GJ UT WOS:000352079500030 PM 25838377 ER PT J AU Walton, HM Chow, L Topor, DR Pepple, JR Fish, S Ahnallen, CG AF Walton, Heather M. Chow, Louis Topor, David R. Pepple, John R. Fish, Scott Ahnallen, Christopher G. TI Treatment of Women Veterans with Posttraumatic Stress Disorder and Serious Mental Illness in an Inpatient Mental Health Treatment Setting: A Case Study SO WOMEN & THERAPY LA English DT Article DE CPT; SMI; PTSD; women; veterans ID TRAUMA AB This article discusses the challenges of providing treatment for women with complex dual diagnostic mental health needs. In particular, the focus is on the intersections between posttraumatic stress disorder (PTSD), serious mental illness (SMI), female gender, and veteran status. Utilizing a clinical case example, we focus our discussion on psychotherapy goals and interventions, including the advisability of engaging in trauma-focused therapy on an inpatient unit with a patient who carries an SMI diagnosis. We also address benefits and challenges of providing this type of treatment, provider reactions including burnout and diagnostic bias, and recommendations for future care for persons with similar presentations and needs. C1 [Walton, Heather M.; Chow, Louis; Topor, David R.; Pepple, John R.; Fish, Scott; Ahnallen, Christopher G.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Walton, Heather M.; Chow, Louis; Topor, David R.; Pepple, John R.; Fish, Scott; Ahnallen, Christopher G.] Harvard Univ, Sch Med, Boston, MA USA. [Chow, Louis] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Walton, HM (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM heather.walton@va.gov NR 13 TC 1 Z9 1 U1 0 U2 18 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0270-3149 EI 1541-0315 J9 WOMEN THER JI Women Ther. PD APR 3 PY 2015 VL 38 IS 1-2 SI SI BP 128 EP 140 DI 10.1080/02703149.2014.978227 PG 13 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA CB0PQ UT WOS:000349329200009 ER PT J AU Wu, E Barnes, DE Ackerman, SL Lee, J Chesney, M Mehling, WE AF Wu, Eveline Barnes, Deborah E. Ackerman, Sara L. Lee, Jennifer Chesney, Margaret Mehling, Wolf E. TI Preventing Loss of Independence through Exercise (PLIe): qualitative analysis of a clinical trial in older adults with dementia SO AGING & MENTAL HEALTH LA English DT Article DE qualitative methods; general; Alzheimer's disease; other dementias ID RANDOMIZED-CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; TAI-CHI; PHYSICAL-ACTIVITY; SUPPORTING SELF; INTERVENTIONS; BALANCE; PEOPLE; METAANALYSIS; INDIVIDUALS AB Objectives: Preventing Loss of Independence through Exercise (PLIe) is a novel, integrative exercise program for individuals with dementia that combines elements of different conventional and complementary exercise modalities (e.g. tai-chi, yoga, Feldenkrais, and dance movement therapy) and focuses on training procedural memory for basic functional movements (e.g., sit-to-stand) while increasing mindful body awareness and facilitating social connection. This study presents analyses of qualitative data collected during a 36-week cross-over pilot clinical trial in 11 individuals. Methods: Qualitative data included exercise instructors' written notes, which were prepared after each class and also following biweekly telephone calls with caregivers and monthly home visits; three video-recorded classes; and written summaries prepared by research assistants following pre- and post-intervention quantitative assessments. Data were extracted for each study participant and placed onto a timeline for month of observation. Data were coded and analyzed to identify themes that were confirmed and refined through an iterative, collaborative process by the entire team including a qualitative researcher (SA) and the exercise instructors. Results: Three overarching themes emerged: (1) Functional changes included increasing body awareness, movement memory and functional skill. (2) Emotional changes included greater acceptance of resting, sharing of personal stories and feelings, and positive attitude toward exercise. (3) Social changes included more coherent social interactions and making friends. Conclusions: These qualitative results suggest that the PLIe program may be associated with beneficial functional, emotional, and social changes for individuals with mild to moderate dementia. Further study of the PLIe program in individuals with dementia is warranted. C1 [Wu, Eveline; Lee, Jennifer; Chesney, Margaret; Mehling, Wolf E.] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Wu, Eveline] Calif Inst Integral Studies, Dept Counseling Psychol, San Francisco, CA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerman, Sara L.] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA USA. [Mehling, Wolf E.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. RP Mehling, WE (reprint author), Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. EM mehlingw@ocim.ucsf.edu NR 55 TC 5 Z9 6 U1 9 U2 199 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PD APR 3 PY 2015 VL 19 IS 4 BP 353 EP 362 DI 10.1080/13607863.2014.935290 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AZ6EP UT WOS:000348311900007 PM 25022459 ER PT J AU Atwiine, B Kiwanuka, J Musinguzi, N Atwine, D Haberer, JE AF Atwiine, Barnabas Kiwanuka, Julius Musinguzi, Nicholas Atwine, Daniel Haberer, Jessica E. TI Understanding the role of age in HIV disclosure rates and patterns for HIV-infected children in southwestern Uganda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE children; disclosure; AIDS; Uganda; HIV ID ADHERENCE AB Highly active antiretroviral therapy has enabled HIV-infected children to survive into adolescence and adulthood, creating need for their own HIV diagnosis disclosure. Disclosure has numerous social and medical benefits for the child and family; however, disclosure rates tend to be low, especially in developing countries, and further understanding of the barriers is needed. This study describes the patterns and correlates of disclosure among HIV-infected children in southwestern Uganda. A cross-sectional study was conducted in a referral hospital pediatric HIV clinic between February and April 2012. Interviews were administered to caregivers of HIV-infected children aged 5-17 years. Data collected included socio-demographic characteristics of the child and caregiver, reported disclosure status, and caregivers' reasons for full disclosure or non-full disclosure of HIV status to their children. Bivariate and multivariate analysis was done to establish the socio-demographic correlates of disclosure. Caregivers provided data for 307 children; the median age was eight years (interquartile range [IQR] 7-11) and 52% were males. Ninety-five (31%) children had received full disclosure (48% of whom were >12 years), 22 children (7%) had received partial disclosure, 39 (13%) misinformation, and 151 (49%) no disclosure. Full disclosure was significantly more prevalent among the 9-11 and 12- to 17-year-olds compared to 5- to 8-year-olds (p-value < 0.001). The most frequently stated reason for disclosure was the hope that disclosure would improve medication adherence; the most frequently stated reason for nondisclosure was the belief that the child was too young to understand his/her illness. There was an inverse relationship between age and full disclosure and partial disclosure was rare across all age groups, suggesting a pattern of rapid, late disclosure. Disclosure programs should emphasize the importance of gradual disclosure, starting at younger ages, to maximize the benefits to the child and caregiver. C1 [Atwiine, Barnabas; Kiwanuka, Julius] Mbarara Univ Sci & Technol, Dept Paediat & Child Hlth, Mbarara, Uganda. [Atwiine, Barnabas; Kiwanuka, Julius] Mbarara Reg Referral Hosp, Dept Paediat & Child Hlth, Mbarara, Uganda. [Musinguzi, Nicholas] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Atwine, Daniel] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. [Atwine, Daniel] Mbarara Res Ctr, Epictr, Mbarara, Uganda. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Atwiine, B (reprint author), Mbarara Univ Sci & Technol, Dept Paediat & Child Hlth, Mbarara, Uganda. EM atwiine78@gmail.com NR 17 TC 2 Z9 2 U1 2 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD APR 3 PY 2015 VL 27 IS 4 BP 424 EP 430 DI 10.1080/09540121.2014.978735 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CA1HG UT WOS:000348662800003 PM 25397994 ER PT J AU Di Savino, A Panuzzo, C Rocca, S Familiari, U Piazza, R Crivellaro, S Carra, G Ferretti, R Fusella, F Giugliano, E Camporeale, A Franco, I Miniscalco, B Cutrin, JC Turco, E Silengo, L Hirsch, E Rege-Cambrin, G Gambacorti-Passerini, C Pandolfi, PP Papotti, M Saglio, G Tarone, G Morotti, A Brancaccio, M AF Di Savino, Augusta Panuzzo, Cristina Rocca, Stefania Familiari, Ubaldo Piazza, Rocco Crivellaro, Sabrina Carra, Giovanna Ferretti, Roberta Fusella, Federica Giugliano, Emilia Camporeale, Annalisa Franco, Irene Miniscalco, Barbara Cutrin, Juan Carlos Turco, Emilia Silengo, Lorenzo Hirsch, Emilio Rege-Cambrin, Giovanna Gambacorti-Passerini, Carlo Pandolfi, Pier Paolo Papotti, Mauro Saglio, Giuseppe Tarone, Guido Morotti, Alessandro Brancaccio, Mara TI Morgana acts as an oncosuppressor in chronic myeloid leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; BCR-ABL; CHROMOSOMAL INSTABILITY; CENTROSOME DUPLICATION; KINASE INHIBITORS; CANCER; IMATINIB; CELLS; MUTATIONS AB We recently described morgana as an essential protein able to regulate centrosome duplication and genomic stability, by inhibiting ROCK. Here we show that morgana(+/-) mice spontaneously develop a lethal myeloproliferative disease resembling human atypical chronic myeloid leukemia (aCML), preceded by ROCK hyperactivation, centrosome amplification, and cytogenetic abnormalities in the bone marrow (BM). Moreover, we found that morgana is underexpressed in the BM of patients affected by atypical CML, a disorder of poorly understood molecular basis, characterized by nonrecurrent cytogenetic abnormalities. Morgana is also underexpressed in the BM of a portion of patients affected by Philadelphia-positive CML (Ph+ CML) caused by the BCR-ABL oncogene, and in this condition, morgana underexpression predicts a worse response to imatinib, the standard treatment for Ph+ CML. Thus, morgana acts as an oncosuppressor with different modalities: (1) Morgana underexpression induces centrosome amplification and cytogenetic abnormalities, and (2) in Ph+ CML, it synergizes with BCR-ABL signaling, reducing the efficacy of imatinib treatment. Importantly, ROCK inhibition in the BM of patients underexpressing morgana restored the efficacy of imatinib to induce apoptosis, suggesting that ROCK inhibitors, combined with imatinib treatment, can overcome suboptimal responses in patients in which morgana is underexpressed. C1 [Di Savino, Augusta; Rocca, Stefania; Ferretti, Roberta; Fusella, Federica; Camporeale, Annalisa; Franco, Irene; Cutrin, Juan Carlos; Turco, Emilia; Silengo, Lorenzo; Hirsch, Emilio; Pandolfi, Pier Paolo; Tarone, Guido; Brancaccio, Mara] Univ Turin, Dept Mol Biotechnol & Hlth Sci, I-10126 Turin, Italy. [Panuzzo, Cristina; Crivellaro, Sabrina; Carra, Giovanna; Giugliano, Emilia; Rege-Cambrin, Giovanna; Saglio, Giuseppe; Morotti, Alessandro] Univ Turin, Dept Clin & Biol Sci, Div Internal Med & Hematol, I-10126 Turin, Italy. [Familiari, Ubaldo; Papotti, Mauro] Univ Turin, St Luigi Hosp, Dept Oncol, Div Pathol, I-10126 Turin, Italy. [Piazza, Rocco; Gambacorti-Passerini, Carlo] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy. [Miniscalco, Barbara] Dept Vet Sci, Clin Sect, Grugliasco, Italy. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Med & Pathol, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA. RP Brancaccio, M (reprint author), Univ Turin, Ctr Mol Biotechnol, Via Nizza 52, I-10126 Turin, Italy. EM alessandro.morotti@unito.it; mara.brancaccio@unito.it OI Morotti, Alessandro/0000-0002-8407-2903; GAMBACORTI PASSERINI, CARLO/0000-0001-6058-515X; Panuzzo, Cristina/0000-0002-2814-6453; Carra, Giovanna/0000-0002-6263-6800; Hirsch, Emilio/0000-0002-9073-6024 FU AIRC [IG 11456]; Italian Ministry of Health [GR-2010-2312984]; AIRC FX This work was supported by AIRC grant IG 11456 AIRC 2011 (M.B.), the Italian Ministry of Health (Giovani Ricercatori-Ricerca Finalizzata 2010; GR-2010-2312984) (A.M.), and a fellowship from AIRC (annual fellowship "Marco Fabio Sartori") (A.D.). NR 49 TC 6 Z9 6 U1 0 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 APR 2 PY 2015 VL 125 IS 14 BP 2245 EP 2253 DI 10.1182/blood-2014-05-575001 PG 9 WC Hematology SC Hematology GA CI3DD UT WOS:000354626900012 PM 25678499 ER PT J AU Sridhar, BV Brock, JL Silver, JS Leight, JL Randolph, MA Anseth, KS AF Sridhar, Balaji V. Brock, John L. Silver, Jason S. Leight, Jennifer L. Randolph, Mark A. Anseth, Kristi S. TI Development of a Cellularly Degradable PEG Hydrogel to Promote Articular Cartilage Extracellular Matrix Deposition SO ADVANCED HEALTHCARE MATERIALS LA English DT Article ID MESENCHYMAL STEM-CELLS; POLY(ETHYLENE GLYCOL) HYDROGELS; TISSUE-ENGINEERED CARTILAGE; CROSS-LINKING DENSITY; GROWTH-FACTOR-BETA; CHONDROGENIC DIFFERENTIATION; CHONDROCYTE METABOLISM; REPAIR; POLYMER; CULTURE AB Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene hydrogel is functionalized with thiolated transforming growth factor (TGF-beta 1) and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated with a smaller population of mesenchymal stem cells, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. The co-encapsulated cells cleave the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly degraded materials show significantly increased glycosaminoglycan and collagen deposition over just 14 d of culture, while maintaining high levels of viability and producing a more widely-distributed matrix. These results indicate the potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. C1 [Sridhar, Balaji V.; Brock, John L.; Silver, Jason S.; Leight, Jennifer L.; Anseth, Kristi S.] Univ Colorado, Dept Chem & Biol Engn, Boulder, CO 80303 USA. [Sridhar, Balaji V.; Brock, John L.; Silver, Jason S.; Leight, Jennifer L.; Anseth, Kristi S.] Univ Colorado, Biofrontiers Inst, Boulder, CO 80303 USA. [Leight, Jennifer L.] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. [Leight, Jennifer L.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Leight, Jennifer L.; Anseth, Kristi S.] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80303 USA. [Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Dept Orthopaed Surg,Med Sch, Boston, MA 02114 USA. [Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Plast Surg Res Lab, Div Plast Surg,Med Sch, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Dept Orthopaed Surg,Med Sch, 55 Fruit St,WAC 435, Boston, MA 02114 USA. EM randolph.mark@mgh.harvard.edu; kristi.anseth@colorado.edu RI Randolph, Mark/A-4406-2009 FU Howard Hughes Medical Institute; Department of Defense [W81XWH-10-1-0791] FX The authors acknowledge Kyle Kyburz and Chun Yang for providing MSCs, as well as Amanda Meppelink and Richard Erali for providing knees on which chondrocyte isolations were performed. The authors would also like to acknowledge Emi Tokuda for helping purify the fluorescent peptide sensor as well as Dr. William Wan, Dr. Huan Wang for assistance on experimental design, and Russell Chagolla for help with image analysis. Funding for these studies was provided by the Howard Hughes Medical Institute and Department of Defense award number W81XWH-10-1-0791. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. NR 54 TC 17 Z9 18 U1 15 U2 101 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 APR 2 PY 2015 VL 4 IS 5 BP 702 EP 713 DI 10.1002/adhm.201400695 PG 12 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA CF5TR UT WOS:000352620500009 PM 25607633 ER PT J AU Bayes-Genis, A Januzzi, JL AF Bayes-Genis, Antoni Januzzi, James L. TI The International ST2 Consensus Panel: Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID HEART-FAILURE; BIOMARKERS C1 [Bayes-Genis, Antoni] Hosp Univ Germans Trias i Pujol, Dept Cardiol, Barcelona, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bayes-Genis, A (reprint author), UAB, Hosp Univ Germans Trias i Pujol, Dept Med, Carretera Canyet S-N, Barcelona 08916, Spain. EM abayesgenis@gmail.com OI Bayes-Genis, Antoni/0000-0002-3044-197X NR 5 TC 0 Z9 0 U1 2 U2 3 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 APR 2 PY 2015 VL 115 IS 7 SU S BP 1B EP 2B DI 10.1016/j.amjcard.2015.01.033 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200001 PM 25665760 ER PT J AU Pascual-Figal, DA Januzzi, JL AF Pascual-Figal, Domingo A. Januzzi, James L. TI The Biology of ST2: The International ST2 Consensus Panel SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RECEPTOR FAMILY-MEMBER; INTERLEUKIN-1 RECEPTOR; IL-1 RECEPTOR; MYOCARDIAL-INFARCTION; ACUTE DYSPNEA; SOLUBLE ST2; PROTEIN; CELLS; CYTOKINE; GENE AB ST2 is a member of the interleukin 1 receptor family with 2 main isoforms: transmembrane or cellular (ST2L) and soluble or circulating (sST2) forms. ST2 is the receptor of the IL-33, which is an IL-1-like cytokine that can be secreted by living cells in response to cell damage. IL-33 exerts its cellular functions by binding a receptor complex composed of ST2L and IL-1R accessory protein. The IL-33/ST2 system is upregulated in cardiomyocytes and fibroblasts as response to mechanical stimulation or injury. The interaction between IL33 and ST2L has been demonstrated to be cardioprotective: in experimental models, this interaction reduces myocardial fibrosis, prevents cardiomyocyte hypertrophy, reduces apoptosis, and improves myocardial function. The beneficial effects of IL-33 are specifically through the ST2L receptor. sST2 avidly binds IL-33 which results in interruption of the interaction between IL-33/ST2L and consequently eliminates the antiremodeling effects; thus, sST2 is viewed as a decoy receptor. In recent years, knowledge about ST2 role in the pathophysiology of cardiovascular diseases has broadly expanded, with strong links to myocardial dysfunction, fibrosis, and remodeling. Beyond its myocardial role, the IL-33/ST2 system could have an additional role in the development and progression of atherosclerosis. In conclusion, IL-33/ST2L signaling is a mechanically activated, cardioprotective fibroblast cardiomyocyte paracrine system, which may have therapeutic potential for beneficially regulating the myocardial response to overload and injury. In contrast, sST2 acts as a decoy receptor and, by sequestering IL-33, antagonizes the cardioprotective effects of IL-33/ST2L interaction. (C) 2015 Elsevier Inc. All rights reserved. C1 [Pascual-Figal, Domingo A.] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pascual-Figal, DA (reprint author), Univ Hosp Virgen Arrixaca, Dept Cardiol, Heart Failure Unit, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM dpascual@um.es OI Pascual Figal, Domingo A./0000-0002-4993-9540 FU Critical Diagnostics, San Diego, CA FX Publication of this supplement was supported by funding from Critical Diagnostics, San Diego, CA. NR 23 TC 15 Z9 17 U1 1 U2 9 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 APR 2 PY 2015 VL 115 IS 7 SU S BP 3B EP 7B DI 10.1016/j.amjcard.2015.01.034 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200002 PM 25665766 ER PT J AU Januzzi, JL Mebazaa, A Di Somma, S AF Januzzi, James L. Mebazaa, Alexandre Di Somma, Salvatore TI ST2 and Prognosis in Acutely Decompensated Heart Failure: The International ST2 Consensus Panel SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FAMILY-MEMBER ST2; SOLUBLE ST2; PLASMA-CONCENTRATIONS; ACUTE DYSPNEA; MORTALITY; BIOMARKERS; RECEPTOR; OUTCOMES; ASSAY AB ST2 is a member of the interleukin (IL) 1 receptor fatnily that exists in 2 forms, a transmembrane receptor (ST2L) and a soluble receptor (sST2). The ligand of ST2 is IL-33, known to be involved in reducing tissue fibrosis and myocyte hypertrophy in mechanically strained hearts. Through its ability to act as a decoy receptor, sST2 blocks the beneficial effects that occur when IL-33 attempts to bind to ST2L; experimentally, this leads to cardiac hypertrophy, fibrosis, and ventricular dysfunction. In patients with acutely decompensated heart failure, elevated concentrations of sST2 are strongly associated with the presence and severity of the diagnosis and powerfully predict increased risk of heart failure complications including arrhythmia, pump failure, or death, independent of natriuretic peptides and other established or emerging biomarkers. The role of sST2 measurement in acutely decompensated heart failure evaluation and management will be discussed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mebazaa, Alexandre] Univ Paris Diderot, Dept Anesthesia & Intens Care, PRES Sorbonne Paris Cite, Paris, France. [Mebazaa, Alexandre] Univ Hosp, St Louis Lariboisiere, Paris, France. [Di Somma, Salvatore] Univ Roma La Sapienza, St Andrea Hosp, Dept Med Sci & Translat Med, I-00185 Rome, Italy. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Critical Diagnostics, San Diego, CA FX Publication of this supplement was supported by funding from Critical Diagnostics, San Diego, CA. NR 23 TC 7 Z9 10 U1 2 U2 2 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 APR 2 PY 2015 VL 115 IS 7 SU S BP 26B EP 31B DI 10.1016/j.amjcard.2015.01.037 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200005 PM 25665762 ER PT J AU Bajwa, EK Mebazaa, A Januzzi, JL AF Bajwa, Ednan K. Mebazaa, Alexandre Januzzi, James L. TI ST2 in Pulmonary Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EMERGENCY-DEPARTMENT PATIENTS; RECEPTOR FAMILY-MEMBER; SOLUBLE ST2; ALLERGIC RHINITIS; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; ACUTE EXACERBATION; IL-33; PROTEIN; ASTHMA AB In recent years, numerous studies have focused on the use of soluble ST2 (sST2) as a clinical biomarker for cardiovascular disease. However, much preclinical data points to involvement of the ST2 pathway in inflammation, and specifically in pulmonary inflammation. This report summarizes the current body of clinical data suggesting the potential role of the ST2 pathway in clinical disease, including evidence that sST2 could be a useful biomarker in both allergic and nonallergic pulmonary disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bajwa, Ednan K.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Mebazaa, Alexandre] Univ Paris Diderot, Dept Anesthesiol & Crit Care Med, Paris, France. RP Bajwa, EK (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM ebajwa@mgh.harvard.edu FU Critical Diagnostics, San Diego, CA FX Publication of this supplement was supported by funding from Critical Diagnostics, San Diego, CA. NR 25 TC 2 Z9 2 U1 0 U2 0 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 APR 2 PY 2015 VL 115 IS 7 SU S BP 44B EP 47B DI 10.1016/j.amjcard.2015.01.040 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200008 PM 25665765 ER PT J AU Januzzi, JL Pascual-Figal, D Daniels, LB AF Januzzi, James L. Pascual-Figal, Domingo Daniels, Lori B. TI ST2 Testing for Chronic Heart Failure Therapy Monitoring: The International ST2 Consensus Panel SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FAMILY-MEMBER ST2; SOLUBLE ST2; CARDIAC STRUCTURE; ASSOCIATION; MORTALITY AB Among patients with chronic heart failure (HF), it is known that soluble concentrations of the interleukin receptor family member ST2 (sST2) are prognostic for adverse outcome, including risk for progression of HF and death. Considerably less was known about the merits of serial testing of sST2 and whether such testing provides incremental information beyond single measurements; additionally, the influence of HF therapies on sST2 concentrations and whether sST2 values predicted benefit of therapy changes remained unclear. Recently, several studies indicate that serial testing for sST2 increases the prognostic information gained compared with a single measurement. When measured in patients with chronic HF, concentrations of sST2 appear to predict worsening left ventricular remodeling, and serial measurements of sST2 appear particularly useful for predicting HF events, such as worsening HF and risk for either hospitalization or death from HF. Values for sST2 are lower in those treated with several HF therapies; in turn, sST2 concentrations may predict benefit from specific HF therapy changes. Using an upper reference limit of 35 ng/ml, serial testing for sST2 in chronic HF thus appears useful. The promising role of sST2 for serial chronic HF therapy monitoring will be discussed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pascual-Figal, Domingo] Univ Hosp Virgen Arrixaca, Div Cardiol, Murcia, Spain. [Daniels, Lori B.] Univ Calif San Diego, Div Cardiol, San Diego, CA 92103 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI Pascual Figal, Domingo A./0000-0002-4993-9540 FU Critical Diagnostics, San Diego, CA FX Publication of this supplement was supported by funding from Critical Diagnostics, San Diego, CA. NR 13 TC 9 Z9 9 U1 0 U2 1 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 APR 2 PY 2015 VL 115 IS 7 SU S BP 70B EP 75B DI 10.1016/j.amjcard.2015.01.044 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200012 PM 25670638 ER PT J AU Germain, M Chasman, DI de Haan, H Tang, W Lindstrom, S Weng, LC de Andrade, M de Visser, MCH Wiggins, KL Suchon, P Saut, N Smadja, DM Le Gal, G Vlieg, AV Di Narzo, A Hao, K Nelson, CP Rocanin-Arjo, A Folkersen, L Monajemi, R Rose, LM Brody, JA Slagboom, E Aissi, D Gagnon, F Deleuze, JF Deloukas, P Tzourio, C Dartigues, JF Berr, C Taylor, KD Civelek, M Eriksson, P Psaty, BM Houwing-Duitermaat, J Goodall, AH Cambien, F Kraft, P Amouyel, P Samani, NJ Basu, S Ridker, PM Rosendaal, FR Kabrhel, C Folsom, AR Heit, J Reitsma, PH Tregouet, DA Smith, NL Morange, PE AF Germain, Marine Chasman, Daniel I. de Haan, Hugoline Tang, Weihong Lindstroem, Sara Weng, Lu-Chen de Andrade, Mariza de Visser, Marieke C. H. Wiggins, Kerri L. Suchon, Pierre Saut, Noemie Smadja, David M. Le Gal, Gregoire Vlieg, Astrid van Hylckama Di Narzo, Antonio Hao, Ke Nelson, Christopher P. Rocanin-Arjo, Ares Folkersen, Lasse Monajemi, Ramin Rose, Lynda M. Brody, Jennifer A. Slagboom, Eline Aissi, Dylan Gagnon, France Deleuze, Jean-Francois Deloukas, Panos Tzourio, Christophe Dartigues, Jean-Francois Berr, Claudine Taylor, Kent D. Civelek, Mete Eriksson, Per Psaty, Bruce M. Houwing-Duitermaat, Jeanine Goodall, Alison H. Cambien, Francois Kraft, Peter Amouyel, Philippe Samani, Nilesh J. Basu, Saonli Ridker, Paul M. Rosendaal, Frits R. Kabrhel, Christopher Folsom, Aaron R. Heit, John Reitsma, Pieter H. Tregouet, David-Alexandre Smith, Nicholas L. Morange, Pierre-Emmanuel CA Cardiogenics Consortium TI Meta-analysis of 65,734 Individuals Identifies TSPAN15 and SLC44A2 as Two Susceptibility Loci for Venous Thromboembolism SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ENDOTHELIAL-CELLS; GENE-EXPRESSION; PLASMA-LEVELS; CARDIOVASCULAR-DISEASE; GENOTYPING ARRAYS; AGING RESEARCH; BREAST-CANCER; RISK VARIANTS; PROTEIN-C AB Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 x 10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 x 10(-16)) and 1.21 (p = 2.75 x 10(-15)), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology. C1 [Germain, Marine; Rocanin-Arjo, Ares; Aissi, Dylan; Cambien, Francois; Tregouet, David-Alexandre] INSERM, UMR S 1166, F-75013 Paris, France. [Germain, Marine; Rocanin-Arjo, Ares; Aissi, Dylan; Cambien, Francois; Tregouet, David-Alexandre] Univ Paris 06, Univ Sorbonne, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, F-75013 Paris, France. [Germain, Marine; Rocanin-Arjo, Ares; Aissi, Dylan; Cambien, Francois; Tregouet, David-Alexandre] ICAN, F-75013 Paris, France. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [de Haan, Hugoline; Vlieg, Astrid van Hylckama; Rosendaal, Frits R.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Dept Thrombosis & Hemostasis, NL-2333 ZA Leiden, Netherlands. [Tang, Weihong; Weng, Lu-Chen; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Lindstroem, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [de Visser, Marieke C. H.; Reitsma, Pieter H.] Leiden Univ, Med Ctr, Dept Thrombosis & Hemostasis, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands. [Wiggins, Kerri L.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Suchon, Pierre; Saut, Noemie; Morange, Pierre-Emmanuel] Hop Enfants La Timone, Haematol Lab, F-13385 Marseille, France. [Suchon, Pierre; Saut, Noemie; Morange, Pierre-Emmanuel] INSERM, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Suchon, Pierre; Saut, Noemie; Morange, Pierre-Emmanuel] Aix Marseille Univ, UMR S 1062, Nutr Obes & Risk Thrombosis, F-13385 Marseille, France. [Smadja, David M.] Univ Paris 05, Sorbonne Paris Cite, F-75006 Paris, France. [Smadja, David M.] Hop Europeen Georges Pompidou, AP HP, Serv Hematol Biol, F-75015 Paris, France. [Smadja, David M.] Fac Pharm, INSERM, UMR S 1140, F-75006 Paris, France. [Le Gal, Gregoire] Univ Brest, EA3878, F-29238 Brest, France. [Le Gal, Gregoire] Univ Brest, CIC1412, F-29238 Brest, France. [Le Gal, Gregoire] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON K1Y 4E9, Canada. [Di Narzo, Antonio; Hao, Ke] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Nelson, Christopher P.; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England. [Nelson, Christopher P.; Goodall, Alison H.; Samani, Nilesh J.] Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England. [Folkersen, Lasse] Dept PharmacoGenet, DK-2400 Copenhagen, Denmark. [Monajemi, Ramin; Houwing-Duitermaat, Jeanine] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands. [Rose, Lynda M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Slagboom, Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Gagnon, France] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. [Deleuze, Jean-Francois] Commissariat Energie Atom, Direct Sci Vivant, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France. [Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London E1 4NS, England. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia. [Tzourio, Christophe; Dartigues, Jean-Francois] Univ Bordeaux, INSERM, Res Ctr, U897, F-33000 Bordeaux, France. [Berr, Claudine] Univ Montpellier I, INSERM, Res Unit, U1061, F-34000 Montpellier, France. [Taylor, Kent D.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Taylor, Kent D.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA. [Civelek, Mete] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Eriksson, Per] Karolinska Inst, Dept Med, Ctr Mol Med, Atherosclerosis Res Unit, S-17177 Stockholm, Sweden. [Psaty, Bruce M.; Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Amouyel, Philippe] Univ Lille Nord France, INSERM, UMR S 744, Inst Pasteur Lille, F-59000 Lille, France. [Amouyel, Philippe] Ctr Hosp Reg Univ Lille, F-59000 Lille, France. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. [Kabrhel, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Channing Network Med, Boston, MA USA. [Heit, John] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Smith, Nicholas L.] VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. RP Smith, NL (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. EM nlsmith@u.washington.edu; pierre.morange@ap-hm.fr RI Tregouet, David-Alexandre/E-3961-2016; Deloukas, Panos/B-2922-2013; berr, Claudine/D-5238-2014; Slagboom, P. Eline/R-4790-2016; Tzourio, christophe/B-4015-2009; van Hylckama Vlieg, Astrid/A-3323-2017; OI Civelek, Mete/0000-0002-8141-0284; Folkersen, Lasse/0000-0003-0708-9530; Deloukas, Panos/0000-0001-9251-070X; berr, Claudine/0000-0001-5254-7655; Slagboom, P. Eline/0000-0002-2875-4723; Tzourio, christophe/0000-0002-6517-2984; Kabrhel, Christopher/0000-0002-8699-7176; Aissi, Dylan/0000-0002-5858-6468 FU French National Institute for Health and Medical Research; French Ministry of Health; French Medical Research Foundation; French Agency for Research; National Heart, Lung, and Blood Institute (USA); National Institute for Health Research (USA); National Human Genome Research Institute (USA); National Cancer Institute (USA); Donald W. Reynolds Foundation; Fondation Leducq; European Commission; Netherlands Organisation for Scientific Research; Netherlands Heart Foundation; Dutch Cancer Foundation; Canadian Institutes of Health Research; Heart and Stroke Foundation of Canada; British Heart Foundation; ICAN Institute for Cardiometabolism and Nutrition FX This work is the product of the International Network against Thrombosis (INVENT) collaboration. This work was financially supported by the French National Institute for Health and Medical Research; French Ministry of Health; French Medical Research Foundation; French Agency for Research; National Heart, Lung, and Blood Institute (USA); National Institute for Health Research (USA); National Human Genome Research Institute (USA); National Cancer Institute (USA); the Donald W. Reynolds Foundation; Fondation Leducq; The European Commission; Netherlands Organisation for Scientific Research; Netherlands Heart Foundation; Dutch Cancer Foundation; Canadian Institutes of Health Research; Heart and Stroke Foundation of Canada; British Heart Foundation; and ICAN Institute for Cardiometabolism and Nutrition. The lists of grants supporting this research can be found in the Supplemental Data. NR 57 TC 33 Z9 34 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 2 PY 2015 VL 96 IS 4 BP 532 EP 542 DI 10.1016/j.ajhg.2015.01.019 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CF0DJ UT WOS:000352212600002 PM 25772935 ER PT J AU Ramos, AD Andersen, RE Liu, SJ Nowakowski, TJ Hong, SJ Gertz, CC Salinas, RD Zarabi, H Kriegstein, AR Lim, DA AF Ramos, Alexander D. Andersen, Rebecca E. Liu, Siyuan John Nowakowski, Tomasz Jan Hong, Sung Jun Gertz, Caitlyn C. Salinas, Ryan D. Zarabi, Hosniya Kriegstein, Arnold R. Lim, Daniel A. TI The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells SO CELL STEM CELL LA English DT Article ID TRACT-BINDING-PROTEINS; ADULT MAMMALIAN BRAIN; SUBVENTRICULAR ZONE; EPIGENETIC REGULATION; GENE-EXPRESSION; IN-VIVO; PTBP2; NEUROGENESIS; TRANSCRIPTS; PROGRESSION AB While thousands of long noncoding RNAs (IncRNAs) have been identified, few IncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific IncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved IncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations. C1 [Ramos, Alexander D.; Andersen, Rebecca E.; Liu, Siyuan John; Hong, Sung Jun; Salinas, Ryan D.; Zarabi, Hosniya; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Ramos, Alexander D.; Andersen, Rebecca E.; Liu, Siyuan John; Nowakowski, Tomasz Jan; Hong, Sung Jun; Gertz, Caitlyn C.; Salinas, Ryan D.; Zarabi, Hosniya; Kriegstein, Arnold R.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Ramos, Alexander D.; Liu, Siyuan John] Univ Calif San Francisco, Med Sci Training Program, Biomed Sci Grad Program, San Francisco, CA 94143 USA. [Andersen, Rebecca E.] Univ Calif San Francisco, Dev & Stem Cell Biol Grad Program, San Francisco, CA 94143 USA. [Nowakowski, Tomasz Jan; Gertz, Caitlyn C.; Kriegstein, Arnold R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Gertz, Caitlyn C.] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94143 USA. [Hong, Sung Jun] San Francisco State Univ, CIRM Bridges Scholar Program, San Francisco, CA 94132 USA. [Lim, Daniel A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. EM daniel.lim@ucsf.edu FU NIH [DP2-OD006505-01, VA 1I01 BX000252-04, R01 NS35710, 1F31NS080501-01A1]; Shurl and Kay Curci Foundation Award; National Science Foundation Graduate Research Fellowship [1144247]; MSTP [2T32GM007618-34]; SFSU CIRM Bridges fellowship [TB1-01194]; HHMI Medical Research Fellowship FX We thank Robert Darnell for the PTBP2 antibody; David Weinberg for helpful discussions; Kenneth Probst for help with the graphical abstract; and Ewa Witkowski, Steven Hall, and The Sandler-Moore Mass Spectrometry Core Facility at UCSF for help with mass spectrometry. This project was supported by NIH DP2-OD006505-01, VA 1I01 BX000252-04, and a Shurl and Kay Curci Foundation Award to D.A.L; NIH R01 NS35710 to A.R.K.; NIH 1F31NS080501-01A1 to A.D.R.; National Science Foundation Graduate Research Fellowship Grant No. 1144247 to R.E.A.; MSTP training grant 2T32GM007618-34 to S.J.L.; SFSU CIRM Bridges TB1-01194 fellowship to S.H.; HHMI Medical Research Fellowship to H.Z.; and facilities and resources provided by the San Francisco Veterans Affairs Medical Center. NR 44 TC 42 Z9 46 U1 3 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 2 PY 2015 VL 16 IS 4 BP 439 EP 447 DI 10.1016/j.stem.2015.02.007 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CF0JD UT WOS:000352228600015 PM 25800779 ER PT J AU Senol, O Schaaij-Visser, TBM Erkan, EP Dorfer, C Lewandrowski, G Pham, TV Piersma, SR Peerdeman, M Strobel, T Tannous, B Saydam, N Slavc, I Knosp, E Jimenez, CR Saydam, O AF Senol, O. Schaaij-Visser, T. B. M. Erkan, E. P. Dorfer, C. Lewandrowski, G. Pham, T. V. Piersma, S. R. Peerdeman, M. Stroebel, T. Tannous, B. Saydam, N. Slavc, I. Knosp, E. Jimenez, C. R. Saydam, O. TI miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo SO ONCOGENE LA English DT Article ID MYOSIN-II; MESENCHYMAL TRANSITION; CANCER; INVASION AB miR-200a has been implicated in the pathogenesis of meningiomas, one of the most common central nervous system tumors in humans. To identify how miR-200a contributes to meningioma pathogenesis at the molecular level, we used a comparative protein profiling approach using Gel-nanoLC-MS/MS and identified approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma cells. Following the bioinformatic analysis to identify potential genes targeted by miR-200a, we focused on the nonmuscle heavy chain IIb (NMHCIIb), and showed that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in cell division and cell migration, we aimed to identify whether miR-200a regulated these processes through NMHCIIb. We found that NMHCIIb overexpression partially rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression resulted in a similar migration phenotype in these cells and inhibited meningioma tumor growth in mice. Taken together, these results suggest that NMHCIIb might serve as a novel therapeutic target in meningiomas. C1 [Senol, O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, Boston, MA USA. [Schaaij-Visser, T. B. M.; Pham, T. V.; Piersma, S. R.; Jimenez, C. R.] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, OncoProte Lab, Amsterdam, Netherlands. [Erkan, E. P.; Saydam, N.; Slavc, I.; Saydam, O.] Med Univ Vienna, Dept Pediat, Mol Neurooncol Res Unit, A-1090 Vienna, Austria. [Dorfer, C.; Knosp, E.] Med Univ Vienna, Dept Neurosurg, A-1090 Vienna, Austria. [Lewandrowski, G.; Tannous, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Expt Therapeut & Mol Imaging Lab, Boston, MA USA. [Peerdeman, M.] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. [Stroebel, T.] Med Univ Vienna, Inst Neurol, A-1090 Vienna, Austria. RP Saydam, O (reprint author), Med Univ Vienna, Dept Pediat, Mol Neurooncol Res Unit, A-1090 Vienna, Austria. EM okay.saydam@meduniwien.ac.at OI Dorfer, Christian/0000-0002-1843-7732 FU Forschungsgesellschaft for Brain Tumors; EU-FP7-PEOPLE-CIG; Association for Conduct of Scientific Research in the Field of Neonatology and Pediatric Intensive Care: 'Unser Kind' FX Support for this work was provided, in part, by Forschungsgesellschaft for Brain Tumors (to OS, NS), EU-FP7-PEOPLE-2011-CIG (to OS) and Association for Conduct of Scientific Research in the Field of Neonatology and Pediatric Intensive Care: 'Unser Kind' (to OS). We thank Dr Marianne F James for providing us with AC030 cells. NR 29 TC 8 Z9 8 U1 1 U2 7 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 APR 2 PY 2015 VL 34 IS 14 BP 1790 EP 1798 DI 10.1038/onc.2014.120 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CE9IQ UT WOS:000352158000006 PM 24858044 ER PT J AU Weis, B Schmidt, J Maamar, H Raj, A Lin, H Toth, C Riedmann, K Raddatz, G Seitz, HK Ho, AD Lyko, F Linhart, HG AF Weis, B. Schmidt, J. Maamar, H. Raj, A. Lin, H. Toth, C. Riedmann, K. Raddatz, G. Seitz, H-K Ho, A. D. Lyko, F. Linhart, H. G. TI Inhibition of intestinal tumor formation by deletion of the DNA methyltransferase 3a SO ONCOGENE LA English DT Article ID DE-NOVO METHYLATION; IN-VIVO; DNMT3A; CANCER; MOUSE; GENE; HYPOMETHYLATION; OVEREXPRESSION; EXPRESSION; 3B AB Aberrant de novo methylation of DNA is considered an important mediator of tumorigenesis. To investigate the role of de novo DNA methyltransferase 3a (Dnmt3a) in intestinal tumor development, we analyzed the expression of Dnmt3a in murine colon crypts, murine colon adenomas and human colorectal cancer using RNA fluorescence in situ hybridization (FISH), quantitative PCR and immunostaining. Following conditional deletion of Dnmt3a in the colon of APC((Min/+)) mice, we analyzed tumor numbers, genotype of macroadenomas and laser dissected microadenomas, global and regional DNA methylation and gene expression. Our results showed increased Dnmt3a expression in colon adenomas of APC((Min/+)) mice and human colorectal cancer samples when compared with control tissue. Interestingly, in tumor tissue, RNA FISH analysis showed highest Dnmt3a expression in Lgr5-positive stem/progenitor cells. Deletion of Dnmt3a in APC((Min/+)) mice reduced colon tumor numbers by similar to 40%. Remaining adenomas and microadenomas almost exclusively contained the non-recombined Dnmt3a allele; no tumors composed of the inactivated Dnmt3a allele were detected. DNA methylation was reduced at the Oct4, Nanog, Tff2 and Cdkn1c promoters and expression of the tumor-suppressor genes Tff2 and Cdkn1c was increased. In conclusion, our results show that Dnmt3a is predominantly expressed in the stem/progenitor cell compartment of tumors and that deletion of Dnmt3a inhibits the earliest stages of intestinal tumor development. C1 [Weis, B.; Schmidt, J.; Riedmann, K.; Raddatz, G.; Lyko, F.; Linhart, H. G.] German Canc Res Ctr, Div Epigenet A130, D-69120 Heidelberg, Germany. [Maamar, H.; Raj, A.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Lin, H.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Toth, C.] Heidelberg Univ, Dept Pathol, Natl Ctr Tumor Dis NCT, Tissue Bank, Heidelberg, Germany. [Toth, C.] Univ Dusseldorf, Dept Pathol, Dusseldorf, Germany. [Seitz, H-K; Linhart, H. G.] Heidelberg Univ, Dept Med, Salem Med Ctr, Alcohol Res Ctr, Heidelberg, Germany. [Ho, A. D.; Linhart, H. G.] Heidelberg Univ, Dept Hematol Oncol, Med Ctr, Heidelberg, Germany. RP Linhart, HG (reprint author), German Canc Res Ctr, Div Epigenet A130, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM heinz.linhart@nct-heidelberg.de OI Raj, Arjun/0000-0002-2915-6960 FU DKFZ Light Microscopy Facility; Helmholtz International Graduate School for Cancer Research; Burroughs-Wellcome Fund Career Award at the Scientific Interface; NIH [1DP2OD008514-01]; Lautenschlager foundation FX Support by the DKFZ Light Microscopy Facility is gratefully acknowledged. We also thank E Herpel and the tissue bank of the NCT Heidelberg for providing human tissue samples and for technical support in histology and immunohistochemistry. We also thank J Gutekunst for bioinformatical support and R Jaenisch for critical discussions. This study was supported by a graduate scholarship from the Helmholtz International Graduate School for Cancer Research (B Weis), a Burroughs-Wellcome Fund Career Award at the Scientific Interface (A Raj, H Maamar), a NIH Director's New Innovator award (1DP2OD008514-01 to A Raj) and the Lautenschlager foundation (HK Seitz). NR 38 TC 2 Z9 2 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 2 PY 2015 VL 34 IS 14 BP 1822 EP 1830 DI 10.1038/onc.2014.114 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CE9IQ UT WOS:000352158000009 PM 24837369 ER PT J AU Turner, TN Sharma, K Oh, EC Liu, YFP Collins, RL Sosa, MX Auer, DR Brand, H Sanders, SJ Moreno-De-Luca, D Pihur, V Plona, T Pike, K Soppet, DR Smith, MW Cheung, SW Martin, CL State, MW Talkowski, ME Cook, E Huganir, R Katsanis, N Chakravarti, A AF Turner, Tychele N. Sharma, Kamal Oh, Edwin C. Liu, Yangfan P. Collins, Ryan L. Sosa, Maria X. Auer, Dallas R. Brand, Harrison Sanders, Stephan J. Moreno-De-Luca, Daniel Pihur, Vasyl Plona, Teri Pike, Kristen Soppet, Daniel R. Smith, Michael W. Cheung, Sau Wai Martin, Christa Lese State, Matthew W. Talkowski, Michael E. Cook, Edwin Huganir, Richard Katsanis, Nicholas Chakravarti, Aravinda TI Loss of delta-catenin function in severe autism SO NATURE LA English DT Article ID SPECTRUM DISORDERS; STRUCTURAL VARIATION; MENTAL-RETARDATION; SIGNALING PATHWAY; SEQUENCING DATA; PROTEIN; KAISO; MORPHOGENESIS; EXPRESSION; GENETICS AB Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from female-enriched multiplex families with severe disease, enhancing the detection of key autism genes in modest numbers of cases. Here we show the use of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated delta-catenin protein (CTNND2) in female-enriched multiplex families and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wild-type and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as female-enriched multiplex families, are of innate value in multifactorial disorders. C1 [Turner, Tychele N.; Sosa, Maria X.; Auer, Dallas R.; Pihur, Vasyl; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA. [Turner, Tychele N.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet & Mol Bi, Baltimore, MD 21205 USA. [Turner, Tychele N.; Sosa, Maria X.; Auer, Dallas R.; Sanders, Stephan J.; Moreno-De-Luca, Daniel; Pihur, Vasyl; Martin, Christa Lese; State, Matthew W.; Chakravarti, Aravinda] Univ Calif Los Angeles, NIMH, Autism Ctr Excellence ACE Genet Consortium, Los Angeles, CA 90095 USA. [Sharma, Kamal; Huganir, Richard] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. [Oh, Edwin C.; Liu, Yangfan P.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Collins, Ryan L.; Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Collins, Ryan L.; Brand, Harrison; Talkowski, Michael E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sanders, Stephan J.; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. [Moreno-De-Luca, Daniel] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. [Plona, Teri; Pike, Kristen; Soppet, Daniel R.] Leidos Biomed Res Inc, Frederick, MD 21702 USA. [Smith, Michael W.] NHGRI, Bethesda, MD 20892 USA. [Cheung, Sau Wai] Baylor Coll Med, Houston, TX 77030 USA. [Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Lewisburg, PA 17837 USA. [Cook, Edwin] Univ Illinois, Chicago, IL 60608 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu OI Collins, Rachel/0000-0002-1559-8135 FU National Institute of Mental Health [1U24MH081810]; Simons Foundation; NIMH [MH095867, 5R25MH071584-07, MH19961-14, R01MH081754]; National Institutes of Health [RO1MH074090]; Autism Speaks Dennis Weatherstone pre-doctoral fellowship [7863] FX We acknowledge the participation of all of the families in the AGRE, NIMH and SSC studies that have been amodel of public participatory research. The AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health. The SSC used here was developed by the following principal investigators: A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, E. Wijsman. We thank the Allen Brain Atlas for use of their publicly available developing human brain expression data. Finally, we thank V. Kustanovich (AGRE) for helping with access to Autism Diagnostic Observation Schedule severity score data, D. Arking for sharing DNA from the SSC for Taqman genotyping, S. Maragh for zebrafish complementary DNA (cDNA) libraries and eef1a1l1 primers, A. Kapoor for discussions, Q. Jiang for the translation of ref. 43, and J. A. Rosenfeld, L. G. Shaffer, Y. Shenand B.-L. Wufor sharing CNV data sets. Sequencing services were provided by the Johns Hopkins University Next Generation Sequencing Center, Sidney Kimmel Comprehensive Cancer Center, Illumina Sequencing Services and the Johns Hopkins University Genetic Resources Core Facility. E. C. O. is a National Alliance for Research on Schizophrenia and Depression young investigator. N.K. is a Distinguished George W. Brumley Professor. This work was funded by grants from the Simons Foundation to A. C. and to N.K., NIMH grant MH095867 to M.E.T., NIMH grants 5R25MH071584-07 and MH19961-14 to D. M. D. L. (Malison), National Institutes of Health grant RO1MH074090 to C. L. M., NIMH grant R01MH081754 to A. C. and an Autism Speaks Dennis Weatherstone pre-doctoral fellowship (number 7863) to T.T. NR 54 TC 34 Z9 37 U1 3 U2 37 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 APR 2 PY 2015 VL 520 IS 7545 BP 51 EP + DI 10.1038/nature14186 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700034 PM 25807484 ER PT J AU Hooli, BV Lill, C Mullin, K Qiao, D Lange, C Bertram, L Tanzi, RE AF Hooli, Basavaraj V. Lill, ChristinaM. Mullin, Kristina Qiao, Dandi Lange, Christoph Bertram, Lars Tanzi, Rudolph E. TI PLD3 gene variants and Alzheimer's disease SO NATURE LA English DT Letter C1 [Hooli, Basavaraj V.; Mullin, Kristina; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Lill, ChristinaM.; Bertram, Lars] Med Univ Lubeck, Platform Genome Analyt, Inst Neurogenet, D-23552 Lubeck, Germany. [Lill, ChristinaM.; Bertram, Lars] Med Univ Lubeck, Platform Genome Analyt, Inst Integrat & Expt Genom, D-23552 Lubeck, Germany. [Lill, ChristinaM.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, Focus Program Translat Neurosci, D-55131 Mainz, Germany. [Lill, ChristinaM.; Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Qiao, Dandi; Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London W6 8RP, England. RP Hooli, BV (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. EM lars.bertram@uni-luebeck.de; tanzi@helix.mgh.harvard.edu RI Lill, Christina/J-9449-2015; Bertram, Lars/K-3889-2015 OI Lill, Christina/0000-0002-2805-1307; Bertram, Lars/0000-0002-0108-124X NR 11 TC 14 Z9 14 U1 0 U2 9 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 APR 2 PY 2015 VL 520 IS 7545 BP E7 EP E9 DI 10.1038/nature14040 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700005 PM 25832413 ER PT J AU Douglas, PS Hoffmann, U Patel, MR Mark, DB Al-Khalidi, HR Cavanaugh, B Cole, J Dolor, RJ Fordyce, CB Huang, MG Khan, MA Kosinski, AS Krucoff, MW Malhotra, V Picard, MH Udelson, JE Velazquez, EJ Yow, E Cooper, LS Lee, KL AF Douglas, Pamela S. Hoffmann, Udo Patel, Manesh R. Mark, Daniel B. Al-Khalidi, Hussein R. Cavanaugh, Brendan Cole, Jason Dolor, Rowena J. Fordyce, Christopher B. Huang, Megan Khan, Muhammad Akram Kosinski, Andrzej S. Krucoff, Mitchell W. Malhotra, Vinay Picard, Michael H. Udelson, James E. Velazquez, Eric J. Yow, Eric Cooper, Lawton S. Lee, Kerry L. CA PROMISE Investigators TI Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIAGNOSTIC PERFORMANCE; IONIZING-RADIATION; BLOOD-INSTITUTE; CT ANGIOGRAPHY; UNITED-STATES; CHEST-PAIN; HEART; MANAGEMENT; RADIOLOGY; MORTALITY AB BACKGROUND Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS The mean age of the patients was 60.8 +/- 8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3 +/- 21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.) C1 [Douglas, Pamela S.; Patel, Manesh R.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Dolor, Rowena J.; Fordyce, Christopher B.; Huang, Megan; Kosinski, Andrzej S.; Krucoff, Mitchell W.; Velazquez, Eric J.; Yow, Eric; Lee, Kerry L.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA. [Hoffmann, Udo; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Udelson, James E.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Cavanaugh, Brendan] New Mexico Heart Inst, Albuquerque, NM USA. [Cole, Jason] Cardiol Associates, Mobile, AL USA. [Khan, Muhammad Akram] North Dallas Res Associates, Dallas, TX USA. [Malhotra, Vinay] Cardiac Study Grp, Puyallup, WA USA. [Cooper, Lawton S.] NHLBI, Bethesda, MD 20892 USA. RP Douglas, PS (reprint author), Duke Univ, Sch Med, Med Ctr, 7022 North Pavil,POB 17969, Durham, NC 27715 USA. EM pamela.douglas@duke.edu OI Picard, Michael/0000-0002-9264-3243 FU National Heart, Lung, and Blood Institute FX Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550. NR 32 TC 189 Z9 192 U1 5 U2 25 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 APR 2 PY 2015 VL 372 IS 14 BP 1291 EP 1300 DI 10.1056/NEJMoa1415516 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CE7NL UT WOS:000352028500004 PM 25773919 ER PT J AU Mauri, L Yeh, RW Kereiakes, DJ AF Mauri, Laura Yeh, Robert W. Kereiakes, Dean J. TI Duration of Dual Antiplatelet Therapy after Drug-Eluting Stents REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kereiakes, Dean J.] Christ Hosp Heart & Vasc Ctr, Cincinnati, OH USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org NR 2 TC 5 Z9 5 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 APR 2 PY 2015 VL 372 IS 14 BP 1373 EP 1374 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CE7NL UT WOS:000352028500021 PM 25830429 ER PT J AU Aikens, JE Vogel, M Illes, RA Safford, MM Andreae, SJ Koenig, CJ Maguen, S Seal, K Mayott, LK AF Aikens, James E. Vogel, Mark Illes, Rose Ann Safford, Monika M. Andreae, Susan J. Koenig, Christopher J. Maguen, Shira Seal, Karen Mayott, Lindsay K. TI IMPROVING PRIMARY CARE THROUGH CULTURALLY RESPONSIVE INITIATIVES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Aikens, James E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Vogel, Mark] Genesys Reg Med Ctr, Burton, MI USA. [Illes, Rose Ann] Florida State Univ, Ft Myers, FL USA. [Safford, Monika M.; Andreae, Susan J.] Univ Alabama Birmingham, Birmingham, AL USA. [Koenig, Christopher J.] UCSF, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Maguen, Shira] San Francis VA Med Ctr, San Francisco, CA USA. [Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Seal, Karen] UCSF, San Francisco VA Med Ctr, San Francisco, CA USA. [Mayott, Lindsay K.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. EM roseanne.illes@leememorial.org; msafford@uab.edu; christopher.koenig@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 31 BP S132 EP S132 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002009 ER PT J AU Amoyal, N Nisotel, L Traeger, L Stagl, J Greer, J AF Amoyal, Nicole Nisotel, Lauren Traeger, Lara Stagl, Jamie Greer, Joseph TI SEXUAL SATISFACTION IN PATIENTS WITH ADVANCE CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Amoyal, Nicole; Nisotel, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Traeger, Lara; Stagl, Jamie; Greer, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM namoyal@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA B001 BP S92 EP S92 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001357 ER PT J AU Earnshaw, VA Logie, C Bowleg, L Bogart, LM Dale, SK AF Earnshaw, Valerie A. Logie, Carmen Bowleg, Lisa Bogart, Laum M. Dale, Sannisha K. TI ADVANCES IN INTERSECTIONALITY: METHODOLOGICAL APPROACHES, RESEARCH FINDINGS, INTERVENTION STRATEGIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Earnshaw, Valerie A.; Bogart, Laum M.] Harvard Univ, Sch Med, Boston, MA USA. [Logie, Carmen] Univ Toronto, Toronto, ON, Canada. [Bowleg, Lisa] George Washington Univ, Washington, DC USA. [Dale, Sannisha K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston Childrens Hosp, Dorchester, MA USA. EM valerie.earnshaw@childrens.harvard.edu; logiech@yahoo.com; lbowleg@email.gwu.edu; laura.bogart@childrens.harvard.edu; skdale@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 15 BP S62 EP S62 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001243 ER PT J AU Earnshaw, VA Logie, C Bowleg, L Bogart, L Dale, SK AF Earnshaw, Valerie A. Logie, Carmen Bowleg, Lisa Bogart, LauraM. Dale, Sannisha K. TI ADVENTURES IN INTERSECTIONALITY RESEARCH: ISSUES OF THEORY, MEASUREMENT, AND APPLICATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Earnshaw, Valerie A.; Bogart, LauraM.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Logie, Carmen] Univ Toronto, Toronto, ON M6P 3A5, Canada. [Bowleg, Lisa] George Washington Univ, Washington, DC 20052 USA. [Dale, Sannisha K.] Harvard Univ, Sch Med, Dorchester, MA 02122 USA. [Dale, Sannisha K.] Massachusetts Gen Hosp, Dorchester, MA 02122 USA. [Dale, Sannisha K.] Boston Childrens Hosp, Dorchester, MA 02122 USA. EM logiech@yahoo.com; lbowleg@email.gwu.edu; laura.bogart@childrens.harvard.edu; skdale@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 07 BP S53 EP S53 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001209 ER PT J AU Graves, KD Tucker-Seeley, R Gonzalez, BD Deshpande, A Lowenstein, LM Rowland, JH AF Graves, Kristi D. Tucker-Seeley, Reginald Gonzalez, Brian D. Deshpande, Anjali Lowenstein, Lisa M. Rowland, Julia H. TI AGING AND CANCER: IMPLICATIONS FOR COGNITIVE OUTCOMES AND CLINICAL ENCOUNTERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Graves, Kristi D.] Georgetown Univ, Washington, DC USA. [Tucker-Seeley, Reginald] Harvard Univ, Sch Publ Hlth, DFCI, Boston, MA 02115 USA. [Gonzalez, Brian D.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Deshpande, Anjali] Washington Univ, St Louis, MO USA. [Lowenstein, Lisa M.] Univ Rochester, Rochester, NY USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. EM brian.gonzalez@moffitt.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 29 BP S130 EP S130 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002001 ER PT J AU Hyland, KA Streck, J Temel, B Park, ER Luberto, C AF Hyland, Kelly A. Streck, Joanna Temel, Brandon Park, Elyse R. Luberto, Christina TI PUBLIC PERSPECTIVES ON CANCER PATIENTS WHO SMOKE: A QUALITATIVE ANALYSIS OF THE INFLUENCE OF STIGMA SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hyland, Kelly A.; Temel, Brandon; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Streck, Joanna] Univ Vermont, Burlington, VT USA. EM khyland@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA B134 BP S124 EP S124 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001487 ER PT J AU Lemos, MAM Reese, RL Freedland, KE Steinmeyer, BC Carney, RM AF Mariantonia Lemos, M. A. Reese, Rebecca L. Freedland, Kenneth E. Steinmeyer, Brian C. Carney, Robert M. TI CHANGES IN ILLNESS PERCEPTIONS AFTER COGNITIVE BEHAVIOR THERAPY IN DEPRESSED CARDIAC PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mariantonia Lemos, M. A.] Univ Los Andes, Bogota, Colombia. [Reese, Rebecca L.] VA Boston Healthcare Syst, Boston, MA USA. [Freedland, Kenneth E.; Steinmeyer, Brian C.; Carney, Robert M.] Washington Univ, Sch Med, St Louis, MO USA. EM m.lemos70@uniandes.edu.co NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A030 BP S11 EP S11 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001041 ER PT J AU McGinty, HL Traeger, L Yanez, B Wang, N Antoni, MH Kava, BR Penedo, FJ AF McGinty, Heather L. Traeger, Lara Yanez, Betina Wang, Nicholas Antoni, Michael H. Kava, Bruce R. Penedo, Frank J. TI PRE-TREATMENT PSYCHOSOCIAL CONCERNS PREDICT POST-TREATMENT QUALITY OF LIFE IN PROSTATE CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [McGinty, Heather L.; Yanez, Betina; Wang, Nicholas] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Traeger, Lara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Antoni, Michael H.] Univ Miami, Miami, FL USA. [Kava, Bruce R.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Penedo, Frank J.] Northwestern Univ, Chicago, IL 60611 USA. EM heather.mcginty@northwestern.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C021 BP S179 EP S179 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002192 ER PT J AU Mello, S Tan, ASL Sanders-Jackson, A Bigman, C AF Mello, Susan Tan, Andy S. L. Sanders-Jackson, Ashley Bigman, Cabral TI PERCEIVED HARM OF SECONDHAND E-CIGARETTE VAPORS AND POLICY SUPPORT TO RESTRICT PUBLIC VAPING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mello, Susan] Northeastern Univ, Boston, MA 02115 USA. [Tan, Andy S. L.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Div Populat Sci,Ctr Community Based Res,Dept Soci, Boston, MA 02115 USA. [Sanders-Jackson, Ashley] Stanford Univ, Stanford Prevent Res Ctr, Palo Alto, CA 94304 USA. [Bigman, Cabral] Univ Illinois, Urbana, IL USA. EM s.mello@neu.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001316 ER PT J AU Millstein, R Hoerster, K Rosenberg, D Nelson, K Reiber, GE Saelens, B AF Millstein, Rachel Hoerster, Katherine Rosenberg, Dori Nelson, Karin Reiber, Gayle E. Saelens, Brian TI INDIVIDUAL, SOCIAL, AND NEIGHBORHOOD ASSOCIATIONS WITH SITTING TIME AMONG VETERANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Millstein, Rachel] MGH, Boston, MA 02114 USA. [Hoerster, Katherine] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Rosenberg, Dori] Grp Hlth Res Inst, Seattle, WA USA. [Nelson, Karin] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Reiber, Gayle E.] VA Puget Sound, Lake Forest Pk, WA USA. [Saelens, Brian] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. EM rmillstein@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C104 BP S200 EP S200 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002275 ER PT J AU Minges, KE Ritholz, MD Boyer, B Marko-witz, JT Pyatak, E Helgeson, V AF Minges, Karl E. Ritholz, Marilyn D. Boyer, Bret Marko-witz, Jessica T. Pyatak, Elizabeth Helgeson, Vicki TI EMERGING ADULTHOOD IN ADOLESCENTS & YOUNG ADULTS WITH DIABETES: OPPORTUNITY FOR BEHAVIORAL MEDICINE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Minges, Karl E.] Yale Univ, Wallingford, CT USA. [Ritholz, Marilyn D.; Marko-witz, Jessica T.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Boyer, Bret] Widener Univ, Philadelphia, PA 19119 USA. [Pyatak, Elizabeth] Univ So Calif, Los Angeles, CA 90089 USA. [Helgeson, Vicki] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. EM baboyer@mail.widener.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 02 BP S40 EP S40 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001155 ER PT J AU Park, ER Kirchhoff, A Perez, GK Leisenring, W Weissman, J Donelan, K Hyland, KA Armstrong, G Robison, L Kuhlthau, KA AF Park, Elyse R. Kirchhoff, Anne Perez, Giselle K. Leisenring, Wendy Weissman, Joel Donelan, Karen Hyland, Kelly A. Armstrong, Gregory Robison, Leslie Kuhlthau, Karen A. TI CHILDHOOD CANCER SURVIVOR STUDY PARTICIPANTS' HEALTH INSUR ANCE COVERAGE EXPERIENCES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Park, Elyse R.; Perez, Giselle K.; Donelan, Karen; Hyland, Kelly A.; Kuhlthau, Karen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirchhoff, Anne] Huntsman Canc Inst, Salt Lake City, UT USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Weissman, Joel] Brigham & Womens Hosp, Boston, MA 02115 USA. [Armstrong, Gregory; Robison, Leslie] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. EM epark@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A022 BP S9 EP S9 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001033 ER PT J AU Resnick, B Boltz, M Cooley, ME Hayman, LL AF Resnick, Barbara Boltz, Marie Cooley, Mary E. Hayman, Laura L. TI ADVANCING THE NATIONAL PREVENTION STRATEGY STARTING WITH ACUTE CARE AND ACUTE EVENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Resnick, Barbara] Univ Maryland, Baltimore, MD 21201 USA. [Boltz, Marie] Boston Coll, Boston, MA USA. [Cooley, Mary E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hayman, Laura L.] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 10 BP S48 EP S48 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001190 ER PT J AU Richardson, CR Damschroder, L Moin, T Estabrooks, P AF Richardson, Caroline R. Damschroder, Laura Moin, Tannaz Estabrooks, Paul TI IMPLEMENTING DIABETES PREVENTION IN THE VA - RESULTS FROM A CLINICAL DEMONSTRATION PROJECT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Richardson, Caroline R.] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. [Damschroder, Laura] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Moin, Tannaz] VA Greater Los Angeles, Los Angeles, CA USA. [Estabrooks, Paul] Virginia Tech, Caril Clin, Virginia Tech Caril Sch Med, Blacksburg, VA USA. EM caroli@umich.edu; laura.damschroder@va.gov; tmoin@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 30 BP S131 EP S131 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002005 ER PT J AU Schulman, D Mori, D Niles, B Reese, RL Allsup, K Forman, D Bachand, A AF Schulman, Daniel Mori, DeAnna Niles, Barbara Reese, Rebecca L. Allsup, Kelly Forman, Daniel Bachand, Amy TI IMPROVING ACCELEROMETER ESTIMATES OF PHYSICAL ACTIVITY IN A SEDENTARY DIABETIC POPULATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Schulman, Daniel; Mori, DeAnna; Reese, Rebecca L.; Allsup, Kelly] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Niles, Barbara] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Forman, Daniel] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Bachand, Amy] ENRM VA Med Ctr, Bedford, MA USA. EM daniel.schulman@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C102 BP S199 EP S199 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002273 ER PT J AU Stagl, J Bouchard, LC Lechner, SC Blomberg, B Gudenkauf, L Jutagir, DR Gluck, S Carver, C Antoni, MH AF Stagl, Jamie Bouchard, Laura C. Lechner, Suzanne C. Blomberg, Bonnie Gudenkauf, Lisa Jutagir, Devika R. Glueck, Stefan Carver, Charles Antoni, Michael H. TI LONG-TERM PSYCHOLOGICAL BENEFITS OF A PSYCHOSOCIAL INTERVENTION DURING BREAST CANCER TREATMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stagl, Jamie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Bouchard, Laura C.; Gudenkauf, Lisa; Jutagir, Devika R.; Carver, Charles] Univ Miami, Coral Gables, FL 33124 USA. [Lechner, Suzanne C.; Blomberg, Bonnie] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Glueck, Stefan] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Miami, FL 33136 USA. [Antoni, Michael H.] Univ Miami, Miami, FL USA. EM jstagl@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA B028 BP S98 EP S98 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001383 ER PT J AU Teo, AR AF Teo, Alan R. TI SHALL WE MEET UP? MODE AND FREQUENCY OF SOCIAL CONTACT AS A PREDICTOR FOR DEPRESSION IN THE ELDERLY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Teo, Alan R.] Portland VA Med Ctr, Portland, OR USA. EM teoa@ohsu.edu NR 0 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA D045 BP S234 EP S234 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002411 ER PT J AU Tucker-Seeley, R Leach, C Resnick, B Bellizzi, K AF Tucker-Seeley, Reginald Leach, Corinne Resnick, Barbara Bellizzi, Keith TI RESEARCH AT THE INTERSECTION OF CANCER AND AGING: A DISCUSSION BETWEEN AGING AND CANCER RESEARCHERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tucker-Seeley, Reginald] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leach, Corinne] Amer Canc Soc, Atlanta, GA 30309 USA. [Resnick, Barbara] Univ Maryland, Baltimore, MD 21201 USA. [Bellizzi, Keith] Univ Connecticut, Storrs, CT 06269 USA. EM corinne.leach@cancer.org; barbresnick@gmail.com; keith.m.bellizzi@uconn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 16 BP S141 EP S141 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002044 ER PT J AU Zhou, ES Partridge, AH Recklitis, CJ AF Zhou, Eric S. Partridge, Ann H. Recklitis, Christopher J. TI BRIEF, GROUP BEHAVIORAL TREATMENT FOR INSOMNIA IN A CANCER SURVIVORSHIP PROGRAM: DOES IT WORK? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Zhou, Eric S.; Partridge, Ann H.; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02215 USA. EM eric_zhou@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A017 BP S8 EP S8 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001028 ER PT J AU Raffetto, JD Eberhardt, RT AF Raffetto, Joseph D. Eberhardt, Robert T. TI Benefit of anticoagulation for the treatment of lower extremity superficial venous thrombosis SO JOURNAL OF VASCULAR SURGERY-VENOUS AND LYMPHATIC DISORDERS LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; DOUBLE-BLIND; THROMBOPHLEBITIS; LEGS; FONDAPARINUX AB Superficial venous thrombosis (SVT) of the lower extremity is an acute disorder characterized by thrombosis and inflammation of superficial veins. This most commonly affects varicose veins but can also occur in patients with nonvaricose veins, who may have an underlying condition such as a malignant disease or thrombophilia. It is important to be aware that SVT confers a significant risk for the development of the more serious and debilitating condition of deep venous thrombosis and the potentially life -threatening condition of pulmonary embolism. Recognition of SVT, determination of appropriateness of therapy, and institution of timely therapy are paramount to prevention of deep venous thrombosis and pulmonary embolism in properly selected patients. The objective of this evidence -based summary was to provide clinically applicable information from the current literature and guidelines regarding the best treatment options for SVT. There are no randomized trials that compare the efficacy and outcomes of newer therapies, such as the novel oral anticoagulants and endovenous ablation, with traditional therapies, such as traditional anticoagulant and surgery exclusion, in the treatment of SVT. C1 [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, Boston, MA USA. [Raffetto, Joseph D.] Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Eberhardt, Robert T.] Boston Med Ctr, Div Cardiol, Boston, MA USA. [Eberhardt, Robert T.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Raffetto, JD (reprint author), VA Boston Healthcare Syst, Surg 112, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-333X J9 J VASC SURG-VENOUS L JI J. Vasc. Surg.-Venous Lymphat. Dis. PD APR PY 2015 VL 3 IS 2 BP 236 EP 241 DI 10.1016/j.jvsv.2014.11.005 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DE9WI UT WOS:000370989700017 PM 26993846 ER PT J AU Eisen, SV Mueller, LN Chang, BH Resnick, SG Schultz, MR Clark, JA AF Eisen, Susan V. Mueller, Lisa N. Chang, Bei Hung Resnick, Sandra G. Schultz, Mark R. Clark, Jack A. TI Mental Health and Quality of Life Among Veterans Employed as Peer and Vocational Rehabilitation Specialists SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHIATRIC DISABILITIES; SUPPORTED EMPLOYMENT; NATIONAL-SURVEY; RECOVERY; PROVIDERS; BENEFITS; WORK; VA; SATISFACTION AB Objective: The study compared employment experiences, mental health recovery, and quality of life among peer specialists and vocational rehabilitation (VR) specialists hired by the U.S. Department of Veterans Affairs (VA), the VR specialists under the Homeless Veterans Supported Employment Program. Employment characteristics associated with mental health recovery were examined. Methods: The study was a national, observational survey of 152 peer specialists and 222 VR specialists across 138 VA health care systems in 49 states. The survey, administered over the Internet, included measures describing participant characteristics, employment factors, mental health, and quality of life. The two cohorts were compared by using t tests or chi square tests. Multiple regression analysis controlling for participant characteristics was used to identify employment factors associated with mental health and quality of life. Results: Peer specialists were more likely than VR specialists to share recovery stories, serve as a role model or mentor, and advocate for veterans. Activities by VR specialists tended to focus more narrowly on job skills. Overall, after adjusting for multiple comparisons, the analysis found high levels of mental health and average quality of life for both cohorts, with no significant differences between the groups. Satisfaction with amount of supervision was consistently associated with aspects of mental health recovery, including work-related and helping-related quality of life, for both cohorts. Conclusions: The results highlight the value of work and the importance of supervision in realizing both the adoption of recovery-oriented services and the promotion of mental health in a community of veterans serving each other. C1 [Eisen, Susan V.; Schultz, Mark R.; Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Eisen, Susan V.; Clark, Jack A.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Mueller, Lisa N.] Edith Nourse Rogers Mem Vet Hosp, MIRECC, Bedford, MA USA. [Chang, Bei Hung] Boston Healthcare Syst, US Dept Vet Affairs VA, Boston, MA USA. [Chang, Bei Hung] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Resnick, Sandra G.] VA New England Healthcare Syst, MIRECC, West Haven, CT USA. [Resnick, Sandra G.] Yale Univ, Sch Med, New Haven, CT USA. RP Eisen, SV (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. EM susan.eisen@va.gov FU VA Health Services Research and Development [IIR 10-332]; Edith Nourse Rogers Memorial Veterans Hospital FX This study was supported by VA Health Services Research and Development grant IIR 10-332 and the Edith Nourse Rogers Memorial Veterans Hospital. The authors thank Dan O'Brien-Mazza, M.S., and Anthony Campinell, Ph.D., for their support of this study and Patrick Furlong, B.A., Moe Armstrong, M.B.A., M.A., Alexandra Howard, B.S., Kevin Henze, Ph.D., Patricia Sweeney, Psy.D., and Matthew Chinman, Ph.D., for their contributions to this study. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 45 TC 3 Z9 3 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2015 VL 66 IS 4 BP 381 EP 388 DI 10.1176/appi.ps.201400105 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE5QW UT WOS:000370687300009 PM 25555066 ER PT J AU Tawakol, A Grinspoon, SK AF Tawakol, Ahmed Grinspoon, Steven K. TI Imaging atherosclerotic burden and inflammation: Insights into the spectrum of atherosclerotic disease in HIV SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; SUBCLINICAL CORONARY ATHEROSCLEROSIS; ACUTE MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; ARTERIAL INFLAMMATION; ANTIRETROVIRAL THERAPY; ACTIVATED MACROPHAGES; MICROBIAL TRANSLOCATION; INFECTED PATIENTS; RISK-FACTORS C1 [Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Tawakol, Ahmed; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA USA. [Grinspoon, Steven K.] Massachusetts Gen Hosp, Dept Med, Program Nutr Metab, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. EM atawakol@partners.org FU NIDDK NIH HHS [P30 DK040561] NR 39 TC 2 Z9 2 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 APR PY 2015 VL 22 IS 2 BP 381 EP 384 DI 10.1007/s12350-014-0044-9 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DD4LB UT WOS:000369893300002 PM 25537613 ER PT J AU Sarris, J Stough, C Bousman, C Murphy, J Savage, K Smith, DJ Menon, R Chamoli, S Oliver, G Berk, M Byrne, GJ Ng, C Mischoulon, D AF Sarris, Jerome Stough, Con Bousman, Chad Murphy, Jenifer Savage, Karen Smith, Deidre J. Menon, Ranjit Chamoli, Suneel Oliver, Georgina Berk, Michael Byrne, Gerard J. Ng, Chee Mischoulon, David TI An adjunctive antidepressant nutraceutical combination in treating major depression: Study protocol, and clinical considerations SO ADVANCES IN INTEGRATIVE MEDICINE LA English DT Article DE S-Adenosyl methionine; SAMe; Omega-3; Antidepressant; Nutraceutical; Nutrient; Depression; RCT; Protocol ID RANDOMIZED CONTROLLED-TRIALS; S-ADENOSYL METHIONINE; TAIL SUSPENSION TEST; STAR-ASTERISK-D; DOUBLE-BLIND; BIPOLAR DISORDER; FOLIC-ACID; EFFICACY; METAANALYSIS; ZINC AB Current treatment for major depressive disorder (MDD), a prevalent and disabling mental illness, is inadequate, with two-thirds of people treated with first-line antidepressants not achieving remission. MDD is for many a chronic condition, often requiring multiple treatment attempts, thus development of additional interventions is urgently required. An emerging approach to improve non-response to antidepressants is the use of adjunctive nutraceuticals. The pathophysiology of MDD is considered to involve a range of abnormalities (monoamine impairment, neuro-endocrinological changes, reduced brain-derived neurotrophic factor, and cytokine alterations). By targeting an array of these key neurobiological pathways via specific nutraceuticals (S-adenosyl methionine; [SAMe], 5-HTP [active tryptophan], folinic acid [active folic acid], omega-3 fatty acids, and zinc), there is the potential to provide a more comprehensive therapeutic biological approach to treat depression. We are currently conducting a National Health and Medical Research Council funded study in Australia (APP1048222). The clinical trial is phase II/III, multi-site, 3-arm, 8-week, randomised, double-blind, placebo-controlled study using SAMe + folinic [acid versus a combination nutraceutical (SAMe, 5-HTP, folinic acid, omega-3, and zinc) or matching placebo in 300 currently depressed participants with diagnosed MDD who are non-responsive to current antidepressants (ANZCTR, protocol number: 12613001300763). The results may provide evidence for a novel adjunctive neurobiological approach for treating depression. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Sarris, Jerome; Murphy, Jenifer; Savage, Karen; Smith, Deidre J.; Menon, Ranjit; Oliver, Georgina; Ng, Chee] Univ Melbourne, Dept Psychiat, Melbourne Clin, Melbourne, Vic, Australia. [Sarris, Jerome; Stough, Con; Bousman, Chad; Savage, Karen] Swinburne Univ Technol, Ctr Human Psychopharmacol, Hawthorn, Vic 3122, Australia. [Bousman, Chad; Berk, Michael] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. [Bousman, Chad] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Bousman, Chad] Univ Melbourne, Dept Gen Practice, Parkville, Vic 3052, Australia. [Chamoli, Suneel; Byrne, Gerard J.] Univ Queensland, Discipline Psychiat, Brisbane, Qld 4072, Australia. [Mischoulon, David] Harvard Univ, Sch Med, Dept Psychiat, Depress Clin & Res Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne Clin, 2 Salisbury St, Melbourne, Vic, Australia. EM jsarris@unimelb.edu.au OI stough, con/0000-0002-3628-3220 NR 36 TC 3 Z9 3 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-9626 J9 ADV INTEGR MED JI Adv. Integr. Med. PD APR PY 2015 VL 2 IS 1 SI SI BP 49 EP 55 DI 10.1016/j.aimed.2015.02.001 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CZ8KC UT WOS:000367347600008 ER PT J AU Douw, L DeSalvo, MN Tanaka, N Cole, AJ Liu, HS Reinsberger, C Stufflebeam, SM AF Douw, Linda DeSalvo, Matthew N. Tanaka, Naoaki Cole, Andrew J. Liu, Hesheng Reinsberger, Claus Stufflebeam, Steven M. TI Dissociated multimodal hubs and seizures in temporal lobe epilepsy SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID DEFAULT-MODE NETWORK; INTRINSIC FUNCTIONAL CONNECTIVITY; RESTING-STATE NETWORKS; HUMAN CEREBRAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; EPISODIC MEMORY CAPACITY; HUMAN BRAIN; SMALL-WORLD; STRUCTURAL CONNECTIVITY; HIPPOCAMPAL NETWORKS AB Objective: Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in "hub" areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We aim to clarify these associations using connectivity measures specifically sensitive to hubs. Methods: Connectivity between 1000 cortical surface parcels was determined in 49 TLE patients and 23 controls with diffusion and resting-state functional magnetic resonance imaging. Two types of hub connectivity were investigated across multiple brain modules (the DMN, motor system, etcetera): (1) within-module connectivity (a measure of local importance that assesses a parcel's communication level within its own subnetwork) and (2) between-module connectivity (a measure that assesses connections across multiple modules). Results: In TLE patients, there was lower overall functional integrity of the DMN as well as an increase in posterior hub connections with other modules. Anatomical between-module connectivity was globally decreased. Higher DMN disintegration (DD) coincided with higher anatomical between-module connectivity, whereas both were associated with increased seizure frequency. DD related to seizure frequency through mediating effects of anatomical connectivity, but seizure frequency also correlated with anatomical connectivity through DD, indicating a complex interaction between multimodal networks and symptoms. Interpretation: We provide evidence for dissociated anatomical and functional hub connectivity in TLE. Moreover, shifts in functional hub connections from within to outside the DMN, an overall loss of integrative anatomical communication, and the interaction between the two increase seizure frequency. C1 [Douw, Linda; DeSalvo, Matthew N.; Tanaka, Naoaki; Liu, Hesheng; Reinsberger, Claus; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Douw, Linda; DeSalvo, Matthew N.; Tanaka, Naoaki; Liu, Hesheng; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Douw, Linda] Vrije Univ Amsterdam Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Reinsberger, Claus] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Douw, L (reprint author), Dept Anat & Neurosci, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM douw@nmr.mgh.harvard.edu OI Cole, Andrew/0000-0002-0828-826X FU NIMH NIH HHS [U01 MH093765]; NINDS NIH HHS [K25 NS069805, R01 NS060918, R01 NS069696, R01 NS091604] NR 66 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD APR PY 2015 VL 2 IS 4 BP 338 EP 352 DI 10.1002/acn3.173 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ3CJ UT WOS:000366981500002 PM 25909080 ER PT J AU Mitsui, J Matsukawa, T Sasaki, H Yabe, I Matsushima, M Durr, A Brice, A Takashima, H Kikuchi, A Aoki, M Ishiura, H Yasuda, T Date, H Ahsan, B Iwata, A Goto, J Ichikawa, Y Nakahara, Y Momose, Y Takahashi, Y Hara, K Kakita, A Yamada, M Takahashi, H Onodera, O Nishizawa, M Watanabe, H Ito, M Sobue, G Ishikawa, K Mizusawa, H Kanai, K Hattori, T Kuwabara, S Arai, K Koyano, S Kuroiwa, Y Hasegawa, K Yuasa, T Yasui, K Nakashima, K Ito, H Izumi, Y Kaji, R Kato, T Kusunoki, S Osaki, Y Horiuchi, M Kondo, T Murayama, S Hattori, N Yamamoto, M Murata, M Satake, W Toda, T Filla, A Klockgether, T Wullner, U Nicholson, G Gilman, S Tanner, CM Kukull, WA Stern, MB Lee, VMY Trojanowski, JQ Masliah, E Low, PA Sandroni, P Ozelius, LJ Foroud, T Tsuji, S AF Mitsui, Jun Matsukawa, Takashi Sasaki, Hidenao Yabe, Ichiro Matsushima, Masaaki Duerr, Alexandra Brice, Alexis Takashima, Hiroshi Kikuchi, Akio Aoki, Masashi Ishiura, Hiroyuki Yasuda, Tsutomu Date, Hidetoshi Ahsan, Budrul Iwata, Atsushi Goto, Jun Ichikawa, Yaeko Nakahara, Yasuo Momose, Yoshio Takahashi, Yuji Hara, Kenju Kakita, Akiyoshi Yamada, Mitsunori Takahashi, Hitoshi Onodera, Osamu Nishizawa, Masatoyo Watanabe, Hirohisa Ito, Mizuki Sobue, Gen Ishikawa, Kinya Mizusawa, Hidehiro Kanai, Kazuaki Hattori, Takamichi Kuwabara, Satoshi Arai, Kimihito Koyano, Shigeru Kuroiwa, Yoshiyuki Hasegawa, Kazuko Yuasa, Tatsuhiko Yasui, Kenichi Nakashima, Kenji Ito, Hijiri Izumi, Yuishin Kaji, Ryuji Kato, Takeo Kusunoki, Susumu Osaki, Yasushi Horiuchi, Masahiro Kondo, Tomoyoshi Murayama, Shigeo Hattori, Nobutaka Yamamoto, Mitsutoshi Murata, Miho Satake, Wataru Toda, Tatsushi Filla, Alessandro Klockgether, Thomas Wuellner, Ullrich Nicholson, Garth Gilman, Sid Tanner, Caroline M. Kukull, Walter A. Stern, Mathew B. Lee, Virginia M. -Y. Trojanowski, John Q. Masliah, Eliezer Low, Phillip A. Sandroni, Paola Ozelius, Laurie J. Foroud, Tatiana Tsuji, Shoji TI Variants associated with Gaucher disease in multiple system atrophy SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID GLIAL CYTOPLASMIC INCLUSIONS; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; OLIVOPONTOCEREBELLAR ATROPHY; LEWY BODIES; TYPE-1; SNCA; MULTICENTER; ALLELES AB Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10(-3)). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA. C1 [Mitsui, Jun; Matsukawa, Takashi; Ishiura, Hiroyuki; Yasuda, Tsutomu; Date, Hidetoshi; Ahsan, Budrul; Iwata, Atsushi; Goto, Jun; Ichikawa, Yaeko; Nakahara, Yasuo; Momose, Yoshio; Takahashi, Yuji; Tsuji, Shoji] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo, Japan. [Sasaki, Hidenao; Yabe, Ichiro; Matsushima, Masaaki] Hokkaido Univ, Grad Sch Med, Dept Neurol, Sapporo, Hokkaido, Japan. [Duerr, Alexandra; Brice, Alexis] Univ Paris 06, Univ Sorbonne 3, Hop La Pitie Salpetriere,CNRS,UMR 7225,UM 75,ICM, AP HP,Dept Genet & Cytogenet,INSERM,U1127, F-75013 Paris, France. [Takashima, Hiroshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Neurol & Geriatr, Kagoshima 890, Japan. [Kikuchi, Akio; Aoki, Masashi] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. [Hara, Kenju; Onodera, Osamu; Nishizawa, Masatoyo] Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan. [Kakita, Akiyoshi; Yamada, Mitsunori; Takahashi, Hitoshi] Niigata Univ, Brain Res Inst, Dept Pathol, Niigata, Japan. [Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen] Natl Hosp Org, Dept Clin Res, Saigata Med Ctr, Niigata, Japan. [Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen] Nagoya Univ, Grad Sch Med, Dept Neurol, Nagoya, Aichi 4648601, Japan. [Ishikawa, Kinya; Mizusawa, Hidehiro] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Neurol & Neurol Sci, Tokyo, Japan. [Kanai, Kazuaki; Hattori, Takamichi; Kuwabara, Satoshi] Chiba Univ, Sch Med, Dept Neurol, Chiba 280, Japan. [Arai, Kimihito] Natl Hosp Org, Chiba East Hosp, Div Neurol, Chiba, Japan. [Koyano, Shigeru] Yokohama City Univ, Grad Sch Med, Dept Clin Neurol & Stroke Med, Yokohama, Kanagawa 232, Japan. [Kuroiwa, Yoshiyuki] Teikyo Univ, Sch Med, Univ Hosp, Dept Neurol, Kawasaki, Kanagawa, Japan. [Hasegawa, Kazuko] Natl Hosp Org, Sagamihara Natl Hosp, Div Neurol, Sagamihara, Kanagawa, Japan. [Yuasa, Tatsuhiko] Kamagaya Gen Hosp, Kamagaya Chiba Med Ctr Intractable Neurol Dis, Dept Neurol, Chiba, Japan. [Yasui, Kenichi; Nakashima, Kenji] Tottori Univ, Fac Med, Dept Brain & Neurosci, Div Neurol, Yonago, Tottori 683, Japan. [Ito, Hijiri] Mifukai Vihara Hananosato Hosp, Dept Neurol, Hiroshima, Japan. [Izumi, Yuishin; Kaji, Ryuji] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Clin Neurosci, Tokushima 770, Japan. [Kato, Takeo] Yamagata Univ, Fac Med, Dept Neurol, Yamagata 990, Japan. [Kato, Takeo] Yamagata Univ, Fac Med, Dept Hematol, Yamagata 990, Japan. [Kato, Takeo] Yamagata Univ, Fac Med, Dept Metab, Yamagata 990, Japan. [Kato, Takeo] Yamagata Univ, Fac Med, Dept Endocrinol, Yamagata 990, Japan. [Kato, Takeo] Yamagata Univ, Fac Med, Dept Diabetol, Yamagata 990, Japan. [Kusunoki, Susumu] Kinki Univ, Sch Med, Dept Neurol, Osaka 589, Japan. [Osaki, Yasushi] Kochi Med Sch, Dept Geriatr Cardiol & Neurol, Nankoku, Kochi, Japan. [Horiuchi, Masahiro] St Marianna Univ, Sch Med, Dept Internal Med, Div Neurol, Kawasaki, Kanagawa, Japan. [Kondo, Tomoyoshi] Wakayama Med Univ, Dept Neurol, Wakayama, Japan. [Murayama, Shigeo] Tokyo Metropolitan Geriatr Hosp, Dept Neuropathol, Tokyo 173, Japan. [Murayama, Shigeo] Tokyo Metropolitan Geriatr Hosp, Brain Bank Aging Res, Tokyo 173, Japan. [Murayama, Shigeo] Inst Gerontol, Tokyo, Japan. [Hattori, Nobutaka] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. [Yamamoto, Mitsutoshi] Kagawa Prefectural Cent Hosp, Dept Neurol, Takamatsu, Kagawa, Japan. [Murata, Miho] Natl Ctr Hosp Neurol & Psychiat, Dept Neurol, Tokyo, Japan. [Satake, Wataru; Toda, Tatsushi] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan. [Filla, Alessandro] Univ Naples Federico II, Dept Neurol Sci, Naples, Italy. [Klockgether, Thomas; Wuellner, Ullrich] Univ Bonn, Dept Neurol, Bonn, Germany. [Klockgether, Thomas; Wuellner, Ullrich] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Nicholson, Garth] Univ Sydney, Concord Hosp, Australian & New Zealand Army Corps ANZAC Res Ins, Sydney, NSW 2006, Australia. [Gilman, Sid] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Kukull, Walter A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Stern, Mathew B.] Univ Penn, Dept Neurol, Perelman Sch Med, Parkinsons Dis & Movement Disorders Ctr, Philadelphia, PA 19104 USA. [Kikuchi, Akio; Lee, Virginia M. -Y.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Udall Parkinsons Res Ctr, Inst Aging, Philadelphia, PA 19104 USA. [Lee, Virginia M. -Y.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Lee, Virginia M. -Y.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Low, Phillip A.; Sandroni, Paola] Mayo Clin, Dept Neurol, Rochester, MN USA. [Ozelius, Laurie J.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Ozelius, Laurie J.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. RP Tsuji, S (reprint author), 7-3-1 Hongo, Tokyo 1138655, Japan. EM tsuji@m.u-tokyo.ac.jp RI Iwata, Atsushi/A-9598-2013; Onodera, Osamu/K-7327-2013 OI Iwata, Atsushi/0000-0001-7308-5314; Onodera, Osamu/0000-0003-3354-5472 FU NIA NIH HHS [P50 AG005131, U01 AG016976]; NINDS NIH HHS [P01 NS044233, P50 NS053488] NR 36 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD APR PY 2015 VL 2 IS 4 BP 417 EP 426 DI 10.1002/acn3.185 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ3CJ UT WOS:000366981500008 PM 25909086 ER PT J AU Sullivan, ZA Wong, EB Ndung'u, T Kasprowicz, VO Bishai, WR AF Sullivan, Zuri A. Wong, Emily B. Ndung'u, Thumbi Kasprowicz, Victoria O. Bishai, William R. TI Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV SO EBIOMEDICINE LA English DT Article DE HIV; Tuberculosis; Immune activation; Inflammation ID T-CELL-ACTIVATION; ANTIRETROVIRAL THERAPY; MICROBIAL TRANSLOCATION; PREVENTIVE THERAPY; LYMPHOCYTE ACTIVATION; DISEASE PROGRESSION; SOLUBLE CD14; SOUTH-AFRICA; VIRAL LOAD; BURDEN AB In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states of Mycobacterium tuberculosis co-infection contribute to elevated immune activation as measured by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB-and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression. Significance: Latent tuberculosis, which affects an estimated 1/3 of the world's population, has long been thought to be a relatively benign, quiescent state of M. tuberculosis infection. While HIV co-infection is known to exacerbate M. tuberculosis infection and increase the risk of developing active TB, little is known about the potential effect of latent TB infection on HIV disease. This study shows that HIV-infected individuals with both active and latent TB have elevated levels of inflammation and immune activation, biomarkers of HIV disease progression and elevated risk of mortality. These results suggest that, in the context of HIV, latent TB infection may be associated with increased risk of progression to AIDS and mortality. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Sullivan, Zuri A.; Wong, Emily B.; Ndung'u, Thumbi; Kasprowicz, Victoria O.; Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Sullivan, Zuri A.; Bishai, William R.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Wong, Emily B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ndung'u, Thumbi; Kasprowicz, Victoria O.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Durban, South Africa. [Ndung'u, Thumbi; Kasprowicz, Victoria O.] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Cambridge, MA 02138 USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. RP Sullivan, ZA (reprint author), Yale Univ, Dept Immunobiol, Anlyan Ctr Med Res & Educ, 300 Cedar St,POB 208011, New Haven, CT 06520 USA. EM wbishai@jhmi.edu OI Ndung'u, Thumbi/0000-0003-2962-3992 FU NIAID NIH HHS [R01 AI036973, R01 AI037856, R01 AI097138, T32 AI007387] NR 40 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD APR PY 2015 VL 2 IS 4 BP 334 EP 340 DI 10.1016/j.ebiom.2015.03.005 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CX8KL UT WOS:000365952100013 PM 26114158 ER PT J AU Anselmi, L Huynh, J Duraffourd, C Jaramillo, I Vegezzi, G Saccani, F Boschetti, E Brecha, NC De Giorgio, R Sternini, C AF Anselmi, L. Huynh, J. Duraffourd, C. Jaramillo, I. Vegezzi, G. Saccani, F. Boschetti, E. Brecha, N. C. De Giorgio, R. Sternini, C. TI Activation of mu opioid receptors modulates inflammation in acute experimental colitis SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE antiapoptotic factor; cytokines; inflammatory indexes; transcriptional nuclear factor-kB ID NF-KAPPA-B; RAT GASTROINTESTINAL-TRACT; GUINEA-PIG ILEUM; IMMUNE-SYSTEM; CELL-DEATH; INTESTINAL ISCHEMIA/REPERFUSION; GENE-EXPRESSION; BOWEL DISEASES; MICE LACKING; MECHANISMS AB Background mu opioid receptors (mu ORs) are expressed by neurons and inflammatory cells, and mediate immune response. We tested whether activation of peripheral mu ORs ameliorates the acute and delayed phase of colitis. Methods C57BL/6J mice were treated with 3% dextran sodium sulfate (DSS) in water, 5 days with or without the peripherally acting mu OR agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or with DAMGO+mu OR antagonist at day 2-5, then euthanized. Other mice received DSS followed by water for 4 weeks, or DSS with DAMGO starting at day 2 of DSS for 2 or 3 weeks followed by water, then euthanized at 4 weeks. Disease activity index (DAI), histological damage, and myeloperoxidase assay (MPO), as index of neutrophil infiltration, were evaluated. Cytokines and mu OR mRNAs were measured with RT-PCR, and nuclear factor-kB (NF-kB), the antiapoptotic factor Bcl-xL, and caspase 3 and 7 with Western blot. Key Results DSS induced acute colitis with elevated DAI, tissue damage, apoptosis and increased MPO, cytokines, mu OR mRNA, and NF-kB. DAMGO significantly reduced DAI, inflammatory indexes, cytokines, caspases, and NF-kB, and upregulated Bcl-xL, effects prevented by lOR antagonist. In DSS mice plus 4 weeks of water, DAI, NF-kB, and lOR were normal, whereas MPO, histological damage, and cytokines were still elevated; DAMGO did not reduce inflammation, and did not upregulate Bcl-xL. Conclusions & Inferences lOR activation ameliorated the acute but not the delayed phase of DSS colitis by reducing cytokines, likely through activation of the antiapoptotic factor, Bcl-xL, and suppression of NF-kB, a potentiator of inflammation. C1 [Anselmi, L.; Huynh, J.; Duraffourd, C.; Jaramillo, I.; Vegezzi, G.; Saccani, F.; Brecha, N. C.; Sternini, C.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Anselmi, L.; Huynh, J.; Duraffourd, C.; Jaramillo, I.; Vegezzi, G.; Saccani, F.; Brecha, N. C.; Sternini, C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Duraffourd, C.; Brecha, N. C.; Sternini, C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Boschetti, E.; De Giorgio, R.] Univ Bologna, St Orsola Malpighi Hosp, CRBA, Dept Med & Surg Sci, Bologna, Italy. [Brecha, N. C.; Sternini, C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. RP Sternini, C (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE DDRC, 650 C Young Dr South,CHS 44-146, Los Angeles, CA 90095 USA. EM csternin@ucla.edu RI Boschetti, Elisa/J-3684-2016 OI Boschetti, Elisa/0000-0003-4503-2770 FU National Institutes of Health [R01 DK54155, P30 DK41301]; Morphology and Cell Imaging Core; VA Career Research Scientist Award; Italian Ministry of Education, University and Research (MIUR) (PRIN); Fondazione Del Monte di Bologna e Ravenna, Italy FX This work was supported by the National Institutes of Health, R01 DK54155 (to C.S.) and P30 DK41301, Morphology and Cell Imaging Core (to C.S.), a VA Career Research Scientist Award (to N.C.B) and Italian Ministry of Education, University and Research (MIUR) (PRIN2009) and Fondazione Del Monte di Bologna e Ravenna, Italy (to R.D.G.). NR 58 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD APR PY 2015 VL 27 IS 4 BP 509 EP 523 DI 10.1111/nmo.12521 PG 15 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CW1HR UT WOS:000364740900007 PM 25690069 ER PT J AU Lin, MV Sise, ME Pavlakis, M Hanifi, JM Rutherford, AE Elias, N Heher, EC Curry, MP Riella, LV AF Lin, M. V. Sise, M. E. Pavlakis, M. Hanifi, J. M. Rutherford, A. E. Elias, N. Heher, E. C. Curry, M. P. Riella, L. V. TI SAFETY AND EFFICACY OF NOVEL ANTIVIRALS IN KIDNEY TRANSPLANT RECIPIENTS WITH CHRONIC HEPATITIS C VIRUS (HCV) INFECTION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Lin, M. V.; Rutherford, A. E.] Brigham & Womens Hosp, Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Sise, M. E.; Heher, E. C.] Massachusetts Gen Hosp, Nephrol, Boston, MA 02114 USA. [Pavlakis, M.] Beth Israel Deaconess Med Ctr, Nephrol, Boston, MA USA. [Hanifi, J. M.] Brigham & Womens Hosp, Internal Med, Boston, MA 02115 USA. [Elias, N.] Massachusetts Gen Hosp, Transplant Surg, Boston, MA 02114 USA. [Curry, M. P.] Beth Israel Deaconess Med Ctr, Gastroenterol Liver Ctr, Boston, MA USA. [Riella, L. V.] Brigham & Womens Hosp, Nephrol, Boston, MA 02115 USA. EM mvlin@partners.org NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP42 BP S284 EP S285 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600196 ER PT J AU Saxena, V Koraishy, FM Sise, M Lim, JK Chung, RT Liapakis, A Nelson, DR Schmidt, M Fried, MW Terrault, N AF Saxena, V. Koraishy, F. M. Sise, M. Lim, J. K. Chung, R. T. Liapakis, A. Nelson, D. R. Schmidt, M. Fried, M. W. Terrault, N. CA HCV-TARGET TI SAFETY AND EFFICACY OF SOFOSBUVIR-CONTAINING REGIMENS IN HEPATITIS C INFECTED PATIENTS WITH REDUCED RENAL FUNCTION: REAL-WORLD EXPERIENCE FROM HCV-TARGET SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Saxena, V.; Terrault, N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koraishy, F. M.] St Louis Univ, Sch Med, St Louis, MO USA. [Sise, M.; Chung, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lim, J. K.; Liapakis, A.] Yale Univ, Sch Med, New Haven, CT USA. [Nelson, D. R.] Univ Florida, Gainesville, FL USA. [Schmidt, M.; Fried, M. W.] Univ N Carolina, Chapel Hill, NC USA. EM varun.saxena@ucsf.edu NR 0 TC 19 Z9 19 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP08 BP S267 EP S267 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600162 ER PT J AU Westlin, WF Harwood, HJ DePeralta, DK Moaven, O Wei, L Greenwood, J Bhat, S Fuchs, BC Kapeller, R Harriman, G AF Westlin, W. F. Harwood, H. J. DePeralta, D. K. Moaven, O. Wei, L. Greenwood, J. Bhat, S. Fuchs, B. C. Kapeller, R. Harriman, G. TI LIVER-DIRECTED ALLOSTERIC INHIBITORS OF ACETYL-CoA CARBOXYLASE FAVORABLY IMPACT PATHOPHYSIOLOGY IN THE PROGRESSION FROM NAFLD TO NASH AND HEPATOCELLULAR CARCINOMA, INCLUDING HEPATIC STEATOSIS, INFLAMMATION, AND FIBROSIS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Westlin, W. F.; Harwood, H. J.; Kapeller, R.; Harriman, G.] Nimbus Therapeut, Cambridge, MA USA. [DePeralta, D. K.; Moaven, O.; Wei, L.; Fuchs, B. C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Greenwood, J.; Bhat, S.] Schrodinger, New York, NY USA. EM wwestlin@nimbusdiscovery.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP30 BP S279 EP S279 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600184 ER PT J AU Basu, PP Shah, NJ Brown, R AF Basu, P. P. Shah, N. J. Brown, R., Jr. TI SIMEPREVIR AND SOFOSBUVIR WITH MODIFIED DOSES OF RIBAVIRIN (RBV) THERAPY ON TELAPREVIR EXPERIENCED CO INFECTED (WITH HIV) CIRRHOTICS WITH CHRONIC HEPATITIS C (CHC). A RANDOMIZED OPEN LABEL CLINICAL PILOT STUDY: STOP C SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Basu, P. P.; Brown, R., Jr.] Columbia Univ Coll Phys & Surg, New York, NY USA. [Basu, P. P.] Kings Cty Hosp, Med Ctr, Brooklyn, NY USA. [Shah, N. J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. EM basu.patrick@gmail.com NR 0 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0819 BP S643 EP S643 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900014 ER PT J AU Khalili, M Lombardero, M Feld, J Shuhart, M Chung, R Terrault, N Kowdley, K Lisker-Melman, M Ghany, M Kim, WR Sanyal, A Lok, A AF Khalili, M. Lombardero, M. Feld, J. Shuhart, M. Chung, R. Terrault, N. Kowdley, K. Lisker-Melman, M. Ghany, M. Kim, W. R. Sanyal, A. Lok, A. CA HBRN TI THE IMPACT OF METABOLIC SYNDROME ON ALT LEVELS AMONG THE LARGE MULTIETHNIC COHORT OF NORTH AMERICAN PATIENTS WITH CHRONIC HEPATITIS B INFECTION ENROLLED IN THE HEPATITIS B RESEARCH NETWORK (HBRN) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Khalili, M.; Terrault, N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lombardero, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Feld, J.] Univ Toronto, Toronto, ON, Canada. [Shuhart, M.] Univ Washington, Seattle, WA 98195 USA. [Chung, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kowdley, K.] Swedish Med Ctr, Seattle, WA USA. [Lisker-Melman, M.] Washington Univ, St Louis, MO USA. [Ghany, M.] NIH, Bethesda, MD 20892 USA. [Kim, W. R.] Stanford Univ, Palo Alto, CA 94304 USA. [Sanyal, A.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Lok, A.] Univ Michigan, Ann Arbor, MI 48109 USA. EM mandana.khalili@ucsf.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 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P1019 BP S729 EP S730 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900212 ER PT J AU Linas, BP Morgan, JR Pho, MT Leff, JA Schackman, BR Assoumou, SA Salomon, JA Freedberg, KA Kim, AY AF Linas, B. P. Morgan, J. R. Pho, M. T. Leff, J. A. Schackman, B. R. Assoumou, S. A. Salomon, J. A. Freedberg, K. A. Kim, A. Y. TI THE COST-EFFECTIVENESS OF SOFOSBUVIR- AND SIMEPREVIR-BASED THERAPIES FOR HCV GENOTYPE 1 INFECTION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Linas, B. P.; Assoumou, S. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Morgan, J. R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Pho, M. T.] Univ Chicago, Sch Med, Chicago, IL 60637 USA. [Leff, J. A.; Schackman, B. R.] Cornell Univ, Weill Cornell Sch Med, New York, NY 10021 USA. [Salomon, J. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Freedberg, K. A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Kim, A. Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM benjamin.linas@bmc.org RI Salomon, Joshua/D-3898-2009 OI Salomon, Joshua/0000-0003-3929-5515 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0798 BP S633 EP S633 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EJ UT WOS:000362830600515 ER PT J AU Sonntag, R Moro, N Nevzorova, YA Bangen, JM Fahrenkamp, D Lambertz, D Hu, W Gassler, N Muller-Newen, G Weiskirchen, R Barbacid, M Sicinski, P Trautwein, C Liedtke, C AF Sonntag, R. Moro, N. Nevzorova, Y. A. Bangen, J. M. Fahrenkamp, D. Lambertz, D. Hu, W. Gassler, N. Mueller-Newen, G. Weiskirchen, R. Barbacid, M. Sicinski, P. Trautwein, C. Liedtke, C. TI INACTIVATION OF CYCLIN E1 ACTS PRO-APOPTOTIC AND ANTI-PROLIFERATIVE IN PRIMARY HEPATOMA CELLS AND PROTECTS FROM HEPATOCARCINOGENESIS IN MICE SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Sonntag, R.; Nevzorova, Y. A.; Bangen, J. M.; Lambertz, D.; Hu, W.; Trautwein, C.; Liedtke, C.] Rhein Westfal TH Aachen, Dept Internal Med 3, Aachen, Germany. [Moro, N.] Univ Hosp Koln, Dept Dermatol, Cologne, Germany. [Fahrenkamp, D.; Mueller-Newen, G.] Rhein Westfal TH Aachen, Inst Biochem & Mol Biol, Aachen, Germany. [Gassler, N.] Rhein Westfal TH Aachen, Inst Pathol, Aachen, Germany. [Weiskirchen, R.] Rhein Westfal TH Aachen, Inst Mol Pathobiochem Expt Gene Therapy & Clin Ch, Aachen, Germany. [Barbacid, M.] CNIO, Madrid, Spain. [Sicinski, P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM rsonntag@ukaachen.de NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0285 BP S414 EP S415 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EJ UT WOS:000362830600008 ER PT J AU Ahmad, R Alam, M Rajabi, H Kufe, D AF Ahmad, Rehan Alam, Maroof Rajabi, Hasan Kufe, Donald TI MUC1-C Induces the LIN28B -> LET-7 -> HMGA2 Axis to Regulate Self-renewal in NSCLC SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Ahmad, Rehan] King Saud Univ, Colorectal Res Ctr, Riyadh, Saudi Arabia. [Alam, Maroof; Rajabi, Hasan; Kufe, Donald] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 728.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701397 ER PT J AU Arystarkhova, E Liu, YB Ralph, D Figtree, G McDonough, A Sweadner, K AF Arystarkhova, Elena Liu, Yi Bessie Ralph, Donna Figtree, Gemma McDonough, Alicia Sweadner, Kathleen TI Sodium balance and resistance to Ang II-induced hypertension, despite NCC and NKCC2 activation, in mice with global deletion of Na,K-ATPase regulatory subunit FXYD2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Arystarkhova, Elena; Liu, Yi Bessie; Sweadner, Kathleen] Massachusetts Gen Hosp, Neurosurg, Boston, MA 02114 USA. [Ralph, Donna; McDonough, Alicia] Univ So Calif, Keck Sch Med, Cell & Neurobiol, Los Angeles, CA 90033 USA. [Figtree, Gemma] Univ Sydney, Kolling Inst, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 960.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706386 ER PT J AU Baer, L Song, JQ Stanford, K Wolf, S Wade, C AF Baer, Lisa Song, Juquan Stanford, Kristin Wolf, Steven Wade, Charles TI Effects of Burn and Disuse with Resistance Exercise on Free Fatty Acids and Fibroblast Growth Factor-21 in Rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Baer, Lisa; Wade, Charles] Univ Texas Hlth Sci Ctr Houston, CeTIR, Houston, TX 77030 USA. [Baer, Lisa; Wade, Charles] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA. [Song, Juquan; Wolf, Steven] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Stanford, Kristin] Joslin Diabet Ctr, Int Phys & Met, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1037.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722708012 ER PT J AU Beauchamp, R James, M Wagh, V DeSouza, P Zhao, WN Stemmer-Rachamimov, A Plotkin, S Gusella, J Haggarty, S Ramesh, V AF Beauchamp, Roberta James, Marianne Wagh, Vilas DeSouza, Patrick Zhao, Wen-Ning Stemmer-Rachamimov, Anat Plotkin, Scott Gusella, James Haggarty, Stephen Ramesh, Vijaya TI Kinome Screen Reveals SGK1 as a Therapeutic Target for NF2: Inhibition of mTORC1/2 is More Effective than Rapamycin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Beauchamp, Roberta; James, Marianne; Wagh, Vilas; DeSouza, Patrick; Zhao, Wen-Ning; Stemmer-Rachamimov, Anat; Plotkin, Scott; Gusella, James; Haggarty, Stephen; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 889.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705090 ER PT J AU Bunch, H Lawney, B Asaithamby, A Murshid, A Wang, YY Chen, B Calderwood, S AF Bunch, Heeyoun Lawney, Brian Asaithamby, Aroumougame Murshid, Ayesha Wang, Yaoyu Chen, Benjamin Calderwood, Stuart TI Transcriptional Elongation Requires DNA Double Stand Break and Repair SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Bunch, Heeyoun; Murshid, Ayesha; Calderwood, Stuart] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Radiat Oncol, Boston, MA 02215 USA. [Lawney, Brian; Wang, Yaoyu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Asaithamby, Aroumougame] Univ Texas SW Med Ctr Dallas, Div Dept Radiat Oncol, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 877.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704281 ER PT J AU Chandler, P Kochupurakkal, B Lopez, V Alam, S Soybel, D Kelleher, S AF Chandler, Paige Kochupurakkal, Bose Lopez, Veronica Alam, Samina Soybel, David Kelleher, Shannon TI The Zinc Transporting Network is a Central Component of Dysregulation in Breast Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Chandler, Paige; Alam, Samina; Soybel, David; Kelleher, Shannon] Penn State Univ, Cell & Mol Physiol, University Pk, PA 16802 USA. [Kochupurakkal, Bose] Dana Farber Canc Inst, Surg, Boston, MA USA. [Lopez, Veronica] Consumnes River Coll, Nutr, Sacramento, CA USA. [Soybel, David; Kelleher, Shannon] Penn State Univ, Surg, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 921.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706089 ER PT J AU Cheung, P Nomura, N Nair, A Lu, H Bouley, R Brown, D AF Cheung, Pui Nomura, Naohiro Nair, Anil Lu, Hua Bouley, Richard Brown, Dennis TI Erlotinib, an EGF receptor antagonist, induces aquaporin 2 (AQP2) phosphorylation and increases water reabsorption in lithium treated mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Cheung, Pui; Nomura, Naohiro; Nair, Anil; Lu, Hua; Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 809.16 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722703146 ER PT J AU Cotten, J Chokshi, R Larsen, A AF Cotten, Joseph Chokshi, Rikki Larsen, Aaron TI Mutations in the TASK-3 Potassium Channel Pore Modify Its Inhibition by Breathing Stimulant Compounds SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Cotten, Joseph; Chokshi, Rikki] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Larsen, Aaron] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol & Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 860.14 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704112 ER PT J AU DiPasquale, D Strangman, G Harris, NS Muza, S AF DiPasquale, Dana Strangman, Gary Harris, N. Stuart Muza, Stephen TI Acute Mountain Sickness, Hypobaria, Hypoxia and Exercise Duration All Differentially Affect Fluid Balance Hormones SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [DiPasquale, Dana] Univ Pittsburgh, Dept Sports Med & Nutr, Pittsburgh, PA 15260 USA. [DiPasquale, Dana; Strangman, Gary; Harris, N. Stuart] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Muza, Stephen] USARIEM, Thermal & Mt Med Div, Natick, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 859.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704095 ER PT J AU Feng, Y Chen, HL Xu, GQ Zou, L Chao, W AF Feng, Yan Chen, Hongliang Xu, Ganqiong Zou, Lin Chao, Wei TI Extracellular RNA Activates Neutrophils via Toll-like Receptor 7 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Feng, Yan; Chen, Hongliang; Xu, Ganqiong; Zou, Lin; Chao, Wei] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 888.24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705085 ER PT J AU Fernandez-Godino, R Pierce, E Garland, D AF Fernandez-Godino, Rosario Pierce, Eric Garland, Donita TI The Role of Complement and the Extracellular Matrix in Early Stage Macular Degeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Fernandez-Godino, Rosario; Pierce, Eric; Garland, Donita] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol Ocular Genom Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 719.21 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701222 ER PT J AU Gilpin, S Charest, J Tapias, L Ren, X Wu, T Ott, H AF Gilpin, Sarah Charest, Jonathan Tapias, Luis Ren, Xi Wu, Tong Ott, Harald TI Extended Biomimetic Culture and Functional Assessment of Recellularized Human Lungs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Gilpin, Sarah; Charest, Jonathan; Tapias, Luis; Ren, Xi; Wu, Tong; Ott, Harald] Massachusetts Gen Hosp, CRM, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1029.18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707437 ER PT J AU Haspel, J Chettimada, S Lane, B Choi, A AF Haspel, Jeffrey Chettimada, Sukrutha Lane, Bill Choi, Augustine TI The Lung Macroautophagy Substrate Proteome: A SYSTEMS BIOLOGY Analysis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Haspel, Jeffrey] Washington Univ, Sch Med, Med, St Louis, MO USA. [Chettimada, Sukrutha] Dana Farber Canc Ctr, Med, Boston, MA USA. [Lane, Bill] Harvard Univ, Biol, Cambridge, MA 02138 USA. [Choi, Augustine] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1015.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707403 ER PT J AU Hindle, A Horning, M Mellish, JA AF Hindle, Allyson Horning, Markus Mellish, Jo-Ann TI Thermoregulatory Scope Associated with Underwater Exercise in a Polar Seal SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Hindle, Allyson] Massachusetts Gen Hosp, Anesthesia, Boston, MA 02114 USA. [Hindle, Allyson; Mellish, Jo-Ann] Alaska Sea Life Ctr, Sci, Seward, AK USA. [Horning, Markus] Oregon State Univ, Fisheries & Wildlife, Newport, OR USA. [Mellish, Jo-Ann] Univ Alaska Fairbanks, Sch Fisheries & Ocean Sci, Fairbanks, AK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 982.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707110 ER PT J AU Jeong, HW Choi, RH McClellan, J Tseng, YH Goodyear, L Koh, HJ AF Jeong, Ha-Won Choi, Ran Hee McClellan, Jamie Tseng, Yu-Hua Goodyear, Laurie Koh, Ho-Jin TI TRB3 Inhibits Brown Adipocyte Differentiation and Function by Suppressing Insulin Signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie; Koh, Ho-Jin] Univ S Carolina, Exercise Sci, Columbia, SC 29208 USA. [Tseng, Yu-Hua; Goodyear, Laurie] Joslin Diabet Ctr, IPM, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 995.12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707267 ER PT J AU Kalin, J Wu, MZ Hayward, D Wang, LQ Roberts, J Prusevich, P Hancock, W Bradner, J Ryu, B Alani, R Cole, P AF Kalin, Jay Wu, Muzhou Hayward, Dawn Wang, Liqing Roberts, Justin Prusevich, Polina Hancock, Wayne Bradner, James Ryu, Byungwoo Alani, Rhoda Cole, Philip TI CoREST in Peace: Dual Action Inhibitors of Histone Deacetylase and Lysine Specific Demethylase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Kalin, Jay; Hayward, Dawn; Prusevich, Polina; Cole, Philip] Johns Hopkins Univ, Pharmacol, Baltimore, MD USA. [Wu, Muzhou; Ryu, Byungwoo; Alani, Rhoda] Boston Univ, Dermatol, Boston, MA 02215 USA. [Wang, Liqing; Hancock, Wayne] Univ Penn, Pathol, Philadelphia, PA 19104 USA. [Bradner, James] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 723.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701301 ER PT J AU Kato, S Chen, JS Zhang, HL Cornog, K Roberts, J AF Kato, Shin Chen, Jingsi Zhang, Huili Cornog, Katherine Roberts, Jesse, Jr. TI The Golgi apparatus regulates cGMP-dependent protein kinase I (PKGI) proteolytic cleavage in vascular smooth muscle cells (SMC) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Kato, Shin; Chen, Jingsi; Zhang, Huili; Roberts, Jesse, Jr.] Mass Gen Hosp, CVRC, Boston, MA USA. [Cornog, Katherine] Appl Video Res, Res & Dev, Medford, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1031.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707453 ER PT J AU Lee, A Polgar, N Lui, V Tamashiro, KK Napoli, JA Lipschutz, J Fogelgren, B AF Lee, Amanda Polgar, Noemi Lui, Vanessa Tamashiro, Kadee-Kalia Napoli, Josephine Andrea Lipschutz, Joshua Fogelgren, Ben TI A Novel Transgenic Mouse Model for Congenital Obstructive Nephropathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Lee, Amanda; Polgar, Noemi; Lui, Vanessa; Tamashiro, Kadee-Kalia; Napoli, Josephine Andrea; Fogelgren, Ben] Univ Hawaii, Anat Biochem & Physiol, Honolulu, HI 96822 USA. [Lipschutz, Joshua] Med Univ S Carolina, Med, Charleston, SC 29425 USA. [Lipschutz, Joshua] Ralph Johnson Vet Affairs Med Ctr, Med, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 663.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722700017 ER PT J AU Lessard, S Rivas, D So, K Koh, HJ Hirshman, M Fielding, R Goodyear, L AF Lessard, Sarah Rivas, Donato So, Kawai Koh, Ho-Jin Hirshman, Michael Fielding, Roger Goodyear, Laurie TI SNARK is a Novel Regulator of Muscle Mass and Myocyte Apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Lessard, Sarah; So, Kawai; Koh, Ho-Jin; Hirshman, Michael; Goodyear, Laurie] Joslin Diabet Ctr, Integrat Physiol & Metab, Boston, MA USA. [Rivas, Donato; Fielding, Roger] Tufts Univ, USDA Human Nutr Res Ctr, Medford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 825.19 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722703334 ER PT J AU Mangano, K Sahni, S Tucker, K Douglas, K Dufour, A McLean, R Hannan, M AF Mangano, Kelsey Sahni, Shivani Tucker, Katherine Douglas, Kiel Dufour, Alyssa McLean, Robert Hannan, Marian TI Dietary Protein Food Pattern is Not Associated with Muscle Mass or Strength Among Protein Replete Adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Mangano, Kelsey; Sahni, Shivani; Douglas, Kiel; Dufour, Alyssa; McLean, Robert; Hannan, Marian] Harvard Univ, Sch Med, BIDMC, Inst Aging Res IFAR,Hebrew SeniorLife, Boston, MA USA. [Tucker, Katherine] Univ Massachusetts, Clin Lab & Nutr Sci, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 737.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702085 ER PT J AU Murshid, A Gong, JL Calderwood, S AF Murshid, Ayesha Gong, Jianlin Calderwood, Stuart TI LPS-activated Scavenger Receptor SREC-I can Induce entry of TLR4 into Lipid Microdomains, Mediate Signal Transduction and trigger cytokine release SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Murshid, Ayesha; Calderwood, Stuart] Harvard Univ, Sch Med, Radiat Oncol BIDMC, Boston, MA USA. [Gong, Jianlin] Boston Univ, Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 888.25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705086 ER PT J AU Nair, A Keliher, E Core, A Brown, D Weissleder, R AF Nair, Anil Keliher, Edmund Core, Amanda Brown, Dennis Weissleder, Ralph TI Nanoparticle Interactions With Renal Epithelial Cells in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Nair, Anil; Core, Amanda; Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Nair, Anil; Core, Amanda; Brown, Dennis] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Keliher, Edmund; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 664.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722700023 ER PT J AU Nair, A Paunescu, T Bouley, R Brown, D AF Nair, Anilkumar Paunescu, Teodor Bouley, Richard Brown, Dennis TI V-ATPase B1 Subunit Knockout Mice Have A Gender-Dependent Defect In Urine Concentrating Ability SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Nair, Anilkumar; Paunescu, Teodor; Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Nair, Anilkumar; Paunescu, Teodor; Bouley, Richard; Brown, Dennis] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 962.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706416 ER PT J AU Ozaki, M Liu, BH Kushak, R Rosales, I Kang, YL Pavlov, V Grabowski, E Stahl, G AF Ozaki, Masayuki Liu, Bohan Kushak, Rafail Rosales, Ivy Kang, Yulin Pavlov, Vasile Grabowski, Eric Stahl, Gregory TI Human Mannose-Binding Lectin (MBL2) Inhibitor Prevents Renal Injury in a Novel Animal Model of Endemic Hemolytic Uremic Syndrome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Ozaki, Masayuki; Kang, Yulin; Pavlov, Vasile; Stahl, Gregory] Brigham & Womens Hosp, Anesthesia, Boston, MA 02115 USA. [Liu, Bohan; Kushak, Rafail; Grabowski, Eric] Massachusetts Gen Hosp, Pediat Hematol Oncol, Boston, MA 02114 USA. [Rosales, Ivy] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 664.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722700020 ER PT J AU Patton, C Van, H Hoffman, M Dhe-Paganon, S Gilbert, R AF Patton, Connor Van, Heidi Hoffman, Matthew Dhe-Paganon, Sirano Gilbert, Richard TI Binding of F-actin to the Cardiac Myosin Binding Protein C (MYBPC3) M Domain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Patton, Connor; Van, Heidi; Hoffman, Matthew; Gilbert, Richard] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 712.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701056 ER PT J AU Roy, A Goodman, J Pittman, G Begum, G Donnelly, B Sun, D Subramanya, A AF Roy, Ankita Goodman, Joshua Pittman, Gabrielle Begum, Gulnaz Donnelly, Bridget Sun, Dandan Subramanya, Arohan TI CRISPR/Cas mediated genome editing reveals new insights into the WNK-SPAK/OSR1 network SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Roy, Ankita; Goodman, Joshua; Pittman, Gabrielle; Donnelly, Bridget; Subramanya, Arohan] Univ Pittsburgh, Med, Pittsburgh, PA 15260 USA. [Begum, Gulnaz; Sun, Dandan] Univ Pittsburgh, Neurol, Pittsburgh, PA 15260 USA. [Subramanya, Arohan] VA Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 969.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706486 ER PT J AU Sakadzic, S Mandeville, E Gagnon, L Musacchia, J Yaseen, M Yucel, M Lefebvre, J Lesage, F Dale, A Eikermann-Haerter, K Ayata, C Srinivasan, V Lo, E Devor, A Boas, D AF Sakadzic, Sava Mandeville, Emiri Gagnon, Louis Musacchia, Joseph Yaseen, Mohammad Yucel, Meryem Lefebvre, Joel Lesage, Frederic Dale, Anders Eikermann-Haerter, Katharina Ayata, Cenk Srinivasan, Vivek Lo, Eng Devor, Anna Boas, David TI Large Arteriolar Component of Oxygen Delivery Implies Safe Margin of Oxygen Supply to Cerebral Tissue SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Sakadzic, Sava; Mandeville, Emiri; Gagnon, Louis; Musacchia, Joseph; Yaseen, Mohammad; Yucel, Meryem; Eikermann-Haerter, Katharina; Ayata, Cenk; Srinivasan, Vivek; Lo, Eng; Devor, Anna; Boas, David] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Lefebvre, Joel; Lesage, Frederic] Ecole Polytech, Dept Genie Elect, Montreal, PQ H3C 3A7, Canada. [Dale, Anders; Devor, Anna] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders; Devor, Anna] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Mandeville, Emiri; Ayata, Cenk; Lo, Eng] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Srinivasan, Vivek] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 794.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702482 ER PT J AU Sulciner, M Mudge, D Ramon, S Dalli, J Kieran, M Huang, S Serhan, C Panigrahy, D AF Sulciner, Megan Mudge, Dayna Ramon, Sesquile Dalli, Jesmond Kieran, Mark Huang, Sui Serhan, Charles Panigrahy, Dipak TI Suppression of Cell Debris-Stimulated Tumor Growth by Resolvin Mediated Clearance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Sulciner, Megan; Mudge, Dayna; Panigrahy, Dipak] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Vasc Biol,Dept Pathol, Boston, MA 02215 USA. [Ramon, Sesquile; Dalli, Jesmond; Serhan, Charles] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Sch Med, Boston, MA 02115 USA. [Kieran, Mark] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Huang, Sui] Huang Grp Inst Syst Biol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 926.14 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706203 ER PT J AU Sung, V Kallert, S AF Sung, Vicky Kallert, Stephanie TI Diversification of a Bacterial ADP-Ribosyltransferase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Sung, Vicky] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sung, Vicky] Harvard Univ, Dept Genet, Harvard Med Sch, Boston, MA 02115 USA. [Kallert, Stephanie] Univ Tubingen, Interfac Inst Biochem, Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 712.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701042 ER PT J AU Teichert, K Iacob, R St Pierre, R Ishoey, M Chen, SX Paulk, J Engen, J Bradner, J AF Teichert, Kristian Iacob, Roxana St Pierre, Roodolph Ishoey, Mette Chen, Sixun Paulk, Joshiawa Engen, John Bradner, James TI Structural Dynamics of the NSD Family Histone Methyltransferases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Teichert, Kristian; Iacob, Roxana; Engen, John] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Teichert, Kristian; St Pierre, Roodolph; Ishoey, Mette; Paulk, Joshiawa; Bradner, James] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Sixun] Broad Inst, Ctr Sci Therapeut, Cambridge, MA USA. [Bradner, James] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 5 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 717.13 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701168 ER PT J AU Toba, H Bras, LD Baicu, C Zile, M Lindsey, M Bradshaw, A AF Toba, Hiroe Bras, Lisandra de Castro Baicu, Catalin Zile, Michael Lindsey, Merry Bradshaw, Amy TI SPARC Facilitates Inflammation in the Aging Heart and Suppresses Macrophage M2 Polarization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Toba, Hiroe; Bras, Lisandra de Castro; Lindsey, Merry] UMMC, Physiol & Biophys, MS Ctr Heart Res, Jackson, MS USA. [Toba, Hiroe; Bras, Lisandra de Castro; Lindsey, Merry] UMMC, Physiol & Biophys, San Antonio CV Prote Ctr, Jackson, MS USA. [Toba, Hiroe] Kyoto Pharmaceut Univ, Clin Pharmacol, Kyoto 607, Japan. [Baicu, Catalin; Zile, Michael; Bradshaw, Amy] Med MUSC, Gazes Cardiac Res Inst, Charleston, SC USA. [Zile, Michael; Bradshaw, Amy] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lindsey, Merry] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1047.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722708092 ER PT J AU Vorobjev, I Barteneva, N AF Vorobjev, Ivan Barteneva, Natasha TI Temporal Heterogeneity In Apoptosis Execution SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Vorobjev, Ivan] Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Moscow, Russia. [Vorobjev, Ivan] AN Belozersky Inst Physicochem Biol, Dept Electron Microscopy, Moscow, Russia. [Barteneva, Natasha] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Barteneva, Natasha] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 978.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707085 ER PT J AU Voruganti, VS Haack, K Laston, S Goring, H Best, L Howard, B MacCluer, J Umans, J Cole, S Cohen, D AF Voruganti, V. Saroja Haack, Karin Laston, Sandra Goring, Harald Best, Lyle Howard, Barbara MacCluer, Jean Umans, Jason Cole, Shelley Cohen, David TI Sex-Specific Effects Of NPHP1 And SLC9A2 SNPs On Systemic Water Balance In American Indians SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Voruganti, V. Saroja] UNC, Nutr, Chapel Hill, NC USA. [Voruganti, V. Saroja] UNC, Inst Nutr Res, Chapel Hill, NC USA. [Haack, Karin; Laston, Sandra; Goring, Harald; MacCluer, Jean; Cole, Shelley] Texas Biomed Res Inst, Genet, Houston, TX USA. [Best, Lyle] Missouri Breaks Ind Res Inc, Kansas City, MO USA. [Howard, Barbara; Umans, Jason] Medstar, Hlth Res Inst, Washington, DC USA. [Howard, Barbara; Umans, Jason] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC USA. [Cohen, David] Oregon Hlth & Sci Univ, Med, Portland, OR 97201 USA. [Cohen, David] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 748.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702210 ER PT J AU Zheng, Y Wu, J Muthupalani, S Wang, YY Ang, LH Fox, J Hagen, S AF Zheng, Yi Wu, Jessica Muthupalani, Sureshkumar Wang, Yaoyu Ang, Lay-Hong Fox, James Hagen, Susan TI Attenuation of Claudin-18 in Mouse Stomach Promotes the Development of Intramucosal Carcinoma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Zheng, Yi; Wu, Jessica; Ang, Lay-Hong; Hagen, Susan] BIDMC, Dept Surg, Boston, MA USA. [Wang, Yaoyu] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Muthupalani, Sureshkumar; Fox, James] DFCI, Ctr Canc Computat Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 999.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707303 ER PT J AU Barksdale, C Sulciner, M Ramon, S Colas, R Bandopadhayay, P Huang, S Kieran, M Serhan, C Panigrahy, D AF Barksdale, Chantal Sulciner, Megan Ramon, Sesquile Colas, Romain Bandopadhayay, Pratiti Huang, Sui Kieran, Mark Serhan, Charles Panigrahy, Dipak TI Stimulating the Resolution of Tumor Debris to Control Medulloblastoma SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Barksdale, Chantal; Sulciner, Megan; Panigrahy, Dipak] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Vasc Biol Res,Dept Pathol, Boston, MA 02215 USA. [Ramon, Sesquile; Colas, Romain; Serhan, Charles] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. [Bandopadhayay, Pratiti; Kieran, Mark] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Huang, Sui] Inst Syst Biol, Huang Grp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 147.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502023 ER PT J AU Carman, C Kamei, M Varghese, L Sciuto, T Dvorak, A Martinelli, R AF Carman, Christopher Kamei, Masataka Varghese, Laya Sciuto, Tracey Dvorak, Ann Martinelli, Roberta TI Vascular Endothelia Mechanically Sense Barrier Quality and Mainta. Functional Integrity through ROS-Dependent A Remodeling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Carman, Christopher; Kamei, Masataka; Varghese, Laya; Sciuto, Tracey; Dvorak, Ann; Martinelli, Roberta] Harvard Univ, Sch Med, BIDMC, Med & Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 85.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501315 ER PT J AU Cheng, F Li, YP Winkelman, J Hu, F Rimm, E Gao, X AF Cheng, Feon Li, Yanping Winkelman, John Hu, Frank Rimm, Eric Gao, Xiang TI The Association between Insomnia Symptoms and Diet Quality and Energy Intake SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Cheng, Feon; Gao, Xiang] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Li, Yanping; Hu, Frank; Rimm, Eric] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Winkelman, John] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 260.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502211 ER PT J AU Drummond, L AF Drummond, Lain TI Motile and Sensory Cilia Function Zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Drummond, Lain] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Drummond, Lain] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 82.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501302 ER PT J AU Fasler-Kan, E Sautbayeva, Z Barteneva, N AF Fasler-Kan, Elizaveta Sautbayeva, Zarina Barteneva, Natasha TI Activation of Phospho Signaling Pathways in Human Colorectal Cell Lines in Response to Cytokines SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Fasler-Kan, Elizaveta] Univ Basel, Dept Biomed, Basel, Switzerland. [Fasler-Kan, Elizaveta] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Fasler-Kan, Elizaveta] Fachhsch Nordwestschweiz, Inst Chem & Bioanalyt, Muttenz, Switzerland. [Sautbayeva, Zarina] Nazarbayev Univ, Res & Innovat Syst, Astana, Kazakhstan. [Barteneva, Natasha] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB453 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500450 ER PT J AU Foks, A Engelbertsen, D Alberts-Grill, N Kuperwaser, F DeKruyff, R Freeman, G Lichtman, A AF Foks, Amanda Engelbertsen, Daniel Alberts-Grill, Noah Kuperwaser, Felicia DeKruyff, Rosemarie Freeman, Gordon Lichtman, Andrew TI Blockade of Tim-4 Aggravates Atherosclerosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Foks, Amanda; Engelbertsen, Daniel; Alberts-Grill, Noah; Kuperwaser, Felicia; Lichtman, Andrew] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeKruyff, Rosemarie] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 418.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503128 ER PT J AU Gygli, P Chang, J Gokozan, H Catacutan, F Schmidt, T Griveau, A Michowski, W Wong, M Palanichamy, K Sicinski, P Czeisler, C Otero, J AF Gygli, Patrick Chang, Joshua Gokozan, Hamza Catacutan, Fay Schmidt, Theresa Griveau, Amelie Michowski, Wojciech Wong, Michael Palanichamy, Kamalakannan Sicinski, Peter Czeisler, Catherine Otero, Jose TI Cyclin A2 Promotes DNA Repair and Neural Stem Cell Growth SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gygli, Patrick; Gokozan, Hamza; Catacutan, Fay; Schmidt, Theresa; Czeisler, Catherine; Otero, Jose] Ohio State Univ, Pathol, Columbus, OH 43210 USA. [Chang, Joshua] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA. [Griveau, Amelie; Wong, Michael] Univ Calif San Francisco, Pediat, San Francisco, CA 94143 USA. [Michowski, Wojciech; Sicinski, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palanichamy, Kamalakannan] Ohio State Univ, Radiat Oncol, Columbus, OH 43210 USA. RI Palanichamy, Kamalakannan/E-3807-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 613.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505319 ER PT J AU Hacohen, N AF Hacohen, Nir TI Genetic Control of Immune Variation across the Human Population SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hacohen, Nir] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 369.2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502427 ER PT J AU Hobai, I Aziz, K Siwik, D Colucci, W AF Hobai, Ion Aziz, Kanwal Siwik, Deborah Colucci, Wilson TI Distinct Mechanisms Underlie Cardiomyocyte Contractile Dysfunction in Male and Female Endotoxemic Mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hobai, Ion; Aziz, Kanwal; Siwik, Deborah; Colucci, Wilson] Boston Univ, Med Ctr, Cardiovasc Med, Boston, MA USA. [Hobai, Ion] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 641.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505425 ER PT J AU Hobai, I Morse, J Siwik, D Colucci, W AF Hobai, Ion Morse, Justin Siwik, Deborah Colucci, Wilson TI Myocardial Calcium Handling is Up-Regulated During the Spontaneous Resolution of Endotoxemic Cardiomyopathy in Mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hobai, Ion; Morse, Justin; Siwik, Deborah; Colucci, Wilson] Boston Univ, Med Ctr, Cardiovasc Med, Boston, MA USA. [Hobai, Ion] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 641.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505424 ER PT J AU Hua, A Casper, J Bielenberg, D Schmidt, B Kieran, M Panigrahy, D Gus-Brautbar, Y AF Hua, Alexander Casper, Jessica Bielenberg, Diane Schmidt, Birgitta Kieran, Mark Panigrahy, Dipak Gus-Brautbar, Yael TI PPAR alpha: A Novel Target in Pancreatic Cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hua, Alexander; Casper, Jessica; Panigrahy, Dipak; Gus-Brautbar, Yael] Beth Israel Deaconess, Ctr Vasc Biol Res, Boston, MA USA. [Hua, Alexander; Casper, Jessica; Panigrahy, Dipak; Gus-Brautbar, Yael] Beth Israel Deaconess, Dept Pathol, Boston, MA USA. [Bielenberg, Diane] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Schmidt, Birgitta] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kieran, Mark] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 147.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502024 ER PT J AU Khadka, A Iacovelli, J Saint-Geniez, M AF Khadka, Arogya Iacovelli, Jared Saint-Geniez, Magali TI PGC1a rescue retinal pigment epithelial cells from oxidative damage: implication for age-related macular degeneration SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Khadka, Arogya; Iacovelli, Jared; Saint-Geniez, Magali] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 148.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502029 ER PT J AU Krishnan, R Hardin, C Dang, Q Manomohan, G Tian, XY Dubrovski, O Tambe, D Jader, C Gado, E Butler, J Fredberg, J Birukov, K AF Krishnan, Ramaswamy Hardin, Corey Dang, Quynh Manomohan, Greeshma Tian, Xinyong Dubrovski, Oleksii Tambe, Dhananjay Jader, Colombo Gado, Emanuela Butler, James Fredberg, Jeffrey Birukov, Konstantin TI Force Chains And Gap Formation Thrombin-induced Endothelial Permeability SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Krishnan, Ramaswamy; Dang, Quynh; Manomohan, Greeshma] BIDMC, Ctr Vasc Biol Res, Boston, MA 02215 USA. [Hardin, Corey] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Tian, Xinyong; Dubrovski, Oleksii; Birukov, Konstantin] Univ Chicago, Sect Pulm & Crit Care, Chicago, IL 60637 USA. [Butler, James; Fredberg, Jeffrey] Harvard Univ, T Chen Sch Publ Hlth, Environm Hlth, Cambridge, MA 02138 USA. [Jader, Colombo; Gado, Emanuela] ETH, Microstruct & Rheol, Zurich, Switzerland. [Gado, Emanuela] Georgetown Univ, Dept Phys, Washington, DC 20057 USA. [Tambe, Dhananjay] Univ S Alabama, Dept Mech Engn, Mobile, AL 36688 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 85.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501316 ER PT J AU Lee, J Sarma, K Cifuentes-Rojas, C Ergun, A del Rosario, A Jeon, Y White, F Sadreyev, R AF Lee, Jeannie Sarma, Kavitha Cifuentes-Rojas, Catherine Ergun, Ayla del Rosario, Amanda Jeon, Yesu White, Forest Sadreyev, Ruslan TI ATRX Promotes Binding of PRC2 to Xist RNA and Polycomb Targets SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lee, Jeannie; Sarma, Kavitha; Cifuentes-Rojas, Catherine; Jeon, Yesu] Howard Hughes Med Inst, Chicago, IL USA. [Lee, Jeannie; Sarma, Kavitha; Cifuentes-Rojas, Catherine; Ergun, Ayla; Jeon, Yesu; Sadreyev, Ruslan] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lee, Jeannie; Sarma, Kavitha; Cifuentes-Rojas, Catherine; Ergun, Ayla; Jeon, Yesu; Sadreyev, Ruslan] Dept Mol Biol, Providence, RI USA. [Sadreyev, Ruslan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadreyev, Ruslan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [del Rosario, Amanda; White, Forest] MIT, Dept Bioengn, Cambridge, MA 02139 USA. [del Rosario, Amanda; White, Forest] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 361.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502409 ER PT J AU Sahni, S Mangano, K Tucker, K Fox, C Kiel, D Dufour, A Zhang, XC Hannan, M AF Sahni, Shivani Mangano, Kelsey Tucker, Katherine Fox, Caroline Kiel, Douglas Dufour, Alyssa Zhang, Xiaochun Hannan, Marian TI Protective Association of Serum Uric Acid on Hip Fracture Risk among Older Men But Not Women SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sahni, Shivani; Mangano, Kelsey; Kiel, Douglas; Dufour, Alyssa; Zhang, Xiaochun; Hannan, Marian] Harvard Univ, Sch Med, BIDMC, IFAR HSL, Boston, MA USA. [Tucker, Katherine] Univ Massachusetts, Lowell, MA USA. [Fox, Caroline] Harvard Univ, Sch Med, Framingham Heart Study NHLBI, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 383.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502476 ER PT J AU Senkal, C Hannun, Y Obeid, L AF Senkal, Can Hannun, Yusuf Obeid, Lina TI Interaction of Ceramide Synthase with Long Chain Fatty Acyl-CoA Synthase 5 Channels de novo Ceramide to Acylceramide Generation by Diacylglycerol Acyltransferase 2 on Lipid Droplets SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Senkal, Can; Hannun, Yusuf; Obeid, Lina] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Hannun, Yusuf] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA. [Obeid, Lina] US Dept Vet Affairs, Northport Vet Affairs Med Ctr, Northport, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 568.21 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504100 ER PT J AU Solano-Aguilar, G Molokin, A Botelho, C Fiorino, AM Vinyard, B Urban, J Haverkamp, M Hibberd, P AF Solano-Aguilar, Gloria Molokin, Aleksey Botelho, Christine Fiorino, Anne-Maria Vinyard, Bryan Urban, Joseph Haverkamp, Miriam Hibberd, Patricia TI Lactobacillus rhamnosus GG ATCC 53103 (LGG) as an Immune Adjuvant for Influenza Vaccination in the Elderly SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Solano-Aguilar, Gloria; Molokin, Aleksey; Urban, Joseph] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. [Botelho, Christine; Fiorino, Anne-Maria; Haverkamp, Miriam; Hibberd, Patricia] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Vinyard, Bryan] ARS, Biometr Consulting Serv, USDA, Belstville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 593.13 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505045 ER PT J AU Sung, V Tsai, CL AF Sung, Vicky Tsai, Chia-Lun TI ADP-ribosylargininyl Activity of Cholix Toxin Is Mediated Through Diffusible Intermediates SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sung, Vicky; Tsai, Chia-Lun] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sung, Vicky] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 572.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504184 ER PT J AU Tashjian, T Lin, I Cafarelli, T Godoy, V AF Tashjian, Tommy Lin, Ida Cafarelli, Tiziana Godoy, Veronica TI Investigating the Importance of DinB-RecA Interactions to the Regulation of DinB's Activity and the Fidelity of the DNA Damage Response SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tashjian, Tommy; Lin, Ida; Godoy, Veronica] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Cafarelli, Tiziana] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Cafarelli, Tiziana] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 561.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503449 ER PT J AU Yoder, B Lewis, W Malarkey, E Parant, J Drummond, I Hildebrandt, F Berbari, N AF Yoder, Bradley Lewis, Wes Malarkey, Erik Parant, John Drummond, Iain Hildebrandt, Fridhelm Berbari, Nicolas TI Mammalian DRC, Ciliary, Motility and Left-Right Body Asymmetry SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Yoder, Bradley; Lewis, Wes; Malarkey, Erik] Univ Alabama Birmingham, Cell Dev & Integrat Biol, Birmingham, AL USA. [Drummond, Iain] Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Berbari, Nicolas] Indiana Univ Purdue Univ, Biol, Indianapolis, IN 46202 USA. [Hildebrandt, Fridhelm] Harvard Univ, Sch Med, Pediat, Boston, MA USA. [Parant, John] Univ Alabama Birmingham, Pharmacol & Toxicol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 82.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501303 ER PT J AU Zou, L Xu, GQ Feng, Y Chao, W AF Zou, Lin Xu, Ganqiong Feng, Yan Chao, Wei TI Extracellular RNA Induces Complement Factor B in Macrophages via MyD88 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Zou, Lin; Xu, Ganqiong; Feng, Yan; Chao, Wei] Harvard Univ, Sch Med, Dept Anesthesia, Crit Care & Pain Med,Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 507.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503183 ER PT J AU Bruinsma, BG Avruch, JH Weeder, PD Sridharan, GV Uygun, BE Karimian, NG Porte, RJ Markmann, JF Yeh, H Uygun, K AF Bruinsma, Bote G. Avruch, James H. Weeder, Pepijn D. Sridharan, Gautham V. Uygun, Basak E. Karimian, Negin G. Porte, Robert J. Markmann, James F. Yeh, Heidi Uygun, Korkut TI Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 98; Liver; transplantation; organ preservation; subnormothermic; machine perfusion; viability ID ORGAN PRESERVATION; CARDIAC DEATH; DONOR LIVERS; TRANSPLANTATION; DONATION; CHALLENGES; CRITERIA AB There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic machine perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, machine perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of machine perfusion and utilized for transplantation. Here we describe this technique of subnormothermic machine perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 degrees C. C1 [Bruinsma, Bote G.; Weeder, Pepijn D.; Sridharan, Gautham V.; Uygun, Basak E.; Karimian, Negin G.; Uygun, Korkut] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Dept Surg, Cambridge, MA 02138 USA. [Avruch, James H.; Markmann, James F.; Yeh, Heidi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr,Dept Surg, Cambridge, MA 02138 USA. [Porte, Robert J.] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, Groningen, Netherlands. RP Yeh, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr,Dept Surg, Cambridge, MA 02138 USA. EM hyeh@partners.org; korkut.uygun@gmail.com FU US National Institutes of Health [R01EB008678, R01DK096075, R01DK084053, R00DK088962, F32 DK103500]; CIMIT [12-1732]; Shriners Hospitals; New England Organ Bank FX Funding from the US National Institutes of Health (grants R01EB008678, R01DK096075, R01DK084053, R00DK088962 and F32 DK103500), CIMIT Project No. 12-1732 and the Shriners Hospitals for Children is gratefully acknowledged. We would like to gratefully acknowledge the New England Organ Bank for supporting this work. NR 22 TC 0 Z9 0 U1 0 U2 5 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD APR PY 2015 IS 98 AR e52777 DI 10.3791/52777 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7MR UT WOS:000361534800070 ER PT J AU Gross, AH AF Gross, Anne H. TI What Matters to the Patient Is What Really Matters: Quality in Oncology Nursing SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE human caring; patient centeredness; patient experience AB On the occasion of the Oncology Nursing Society's 40th anniversary, it is fitting to look back and appreciate how far we have come in the area of quality cancer care. So much has changed, fueled in part by advances in health-care quality improvement across the United States. At a Glance The past 40 years have brought many improvements in the quality and safety of oncology nursing practice. Beyond the technical aspects of care, advances in patient-centered care have improved patient experiences and outcomes. Consistent, personalized, human caring may be the focus of change in the next 40 years. C1 Dana Farber Canc Inst, Adult Nursing & Clin Serv, Boston, MA 02115 USA. RP Gross, AH (reprint author), Dana Farber Canc Inst, Adult Nursing & Clin Serv, Boston, MA 02115 USA. EM anne_gross@dfci.harvard.edu NR 7 TC 1 Z9 1 U1 2 U2 4 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2015 VL 19 IS 2 BP 144 EP 145 DI 10.1188/15.CJON.144-145 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA CF3LI UT WOS:000352449700009 PM 25840377 ER PT J AU Kwon, JY Gitajn, IL Walton, P Miller, TJ Appleton, P Rodriguez, EK AF Kwon, John Y. Gitajn, Ida Leah Walton, Phillip Miller, Timothy J. Appleton, Paul Rodriguez, Edward K. TI A Cadaver Study Revisiting the Original Methodology of Lauge-Hansen and a Commentary on Modern Usage SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID ANKLE FRACTURES; CLASSIFICATION SYSTEMS; MALLEOLAR FRACTURES; OBSERVER VARIATION; MECHANISM; INJURY; AO; EPIDEMIOLOGY; BONE AB Background: The study by Lauge-Hansen published in the Archives of Surgery in 1950 still stands as the seminal work for our understanding of the pathomechanics of ankle fractures. The purpose of the present study was to recreate LaugeHansen's experiments for the supination-external rotation (SER) fracture mechanism and to determine whether the predicted sequence of osseous and soft-tissue injury is reproducible on the basis of his originally described methodology. Methods: Ten fresh-frozen cadaver specimens amputated above the knee were utilized. The foot was axially loaded in a position of neutral dorsiflexion and supination. External rotation was applied manually in accordance with Lauge-Hansen's description until osseous and/or soft-tissue injury occurred. Fluoroscopic images were made and anatomic dissection was performed. Results: Although several specimens exhibited findings consistent with certain stages of the SER injury pattern, no specimen demonstrated the complete sequence of predicted osseous and soft-tissue injury. Conclusions: Loading cadaver specimens with an SER mechanism utilizing a methodology similar to that in the original experiments by Lauge-Hansen does not reliably produce the sequence of osseous and soft-tissue injury predicted by Lauge-Hansen. C1 [Kwon, John Y.; Appleton, Paul; Rodriguez, Edward K.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. [Gitajn, Ida Leah; Walton, Phillip] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02115 USA. RP Kwon, JY (reprint author), Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, 330 Brookline Ave, Boston, MA 02215 USA. EM johnkwonmd@gmail.com NR 26 TC 1 Z9 1 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR 1 PY 2015 VL 97A IS 7 BP 604 EP 609 DI 10.2106/JBJS.N.00970 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CQ8AU UT WOS:000360829200014 PM 25834086 ER PT J AU Oreskovic, NM Huang, TT Moon, J AF Oreskovic, Nicolas Michel Huang, Terry T. Moon, Jon TI Integrating mHealth and Systems Science: A Combination Approach to Prevent and Treat Chronic Health Conditions SO JMIR MHEALTH AND UHEALTH LA English DT Editorial Material DE mHealth; systems science; chronic health conditions; obesity; physical activity ID OBESITY; CARE; DISPARITIES; PROMOTION AB Chronic health conditions are a growing global health concern and account for over half of all deaths worldwide. Finding ways to decrease the burden of and resources allotted to chronic health conditions is of primary importance. Recent advances in technology and insights into modeling techniques offer promising approaches, which if combined, represent a novel direction that would further advance the prevention and treatment of chronic health conditions. C1 [Oreskovic, Nicolas Michel] Massachusetts Gen Hosp, Dept Pediat, Div Gen Acad Pediat, Boston, MA 02116 USA. [Oreskovic, Nicolas Michel] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Huang, Terry T.] CUNY, Sch Publ Hlth, New York, NY 10021 USA. [Moon, Jon] MEI Res Ltd, Edina, MN USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Gen Acad Pediat, 100 Cambridge St,5th Fl, Boston, MA 02116 USA. EM noreskovic@mgh.harvard.edu NR 18 TC 1 Z9 1 U1 0 U2 2 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-5222 J9 JMIR MHEALTH UHEALTH JI JMIR mHealth uHealth PD APR-JUN PY 2015 VL 3 IS 2 AR e62 DI 10.2196/mhealth.4150 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CP3PE UT WOS:000359791800001 PM 26036753 ER PT J AU Zan, SY Agboola, S Moore, SA Parks, KA Kvedar, JC Jethwani, K AF Zan, Shiyi Agboola, Stephen Moore, Stephanie A. Parks, Kimberly A. Kvedar, Joseph C. Jethwani, Kamal TI Patient Engagement With a Mobile Web-Based Telemonitoring System for Heart Failure Self-Management: A Pilot Study SO JMIR MHEALTH AND UHEALTH LA English DT Article DE heart failure; disease self-management; remote monitoring; telemonitoring; interactive voice response system; mobile health; Web portal; patient engagement; quality of life ID RANDOMIZED CONTROLLED-TRIAL; ASSOCIATION; INTERNET; RECOMMENDATIONS; IMPACT AB Background: Intensive remote monitoring programs for congestive heart failure have been successful in reducing costly readmissions, but may not be appropriate for all patients. There is an opportunity to leverage the increasing accessibility of mobile technologies and consumer-facing digital devices to empower patients in monitoring their own health outside of the hospital setting. The iGetBetter system, a secure Web-and telephone-based heart failure remote monitoring program, which leverages mobile technology and portable digital devices, offers a creative solution at lower cost. Objective: The objective of this pilot study was to evaluate the feasibility of using the iGetBetter system for disease self-management in patients with heart failure. Methods: This was a single-arm prospective study in which 21 ambulatory, adult heart failure patients used the intervention for heart failure self-management over a 90-day study period. Patients were instructed to take their weight, blood pressure, and heart rate measurements each morning using a WS-30 bluetooth weight scale, a self-inflating blood pressure cuff (Withings LLC, Issy les Moulineaux, France), and an iPad Mini tablet computer (Apple Inc, Cupertino, CA, USA) equipped with cellular Internet connectivity to view their measurements on the Internet. Outcomes assessed included usability and satisfaction, engagement with the intervention, hospital resource utilization, and heart failure-related quality of life. Descriptive statistics were used to summarize data, and matched controls identified from the electronic medical record were used as comparison for evaluating hospitalizations. Results: There were 20 participants (mean age 53 years) that completed the study. Almost all participants (19/20, 95%) reported feeling more connected to their health care team and more confident in performing care plan activities, and 18/20 (90%) felt better prepared to start discussions about their health with their doctor. Although heart failure-related quality of life improved from baseline, it was not statistically significant (P=.55). Over half of the participants had greater than 80% (72/90 days) weekly and overall engagement with the program, and 15% (3/20) used the interactive voice response telephone system exclusively for managing their care plan. Hospital utilization did not differ in the intervention group compared to the control group (planned hospitalizations P=.23, and unplanned hospitalizations P=.99). Intervention participants recorded shorter average length of hospital stay, but no significant differences were observed between intervention and control groups (P=.30). Conclusions: This pilot study demonstrated the feasibility of a low-intensive remote monitoring program leveraging commonly used mobile and portable consumer devices in augmenting care for a fairly young population of ambulatory patients with heart failure. Further prospective studies with a larger sample size and within more diverse patient populations is necessary to determine the effect of mobile-based remote monitoring programs such as the iGetBetter system on clinical outcomes in heart failure. C1 [Zan, Shiyi; Agboola, Stephen; Kvedar, Joseph C.; Jethwani, Kamal] Partners HealthCare, Ctr Connected Hlth, Boston, MA 02114 USA. [Zan, Shiyi; Agboola, Stephen; Moore, Stephanie A.; Parks, Kimberly A.; Kvedar, Joseph C.; Jethwani, Kamal] Harvard Univ, Sch Med, Boston, MA USA. [Agboola, Stephen; Moore, Stephanie A.; Parks, Kimberly A.; Kvedar, Joseph C.; Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jethwani, K (reprint author), Partners HealthCare, Ctr Connected Hlth, 25 New Chardon St,Suite 300, Boston, MA 02114 USA. EM kjethwani@partners.org NR 19 TC 6 Z9 6 U1 1 U2 14 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-5222 J9 JMIR MHEALTH UHEALTH JI JMIR mHealth uHealth PD APR-JUN PY 2015 VL 3 IS 2 AR e33 DI 10.2196/mhealth.3789 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CP3PE UT WOS:000359791800024 PM 25842282 ER PT J AU Mocco, J Zaidat, O von Kummer, R Yoo, A Gupta, R Lopes, D Frei, DON Sit, S Bose, A Khatri, P AF Mocco, J. Zaidat, O. von Kummer, R. Yoo, A. Gupta, R. Lopes, D. Frei, D. O. N. Sit, S. Bose, A. Khatri, P. TI Results of the therapy trial: A prospective, randomized trial to define the role of mechanical thrombectomy as adjunctive treatment to IV rtPA in acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Mocco, J.] Icahn Sch Med Mt Sinai, Neurosurg, New York, NY 10029 USA. [Zaidat, O.] Med Coll Wisconsin, Neurol, Milwaukee, WI 53226 USA. [von Kummer, R.] Univ Klinikum, Radiol, Dresden, Germany. [Yoo, A.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Gupta, R.] Welter Hlth Syst, Neurol, Marietta, GA USA. [Lopes, D.] Rush Univ, Neurosurg, Chicago, IL 60612 USA. [Frei, D. O. N.] Swedish Med Ctr, Radiol, Denver, CO USA. [Sit, S.; Bose, A.] Penumbra Inc, Penumbra, Alameda, CA USA. [Khatri, P.] Univ Cincinnati, Neurol, Cincinnati, OH 45220 USA. NR 0 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1614 BP 10 EP 10 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304000022 ER PT J AU Jansen, IGH Berkhemer, OA Yoo, AJ Lycklama, GJ Sprengers, MES van Zwam, WH van Oostenbrugge, RJ van der Lugt, A Marquering, HA Majoie, CBLM AF Jansen, I. G. H. Berkhemer, O. A. Yoo, A. J. Lycklama, G. J. Sprengers, M. E. S. van Zwam, W. H. van Oostenbrugge, R. J. van der Lugt, A. Marquering, H. A. Majoie, C. B. L. M. TI Comparison of CTA and DSA based cerebral collateral flow scores in patients with proximal anterior circulation stroke: Post hoc analysis of MRCLEAN SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Jansen, I. G. H.; Berkhemer, O. A.; Sprengers, M. E. S.; Majoie, C. B. L. M.] Univ Amsterdam, Acad Med Ctr, Radiol, NL-1105 AZ Amsterdam, Netherlands. [Yoo, A. J.] Massachusetts Gen Hosp, Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Lycklama, G. J.] Haaglanden Med Ctr, Radiol, The Hague, Netherlands. [van Zwam, W. H.] Maastricht Univ Med Ctr, Radiol, Maastricht, Netherlands. [van Oostenbrugge, R. J.] Maastricht Univ Med Ctr, Neurol, Maastricht, Netherlands. [van der Lugt, A.] Erasmus Univ, Med Ctr, Radiol, Rotterdam, Netherlands. [Marquering, H. A.] Univ Amsterdam, Acad Med Ctr, Biomed Engn & Phys, NL-1105 AZ Amsterdam, Netherlands. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1399 BP 28 EP 29 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304000063 ER PT J AU Charidimou, A Martinez-Ramirez, S Shoamanesh, A Oliveira, J Frosch, M Vashkevich, A Ayres, A Rosand, J Gurol, ME Greenberg, SM Viswanathan, A AF Charidimou, A. Martinez-Ramirez, S. Shoamanesh, A. Oliveira-Filho, J. Frosch, M. Vashkevich, A. Ayres, A. Rosand, J. Gurol, M. E. Greenberg, S. M. Viswanathan, A. TI Cerebral amyloid angiopathy with and without hemorrhage: MRI-neuropathological evidence for distinct phenotypes SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Charidimou, A.; Martinez-Ramirez, S.; Shoamanesh, A.; Oliveira-Filho, J.; Vashkevich, A.; Ayres, A.; Rosand, J.; Gurol, M. E.; Greenberg, S. M.; Viswanathan, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program,Stroke R, Boston, MA USA. [Frosch, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0874 BP 67 EP 68 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304000154 ER PT J AU Lorenzano, S Rost, NS Furie, KL AF Lorenzano, S. Rost, N. S. Furie, K. L. TI Hyperacute levels of high sensitivity C-reactive protein and changes of metalloproteinase 2 improve the accuracy of outcome prediction in acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Lorenzano, S.; Rost, N. S.; Furie, K. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1589 BP 245 EP 246 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304001285 ER PT J AU Lorenzano, S Rost, NS Furie, KL AF Lorenzano, S. Rost, N. S. Furie, K. L. TI Mismatch salvage volume up to 24 h from stroke onset predicts favorable outcome in acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Lorenzano, S.; Rost, N. S.; Furie, K. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1590 BP 246 EP 246 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304001286 ER PT J AU Coull, B Kidwell, C Norato, G Dixon, S Osborne, J Rosand, J Vashkevich, A Mehndiratta, P Martini, SR Worrall, BB Sheth, KN James, ML Elkind, MS Miller, T Kittner, S Barton, L Clapham, R Moomaw, CJ Langefeld, CD Woo, D AF Coull, B. Kidwell, C. Norato, G. Dixon, S. Osborne, J. Rosand, J. Vashkevich, A. Mehndiratta, P. Martini, S. R. Worrall, B. B. Sheth, K. N. James, M. L. Elkind, M. S. Miller, T. Kittner, S. Barton, L. Clapham, R. Moomaw, C. J. Langefeld, C. D. Woo, D. TI An analysis of cerebral amyloid angiopathy by the Boston Criteria in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Coull, B.; Kidwell, C.; Norato, G.; Dixon, S.] Univ Arizona, Neurol, Tucson, AZ USA. [Osborne, J.; Mehndiratta, P.; Moomaw, C. J.; Woo, D.] Univ Cincinnati, Neurol, Cincinnati, OH USA. [Rosand, J.] Massachusetts Gen Hosp Harvard Med Sch Broad Inst, Neurol, Boston, MA USA. [Vashkevich, A.; Barton, L.; Clapham, R.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Martini, S. R.] Michael E DeBakey VA Med Ctr, Neurol, Houston, TX USA. [Worrall, B. B.] Univ Virginia, Neurol, Charlottesville, VA USA. [Sheth, K. N.] Yale Univ, Neurol, New Haven, CT USA. [James, M. L.] Duke Univ, Neurol, Durham, NC 27706 USA. [Elkind, M. S.] Columbia Univ, Neurol, New York, NY USA. [Miller, T.] Univ Maryland, Radiol, Baltimore, MD 21201 USA. [Kittner, S.] Univ Maryland, Neurol, Baltimore, MD 21201 USA. [Langefeld, C. D.] Wake Forest Sch Med, Biostat Sci, Winston Salem, NC 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0454 BP 290 EP 291 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002038 ER PT J AU van Etten, ES Gurol, ME Terwindt, GM Viswanathan, A Schwab, K van der Grond, J Rosand, J van Buchem, MA Greenberg, SM Wermer, MJH AF van Etten, E. S. Gurol, M. E. Terwindt, G. M. Viswanathan, A. Schwab, K. van der Grond, J. Rosand, J. van Buchem, M. A. Greenberg, S. M. Wermer, M. J. H. TI Recurrent hemorrhage risk and long-term mortality after a first intracerebral hemorrhage in hereditary and sporadic cerebral amyloid angiopathy SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [van Etten, E. S.; Terwindt, G. M.; Wermer, M. J. H.] Leiden Univ, Med Ctr, Neurol, Leiden, Netherlands. [Gurol, M. E.; Viswanathan, A.; Schwab, K.; Rosand, J.; Greenberg, S. M.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [van der Grond, J.; van Buchem, M. A.] Leiden Univ, Med Ctr, Radiol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0798 BP 299 EP 299 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002062 ER PT J AU Santos, EMM Yoo, AJ Beenen, LF den Blanken, MB Berkhemer, OA Niessen, WJ Majoie, CB Marquering, HA AF Santos, E. M. M. Yoo, A. J. Beenen, L. F. den Blanken, M. B. Berkhemer, O. A. Niessen, W. J. Majoie, C. B. Marquering, H. A. TI Absolute thrombus density measurement on non-contrast CT in patients with acute ischemic stroke has superior interobserver agreement than relative ratio SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Santos, E. M. M.; Niessen, W. J.] Erasmus Univ, Med Ctr, BIGR Biomed Imaging Grp, Rotterdam, Netherlands. [Yoo, A. J.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Beenen, L. F.; Berkhemer, O. A.; Majoie, C. B.] Univ Amsterdam, Acad Med Ctr, Radiol, NL-1105 AZ Amsterdam, Netherlands. [den Blanken, M. B.; Marquering, H. A.] Univ Amsterdam, Acad Med Ctr, BMEP Biomed Engn & Phys, NL-1105 AZ Amsterdam, Netherlands. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1258 BP 323 EP 323 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002117 ER PT J AU Santos, EMM Yoo, AJ Beenen, LF den Blanken, MB Berkhemer, OA Niessen, WJ Majoie, CB Marquering, HA AF Santos, E. M. M. Yoo, A. J. Beenen, L. F. den Blanken, M. B. Berkhemer, O. A. Niessen, W. J. Majoie, C. B. Marquering, H. A. TI Difference of thrombus attenuation between CT and CT angiography measured in patients with acute ischemic stroke: An expression of thrombus porosity? SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Santos, E. M. M.; den Blanken, M. B.; Marquering, H. A.] AMC Acad Med Ctr Amsterdam, BMEP Biomed Engn & Phys, Amsterdam, Netherlands. [Yoo, A. J.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Beenen, L. F.; Berkhemer, O. A.; Majoie, C. B.] AMC Acad Med Ctr Amsterdam, Radiol, Amsterdam, Netherlands. [Niessen, W. J.] Erasmus Univ, Med Ctr, BIGR Biomed Imaging Grp, Rotterdam, Netherlands. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0956 BP 323 EP 323 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002116 ER PT J AU Schroeder, J Cheng, B Ebinger, M Kohrmann, M Wu, O Kang, D Liebeskind, D Tourdias, T Singer, O Christensen, S Campbell, B Luby, M Warach, S Fiehler, J Fiebach, J Gerloff, C Thomalla, G AF Schroeder, J. Cheng, B. Ebinger, M. Koehrmann, M. Wu, O. Kang, D. Liebeskind, D. Tourdias, T. Singer, O. Christensen, S. Campbell, B. Luby, M. Warach, S. Fiehler, J. Fiebach, J. Gerloff, C. Thomalla, G. TI Validity of acute stroke lesion volume estimation by DWI-ASPECTS depends on lesion location in 496 MCA stroke patients SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Schroeder, J.; Cheng, B.] Univ Med Ctr Hamburg Eppendorf, Neurol, Hamburg, Germany. [Ebinger, M.; Fiebach, J.] Charite, Neurol, Berlin, Germany. [Koehrmann, M.] Univ Erlangen Nurnberg, Neurol, D-91054 Erlangen, Germany. [Wu, O.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Kang, D.] Asan Med Ctr, Neurol, Seoul, South Korea. [Liebeskind, D.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Tourdias, T.] CHU Bordeaux, Neurol, Bordeaux, France. [Singer, O.] Univ Frankfurt Klinikum, Neurol, Frankfurt, Germany. [Christensen, S.; Campbell, B.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Neurol, Melbourne, Vic 3050, Australia. [Luby, M.] NINDS, Neurol, Bethesda, MD 20892 USA. [Warach, S.] UT SW Med Ctr, Neurol, Austin, TX USA. [Fiehler, J.; Gerloff, C.; Thomalla, G.] Univ Med Ctr Hamburg Eppendorf, Neurol, Hamburg, Germany. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0623 BP 336 EP 336 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002153 ER PT J AU Gesierich, B Opherk, C Rosand, J Gonik, M Malik, R Dichgans, M Ewers, M During, M AF Gesierich, B. Opherk, C. Rosand, J. Gonik, M. Malik, R. Dichgans, M. Ewers, M. Duering, M. CA CADASIL-GEWAS Consortium TI APOE epsilon 2 increases white matter hyperintensity burden in pure small vessel disease SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Gesierich, B.; Opherk, C.; Gonik, M.; Malik, R.; Dichgans, M.; Ewers, M.; Duering, M.] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rosand, J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1191 BP 368 EP 368 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002240 ER PT J AU Sakamoto, M Hilsabeck, RC Hammel, M Barakat, F Hassanein, T Perry, W AF Sakamoto, Maiko Hilsabeck, Robin C. Hammel, Meghan Barakat, Fatma Hassanein, Tarek Perry, William TI Neuropsychological functioning among individuals infected with hepatitis C: a comparison of pre- and post-transplant performance SO NEUROPSYCHOLOGICAL TRENDS LA English DT Article DE Hepatitis C; Liver transplantation; Cognitive impairment; Depressive symptoms; End stage liver disease ID QUALITY-OF-LIFE; STAGE LIVER-DISEASE; COGNITIVE DYSFUNCTION; TRANSPLANT RECIPIENTS; HIV-INFECTION; ENCEPHALOPATHY; IMPAIRMENT; IMPACT; CIRRHOSIS; VIRUS AB It is well established that patients with end stage liver disease (ESLD) experience cognitive and mood problems; however, little is known about changes in cognitive and emotional functioning following liver transplantation, especially over the past decade with the epidemic of hepatitis C virus (HCV) infection taking over as the leading indication for liver transplantation. Seventeen patients with ESLD secondary to chronic HCV were assessed pre- and post-liver transplantation using a comprehensive neuropsychological battery. After an average of four years post-transplant, patients demonstrated significant improvements in most cognitive functioning and depressive symptoms. However, 18% of liver recipients continued to exhibit mild cognitive impairment mainly in areas of attention/executive functioning, motor speed, and learning. Liver transplantation is a life-extending surgery that reverses most, but not all, cognitive and mood difficulties. It is crucial to evaluate cognition after liver transplantation, especially in these three domains, and to consider the effect on daily functioning. C1 [Sakamoto, Maiko; Hilsabeck, Robin C.; Hammel, Meghan; Perry, William] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Sakamoto, Maiko] Saga Univ, Sch Med, Saga 840, Japan. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Barakat, Fatma; Hassanein, Tarek] Southern Calif Liver Ctr, Coronado, CA USA. RP Sakamoto, M (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. EM thassanein@livercenters.com NR 60 TC 0 Z9 0 U1 2 U2 2 PU EDIZIONI UNIV LETTERE ECONOMIC DIRITTO-LED PI MILAN PA VIA CERVIGNANO 4,, MILAN, 20137, ITALY SN 1970-321X EI 1970-3201 J9 NEUROPSYCHOL TRENDS JI Neuropsychol. Trends PD APR PY 2015 IS 17 BP 67 EP 83 DI 10.7358/neur-2015-017-saka PG 17 WC Psychology SC Psychology GA CM2MC UT WOS:000357513400007 ER PT J AU Linsky, A Simon, SR Marcello, TB Bokhour, B AF Linsky, Amy Simon, Steven R. Marcello, Thomas B. Bokhour, Barbara TI Clinical Provider Perceptions of Proactive Medication Discontinuation SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ELECTRONIC HEALTH RECORDS; ADVERSE DRUG EVENTS; AMBULATORY-CARE; POLYPHARMACY; THERAPY; ADHERENCE; QUALITY; PEOPLE; IMPACT; OLDER AB Objectives: Polypharmacy and adverse drug events lead to considerable healthcare costs and morbidity, yet there is little to guide clinical providers in the area of discontinuing medications that may not be necessary. We sought to understand providers' beliefs and attitudes about polypharmacy and medication discontinuation. Study Design: Qualitative study using semi-structured interviews of 20 providers with prescribing privileges at 2 US Veterans Affairs Medical Centers, from April 2012 to October 2012. Methods: Transcribed interviews were analyzed using grounded thematic analysis, a systematic approach to deriving qualitative themes from textual data. Results: We identified 10 themes within 4 domains of medication discontinuation. Within the first domain (medication factors), we identified 2 themes: 1) medication characteristics, and 2) uncertainties of why a patient was taking a particular drug. Within the second domain (patient factors), we identified 3 themes: 3) clinical picture of the patient, 4) clinicians' understanding of the patients' knowledge and beliefs, and 5) patients' adherence. Within the third domain (clinical provider factors), we identified 2 themes: 6) professional identity, and 7) providers' decisions related to their own beliefs about medications. Within the fourth domain (system factors), we identified 3 themes: 8) multiple providers, 9) workload, and 10) external directives and policies such as structural components of a healthcare system. Conclusions: Provider decisions to discontinue medications are affected by factors at all levels of the clinical encounter. Our findings have implications for development and implementation of interventions to improve appropriate medication discontinuation via enhanced medication reviews, enriched patient-provider communication, and better system-level structures. This, in turn, may reduce the continued prescribing of potentially inappropriate medications that can lead to adverse outcomes or increased healthcare costs. C1 [Linsky, Amy; Simon, Steven R.; Marcello, Thomas B.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Bokhour, Barbara] ENRM VA Med Ctr, Bedford, MA USA. [Linsky, Amy; Simon, Steven R.] Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. [Linsky, Amy; Simon, Steven R.; Marcello, Thomas B.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Bokhour, Barbara] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Linsky, A (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Bldg 9,Rm 425 152G, Boston, MA 02130 USA. EM amy.linsky@va.gov FU Department of Veterans Affairs (VA), Veterans Health Administration, Veterans Integrated Service Network (VISN1) Career Development Award FX The principal investigator was supported by a Department of Veterans Affairs (VA), Veterans Health Administration, Veterans Integrated Service Network (VISN1) Career Development Award, and the study was conducted using resources of the VA Boston Healthcare System. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. NR 24 TC 1 Z9 1 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2015 VL 21 IS 4 BP 277 EP U69 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN7ZZ UT WOS:000358656900010 PM 26014466 ER PT J AU Gerrard, P Goldstein, R DiVita, MA Slocum, C Ryan, CM Mix, J Niewczyk, P Kazis, L Zafonte, R Schneider, JC AF Gerrard, Paul Goldstein, Richard DiVita, Margaret A. Slocum, Chloe Ryan, Colleen M. Mix, Jacqueline Niewczyk, Paulette Kazis, Lewis Zafonte, Ross Schneider, Jeffrey C. TI Functional Status and Readmissions in Unilateral Hip Fractures SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID EARLY PHYSICAL REHABILITATION; INDEPENDENCE MEASURE; STROKE REHABILITATION; HOSPITAL READMISSION; COMORBIDITY INDEX; ASSESSMENT SCALES; CARE; RELIABILITY; POPULATION; VALIDATION AB Objectives: To test whether functional status is a robust predictor of acute care readmission risk in patients who have been discharged to an inpatient rehabilitation facility (IRF) following a unilateral hip fracture. Study Design: Retrospective database study using a large administrative data set. Methods: A retrospective analysis of data from the Uniform Data System for Medical Rehabilitation from the years 2002 to 2011 was performed, examining patients with an impairment of unilateral hip fracture. A basic prediction model based on functional status was compared with competing models incorporating medical comorbidities. C statistics were compared to evaluate model performance. Results: There were a total of 433,154 patients: 32,783 (7.87%) patients were transferred back to an acute hospital, including 7937 (1.91%) transferred within 3 days, 16,150 (3.88%) transferred within 7 days, and 32,607 (7.83%) transferred within 30 days after IRF admission. The C statistics for the Basic Model are 0.710, 0.674, and 0.667 at days 3, 7, and 30, respectively. Compared with the Basic Model, the best performing Basic-Plus model was the Basic + Elixhauser Model with C statistic differences of +0.013, +0.014, and +0.019, and the best performing Age-Comorbidity Model was the Age + Elixhauser Model with C statistic differences of -0.110, -0.079, and -0.065 at days 3, 7, and 30, respectively. Conclusions: Functional status is a robust and potentially modifiable risk factor for patients admitted to IRFs following a unilateral hip fracture. C1 [Gerrard, Paul] New England Rehabil Hosp Portland, Portland, ME 04102 USA. [Gerrard, Paul; Goldstein, Richard; Slocum, Chloe; Zafonte, Ross; Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Gerrard, Paul; Slocum, Chloe; Zafonte, Ross; Schneider, Jeffrey C.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA USA. [DiVita, Margaret A.] SUNY Coll Cortland, Cortland, NY 13045 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA USA. [Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Gerrard, P (reprint author), New England Rehabil Hosp Portland, 335 Brighton Ave, Portland, ME 04102 USA. EM pbgerrard@gmail.com NR 45 TC 3 Z9 3 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2015 VL 21 IS 4 BP E282 EP E287 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN7ZZ UT WOS:000358656900007 PM 26244792 ER PT J AU Ahluwalia, S Cromer, R Giannitrapani, K Schreibeis-Baum, H Dobscha, S Krebs, EE Lorenz, K AF Ahluwalia, Sangeeta Cromer, Risa Giannitrapani, Karleen Schreibeis-Baum, Hannah Dobscha, Steven Krebs, Erin E. Lorenz, Karl TI "IT ENCOURAGES THEM TO COMPLAIN": POTENTIAL UNINTENDED CONSEQUENCES OF ROUTINE PAIN SCREENING AND IMPLICATIONS FOR IMPROVEMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Krebs, Erin E.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Dobscha, Steven] Portland VA Med Ctr, Portland, OR USA. [Ahluwalia, Sangeeta] RAND Corp, Encino, CA USA. [Cromer, Risa] Vet Hlth Adm, Portland, OR USA. [Giannitrapani, Karleen; Schreibeis-Baum, Hannah; Lorenz, Karl] Vet Hlth Adm, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2192233 BP S46 EP S46 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900004 ER PT J AU Ali, N Nieva, HR Percac-Lima, S Shields, HM Linder, JA Osman, N AF Ali, Nadaa Nieva, Harry Reyes Percac-Lima, Sanja Shields, Helen M. Linder, Jeffrey A. Osman, Nora TI MUSLIM PATIENTS AND HEALTH CARE UTILIZATION DURING RAMADAN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Ali, Nadaa; Shields, Helen M.; Linder, Jeffrey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nieva, Harry Reyes; Osman, Nora] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Chelsea, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2191681 BP S212 EP S213 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900373 ER PT J AU Asch, DA Troxel, AB Stewart, WF Sequist, TD Jones, JB Hirsch, AG Hoffer, K Zhu, JS Wang, WL Hodlofski, AT Frasch, AB Weiner, MG Finnerty, DD Rosenthal, M Gangemi, K Volpp, KG AF Asch, David A. Troxel, Andrea B. Stewart, Walter F. Sequist, Thomas D. Jones, J. B. Hirsch, Annemarie G. Hoffer, Karen Zhu, Jingsan Wang, Wenli Hodlofski, Amanda T. Frasch, Antonette B. Weiner, Mark G. Finnerty, Darra D. Rosenthal, Meredith Gangemi, Kelsey Volpp, Kevin G. TI A MULTICENTER RANDOMIZED TRIAL OF PHYSICIAN, PATIENT, AND PHYSICIAN/PATIENT INCENTIVES TO IMPROVE LIPID MANAGEMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Sequist, Thomas D.] Partners Healthcare Syst, Boston, MA 19104 USA. [Asch, David A.; Hoffer, Karen; Wang, Wenli; Frasch, Antonette B.; Finnerty, Darra D.] Univ Penn, Philadelphia, PA USA. [Troxel, Andrea B.; Zhu, Jingsan; Hodlofski, Amanda T.; Gangemi, Kelsey; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 02115 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Rosenthal, Meredith] Harvard Univ, Sch Publ Hlth, Boston, MA USA. [Stewart, Walter F.; Jones, J. B.] Sutter Hlth, San Francisco, CA USA. [Hirsch, Annemarie G.] Geisinger Hlth Syst, Danville, PA USA. [Weiner, Mark G.] Temple Univ Hlth Syst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2200183 BP S86 EP S86 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900094 ER PT J AU Barnett, M Song, ZR Rose, S Bitton, A Chernew, ME Landon, BE AF Barnett, Michael Song, Zirui Rose, Sherri Bitton, Asaf Chernew, Michael E. Landon, Bruce E. TI INSURANCE TURNOVER, CARE FRAGMENTATION AND EMERGENCY DEPARTMENT UTILIZATION IN MASSACHUSETTS, 2011-2012 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Barnett, Michael; Bitton, Asaf] Brigham & Womens Hosp, Brookline, MA USA. [Song, Zirui] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barnett, Michael; Song, Zirui; Rose, Sherri; Bitton, Asaf; Chernew, Michael E.; Landon, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Landon, Bruce E.] Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193561 BP S194 EP S194 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900333 ER PT J AU Barnett, M Hsu, J McWilliams, JM AF Barnett, Michael Hsu, John McWilliams, J. Michael TI CONTRIBUTION OF PATIENTS' CLINICAL AND SOCIAL CHARACTERISTICS TO DIFFERENCES IN HOSPITAL READMISSION RATES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Barnett, Michael; McWilliams, J. Michael] Brigham & Womens Hosp, Brookline, MA USA. [Barnett, Michael; Hsu, John; McWilliams, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193546 BP S128 EP S129 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900190 ER PT J AU Becker, W Tate, JP Edelman, EJ Gaither, J Akgun, K Barry, D Crystal, S Gordon, A Merlin, JS Kerns, RD Justice, AC Fiellin, DA AF Becker, William Tate, Janet P. Edelman, Eva J. Gaither, Julie Akgun, Kathleen Barry, Declan Crystal, Stephen Gordon, Adam Merlin, Jessica S. Kerns, Robert D. Justice, Amy C. Fiellin, David A. TI THE RELATIONSHIP AMONG OPIOID USE, HIV, AND ACCIDENTAL DEATH: IS IT IN THE EYE OF THE BEHOLDER? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Gordon, Adam] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Becker, William; Akgun, Kathleen; Kerns, Robert D.] VA Connecticut, West Haven, CT USA. [Gaither, Julie; Barry, Declan] Yale Univ, New Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Birmingham, AL USA. [Tate, Janet P.; Edelman, Eva J.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Internal Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198782 BP S74 EP S75 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900068 ER PT J AU Berkowitz, SA Atlas, SJ Barnard, L Traore, CY Meigs, JB Wexler, DJ AF Berkowitz, Seth A. Atlas, Steven J. Barnard, Lily Traore, Carine Y. Meigs, James B. Wexler, Deborah J. TI FOOD INSECURITY, FOOD DESERTS, AND GLYCEMIC CONTROL: A MULTI-LEVEL LONGITUDINAL ANALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Berkowitz, Seth A.; Atlas, Steven J.; Traore, Carine Y.; Meigs, James B.; Wexler, Deborah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barnard, Lily] Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2191915 BP S166 EP S166 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900272 ER PT J AU Berkowitz, SA Fabreau, GE Raghavan, S Kentoffio, K He, W Atlas, SJ Percac-Lima, S AF Berkowitz, Seth A. Fabreau, Gabriel E. Raghavan, Sridharan Kentoffio, Katherine He, Wei Atlas, Steven J. Percac-Lima, Sanja TI DIABETES RISK AND MEDIATORS AMONG REFUGEES AND IMMIGRANTS: A LONGITUDINAL ANALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Berkowitz, Seth A.; He, Wei] MGH, Boston, MA USA. [Raghavan, Sridharan; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Percac-Lima, Sanja] Massachussetts Gen Hosp, Chelsea, MA USA. [Fabreau, Gabriel E.] Univ Calgary, Calgary, AB, Canada. [Kentoffio, Katherine] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2191910 BP S139 EP S139 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900213 ER PT J AU Berkowitz, SA Traore, CY Atlas, SJ AF Berkowitz, Seth A. Traore, Carine Y. Atlas, Steven J. TI ADDRESSING BASIC RESOURCE NEEDS IN PRIMARY CARE IMPROVES BLOOD PRESSURE AND CHOLESTEROL CONTROL: A PRAGMATIC INTERVENTION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Berkowitz, Seth A.; Traore, Carine Y.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2191912 BP S95 EP S95 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900117 ER PT J AU Blazey-Martin, D Carr, P Terrin, N Breeze, J Luk, C Raj, A Kaplan, SE Freund, K AF Blazey-Martin, Deborah Carr, Phyllis Terrin, Norma Breeze, Janis Luk, Carolyn Raj, Anita Kaplan, Samantha E. Freund, Karen TI LOWER RATES OF PROMOTION OF GENERALISTS IN ACADEMIC MEDICINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Blazey-Martin, Deborah; Terrin, Norma; Breeze, Janis; Luk, Carolyn; Freund, Karen] Tufts Med Ctr, Boston, MA USA. [Carr, Phyllis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raj, Anita] Univ Calif San Diego, San Diego, CA 92103 USA. [Kaplan, Samantha E.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2181792 BP S205 EP S205 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900358 ER PT J AU Burke, RE Whitfield, E Coleman, EA Schwartz, R Ginde, AA Hittle, D AF Burke, Robert E. Whitfield, Emily Coleman, Eric A. Schwartz, Robert Ginde, Adit A. Hittle, David TI TIMING OF READMISSIONS FROM POST-ACUTE CARE: IMPLICATIONS FOR IMPROVING THE QUALITY OF TRANSITIONAL CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Burke, Robert E.] Denver VA Med Ctr, Denver, CO USA. [Burke, Robert E.; Coleman, Eric A.; Schwartz, Robert; Hittle, David] Univ Colorado, Sch Med, Aurora, CO USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Denver, CO USA. RI bebarta, vikhyat/K-3476-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199110 BP S282 EP S283 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901142 ER PT J AU Cai, JX Campbell, EJ Richter, JM AF Cai, Jennifer X. Campbell, Emily J. Richter, James M. TI EVALUATION OF DISCORDANT UPPER ENDOSCOPY IN OUTPATIENTS WITH GASTROESOPHAGEAL REFLUX DISORDER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Cai, Jennifer X.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Campbell, Emily J.; Richter, James M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199270 BP S153 EP S153 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900243 ER PT J AU Carter, A Borrero, S Wessel, C Bean-Mayberry, B Washington, DL Corbelli, J AF Carter, Andrea Borrero, Sonya Wessel, Charles Bean-Mayberry, Bevanne Washington, Donna L. Corbelli, Jennifer TI RACIAL AND ETHNIC DISPARITIES IN HEALTHCARE AMONG WOMEN IN THE VA: A SYSTEMATIC REVIEW SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Carter, Andrea; Borrero, Sonya; Wessel, Charles; Corbelli, Jennifer] Univ Pittsburgh, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RI Wessel, Charles/B-2318-2013 OI Wessel, Charles/0000-0002-5018-0156 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2194054 BP S241 EP S241 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901053 ER PT J AU Carter, JA Wexler, D Donelan, K Ward, C Kaiser, CL AF Carter, Jocelyn A. Wexler, Deborah Donelan, Karen Ward, Charlotte Kaiser, Courtney L. TI REDUCING READMISSIONS WHY PATIENT AND PROVIDER PERCEPTIONS MAY MATTER MORE THAN YOU THINK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Donelan, Karen] Massachusetts Gen Hosp, Lebanon, NH USA. [Carter, Jocelyn A.; Wexler, Deborah; Ward, Charlotte; Kaiser, Courtney L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2200333 BP S544 EP S545 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902231 ER PT J AU Centor, RM Atkinson, TP Waites, K Estrada, C AF Centor, Robert M. Atkinson, Thomas P. Waites, Ken Estrada, Carlos TI CENTOR SCORE PREDICTS COMMON BACTERIAL CAUSES OF SORE THROAT-NOT JUST GROUP A BETA HEMOLYTIC STREPTOCOCCUS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Centor, Robert M.] Univ Alabama, Huntsville, AL 35899 USA. [Atkinson, Thomas P.; Waites, Ken; Estrada, Carlos] Univ Alabama Birmingham, Birmingham, AL USA. [Estrada, Carlos] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2168431 BP S118 EP S118 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900166 ER PT J AU Cordasco, KM Zuchowski, JL Hamilton, A Mark, C Bell-Lewis, L Chrystal, JG Kirsh, S Washington, DL AF Cordasco, Kristina M. Zuchowski, Jessica L. Hamilton, Alison Mark, Canning Bell-Lewis, LaShawnta Chrystal, Joya G. Kirsh, Susan Washington, Donna L. TI VETERANS HEALTH ADMINISTRATION ELECTRONIC CONSULTATIONS: WOMEN'S HEALTH PRIMARY CARE PROVIDERS' PERCEPTIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Cordasco, Kristina M.; Zuchowski, Jessica L.; Hamilton, Alison; Mark, Canning; Bell-Lewis, LaShawnta; Chrystal, Joya G.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina M.; Hamilton, Alison; Washington, Donna L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Kirsh, Susan] Cleveland VA Med Ctr, Cleveland, OH USA. [Kirsh, Susan] VA Cent Off, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2195043 BP S298 EP S298 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901175 ER PT J AU Dailey, FE Burstein, S AF Dailey, Francis E. Burstein, Samuel TI AN ADULT WITH ATOMOXETINE-INDUCED HEPATITIS: A REPORT OF A RARE CASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dailey, Francis E.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Burstein, Samuel] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2200271 BP S357 EP S357 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901328 ER PT J AU Dalleur, O Seger, DL Slight, SP Amato, M Eguale, T Nanji, KC Swerdloff, M Dykes, PC Fiskio, J Bates, DW AF Dalleur, Olivia Seger, Diane L. Slight, Sarah P. Amato, Mary Eguale, Tewodros Nanji, Karen C. Swerdloff, Michael Dykes, Patricia C. Fiskio, Julie Bates, David W. TI INAPPROPRIATE OVERRIDES OF AGE-RELATED ALERTS IN PRESCRIBER ORDER ENTRY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dalleur, Olivia; Seger, Diane L.; Slight, Sarah P.; Amato, Mary; Eguale, Tewodros; Swerdloff, Michael; Dykes, Patricia C.; Fiskio, Julie; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Durham, Stockton On Tees, England. [Seger, Diane L.; Nanji, Karen C.; Swerdloff, Michael; Fiskio, Julie] Partners Healthcare Syst, Wellesley, MA USA. [Dalleur, Olivia] Catholic Univ Louvain, B-1200 Brussels, Belgium. [Amato, Mary] MCPHS Univ, Boston, MA USA. [Eguale, Tewodros] McGill Univ, Dept Med, Montreal, PQ, Canada. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Dykes, Patricia C.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197513 BP S189 EP S190 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900324 ER PT J AU Donze, J Williams, M Robinson, E Zimlichman, E Aujesky, D Vasilevskis, EE Kripalini, S Metlay, J Wallington, T Fletcher, G Auerbach, AD Schnipper, JL AF Donze, Jacques Williams, Mark Robinson, Edmondo Zimlichman, Eyal Aujesky, Drahomir Vasilevskis, Eduard E. Kripalini, Sunil Metlay, Joshua Wallington, Tamara Fletcher, Grant Auerbach, Andrew D. Schnipper, Jeffrey L. TI INTERNATIONAL MULTICENTER VALIDATION OF THE "HOSPITAL" SCORE TO PREDICT 30-DAY POTENTIALLY AVOIDABLE READMISSIONS IN MEDICAL PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Donze, Jacques; Schnipper, Jeffrey L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Robinson, Edmondo] Christiana Care Hlth Syst, Wilmington, DE USA. [Metlay, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Auerbach, Andrew D.] UCSF Div Hosp Med, San Francisco, CA USA. [Vasilevskis, Eduard E.; Kripalini, Sunil] Vanderbilt Univ, Nashville, TN 37235 USA. [Donze, Jacques; Aujesky, Drahomir] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Williams, Mark] Univ Kentucky, Lexington, KY USA. [Zimlichman, Eyal] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Wallington, Tamara] William Osler Hlth Syst, Brampton, ON, Canada. [Fletcher, Grant] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2191115 BP S63 EP S63 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900046 ER PT J AU Dulay, MH Bachhuber, M Shunk, RL OBrien, BC AF Dulay, Maya H. Bachhuber, Melissa Shunk, Rebecca L. OBrien, Bridget C. TI IMPROVING IDENTIFICATION OF HIGH-RISK PRIMARY CARE PATIENTS FOR INTERNAL MEDICINE RESIDENTS' YEAR-END HANDOFFS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dulay, Maya H.; Bachhuber, Melissa; Shunk, Rebecca L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Dulay, Maya H.; Bachhuber, Melissa; Shunk, Rebecca L.; OBrien, Bridget C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199524 BP S539 EP S539 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902219 ER PT J AU Duru, OK Turk, N Ettner, S Moin, T Li, JN Keckhafer, AM Luchs, RH Chan, C Steers, N Mangione, C AF Duru, O. Kenrik Turk, Norman Ettner, Susan Moin, Tannaz Li, Jinnan Keckhafer, Abigail M. Luchs, Robert H. Chan, Charles Steers, Neil Mangione, Carol TI RESULTS FROM NEXT-D: PROMOTING BREAST CANCER SCREENING IN A DIABETES/PRE-DIABETES SPECIFIC HEALTH PLAN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Duru, O. Kenrik; Turk, Norman; Ettner, Susan; Li, Jinnan; Steers, Neil; Mangione, Carol] Univ Calif Los Angeles, Los Angeles, CA USA. [Moin, Tannaz] Univ Calif Los Angeles, VA Greater Los Angeles, Los Angeles, CA USA. [Keckhafer, Abigail M.; Luchs, Robert H.; Chan, Charles] UnitedHealthcare, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196155 BP S247 EP S247 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901068 ER PT J AU Edelman, EJ Tate, JP Gordon, KS Becker, W Bryant, K Crothers, K Gaither, JR Gibert, C Gordon, A Marshall, BD Rodriguez-Barradas, M Samet, JH Skanderson, M Justice, AC Fiellin, DA AF Edelman, E. J. Tate, Janet P. Gordon, Kirsha S. Becker, William Bryant, Kendall Crothers, Kristina Gaither, J. R. Gibert, Cynthia Gordon, Adam Marshall, Brandon D. Rodriguez-Barradas, Maria Samet, Jeffrey H. Skanderson, Melissa Justice, Amy C. Fiellin, David A. TI DO PRESCRIBED OPIOIDS IMPACT CD4 COUNT RESTORATION AMONG HIV plus PATIENTS INITIATING ANTIRETROVIRAL THERAPY? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Edelman, E. J.; Tate, Janet P.; Gordon, Kirsha S.; Becker, William; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Becker, William; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIH, Bethesda, MD 20892 USA. [Crothers, Kristina] Univ Washington, Seattle, WA 98195 USA. [Gaither, J. R.] Yale Univ, New Haven, CT USA. [Gibert, Cynthia] DC VAMC, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Washington, DC USA. [Gordon, Adam; Skanderson, Melissa] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Marshall, Brandon D.] Brown Univ, Providence, RI 02912 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VAMC, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199293 BP S142 EP S142 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900221 ER PT J AU Edwards, ST Rubenstein, LV Meredith, LS Schmidt, N Stockdale, SE Cordasco, KM Lanto, A Roos, P Yano, EM AF Edwards, Samuel T. Rubenstein, Lisa V. Meredith, Lisa S. Schmidt, Nicole Stockdale, Susan E. Cordasco, Kristina M. Lanto, Andrew Roos, Philip Yano, Elizabeth M. TI WHO IS RESPONSIBLE FOR WHAT TASKS WITHIN PRIMARY CARE: PERCEIVED TASK ALLOCATION AMONG PRIMARY CARE PROVIDERS AND INTERDISCIPLINARY TEAM MEMBERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rubenstein, Lisa V.; Stockdale, Susan E.; Lanto, Andrew; Yano, Elizabeth M.] Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. [Meredith, Lisa S.; Schmidt, Nicole] RAND Corp, Santa Monica, CA USA. [Cordasco, Kristina M.] Univ Calif Los Angeles, VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. [Roos, Philip] VA Loma Linda Healthcare Syst, Loma Linda, CA USA. [Edwards, Samuel T.] VA Portland Hlth Care Syst, Portland, OR USA. [Edwards, Samuel T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2185177 BP S303 EP S303 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901186 ER PT J AU Essien, UR AF Essien, Utibe R. TI A 21-YEAR-OLD WOMAN WITH FEVER AND SORE THROAT: LEMIERRE'S SYNDROME WITH FUSOBACTERIUM NECROPHORUM BACTEREMIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Essien, Utibe R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193416 BP S326 EP S326 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901246 ER PT J AU Fabreau, GE Berkowitz, SA He, W Kayitesi, C Oo, S Atlas, SJ Percac-Lima, S AF Fabreau, Gabriel E. Berkowitz, Seth A. He, Wei Kayitesi, Chantal Oo, Sarah Atlas, Steven J. Percac-Lima, Sanja TI ACQUISITION OF CARDIOVASCULAR DISEASE RISK FACTORS AMONG REFUGEES AND IMMIGRANTS: A LONGITUDINAL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kayitesi, Chantal; Oo, Sarah] Massachusetts Gen Hosp, Chelsea, MA USA. [Fabreau, Gabriel E.] Univ Calgary, Calgary, AB, Canada. [Berkowitz, Seth A.; He, Wei; Atlas, Steven J.; Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fabreau, Gabriel E.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2196070 BP S93 EP S94 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900115 ER PT J AU Gerber, MR King, M Pineles, S Iverson, K Haskell, SG AF Gerber, Megan R. King, Matthew Pineles, Suzanne Iverson, Katherine Haskell, Sally G. TI ASSOCIATIONS BETWEEN MENTAL HEALTH BURDEN, SMOKING AND CARDIOVASCULAR DISEASE IN WOMEN VETERANS OVER 45 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Gerber, Megan R.] Boston Univ, Jamaica Plain, MA USA. [Haskell, Sally G.] Yale Univ, VA CT, Madison, CT USA. [Haskell, Sally G.] VA Cent Off, Madison, CT USA. [King, Matthew; Pineles, Suzanne; Iverson, Katherine] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Gerber, Megan R.; King, Matthew; Pineles, Suzanne; Iverson, Katherine] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2198075 BP S106 EP S107 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900143 ER PT J AU Giannitrapani, K Hamilton, A Huynh, AK Stockdale, SE Rubenstein, LV AF Giannitrapani, Karleen Hamilton, Alison Huynh, Alexis K. Stockdale, Susan E. Rubenstein, Lisa V. TI STAFF ROLES ON PRIMARY CARE TEAMS ARE FAILING TO ALIGN WITH PHYSICIANS' EXPECTATIONS AND NEEDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rubenstein, Lisa V.] GLA VA, North Hills, CA USA. [Stockdale, Susan E.] Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. [Giannitrapani, Karleen] UCLA VA GLA, Los Angeles, CA USA. [Hamilton, Alison] US Dept Vet Affairs, Los Angeles, CA USA. [Huynh, Alexis K.] Vet Affairs, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196596 BP S257 EP S257 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901089 ER PT J AU Giannitrapani, K Ahluwalia, S Pisciotta, M Cromer, R Schreibeis-Baum, HC Dobscha, S Krebs, EE Lorenz, K AF Giannitrapani, Karleen Ahluwalia, Sangeeta Pisciotta, Maura Cromer, Risa Schreibeis-Baum, Hannah C. Dobscha, Steven Krebs, Erin E. Lorenz, Karl TI IMPROVING OPIOID PRESCRIBING IN THE CONTEXT OF ROUTINE PAIN SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Krebs, Erin E.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Pisciotta, Maura; Dobscha, Steven] Portland VA Med Ctr, Portland, OR USA. [Ahluwalia, Sangeeta] RAND Corp, Encino, CA USA. [Giannitrapani, Karleen] Univ Calif Los Angeles, VA GLA, Los Angeles, CA USA. [Schreibeis-Baum, Hannah C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cromer, Risa] VA, Portland, OR USA. [Lorenz, Karl] Univ Calif Los Angeles, RAND, VA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196337 BP S188 EP S188 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900320 ER PT J AU Giannitrapani, K Huynh, AK Lanto, A Stockdale, SE Meredith, LS Rubenstein, LV AF Giannitrapani, Karleen Huynh, Alexis K. Lanto, Andrew Stockdale, Susan E. Meredith, Lisa S. Rubenstein, Lisa V. TI FACILITATORS OF TEAM FUNCTIONING DURING THE EARLY STAGES OF PCMH IMPLEMENTATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rubenstein, Lisa V.] GLA VA, North Hills, CA USA. [Stockdale, Susan E.] Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. [Meredith, Lisa S.] RAND Corp, Santa Monica, CA USA. [Giannitrapani, Karleen] UCLA VA GLA, Los Angeles, CA USA. [Lanto, Andrew] VA Greater LA Healthcare Syst, Sepulveda, CA USA. [Huynh, Alexis K.] Vet Affairs, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196640 BP S157 EP S157 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900252 ER PT J AU Goldstein, KM Frayne, SM Gierisch, J Blakeney, J Yano, EM Sadler, A Bean-Mayberry, B Carney, D DiLeone, B Fox, A Klap, R Hamilton, A Yee, E Vogt, D AF Goldstein, Karen M. Frayne, Susan M. Gierisch, Jennifer Blakeney, Jill Yano, Elizabeth M. Sadler, Anne Bean-Mayberry, Bevanne Carney, Diane DiLeone, Brooke Fox, Annie Klap, Ruth Hamilton, Alison Yee, Ellen Vogt, Dawne TI EVIDENCE-BASED QUALITY IMPROVEMENT IN AVA WOMEN'S HEALTH PRACTICE BASED RESEARCH NETWORK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Goldstein, Karen M.; Gierisch, Jennifer] Durham VA, Durham, NC USA. [Goldstein, Karen M.; Gierisch, Jennifer] Duke Univ, Durham, NC USA. [Yee, Ellen] NMVAHCS, Albuquerque, NM USA. [Hamilton, Alison] US Dept Vet Affairs, Los Angeles, CA USA. [Yano, Elizabeth M.; Bean-Mayberry, Bevanne; Klap, Ruth] VA Greater Los Angeles HSR&D Ctr, Sepulveda, CA USA. [Frayne, Susan M.; Carney, Diane] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Frayne, Susan M.] Stanford Univ, Palo Alto, CA 94304 USA. [Yano, Elizabeth M.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, Los Angeles, CA USA. [Sadler, Anne] Dept Vet Affairs, Iowa City, IA USA. [Sadler, Anne] Univ Iowa, Iowa City, IA USA. [DiLeone, Brooke] Philadelphia VAMC, Philadelphia, PA USA. [Fox, Annie; Vogt, Dawne] VA Boston Med Ctr, Boston, MA USA. [Vogt, Dawne] Boston Univ, Boston, MA 02215 USA. [Blakeney, Jill] Durham VAMC, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2194776 BP S153 EP S153 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900244 ER PT J AU Gopalan, A Cain, LR Makelarski, JA Garibay, LB Merchant, RM Lindau, ST AF Gopalan, Anjali Cain, Loretta R. Makelarski, Jennifer A. Garibay, Lori B. Merchant, Raina M. Lindau, Stacy T. TI HEALTH-SPECIFIC INFORMATION AND COMMUNICATION TECHNOLOGY USE AND ITS RELATIONSHIP TO CHRONIC DISEASE STATUS IN COMMUNITIES ON THE SOUTH SIDE OF CHICAGO SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Gopalan, Anjali] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gopalan, Anjali] Robert Wood Johnson Clin Scholars Program, Philadelphia, PA USA. [Merchant, Raina M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cain, Loretta R.; Makelarski, Jennifer A.; Lindau, Stacy T.] Univ Chicago, Chicago, IL 60637 USA. [Garibay, Lori B.] Rescue Social Change Grp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2192280 BP S172 EP S172 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900284 ER PT J AU Gupta, S Heaton, K Alladina, J Puig, A Miloslavsky, E AF Gupta, Shruti Heaton, Kevin Alladina, Jehan Puig, Alberto Miloslavsky, Eli TI A RANDOMIZED TRIAL OF AN INTERVENTION TO IMPROVE RESIDENT-FELLOW TEACHING INTERACTIONS ON THE WARDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Puig, Alberto] Harvard Univ, Sch Med, MGH, Boston, MA USA. [Gupta, Shruti; Heaton, Kevin; Alladina, Jehan; Miloslavsky, Eli] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196445 BP S485 EP S485 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902100 ER PT J AU Hamilton, AB Maisel, N Yano, EM Klap, R Oishi, S Balasubramanian, V Saechao, F Frayne, SM AF Hamilton, Alison B. Maisel, Natalya Yano, Elizabeth M. Klap, Ruth Oishi, Sabine Balasubramanian, Vidhya Saechao, Fay Frayne, Susan M. TI WOMEN VETERANS WITH CO-OCCURRING MENTAL HEALTH CONDITIONS IN VA PRIMARY CARE CLINICS: A MIXED METHODS STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr, Sepulveda, CA USA. [Hamilton, Alison B.; Klap, Ruth; Oishi, Sabine] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Frayne, Susan M.] VA Palo Alto Hlth Care Syst Stanford, Menlo Pk, CA USA. [Saechao, Fay] VAPAHCS, Menlo Pk, CA USA. [Maisel, Natalya; Balasubramanian, Vidhya] Vet Affairs Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197845 BP S305 EP S306 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901192 ER PT J AU Hanchate, AD Paasche-Orlow, M Baker, WE Dyer, S Feng, C Feldman, J AF Hanchate, Amresh D. Paasche-Orlow, Michael Baker, William E. Dyer, Sophia Feng, Chen Feldman, James TI RACIAL/ETHNIC DIFFERENCES IN DESTINATION EMERGENCY DEPARTMENTS FOR ACUTE CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Hanchate, Amresh D.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Paasche-Orlow, Michael; Feng, Chen] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Baker, William E.; Dyer, Sophia; Feldman, James] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197883 BP S242 EP S242 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901056 ER PT J AU Hanchate, AD Feldman, J Shankar, KN McCormick, D Lasser, KE Feng, C Kressin, NR AF Hanchate, Amresh D. Feldman, James Shankar, Kalpana N. McCormick, Danny Lasser, Karen E. Feng, Chen Kressin, Nancy R. TI MASSACHUSETTS HEALTH CARE REFORM REDUCED EMERGENCY DEPARTMENT VISITS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Lasser, Karen E.; Feng, Chen; Kressin, Nancy R.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Feldman, James; Shankar, Kalpana N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [McCormick, Danny] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197977 BP S205 EP S206 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900359 ER PT J AU Hermann, EA Atlas, SJ Ashburner, JM Percac-Lima, S AF Hermann, Emilia A. Atlas, Steven J. Ashburner, Jeffrey M. Percac-Lima, Sanja TI SATISFACTION WITH HEALTH CARE AMONG PATIENTS NAVIGATED FOR PREVENTIVE CANCER SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Atlas, Steven J.; Ashburner, Jeffrey M.; Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hermann, Emilia A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198829 BP S250 EP S250 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901075 ER PT J AU Hoffman, R Shi, Y Freedland, S Keating, NL Walter, L AF Hoffman, Richard Shi, Ying Freedland, Stephen Keating, Nancy L. Walter, Louise TI TREATMENT PATTERNS FOR OLDER VETERANS WITH LOCALIZED PROSTATE CANCER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Shi, Ying; Walter, Louise] San Francisco VA Med Ctr, San Francisco, CA USA. [Walter, Louise] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hoffman, Richard] Albuquerque VA Med Ctr, Albuquerque, NM USA. [Hoffman, Richard] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Freedland, Stephen] Duke Univ, Durham, NC USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2190732 BP S286 EP S287 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901151 ER PT J AU Hong, JS Atlas, SJ Ashburner, JM Hong, CS AF Hong, Johan S. Atlas, Steven J. Ashburner, Jeffrey M. Hong, Clemens S. TI DEFINING PRIMARY CARE TEAM EFFORT FROM THE PRIMARY CARE PHYSICIAN'S PERSPECTIVE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Atlas, Steven J.; Ashburner, Jeffrey M.; Hong, Clemens S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hong, Johan S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199904 BP S132 EP S133 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900198 ER PT J AU Howell, BA Long, J Edelman, EJ McGinnis, KA Rimland, D Fiellin, DA Justice, AC Wang, EA AF Howell, Benjamin A. Long, Jessica Edelman, E. J. McGinnis, Kathleen A. Rimland, David Fiellin, David A. Justice, Amy C. Wang, Emily A. TI LIFETIME AND RECENT INCARCERATION AND RISK OF UNCONTROLLED BLOOD PRESSURE CONTROL IN A MULTI-SITE COHORT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rimland, David] VA Med Ctr, Decatur, GA USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Howell, Benjamin A.; Long, Jessica; Edelman, E. J.; Fiellin, David A.; Justice, Amy C.; Wang, Emily A.] Yale Univ, Sch Med, New Haven, CT USA. [Fiellin, David A.; Justice, Amy C.] Ctr Interdisciplinary Res AIDS, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2182563 BP S203 EP S203 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900352 ER PT J AU Jones, CD Wald, H Boxer, RS Masoudi, FA Burke, RE Capp, R Ginde, AA AF Jones, Christine D. Wald, Heidi Boxer, Rebecca S. Masoudi, Frederick A. Burke, Robert E. Capp, Roberta Ginde, Adit A. TI REGIONAL VARIATION IN HOME HEALTH CARE REFERRALS AT HOSPITAL DISCHARGE: RESULTS FROM THE 2012 NATIONAL INPATIENT SAMPLE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Burke, Robert E.] Denver VA Med Ctr, Denver, CO USA. [Jones, Christine D.] Univ Colorado, Aurora, CO USA. [Wald, Heidi; Boxer, Rebecca S.; Masoudi, Frederick A.; Capp, Roberta; Ginde, Adit A.] Univ Colorado, Denver, CO 80202 USA. RI bebarta, vikhyat/K-3476-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197874 BP S245 EP S245 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901063 ER PT J AU Kentoffio, K Berkowitz, SA Atlas, SJ Oo, S Percac-Lima, S AF Kentoffio, Katherine Berkowitz, Seth A. Atlas, Steven J. Oo, Sarah Percac-Lima, Sanja TI MATERNAL HEALTH SERVICES USE: COMPARING REFUGEE, IMMIGRANT AND NATIVE POPULATIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Oo, Sarah] Massachusetts Gen Hosp, Chelsea, MA USA. [Berkowitz, Seth A.; Atlas, Steven J.; Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kentoffio, Katherine] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2198223 BP S206 EP S206 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900360 ER PT J AU Kertesz, S Austin, EL Elam, C Johnson, N AF Kertesz, Stefan Austin, Erika L. Elam, Calvin Johnson, Nancy TI A SURVEY TO ASSESS PATIENT EXPERIENCES IN PATIENT-CENTERED MEDICAL HOMES FOR PATIENTS WHO ARE HOMELESS AND FORMERLY HOMELESS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kertesz, Stefan; Austin, Erika L.; Elam, Calvin; Johnson, Nancy] Birmingham VAMC, Birmingham, AL USA. [Kertesz, Stefan] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198318 BP S514 EP S515 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902170 ER PT J AU Kidwai-Khan, F McGinnis, KA Tate, JP Bryant, K Justice, AC AF Kidwai-Khan, Farah McGinnis, Kathleen A. Tate, Janet P. Bryant, Kendall Justice, Amy C. TI VACS-TLFB FOR ALCOHOL USE: A WEB BASED TIMELINE FOLLOWBACK APPLICATION - A HEALTH TECHNOLOGY ASSESSMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kidwai-Khan, Farah] Yale Univ, Sleepy Hollow, NY USA. [Justice, Amy C.] Yale Univ, West Haven, CT USA. [Tate, Janet P.] Yale Univ, SOM, West Haven, CT USA. [Kidwai-Khan, Farah; Bryant, Kendall] VA Connecticut Healthcare Syst, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198915 BP S297 EP S297 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901173 ER PT J AU Lagisetty, PA Piccolo, R Yang, M Marceau, LD Grant, RW McKinlay, JB Meigs, JB AF Lagisetty, Pooja A. Piccolo, Rebecca Yang, May Marceau, Lisa D. Grant, Richard W. McKinlay, John B. Meigs, James B. TI FOOD ENVIRONMENT, DIET BEHAVIOR AND WEIGHT GAIN IN A MULTI-ETHNIC URBAN COHORT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Grant, Richard W.] Kaiser Permanente No Calif, Oakland, CA USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piccolo, Rebecca; Yang, May; Marceau, Lisa D.; McKinlay, John B.] NERI, Watertown, MA USA. [Lagisetty, Pooja A.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2015 VL 30 SU 2 MA 2198103 BP S165 EP S165 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900271 ER PT J AU Langer, T Martinez, W Browning, D Varrin, P Lee, BS Bell, SK AF Langer, Thorsten Martinez, William Browning, David Varrin, Pam Lee, Barbara Sarnoff Bell, Sigall K. TI PATIENTS AS TEACHERS IN PATIENT SAFETY: A NEW INTERPROFESSIONAL EDUCATIONAL MODEL FOR COLLABORATIVE LEARNING ABOUT MEDICAL ERROR DISCLOSURE AND PREVENTION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Lee, Barbara Sarnoff; Bell, Sigall K.] BIDMC, Boston, MA USA. [Langer, Thorsten; Browning, David; Varrin, Pam] Boston Childrens Hosp, Brookline, MA USA. [Martinez, William] Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 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 APR PY 2015 VL 30 SU 2 MA 2201116 BP S504 EP S504 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902146 ER PT J AU Lebduska, E Kohli, A Hoffman, EL Fischer, G Spagnoletti, C Hariharan, J AF Lebduska, Elena Kohli, Amar Hoffman, Erika L. Fischer, Gary Spagnoletti, Carla Hariharan, Jaishree TI TEAM QI: AN INNOVATIVE STEPWISE APPROACH TO INVOLVE RESIDENTS IN QUALITY IMPROVEMENT INITIATIVES IN THE OUTPATIENT SETTING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Kohli, Amar] UPMC, Pittsburgh, PA USA. [Fischer, Gary; Spagnoletti, Carla] Univ Pittsburgh, Pittsburgh, PA USA. [Lebduska, Elena; Hariharan, Jaishree] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Hoffman, Erika L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199104 BP S508 EP S509 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902155 ER PT J AU Linsky, A Simon, SR Stolzmann, K Meterko, M AF Linsky, Amy Simon, Steven R. Stolzmann, Kelly Meterko, Mark TI CLINICAL PROVIDER EXPERIENCES WITH MEDICATION DISCONTINUATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Linsky, Amy; Simon, Steven R.; Stolzmann, Kelly; Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197763 BP S122 EP S122 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900176 ER PT J AU Martinez, W Browning, D Varrin, P Sarnoff, B Bell, SK AF Martinez, William Browning, David Varrin, Pamela Sarnoff, Barbara Bell, Sigall K. TI PATIENT TEACHER IN PATIENT SAFETY: LEARNING ALONGSIDE PATIENTS AND FAMILIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Sarnoff, Barbara; Bell, Sigall K.] BIDMC, Boston, MA USA. [Martinez, William] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Browning, David; Varrin, Pamela] Boston Childrens, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2201064 BP S222 EP S223 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901009 ER PT J AU Mehta, A Stock, S Gray, S Nerenz, D Ayanian, JZ Keating, NL AF Mehta, Anish Stock, Shannon Gray, Stacy Nerenz, David Ayanian, John Z. Keating, Nancy L. TI MEDIATORS OF DISPARITIES IN SURVIVAL AMONG PATIENTS WITH NON-SMALL CELL LUNG CANCER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mehta, Anish] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Ayanian, John Z.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mehta, Anish] Harvard Univ, Cambridge, MA 02138 USA. [Stock, Shannon] Coll Holy Cross, Worcester, MA 01610 USA. [Gray, Stacy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nerenz, David] Henry Ford Hlth Syst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2190348 BP S206 EP S207 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900361 ER PT J AU Meterko, M Baker, E Pilver, C Barker, AM Elwy, AR Reisman, J Dvorin, K Bokhour, BG AF Meterko, Mark Baker, Errol Pilver, Corey Barker, Anna M. Elwy, A. Rani Reisman, Joel Dvorin, Kelly Bokhour, Barbara G. TI CAN PATIENT-CENTERED CARE INNOVATION AFFECT PATIENTS' EXPERIENCES OF CARE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Barker, Anna M.; Elwy, A. Rani; Reisman, Joel; Dvorin, Kelly; Bokhour, Barbara G.] ENRM Vet Affairs Med Ctr, Bedford, MA USA. [Meterko, Mark; Baker, Errol; Pilver, Corey] VA Boston Healthcare Syst, Boston, MA USA. [Elwy, A. Rani] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198142 BP S116 EP S117 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900163 ER PT J AU Moin, T Li, JN Duru, OK Ettner, S Turk, N Kimbro, L Keckhafer, AM Luchs, RH Ho, S Mangione, C AF Moin, Tannaz Li, Jinnan Duru, O. Kenrik Ettner, Susan Turk, Norman Kimbro, Lindsay Keckhafer, Abigail M. Luchs, Robert H. Ho, Sam Mangione, Carol TI RESULTS FROM NEXT-D: DOES A DISEASE SPECIFIC HEALTH PLAN REDUCE INCIDENT DIABETES DEVELOPMENT AMONG A NATIONAL SAMPLE OF WORKING-AGE ADULTS WITH PRE-DIABETES? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Moin, Tannaz; Mangione, Carol] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Li, Jinnan; Duru, O. Kenrik; Ettner, Susan; Turk, Norman; Kimbro, Lindsay] Univ Calif Los Angeles, Los Angeles, CA USA. [Moin, Tannaz] VA Greater Los Angeles, Los Angeles, CA USA. [Keckhafer, Abigail M.; Luchs, Robert H.; Ho, Sam] UnitedHealthCare, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198946 BP S246 EP S247 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901067 ER PT J AU Mortensen, E Bollinger, M Fine, M AF Mortensen, Eric Bollinger, Mary Fine, MIchael TI ELECTRONIC MEDICAL RECORD BASED INTERVENTION TO REDUCE LENGTH OF STAY FOR VETERANS HOSPITALIZED WITH PNEUMONIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Mortensen, Eric] VANTHCS, Dallas, TX USA. [Mortensen, Eric] UT Southwestern Med Ctr, Dallas, TX USA. [Bollinger, Mary] STVHCS, San Antonio, TX USA. [Fine, MIchael] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2194967 BP S56 EP S56 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900028 ER PT J AU Nelson, KM Schwartz, GJ Hernandez, S Simonetti, JA Curtis, I Fihn, SD AF Nelson, Karin M. Schwartz, Gregory J. Hernandez, Susan Simonetti, Joseph A. Curtis, Idamay Fihn, Stephan D. TI THE ASSOCIATION OF NEIGHBORHOOD ENVIRONMENT AND MORTALITY: RESULTS FROM A NATIONAL STUDY OF VETERANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Nelson, Karin M.; Simonetti, Joseph A.; Fihn, Stephan D.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Schwartz, Gregory J.; Hernandez, Susan; Simonetti, Joseph A.] VA, Seattle, WA USA. [Curtis, Idamay; Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198108 BP S267 EP S267 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901107 ER PT J AU Nelson, KM Sylling, PW Wong, E Taylor, L Helfrich, CD Curtis, I Schectman, G Stark, R Fihn, SD AF Nelson, Karin M. Sylling, Philip W. Wong, Edwin Taylor, Leslie Helfrich, Christian D. Curtis, Idamay Schectman, Gordon Stark, Richard Fihn, Stephan D. TI IMPLEMENTATION OF THE PATIENT CENTERED MEDICAL HOME (PCMH) IN THE VETERANS HEALTH ADMINISTRATION (VHA): ASSOCIATIONS WITH CLINICAL OUTCOMES, PATIENT SATISFACTION, PROVIDER BURNOUT AND HEALTH CARE USE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Stark, Richard] Dept Vet Affairs, Washington, DC USA. [Wong, Edwin] Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Nelson, Karin M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Nelson, Karin M.; Taylor, Leslie] VA, Seattle, WA USA. [Helfrich, Christian D.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Schectman, Gordon] Vet Affairs Cent Off, Milwaukee, WI USA. [Sylling, Philip W.; Curtis, Idamay; Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2198377 BP S185 EP S185 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900313 ER PT J AU Nikiforova, T Benson, MK Hamm, M Williams, K Zickmund, SL Donovan, AK AF Nikiforova, Tanya Benson, Maggie K. Hamm, Megan Williams, Kelly Zickmund, Susan L. Donovan, Anna K. TI FITTING THE BILL: A QUALITATIVE ANALYSIS OF GROUP REFLECTIONS ON PATIENTS' HOSPITAL CHARGES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Nikiforova, Tanya; Benson, Maggie K.; Donovan, Anna K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Zickmund, Susan L.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hamm, Megan; Williams, Kelly] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198694 BP S496 EP S496 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902127 ER PT J AU Pace, LE Dusengimana, JMV Hategekimana, V Habineza, H Bigirimana, JB Tapela, N Mutumbira, C Mpanumusingo, E Keating, NL Brock, JE Lester, S Ignace, N Dillon, D Shulman, L Mpunga, T AF Pace, Lydia E. Dusengimana, Jean-Marie Vianney Hategekimana, Vedaste Habineza, Hamissy Bigirimana, Jean Bosco Tapela, Neo Mutumbira, Cadet Mpanumusingo, Egide Keating, Nancy L. Brock, Jane E. Lester, Susan Ignace, Nzayisenga Dillon, Deborah Shulman, Lawrence Mpunga, Tharcisse TI SPECTRUM OF BREAST DISEASE AT RWANDA'S FIRST NATIONAL CANCER REFERRAL CENTER, JULY 2012-DECEMBER 2013 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Pace, Lydia E.; Tapela, Neo; Keating, Nancy L.; Brock, Jane E.; Lester, Susan; Dillon, Deborah; Shulman, Lawrence] Brigham & Womens Hosp, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Dusengimana, Jean-Marie Vianney; Habineza, Hamissy; Bigirimana, Jean Bosco; Tapela, Neo; Ignace, Nzayisenga] Partners Hlth, Butaro, Rwanda. [Hategekimana, Vedaste; Mutumbira, Cadet; Mpanumusingo, Egide; Mpunga, Tharcisse] Minist Hlth, Butaro, Rwanda. [Shulman, Lawrence] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197897 BP S256 EP S256 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901087 ER PT J AU Patel, M Asch, DA Troxel, AB Wesby, L Ulrich, V Zhu, JS Wang, WL Volpp, KG AF Patel, Mitesh Asch, David A. Troxel, Andrea B. Wesby, Lisa Ulrich, Victoria Zhu, Jingsan Wang, Wenli Volpp, Kevin G. TI WORKPLACE WELLNESS INCENTIVES FOR WEIGHT LOSS-A RANDOMIZED, CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Patel, Mitesh; Asch, David A.; Troxel, Andrea B.; Wesby, Lisa; Ulrich, Victoria; Zhu, Jingsan; Wang, Wenli; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Patel, Mitesh; Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. 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 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196639 BP S306 EP S307 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901195 ER PT J AU Patel, M Reed, D Smith, CD Arora, VM AF Patel, Mitesh Reed, Darcy Smith, Cynthia D. Arora, Vineet M. TI ROLE-MODELING COST-CONSCIOUS CARE-A NATIONAL EVALUATION OF FACULTY AT TEACHING HOSPITALS IN THE UNITED STATES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Reed, Darcy] Mayo Clin, Rochester, MN USA. [Arora, Vineet M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Patel, Mitesh] Univ Penn, Philadelphia, PA 19104 USA. [Patel, Mitesh] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Smith, Cynthia D.] Amer Coll Physicians, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196655 BP S249 EP S249 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901073 ER PT J AU Patel, M Asch, DA Rosin, R Small, D Bellamy, S Haff, N Lee, S Wesby, L Hoffer, K Shuttleworth, D Taylor, D Ulrich, V Zhu, JS Yang, L Wang, XM Volpp, KG AF Patel, Mitesh Asch, David A. Rosin, Roy Small, Dylan Bellamy, Scarlett Haff, Nancy Lee, Samantha Wesby, Lisa Hoffer, Karen Shuttleworth, David Taylor, Devon Ulrich, Victoria Zhu, Jingsan Yang, Lin Wang, Xingmei Volpp, Kevin G. TI INDIVIDUAL VERSUS TEAM-BASED FINANCIAL INCENTIVES FOR PHYSICAL ACTIVITY-A RANDOMIZED, CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Patel, Mitesh; Asch, David A.; Rosin, Roy; Small, Dylan; Bellamy, Scarlett; Lee, Samantha; Wesby, Lisa; Hoffer, Karen; Shuttleworth, David; Taylor, Devon; Ulrich, Victoria; Zhu, Jingsan; Yang, Lin; Wang, Xingmei; Volpp, Kevin G.] Univ Penn, Philadelphia, PA 19104 USA. [Patel, Mitesh; Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Haff, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196516 BP S192 EP S193 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900330 ER PT J AU Patel, M Volpp, KG Rosin, R Small, D Bellamy, S Haff, N Lee, S Wesby, L Hoffer, K Shuttleworth, D Taylor, D Ulrich, V Zhu, JS Yang, L Wang, XM Asch, DA AF Patel, Mitesh Volpp, Kevin G. Rosin, Roy Small, Dylan Bellamy, Scarlett Haff, Nancy Lee, Samantha Wesby, Lisa Hoffer, Karen Shuttleworth, David Taylor, Devon Ulrich, Victoria Zhu, Jingsan Yang, Lin Wang, Xingmei Asch, David A. TI A RANDOMIZED TRIAL OF SOCIAL NORMS FEEDBACK AND FINANCIAL INCENTIVES FOR PHYSICAL ACTIVITY USING A TEAM-BASED APPROACH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Patel, Mitesh; Volpp, Kevin G.; Rosin, Roy; Small, Dylan; Bellamy, Scarlett; Lee, Samantha; Wesby, Lisa; Hoffer, Karen; Shuttleworth, David; Taylor, Devon; Ulrich, Victoria; Zhu, Jingsan; Yang, Lin; Wang, Xingmei; Asch, David A.] Univ Penn, New York, NY USA. [Patel, Mitesh; Volpp, Kevin G.; Asch, David A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Haff, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 APR PY 2015 VL 30 SU 2 MA 2196543 BP S90 EP S91 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900106 ER PT J AU Percac-Lima, S Ashburner, JM Zai, A Chang, YC Oo, S Guimaraes, E Atlas, SJ AF Percac-Lima, Sanja Ashburner, Jeffrey M. Zai, Adrian Chang, Yuchiao Oo, Sarah Guimaraes, Erica Atlas, Steven J. TI PATIENT NAVIGATION FOR COMPREHENSIVE CANCER SCREENING IN VULNERABLE PATIENTS USING A POPULATION-BASED HEALTH IT SYSTEM: RESULTS OF A RANDOMIZED CONTROL TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Oo, Sarah; Guimaraes, Erica] Massachusetts Gen Hosp, Chelsea, MA USA. [Percac-Lima, Sanja; Ashburner, Jeffrey M.; Zai, Adrian; Chang, Yuchiao; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198588 BP S221 EP S221 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901005 ER PT J AU Percac-Lima, S Ashburner, JM Rimmelin, D Atlas, SJ AF Percac-Lima, Sanja Ashburner, Jeffrey M. Rimmelin, Dorothy Atlas, Steven J. TI FOLLOW-UP OF ABNORMAL CHEST CT IN SMOKERS AT HIGH RISK FOR DEVELOPING LUNG CANCER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rimmelin, Dorothy] Harvard Univ, Sch Med, Boston, MA USA. [Percac-Lima, Sanja; Ashburner, Jeffrey M.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198516 BP S164 EP S165 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900269 ER EF